Abstract 18012: Insights into the Cardiorenal Syndrome Type II in the Rat
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 (MCT) treated rats.
Methods: 10 Sprague-Dawley rats were treated with MCT for 4 weeks until they developed HF. 11 were taken as control (C). Heart failure was confirmed on transverse heart histologic sections looking at RV hypetrophy /dilatation and BNP plasma levels. Cytokine profile was assessed by Multiplex array on sera. pNGAL, pCreatinine (ELISA), kidney tissue NGAL (RT-PCR) were performed. Kidney cell apoptosis was assessed by TUNEL.
Results: MCT rats showed higher BNP values (MCT 4.7±1.2 vs C 1.5±0.5pg/mL p<0.004 ), marked RV Hypetrophy and dilatation (RVMass/RVVolume MCT 1.46±0.31vs C 2.4±0.8 p<0.01). TNFα (MCT 1325.37±559.95vsC84.46±64.50 pg/ml ), IL1(MCT183.71±51.61vsC78.31±26.07), IL4 (MCT 731.67±154.83 vs C 316.62±12.55pg/ml), IL6 (MCT 5314.983±1632.98 vs C1754.01±188.85), IL10 (MCT2613.10±934.04vs C847.70±152.19 pg/ml) were all increased (p<0.05) as well as Creatinine (MCT 0.95±0.4 vs C 0.57±0.4 ug/mL, p<0.05). Both plasma (MCT 0.56±0.28 vs C 0.25±0.16 ug/mL,p<0.02) and kidney tissue NGAL (MCT 70.7±8.7vs C 32.1±9.9 AU, p<0.001) were significantly increased and a higher number of kidney apoptotic cells was found (MCT 184.01±47.6 vs C 16.3±11.6 cells/mm2, p< 0.0001). In C rats apoptosis was found only on tubular or vascular cells, while in MCT also a lot of interstitial cells was found. In MCT rats apoptosis was found in medullar part of kidney with focal aspect.
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.
- © 2013 by American Heart Association, Inc.