Insights into the pathophisiology of cardiorenal syndrome type II in the rat

Abstract

Background: Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence of Chronic Heart Failure (CHF). The mechanisms leading to kidney damage in CHF are however still obscure.We studied the development of kidney injury in a model of right CHF (monocrotaline (MC) treated rats). Methods: 10 animals were treated with MC for 4 weeks until they developed HF. 11 were taken as control. The occurrence of HF wasdemonstrated by signs of congestion, hypertrophy and dilatation of the right ventricle, and by the determination of BNP. We measured pNGAL, pCreatinine (ELISA), kidney NGAL (RT-PCR), and pTNFα, IL1, IL4, IL6, IL10 (Multiplex protein microarray). Kidney cell apoptosis was assessed by TUNEL. Results: MC treated rats showed higher BNP values (MC 4.7±1.2, C 1.5±0.5 pg/mL p<0.004), marked RV Hypetrophy and dilatation (RVMass/RVVolume MC 1.46±0.31 C 2.4±0.8 p<0.01), pleural and peritoneal effusions. TNFα (MC 1325.37±559.95 vs C 84.46±64.50 pg/ml), IL1 (MC183.71±51.61 vs C 78.31±26.07 pg/ml), IL4 (MC 731.67±154.83 vs C 316.62±12.55 pg/ml), IL6 (MC 5314.983±1632.98 vs C 1754.01±188.85 pg/ml), IL10 (MC 2613.10±934.04 vs C 847.70±152.19 pg/ml) were all increased (p<0.05) as well as Creatinine (MC 0.95±0.4 vs C 0.57±0.4 pg/ml p<0.05). Both plasma (MC 0.56±0.28 vs C 0.25±0.16 ug/mL,p<0.02) and renal NGAL (MC 70.7±8.7 vs C 32.1±9.9 AU, p<0.001) were significantly increased and a higher number of kidney apoptotic cells was found (MC 69.3±1.6 vs C32.2±2.9 cells/mm2, p<0.04). Conclusion: CHF in the rat is accompanied by deterioration of kidney function (CRSII). A rise of creatinine and NGAL, an early biomarker of kidney damage, was detected. Kidney cells apoptosis triggered by circulating pro-inflammatory cytokines represent the final insult to the kidney due to the CHF-induced perturbation of neuro-endocrine and inflammatory milieu