The predictive value of attenuated proteinuria at 1 year after steroid therapy for renal survival in patients with IgA nephropathy

Abstract

Background: The relationship between the urinary protein excretion (UPE) initially achieved after steroid therapy and the long-term renal outcome of IgA nephropathy (IgAN) has not been clarified. We investigated the threshold UPE at 1 year after steroid therapy which predicts a favorable renal survival.

Methods: We enrolled 141 IgAN patients who received 6 months of steroid therapy. The endpoint was defined as a 50 % increase in serum creatinine from baseline. The spline model was used to define the threshold UPE predicting renal survival.

Results: Thirteen patients (9.2 %) reached the endpoint at a median follow-up of 3.8 years. When evaluating the relative hazard ratio (HR) of the UPE at 1 year for the endpoint, we found an inflection point at 0.40 g/day on the spline curve. The multivariate Cox model revealed that, in addition to the Disappeared category of UPE (range <0.30 g/day), the Mild category (range 0.30-0.39 g/day) was associated with more reduced risk of the endpoint [HR 0.02, 95 % confidence intervals (CI) 0.00-0.29] relative to the Severe category (range ≥1.00 g/day), whereas the Moderate category (range 0.40-0.99 g/day) was not. The estimated glomerular filtration rate <60 ml/min/1.73 m(2) was also an independent predictor of the endpoint. When renal survival was adjusted with pathological parameters in the Cox model, UPE <0.40 g/day was still an independent favorable predictor (HR 0.08, 95 % CI 0.01-0.45).

Conclusions: In IgAN patients receiving 6 months of steroid therapy, the achievement of proteinuria <0.4 g/day at 1 year could be a therapeutic indicator for a favorable renal outcome.

Fig. 1

Changes in proteinuria at baseline, 6 months, 1 year and at the last follow-up. The lines in the middle and those delimiting the boxes indicate the median, 25th and 75th percentile values, respectively. The whiskers at the ends of the boxes are lines that show the distance from the end of the box to the largest and smallest observed values that are <1.5 box-length from either end. Dots indicate outliers

Fig. 2

Risk ratio for the endpoint associated with the UPE at the 1-year follow-up. Plots of the risk ratios and 95 % confidence intervals adjusted for the baseline eGFR for the endpoint using the level of proteinuria at the 1-year follow-up examination as the continuous variable are shown (reference: the highest decile, the median of which was 1.44 g/day). The degree of proteinuria was log transformed

Fig. 3

Renal survival determined by the Kaplan–Meier method, stratified by the category of UPE at 1 year after 6 months of steroid therapy. These unadjusted curves demonstrate that, in addition to the Disappeared category, the Mild category showed significantly better renal survival compared to that in the Moderate or Severe categories (log-rank, p < 0.05 for both strata)