Differentiation of glomerular, tubular, and normal proteinuria: determinations of urinary excretion of beta-2-macroglobulin, albumin, and total protein.

A low molecular weight beta(2)-globulin (beta(2)-microglobulin), albumin, and total protein were measured in concentrated 24-hr urine specimens from 20 healthy subjects and 30 patients with clinical proteinuria of glomerular or tubular type. Classification of proteinuria was made on the basis of clinical diagnosis and size distribution of urinary proteins after gel chromatography. The molecular radii (Stokes' radii) of beta(2)-microglobulin and albumin, estimated by gel chromatography, were 15 A and 35 A. The average 24-hr urinary excretion in healthy subjects was 0.12 mg for beta(2)-microglobulin, 10 mg for albumin, and 80 mg for total protein. The patients with renal glomerular disorders had normal or only somewhat increased excretion of beta(2)-microglobulin, despite considerably increased excretion of albumin and total protein. Most of the patients with tubular dysfunction excreted large amounts of beta(2)-microglobulin, although they excreted normal or only slightly increased amounts of albumin and only moderately increased quantities of total protein. Consequently, the ratio or urinary albumin/urinary beta(2)-microglobulin was high in glomerular proteinuria (1100: 14,200), intermediate in normal proteinuria (33: 163), and low in tubular proteinuria (1.0: 13.3). Determinations of urinary clearances of beta(2)-microglobulin and albumin in four healthy subjects and 11 patients indicated that increased excretions of the two proteins were associated with increased clearances. The results suggest that quantitative determinations of urinary beta(2)-microglobulin and urinary albumin may be useful for detecting disorders of the renal handling of plasma proteins. The findings also seem to suggest a selective tubular reabsorption of the two proteins. Estimates on sera revealed a close correlation between serum levels of beta(2)-microglobulin and creatinine and also a greatly raised serum concentration of beta(2)-microglobulin after bilateral nephrectomy.

Bardet-Biedl syndrome and cystinuria.

An unusual association of Bardet-Biedl syndrome with cystinuria was described in one patient. A 21-year-old male was admitted to hospital because of renal failure, severe deterioration of visual acuity, polydactyly, brachydactyly, and mental retardation. Laboratory investigations revealed a serum creatinine of 292 mumol/L (3.3 mg/dL) and a GFR of 25 mL/min per 1.73 m2. Quantitative ion exchange chromatography demonstrated an increased urinary excretion rate of cystine, lysine, arginine, and ornithine. The ophthalmologic examination showed a severe atypical retinal dystrophy. Visual acuity was severely deteriorated and the patient could only count the examining physician's fingers. The patient had been previously evaluated at the age of 7 years for polyuria, polydipsia, and growth failure. His workup at that time demonstrated nephrogenic diabetes insipidus, normal GFR, and a urinary amino acid pattern consistent with the cystinuric phenotype. There was mental retardation notwithstanding the normal ophthalmologic examination. Intravenous pyelography showed calyceal clubbing, calyceal cysts, and lobulated renal outlines of the fetal type. The patient was evaluated again at the age of 13 years for deterioration of visual acuity and the ophthalmologic examination showed an atypical retinal dystrophy, with sparse pigmentation, central and peripheral atrophy, attenuated vessels, and marked optic disk pallor. To our knowledge the association of Bardet-Biedl syndrome with cystinuria has never been reported. It is unlikely that cystinuria may have contributed to the kidney damage. The possibility that mental retardation has been induced or aggravated by cystinuria cannot be excluded.