Early elimination of uremic toxin ameliorates AKI-to-CKD transition.

Acute kidney injury (AKI)-related fibrosis is emerging as a major driver of chronic kidney disease (CKD) development. Aberrant kidney recovery after AKI is multifactorial and still poorly understood. The accumulation of indoxyl sulfate (IS), a protein-bound uremic toxin, has been identified as a detrimental factor of renal fibrosis. However, the mechanisms underlying IS-related aberrant kidney recovery after AKI is still unknown. The present study aims to elucidate the effects of IS on tubular damage and its involvement in the pathogenesis of AKI-to-CKD transition. Our results showed that serum IS started to accumulate associated with the downregulation of tubular organic anion transporter but not observed in the small-molecule uremic toxins of the unilateral ischemia-reperfusion injury (UIRI) without a contralateral nephrectomy model. Serum IS is positively correlated with renal fibrosis and binding immunoglobulin protein (BiP) and CAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) expression induction in the UIRI with a contralateral nephrectomy model (UIRI+Nx). To evaluate the effects of IS in the AKI-to-CKD transition, we administered indole, a precursor of IS, at the early stage of UIRI. Our results demonstrated IS potentiates renal fibrosis, senescence-associated secretory phenotype (SASP), and activation of endoplasmic reticulum (ER) stress, which is attenuated by synergistic AST-120 administration. Furthermore, we clearly demonstrated that IS exposure potentiated hypoxia-reperfusion (H/R) induced G2/M cell cycle arrest, epithelial-mesenchymal transition (EMT) and aggravated ER stress induction in vitro. Finally, the ER chemical chaperon, 4-phenylbutyric acid (4-PBA), successfully reversed the above-mentioned AKI-to-CKD transition. Taken together, early IS elimination in the early stage of AKI is likely to be a useful strategy in the prevention and/or treatment of the AKI-to-CKD transition.

[Clinical study on zhengan xifeng decoction in preventing and treating hypertensive nephropathy].

Seventeen cases of hypertensive nephropathy with azotemia (test group) treated with Zhengan Xifeng Decoction (ZGXFI) and routine regimen of Western Medicine were observed. The result was compared with that of 15 cases treated with routine regimen alone (control group). After 3 months of treatment, the blood pressure, sodium excretion, blood urea nitrogen and creatinine were all reduced, while creatinine clearance rate (CCr) and residual renal function index (RRFI) were improved significantly in both groups. Compared with control group, the treatment on test group showed a more prominent effect on lowering of diastolic blood pressure, elevating the hemoglobin, reducing the blood level of triglyceride and creatinine as well as improving on CCr and RRFI, suggesting the deterioration of residual renal function could be restrained by ZGXFD, through improve the disorder of lipid metabolism, osmolality gradient and creatinine kinetics.