Prediction of outcomes in crescentic IgA nephropathy in a multicenter cohort study

Abstract

Crescentic IgA nephropathy (IgAN), defined as >50% crescentic glomeruli on kidney biopsy, is one of the most common causes of rapidly progressive GN. However, few studies have characterized this condition. To identify risk factors and develop a prediction model, we assessed data from patients ≥ 14 years old with crescentic IgAN who were followed ≥ 12 months. The discovery cohort comprised 52 patients from one kidney center, and the validation cohort comprised 61 patients from multiple centers. At biopsy, the mean serum creatinine (SCr) level ± SD was 4.3 ± 3.4 mg/dl, and the mean percentage of crescents was 66.4%± 15.8%. The kidney survival rates at years 1, 3, and 5 after biopsy were 57.4%± 4.7%, 45.8%± 5.1%, and 30.4%± 6.6%, respectively. Multivariate Cox regression revealed initial SCr as the only independent risk factor for ESRD (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.10 to 1.57; P=0.002). Notably, the percentage of crescents did not associate independently with ESRD. Logistic regression showed that the risk of ESRD at 1 year after biopsy increased rapidly at SCr>2.7 mg/dl and reached 90% at SCr>6.8 mg/dl (specificity=98.5%, sensitivity=64.6% for combined cohorts). In both cohorts, patients with SCr>6.8 mg/dl were less likely to recover from dialysis. Analyses in additional cohorts revealed a similar association between initial SCr and ESRD in patients with antiglomerular basement membrane disease but not ANCA-associated systemic vasculitis. In conclusion, crescentic IgAN has a poor prognosis, and initial SCr concentration may predict kidney failure in patients with this disease.

Figures

Figure 1.

Renal survival of crescentic IgA nephropathy treated with different regimens. Aggressive immunosuppressive therapy was defined as high-dose pulse methylprednisolone (7–15 mg/kg per day) plus cyclophosphamide therapy.

Figure 2.

The logistic regression curves for crescentic GN due to IgAN, Anti-GBM disease, and AASV. Blue line, logistic curve; green triangles, renal survival during follow-up; purple line, SCr concentration=6.8 mg/dl (600 μmol/L); red crosses, renal survival at 1 year after renal biopsy. A value of 0% means that the patient did not develop ESRD, whereas 100% means that the patient developed ESRD. (A) Logistic curve in the discovery cohort (n=52). The curve is S-shaped. In patients with SCr>6.8 mg/dl (600 μmol/L), the cumulative probability of ESRD at 1 year is >90%. (B) A similar result is observed in the discovery cohort patients under aggressive immunosuppressive therapy. (C) Logistic curve in the validation cohort (n=61). The threshold for predicting renal mortality was identical to the value calculated for the discovery cohort. (D) Logistic curve of the entire crescentic IgAN cohort. (E) The logistic curve of anti-GBM disease is S-shaped. (F) The logistic curve of AASV is nearly linear.

Figure 3.

The prediction ability of SCr threshold (6.8mg/dl) for ESRD event. (A) Percentage of patients who developed ESRD at 1 year after renal biopsy and during follow-up in the discovery cohort (n=52). (B) Percentage of patients who developed ESRD at 1 year after renal biopsy and during follow-up in the validation cohort (n=61). (C) Percentage of patients who developed ESRD at 1 year after renal biopsy and during follow-up in the entire crescentic IgAN cohort (n=113). The SCr threshold of 6.8 mg/dl (600 μmol/L) showed good power in predicting renal mortality at 1 year and during follow-up.