Peculiarities in the physical examination of the patients with renal diseases

Main symptoms and syndromes iephrology.

Complaints. History taking.

Specific complaints: kidneys pain is felt at or below the costal margin posteriorly, near the costovertebral angle; edema; disturbance of the urine production and urine excretion; polyuria, oligoyria, anuria, nocturia, disuria, enuresis.

Nonspecific complaints: intoxication, arterial hypertension, functional insufficiency others systems.

In many patients suffering from renal disease, symptoms and signs are not referred to the anatomical site of the kidneys. Clinical features commonly arise from abnormalities in the hypertension, anaemia, or metabolic bone disease. Their origin may be suspected only after detection of urinary abnormalities.

Kidneys pain occurs in acute pyelonephritis. Kidneys pain is felt at or below the costal margin posteriorly, near the costovertebral angle. It may radiate anteriorly toward the umbilicus. A stone can traverse the ureter without symptoms, but passage usually produces pain and bleeding. The pain begins gradually, usually in the flank, but increases over the next 20 to 60 min to become so severe that narcotic drugs may be needed for its control. The pain may remain in the flank or spread downward and anteriorly toward the ipsilateral loin, testis, or vulva. Pain that migrates downward indicates that the stone has passed to the lower third of the ureter, but if the pain does not migrate, the position of the stone cannot be predicted. A stone in the portion of the ureter within the bladder wall causes frequency, urgency, and dysuria that may be confused with urinary tract infection. The vast majority of ureteral stones less than 0.5 cm in diameter will pass spontaneously.

Studying of pain in costovertebral angle.

 

Patients with cystitis usually report dysuria, frequency, urgency, and suprapubic pain.

Symptoms of acute pyelonephritis generally develop rapidly over a few hours or a day and include a fever, shaking chills, nausea, vomiting, and diarrhea. Symptoms of cystitis may or may not be present. Besides fever, tachycardia, and generalized muscle tenderness, physical examination reveals marked tenderness on deep pressure in one or both costovertebral angles or on deep abdominal palpation.

Approximately 30% of women with acute dysuria, frequency, and pyuria have midstream urine cultures that show either no growth or insignificant bacterial growth. Clinically, these women cannot always be readily distinguished from those with cystitis.

Painful bladder disease is a general term for any bladder pathology that causes suprapubic, urethral, or pelvic pain. IC is the most common cause of bladder pain, but endometriosis, bacterial cystitis, and outlet obstruction that causes bladder instability can mimic the symptoms of IC.

Incontinence is a condition where involuntary loss of urine is objectively demonstrated and is a social or hygienic problem. A common variant, stress incontinence, denotes involuntary loss of urine with physical exercise (coughing, sneezing, sports, sexual activity). Urge incontinence is an involuntary loss of urine associated with a strong desire to void, and overflow incontinence is an involuntary loss of urine when the elevation of intravesical pressure with bladder overfilling or distention exceeds the maximal urethral pressure. Loss of urine through channels other than the urethra is rare (ectopic ureter, fistulae) but causes total or continuous incontinence.

Clinical clues to prerenal ARF are symptoms of thirst and orthostatic dizziness.

Flank pain may be a prominent symptom following occlusion of a renal artery or vein and with other parenchymal diseases distending the renal capsule (e.g., severe glomerulonephritis or pyelonephritis).

Postrenal ARF presents with suprapubic and flank pain due to distention of the bladder and of the renal collecting system and capsule, respectively. Colicky flank pain radiating to the groin suggests acute ureteric obstruction. Prostatic disease is likely if there is a history of nocturia, frequency, and hesitancy.

In the past history you can find following: frequency of urination, polyuria, nocturia, burning or pain on urination, hematuria, urgency, reduced caliber or force of the urinary stream, hesitancy, dribbling, incontinence; urinary infections, stones.

1.                Cardinal manifestations of renal disease.

Body homeostasis is maintained predominantly through the cellular processes that together comprise normal kidney function. Disturbances to any of these functions can lead to a constellation of abnormalities that may be detrimental to survival. The clinical manifestations of these diseases will depend upon the pathophysiology of the renal injury and will often be initially identified as a complex of symptoms, abnormal physical findings, and laboratory changes that will allow the identification of specific syndromes. These renal syndromes (Table) may arise as the consequence of a systemic illness or can occur as a primary renal disease.

 

Nephrologic syndromes usually consist of several elements that reflect the underlying pathologic processes and the duration of the disease and typically include one or more of the following features:

(1) disturbances in urine volume (oliguria, anuria, polyuria);

(2) abnormalities of urine sediment [red blood cells (RBC); white blood cells, casts, and crystals];

(3) abnormal excretion of serum proteins (proteinuria);

(4) reduction in glomerular filtration rate (GFR) (azotemia);

(5) presence of hypertension and/or expanded total body volume (edema);

(6) electrolyte abnormalities, or

(7) in some syndromes, fever/pain.

The combination of these findings should permit identification of one of the major nephrologic syndromes (Table 1) and will allow the differential diagnoses to be narrowed and the appropriate diagnostic evaluation and therapeutic course to be determined. Each of these syndromes and their associated diseases are discussed in more detail in subsequent chapters.

2. 1. Acute nephritic syndrome.

CLINICAL FEATURES AND CLINICOPATHOLOGIC CORRELATES

The acute nephritic syndrome is the clinical correlate of acute glomerular inflammation. In its most dramatic form, the acute nephritic syndrome is characterized by sudden onset (i.e., over days to weeks) of acute renal failure and oliguria (<400 mL of urine per day). Renal blood flow and glomerular filtration rate (GFR) fall as a result of obstruction of the glomerular capillary lumen by infiltrating inflammatory cells and proliferating resident glomerular cells. Renal blood flow and GFR are further compromised by intrarenal vasoconstriction and mesangial cell contraction that result from local imbalances of vasoconstrictor (e.g., leukotrienes, platelet-activating factor, thromboxanes, endothelins) and vasodilator substances (e.g., nitric oxide, prostacyclin) within the renal microcirculation. Extracellular fluid volume expansion, edema, and hypertension develop because of impaired GFR and enhanced tubular reabsorption of salt and water. As a result of injury to the glomerular capillary wall, urinalysis typically reveals red blood cell casts, dysmorphic red blood cells, leukocytes, and subnephrotic proteinuria of <3.5 g per 24 h (“nephritic urinary sediment”). Hematuria is often macroscopic.

The classic pathologic correlate of the nephritic syndrome is proliferative glomerulonephritis. The proliferation of glomerular cells is due initially to infiltration of the glomerular tuft by neutrophils and monocytes and subsequently to proliferation of resident glomerular endothelial and mesangial cells (endocapillary proliferation). In its most severe form, the nephritic syndrome is associated with acute inflammation of most glomeruli, i.e., acute diffuse proliferative glomerulonephritis. When less vigorous, fewer than 50% of glomeruli may be involved, i.e., focal proliferative glomerulonephritis. In milder forms of nephritic injury, cellular proliferation may be confined to the mesangium, i.e., mesangioproliferative glomerulonephritis.

RPGN is the clinical correlate of more subacute glomerular inflammation. Patients develop renal failure over weeks to months in association with a nephritic urinary sediment, subnephrotic proteinuria and variable oliguria, hypervolemia, edema, and hypertension. The classic pathologic correlate of RPGN is crescent formation involving most glomeruli (crescentic glomerulonephritis), crescents being half-moon-shaped lesions in Bowman’s space composed of proliferating parietal epithelial cells and infiltrating monocytes (extracapillary proliferation). In practice, the clinical term rapidly progressive glomerulonephritis and the pathologic term crescentic glomerulonephritis are often used interchangeably. In addition to classic crescentic glomerulonephritis, in which crescents dominate the glomerular pathology, crescents can also develop concomitantly with proliferative glomerulonephritis or as a complication of membranous glomerulopathy and other more indolent forms of glomerular inflammation.

The acute nephritic syndrome and RPGN are part of a spectrum of presentations of immunologically mediated proliferative glomerulonephritis. Studies of experimental models suggest that nephritic syndrome and diffuse proliferative glomerulonephritis represent an acute immune response to a sudden large antigen load, whereas RPGN and crescentic glomerulonephritis represent a more subacute immune response to a smaller antigen load in presensitized individuals. At the other end of the spectrum, chronic low-grade immune injury presents with slowly progressive renal insufficiency or asymptomatic hematuria in association with focal proliferative or mesangioproliferative glomerulonephritis. These more indolent forms of immune-mediated glomerulonephritis are discussed later in this chapter.

ETIOLOGY AND DIFFERENTIAL DIAGNOSIS

Acute nephritic syndrome and RPGN can result from renal-limited primary glomerulopathy or from secondary glomerulopathy complicating systemic disease. Figure 1 highlights the histopathologic and serologic features that help distinguish among the major causes of nephritic syndrome and RPGN. In general, rapid diagnosis and prompt treatment are critical to avoid the development of irreversible renal failure. Renal biopsy remains the “gold standard” for diagnosis. Immunofluorescence microscopy is particularly helpful and identifies three major patterns of deposition of immunoglobulin that define three broad diagnostic categories:

(1) granular deposits of immunoglobulin, a hallmark of immune-complex glomerulonephritis;

(2) linear deposition of immunoglobulin along the glomerular basement membrane (GBM), characteristic of anti-GBM disease; and

(3) paucity or absence of immunoglobulin, so-called pauci-immune glomerulonephritis. Most patients (>70%) with full-blown acute nephritic syndrome have immune-complex glomerulonephritis.

Pauci-immune glomerulonephritis is less common in this setting (<30%) and anti-GBM disease is rare (<1%). Among patients with RPGN, immune-complex glomerulonephritis and pauci-immune glomerulonephritis are equally prevalent (~45% each), whereas anti-GBM disease again accounts for a minority of cases (<10%).

Three serologic markers often predict the immunofluorescence microscopy findings iephritic syndrome and RPGN and may obviate the need for renal biopsy in classic cases. They are the serum C3 level and titers of anti-GBM antibody and antineutrophil cytoplasmic antibody (ANCA) (Fig. 1). The kidney is host to immune attack in immune-complex glomerulonephritis, most cases being initiated either by in situ formation of immune complexes or less commonly by glomerular trapping of circulating immune complexes. These patients typically have hypocomplementemia (low C3 and CH50 in 90%) and negative anti-GBM and ANCA serology. The glomerulus is the direct target of immune attack in anti-GBM disease, glomerular inflammation being initiated by an autoantibody directed at a 28-kDa autoantigen on the a3 chain of type IV collagen. Approximately 90 to 95% of patients with anti-GBM disease have circulating anti-GBM autoantibodies detectable by immunoassay; serum complement levels are typically normal, and ANCA are usually not detected. The pathogenesis of pauci-immune glomerulonephritis is still being defined; however, most patients have circulating ANCA, implicating dysregulation of humoral immunity. The presence of mononuclear leukocytes in glomeruli and the paucity of glomerular immune deposits suggest that cellular mechanisms are also involved. Serum complement levels are typically normal, and anti-GBM titers are usually negative in ANCA-associated renal disease.

2.                2.  Renal arterial hypertension.

Renal hypertension

A. Chronic pyelonephritis

B. Acute and chronic glomerulonephritis

C. Polycystic renal disease

D. Renovascular stenosis or renal infarction

E. Most other severe renal diseases (arteriolar nephrosclerosis, diabetic nephropathy, etc.)

F. Renin-producing tumors

Renovascular Hypertension. Over the past decades the standard approach to screen for renovascular hypertension has progressed from the rapid-sequence IVP to one of three noninvasive techniques: the captopril-enhanced radionuclide renal scan (the preferred choice), a duplex Doppler flow study, or magnetic resonance (MRI) angiography. However, perhaps the most sensitive and specific screening test, the spiral computed tomography (CT) scan, which gives a three-dimensional view, unfortunately also requires giving an intravenous contrast agent.

The definitive test for surgically correctable renal disease is the combination of a renal angiogram and renal vein renin determinations. The renal arteriogram both establishes the presence of a renal arterial lesion and aids in the determination of whether the lesion is due to atherosclerosis or to one of the fibrous or fibromuscular dysplasias.

It does not, however, prove that the lesion is responsible for the hypertension, nor does it permit prediction of the chances of surgical cure. It must be noted that (1) renal artery stenosis is a frequent finding by angiography and at postmortem iormotensive individuals, and (2) essential hypertension is a common condition and may occur in combination with renal arterial stenosis that is not responsible for the hypertension. Bilateral renal vein catheterization for measurement of plasma renin activity is therefore used to assess the functional significance of any lesiooted on arteriography. When one kidney is ischemic and the other is normal, all the renin released comes from the involved kidney. In the most straightforward situation, the ischemic kidney has a significantly higher venous plasma renin activity than the normal kidney, by a factor of 1.5 or more. Moreover, the renal venous blood draining the uninvolved kidney exhibits levels similar to those in the inferior vena cava below the entrance of the renal veins.

Significant benefit from operative correction may be anticipated in at least 80% of patients with the findings described above if care is taken to prepare the patient properly before renal vein blood sampling, i.e., by discontinuing renin-suppressing drugs, such as beta blockers, for at least 10 days; restricting the patient to a low-sodium intake for 4 days; and/or giving a converting-enzyme inhibitor for 24 h. When obstructing lesions in the branches of the renal arteries are demonstrated by arteriography, an attempt to obtain blood samples from the main branches of the renal vein should be made in an effort to identify a localized intrarenal arterial lesion responsible for the hypertension.

Hypertension and Left Ventricular Hypertrophy.

Hypertension is the most common complication of chronic renal disease and end-stage renal disease. When it is not found, the patient may have a salt-wasting form of renal disease (e.g., medullary cystic disease, chronic tubulointerstitial disease, or papillary necrosis), may be receiving antihypertensive therapy, or be volume-depleted, the last condition usually due to excessive gastrointestinal fluid losses or overzealous diuretic therapy. Since volume overload is the major cause of hypertension in uremia, the normotensive state can often be restored by appropriate use of diuretics in the predialysis patient or with aggressive ultrafiltration in dialysis patients. Nevertheless, because of hyperreninemia, some patients remain hypertensive despite rigorous salt and water restriction and ultrafiltration. Rarely, patients develop accelerated or malignant hypertension. Intravenous nitroprusside, labetolol, or more recently approved agents such as fenoldopam or urapidil, together with control of ECFV, generally controls such hypertension. Subsequently, such patients usually require more than one oral antihypertensive drug. Enalaprilat or other ACE inhibitors may also be considered, but in the face of bilateral renovascular disease they have the potential to further reduce GFR abruptly. Administration of erythropoietin (EPO) may raise blood pressure and increase the requirement for antihypertensive drugs. A high percentage of patients with CRD present with left ventricular hypertrophy or dilated cardiomyopathy. These are among the most ominous risk factors for excess cardiovascular morbidity and mortality in patients with CRD and ESRD and are thought to be related primarily to prolonged hypertension and ECFV overload. In addition, anemia and the surgical placement of an arteriovenous anastomosis for future or ongoing dialysis access may generate a high cardiac output state, which also intensifies the burden placed on the left ventricle.

2. 3. Nephrotic syndrome.

GENERAL FEATURES AND COMPLICATIONS

The nephrotic syndrome is a clinical complex characterized by a number of renal and extrarenal features, the most prominent of which are proteinuria of >3.5 g per 1.73 m2 per 24 h (in practice, >3.0 to 3.5 g per 24 h), hypoalbuminemia, edema, hyperlipidemia, lipiduria, and hypercoagulability. It should be stressed that the key component is proteinuria, which results from altered permeability of the glomerular filtration barrier for protein, namely the GBM and the podocytes and their slit diaphragms. The other components of the nephrotic syndrome and the ensuing metabolic complications are all secondary to urine protein loss and can occur with lesser degrees of proteinuria or may be absent even in patients with massive proteinuria.

In general, the greater the proteinuria, the lower the serum albumin level. Hypoalbuminemia is compounded further by increased renal catabolism and inadequate, albeit usually increased, hepatic synthesis of albumin. The pathophysiology of edema formation iephrotic syndrome is poorly understood. The underfilling hypothesis postulates that hypoalbuminemia results in decreased intravascular oncotic pressure, leading to leakage of extracellular fluid from blood to the interstitium. Intravascular volume falls, thereby stimulating activation of the renin-angiotensin-aldosterone axis and the sympathetic nervous system and release of vasopressin (antidiuretic hormone), and suppressing atrial natriuretic peptide release. These neural and hormonal responses promote renal salt and water retention, thereby restoring intravascular volume and triggering further leakage of fluid to the interstitium. This hypothesis does not, however, explain the occurrence of edema in many patients in whom plasma volume is expanded and the renin-angiotensin-aldosterone axis is suppressed. The latter finding suggests that primary renal salt and water retention may also contribute to edema formation in some cases.

Hyperlipidemia is believed to be a consequence of increased hepatic lipoprotein synthesis that is triggered by reduced oncotic pressure and may be compounded by increased urinary loss of proteins that regulate lipid homeostasis. Low-density lipoproteins and cholesterol are increased in the majority of patients, whereas very low density lipoproteins and triglycerides tend to rise in patients with severe disease. Although not proven conclusively, hyperlipidemia may accelerate atherosclerosis and progression of renal disease.

Hypercoagulability is probably multifactorial in origin and is caused, at least in part, by increased urinary loss of antithrombin III, altered levels and/or activity of proteins C and S, hyperfibrinogenemia due to increased hepatic synthesis, impaired fibrinolysis, and increased platelet aggregability. As a consequence of these perturbations, patients can develop spontaneous peripheral arterial or venous thrombosis, renal vein thrombosis, and pulmonary embolism. Clinical features that suggest acute renal vein thrombosis include sudden onset of flank or abdominal pain, gross hematuria, a left-sided varicocele (the left testicular vein drains into the renal vein), increased proteinuria, and an acute decline in GFR. Chronic renal vein thrombosis is usually asymptomatic. Renal vein thrombosis is particularly common (up to 40%) in patients with nephrotic syndrome due to membranous glomerulopathy, membranoproliferative glomerulonephritis, and amyloidosis.

Other metabolic complications of nephrotic syndrome include protein malnutrition and iron-resistant microcytic hypochromic anemia due to transferrin loss. Hypocalcemia and secondary hyperparathyroidism can occur as a consequence of vitamin D deficiency due to enhanced urinary excretion of cholecalciferol-binding protein, whereas loss of thyroxine-binding globulin can result in depressed thyroxine levels. An increased susceptibility to infection may reflect low levels of IgG that result from urinary loss and increased catabolism. In addition, patients are prone to unpredictable changes in the pharmacokinetics of therapeutic agents that are normally bound to plasma proteins.

ETIOLOGY AND DIFFERENTIAL DIAGNOSIS

Proteinuria >150 mg per 24 h is abnormal and can result from a number of mechanisms. Glomerular proteinuria results from leakage of plasma proteins through a perturbed glomerular filtration barrier; tubular proteinuria results from failure of tubular reabsorption of low-molecular-weight plasma proteins that are normally filtered and then reabsorbed and metabolized by tubular epithelium; overflow proteinuria results from filtration of proteins, usually immunoglobulin light chains, that are present in excess in the circulation. Tubular proteinuria virtually never exceeds 2 g per 24 h and thus, by definition, never causes nephrotic syndrome. Overflow proteinuria should be suspected in patients with clinical or laboratory evidence of multiple myeloma or other lymphoproliferative malignancy. Suspicion is heightened when there is a discrepancy between proteinuria detected by dipsticks, which are sensitive to albumin but not light chains, and the sulfosalicylic acid precipitation method, which detects both.

Nephrotic syndrome can complicate any disease that perturbs the negative electrostatic charge or architecture of the GBM and the podocytes and their slit diaphragms. Six entities account for greater than 90% of cases of nephrotic syndrome in adults: minimal change disease (MCD), focal and segmental glomerulosclerosis (FSGS), membranous glomerulopathy, MPGN, diabetic nephropathy, and amyloidosis. Renal biopsy is a valuable tool in adults with nephrotic syndrome for establishing a definitive diagnosis, guiding therapy, and estimating prognosis. Renal biopsy is not required in the majority of children with nephrotic syndrome as most cases are due to MCD and respond to empiric treatment with glucocorticoids.

MINIMAL CHANGE DISEASE

This glomerulopathy accounts for about 80% of nephrotic syndrome in children of younger than 16 years and 20% in adults (Table 2). The peak incidence is between 6 and 8 years. Patients typically present with nephrotic syndrome and benign urinary sediment. Microscopic hematuria is present in 20 to 30%. Hypertension and renal insufficiency are very rare.

Minimal Change Disease (also called nil disease, lipoid nephrosis, or foot process disease) is so named because glomerular size and architecture are normal by light microscopy. Immunofluorescence studies are typically negative for immunoglobulin and C3. Mild mesangial hypercellularity and sparse deposits of C3 and IgM may be detected. Occasionally, mesangial proliferation is associated with scanty IgA deposits, similar to those found in IgA nephropathy. However, the natural history of this variant and response to therapy resemble classic MCD. Electron microscopy reveals characteristic diffuse effacement of the foot processes of visceral epithelial cells. This morphologic finding is referred to as foot process fusion in the older literature.

The etiology of MCD is unknown and the vast majority of cases are idiopathic. MCD occasionally develops after upper respiratory tract infection, immunizations, and atopic attacks. Patients with atopy and MCD have an increased incidence of HLA-B12, suggesting a genetic predisposition. MCD, often in association with interstitial nephritis, is a rare side effect of nonsteroidal anti-inflammatory drugs (NSAIDs), rifampin, and interferon-a. The occasional association with lymphoproliferative malignancies (such as Hodgkin’s lymphoma), the tendency for idiopathic MCD to remit during intercurrent viral infection such as measles, and the good response of idiopathic forms to immunosuppressive agents (see below) suggest an immune etiology. In children, the urine contains albumin principally and minimal amounts of higher molecular weight proteins such as IgG and a2-macroglobulin. This selective proteinuria in conjunction with foot process effacement suggests injury to podocytes and loss of the fixed negative charge in the glomerular filtration barrier for protein. Proteinuria is typically nonselective in adults, suggesting more extensive perturbation of membrane permeability.

Source: http://www.unckidneycenter.org/kidneyhealthlibrary/minimalchange.html

TREATMENT

MCD is highly steroid-responsive and carries an excellent prognosis. Spontaneous remission occurs in 30 to 40% of childhood cases but is less common in adults. Approximately 90% of children and 50% of adults enter remission following 8 weeks of high-dose oral glucocorticoids. In a typical regimen using prednisone, children receive 60 mg/m2 of body surface area daily for 4 weeks, followed by 40 mg/m2 on alternate days for an additional 4 weeks; adults receive 1 to 1.5 mg/kg body weight per day for 4 weeks, followed by 1 mg/kg per day on alternate days for 4 weeks. Up to 90% of adults enter remission if therapy is extended for 20 to 24 weeks. Nephrotic syndrome relapses in over 50% of cases following withdrawal of glucocorticoids. Alkylating agents are reserved for the small number of patients who fail to achieve lasting remission. These include patients who relapse during or shortly after withdrawal of steroids (steroid-dependent) and those who relapse more than three times per year (frequently relapsing). In these settings, cyclophosphamide (2 to 3 mg/kg per day) or chlorambucil (0.1 to 0.2 mg/kg per day) is started after steroid-induced remission and continued for 8 to 12 weeks. Cytotoxic agents may also induce remission in occasional steroid-resistant cases. These benefits must be balanced against the risk of infertility, cystitis, alopecia, infection, and secondary malignancies, particularly in children and young adults. Azathioprine has not been proven to be a useful adjunct to steroid therapy. Cyclosporine induces remission in 60 to 80% of patients; it is an alternative to cytotoxic agents and an option in patients who are resistant to cytotoxic agents. Unfortunately, relapse is usual when cyclosporine is withdrawn, and long-term therapy carries the risk of nephrotoxicity and other side effects. Long-term renal and patient survival is excellent in MCD.

2. 4. Acute renal failure.

Acute renal failure (ARF) is a syndrome characterized by rapid decline in glomerular filtration rate (hours to days), retention of nitrogenous waste products, and perturbation of extracellular fluid volume and electrolyte and acid-base homeostasis. acute renal failure complicates approximately 5% of hospital admissions and up to 30% of admissions to intensive care units. Oliguria (urine output < 500 mL/d) is a frequent but not invariable clinical feature (~50%). acute renal failure is usually asymptomatic and is diagnosed when biochemical screening of hospitalized patients reveals a recent increase in plasma urea and creatinine concentrations. It may complicate a wide range of diseases, which for purposes of diagnosis and management are conveniently divided into three categories: (1) diseases that cause renal hypoperfusion without compromising the integrity of renal parenchyma (prerenal acute renal failure, prerenal azotemia) (~55%); (2) diseases that directly involve renal parenchyma (intrinsic renal acute renal failure, renal azotemia) (~40%); and (3) diseases associated with urinary tract obstruction (postrenal acute renal failure, postrenal azotemia) (~5%). Most acute renal failure is reversible, the kidney being relatively unique among major organs in its ability to recover from almost complete loss of function. Nevertheless, acute renal failure is associated with major in-hospital morbidity and mortality, in large part due to the serious nature of the illnesses that precipitate the acute renal failure.

Acute renal failure (continue).

CLINICAL FEATURES AND DIFFERENTIAL DIAGNOSIS

Patients presenting with renal failure should be assessed initially to determine if the decline in GFR is acute or chronic. An acute process is easily established if a review of laboratory records reveals a recent rise in blood urea and creatinine levels, but previous measurements are not always available. Findings that suggest chronic renal failure include anemia, neuropathy, and radiologic evidence of renal osteodystrophy or small scarred kidneys. However, it should be noted that anemia may also complicate ARF, and renal size may be normal or increased in several chronic renal diseases (e.g., diabetic nephropathy, amyloidosis, polycystic kidney disease). Once a diagnosis of ARF has been established, several issues should be addressed promptly:

(1) the identification of the cause of ARF,

(2) the elimination of the triggering insult (e.g., nephrotoxin) and/or institution of disease-specific therapies, and

(3) the prevention and management of uremic complications.

CLINICAL ASSESSMENT

Clinical clues to prerenal ARF are symptoms of thirst and orthostatic dizziness and physical evidence of orthostatic hypotension and tachycardia, reduced jugular venous pressure, decreased skin turgor, dry mucous membranes, and reduced axillary sweating. Case records should be reviewed for documentation of a progressive fall in urine output and body weight and treatment with NSAIDs or ACE inhibitors. Careful clinical examination may reveal stigmata of chronic liver disease and portal hypertension, advanced cardiac failure, sepsis, or other causes of reduced “effective” arterial blood volume (Table 3).

Intrinsic renal ARF due to ischemia is likely following severe renal hypoperfusion complicating hypovolemic or septic shock or following major surgery. The likelihood of ischemic ARF is increased further if ARF persists despite normalization of systemic hemodynamics. Diagnosis of nephrotoxic ARF requires careful review of the clinical data and pharmacy, nursing, and radiology records for evidence of recent exposure to nephrotoxic medications or radiocontrast agents or to endogenous toxins (e.g., myoglobin, hemoglobin, uric acid, myeloma protein, or elevated levels of serum calcium).

Although ischemic and nephrotoxic ARF account for more than 90% of cases of intrinsic renal ARF, other renal parenchymal diseases must be considered. Flank pain may be a prominent symptom following occlusion of a renal artery or vein and with other parenchymal diseases distending the renal capsule (e.g., severe glomerulonephritis or pyelonephritis). Subcutaneous nodules, livido reticularis, bright orange retinal arteriolar plaques, and digital ischemia, despite palpable pedal pulses, are clues to atheroembolization. ARF in association with oliguria, edema, hypertension, and an “active” urine sediment (nephritic syndrome) suggests acute glomerulonephritis or vasculitis. Malignant hypertension is a likely cause of ARF in patients with severe hypertension and evidence of hypertensive injury to other organs (e.g., left ventricular hypertrophy and failure, hypertensive retinopathy and papilledema, neurologic dysfunction). Fever, arthralgias, and a pruritic erythematous rash following exposure to a new drug suggest allergic interstitial nephritis, although systemic features of hypersensitivity are frequently absent.

Postrenal ARF presents with suprapubic and flank pain due to distention of the bladder and of the renal collecting system and capsule, respectively. Colicky flank pain radiating to the groin suggests acute ureteric obstruction. Prostatic disease is likely if there is a history of nocturia, frequency, and hesitancy and enlargement or induration of the prostate on rectal examination. Neurogenic bladder should be suspected in patients receiving anticholinergic medications or with physical evidence of autonomic dysfunction. Definitive diagnosis of postrenal ARF hinges on judicious use of radiologic investigations and rapid improvement in renal function following relief of obstruction.

URINALYSIS

Anuria suggests complete urinary tract obstruction but may complicate severe cases of prerenal or intrinsic renal ARF. Wide fluctuations in urine output raise the possibility of intermittent obstruction, whereas patients with partial urinary tract obstruction can present with polyuria due to impairment of urine concentrating mechanisms.

In prerenal ARF, the sediment is characteristically acellular and contains transparent hyaline casts (“bland,” “benign,” “inactive” urine sediment). Hyaline casts are formed in concentrated urine from normal constitutents of urine–principally Tamm-Horsfall protein, which is secreted by epithelial cells of the loop of Henle. Postrenal ARF may also present with an inactive sediment, although hematuria and pyuria are common in patients with intraluminal obstruction or prostatic disease. Pigmented “muddy brown” granular casts and casts containing tubule epithelial cells are characteristic of ATN and suggest ischemic or nephrotoxic ARF. They are usually found in association with microscopic hematuria and mild “tubular” proteinuria (<1 g/d); the latter reflects impaired reabsorption and processing of filtered proteins by injured proximal tubules. Casts are absent, however, in 20 to 30% of patients with ischemic or nephrotoxic ARF and are not a requisite for diagnosis. In general, red blood cell casts indicate glomerular injury or, less often, acute tubulointerstitial nephritis. White cell casts and nonpigmented granular casts suggest interstitial nephritis, whereas broad granular casts are characteristic of chronic renal disease and probably reflect interstitial fibrosis and dilatation of tubules. Eosinophiluria (>5% of urine leukocytes) is a common finding (~90%) in antibiotic-induced allergic interstitial nephritis when studied using Hansel’s stain; however, lymphocytes may predominate in allergic interstitial nephritis induced by NSAIDs. Eosinophiluria is also a feature of atheroembolic ARF. Occasional uric acid crystals (pleomorphic in shape) are common in the concentrated urine of prerenal ARF but suggest acute urate nephropathy if seen in abundance. Oxalate (envelope-shaped) and hippurate (needle-shaped) crystals raise the possibility of ethylene glycol ingestion and toxicity.

Increased urine protein excretion, but <1 g/d, is common in ATN due to failure of injured proximal tubules to reabsorb filtered protein and excretion of cellular debris (“tubular proteinuria”). Proteinuria of >1 g/d suggests injury to the glomerular ultrafiltration barrier (“glomerular proteinuria”) or excretion of myeloma light chains. The latter are not detected by conventional dipsticks (which detect albumin) and must be sought by other means (e.g., sulfosalicylic acid test, immunoelectrophoresis). Heavy proteinuria is also a frequent finding (~80%) in patients who develop combined allergic interstitial nephritis and minimal change glomerulopathy when treated with NSAIDs. A similar syndrome can be triggered by ampicillin, rifampicin, or interferon a. Hemoglobinuria or myoglobinuria should be suspected if urine is strongly positive for heme by dipstick, but contains few red cells, and if the supernatant of centrifuged urine is positive for free heme. Bilirubinuria may provide a clue to the presence of hepatorenal syndrome.

Fig. Red blood cell casts

(Source: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/evaluation-of-hematuria/)

Differential of Causes of Hematuria

Source: http://www.robotic-prostatectomy.com/resources/last-minute-internal-medicine

Evaluation of asymptomatic, atraumatic hematuria in children and adults (Nature Reviews Urology 7, 189-194 (April 2010) doi:10.1038/nrurol.2010.27)

 

RENAL FAILURE INDICES

Analysis of urine and blood biochemistry is particularly useful for distinguishing prerenal ARF from ischemic or nephrotoxic intrinsic renal ARF. The fractional excretion of sodium (FENa) is most useful in this regard. The FENa relates sodium clearance to creatinine clearance. Sodium is reabsorbed avidly from glomerular filtrate in patients with prerenal ARF, in an attempt to restore intravascular volume, but not in patients with ischemic or nephrotoxic intrinsic ARF, as a result of tubular epithelial cell injury. In contrast, creatinine is not reabsorbed in either setting. Consequently, patients with prerenal ARF typically have a FENa of <1.0% (frequently <0.1%), whereas the FENa in patients with ischemic or nephrotoxic ARF is usually >1.0%. The renal failure index provides comparable information, since clinical variations in serum sodium concentration are relatively small. Urine sodium concentration is a less sensitive index for distinguishing prerenal ARF from ischemic and nephrotoxic ARF as values overlap between groups. Similarly, indices of urinary concentrating ability such as urine specific gravity, urine osmolality, urine-to-plasma urea ratio, and blood urea-to-creatinine ratio are of limited value in differential diagnosis.

Many caveats apply when interpreting biochemical renal failure indices. FENa may be >1.0% in prerenal ARF if patients are receiving diuretics or have bicarbonaturia (accompanied by sodium to maintain electroneutrality), preexisting chronic renal failure complicated by salt wasting, or adrenal insufficiency. In contrast, the FENa is <1.0% in approximately 15% of patients with nonoliguric ischemic or nephrotoxic ARF. The FENa is often <1.0% in ARF due to urinary tract obstruction, glomerulonephritis, and vascular diseases.

LABORATORY FINDINGS

Serial measurements of serum creatinine can provide useful pointers to the cause of ARF. Prerenal ARF is typified by fluctuating levels that parallel changes in hemodynamic function. Creatinine rises rapidly (within 24 to 48 h) in patients with ARF following renal ischemia, atheroembolization, and radiocontrast exposure. Peak creatinine levels are observed after 3 to 5 days with contrast nephropathy and return to baseline after 5 to 7 days. In contrast, creatinine levels typically peak later (7 to 10 days) in ischemic ARF and atheroembolic disease. The initial rise in serum creatinine is characteristically delayed until the second week of therapy with many tubule epithelial cell toxins (e.g., aminoglycosides, cisplatin) and probably reflects the need for accumulation of these agents within cells before GFR falls.

Hyperkalemia, hyperphosphatemia, hypocalcemia, and elevations in serum uric acid and creatine kinase (MM isoenzyme) levels at presentation suggest a diagnosis of rhabdomyolysis. Hyperuricemia [>890 umol/L (>15 mg/dL)] in association with hyperkalemia, hyperphosphatemia, and increased circulating levels of intracellular enzymes such as lactate dehydrogenase may indicate acute urate nephropathy and tumor lysis syndrome following cancer chemotherapy. A wide serum anion and osmolal gap (measured serum osmolality minus the serum osmolality calculated from serum sodium, glucose, and urea concentrations) indicate the presence of an unusual anion or osmole in the circulation and are clues to diagnosis of ethylene glycol or methanol ingestion. Severe anemia in the absence of hemorrhage raises the possibility of hemolysis, multiple myeloma, or thrombotic microangiopathy. Systemic eosinophilia suggests allergic interstitial nephritis but is also a feature of atheroembolic disease and polyangiitis nodosa.

RADIOLOGIC FINDINGS

Imaging of the urinary tract by ultrasonography is useful to exclude postrenal ARF. Computed tomography and magnetic resonance imaging are alternative imaging modalities. Whereas pelvicalyceal dilatation is usual with urinary tract obstruction (98% sensitivity), dilatation may be absent immediately following obstruction or in patients with ureteric encasement (e.g., retroperitoneal fibrosis, neoplasia). Retrograde or anterograde pyelography are more definitive investigations in complex cases and provide precise localization of the site of obstruction. A plain film of the abdomen, with tomography if necessary, is a valuable initial screening technique in patients with suspected nephrolithiasis. Doppler ultrasonography and magnetic resonance flow imaging appear promising for assessment of patency of renal arteries and veins in patients with suspected vascular obstruction; however, contrast angiography is usually required for definitive diagnosis.

RENAL BIOPSY

Biopsy is reserved for patients in whom prerenal and postrenal ARF have been excluded and the cause of intrinsic renal ARF is unclear. Renal biopsy is particularly useful when clinical assessment and laboratory investigations suggest diagnoses other than ischemic or nephrotoxic injury that may respond to disease-specific therapy. Examples include glomerulonephritis, vasculitis, hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, and allergic interstitial nephritis.

COMPLICATIONS

ARF impairs renal excretion of sodium, potassium, and water and perturbs divalent cation homeostasis and urinary acidification mechanisms. As a result, ARF is frequently complicated by intravascular volume overload, hyponatremia, hyperkalemia, hyperphosphatemia, hypocalcemia, hypermagnesemia, and metabolic acidosis. In addition, patients are unable to excrete nitrogenous waste products and are prone to develop the uremic syndrome. The speed of development and the severity of these complications reflect the degree of renal impairment and catabolic state of the patient.

Expansion of extracellular fluid volume is an inevitable consequence of diminished salt and water excretion in oliguric or anuric individuals. Whereas milder forms are characterized by weight gain, bibasilar lung rales, raised jugular venous pressure, and dependent edema, continued volume expansion may precipitate life-threatening pulmonary edema. Hypervolemia may be particularly problematic in patients receiving multiple intravenous medications and enteral or parenteral nutrition. Excessive administration of free water either through ingestion and nasogastric administration or as hypotonic saline or isotonic dextrose solutions (dextrose being metabolized) can induce hypoosmolality and hyponatremia, which, if severe, lead to cerebral edema and neurologic abnormalities, including seizures.

Hyperkalemia is a frequent complication of ARF. Serum potassium typically rises by 0.5 mmol/L per day in oliguric and anuric patients due to impaired excretion of ingested or infused potassium and potassium released from injured tissue. Coexistent metabolic acidosis may exacerbate hyperkalemia by promoting potassium efflux from cells. Hyperkalemia may be particularly severe, even at the time of diagnosis, in patients with rhabdomyolysis, hemolysis, and tumor lysis syndrome. Mild hyperkalemia (<6.0 mmol/L) is usually asymptomatic. Higher levels are typically associated with electrocardiographic abnormalities and/or increased cardiac excitability.

Metabolism of dietary protein yields between 50 and 100 mmol/d of fixed nonvolatile acids that are normally excreted by the kidneys. Consequently, ARF is typically complicated by metabolic acidosis, often with an increased serum anion gap. Acidosis can be particularly severe when endogenous production of hydrogen ions is increased by other mechanisms (e.g., diabetic or fasting ketoacidosis; lactic acidosis complicating generalized tissue hypoperfusion, liver disease, or sepsis; metabolism of ethylene glycol or methanol).

Mild hyperphosphatemia is an almost invariable complication of ARF. Severe hyperphosphatemia may develop in highly catabolic patients or following rhabdomyolysis, hemolysis, or tumor lysis. Metastatic deposition of calcium phosphate can lead to hypocalcemia, particularly when the product of serum calcium (mg/dL) and phosphate (mg/dL) concentrations exceeds 70. Other factors that contribute to hypocalcemia include tissue resistance to the actions of parathyroid hormone and reduced levels of 1,25-dihydroxyvitamin D. Hypocalcemia is often asymptomatic but can cause perioral paresthesias, muscle cramps, seizures, hallucinations and confusion, and prolongation of the QT interval and nonspecific T-wave changes on electrocardiography.

Anemia develops rapidly in ARF and is usually mild and multifactorial in origin. Contributing factors include impaired erythropoiesis, hemolysis, bleeding, hemodilution, and reduced red cell survival time. Prolongation of the bleeding time and leukocytosis are also common. Common contributors to the bleeding diathesis include mild thrombocytopenia, platelet dysfunction, and/or clotting factor abnormalities (e.g., factor VIII dysfunction), whereas leukocytosis usually reflects sepsis, a stress response, or other concurrent illness. Infection is a common and serious complication of ARF, occurring in 50 to 90% of cases and accounting for up to 75% of deaths. It is unclear whether patients with ARF have a clinically significant defect in host immune responses or whether the high incidence of infection reflects repeated breaches of mucocutaneous barriers (e.g., intravenous cannulae, mechanical ventilation, bladder catheterization). Cardiopulmonary complications of ARF include arrhythmias, myocardial infarction, pericarditis and pericardial effusion, pulmonary edema, and pulmonary embolism. Mild gastrointestinal bleeding is common (10 to 30%) and is usually due to stress ulceration of gastric or small intestinal mucosa.

Protracted periods of severe ARF are invariably associated with the development of the uremic syndrome.

A vigorous diuresis can occur during the recovery phase of ARF (see above) and lead to intravascular volume depletion and delayed recovery of GFR by causing secondary prerenal ARF. Hypernatremia can also complicate recovery if water losses via hypotonic urine are not replaced or if losses are inappropriately replaced by relatively hypertonic saline solutions. Hypokalemia, hypomagnesemia, hypophosphatemia, and hypocalcemia are less common metabolic complications during this period.

Supportive Measures (Table)

2. 5. Renal colic. STONE PASSAGE

A stone can traverse the ureter without symptoms, but passage usually produces pain and bleeding. The pain begins gradually, usually in the flank, but increases over the next 20 to 60 min to become so severe that narcotic drugs may be needed for its control. The pain may remain in the flank or spread downward and anteriorly toward the ipsilateral loin, testis, or vulva. Pain that migrates downward indicates that the stone has passed to the lower third of the ureter, but if the pain does not migrate, the position of the stone cannot be predicted. A stone in the portion of the ureter within the bladder wall causes frequency, urgency, and dysuria that may be confused with urinary tract infection. The vast majority of ureteral stones less than 0.5 cm in diameter will pass spontaneously.

It has been standard practice to diagnose acute renal colic by intravenous pyelography; however, helical computed tomography (CT) scan without radiocontrast enhancement is now the preferred procedure. CT has the advantage of detecting uric acid stones in addition to the traditional radioopaque stones, and CT does not expose the patient to the risk of radio-contrast agents.

OTHER SYNDROMES

Staghorn Calculi  Struvite, cystine, and uric acid stones often grow too large to enter the ureter. They gradually fill the renal pelvis and may extend outward through the infundibula to the calyces themselves.

Nephrocalcinosis  Calcium stones grow on the papillae. Most break loose and cause colic, but they may remain in place so that multiple papillary calcifications are found by x-ray, a condition termed nephrocalcinosis. Papillary nephrocalcinosis is common in hereditary distal renal tubular acidosis (RTA) and in other types of severe hypercalciuria. In medullary sponge kidney disease  calcification may occur in dilated distal collecting ducts.

Sludge  Sufficient uric acid or cystine in the urine may plug both ureters with precipitate. Calcium oxalate crystals do not do this because less than 100 mg oxalate usually is excreted daily in the urine even in severe hyperoxaluric states, compared with 1000 mg uric acid in patients with hyperuricosuria and 400 to 800 mg cystine in patients with cystinuria. Calcium phosphate crystals can render the urine milky but do not plug the urinary tract.

2. 6. Haematuria.

Isolated hematuria without proteinuria, other cells, or casts is often indicative of bleeding from the urinary tract. Normal red blood cell excretion is up to 2 million RBCs per day. Hematuria is defined as two to five RBCs per high-power field (HPF) and can be detected by dipstick. Common causes of isolated hematuria include stones, neoplasms, tuberculosis, trauma, and prostatitis. Gross hematuria with blood clots is almost never indicative of glomerular bleeding; rather, it suggests a postrenal source in the urinary collecting system. Evaluation of patients presenting with microscopic hematuria is outlined in Fig. 47-2. A single urinalysis with hematuria is common and can result from menstruation, viral illness, allergy, exercise, or mild trauma. Annual urinalysis of servicemen over a 10-year period showed an incidence of 38%. However, persistent or significant hematuria (>three RBCs/HPF on three urinalyses, or single urinalysis with >100 RBCs, or gross hematuria) identified significant renal or urologic lesions in 9.1% of over 1000 patients.

The suspicion for urogenital neoplasms in patients with isolated painless hematuria (nondysmorphic RBCs) increases with age. Neoplasms are rare in the pediatric population, and isolated hematuria is more likely to be “idiopathic” or associated with a congenital anomaly. Hematuria with pyuria and bacteriuria is typical of infection and should be treated with antibiotics after appropriate cultures. Acute cystitis or urethritis in women can cause gross hematuria. Hypercalciuria and hyperuricosuria are also risk factors for unexplained isolated hematuria in both children and adults. In some of these patients (50 to 60%), reducing calcium and uric acid excretion through dietary interventions can eliminate the microscopic hematuria.

Isolated microscopic hematuria can be a manifestation of glomerular diseases. The RBCs of glomerular origin are often dysmorphic when examined by phase-contrast microscopy. Irregular shapes of RBCs may also occur due to pH and osmolarity changes found in the distal tubule. There is, however, significant observer variability in detecting dysmorphic RBCs, especially if a phase-contrast microscope is not available. The most common etiologies of isolated glomerular hematuria are IgA nephropathy, hereditary nephritis, and thin basement membrane disease. IgA nephropathy and hereditary nephritis can have episodic gross hematuria. A family history of renal failure is often present in patients with hereditary nephritis, and patients with thin basement membrane disease often have other family members with microscopic hematuria. Hematuria with dysmorphic RBCs, RBC casts, and protein excretion >500 mg/d is virtually diagnostic of glomerulonephritis. RBC casts form as RBCs that enter the tubular fluid become trapped in a cylindrical mold of gelled Tamm-Horsfall protein. Even in the absence of azotemia, these patients should undergo serologic evaluation and renal biopsy.

2. 7. Chronic renal failure.

Chronic renal disease (CRD) is a pathophysiologic process with multiple etiologies, resulting in the inexorable attrition of nephroumber and function, and frequently leading to end-stage renal disease (ESRD). In turn, ESRD represents a clinical state or condition in which there has been an irreversible loss of endogenous renal function, of a degree sufficient to render the patient permanently dependent upon renal replacement therapy (dialysis or transplantation) in order to avoid life-threatening uremia. Uremia is the clinical and laboratory syndrome, reflecting dysfunction of all organ systems as a result of untreated or undertreated acute or chronic renal failure. Given the capacity of the kidneys to regain function following acute injury, the vast majority (>90%) of patients with ESRD have reached this state as a result of CRD.

Source: http://www.docstoc.com/docs/158450892/CKD–THE-PATIENT-AND-HIS-ILLNESS—Nurseslabs

PATHOPHYSIOLOGY OF CRD

The pathophysiology of CRD involves initiating mechanisms specific to the underlying etiology as well as a set of progressive mechanisms that are a common consequence following long-term reduction of renal mass, irrespective of etiology. Such reduction of renal mass causes structural and functional hypertrophy of surviving nephrons. This compensatory hypertrophy is mediated by vasoactive molecules, cytokines, and growth factors and is due initially to adaptive hyperfiltration, in turn mediated by increases in glomerular capillary pressure and flow. Eventually, these short-term adaptations prove maladaptive, in that they predispose to sclerosis of the remaining viable nephron population. This final common pathway for inexorable attrition of residual nephron function may persist even after the initiating or underlying disease process has become inactive. Increased intrarenal activity of the renin-angiotensin axis appears to contribute both to the initial adaptive hyperfiltration and to the subsequent maladaptive hypertrophy and sclerosis. These maladaptive long-term actions of renin-angiotensin axis activation are mediated in part through downstream growth factors such as transforming growth factor b. Interindividual variability in the risk and rate of CRD progression can be explained in part by variations in the genes encoding components of these and other pathways involved in glomerular and tubulointerstitial fibrosis and sclerosis.

The earliest stage common to all forms of CRD is a loss of renal reserve. When kidney function is entirely normal, glomerular filtration rate (GFR) can be augmented by 20 to 30% in response to the stimulus of a protein challenge. During the earliest stage of loss of renal reserve, basal GFR may be normal or even elevated (hyperfiltration), but the expected further rise in response to a protein challenge is attenuated. This early stage is particularly well documented in diabetic nephropathy. At this stage, the only clue may be at the level of laboratory measurements, which estimate GFR. The most commonly utilized laboratory measurements are the serum urea and creatinine concentrations. By the time serum urea and creatinine concentrations are even mildly elevated, substantial chronic nephron injury has already occurred.

As GFR declines to levels as low as 30% of normal, patients may remain asymptomatic with only biochemical evidence of the decline in GFR, i.e., rise in serum concentrations of urea and creatinine. However, careful scrutiny usually reveals early additional clinical and laboratory manifestations of renal insufficiency. These may include nocturia, mild anemia and loss of energy, decreasing appetite and early disturbances in nutritional status, and abnormalities in calcium and phosphorus metabolism (moderate renal insufficiency). As GFR falls to below 30% of normal, an increasing number and severity of uremic clinical manifestations and biochemical abnormalities supervene (severe renal insufficiency). At the stages of mild and moderate renal insufficiency, intercurrent clinical stress may compromise renal function still further, inducing signs and symptoms of overt uremia. Such intercurrent clinical conditions to which patients with CRD may be particularly susceptible include infection (urinary, respiratory, or gastrointestinal), poorly controlled hypertension, hyper- or hypovolemia, and drug or radiocontrast nephrotoxicity, among others. When GFR falls below 5 to 10% of normal (ESRD), continued survival without renal replacement therapy becomes impossible.

ETIOLOGY

There has been a dramatic increase in the incidence of ESRD as well as a shift in the relative incidence of etiologies of CRD during the past two decades. Whereas glomerulonephritis was the leading cause of CRD in the past, diabetic and hypertensive nephropathy are now much more frequent underlying etiologies. This may be a consequence of more effective prevention and treatment of glomerulonephritis or of diminished mortality from other causes among individuals with diabetes and hypertension. Greater overall longevity and diminished premature cardiovascular mortality have also increased the mean age of patients presenting with ESRD. Hypertension is a particularly common cause of CRD in the elderly, in whom chronic renal ischemia due to renovascular disease may be an underrecognized additional contribution to the pathophysiologic process. Many patients present at an advanced stage of CRD, precluding definitive determination of etiology.

CLINICAL AND LABORATORY MANIFESTATIONS OF CHRONIC RENAL FAILURE AND UREMIA

Uremia leads to disturbances in the function of every organ system. Chronic dialysis reduces the incidence and severity of these disturbances, so that, where modern medicine is practiced, the overt and florid manifestations of uremia have largely disappeared. Unfortunately, as indicated in Table 6, even optimal dialysis therapy is not a panacea, because some disturbances resulting from impaired renal function fail to respond fully, while others continue to progress.

Source: http://www.elsevierimages.com/image/60320.htm

 

Laboratory investigations of the renal function.

3. 1. Routine urine analysis.

Evaluation of the routine urine analysis includes amount of the urine; colour, smell, transparence, reaction, specific gravity of the urine, urine sediment.

Urineanalysis should include a dipstick examination followed by microscopic examination if the dipstick has positive findings. The dipstick examination should include measurement of urinary specific gravity, pH, protein, hemoglobin, glucose, ketones, bilirubin, nitrites, and leukocyte esterase. Microscopic examination should check for all formed elements – crystals, cells, casts, and infecting organisms.

Proteinuria

Usually dipstick-positive. Recall, though, that the dipstick detects only albumin. If there is any reason to suspect proteinuria and the dipstick is negative, confirm UA with sulfosalicylic acid (SSA), as this detects both albumin and nonalbumin proteins.

Classifications:  Transient, Orthostatic, Persistent

Transient

Transient Idiopathic: Usually seen in children, adolescents, and young adults who are otherwise asymptomatic and healthy, and whose urinalysis shows no other abnormalities. Repeat test 2-3 times to confirm not persistent.

Intermittent Idiopathic:  Proteinuria present in ~50% of urine samples tested for any individual in the absence of orthostasis or another attributable etiology. Usually occurs in those <30 years old and long term prognosis is favorable. Yearly monitoring is recommended.

Functional: Occurs without evidence of intrinsic renal disease in the face of acute illness, some chronic conditions, or stressful events such as fever, CHF, exercise, seizures, pregnancy, OSA.

Orthostatic

Increased proteinuria while upright with normal amounts while supine. Present in up to 3-5 % of adolescents and young men; uncommon in patients >30 years old. Long-term follow-up shows no deterioration of renal function with spontaneous resolution in 50% of patients 10 years after diagnosis. Do split 24 hour urine collection to diagnose.

Persistent

Persistent Isolated: Proteinuria that persists at < 3.5 g/24h/1.73 m² in the absence of other renal or systemic disease. Patients should be followed closely and referred to nephrologist for any change in urinary sediment, worsening proteinuria, or onset of renal insufficiency. Renal biopsy probably indicated.

Persistent Proteinuria with Systemic or Other Renal Disease:  

Glomerular: Heavy or nephrotic range proteinuria (>3.5 g/24h/1.73 m².

Tubular: Disease of the tubular epithelium causing inability to reabsorb filtered low-molecular-weight (LMW) proteins (e.g., beta-2 microglobulin or lysozyme). Usually <2 g/24h/1.73 m².

Overflow: LMW protein overproduced in the body, filters across the glomerulus in amounts too great for the reabsorptive capacity of the tubules. Most often this is Ig light chain excretion in conditions like multiple myeloma or amyloidosis. Lysozymuria can occur in acute monocytic leukemia.

 

HEMATURIA, PYURIA, AND CASTS

Isolated hematuria without proteinuria, other cells, or casts is often indicative of bleeding from the urinary tract. Normal red blood cell excretion is up to 2 million RBCs per day. Hematuria is defined as two to five RBCs per high-power field (HPF) and can be detected by dipstick. Common causes of isolated hematuria include stones, neoplasms, tuberculosis, trauma, and prostatitis. Gross hematuria with blood clots is almost never indicative of glomerular bleeding; rather, it suggests a postrenal source in the urinary collecting system. A single urinalysis with hematuria is common and can result from menstruation, viral illness, allergy, exercise, or mild trauma. Annual urinalysis of servicemen over a 10-year period showed an incidence of 38%. However, persistent or significant hematuria (>three RBCs/HPF on three urinalyses, or single urinalysis with >100 RBCs, or gross hematuria) identified significant renal or urologic lesions in 9.1% of over 1000 patients. The suspicion for urogenital neoplasms in patients with isolated painless hematuria (nondysmorphic RBCs) increases with age. Neoplasms are rare in the pediatric population, and isolated hematuria is more likely to be “idiopathic” or associated with a congenital anomaly. Hematuria with pyuria and bacteriuria is typical of infection and should be treated with antibiotics after appropriate cultures. Acute cystitis or urethritis in women can cause gross hematuria. Hypercalciuria and hyperuricosuria are also risk factors for unexplained isolated hematuria in both children and adults. In some of these patients (50 to 60%), reducing calcium and uric acid excretion through dietary interventions can eliminate the microscopic hematuria.

 

Source: http://imannooor.wordpress.com/2010/08/09/hematuria/

Isolated microscopic hematuria can be a manifestation of glomerular diseases. The RBCs of glomerular origin are often dysmorphic when examined by phase-contrast microscopy. Irregular shapes of RBCs may also occur due to pH and osmolarity changes found in the distal tubule. There is, however, significant observer variability in detecting dysmorphic RBCs, especially if a phase-contrast microscope is not available. The most common etiologies of isolated glomerular hematuria are IgA nephropathy, hereditary nephritis, and thin basement membrane disease. IgA nephropathy and hereditary nephritis can have episodic gross hematuria. A family history of renal failure is often present in patients with hereditary nephritis, and patients with thin basement membrane disease often have other family members with microscopic hematuria. Hematuria with dysmorphic RBCs, RBC casts, and protein excretion >500 mg/d is virtually diagnostic of glomerulonephritis. RBC casts form as RBCs that enter the tubular fluid become trapped in a cylindrical mold of gelled Tamm-Horsfall protein. Even in the absence of azotemia, these patients should undergo serologic evaluation and renal biopsy.

Typical morphology of erythrocytes from a urine specimen revealing microscopic hematuria. (phase contrast microscopy, ×100) (Source: http://www.aafp.org/afp/1999/0915/p1143.html)

Dysmorphic erythrocytes from a urine specimen. These cells suggest a glomerular cause of microscopic hematuria. (phase contrast microscopy, × 100) (Source: http://www.aafp.org/afp/1999/0915/p1143.html)

 

Isolated pyuria is unusual since inflammatory reactions in the kidney or collecting system are also associated with hematuria. The presence of bacteria suggests infection, and white blood cell casts with bacteria are indicative of pyelonephritis. White blood cells and/or white blood cell casts may also be seen in tubulointerstitial processes such as interstitial nephritis, systemic lupus erythematosus, and transplant rejection. In chronic renal diseases, degenerated cellular casts called waxy casts can be seen in the urine. Broad casts are thought to arise in the dilated tubules of enlarged nephrons that have undergone compensatory hypertrophy in response to reduced renal mass (i.e., chronic renal failure). A mixture of broad casts typically seen with chronic renal failure together with cellular casts and RBCs may be seen in smoldering processes such as chronic glomerulonephritis with active glomerulitis.

White blood cells seen under a microscope from a urine sample

Read more: http://www.answers.com/topic/pyuria#ixzz2slZxGTbV

Pyuria in a person with urosepsis. Read more: http://www.answers.com/topic/pyuria#ixzz2slZxGTbV

 

3. 2. Urinary examination according to Zimnitsky.

This test is used for evaluation function of the kidneys. The measuring of the specific gravity of urine is determined in eight urine portions. Urinary examination according to Zimnitsky is needed for evaluation of the common diuresis, daily urine, night urine, fluctuation of the specific gravity of urine in every portion. Patient collects urine every 3 hours through 24 hours starting from 6.00. Normal test shows predominant daily urine over night urine (1,5-2:1); specific gravity of urine range from 1.002 to 1.030. This is hyposthenuria when the specific gravity of urine in the each portion is less then 1.010. This is isosthenuria when the specific gravity of urine range in the each portion is 5. The nycturia is wheight urine predominates over daily urine.

3. 2. 1. Urinary examination according to Reyzelman.

Urinary examination according to Reyzelman is the modifying urinary examination according to Zimnitsky. This test isn’t done by patient every 3 hours as in examination according to Zimnitsky, but just when patient has need to the urination. Evaluation of the test is the same that in examination according to Zimnitsky.

3. 3. Test according to Folgard.

Test according to Folgard evaluates the ability kidneys to concentrate urine in the condition of 36-hour or 18-hour water deprivation. The specific gravity of health urinary in the each portion, collected every 4 hours through 36-hour test, increases to 1.030-1.032 even 1.040, urine amount decrease to 50-60 ml, and 24-hour urine is less then 500-600 ml.

3. 4. Dilute test.

It is desirable to test urinary dilution and normal water excretion. The subject should drink 1000 ml water in 20 min. Urine is collected at hourly intervals for 4 hours. Result: At least 750 ml of urine should be excreted in the 4 hours. The osmolality of one sample should be less than 100 mOsm kg.

3. 5. Urinary examination according to Necheporenco.

Urinary examination according to Necheporenco is done if the erythrocytes or leucocytes were found in urine sediment (erythrocytes more than 3-5, leucocytes more than 5-6) and casts. This test determines amount of erythrocytes, leucocytes and casts in 1 ml (or 1 L) of urine. The urine should be collected as a midstream clean catch.

3. 6. Evaluation of the daily proteinuria.

The evaluation of proteinuria is shown schematically in Fig. 2 and is typically initiated after colorimetric detection of proteinuria by dipstick examination. The dipstick measurement detects mostly albumin and gives false-positive results when pH > 7.0 and the urine is very concentrated or contaminated with blood. A very dilute urine may obscure significant proteinuria on dipstick examination, and proteinuria that is not predominantly albumin will be missed. This is particularly important for the detection of Bence Jones proteins in the urine of patients with multiple myeloma. Tests to measure total urine concentration accurately rely on precipitation with sulfosalicylic or trichloracetic acids. Currently, ultrasensitive dipsticks are available to measure microalbuminuria (30 to 300 mg/d), an early marker of glomerular disease that has been shown to predict glomerular injury in early diabetic nephropathy.

The magnitude of proteinuria and the protein composition in the urine depend upon the mechanism of renal injury leading to protein losses. Large amounts of plasma proteins normally course through the glomerular capillaries but do not enter the urinary space. Both charge and size selectivity prevent virtually all of albumin, globulin, and other large-molecular-weight proteins from crossing the glomerular wall. However, if this barrier is disrupted, there can be leakage of plasma proteins into the urine (glomerular proteinuria). Smaller proteins (<20 kDa) are freely filtered but are readily reabsorbed by the proximal tubule. Normal individuals excrete less than 150 mg/d of total protein and only about 30 mg/d of albumin. The remainder of the protein in the urine is secreted by the tubules (Tamm-Horsfall, IgA, and urokinase) or represents small amounts of filtered b2-microglobulin, apoproteins, enzymes, and peptide hormones. Another mechanism of proteinuria occurs when there is excessive production of an abnormal protein that exceeds the capacity of the tubule for reabsorption. This most commonly occurs with plasma cell dyscrasias such as multiple myeloma and lymphomas that are associated with monoclonal production of immunoglobulin light chains.

The normal glomerular endothelial cell forms a barrier penetrated by pores of about 100 nm that holds back cells and other particles but offers little impediment to passage of most proteins. The glomerular basement membrane traps most large proteins (>100 kDa), while the foot processes of epithelial cells (podocytes) cover the urinary side of the glomerular basement membrane and produce a series of narrow channels (slit diaphragms) to allow molecular passage of small solutes and water. The channels are coated with anionic glycoproteins that are rich in glutamate, aspartate, and sialic acid, which are negatively charged at physiologic pH. This negatively charged barrier impedes the passage of anionic molecules such as albumin. Some glomerular diseases, such as minimal change disease, cause fusion of glomerular epithelial cell foot processes, resulting in predominantly “selective” loss of albumin. Other glomerular diseases can present with disruption of the basement membrane and slit diaphragms (e.g., by immune complex deposition), resulting in large amounts of protein losses that include albumin and other plasma proteins. The fusion of foot processes causes increased pressure across the capillary basement membrane, resulting in areas with larger pore sizes. The combination of increased pressure and larger pores results in significant proteinuria (“nonselective”).

When the total daily excretion of protein exceeds 3.5 g, there is often associated hypoalbuminemia, hyperlipidemia, and edema (nephrotic syndrome). However, total daily urinary protein excretion greater than 3.5 g can occur without the other features of the nephrotic syndrome in a variety of other renal diseases. Plasma cell dyscrasias (multiple myeloma) can be associated with large amounts of excreted light chains in the urine, which may not be detected by dipstick (which detects mostly albumin). The light chains produced from these disorders are filtered by the glomerulus and overwhelm the reabsorptive capacity of the proximal tubule. A sulfosalicylic acid precipitate that is out of proportion to the dipstick estimate is suggestive of light chains (Bence Jones protein), and light chains typically redissolve upon warming of the precipitate. Renal failure from these disorders occurs through a variety of mechanisms including tubule obstruction (cast nephropathy) and light chain deposition.

3. 7. Evaluation of the renal excretion.

EFFECTS OF NEPHRON LOSS ON RENAL EXCRETORY MECHANISMS

The volume of urine excreted (averaging 1.5 L/d or roughly 1 mL/min) represents the sum of two large, directionally opposite processes-namely, ultrafiltration of 180 L/d or more of plasma water (or 125 mL/min) and reabsorption of more than 99% of this filtrate by transport processes in the renal tubules. While renal blood flow accounts for about 20% of resting cardiac output, the kidneys comprise only about 1% of total body weight. This disproportionate allocation of cardiac output, greatly exceeding blood flow per gram of brain, heart or liver, is required for the process of ultrafiltration.

GLOMERULAR ULTRAFILTRATION

Urine production begins at the glomerulus where an ultrafiltrate of plasma is formed. The rate of glomerular ultrafiltration (glomerular filtration rate, GFR) is governed chiefly by forces favoring filtration on the one hand (hydraulic pressure in the glomerular capillaries) and forces opposing filtration on the other (the sum of hydraulic pressure in Bowman’s space and colloid osmotic pressure in the glomerular capillaries). The rate of glomerular plasma flow and the total surface area of the glomerular capillaries are also determinants of GFR. Decreased GFR can therefore be expected when glomerular hydraulic pressure is reduced (as in circulatory shock); tubule (hence Bowman’s space) hydraulic pressure is elevated, as in urinary tract obstruction; plasma colloid osmotic pressure rises to high levels (hemoconcentration due to severe volume depletion, myeloma, or other dysproteinemias); renal, and hence glomerular, blood flow is reduced (severe hypovolemia, cardiac failure); permeability is reduced (diffuse glomerular disease); or filtration surface area is diminished, through focal or diffuse nephron loss in progressive renal failure.

Diagram showing the basic physiologic mechanisms of the kidney Source: http://en.wikipedia.org/wiki/Ultrafiltration_(renal)

The glomerular capillary wall is specially adapted to allow passage of extremely large volumes of water while retaining all but the smallest solute molecules. Molecules the size of inulin (approximately 5200 mol wt) pass freely across the glomerular filtration barrier, appearing at approximately the same concentration in Bowman’s space as in plasma. The passage of solutes across the glomerular barrier decreases progressively with increasing molecular size such that, as the molecular weight of albumin is approached, most of the solute is retained in the plasma. Albumin, a polyanionic molecule in plasma, is further retarded at the glomerular filtration barrier by electrostatic forces imparted by negatively charged cell-surface molecules on the epithelial foot processes that form the filtration slits and the slit diaphragms. With disruption of these structural and electrostatic barriers, as in many forms of glomerular injury, large quantities of plasma proteins gain access to the glomerular filtrate.

Glomerular function is best studied by measuring renal clearance C=UV/P, U and P being the urinary and plasma concentrations of any substance and V the volume of urine formed per minute. If a substance is plasma passes freely through the glomerular filter and is neither absorbed by the tubules, the quantity excreted in urine (UV) is identical with the amount filtered by the glomeruli; the clearance of such a substance therefore equals the rate of glomerular filtration (GFR).

The polysaccharide, inulin, appears to be excreted in this way and its clearance is used to estimate GFR, which for the average adult is about 120 ml/min. A similar value is obtained using the clearance of ⁵¹Cr-EDTA, and here a single injection technique is possible. In clinical practice the clearance of creatinine, which approximates to that of inulin, is usually measured by collecting a 24-hour urine sample and withdrawing a sample of blood at the end of the collection. In declining renal function, some creatinine may be secreted by tubules, and this may result in an overestimate of GFR.

ASSESSMENT OF GLOMERULAR FILTRATION RATE

Monitoring the GFR is important in both the hospital and outpatient settings, and several different methodologies are available (discussed below). In most acute clinical circumstances a measured GFR is not available, and it is necessary to estimate the GFR from the serum creatinine level in order to provide appropriate doses of drugs that are excreted into the urine. Serum creatinine is the most widely used marker for GFR and is related directly to the urine creatinine excretion and inversely to the serum creatinine (UCr/PCr). Based upon this relationship and some important caveats (discussed below), the GFR will fall proportionately with the increase in PCr. Failure to account for GFR reductions in drug dosing can lead to significant morbidity and mortality from drug toxicities (e.g., digoxin, aminoglycosides). In the outpatient setting, serial determinations of GFR are helpful for following the progression of chronic renal insufficiency, but again, the serum creatinine is often used as a surrogate for GFR (although much less accurate; see below). In patients with chronic progressive renal insufficiency there is an approximately linear relationship between 1/PCr and time. The slope of this line will remain constant for an individual patient, and when values are obtained that do not fall on this line, an investigation for a superimposed acute process (e.g., volume depletion, drug reaction) should be initiated. It should be emphasized that the signs and symptoms of uremia will develop at significantly different levels of serum creatinine depending upon the patient (size, age, and sex), the underlying renal disease, existence of concurrent diseases, and true GFR. In general, patients do not develop symptomatic uremia until renal insufficiency is usually quite severe (GFR < 15 mL/min) and in some patients it does not occur until the GFR < 5 mL/min.

A reduced GFR leads to retention of nitrogenous waste products (azotemia) such as serum urea nitrogen and creatinine. Azotemia may result from reduced renal perfusion, intrinsic renal disease, or postrenal processes (ureteral obstruction). Precise determination of GFR is problematic as both commonly used markers (urea and creatinine) have characteristics that affect their accuracy as markers of clearance. Urea clearance is generally an underestimate of GFR because of tubule urea reabsorption and may be as low as one-half of GFR measured by other techniques.

Creatinine is a small, freely filtered solute that varies little from day to day (since it is derived from muscle metabolism of creatine). However, serum creatinine can increase acutely from dietary ingestion of cooked meat. Creatinine can be secreted by the proximal tubule through an organic cation pathway. There are many clinical settings where a creatinine clearance is not available, and decisions concerning drug dosing must be made based on the serum creatinine. A formula that allows an estimate of creatinine clearance in men that accounts for age-related decreases in GFR, body weight, and sex has been derived by Cockcroft-Gault:

This value should be multiplied 0.85 for women, since a lower fraction of the body weight is composed of muscle. The gradual loss of muscle from chronic illness, chronic use of glucocorticoids, or malnutrition can mask significant changes in GFR with small or imperceptible changes in serum creatinine. More accurate determinations of GFR are available using inulin clearance or radionuclide-labeled markers such as 125I-iothalamate or EDTA. These methods are highly accurate due to precise quantitation and the absence of any renal reabsorption/secretion and should be used to follow GFR in patients in whom creatinine is not likely to be a reliable indicator (patients with decreased muscle mass secondary to age, malnutrition, concurrent illnesses).

Glomerular Filtration Rate (GFR)

Chronic kidney disease is a worldwide problem that carries a substantial risk for cardiovascular morbidity and death.  Current guidelines define chronic kidney disease as kidney damage or glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m²for three months or more, regardless of cause.  The assay of creatinine in serum or plasma is the most commonly used test to assess renal function.  In addition to the diagnosis and treatment of renal disease and the monitoring of renal dialysis, creatinine measurements are also used for the calculation of the fractional excretion of other urine analytes (e. g., albumin, α-amylase).

Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass). It is freely filtered by the glomeruli and, under normal conditions, is not re-absorbed by the tubules to any appreciable extent. A small but significant amount is also actively secreted.  Since a rise in blood creatinine is observed only with marked damage of the nephrons, it is not suited to detect early stage kidney disease.

A considerably more sensitive test and better estimation of glomerular filtration rate (GFR) is given by the creatinine clearance test based on creatinine concentration in urine and serum/plasma, and urine flow rate.  For this test a precisely timed urine collection (usually 24 hours) and a blood sample are needed.  However, since this test is prone to error due to the inconvenient collection of timed urine, mathematical attempts to estimate GFR based only on the creatinine concentration in serum or plasma have been made.

Among the various approaches suggested to estimate GFR using serum creatinine, one based on the results of the MDRD (Modification of Diet in Renal Disease) trial has found wide recognition to calculate an estimated GFR (eGFR) in adults.  The first derivation of the MDRD equation was derived with the conventional Jaffé creatinine method.  A newer version of the MDRD equation has been developed for IDMS (isotope-dilution mass spectrometry)-traceable enzymatic creatinine methods.

GFR (mL/min/1.73 m²) = 175 x (S_cr)^-1.154 x (Age)^-0.203 x (0.742 if female) x (1.212 if African-American)

where S_cr is serum/plasma creatinine in mg/dL measured by an IDMS-traceable enzymatic creatinine method.

In children, there is not a single formula recommended for all ages. However, the Schwartz formula is frequently used and appropriate for most ages, but should be used with caution or avoided in premature infants in the first several months of life. In the premature infant population, more specialized equations are often used. The pediatric Schwartz equation is

GFR (mL/min/1.73 m²) = (0.41 x Height) / S_cr

were S_cr is serum/plasma creatinine in mg/dL

 

 

4. Instrumental investigations of the kidneys function.

4. 1. Renal ultrasound.

The most useful among these is renal sonography. An ultrasound examination of the kidneys verifies the presence of two symmetric kidneys, provides an estimate of kidney size, and rules out renal masses and obstructive uropathy. The documentation of symmetric small kidneys supports the diagnosis of progressive CRD with an irreversible component of scarring. The occurrence of normal kidney size suggests the possibility of an acute rather than chronic process. However, polycystic kidney disease, amyloidosis, and diabetes may lead to CRD with normal-sized or even enlarged kidneys. Documentation of asymmetric kidney size suggests either a unilateral developmental or urologic abnormality or chronic renovascular disease. In the latter case, a vascular imaging procedure, such as duplex Doppler sonography of the renal arteries, radionuclide scintigraphy, or magnetic resonance angiography should be considered. A computed tomographic scan without contrast may be useful in assessing kidney stone activity, in the appropriate clinical context. Voiding cystourethrography to rule out reflux may be indicated in some younger patients with a history of enuresis or with a family history of reflux. However, in most cases, by the time CRD is established, reflux has resolved; even if present, its repair may not stabilize renal function. In any case, imaging studies should avoid exposure to intravenous radiocontrast dye where possible because of its nephrotoxicity.

Normal kidney in ultrasound:

Measures 9-11 cm‘s

Has the same extent of echoes as liver

Cortex measures about 2.5 cm‘s

Central echoes are from fat surrounding renal pelvis.

Renal pelvis is filled with urine and is echo free. Note the posterior enhancement behind renal pelvis (Source: http://www.meddean.luc.edu/lumen/MedEd/Radio/curriculum/Surgery/Renal_mass.htm).

 

Simple renal cysts:

Most common in patients over 50 years of age.

These cysts are typically asymptomatic.

CT: Well defined mass with water [low] density usually in the renal cortex.

U.S  Well marginated mass with no internal echoes and posterior enhancement indicating fluid.

Renal Cysts

Ultrasound can easily distinguish renal cysts from mass lesions.

Simple Anechoic Renal Cysts

Arrows points to cyst.

* Points to  good through transmission of echoes behind the cyst.

(Source: http://www.meddean.luc.edu/lumen/MedEd/Radio/curriculum/Surgery/Renal_mass.htm).

 

Renal ultrasound is the method of choice for assessing overall renal size and cortical thickness and distinguishing solid tumours from cysts. It is an excellent screening test for polycystic kidney disease. In investigation of suspected malignant renal tumours ultrasound can give additional information by detecting extension of tumour to renal veins, vena cava, lymph nodes or liver. It can demonstrate dilation of the renal pelvis and ureters, which may indicate urinary tract obstruction. It can also be used to assessresidual urine in the bladder after micturition, the presence of which may indicate incomplete bladder emptying and bladder neck obstruction.

Perinephric abscess or haematoma can be demonstrated. Calculi are usually detected but very small stones may be missed. Cyst puncture, renal biopsy and antegrade pyelography are best done under ultrasound screening. It is quick, inexpensive and harmless, and portable equipment is available to investigate seriously ill patients.

The most useful is renal sonography. An ultrasound examination of the kidneys verifies the presence of two symmetric kidneys, provides an estimate of kidney size, and rules out renal masses and obstructive uropathy.

Documentation of asymmetric kidney size suggests either a unilateral developmental or urologic abnormality or chronic renovascular disease. In the latter case, a vascular imaging procedure, such as duplex Doppler sonography of the renal arteries, radionuclide scintigraphy, or magnetic resonance angiography should be considered.

4. 2. X-ray renal examinations.

4. 2. 1. Plain film.

Nephrocalcinosis  Calcium stones grow on the papillae. Most break loose and cause colic, but they may remain in place so that multiple papillary calcifications are found by x-ray, a condition termed nephrocalcinosis. Papillary nephrocalcinosis is common in hereditary distal renal tubular acidosis (RTA) and in other types of severe hypercalciuria. Abdominal x-rays may demonstrate nephrocalcinosis as well as nephrolithiasis, the latter due to the hypercalciuria that often accompanies hypercalcemia.

Diffuse infiltration is seen most commonly in lymphomas other than Hodgkin’s disease. There may be flank pain related to massive renal infiltration, and x-rays may show enlargement of one or both kidneys. Renal insufficiency occurs in a minority of cases, and overt uremia is rare.

Anti-GBM disease commonly presents with hematuria, nephritic urinary sediment, subnephrotic proteinuria, and rapidly progressive renal failure over weeks, with or without pulmonary hemorrhage. When pulmonary hemorrhage occurs, it usually predates nephritis by weeks or months. Hemoptysis can vary from fluffy pulmonary infiltrates on chest x-ray and mild dyspnea on exertion to life-threatening pulmonary hemorrhage. Hypertension is unusual and occurs in fewer than 20% of cases.

4. 2. 2. Intravenous urography.

This is carried out by intravenous injection of an organic iodine-containing contrast compound. Approximately one third of the contrast is excreted, largely by glomerular filtration, within the first hour. It is used, often in association with tomography, to demonstrate the size, shape and position of the kidneys and to study the outflow tract.  Following injection, films are taken at timed intervals. There is first an increase in the radiographic density of the renal substance (nephrogram) as contrast is concentrated in the tubules, and this shows the size and shape of the kidneys. Within a few minutes contrast is excreted into the calyceal system, pelvis and ureters, which are best demonstrated within the first 20 minutes.

In the adult, healthy kidneys usually measure 11-14 cm in length, bi-polar diameter being similar in length to that of three lumbar vertebrae. Renal cortical thickness can be assessed and focal or generalised cortical defect seen, e. g. scars of chronic pyelonephritis. In significant unilateral renal artery stenosis, early films show a delay on the stenotic side in the nephrogram, which subsequently becomes more dense and persists longer compared with the normal side. This is also apparent on angiography. Thus in hypertensive patients it is useful to obtain early films to detect this difference. Abnormalitis of the papillae, e.g. papillary necrosis, may be seen, and the appearance of the pelvi-calyceal system, ureters and bladder will show any structural abnormality or partial or complete obstruction. Clubbed calyces and slow excretion are common in chronic obstruction. Severe obstruction ma result in distention of the pelvis, thinning of the cortex, and extravasation of contrast into extrarenal tissue. In renal tuberculosis calcification and cavitation are common. Adult polycystic disease causes bilateral renal enlargement and the calyces are stretched and spidery. Calculi may be localised.

Angiogram

·                     Neovascularization

Renal Cell Carcinoma

·                     A: IVP shows mass in the lower pole of left kidney.

·                     B: Angiogram showing neovascularization

(Source: http://www.meddean.luc.edu/lumen/MedEd/Radio/curriculum/Surgery/Renal_mass.htm)

 

Excretion urography is not without risk. A few patients may react to the contrast agent. In those with known atopy, diabetes mellitus or renal insufficiency and any with a history of adverse reaction to contrast agents, a special low osmolar contrast medium should be used if the procedure is essential. Formerly, all patients were dehydrated before IVU to increase the concentration of dye in the kidneys and collecting system. In some (diabetic patients, small children, and those with myeloma or renal failure) this resulted in significant renal impairment. Use of tomography and of modern contrast agent, which can be given in large doses, has made water deprivation unnecessary in these patients.

 

4.                2. 3. Infusional urography.

Infusional urography is carried out by intravenous injection of more amount of contrast than in the case of intravenous urography and duration of injection is  4-10 minutes.  The first films are taken after injection and next within 5-10 minutes. Infusional urography should be used in patients with renal failure.

 

4. 2. 4. Cystoscopy and retrograde pyelography.

These investigations are used mainly to investigate lesions of the ureter and renal pelvis and define the cause of ureteric obstruction. Cystoscopy allows direct inspection of the bladder and ureteric orifices. Contrast medium is then injection under the screening control into ureteric catheters inserted during cystoscopy. Antibiotic cover is essential when the urine contains organisms.

 

4. 2. 5. Pneumoren, pneumoretroperitoneum.

X-ray examination using a gas, such as air or carbon dioxide, as a contrast medium, introducing in the perirenal cavity. This method is useful in diagnosis of masses in the kidneys and retroperitoneal cavity.

4. 2. 6. Antegrade pyelography.

This requires percutaneous insertion of the a fine catheter into the pelvi-calceal system under radiograph or ultrasound control. Injection of contrast allows detailed examination of the pelvi-calceal system and ureters and localization of any obstruction. The procedure can be extended to allow percutaneous drainage (nephrostomy) of an obstructed system, which will frequently result in recovery of renal function.

4. 2. 7. Computed tomography.

This is less widely available than ultrasound, but is particularly helpful in the kidneys and in perirenal and retroperitoneal tissues. The information obtained can be increased by used of contrast agent. Extension of renal tumours to perirenal tissue, retroperitoneal nodes, liver and thorax can be identified, It is of value in assessing the extent of renal trauma, particularly when vascular damage is suspected, and in demonstrating radio-opaque stones.

Normal kidney in CT:

Located in retro peritoneum surrounded by fat.

Renal cortex enhances with IV contrast.

In the nephrographic phase the contrast has not been excreted and the renal pelvis appears dark.

Renal pelvis and ureters can be seen as the contrast is excreted by kidneys.

Note the relationship of kidneys

Renal veins drain into IVC

(Source: http://www.meddean.luc.edu/lumen/MedEd/Radio/curriculum/Surgery/Renal_mass.htm)

 

Renal Cell Carcinoma

·                     Arrow: Solid hypo dense mass left kidney

·                     Arrowhead: Normal parenchymal enhancement

(Source: http://www.meddean.luc.edu/lumen/MedEd/Radio/curriculum/Surgery/Renal_mass.htm)

 

Source: http://www.pagepress.org/journals/index.php/nr/article/view/nr.2010.e12/2364

4. 2. 8. Renal arteriography.

This is used to demonstrate the anatomy of the renal arterial system and is valuable when investigating renal artery stenosis, arteriovenous malformation, and persistent bleeding after trauma. It has been largely superseded by ultrasonography and computed tomography when investigating renal masses. Following percutaneous catheterization of the femoral artery the catheter tip is advanced and contrast injected first into the aorta and then into the renal arteries.

Arteriography can be extended to carry out balloon angioplasty to dilate the artery in patients with arterial stenosis, to perform arterial embolisation in patients with inoperable renal carcinoma who have haemorrhage or intractable pain, or to perform arterial embolisation in patients bleeding from the kidney after trauma, or occasionally after renal biopsy.

Diagnosis of thrombosis of the renal arteries and infarction is established by renal arteriography.

Renal artery stenosis should be diagnosed by bilateral arteriography with repeated bilateral renal vein and systemic renin determinations.

Renal arteriography (normal) (Source: http://radiopaedia.org/cases/renal-angiogram-arterial-anatomy

 

4. 2. 9. Selected renal arteriography.

Selective renal arteriography should be performed on donors to rule out the presence of multiple or abnormal renal arteries, because the surgical procedure is difficult and the ischemic time of the transplanted kidney long when vascular abnormalities exist.

 

4. 2. 1, 11. Venacavagraphy. Renal venography.

The renal veins can be catheterized via the femoral vein and blood taken to measure renin. This may be of value in assessing the haemodynamic significance of a renal artery stenosis.

Renal venography is carried out by selected intravenous injection in renal vein of an organic contrast compound. This method is of value in assessing the extent of renal trauma, when renal tumour or renal arterial hypertension is suspected. Venography will demonstrate renal vein thrombosis and invasion by tumour.

 

4. 2. 12. Lymphography.

Lymphography is carried out by injection of an contrast compound when tumour metastases in lymph nodes is suspected.

4. 3. Radionuclide studies.

These studies require the injection of gamma ray-emitting radiopharmaceuticals which are taken up and excreted by the kidney, a process which can be monitored by a computer-linked gamma camera. In this way function of individual kidneys can be assessed.

4. 3. 1. Renography.

Diethylenetriamine penta-acetic acid labeled with technetium (^99mTc-DTPA) is excreted by glomerular filtration. Following injection of DTPA, computer analysis of uptake and excretion can be used to provide information about arterial perfusion of each kidney. In renal artery stenosis transit time is prolonged, peak activity delayed, and excretion reduce. In obstruction of the outflow tract, persistence of nuclide in the renal pelvis is shown by prolongation of phase 2 and absence of phase 3 of renogram. Poor renal function is indicated by curve of low amplitude. The technique can help in distinguishing poor perfusion from tubular necrosis, but it is not diagnostic.

4. 3.2. Scan (scintigraphy) of the kidneys.

Documentation of asymmetric kidney size suggests either a unilateral developmental or urologic abnormality or chronic renovascular disease. In the latter case, a vascular imaging procedure, such as duplex Doppler sonography of the renal arteries, radionuclide scintigraphy, or magnetic resonance angiography should be considered.

Radionuclide scans define less anatomic detail than intravenous urography and, like the urogram, are of limited value when renal function is poor. Nonetheless, such scans are sensitive for the detection of obstruction and provide a substitute test in some patients at high risk for reaction to intravenous contrast.

 

4. 3. 3. Diuretic renography.

Diuretic renography may be used to distinguished a dilated outflow tract from urinary tract obstruction with increased pressure in the calyceal system. The diuretic is given during the course of the renogram and is genuine obstruction is not present, activity drains away.

4. 3. 4. Renal imaging.

Dimercaptosuccinic acid labeled with technetium (^99mTc-DMSA) is filtered by glomeruli and partially bound to proximal tubular cells. Following intravenous injection, images of the renal cortex can be obtained using a gamma camera. These allow comparison of two kidneys as they show the shape, size and function of each. This is a sensitive method of demonstrating early cortical scarring. It is possible to assess the relative contribution of each kidney to total function.

4. 4. Renal biopsy.

This technique has increased greatly our understanding of renal disease and, in particular, knowledge of glomerulinephritis. To obtain the maximum information from this invasive investigation, it is important to examine the tissue obtained by light and electron microscopy and by immunohistological technigues.

General indications

– to determine the nature of the renal disease

– to document the natural history of the a disease

– to establish the response to therapy

Specific indications

–                      adult nephritic syndrome

–                      persistent proteinuria > 1 g/24 hours

–                      adult acute nephritic syndrome

–                      persistent microscopic or macroscopic haemoturia (disordered haemostasis excluded)

–                      systemic diseases with renal involvement

–                      chronic renal failure with normal or near normal sized kidneys

–                      unexplained acute renal failure

–                      occasionally where documentation of specific renal disease is required for insurance or occupational purposes

–                       childhood acute nephritic syndrome, if significant haematuria present or unresponsive to corticosteroid therapy

–                      childhood acute nephritic syndrome, if significant urinary abnormalities persist for longer than 12 months or renal functional impairment present

Contraindications to renal biopsy

–                      disorders coagulation

–                      thrombocytopenia

–                      uncontrolled hypertension

–                      solitary kidney (except in transplanted kidneys)

–                      small contracted kidneys, i.e. less than 60 % of expected bipolar length

Position of patient during conducting of renal biopsy.

Source: http://www.slideshare.net/VishalGolay/renal-biopsy-seminar

In general, percutaneous kidney biopsy is a safe procedure. Possible kidney biopsy risks include:

§                     Bleeding. The most common complication of kidney biopsy is blood in the urine (hematuria). The bleeding usually stops within a few days. Bleeding that’s serious enough to require a blood transfusion affects a very small percentage of people who have a kidney biopsy. Rarely, surgery is needed to control bleeding.

§                     Pain. Pain at the biopsy site is common after a kidney biopsy, but it usually lasts only a few hours.

§                     Arteriovenous fistula. If the biopsy needle accidentally damages the walls of a nearby artery and vein, a fistula, or abnormal connection, can form between the two blood vessels. This type of fistula usually causes no symptoms and closes on its own.

§                     Others. Rarely, a collection of blood (hematoma) around the kidney becomes infected. This complication is treated with antibiotics and surgical drainage. Another uncommon risk is development of high blood pressure related to a large hematoma.

Renal biopsy of kidney : moment of introduction of needle

Source: http://www.slideshare.net/VishalGolay/renal-biopsy-seminar

Ultrasound image showing the biopsy gun inside the lower pole of the kidney (arrows)

Source: http://www.indianjnephrol.org/article

 

4. 5. Diagnosis of the renal arterial hypertension.

Renovascular Hypertension.  Over the past decades the standard approach to screen for renovascular hypertension has progressed from the rapid-sequence IVP to one of three noninvasive techniques: the captopril-enhanced radionuclide renal scan (the preferred choice), a duplex Doppler flow study, or magnetic resonance (MRI) angiography. However, perhaps the most sensitive and specific screening test, the spiral computed tomography (CT) scan, which gives a three-dimensional view, unfortunately also requires giving an intravenous contrast agent.

The definitive test for surgically correctable renal disease is the combination of a renal angiogram and renal vein renin determinations. The renal arteriogram both establishes the presence of a renal arterial lesion and aids in the determination of whether the lesion is due to atherosclerosis or to one of the fibrous or fibromuscular dysplasias. It does not, however, prove that the lesion is responsible for the hypertension, nor does it permit prediction of the chances of surgical cure. It must be noted that (1) renal artery stenosis is a frequent finding by angiography and at postmortem iormotensive individuals, and (2) essential hypertension is a common condition and may occur in combination with renal arterial stenosis that is not responsible for the hypertension. Bilateral renal vein catheterization for measurement of plasma renin activity is therefore used to assess the functional significance of any lesiooted on arteriography. When one kidney is ischemic and the other is normal, all the renin released comes from the involved kidney. In the most straightforward situation, the ischemic kidney has a significantly higher venous plasma renin activity than the normal kidney, by a factor of 1.5 or more. Moreover, the renal venous blood draining the uninvolved kidney exhibits levels similar to those in the inferior vena cava below the entrance of the renal veins.

Renal artery stenosis should be suspected when hypertension develops in a previously normotensive individual over 50 years of age or in the young (under 30 years) with suggestive features: symptoms of vascular insufficiency to other organs, high-pitched epigastric bruit on physical examination, symptoms of hypokalemia secondary to hyperaldosteronism (muscle weakness, tetany, polyuria), and metabolic alkalosis. If renal arterial stenosis is suspected, the best initial screening test is a renal ultrasound, which may reveal unilateral renal hypotrophy (but normal cortical echogenicity). Absence of compensatory hypertrophy in the contralateral kidney should raise the suspicion of bilateral stensosis or superimposed intrinsic (structural) renal disease, most commonly hypertensive or diabetic nephropathy. A positive captopril test, which has a sensitivity and specificity of greater than 95%, constitutes an excellent follow-up procedure to assess the need for more invasive radiographic evaluation. The test relies on the exaggerated increase in plasma renin activity (PRA) after administration of captopril to patients with renovascular hypertension as compared with those with essential hypertension. It is considered positive when all the following criteria are satisfied: stimulated PRA of 12 (ug/L)/h, absolute increase in PRA of 10 (ug/L)/h or more, and increase in PRA of >150% [or 400% if baseline PRA is <3 (ug/L)/h]. Because ACE inhibitors magnify the impairment in renal blood flow and glomerular filtration rate (GFR) caused by functionally significant renal artery stenosis, use of these drugs in association with 99mTc-DTPA or 99mMAG3 renography greatly enhances the predictive value of radionuclide renography (>90% sensitivity and specificity). Magnetic resonance angiography (MRA) has replaced previous modalities as the most sensitive (100%) and specific (95%) test for the diagnosis of renal arterial stenosis. The most definitive diagnostic procedure is bilateral arteriography with repeated bilateral renal vein and systemic renin determinations. If renal vein renin measurements from the two kidneys differ by a factor of 1.5:1 or more (higher value from the affected kidney) in a patient with radiographic unilateral renal artery stenosis, the chance of cure of hypertension by surgical reconstruction or angioplasty is almost 90%, particularly if the renal vein renin level from the unaffected kidney is equal to or less than systemic levels (suppressible). A ratio of less than 1.5:1, however, does not exclude the diagnosis of renovascular hypertension, particularly in the presence of bilateral disease

 

 

 

А – Basic:

1.                Davidson’s Principles and practice of medicine (21^st reviseded.)/by Colledge N.R., Walker B.R., and Ralston S.H., eds.–Churchill Livingstone, 2010.–1376 p.

2.                Harrison’s principles of internal medicine (18^th edition)/by Longo D.L., Kasper D.L., Jameson J.L. et al .(eds.). – McGraw–Hill Professional, 2012. – 4012 p.

3.                The Merck Manual of Diagnosis and Therapy (nineteenth Edition)/Robert Berkow, AndrewJ. Fletcher and others. –published by Merck Research Laboratories, 2011.

4.                Web-sites:

a) http://emedicine.medscape.com/

b )http://meded.ucsd.edu/clinicalmed/introduction.htm

 

B-Additional:

1.                Lawrence M.Tierney,Jr. Et al:Current Medical Diagnosis and treatment 2000, Lange Medical Books, McGraw–Hill,Health Professions Division, 2000.