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The Urinalysis—Inexpensive and Informative Thomas E JOURNAL OF INSURANCE MEDICINE Copyright Q 2004 Journal of Insurance Medicine J Insur Med 2004;36:320±326 BACK TO THE BASICS The UrinalysisÐInexpensive and Informative Thomas E. Murphy, Jr, MD, FACP, FLMI The urinalysis dates back 6000 years. Information has evolved from Address: Jefferson Pilot Financial, tasting it for sugar to computer assisted assessment for the presence One Granite Place, PO Box 515, of cells and casts. The urine gives valuable information about kidney Concord, NH 03302-0515. function in general and the glomeruli in particular. Findings can Correspondent: Thomas E. Murphy, lead to a diagnosis of various medical conditions, most notable be- Jr, MD. ing diabetes mellitus. Proteinuria has many implications, including the presence of systemic disease and the progression of an under- Key words: Urinalysis, proteinuria, lying renal condition. hematuria, casts, creatinine, kidney. Received: June 28, 2004 Accepted: August 6, 2004 he Babylonians were the ®rst to study COLOR urine 6000 years ago. Then Hippocrates T c studied the color and appearance of urine CloudyÐphosphates, urates, and leuko- and was said to use the information to make cytes with bacteria c medical diagnoses and even prognosticate BlackÐmelanin, alkaptonurea, metronida- based on this limited information. Question- zole, methyldopa or carbidopa c 2 able improvement in this prognostication was Brown to Red Ðmyoglobin, blood, free he- made by the ``pisse prophets'' in medieval moglobin, beets, phenothiazines, phenol- times. The 18th and 19th centuries saw the phthalein c dawn of chemical and microscopic analysis. Orange to YellowÐbile pigment c Richard Bright was a strong believer in the GreenÐpseudomonas, elavil (amitrypty- importance of urinalysis, and at one time all line) c kidney disease was referred to as ``Bright's FoamyÐpyridium, proteinuria, conjugated Disease.'' Robert Boyle discovered litmus pa- bilirubin per in 1670 and with it the testing of pH. Mauments described the testing of urine for pH glucose in 1850, but the modern chemistry strips did not appear until 1956.1 The normal pH is 4.5±7.8. An alkaline The ideal specimen is a clean caught, ®rst urine with a pH .7 is indicative of infection voided specimen that is collected midstream with a urea splitting organism, diuretic us- to avoid urethral contamination and exam- age, vomiting, renal tubular acidosis, and re- ined within a matter of hours. The urinalysis spiratory diseases with hyperventilation. contains a large amount of information that An acid urine with a pH ,5 is seen with will be discussed below. acidosis, diarrhea, uncontrolled diabetes mel- 320 MURPHYÐURINALYSIS litus, starvation and dehydration, and respi- are seen in diabetic and alcoholic ketoacidosis ratory diseases with CO2 retention. and in aspirin poisoning. False positive re- sults can be seen with ascorbic acid and from SPECIFIC GRAVITY3 L-DOPA metabolites. The normal speci®c gravity (SG) is 1.008± 1.030, and it declines with advancing age re- PROTEINURIA ¯ecting the decreased ability of the kidney to The normal excretion rate of protein is 150 concentrate the urine. The number and the mg/day. It is made up mostly of Tamm- weight of solutes affect it. By contrast, os- Horsfall mucoprotein, which is produced in molality is determined solely by the number the thick ascending loop of Henle. Low mo- of solutes. As such, glucose and intravenous lecular weight proteins are found in the urine contrast materials raise the speci®c gravity normally, but most are reabsorbed in the much more than the osmolality. Hyposthe- proximal tubule. Only small amounts of al- nuria refers to a SG ,1.007 and is seen in bumin are normally seen in the urine due to diabetes insipidus or ¯uid loading. Isosthe- its charge and molecular weight, both factors nuria is a ®xed SG of 1.010 and is seen fre- inhibiting transport across the glomerular quently in glomerular and tubular disease membrane.6 Excessive protein excretion oc- and especially in renal failure. curs through 4 mechanisms: c Disruption of the capillary wall barrier LEUKOCYTE ESTERASE AND NITRITES4 causing increased ®ltration of various plas- Esterase is released by lysed urine granu- ma proteinsÐnephrotic syndrome locytes. It is usually positive when there are c Tubular damage that inhibits the normal more than 5 leukocytes per high power ®eld. resorptive capacityÐFanconi Syndrome When compared to microscopy the esterase c Over¯ow with excess production of low test has a sensitivity of 80% and a speci®city molecular weight plasma proteinsÐlight of 70% for the presence of infection. chains in multiple myeloma Most bacteria that colonize in the urine c Increased secretion of tissue proteins as- cause nitrates, which are derived from die- sociated with in¯ammationÐpyelonephri- tary metabolites, to be converted to nitrites. tis When both tests are positive, it is highly likely that an infection is present. There are 3 commonly used ways to assess proteinuria: the dipstick, 24-hour urine col- lection, and the protein creatinine ratio (P/ GLUCOSE AND KETONES Cr). The dipstick is useful only if positive, A positive dipstick for glucose generally and then one should proceed with a more ac- occurs when the plasma level exceeds 180 curate measurement of the actual amount of mg/dL. Exceptions are renal glycosuria from protein excreted. It is susceptible to changes a defect in the function of the proximal tubule in the speci®c gravity of the urine, and as and occasionally in pregnancy when the such, is not reliable. threshold is lower. Glycosuria has a speci®c- The 24-hour collection is the gold standard, ity of 98% but a sensitivity of only 17% and but unreasonable for an insurance popula- so is not useful as a screening test for dia- tion. The P/Cr is more convenient and highly betes mellitus.5 False negatives can be found correlated to the 24-hour collection.7 As the in individuals on tetracycline and high dose test assumes an excretion of 1 gm of creati- vitamin C. nine in 24 hours and men frequently excrete Ketones are generally detected with the ni- more and women less, Ginsberg7 in graphic troprusside reaction. They are commonly form showed that the normal range for men seen in fasting and starvation. Large amounts is 17±250 mg/gm, and for women 25±355 321 JOURNAL OF INSURANCE MEDICINE mg/gm. First voided specimens may under- increase in prevalence with advancing age.13 estimate the amount of proteinuria given the The overall prevalence of MA in black males known decrease in excretion seen in the re- is 7.7%, 5.4% in Mexican-Americans, and cumbent position.8 False positive results can 5.7% in non-hispanic, white males. In the be seen in highly alkaline urine and with he- population over 20 years of age without clin- moglobin and vaginal secretions. Neverthe- ical proteinuria, the incidence of MA is 29% less, it is still considered the most ef®cient in those with diabetes mellitus, 16.8% in hy- method of measurement for the insurance pertensives, 15.9% in those with evidence of population. cardiovascular disease, and 3.3% in healthy Proteinuria can present in various forms: adults. Older age, minority race, diabetes, hyper- c Transient tension, abnormal serum creatinine, and left c Functional ventricular hypertrophy were all indepen- c Orthostatic dently associated with the presence of albu- c Disease related, which can be nephrotic or minuria after adjusting for other variables. non-nephrotic Depending on the methodology (units) used Functional proteinuria is seen in dehydra- by the lab, microalbuminuria is de®ned as 3± tion, emotional stress, fever, heat injury, in- 30 mg/dL, 30±300 mg/24-hour, 30±300 mg/ ¯ammatory processes, intense activity, and gm creatinine, 30±300 mcg/mg creatinine, or acute illnesses, mostly because of increased 0.03±0.3 gm/gm creatinine. cardiac output seen in these states. Microalbuminuria is associated with dis- Orthostatic proteinuria is de®ned as signif- turbances in glucose metabolism,14 insulin re- icant proteinuria that appears during the day sistance,15 and a more adverse pattern of car- but is not present in a ®rst voided specimen. diovascular risk factors.16 There are several It is seen in 3%±5% of the healthy young theories as to the mechanism of vascular dis- adult population. It usually is seen in indi- ease associated with MA. Pedrinelle and col- viduals ,35 years old, with excretion of less leagues17 have proposed that the glomerular than 1 gm but occasionally up to 3 gm, and albumin leak re¯ects widespread atheroscle- always with normal urine sediment. It is a rosis-mediated damage to the capillary net- benign condition.9 work. Festa et al18 have shown an association In disease-related proteinuria the degree of of the level of C-reactive protein and ®brin- proteinuria correlates with the progression of ogen with the presence of MA in both type nephrotic syndrome or renal insuf®ciency.10,11 2 diabetic and nondiabetic individuals. They Mild proteinuria, if stable for ``several years,'' feel this is evidence of chronic in¯ammation may not portend a more serious condition. as a potential mediator between MA and ma- However, if it exceeds 1 gm per 24 hours, crovascular disease. In a similar vein, Paisley there is a much greater likelihood that a sig- et al19 provided evidence of an abnormality ni®cant glomerular lesion exists that can be in nitric oxide (NO)-dependent macrovascu- de®ned by biopsy. lar endothelial function remote from the kid- Nevertheless, random screening for pro- ney and of low-grade chronic in¯ammation teinuria in the general population is not cost that was associated with microvascular en- effective, unless it is selectively directed to dothelial dysfunction in patients with pro- high-risk groups such as the elderly and teinuria.
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