Search

High serum adiponectin is noted in several conditions of chronic kidney disease (CKD) and is a predictor for end stage renal disease. However, the relationship between adiponectin level and renal disease progression is not well established. This study aimed to determine the relationship between serum adiponectin levels and CKD progression. This prospective longitudinal study included 2238 patients from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease. Patients were divided into quartiles according to their serum adiponectin level. Composite renal outcome was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate (eGFR) during the follow-up period. A cox proportional hazard ratio model was applied to analyze the relationship between composite renal outcome and serum adiponectin levels. Serum adiponectin level was inversely associated with eGFR (p < 0.001) and positively correlated with urine albumin-creatinine ratio. The highest quartile of serum adiponectin was associated with an increased risk of adverse renal outomes (HR, 1.39; 95%CI, 1.05-1.84; p=0.021). On time-dependent receiver operating characteristic curve analysis, predictive ability of adiponectin for renal outcomes disappeared after adjusting for eGFR. Therefore, serum adiponectin may be a biomarker of renal dysfunction rather than a true risk factor in CKD progression.

Activation of the epidermal growth factor receptor (EGFR)/signal transducer and activator of transcription 3 (Stat3) signaling pathway has been reported to be associated with renal fibrosis. We have recently demonstrated that peroxiredoxin V (PrdxV) acted as an antifibrotic effector by inhibiting the activity of Stat3 in TGF-β-treated NRK49F cells. However, the underlying mechanism of PrdxV remains poorly understood. To investigate molecular mechanism of PrdxV, we used a transgenic mouse model expressing PrdxV siRNA (PrdxV si mice) and performed unilateral ureteral obstruction (UUO) for 7 days. 209/MDCT cells were transiently transfected with HA-tagged WT PrdxV and C48S PrdxV. Transgenic PrdxV si mice displayed an exacerbated epithelial-to-mesenchymal transition (EMT) as well as an increase in oxidative stress induced by UUO. In the UUO kidney of the PrdxV si mouse, knockdown of PrdxV increased Tyr1068-specific EGFR and Stat3 phosphorylation, whereas overexpression of WT PrdxV in 209/MDCT cells showed the opposite results. Immunoprecipitation revealed the specific interaction between WT PrdxV and Stat3 in the absence or presence of TGF-β stimulation, whereas no PrdxV-EGFR or C48S PrdxV-Stat3 interactions were detected under any conditions. In conclusion, PrdxV is an antifibrotic effector that sustains renal physiology. Direct interaction between PrdxV and Stat3 through Cys48 is a major molecular mechanism.