CHARACTERIZATION OF PROTEINURIA IN PRIMARY GLOMERULONEPHRITIDES - URINARY POLYMERS OF ALBUMIN

In 142 patients with primary glomerulonephritis (GN), there were polym ers of albumin (PAs) in the urine samples of 87% of 15 minimal-change disease (MCD) patients, 52% of 27 focal segmental glomerulosclerosis ( FSGS) patients, 51% of 47 membranous glomerulonephritis (MON) patients , 55% of 20 membranoproliferative glomerulonephritis (MPGN) patients, and 9% of 33 immunoglobulin A nephropathy (IgAN) patients (P = 0.000). In IgAN, only three patients with nephrotic syndrome were PA positive . The PAs were significantly correlated with nephrotic syndrome (NS) ( P = 0.000) and with the degree of proteinuria, ranging from 8% in pati ents with proteinuria less than 0.5 g/d to 58% in patients with protei nuria greater than or equal to 15.0 g/d (P = 0.001), but 40% of the ne phrotic syndrome patients were PA-negative despite values of proteinur ia comparable to those of PA-positive patients, suggesting that the pr esence of PAs is not simply related to protein loss, but probably to s ome other unidentified factor or lesion. For 72 patients (43 with NS) (22 FSGS, 36 MGN, and 14 MPGN patients) with normal renal function at entry (serum creatinine, 1.02 +/- 0.23 mg/dL) and a mean follow-up dur ation of 52 +/- 27 months, for whom PAs were determined and urinary pr otein characterized by sodium-dodecyl-sulphate polyacrylamide gel elec trophoresis (SDS-PAGE) at the beginning of the follow-up period, the f unctional outcome was correlated with file patterns of proteinuria. Ch ronic renal failure (CRF) developed in 24% of all 72 patients, in 36% of the PA-positive patients, in 9% of the PA-negative patients (P = 0. 007), in 44% of the SDS-PAGE 10-kd mixed glomerulotubular pattern pati ents, and in 17% of the SDS-PAGE 23-kd mixed-pattern patients (P = 0.0 01). The association of PAs with the 10-kd pattern enhanced the predic tive value for CRF outcome: CRF developed in 62% of the PA-positive pa tients with the 10-kd pattern compared with 11% of the PA-negative pat ients with the 23-kd pattern (P = 0.0001). CRF developed in 32% of 43 patients with the nephrotic syndrome, in 48% of the PA-positive patien ts, and in 11% of the PA-negative patients (P = 0.037); in 50% of the 10-kd patients and in 24% of the 23-kd patients (P = 0.007); and in 70 % of the PA-positive patients with the 10-kd pattern and 14% of the PA -negative patients with the 23-kd pattern (P = 0.001). In a retrospect ive study of 21 treated patients (11 FSGS, nine MGN, and one MPGN pati ent), a response to therapy with complete or partial remission was obs erved in 57% of all 21 patients; in 58% of patients with the nephrotic syndrome; in 88% of the PA-negative patients versus 38% of the PA-pos itive patients (P = 0.027); in 90% of the 23-kd patients versus 27% of the 10-kd patients (P = 0.004); and in 100% of the PA-negative patien ts with the 23-kd pattern versus 12% of the PA-positive patients with the 10-kd pattern (P = 0.001). In conclusion, urinary PAs are associat ed with GN characterized by lesions mainly localized in the glomerular capillary wall, with the presence of the nephrotic syndrome, and with the degree of proteinuria. In patients with FSGS, MGN, MPGN, and norm al renal function at entry, the presence of polymers has a predictive value for CRF outcome; this value is enhanced by the contemporaneous p resence of an SDS-PAGE proteinuric pattern with low molecular weight p roteins up to 10-kd, which is known to be associated with diffuse tubu lointerstitial lesions. Therefore, the best predictive value for eithe r CRF outcome or for response to therapy was provided by a combination between a marker associated with the degree of proteinuria and the ty pes of GN characterized by lesions mainly localized in the glomerular capillary wall and a marker associated with tubulointerstitial damage (SDS-PAGE mixed glomerulotubular pattern with low molecular weight pro teins between 20 and 10 kd). (C) 1997 by the National Kidney Foundatio n, Inc.