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Nephrol Dial Transplant (2002) 17: 1197-1203
© 2002 European Renal Association-European Dialysis and Transplant Association

Proteinuria patterns and their association with subsequent end-stage renal disease in IgA nephropathy

James V. Donadio1,, Erik J. Bergstralh2, Joseph P. Grande3 and Diana M. Rademcher2

1 Division of Nephrology, Department of Internal Medicine, 2 Section of Biostatistics and 3 Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, MN, USA

Background. Proteinuria (UP) >1.0 g/24 h at diagnosis is a well-known indicator of progressive renal disease in patients with IgA nephropathy (IgAN). To determine if persistent UP is a more sensitive marker for later progression of IgAN, the hypothesis was tested that the prior level and trend (slope) in UP for 1 year was better at predicting later end-stage renal disease (ESRD) (dialysis or transplant) than a current 24-h UP, serum creatinine (SC), SC slope, hypertension, or total glomerular histopathological score on index renal biopsy in an observational study of 154 high-risk patients enrolled in two clinical trials (IgAN 1, IgAN 2).

Methods. Measurements of 24-h UP and SC were made at time 0, 6 weeks, 6 months and 1 year in all patients, who were then followed for an additional 5.76 years and 1.63 years in the two studies, respectively. The Cox proportional hazards model was used to identify predictors of ESRD following the 1-year visit.

Results. Adjusting only for randomized treatment, nearly all UP variables (number of high readings, 1-year level, slopes), SC at 1 year, and SC trends (slopes) over the prior year were significantly associated with subsequent ESRD (all P values <0.05) in both studies. However, among the UP variables, the 1-year readings had the strongest association with ESRD in IgAN 1 (hazard ratio (HR), 95% CI, for a 1g increase: 1.5, 1.2,1.9), and the second strongest association (similar to UP trends) in IgAN 2 (1.4, 1.2,1.6). Males had lower rates of ESRD in both studies (IgAN 1 HR: 0.5, 0.2,1.2, P=0.11; IgAN 2 HR: 0.2, 0.1,0.6, P=0.002). In the multivariate analyses that examined all clinical and histological variables, 1-year levels of 24-h UP and SC, and female gender were independently associated with subsequent ESRD.

Conclusion. In a high-risk patient with IgAN, the current 24-h UP and SC measurements are as good predictors of subsequent ESRD as UP and SC trends and levels over the prior year. Additionally, it appears that females have poorer outcomes than males.

Keywords: IgA nephropathy; prognosis; proteinuria

Correspondence and offprint requests to: James V. Donadio MD, Emeritus Staff, Mayo Clinic, 200 First Street South West, Stabile 722, Rochester, MN 55905–0001, USA. Email: donadio.james{at}mayo.edu


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