Generalist's Guide to Diagnostic Tests

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[edit] Generalist's Guide to Diagnostic Tests

James A. Delmez

David W. Windus

[edit] GLOMERULAR FILTRATION RATE

Although the kidney regulates a complex array of physiologic functions, the general health of the kidney is currently assessed with estimates of glomerular filtration and the urinalysis.Loss of glomerular filtration roughly correlates with histologic changes resulting from a variety of kidney diseases.Plasma creatinine concentration and creatinine clearance are clinically useful means of estimating the true glomerular filtration rate (GFR).Optimal use of these clinical tools requires knowledge of factors affecting metabolism and the renal excretion of creatinine.Additional structural and functional information about the kidney can be obtained with imaging tests and the kidney biopsy.

[edit] Concepts

The concept of plasma clearance by the kidneys, developed in the 1920s, refers to the volume of plasma freed of a substance by renal activity per unit time (usually 1 minute).Depending on the substance studied, the renal clearance may be achieved by glomerular filtration, net tubular secretion, or a combination of the two.For clinical purposes, the focus of interest is the volume of plasma cleared per minute of a substance solely by the process of glomerular filtration.If a substance is freely filtered by glomeruli and not subsequently altered by tubular reabsorption or tubular secretion, its plasma clearance represents the GFR.Accurate measurement of GFR is probably the most critical index of renal function.Unfortunately, it is also one of the most difficult.

[edit] Measurements

A number of substances fulfill the criteria as accurate markers of GFR.These include inulin,¹²⁵I-iothalamate, and^99mTc-diethylenetriamine penta-acetic acid (DTPA).The disadvantages of these are that they must be administered exogenously as an intravenous bolus, usually followed by a constant infusion to maintain steady-state plasma levels.During the infusion, four urine collections are obtained over 30-minute intervals to calculate the GFR.These are costly and labor-intensive tests whose use is usually restricted to research protocols at major medical centers.

[edit] Estimations

The endogenous substance used most commonly in the clinical assessment of GFR is creatinine.Creatinine is a waste product derived from the spontaneous degradation of creatine and creatine phosphate.The production and renal excretion of creatinine are constant and proportional to muscle mass.Accordingly, muscular athletes and men produce more creatinine than women, children, and elderly people.Wide-spread acute necrosis of skeletal muscle from any cause will also increase the production rate of creatinine.

Creatinine is freely filtered by the glomerulus but also enters the urine through secretion by the proximal tubule.The component resulting from this secretion causes the GFR to be overestimated.In patients with a normal GFR, the overestimation is only 5% to 10%.As renal function deteriorates, the contribution of creatinine secretion to creatinine clearance assumes a major role.In some subjects with renal insufficiency, the creatinine clearance may exceed the GFR by 70%.Unfortunately, the magnitude of the tubular secretion of creatinine varies from patient to patient and even within a given patient at different times.Another potential problem in assessing creatinine clearances is the use of drugs that interfere with its tubular secretion.Cimetidine and trimethoprim commonly increase serum creatinine levels and decrease creatinine clearance without affecting the GFR.

Despite its limitations, the creatinine clearance is the simplest and standard method for the evaluation of renal function.Nonetheless, it is critical that the urine sample becollected in a complete and precisely timed fashion.The patient should be instructed to void on awakening and discard the urine sample.All subsequent urine should be collected in the next 24 hours.The collection ends when the bladder is emptied at exactly 24 hours, and the final urine specimen is included in the collection.The normal daily creatinine excretion is 18 to 21 mg/kg for men and 15 to 18 mg/kg for women.Values below these may represent an inadequate urine collection, except in individuals with either decreased muscle mass or advanced renal insufficiency.The urine container should be refrigerated during this period to avoid overgrowth of bacteria, which may promote the conversion of creatinine to creatine and therefore spuriously lower the creatinine clearance.The patient's serum may be analyzed for the concentration of creatinine at either the start or the end of urine collection.The formula for creatinine clearance is shown in Box 144-1.The results should be expressed per 1.73 m²(body surface area).The normal ranges depend on the chemical assay used for creatinine.In general, they are:

Women 75 to 115 ml/min/1.73 m²

Men 85 to 125 ml/min/1.73 m²

Measurement of the serum creatinine level is probably the first and easiest test in estimating renal function.The wide range of normal values (usually 0.6 to 1.4 mg/dl) reflects differences in muscle mass from subject to subject.The “rule of thumb” is that for every doubling of serum creatinine values, the GFR decreases by 50%.Thus a healthy but frail subject may have a baseline serum creatinine level of 0.6 mg/dl.If half the renal function is then lost, the corresponding serum creatinine concentration would be only 1.2 mg/dl, still within the normal range (Fig.144-1, solid line).In this example, a further rise to 2.4 mg/dl would represent loss of 75% of renal function.In contrast, the dashed line shows this relationship in a subject with a baseline serum creatinine level of 1.0 mg/dl.Loss of half the renal function results in a serum creatinine value of 2.0 mg/dl, which is outside the normal range.Because of enhanced tubular secretion of creatinine and increased extrarenal metabolism of creatinine with renal failure, the rule of thumb may greatly underestimate the decline in GFR.If there is any question of a possible impairment of renal function despite a normal serum creatinine level, a creatinine clearance should be done.Although creatinine levels are not as affected by protein intake as urea values, a meal with meat (containing creatinine) increases serum creatinine levels by as much as 0.4 mg/dl for up to 10 to 12 hours.To avoid misinterpretation of changes in serum creatinine levels, the clinician should measure values after an overnight fast.Another potential source of error in interpreting creatinine values is the presence of substances in the serum that falsely elevate the values.These include acetoacetate (ketoacidosis) and some cephalosporins (e.g., cephalothin, cefazolin, cefoxitin, cefamandole).

Figure 144-1 Relationship between serum creatine level and creatine clearance in two patients with different baseline values for serum creatine.

Approximately 1 ml/min of GFR is lost per year after the age of 30.Yet the serum creatinine value does not increase with age.This is due to the decreased muscle mass accompanying aging.Thus perceived minor abnormalities in the serum creatinine level in the elderly may represent severe impairment of renal function.

Various nomograms that attempt to estimate creatinine clearance from serum levels of creatinine have been published.The most accepted formulas are those of Cockcroft and Gault, which incorporate the variables of age, gender, and weight (Box 144-2).

In the equations in Box 144-2, age is in years, weight is in kilograms, and creatinine levels are in milligrams per deciliter.There are a number of limitations to these equations.They overestimate creatinine clearance if the subject is obese or edematous.Also, the patient must have relatively stable renal function.Thus these formulas should not be used for a patient experiencing acute renal failure.

The measurement of serum urea as an index of renal function has largely been supplanted by the measurement ofcreatinine because urea levels are more affected by the intake of protein in the diet.In addition, urea levels may rise with gastrointestinal bleeding, accelerated protein catabolism, and glucocorticoid therapy.Nonetheless, many nephrologists feel that urea levels correlate better than creatinine with uremic symptoms, so they monitor both values.

The clinician should know the GFR in patients with severe renal failure.This allows for the orderly planning of transplantation or dialysis.As previously discussed, creatinine clearance may cause the GFR to be greatly overestimated in this situation.The average of simultaneous creatinine and urea clearances provides a more accurate estimate of renal function when the GFR is less than 30 ml/min.Both substances are freely filtered.Creatinine, however, is secreted, whereas urea is reabsorbed by the tubules.These two events tend to offset each other, and the average is fairly accurate.

Occasionally, it is important to determine whether the function of one kidney is significantly different from the function of the other.This issue is usually raised when the consequences of a surgical nephrectomy are being weighed.A renal scan is the test of choice, but there is no agreement concerning the best radiopharmaceutical agent.^99mTc-DTPA,^99mTc-glucoheptonate (GHA), and^99mTc-dimercaptosuccinic acid (DMSA) are widely used.The general procedure is to inject the agent by vein and compare the radioactivity of the two kidneys within the first 3 minutes of the scan.

[edit] MEASUREMENTS OF URINE PROTEINS

Plasma proteins are prevented from entering the urine because of the permselectivity and negative charge of the glomerulus.In addition, much of the protein traversing the glomerulus into the urine space is reabsorbed by the renal tubules.Thus the kidneys normally excrete less than 150 mg/day of protein.Approximately 60% is derived from plasma, with the remainder produced by the kidneys and lower urinary tract.The measurement of urine proteins is often helpful in determining the presence, severity, and prognosis of renal diseases.In addition, a decline in proteinuria may indicate a response to therapy.

The urine dipstick is the simplest and most common way to measure urine proteins.It is fairly sensitive to the presence of negatively charged proteins such as albumin.However, it is insensitive to positively charged proteins such as some immunoglobulin light chains.The lower limit of detection by the standard dipstick is 10 to 20 mg/dl.Assuming a 24-hour urine output of 2 L/day, the dipsticks may not detect proteinuria of up to 200 to 400 mg/day.The dipstick should always be positive for protein in the case of nephrotic-range proteinuria (>3.5 g/day) and no paraproteinuria.Because the dipstick measures only the concentration of proteins in the urine, it is not a useful quantitative test of proteinuria.

The gold standard for quantifying proteinuria is the measurement of a 24-hour urine collection performed in the same manner as a creatinine clearance.The interpretation of proteinuria should always be in the context of renal function.As renal function deteriorates, there is decreased delivery of protein available for filtration, and proteinuria often declines with moderate to severe renal failure.A very low serum albumin level may also cause a decline in proteinuria by similar mechanisms.

An alternative to collecting a 24-hour urine for protein determination is a spot urine test measuring the protein/creatinine ratio.In the presence of stable renal function a protein/creatinine ratio of more than 3.5 (mg/mg) indicates nephrotic-range proteinuria, whereas a ratio of less than 0.2 is within normal limits.The best correlation is found when samples are collected after the first morning void and at bedtime.The estimation of proteinuria by this method should be reserved for those in whom a 24-hour urine sample is not possible or when multiple tests of proteinuria are obtained to monitor treatment.

[edit] Nephrotic-range Proteinuria

Nephrotic-range proteinuria is defined as a urine protein excretion of more than 3.5 g/day.When it is present, there is usually a defect in the permselectivity and/or negative charge of the glomeruli (see Chapter 148 for further discussion).Most of the protein in nephrotic-range proteinuria is albumin.Determining the individual types of urine protein in adults with this condition is of little value in the absence of multiple myeloma.

[edit] Non–Nephrotic Range Proteinuria

Non–nephrotic range proteinuria is defined as a urine protein excretion between 150 mg and 3.5 g/day.Proteinuria within this range renders little information about the etiology of the defect.However, urine protein excretion of less than 2 g/day suggests a tubulointerstitial disease characteristically seen in cystic diseases of the kidney, interstitial nephritis (including pyelonephritis), hypertensive nephrosclerosis, and toxic nephropathies.

[edit] Microalbuminuria

Microalbuminuria is defined as an elevated rate of urinary albumin excretion, with a daily total protein excretion rate of less than 150 mg.A timed specimen or a 24-hour urine collection is used to assess albumin excretion rates.The upper limit of albumin excretion usually ranges between 15 and 30 μg/min depending on the laboratory.A dipstick test is also available for testing for microalbuminuria; it can detect concentrations as low as 2 mg/dl.These tests are used primarily to determine which patients with diabetes are at risk of developing overt diabetic nephropathy (see Chapter 96 ).

[edit] Paraproteinuria

The normal excretion of immunoglobulin light chains is 1 to 7 mg/day.An increased amount of light chains in the urine is always due to overproduction and warrants a search for a lymphoproliferative disorder.Immunofixation electrophoresisis the most sensitive test for detecting and classifying urinary paraproteins.

[edit] URINALYSIS

A careful examination of the urine often provides useful information about diseases of the urinary tract as well as metabolic or systemic diseases not directly related to the kidney.Like all laboratory procedures, the tests should be carefully performed in a standardized fashion.For chemical (dipstick) and microscopic examination, a clean-catch, midstream urine collection is optimal.Urine is a hazardous material and should be handled while wearing gloves.The urine should be visually assessed for color and clarity.The “unspun” urine should then be subjected to a dipstick analysis performed according to the manufacturer's specifications.A sample of the urine (10 to 15 ml) should then be centrifuged in a capped urine tube for 5 minutes at 450 g.The supernatant is poured out and the bottom pellet resuspended by gentle suction pipetting.Cellular elements begin to break down within 2 hours at room temperature.Microscopic examination using a high-power lens should therefore be done promptly.It is important to identify the type and number of cells and casts per high-power field (HPF, ×400) as well as the presence of microorganisms and crystals.Cells may originate from any tissue in the urinary system.Casts are formed only in the renal tubules because of the gelation of Tamm-Horsfall glycoprotein and are most easily seen at the edge of the coverslip.The type of cast refers to the material (cells, fat, filtered proteins) trapped within the cast at the time of formation.The presence of casts of any type strongly suggests significant renal disease.For example, if fatty inclusions are found within a hyaline cast (Fig.144-2), it is likely that the patient has nephrotic syndrome.Epithelial cell casts (Fig.144-3) comprise desquamated renal tubular cells embedded in a protein matrix; their presence suggests an active renal process such as glomerulonephritis or interstitial nephritis.Cellular casts may degenerate into granular casts (Fig.144-4) wherein the outlines of the cells are lost.Brown, muddy granular casts (Fig.144-5) suggest the presence of acute tubular necrosis.

Figure 144-2 Hyaline cast with fatty inclusions.This microscopic finding suggests the presence of the nephrotic syndrome.(×400.) (From Piccoli G, Varese D, Rotunno M:Atlas of urinary sediments: Diagnosis and clinical correlations in nephrology, New York, 1984, Raven.)

Figure 144-3 Epithelial cell cast.(×400.) (From Piccoli G, Varese D, Rotunno M:Atlas of urinary sediments: Diagnosis and clinical correlations in nephrology, New York, 1984, Raven.)

Figure 144-4 Granular cast.(×400.) (From Piccoli G, Varese D, Rotunno M:Atlas of urinary sediments: Diagnosis and clinical correlations in nephrology, New York, 1984, Raven.)

Figure 144-5 Brown, muddy granular cast (×160.) (Courtesy Steve Miller, MD.)

[edit] Hematuria

Gross hematuria is the most frequent cause of an alteration in the color of urine.The color may range from pink to black.The lower the pH and the longer the hemoglobin is in contact with the urine, the darker the color.Hemoglobinuria and myoglobinuria also may cause red-tinged urine.The presence of hemoglobin turns the urine dipstick blue or green in two different patterns.Speckled activity indicates intact erythrocytes whereas a uniform pattern signifies free hemoglobin.Free hemoglobin in the urine is usually the result of the lysis of erythrocytes in the urine as a result of a high pH or a lowspecific gravity.The dipstick also detects urine myoglobin.The normal spun urine contains less than one erythrocyte per HPF.The presence of more than three per HPF suggests bleeding anywhere along the urinary tract.It has been suggested that erythrocytes of glomerular origin have a more distorted (dysmorphic) appearance than those arising elsewhere, but this is controversial.The finding of an erythrocyte cast (Fig.144-6), however, almost always suggests that the hematuria is due to glomerulonephritis or vasculitis (see Chapter 148 ).The urine is often contaminated with blood during menses, so urinalysis should preferably be postponed to avoid menstrual blood.

Figure 144-6 Red cast, which strongly suggests a glomerulonephritis or vasculitis.(×160.) (From Piccoli G, Varese D, Rotunno M:Atlas of urinary sediments: Diagnosis and clinical correlations in nephrology, New York, 1984, Raven.)

[edit] Pyuria and Bacteriuria

The dipstick measures the esterase enzyme of neutrophils and correlates well with the number of these cells in the urine.The presence of cephalexin or cephalothin or high concentrations of oxalic acid may decrease the test result.The most common contamination is vaginal discharge.Overall, however, false-positive and false-negative results are quite low.A positive nitrite test by dipstick indicates the presence of bacteria that reduce urinary nitrate to nitrite.Most Enterobacteriaceae (90%) convert nitrate to nitrite, but some bacteria (e.g., enterococci) cannot.In addition, because it takes up to 4 hours for the conversion to nitrate in the bladder, a sample from the first voiding of the morning is preferable.Thus a positive nitrite test by dipstick, especially when accompanied by pyuria, is very suggestive of a urinary tract infection.A negative test, however, does not rule out the diagnosis.

The normal number of leukocytes is probably less than one per HPF.When present in greater numbers, there is probably inflammation somewhere in the urinary system.If leukocytes are found in casts (Fig.144-7), the inflammation is in the renal parenchyma.Leukocyte casts can be differentiated from epithelial cell casts by the lobulation of the nuclei.Most leukocytes in the urine are neutrophils; however, in certain conditions, such as allergic interstitial nephritis, pyelonephritis, vasculitis, and atheroemboli to the kidneys, the cells may be eosinophils.A Hansel's or Wright's stain (see Chapter 148 ) of the sediment should be performed if pyuria is present and one of these diagnoses is being considered.Bacteria are often seen with unstained urine specimens in the presence of infection.In women, the presence of squamous epithelial cells, which are large, are flat, and have a small central nucleus (Fig.144-8), suggests vaginal contamination.Transitional epithelial cells (Fig.144-9) lining the bladder and ureter are smaller, with a relatively larger nucleus.These may be normally present or may represent some form of irritation of the urinary tract.

Figure 144-7 Granulocyte cast, which indicates inflammation within the renal parenchyma (×400.) (From Piccoli G, Varese D, Rotunno M:Atlas of urinary sediments: Diagnosis and clinical correlations in nephrology, New York, 1984, Raven.)

Figure 144-8 Vaginal squamous cells, which indicate that the urine sample was not collected properly and the diagnosis of urinary tract infection cannot be made with certainty.(×100.) (From Piccoli G, Varese D, Rotunno M:Atlas of urinary sediments: Diagnosis and clinical correlations in nephrology, New York, 1984, Raven.)

Figure 144-9 Transitional epithelial cells.(×400.) (From Piccoli G, Varese D, Rotunno M:Atlas of urinary sediments: Diagnosis and clinical correlations in nephrology, New York, 1984, Raven.)

[edit] Glycosuria

Glucose does not usually appear in the urine until the serum glucose levels exceed 180 to 200 mg/dl.Thus diabetes is by far the most common cause of glycosuria.In pregnancy, however, glycosuria with normal glucose levels is common.In addition, disorders that disrupt the proximal tubules' reabsorption of glucose may lead to glycosuria.These include lead poisoning, myeloma, galactosemia, and cystinosis.Finally, glycosuria may occur as part of a more generalized disorder of tubular transport.With Fanconi's syndrome, there is also impaired reabsorption of sodium, amino acids, bicarbonate, phosphate, and water.The assay for glucose varies according to the manufacturer, but most can detect a urine glucose concentration of 100 mg/dl.

[edit] Crystalluria

A wide variety of crystals may be seen in the urine.However, only the crystals of cystine (Fig.144-10), leucine, tyrosine,and cholesterol have pathologic significance.In patients whose kidneys form stones repeatedly, urinary crystals may assist in predicting the type of stone being produced (see Chapter 147 ).This is particularly true with ammoniomagnesium phosphate crystals (coffin-lid shaped), whose presence suggests struvite stones made by urease-producing bacteria such as Proteus(Fig.144-11).

Figure 144-10 Hexagonal cystine crystals, which indicate cystinuria.(×400.) (From Piccoli G, Varese D, Rotunno M:Atlas of urinary sediments: Diagnosis and clinical correlations in nephrology, New York, 1984, Raven.)

Figure 144-11 Magnesium ammonium phosphate crystals with their typical “coffin-lid” appearance.(×400.) (From Piccoli G, Varese D, Rotunno M:Atlas of urinary sediments: Diagnosis and clinical correlations in nephrology, New York, 1984, Raven.)

[edit] Measurement of Urine Acidity

The dipstick measures the urine pH, usually within the range of 5 to 8.5.A urine pH greater than 6.5 indicates bicarbonaturia or ammonium production resulting from urease-producing organisms.A urine pH less than 5.5 indicates an absence of bicarbonate in the urine.At times, urine pH determination assists in the evaluation of acid-base disorders (see Chapter 145 ) and renal stone diseases (see Chapter 147 ).

[edit] Urinary Concentrating Ability

The volume and concentration of the urine reflect the renal adaptation for maintaining normal water and solute balance.A urine specific gravity of 1.010 corresponds to an osmolality of about 285 mOsm/L (i.e., the same osmolality as that normally measured in plasma).For this reason, urine with an osmolality of around 1.010 is referred to as isosthenuric. Adults with a normal diet generally have a urine specificgravity of 1.016 to 1.022.The urine specific gravity after a 12-hour overnight fast should be 1.022.If the diagnosis of central or nephrogenic diabetes insipidus is being considered, more sophisticated tests of urine and plasma osmolality may be necessary (see Chapter 99 ).

[edit] IMAGING STUDIES

[edit] Renal Ultrasonography with Doppler Echography

In some institutions, ultrasound (US) has supplanted an intravenous pyelogram (IVP) as the most common imaging test for evaluating urologic structures.The advantages of US over IVP are that it requires no intravenous injection of contrast and does not expose the patient to radiation.The size of the kidneys is easily determined by US.The normal length varies according to body size and age, with the right kidney ranging between 8 and 14 cm and the left between 7.5 and 12.5 cm.A US image of a normal kidney is shown in Fig.144-12.Large kidneys are associated with poorly controlled diabetes, acromegaly, acute glomerulonephritis, and infiltrative processes such as amyloidosis, leukemia, and lymphoma.The presence of small kidneys suggests that there has been irreversible renal damage, and further evaluation may not be warranted.Increased echogenicity of the renal cortex relative to that of the liver is an abnormal but nonspecific finding.Doppler flow studies can often detect patency and the direction of flow of the main renal arteries and veins.Doppler studies may also be useful in the evaluation of renal artery stenosis.

Figure 144-12 Ultrasound of a normal kidney.

Unlike some other imaging tests (i.e., IVP), US relies exclusively on structural changes such as dilated calyces (Fig.144-13) to detect obstructive uropathy.Hydronephrosis is diagnosed with a sensitivity rate of 98% to 100% and a specificity rate of 90% to 93%.Causes for false-positive and false-negative results are listed in Box 144-3.

Figure 144-13 An ultrasound of an obstructed kidney with dilated calyces.

Renal US is also the first-line test in evaluating inherited and acquired cysts of the kidneys.With established autosomal dominant polycystic kidney disease, the renal size is large because of the multiple cysts destroying the normal renal parenchyma.The early diagnosis of autosomal dominant polycystic kidney disease may be missed before the age of 30 years because the cysts may be too small to detect.Benign cortical cysts (Fig.144-14) are the most commonly encountered renal masses.Cysts must meet four criteria to be considered benign (Box 144-4).If these criteria are fulfilled, the accuracy of diagnosis of a benign cyst is greater than 95%, and no further workup is warranted.Cysts that do not meet the criteria have a 37% chance of being a neoplasm and must be further evaluated, often by computed tomography (CT).Suggested criteria for the CT diagnosis of a simple cyst include a homogeneous attenuation value of mean water density, no enhancement with intravenous contrast, no measurable thickness of the cyst wall, and smooth interface with renal parenchyma.The probability of a correct diagnosis with CT is quite high.Therefore, if these criteria are not met, many centers do no further testing (i.e., percutaneous cyst puncture and angiogram) but proceed with a surgical exploration.Structures that are poorly evaluated by US include solid renal masses and nondilated ureters.

Figure 144-14 An ultrasound of a kidney with simple cysts.

[edit] Intravenous Pyelography

An IVP may be helpful in evaluating the location of the obstruction in a patient passing a renal stone.For routine imaging of a renal stone, a plain film of the abdomen is often satisfactory, since 85% of stones are radiopaque.It is controversial whether US or IVP should be chosen for the initial renal imaging evaluation of persistent, isolated hematuria.

An IVP requires the administration of intravenous contrast.This may lead to idiosyncratic reactions ranging from mild urticaria (up to 10%) to severe anaphylaxis (1:3000 to 1:4500).Up to 10% of patients also report nausea and a transient sensation of warmth.Acute renal failure may result from contrast with preexisting impaired renal function, with volume depletion, or after multiple contrast studies.The nonionic contrast agents may decrease the incidence of adverse events.

[edit] Computed Tomography and Magnetic Resonance Imaging

If a solid renal mass has been suggested by prior US or IVP, a CT scan should be considered.US detects only 26% of CT-proven solid lesions smaller than 1 cm in diameter.Some 85% of lesions 3 cm or larger are detected.The overall accuracy of CT is 95% to 99% for solid renal masses.This is higher than that of magnetic resonance imaging (MRI).However, with the addition of Gd-DTPA for contrast-enhanced MRI, the accuracy is similar to that of CT.MRI is of little value in evaluating renal stones.

[edit] Renal Scans

Renal scans may be of some value in evaluating renovascular disease, in determining whether mild obstruction is physiologically significant (see Chapter 147 ), or in assessing the leakage of urine from the urinary system.They, however, provide little structural information about the kidneys that cannot be obtained by US.They also provide little valuable information about renal function except when there are marked differences between the two kidneys.

[edit] RENAL BIOPSY

Percutaneous renal biopsies are routinely performed on patients with renal diseases.Biopsies have greatly increased knowledge of the classification, prognosis, epidemiology, and treatment of a variety of renal disorders.An experienced nephrologist or radiologist should perform the renal biopsy.The usual procedure is to have the patient lie prone and to localize the lower pole of either kidney with the assistance of US.After the establishment of a sterile field and the administration of local anesthesia, several cores of renal cortex may be obtained via a variety of biopsy needles.Thespecimens are then analyzed by light, immunofluorescence, and electron microscopy.

The decision to proceed with a renal biopsy is made after considering the impact of the results on further management of the patient balanced against the risks.Common indications are the nephrotic syndrome and unexplained renal failure (see Chapter 148 ).The renal biopsy provides information concerning the type of primary glomerular disease, as well as its severity and degree of irreversible scarring.In addition, a renal biopsy sometimes aids in the diagnosis or management of a systemic disease such as amyloidosis, systemic lupus erythematosus, or vasculitis.The information gained from renal imaging studies and biopsies is summarized in Box 144-5.

The main risk of a renal biopsy is hemorrhage.Although almost 90% of patients have evidence of perirenal hemorrhage as shown on CT, less than 5% require a transfusion.Severe renal hemorrhage is usually successfully treated by selective embolization of the involved vessels.Less than 1% of patients require an emergency nephrectomy.Some patients complain of pain at the site of the biopsy, but this usually resolves within 1 week.Gross hematuria may be observed in about 5% of patients, but this too usually resolves without specific treatment.An open (surgical) renal biopsy is considerably more invasive than a closed (percutaneous) renal biopsy.It should never be considered when a percutaneous biopsy is possible.

The major contraindication to renal biopsy is a coagulopathy.The criteria for exclusion vary but generally involve patients with a platelet count below 100,000 cells/mm³, an elevated prothrombin time or partial thromboplastin time, and a history of ingesting aspirin within the previous week.Relative contraindications include a solitary kidney, an active urinary tract infection, uncontrolled hypertension, and an uncooperative patient.

[edit] ADDITIONAL READINGS

• JM Ginsberg, BS Change, RA Matarese,et al.: Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med 1983; 309:1543 - 1546.
• LB Hilbrands, MA Artz, JFM Wetzels,et al.: Cimetidine improves the reliability of creatinine as a marker of glomerular filtration. Kidney Int 1991; 40:1171 - 1176.
• AJ King, AS Levey: Dietary protein and renal function. J Am Soc Nephrol 1993; 3:1723 - 1737.
• H Kohler, E Wandel, B Brunck: Acanthocyturia: a characteristic marker for glomerular bleeding. Kidney Int 1991; 40:115 - 120.
• AS Levey: Measurement of renal function in chronic renal disease. Kidney Int 1990; 38:167 - 184.
• W MacKenzie, HH Drew, ND LaFrance: Creatinine measurements often yield false estimates of progression in chronic renal failure. Kidney Int 1988; 34:412 - 418.
• CR NolanIII, MS Anger, SP Keheller: Eosinophiluria: a new method of detection and definition of the clinical spectrum. N Engl J Med 1986; 315:1516 - 1519.
• O'Reilly PH George NJR Weiss RM Diagnostic techniques in urology. Philadelphia: WB Saunders; 1996:
• G Piccoli, D Varese, M Rotunno: Atlas of urinary sediments: diagnosis and clinical correlations in nephrology New York: Raven; 1984:
• R Roubenoff, H Drew, M Moyer,et al.: Oral cimetidine improves the accuracy and precision of creatinine clearance in lupus nephritis. Ann Intern Med 1990; 113:501 - 506.
• O Shemesh, H Golbetz, JP Kriss,et al.: Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28:830 - 838.