Yu Sukyong, Cho Jinhee, Park Inwhee, Kim Seung Jung, Kim Heungsoo, Shin Gyu-Tae
Department of Nephrology, Ajou University School of Medicine, Suwon, Korea.
Am J Nephrol. 2009;30(2):135-9. doi: 10.1159/000209317. Epub 2009 Mar 17.
Growth arrest and DNA damage-45gamma (GADD-45gamma) is induced in response to environmental stresses and functions in the regulation of cell cycles. Previous findings by our group suggested that GADD45gamma contributed to renal tubular cell damage through induction of inflammatory and fibrogenic molecules. We examined the effects of urinary GADD45gamma expression on the decline in renal function with IgA nephropathy in the present study.
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.
Kidney function declined more rapidly in the GADD45gamma-positive group compared to the GADD45gamma-negative group. Kidney survival estimates at the end of the study period were 82.9% in the GADD45gamma-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 m2 when adjusted to stratification factors.
The results suggest that urinary GADD45gamma expression is associated with progression of renal disease.
生长停滞和DNA损伤诱导蛋白45γ（GADD-45γ）在环境应激反应中被诱导产生，并在细胞周期调控中发挥作用。我们团队之前的研究结果表明，GADD45γ通过诱导炎症和纤维化分子导致肾小管细胞损伤。在本研究中，我们检测了尿GADD45γ表达对IgA肾病患者肾功能下降的影响。
对62例患者进行了总计710.3±287.5天的随访。通过将血清肌酐倒数和估算肾小球滤过率（GFR）随时间绘制的斜率来评估肾功能下降速率。采用Kaplan-Meier分析计算肾脏生存率，主要终点是血清肌酐水平升高50%或更多。
与GADD45γ阴性组相比，GADD45γ阳性组的肾功能下降更快。在研究期末，GADD45γ阳性组的肾脏生存率估计为82.9%，阴性组为100%（p = 0.03）。当根据分层因素进行调整时，在GFR值<90 ml/min/1.73 m2的组中，这种差异仍然显著。
结果表明，尿GADD45γ表达与肾脏疾病进展相关。
