Characterization of proteinuria in primary glomerulonephritides: Urinary polymers of albumin

Abstract

In 142 patients with primary glomerulonephritis (GN), there were polymers 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 (MGN) 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 patients with proteinuria less than 0.5 g/d to 58% in patients with proteinuria ≥ 15.0 g/d (P = 0.001), but 40% of the nephrotic syndrome patients were PA-negative despite values of proteinuria comparable to those of PA-positive patients, suggesting that the presence of PAs is not simply related to protein loss, but probably to some 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 duration of 52 ± 27 months, for whom PAs were determined and urinary protein characterized by sodium-dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE) at the beginning of the follow-up period, the functional outcome was correlated with the patterns of proteinuria. Chronic 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 patients, and in 17% of the SDS-PAGE 23-kd mixed-pattern patients (P = 0.001). The association of PAs with the 10-kd pattern enhanced the predictive value for CRF outcome: CRF developed in 62% of the PA-positive patients with the 10-kd pattern compared with 11% of the PA-negative patients 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 patients, 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 retrospective study of 21 treated patients (11 FSGS, nine MGN, and one MPGN patient), a response to therapy with complete or partial remission was observed 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-positive 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 patients 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 associated 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 normal renal function at entry, the presence of polymers has a predictive value for CRF outome; this value is enhanced by the contemporaneous presence of an SDS-PAGE proteinuric pattern with low molecular weight proteins up to 10-kd, which is known to be associated with diffuse tubulointerstitial lesions. Therefore, the best predictive value for either CRF outcome or for response to therapy was provided by a combination between a marker associated with the degree of proteinuria and the types 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 proteins between 20 and 10 kd).