scholarly journals Two in one: Neuregulin 1 improves cardiac diastolic and kindney funtcion in chronic kidney disease in rats

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Kiss ◽  
E Acar ◽  
S Watzinger ◽  
Z.S Kovacs ◽  
F Marvanykovi ◽  
...  

Abstract Introduction The prevalence of chronic renal disease (CKD) is continuously increasing in developed countries. Uremic cardiomyopathy characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction (DD) is a common cardiovascular complication of CKD. Cardiac microvascular low-grade inflammation and altered expression of endothelium derived Neuregulin-1 (NRG-1) are contributed to left ventricular DD. Our aim was to charachterize the effects of CKD on the expression of NRG-1 and 2) NRG-1 treatment on myocardial hypertrophy, diastolic dysfunction and renal function in the rat model of CKD. Methods Male Wistar rats were used and randomized into 3 groups: 1) Sham-operated,2) CKD induced by 5/6 nephrectomy (CKD) and 3) NRG-1-treated CKD group (CKD+NRG-1). In this group, 2 weeks after the CKD induction, the rats were treated with recombinant human NRG-1 (rhNRG-1) at the dose of 10 μg/kg/d for consecutive 10 days with tail vein injection of NRG-1. Serum and urea creatinine levels were measured to verify the development of CKD and transthoracic echocardiography was performed to monitor cardiac morphology and function. Furthermore, total RNA was isolated and RT-qPCR was performed to evaluate the expression levels of inflammatory chemokine and cytokines (TNF-α, TGF-β). In addition, NRG-1 protein levels were assessed in both kidney and heart tissue by ELISA. To clarify the underling anti-fibrotic mechanism, human ventricular cardiac fibroblasts (HCF) were cultured and treated with the TGF-β (20 ng/ml), and TGF-β + hrNRG-1 for 24 h, respectively. Confocal microscopy was used to detect α-smooth muscle actin (α-SMA) expression, marker for fibroblast to myofibroblast transtion. Results 10 weeks after the 5/6 nephrectomy, serum carbamide and creatinine levels were significantly increased and creatinine clearence was significantly decreased as compared to sham-operated animals proving the development of chronic kidney disease (CKD). This was accompanied by a significant decrease in NRG-1 protein expression levels in both cardiac and kidney tissue. Of note, NRG-1 treatment markedly reduced these changes, suggesting its renoprotective effects in CKD. In addition, In CKD animals, the significantly increased anterior, posterior and septal wall thicknesses with decreased end-diastolic and end-systolic diameters proved the development of concentric left ventricular hypertrophy. In CKD, the septal e' was significantly decreased and E/e' increased indicating the developemnt of diastolic dysfunction. These parameters were significantly improved by NRG-1 treatment. Mechanistically, NRG-1 treatment reduced the expression of inflammatory cytokines in compared to untreat group. Furthermore, TGF-β induced α-SMA and Col I upregulation was markedly reduced by hrNRG-1 treatment. Conclusions NRG-1 treatment improved both renal and cardiac funtion in CKD, via a mechansim including the anti-inflammatory and anti-fibrotic properties of NRG-1. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Österreichischer Austauschdienst

Author(s):  
Bijaya K. Behera ◽  
Sanjay M.

Background: Present study was conducted with an objective to study the prevalence of left ventricular hyper trophy (LVH) by echocardiography in patients with chronic kidney disease (CKD) and to find out correlation of left ventricular hypertrophy with severity of chronic kidney disease.Methods: From November 2012 to September 2014, 100 chronic kidney disease patients who were admitted in hospital or attended on OPD basis for dialysis were taken for study. Detailed history, clinical evaluation, laboratory investigations and echocardiography was carried out. The diagnosis of CKD was made on basis of serum creatinine more than 1.5 mg/dl which remained constantly for more than 3 months. Patients with mild, moderate and severe CKD were having serum creatinine level 1.5-3mg/dl, 3-6mg/dl and > 6mg/dl respectively. Glomerular filtration rate (GFR) was calculated by modification of diet in renal disease (MDRD) equation. Cut-off for CKD was taken to be <60ml/min / 1.73m2 as per existing guidelines.Results: Out of 100 patients studied, 67 were males and 33 were females. All patients were selected randomly. Majority of the patients were in the age group of 61 -70 years (41%). In the present study, it was found that left ventricular mass index (LVMI) which reflects LVH showed a progressive rise in severity of renal failure with 17 % of mild category of CKD having LVH as compared to 26% of moderate category and 57% of severe category of CKD.Conclusions: Patients with CKD have LVH, which is more marked in patients with severe CKD. So, these patients should have a thorough cardiovascular evaluation even if there were no symptoms, and efforts should be made to prevent LVH, during the early course of renal insufficiency, such as strict control of hypertension, anaemia.


2017 ◽  
Vol 28 ◽  
Author(s):  
Yaw Ampem Amoako ◽  
Dennis Odai Laryea ◽  
George Bedu-Addo ◽  
Bernard Cudjoe Nkum ◽  
Jacob Plange-Rhule

2015 ◽  
Vol 31 (7) ◽  
pp. 1088-1099 ◽  
Author(s):  
Maren Leifheit-Nestler ◽  
Robert große Siemer ◽  
Kathrin Flasbart ◽  
Beatrice Richter ◽  
Felix Kirchhoff ◽  
...  

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