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Urinary Excretion of 2-Microglobulin and IgG Predict Prognosis in Idiopathic Membranous Nephropathy: A Validation Study

Amanda J.W. Branten^*, Peggy W. du Buf-Vereijken^*,, Ina S. Klasen, Frank H. Bosch, Geert W. Feith^||, Daan A. Hollander^¶ and Jack F. Wetzels^*

^* Department of Medicine, Division of Nephrology, and Department of Clinical Chemistry, University Medical Center, Nijmegen, The Netherlands; Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands; Department of Internal Medicine, Hospital Rijnstate, Arnhem, The Netherlands; ^|| Department of Internal Medicine, Hospital Gelderse Vallei, Ede, The Netherlands; and ^¶ Department of Internal Medicine, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands

Address correspondence to: Dr. Amanda J.W. Branten, Department of Medicine, Division of Nephrology 545, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: +31-24-3614761; Fax: +31-24-3540022; E-mail: A.Branten{at}nier.umcn.nl

An accurate prediction of the prognosis of patients with idiopathic membranous nephropathy (iMN) should allow restriction of immunosuppressive treatment to patients who are at highest risk for ESRD. On the basis of retrospective studies, it has previously been suggested that the urinary excretions of 2-microglobulin (U2m) and IgG (UIgG) are useful predictors of renal insufficiency in patients with iMN. The threshold values of 0.5 µg/min (U2m) and 250 mg/24 h (UIgG) have been validated in a new and larger patient cohort. From 1995 onward, 57 patients with iMN (38 men, 19 women; age 48 ± 16 yr), a nephrotic syndrome, and a serum creatinine level 1.5 mg/dl were studied prospectively. At baseline, a standardized measurement was carried out to determine renal function and protein excretion. The end point renal death was defined as a serum creatinine exceeding 1.5 mg/dl or a rise of serum creatinine of >50%. Mean (±SD) follow-up was 53 ± 23 mo. Thus far, 25 (44%) of the patients have reached the end point renal death. Multivariate analysis confirmed U2m as the strongest independent predictor for the development of renal insufficiency. Sensitivity and specificity were 88 and 91%, respectively, for U2m, and both were 88% for UIgG. When the excretions of both proteins were combined, specificity improved to 97%. It is concluded that the present data validate the accuracy of U2m and of UIgG in predicting renal outcome in patients with iMN. These markers can be used to guide decisions on the start of immunosuppressive treatment.

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