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Hematuria is significant if there are more than three red cells per high-power field It is usually detected incidentally by the urine dipstick examination or clinically following an episode of macroscopic hematuria The diagnosis must be confirmed via microscopic examination, as false-positive dipstick tests can be caused by vitamin C, beets and rhubarb, bacteria, and myoglobin Transient hematuria is common, but in patients under 40 years it is less often of clinical significance Hematuria may be due to renal or extrarenal causes Extrarenal causes are addressed in 23; most worrisome are urologic malignancies Renal causes account for approximately 10% of cases and are best considered anatomically as glomerular or nonglomerular The most common extraglomerular sources include cysts, calculi, interstitial nephritis, and renal neoplasia Glomerular causes include immunoglobulin A (IgA) nephropathy, thin GBM disease, postinfectious glomerulonephritis, membranoproliferative glomerulonephritis, and systemic nephritic syndromes Currently, the United States Health Preventive Services Task Force does not recommend screening for hematuria See 23 for evaluation of hematuria
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The GFR provides a useful index of overall renal function; however, patients with renal disease can actually have a normal or increased GFR The GFR measures the amount of plasma ultrafiltered across the glomerular capillaries and correlates with the ability of the kidneys to filter fluids and various
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substances Daily GFR in normal individuals is variable, with a range of 150 250 L/24 h or 100 120 mL/min/173 m2 of body surface area GFR can be measured indirectly by determining the renal clearance of plasma substances that are not bound to plasma proteins, are freely filterable across the glomerulus, and are neither secreted nor reabsorbed along the renal tubules The formula used to determine the renal clearance of a substance is U V C = ----------P where C is the clearance, U and P are the urine and plasma concentrations of the substance (mg/dL), and V is the urine flow rate (mL/min) Inulin and creatinine clearance are used as markers of GFR Inulin clearance following a continuous infusion is one of the most accurate methods for measurement of GFR The cost and the complexity of the administration and analysis of inulin preclude its routine use In clinical practice, the clearance rate of endogenous creatinine, the creatinine clearance, is the usual means of estimating GFR Creatinine is a product of muscle metabolism produced at a relatively constant rate and cleared by renal excretion It is freely filterable by the glomerulus and not reabsorbed by the renal tubules With stable renal function, creatinine production and excretion are equal; thus, plasma creatinine concentrations remain constant However, it is not a perfect indicator of GFR for the following reasons: (1) A small amount is normally eliminated by tubular secretion, and the fraction secreted progressively increases as GFR declines (overestimating GFR); (2) with severe renal failure, gut microorganisms degrade creatinine; (3) an individual s meat intake and muscle mass affect baseline plasma creatinine levels; (4) commonly used drugs such as aspirin, cimetidine, probenecid, and trimethoprim reduce tubular secretion of creatinine, increasing the plasma creatinine concentration and falsely indicating renal dysfunction; and (5) the accuracy of the measurement necessitates a stable plasma creatinine concentration over a 24-hour period, so that during the development of and recovery from acute renal failure, the creatinine clearance is of questionable value (Table 22 2)
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To measure creatinine clearance, collect a 24-hour urine sample and determine the plasma creatinine level on the same day An incomplete or prolonged urine collection is a common source of error One way of estimating the completeness of the collection is to calculate a 24-hour creatinine excretion; the amount should be constant: Ucr V = 15 20 mg/kg for healthy young women Ucr V = 20 25 mg/kg for healthy young men The creatinine clearance (Ccr) is approximately 100 mL/ min/173 m2 in healthy young women and 120 mL/min/ 173 m2 in healthy young men The Ccr declines by an average of 08 mL/min/yr after age 40 years as part of the aging process, but 35% of subjects in one study had no decline in renal function over 10 years Ccr can be estimated from the formula of Cockcroft and Gault, which incorporates age, sex, and weight to estimate Ccr from plasma creatinine levels without any urinary measurements: (140 Age) Weight (kg) C cr = -------------------------------------------------------P cr 72 For women, the estimated GFR is multiplied by 085 because muscle mass is less This formula overestimates GFR in patients who are obese or edematous and is most accurate when normalized for body surface area of 173 m2 Urea is another index helpful in assessing renal function It is synthesized mainly in the liver and is the end product of protein catabolism Urea is freely filtered by the glomerulus, and about 30 70% is reabsorbed in the nephron Unlike creatinine clearance, which overestimates GFR, urea clearance underestimates GFR Urea reabsorption may be decreased in well-hydrated patients, whereas dehydration causes increased reabsorption, increasing BUN A normal BUN:creatinine ratio is 10:1 With dehydration, the ratio can increase to 20:1 or higher Other causes of increased BUN include increased catabolism (gastrointestinal bleeding, cell lysis, and corticosteroid usage), increased dietary protein, and decreased renal perfusion (congestive heart failure, renal artery stenosis) (Table 22 3) Reduced BUN is seen in liver disease and in the syndrome of inappropriate antidiuretic hormone (SIADH) secretion As patients approach end-stage renal disease (ESRD), a more accurate measure of GFR than creatinine clearance is the average of the creatinine and urea clearances The creati-
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