Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China.
Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Kidney Blood Press Res. 2023;48(1):241-248. doi: 10.1159/000530210. Epub 2023 Mar 20.
Renal glycogen synthase kinase-3 beta (GSK3β) overactivity has been associated with a diverse range of kidney diseases. GSK3β activity in urinary exfoliated cells was reported to predict the progression of diabetic kidney disease (DKD). We compared the prognostic value of urinary and intrarenal GSK3β levels in DKD and nondiabetic chronic kidney disease (CKD).
We recruited 118 consecutive biopsy-proved DKD patients and 115 nondiabetic CKD patients. Their urinary and intrarenal GSK3β levels were measured. They were then followed for dialysis-free survival and rate of renal function decline.
DKD group had higher intrarenal and urinary GSK3β levels than nondiabetic CKD (p < 0.0001 for both), but their urinary GSK3β mRNA levels were similar. Urinary p-GSK3β level is statistically significantly correlated with the baseline estimated glomerular filtration rate (eGFR), but urinary GSK3β level by ELISA, its mRNA level, the p-GSK3β level, or the p-GSK3β/GSK3β ratio had no association with dialysis-free survival or the slope of eGFR decline. In contrast, the intrarenal pY216-GSK3β/total GSK3β ratio significantly correlated with the slope of eGFR decline (r = -0.335, p = 0.006) and remained an independent predictor after adjusting for other clinical factors.
Intrarenal and urinary GSK3β levels were increased in DKD. The intrarenal pY216-GSK3β/total GSK3β ratio was associated with the rate of progression of DKD. The pathophysiological roles of GSK3β in kidney diseases deserve further studies.
肾糖原合酶激酶-3β（GSK3β）活性过高与多种肾脏疾病有关。有报道称，尿脱落细胞中的 GSK3β 活性可预测糖尿病肾病（DKD）的进展。我们比较了 DKD 和非糖尿病慢性肾脏病（CKD）患者尿内和肾内 GSK3β 水平的预后价值。
我们招募了 118 例连续活检证实的 DKD 患者和 115 例非糖尿病 CKD 患者。测量了他们的尿内和肾内 GSK3β 水平。然后对他们进行无透析生存和肾功能下降率的随访。
与非糖尿病 CKD 患者相比，DKD 组的肾内和尿内 GSK3β 水平更高（均 p < 0.0001），但尿内 GSK3β mRNA 水平相似。尿 p-GSK3β 水平与基线估计肾小球滤过率（eGFR）呈统计学显著相关，但 ELISA 检测的尿 GSK3β 水平、其 mRNA 水平、p-GSK3β 水平或 p-GSK3β/GSK3β 比值与无透析生存或 eGFR 下降斜率均无相关性。相比之下，肾内 pY216-GSK3β/总 GSK3β 比值与 eGFR 下降斜率显著相关（r = -0.335，p = 0.006），并在调整其他临床因素后仍然是独立的预测因素。
DKD 患者的肾内和尿内 GSK3β 水平升高。肾内 pY216-GSK3β/总 GSK3β 比值与 DKD 的进展速度相关。GSK3β 在肾脏疾病中的病理生理作用值得进一步研究。
