Urinary excretion of IgG and alpha(1)-microglobulin predicts clinical course better than extent of proteinuria in membranous nephropathy

In idiopathic membranous nephropathy (MN), the main predictors for progress ion to chronic renal failure (CRF) are the amount of proteinuria and extent of tubulointerstitial damage. The aim of this study Is to evaluate whether urinary excretion of proteins reflecting the alteration of permselectivity in the glomerular capillary wall, such as immunoglobulin G (IgG), and the reabsorption impairment of low-molecular-weight proteins, such as a,microgl obulin (alpha (1)m), correlates with the extent of tubulointerstitial damag e and have a predictive value for functional outcome and response to therap y better than 24-hour proteinuria. In 78 patients with MN, urinary excretio n of albumin, transferrin, IgG, and alpha (1)m was measured by immunonephel ometry in second-morning urine samples and expressed in milligrams per gram of urinary creatinine (uCr). In 48 patients with characterization of prote inuria and renal biopsy performed at the same time, excretion of IgG (P = 0 .0087) and alpha (1)m (P = 0.0024), but not albumin (P = 0.37), transferrin (P = 0.38), or 24-hour proteinuria (P = 0.32), was associated significantl y with the extent of tubulointerstitial damage (score, 0 to 1 versus greate r than or equal to2). Only alpha (1)m excretion was associated significantl y with global glomerular sclerosis (P = 0.0032) and arteriolar hyalinosis ( P = 0.0004). Moreover, urinary excretion of alpha (1)m was significantly de pendent on IgG excretion (r = 0.67; P = 0.0001), but not on albumin (P = 0. 66) or 24-hour proteinuria (P = 0.07). Functional outcome could be evaluate d in 38 patients with nephrotic syndrome and baseline normal renal function (serum creatinine, 0.99 +/- 0.20 mg/dL; follow-up, 44 +/- 22 months). Remi ssion was 100% versus 20% in patients with IgG excretion less than 110 mg/g uCr versus 110 mg/g uCr or greater (P = 0.0001) and 77% versus 17% in pati ents with alpha (1)m excretion less than 33.5 mg/g uCr versus 33.5 mg/g uCr or greater (P = 0.0009), respectively. In patients with IgG and alpha (1)m excretion less than or greater than the cutoff value, progression to CRF w as 0% versus 35% (P = 0.0026) and 0% versus 58% (P = 0.0001), respectively. Nineteen patients treated with immunosuppressive therapy were compared wit h 19 untreated patients. There was no difference in remission or progressio n between treated and untreated patients when IgG and alpha (1)m excretion were less than the cutoff value. There was a significant difference for pro gression to CRF between treated and untreated patients when alpha (1)m excr etion was greater than the cutoff value (17% versus 100%; P = 0.0076). In c onclusion, IgG excretion Is associated significantly with the extent of tub ulointerstitial damage and alpha (1)m excretion. This observation supports the hypothesis that IgG may be the toxic moiety of proteinuria. Excretion o f IgG and alpha (1)m has a significant predictive value for both remission and progression and is useful to identify patients who are at risk for prog ression and for whom treatment with immunosuppressive therapy is indicated soon after diagnosis. (C) 2001 by the National Kidney Foundation, Inc.