Tubular proteinuria defined by a study of Dent's (CLCN5 mutation) and other tubular diseases

Background. The term tubular proteinuria is often used interchangeably with low molecular weight proteinuria (LMWP), although the former implies a definite etiology. A specific quantitative definition of tubular proteinuria is needed, and we address this by studying five different renal disorders. Methods. Tubular proteinuria was assessed by measuring urinary retinol-binding protein (RBP), beta(2)-microglobulin (beta(2)M), alpha(1)-microglobulin (alpha(1)M), and albumin in 138 patients: 26 affected males and 24 female carriers of the X-linked syndrome Dent's disease, 6 patients with other Fanconi syndromes, 17 with distal renal tubular acidosis (dRTA), 39 with glomerulonephritis (GN), and 26 with Chinese herbs nephropathy (CHN). Results. REP was better than beta(2)M or alpha(1)M in identifying the tubular proteinuria of Dent's disease. Median urinary REP levels in mg/mmol creatinine were: affected male Dent's, 18.2, N = 26; carrier female Dent's, 0.30, N = 24; dRTA, 0.027, N = 17; GN, 0.077, N = 39; and normal adults, 0.0079, N = 61. Elevated urinary REP (>0.017) and albumin < (10 X REP) + 2 identified all patients with the LMWP of Dent's disease and clearly distinguished their LMWP from that of dRTA and GN. This is a quantitative definition of tubular proteinuria. Consistent with this definition, 80% of those patients with CHN who had an elevated REP had tubular proteinuria. Urinary REP and albumin in carriers of Dent's disease were strikingly correlated over a 100-fold range (R = 0.933). Conclusion. The combination of elevated urinary REP (>0.017) and albumin < (10 x REP) + 2 (mg protein/mmol creatinine) is a quantitative definition of tubular proteinuria. Furthermore, our findings suggest that a shared defect in tubular REP and albumin reuptake causes this form of proteinuria.