Urinary GADD45 gamma Expression Is Associated with Progression of IgA Nephropathy

Background: Growth arrest and DNA damage-45 gamma (GADD-45 gamma) is induced in response to environmental stresses and functions in the regulation of cell cycles. Previous findings by our group suggested that GADD45 gamma contributed to renal tubular cell damage through induction of inflammatory and fibrogenic molecules. We examined the effects of urinary GADD45 gamma expression on the decline in renal function with IgA nephropathy in the present study. Methods: Patients (n = 62) were followed for a total of 710.3 +/- 287.5 days. The rate of renal function decline was assessed by the slopes of inverse serum creatinine and estimated glomerular filtration rate (GFR) plotted against time. Renal survival was calculated by Kaplan-Meier analysis and the primary endpoint was an increase in serum creatinine levels by 50% or more. Results: Kidney function declined more rapidly in the GADD45 gamma-positive group compared to the GADD45 gamma-negative group. Kidney survival estimates at the end of the study period were 82.9% in the GADD45 gamma-positive group and 100% in the negative group (p = 0.03). This difference remained significant in the group with GFR values <90 ml/min/1.73 m(2) when adjusted to stratification factors. Conclusion: The results suggest that urinary GADD45 gamma expression is associated with progression of renal disease. Copyright (C) 2009 S. Karger AG, Basel