Renalase attenuates hypertension, renal injury and cardiac remodelling in rats with subtotal nephrectomy

Abstract

Chronic kidney disease is associated with higher risk of cardiovascular complication and this interaction can lead to accelerated dysfunction in both organs. Renalase, a kidney‐derived cytokine, not only protects against various renal diseases but also exerts cardio‐protective effects. Here, we investigated the role of renalase in the progression of cardiorenal syndrome (CRS) after subtotal nephrectomy. Sprague–Dawley rats were randomly subjected to sham operation or subtotal (5/6) nephrectomy (STNx). Two weeks after surgery, sham rats were intravenously injected with Hanks' balanced salt solution (sham), and STNx rats were randomly intravenously injected with adenovirus‐β‐gal (STNx+Ad‐β‐gal) or adenovirus‐renalase (STNx+Ad‐renalase) respectively. After 4 weeks of therapy, Ad‐renalase administration significantly restored plasma, kidney and heart renalase expression levels in STNx rats. We noticed that STNx rats receiving Ad‐renalase exhibited reduced proteinuria, glomerular hypertrophy and interstitial fibrosis after renal ablation compared with STNx rats receiving Ad‐β‐gal; these changes were associated with significant decreased expression of genes for fibrosis markers, proinflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components. At the same time, systemic delivery of renalase attenuated hypertension, cardiomyocytes hypertrophy and cardiac interstitial fibrosis; prevented cardiac remodelling through inhibition of pro‐fibrotic genes expression and phosphorylation of extracellular signal‐regulated kinase (ERK)‐1/2. In summary, these results indicate that renalase protects against renal injury and cardiac remodelling after subtotal nephrectomy via inhibiting inflammation, oxidative stress and phosphorylation of ERK‐1/2. Renalase shows potential as a therapeutic target for the prevention and treatment of CRS in patients with chronic kidney disease.

Transient changes in serum renalase concentration during long-distance running: The case of an amateur runner under continuous training

“…The study of Li et al showed a significant increase in renalase expression with increasing oxidative stress in a mice model of ischemia-reperfusion injury, and it was suppressed by antioxidants 24) . In addition, it has been reported that renalase increases during ischemiareperfusion and has the effect of protecting organs [25][26][27] . There was also a significant increase in oxidative stress in this study, which is presumed to be ischemia of an organ or organ damage due to exercise 28) .…”

Levels of renalase and advanced oxidation protein products with regard to catecholamines in haemodialysed patients

“…Yin et al [45] confirmed the beneficial effects of renalase supplementation on functional and histological alterations of kidney and heart, and investigated the underlying mechanism in a rat model with progressive renal injury. Furthermore, the authors [45] have demonstrated that the systematic delivery of renalase, a kidney-derived protein, attenuated both renal and cardiac fibrosis, improved renal function and prevented cardiac remodeling six weeks after renal ablation through its anti-inflammatory and anti-oxidant effects, inhibition of extracellular signal-regulated kinase (ERK) pathway, which indicate that renalase may play a crucial role in the interaction between kidney and heart. Taken together, these findings indicated renalase supplementation might protect renal injury through inhibiting inflammation activation and oxidative stress in remnant kidney.…”

LCZ696 (Sacubitril/Valsartan), an Angiotensin-Receptor Neprilysin Inhibitor, Attenuates Cardiac Hypertrophy, Fibrosis, and Vasculopathy in a Rat Model of Chronic Kidney Disease

“…23 In addition, cardiac tissue from CKD animals had increased matrix and TGF-β abundance and reduced matrix metalloproteinase-1. 24 It should also be noted that there are other CKD-related factors which play a role in the pathogenesis of uremic cardiomyopathy such as increased concentrations of FGF-23, Klotho deficiency and activation of the RAAS. 25,26 The effectiveness of RAAS inhibition in treatment of HF has been demonstrated in numerous clinical trials using ACEI or ARB therapy.…”