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In Crescentic IgA Nephropathy, Fractional Excretion of IgG in Combination with Nephron Loss Is the Best Predictor of Progression and Responsiveness to Immunosuppression

Claudio Bazzi^*, Virginia Rizza, Sara Raimondi, Daniela Casellato, Pietro Napodano, and Giuseppe D'Amico^*

^* Fondazione D'Amico per la Ricerca sulle Malattie Renali, Biochemical Laboratory, and Nephrological and Dialysis Unit, San Carlo Borromeo Hospital, and Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy

Correspondence: Dr. Claudio Bazzi, Fondazione D'Amico per la Ricerca sulle Malattie Renali, Via Cherubini, 6, 20100 Milan, Italy. Phone: 39-338-8319049; Fax: 39-02-48110814; E-mail: claudio.bazzi{at}alice.it

Background and objectives: The aim of this study was to evaluate the relationship between proteinuric markers (urinary excretion of IgG, 2-macroglobulin, 1-microglobulin) and serum creatinine (sCr), histologic lesions, progression, and immunosuppression responsiveness in crescentic IgA nephropathy.

Design, setting, participants, & measurements: Fractional excretion of IgG (FEIgG) and of 1-microglobulin and urinary excretion of 2-macroglobulin were evaluated in 37 patients, 23 treated with steroids and cyclophosphamide. For assessment of the effective tubular load of proteins in surviving nephrons, new markers that take into account not only the absolute excretion value but also nephron loss were obtained dividing proteinuric markers for percentage of nonobsolescent glomeruli (surviving glomeruli [SG]). For each parameter, low- and high-risk groups were defined according to cutoffs with the highest sensitivity and specificity for progression (ESRD/doubling sCr) assessed by receiver operating characteristic analysis; follow up was 60 ± 40 mo.

Results: FEIgG/SG is the most powerful progression predictor: 5 versus 83% in all patients; in treated patients, 0 versus 89%, increased to 0 versus 100% by sCr and FEIgG/SG in combination (low risk: both markers or only one below cutoff (n = 15); high risk: both markers above cutoff (n = 8). The nonprogressors showed at last observation 65% proteinuria reduction and 10% sCr reduction.

Conclusions: In crescentic IgA nephropathy, FEIgG/SG, which evaluates altered size selectivity in relation to nephron loss, is the best progression predictor. In treated patients, progression prediction was increased by FEIgG/SG and sCr in combination. Treatment may be restricted to low-risk patients.