Proteinuria

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The kidneys normally excrete a small amount of protein daily, usually glycoproteins. Only very small amounts of globulins, light-chain proteins, or albumin are released. Functional proteinuria may result from physiologic changes in glomerular filtration, as occurs with exercise (Venkat, 2004). However, consistent albuminuria implies glomerular or tubular dysfunction.

The urine dipstick is the most convenient measurement, but a more accurate test is the Upr/UCr ratio, obtained by dividing the random urine sample protein level by the urine creatinine level (both in mg/dL). This ratio has proven correlation with 24-hour excretion rates (Ginsberg et al., 1983). Thus, random urine samples are the best way to identify and follow proteinuria, and 24-hour collections are usually not needed (Levey et al., 2003) (Table 40-3). However, results from those with low or high levels of muscle mass may not correlate as well with 24-hour measurements (Venkat, 2004).

Proteinuria in Adults

Proteinuria is a marker of kidney disease in adults and may actually contribute to renal impairment. Patients with diabetes should be periodically tested for microalbuminuria. Others at risk for kidney disease, such as patients with hypertension, should also be tested.

Table 40-3 Proteinuria Values

Test

Protein Value

Dipstick

>1+ if urine specific gravity <1.015 or >2+ if urine specific gravity >1.015

>0.5 (age 6 mo to 2 yr) >0.25 (>2 yr) Adults: >0.2

30-300 mg/24 hr—microalbuminuria

>300 mg/24 hr—albuminuria

>3.5 g/24 hr—nephritic-range proteinuria

*Urine protein/creatinine ratio.

Adults with proteinuria need their UPr/Ucr determined. Those with values outside the normal range should undergo an evaluation for CKD (see later). Patients with dipstick proteinuria but normal-range UPr/UCr values should be rechecked at periodic follow-up (Fig. 40-7).

Proteinuria in Children and Adolescents

Most proteinuria in children is transient when followed up with weekly urine sample testing. Persistent proteinuria found in at least two of three weekly urine samples warrants further evaluation to identify those children who may have chronic renal disease.

Proteinuria in children may be classified as functional, isolated, or symptomatic. Functional proteinuria may occur with fever or exercise. Isolated proteinuria is defined by the absence of abnormal history, physical examination findings, symptoms, or other urinary abnormalities. The most common cause of this form is benign orthostatic proteinuria, defined by normal protein excretion overnight or in the supine position. The initial evaluation for isolated proteinuria involves obtaining a first-morning urine sample for protein and cre-atinine as well as a formal urinalysis for microscopy review (Hogg et al., 2000). The absence of morning proteinuria, as evidenced by normal UPr/UCr, supports the diagnosis of benign orthostatic proteinuria. A more accurate assessment is a split 24-hour urine collection for protein. Benign ortho-static proteinuria may be transient or fixed and in either case has an excellent prognosis (Springberg et al., 1982). In contrast, nonorthostatic isolated proteinuria with a duration of 1 year or longer may represent significant renal pathology (Trachtman et al., 1994). Thus, these patients need yearly or twice-yearly clinical follow-up with assessment of blood pressure, renal function, serum albumin, urine microscopy, and urine protein.

Pathologic proteinuria, whether isolated or symptomatic, occurs in the setting of a variety of glomerular and tubuloin-terstitial diseases (Box 40-5). Some children may present with the nephrotic syndrome (proteinuria, hypoalbuminemia, edema). Depending on the degree of proteinuria and the results of the initial laboratory evaluation, a renal biopsy may be indicated (Fig. 40-8).

>1 +

Negative/trace

Negative

Positive

Figure 40-7 Approach to proteinuria in adults. (Modified from Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;i39:l37-i47, EI48-EI49. Redrawn from National Kidney Foundation/Kidney Disease Quality Initiative. See Web Resources.)

Figure 40-7 Approach to proteinuria in adults. (Modified from Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;i39:l37-i47, EI48-EI49. Redrawn from National Kidney Foundation/Kidney Disease Quality Initiative. See Web Resources.)

Box 40-5 Causes of Pathologic Proteinuria in Children

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