Impact of impaired cardiac function on the progression of chronic kidney disease---role of pharmacomodulation of valsartan.

Although chronic kidney disease (CKD) is known to aggravate cardiovascular disease in the setting of cardiorenal syndrome (CRS), the impact of impaired cardiac function on the progression of CKD has seldom been reported. This study tested the impact of acute myocardial infarction on a rodent CKD model and the therapeutic effect of valsartan in this setting. Adult male Sprague-Dawley rats (n = 50) equally divided into group 1 (sham control), group 2 (CKD induced by 5/6 nephrectomy), group 3 (AMI by ligation of left coronary artery), group 4 (CKD+AMI), group 5 (CKD+AMI+valsartan, orally 10 mg/kg/day). By day 60, kidney injury score, creatinine levels, and ratio of urine to creatinine were highest in group 4 and lowest in group 1, significantly higher in group 4 than those in groups 2 and 5, and significantly higher in group 5 than those in group 2 (all p < 0.001). Protein expressions of inflammation (IL-1β/MMP-9), oxidative stress (NOX-1/NOX-2/oxidized protein, angiotensin-II receptor), apoptosis (Bax, cleaved caspase-3/PARP), fibrosis (Smad3/TGF-β), and kidney injured (KIM-1/FSP-1) markers showed an identical pattern, whereas anti-fibrosis (Smad5/BMP-2) indices exhibited an opposite pattern compared to that of creatinine level among all groups (all p < 0.01). Cellular expressions of inflammation (CD14/CD68), DNA-damage (γ-H2AX, CD90/XRCC1) and proximal-renal tubule (KIM-1) biomarkers displayed an identical pattern, whereas podocyte-integrity markers (podocin/ZO-1/p-cadherin/synaptopodin) showed a pattern opposite to that of creatinine level among all groups (all p < 0.001). In a rodent CKD setting, renal function impairment and parenchymal damage further deteriorated after AMI but were suppressed following valsartan treatment.