Heat Shock Protein 70 Is Involved in the Efficiency of Preconditioning with Cyclosporine A in Renal Ischemia Reperfusion Injury by Modulating Mitochondrial Functions.

Cyclosporine A (CsA) preconditioning is known to target mitochondrial permeability transition pore and protect renal function after ischemia reperfusion (IR). The upregulation of heat-shock protein 70 (Hsp70) expression after CsA injection is thought to be associated with renal protection. The aim of this study was to test the effect of Hsp70 expression on kidney and mitochondria functions after IR. Mice underwent a right unilateral nephrectomy and 30 min of left renal artery clamping, performed after CsA injection and/or administration of the Hsp70 inhibitor. Histological score, plasma creatinine, mitochondrial calcium retention capacity, and oxidative phosphorylation were assessed after 24 h of reperfusion. In parallel, we used a model of hypoxia reoxygenation on HK2 cells to modulate Hsp70 expression using an SiRNA or a plasmid. We assessed cell death after 18 h of hypoxia and 4 h of reoxygenation. CsA significantly improved renal function, histological score, and mitochondrial functions compared to the ischemic group but the inhibition of Hsp70 repealed the protection afforded by CsA injection. In vitro, Hsp70 inhibition by SiRNA increased cell death. Conversely, Hsp70 overexpression protected cells from the hypoxic condition, as well as the CsA injection. We did not find a synergic association between Hsp70 expression and CsA use. We demonstrated Hsp70 could modulate mitochondrial functions to protect kidneys from IR. This pathway may be targeted by drugs to provide new therapeutics to improve renal function after IR.

Brain Natriuretic Peptide Is a Marker of Fluid Overload in Incident Hemodialysis Patients.

BACKGROUND/AIMS: Brain natriuretic peptide (BNP) is secreted by cardiomyocytes under stretch condition. High blood levels are associated with decreased patient survival in heart failure patients and in hemodialysis (HD) patients. We report the monthly BNP change in the first months of HD therapy in incident patients and its relationship with fluid removal and cardiac history (CH). METHODS: All patients starting HD therapy in our unit from May 2008 to December 2012 were retrospectively analyzed. Every month (M1 to M6), BNP was assessed before a midweek dialysis session. CH, monthly pre- and postdialysis blood pressure, and postdialysis body weight were collected. RESULTS: A total of 236 patients were included in the analysis. The median BNP at HD start was 593 (175-1,433) pg/mL, with a significant difference between CH- and CH+ patients (291 vs. 731 pg/mL, p < 0.0001). Mortality was significantly higher in patients in the higher BNP tertile. BNP decreased significantly between M1 and M2 and then plateaued. The BNP change between M1 and M2 and between M1 and M6 was significantly correlated with the initial fluid removal. Applying stepwise multiple regression, the BNP change between M1 and M2 was significantly and independently related to fluid removal. The BNP level at M6 was also related to patient survival. CONCLUSIONS: We confirm that in incident HD patients, BNP level is related to fluid excess and cardiac status. The BNP decrease in the first months of HD therapy is related to fluid excess correction. BNP appears as an important tool to evaluate hydration status correction after HD onset.