genitourinary disorders
Evaluation of the Renal Patient
Testing of the Renal Patient
The initial steps in evaluation of renal disorders are: Urinalysis Serum creatinine level Other urine, blood, and imaging tests (eg, ultrasonography, CT, MRI) are done in specific circumstances. Ideally, after the urethral meatus is cleaned, the urine specimen is collected midstream (clean-catch specimen) during the first void of the morning; the urine should be examined immediately because delays can lead to changes in test results. Bladder Catheterization or suprapubic aspiration can be used for collection when urine cannot be obtained by spontaneous voiding or when vaginal material contaminates the urine specimen. However, the trauma of catheterization may falsely increase the number of red blood cells (RBCs) in the specimen, so catheterization is usually avoided if the outcome of interest is microscopic hematuria. A specimen from a catheter collection bag is not acceptable for microscopic or bacteriologic tests. A complete urinalysis includes the following: Inspection for color, appearance, and odor Measurement of pH, specific gravity, protein, glucose, hemoglobin (suggesting RBCs), nitrites, and white blood cell (WBC) esterase by dipstick reagents Microscopic analysis for casts, crystals, and cells (urine sediment) Bilirubin and urobilinogen, although standard parts of many dipstick tests, no longer play significant roles in evaluation of renal or hepatic disorders. is the most obvious of urine attributes, and observation of color is an integral part of urinalysis (see table Causes Of Urine Color Changes ). Urine color may suggest possible causes and help direct additional testing. , often unintentionally noted during visual inspection, conveys useful information only in rare cases of inherited disorders of amino acid metabolism when urine has a distinctive smell (eg, maple syrup in Maple syrup urine disease , sweaty feet in is normally 5.0 to 6.0 (range 4.5 to 8.0). Measuring with a glass pH electrode is recommended when precise values are necessary for decision making, as when diagnosing Renal Tubular Acidosis ; in these cases, a layer of Specific gravityprovides a rough measure of urine concentration (osmolality). Normal range is 1.001 to 1.035; values may be low in older patients or in those with impaired renal function, who are less able to concentrate urine. It is measured by hydrometer or refractometer or estimated with a dipstick. Accuracy of the dipstick test is controversial, but the test may be sufficient for patients who have calculi and are advised to self-monitor urine concentration to maintain dilute urine. Specific gravity by dipstick may be spuriously elevated when urine pH is<6 or low when pH is>7. Hydrometer and refractometer measurements may be elevated by high levels of large molecules (eg, radiopaque contrast agent,albumin, glucose, carbenicillin) in the urine. 500 mg/dL). Moderately increased albuminuria (formerly known as microalbuminuria), an important marker for renal complications in patients with diabetes, is not detected by standard dipsticks, but special microalbumin dipsticks are available. Light-chain proteins (eg, due to multiple myeloma) also are not detected. Significance of Proteinuria depends on total protein excretion rather than protein concentration estimated by dipstick; thus, when proteinuria is detected with dipstick testing, quantitative measures of urinary protein should be done. False-negative results can be caused by dilute urine. False-positive results can be caused by any of the following: High pH (>9) Presence of cells Radiopaque contrast agents Concentrated urine Glucoseusually appears in the urine when serum glucose increases to>180 mg/dL (>10.0 mmol/L) and renal function is normal. Threshold for detection by urine dipstick is 50 mg/dL (2.8 mmol/L). Any amount is abnormal. Falsely low or negative results can result from any of the following: Ascorbic acid Ketones Aspirin Levodopa Tetracycline Very high urine pH Dilute urine Glucose can appear in the urine despite normal plasma glucose levels in Fanconi Syndrome (proximal tubule defect), . Trace blood (corresponding to 3 to 5 RBCs/high-power field [HPF]) is normal under some circumstances (eg, exercise) in some people. Because the test strip reagent reacts with Hb, free Hb (eg, due to intravascular hemolysis) or myoglobin (eg, due to Rhabdomyolysis ) causes a positive result. Hemoglobinuria and myoglobinuria can be distinguished from hematuria by the absence of RBCs on microscopic examination and by the pattern of color change on the test strip. RBCs create a dotted or speckled pattern; free Hb and myoglobin create a uniform color change. Povidone iodine causes false-positive results (uniform coloring); Nitritesare produced when bacteria reduce urinary nitrates derived from amino acid metabolism. Nitrites are not normally present and signify bacteriuria. The test is either positive or negative. False-negative results may occur with any of the following: Infection with certain pathogens that cannot convert nitrate to nitrite (eg,Enterococcus faecalis,Neisseria gonorrhoeae,Mycobacterium tuberculosis) Urine that has not stayed long enough (<4 hours) in the bladder Low urinary excretion of nitrate Enzymes (of certain bacteria) that reduce nitrates to nitrogen High urine urobilinogen level Presence ofascorbic acid Urine pH<6.0 Nitrites are used mainly with WBC esterase testing to monitor patients with recurrent urine infections, particularly children with Vesicoureteral Reflux (VUR) , and sometimes to confirm the diagnosis of uncomplicated urinary tract infection (UTI) in women of childbearing age. is released by lysed neutrophils. Its presence in urine reflects acute inflammation, most commonly due to bacterial infection but sometimes due to Tubulointerstitial Nephritis , Very dilute urine Glycosuria Urobilinogen Use ofphenazopyridine,nitrofurantoin,rifampin, or large amounts of vitamin C WBC esterase is used mainly with nitrite testing to monitor patients with recurrent urine infections and sometimes to diagnose uncomplicated Bacterial Urinary Tract Infections in women of childbearing age. If both tests are negative, the likelihood of a positive urine culture is small. Detection of solid elements (cells, casts, crystals) requires microscopic analysis, ideally done immediately after voiding, and dipstick testing. The specimen is prepared by centrifuging 10 to 15 mL of urine at 1500 to 2500 rpm for 5 minutes. The supernatant is fully decanted; a small amount of urine remains with the residue at the bottom of the centrifuge tube. The residue can be mixed back into solution by gently agitating the tube or tapping the bottom. A single drop is pipetted onto a slide and covered with a coverslip. For routine microscopic analysis, staining is optional. The specimen is examined under reduced light with the low-power objective and under full-intensity light with the high-power objective; the latter is typically used for semiquantitative estimates (eg, 10 to 15 WBCs/high power field [HPF]). Polarized light is used to identify some crystals and lipids in the urine. Phase-contrast microscopy enhances identification of cells and casts. (renal tubular, transitional, squamous cells) frequently are found in urine; most common are squamous cells lining the end of the urethra and contaminants from the vagina. Only renal tubular cells are diagnostically important; however, except when found in casts, they are difficult to distinguish from transitional cells. A few renal tubular cell casts appear in normal urine, but a large number suggests tubular injury (eg, Acute Tubular Necrosis (ATN) , 5/HPF is sometimes normal, eg, after exercise), and any Isolated Hematuria should be interpreted in clinical context. On microscopic analysis, glomerular RBCs are smaller and dysmorphic, with spicules, folding, and blebs; nonglomerular RBCs retain their normal shape and size. 5/HPF may be normal; special staining can distinguish eosinophils from neutrophils (see Other urine tests ). Pyuria is defined as is most characteristic of the Overview of Nephrotic Syndrome ; renal tubular cells absorb filtered lipids, which appear microscopically as oval fat bodies, and cholesterol, which produces a Maltese cross pattern under polarized light. Lipids and cholesterol can also be free floating or incorporated into casts. Crystalsin urine are common and usually clinically insignificant (see table). Crystal formation depends on all of the following: Urine concentration of crystal constituents pH Absence of crystallization inhibitors Drugs are an underrecognized cause of crystals (see table). Castsare made up of glycoprotein of unknown function (Tamm-Horsfall protein) secreted from the thick ascending loop of Henle. Casts are cylindrical and have regular margins. Their presence indicates renal origin, which may be helpful diagnostically. Types of casts differ in constituents and appearance (see table). Other tests are useful in specific instances. Total protein excretioncan be measured in a 24-hour collection or can be estimated by the protein/creatinine ratio, which, in a random urine sample, correlates well with values in g/1.73 m2BSA (body surface area) from a 24-hour collection (eg, 400 mg/dL protein and 100 mg/dL creatinine in a random sample equal 4 g/1.73 m2in a 24-hour collection). The protein/creatinine ratio is less accurate when creatinine excretion is significantly increased (eg, in muscular athletes) or decreased (eg, in cachexia). Moderately increased albuminuria (formerly known as microalbuminuria)isalbuminexcretion persistently between 30 and 300 mg/day (20 to 200 micrograms [mcg]/min); lesser amounts are considered within the range of normal, and amounts>300 mg/day (>200 mcg/min) are considered overt proteinuria (severely increased albuminuria). Use of the urinealbumin/urine creatinine ratio is a reliable and more convenient screening test because it avoids timed urine specimens and correlates well with 24-hour values. A value>30 mg/g (>0.03 mg/mg) suggests moderately increased albuminuria. The reliability of the test is best when a midmorning specimen is used, vigorous exercise is avoided before the test (because vigorous exercise can cause transient dipstick positivity for protein), and unusual creatinine production (in cachectic or very muscular patients) is not present. Moderately increased albuminuria can occur in all of the following: Diabetes Mellitus (DM) None Hypertension None Complications None Preeclampsia and Eclampsia None Introduction to Urinary Tract Infections (UTIs) None Chronic Kidney Disease None Moderately increased albuminuria is an early stage of diabetic kidney disease in both type 1 and 2 diabetes; the progression of renal disease is more predictable in type 1 than 2 disease. moderately increased albuminuria is a risk factor for cardiovascular disorders and early cardiovascular mortality independent of diabetes or hypertension. Sulfosalicylic acid(SSA) test strips can be used to detect protein other thanalbumin(eg, immunoglobulins in multiple myeloma) when dipstick urine tests are negative; urine supernatant mixed with SSA becomes turbid if protein is present. The test is semiquantitative with a scale of 0 (no turbidity) to 4+(flocculent precipitates). Readings are falsely elevated by radiopaque contrast agents. Ketonesspill into urine with ketonemia, but use of test strips to measure urinary ketones is no longer widely recommended because they measure only acetoacetic acid and acetone, not beta-hydroxybutyric acid. Thus, a false-negative result is possible even without an exogenous cause (eg, vitamin C,phenazopyridine,N-acetylcysteine); direct measurement of serum ketones is more accurate. Ketonuria is caused by endocrine and metabolic disorders and does not reflect renal dysfunction. , the total number of solute particles per unit mass (mOsm/kg [mmol/kg]), can be measured directly by osmometer. Normally, osmolality is 50 to 1200 mOsm/kg (or 50 to 1200 mmol/kg). Measurement is most useful for evaluating Hypernatremia , 10 mEq/L [10 mmol/L]) or Acute Tubular Necrosis (ATN) (urine Na where UNais urine Na, PNais plasma Na, PCris plasma creatinine, and UCris urine creatinine. 1% suggests prerenal causes, such as volume depletion; however, acute glomerulonephritis or certain types of Acute Tubular Necrosis (ATN) (eg, Other useful measurements include the following: ) in evaluation of Renal Tubular Acidosis None Chloride (Cl) levels for Diagnosis None Urine anion gap in evaluation of Diagnosis None Potassium (K) levels in determining the cause of Hypokalemia or Levels of sodium, calcium, magnesium, uric acid, oxalate, citrate, and cystine in evaluation of calculi Eosinophils, cells that stain bright red or pink-white with Wright or Hansel staining, most commonly indicate one of the following: Acute tubulointerstitial nephritis None Rapidly Progressive Glomerulonephritis (RPGN) None Acute Prostatitis None Renal Atheroembolism None Cytologyis used for the following: To screen for cancer in high-risk populations (eg, petrochemical workers) To evaluate persistent painless hematuria of unclear etiology after cystoscopy in the absence of glomerular disease (suggested by the absence of dysmorphic RBCs, proteinuria, and renal failure) in patients with irritative voiding symptoms Sensitivity is about 90% for carcinoma in situ; however, sensitivity is considerably lower for low-grade transitional cell carcinomas. Inflammatory or reactive hyperplastic lesions or cytotoxic drugs for carcinoma may produce false-positive results. Accuracy for detecting bladder tumors may be increased by vigorous bladder lavage with a small volume of 0.9% saline solution (50 mL pushed in and then aspirated by syringe through a catheter). Cells collected in the saline are concentrated and examined. with susceptibility testing are indicated when genitourinary tract infections are suspected; a positive result must be interpreted in the clinical context (see Introduction to Urinary Tract Infections (UTIs) [UTIs]). are normally filtered and reabsorbed by the proximal tubules. They may appear in urine when a hereditary or acquired tubular transport defect (eg, Fanconi Syndrome , cystinuria) is present. Measuring type and amount of amino acids may help in the diagnosis of certain types of Blood tests are useful in evaluation of renal disorders. Serum creatininevalues>1.3 mg/dL (>114 micromol/L) in men and>1 mg/dL (>88.4 micromol/L) in women are usually abnormal. Serum creatinine depends on creatinine generation as well as renal creatinine excretion. Because creatinine turnover increases with higher muscle mass, muscular people have higher serum creatinine levels and older and undernourished people have lower levels. Serum creatinine may also be increased in the following conditions: Use of Angiotensin-Converting Enzyme (ACE) Inhibitors and Consumption of large amounts of meat Use of some drugs (cimetidine,trimethoprim,cefoxitin,flucytosine) ACE inhibitors and ARBs reversibly decrease glomerular filtration rate (GFR) and increase serum creatinine because they vasodilate efferent more than afferent glomerular arterioles, mainly in people who are dehydrated or are receiving diuretics. In general, serum creatinine alone is not a good indicator of kidney function. The Cockcroft-Gault formula and the Modification of Diet in Renal Disease (MDRD) formula estimate GFR based on serum creatinine and other parameters and more reliably evaluate kidney function. Bloodureanitrogen (BUN)/creatinine ratiois used to distinguish prerenal from renal or postrenal (obstructive) azotemia; a value>15 is considered abnormal and may occur in prerenal and postrenal azotemia. However, BUN is affected by protein intake and by several nonrenal processes (eg, trauma, infection, gastrointestinal [GI] bleeding, corticosteroid use) and, although suggestive, is generally inconclusive as evidence of renal dysfunction. , a serine proteinase inhibitor that is produced by all nucleated cells and filtered by the kidneys, can also be used to evaluate kidney function. Its plasma concentration is independent of sex, age, and body weight. Testing is not always available, and values are not standardized across laboratories. Measurement of cystatin C is used to confirm Chronic Kidney Disease in specific circumstances when eGFR calculations based on serum creatinine are less accurate and/or when eGFR is 45 to 59 mL/min with no markers of kidney damage present. ]) may increase in Acute Kidney Injury (AKI) and chronic kidney disease. Serum electrolytes should be monitored periodically in patients with renal disorders. may detect anemia in chronic kidney disease or, rarely, polycythemia in Renal Cell Carcinoma or Renin, a proteolytic enzyme, is stored in the juxtaglomerular cells of the kidneys. Renin secretion is stimulated by reduced blood volume and renal blood flow and is inhibited by sodium and water retention. Plasma renin is assayed by measuring renin activity as the amount of angiotensin I generated per hour. Specimens should be drawn from well-hydrated, sodium- and potassium-replete patients. Plasma renin, aldosterone,cortisol, and adrenocorticotropic hormone (ACTH) should be measured in evaluation of all of the following: Addison Disease None Primary Aldosteronism and Renovascular Hypertension None The plasma aldosterone/renin ratio calculated from measurements obtained with the patient in an upright posture is the best screening test for hyperaldosteronism, provided that plasma renin activity is<0.5 ng/mL/h (<0.5 mcg/L/h) and aldosterone is>12 to 15 ng/dL (333 to 416 pmol/L). 