Synergistic effect of renalase and chronic kidney disease on endothelin-1 in patients with coronary artery disease ‒ a cross-sectional study

Li, Yu-Hsuan; Sheu, Wayne Huey‐Herng; Lee, Wen‐Jane; Wang, Jun‐Sing; Fu, Chia-Po; Liang, Kae‐Woei; Lee, I-Te

doi:10.1038/s41598-018-25763-4

Cited by 15 publications

(12 citation statements)

References 51 publications

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“…The copyright holder for this this version posted September 16, 2021. ; https://doi.org/10.1101/2021.09.13.21263340 doi: medRxiv preprint interaction showed enrichment of genes in the signaling pathways of Rho GTPase small molecules, axon guidance, actin skeleton, VEGFA-NRP1 induced angiogenesis, and the endothelin-1 pathway. Identification of the endothlin-1 41 and TGFB1 pathways in our study is supported by prior literature on the role of these pathways in DKD susceptibility [42][43][44][45][46][47][48][49][50][51][52][53] . The Gas6-AKT pathway was shown to be involved in mesangial hypertrophy in rat models of DKD 54,55 .…”

Section: Discussionsupporting

confidence: 88%

Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

Stefansson

Nair

Melsom

et al. 2021

Preprint

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Hyperfiltration (HF) is a state of high glomerular filtration rate (GFR) observed in early diabetes that damages glomeruli, resulting in an iterative process of increasing filtration load on fewer and fewer remaining functional glomeruli. To delineate underlying cellular mechanisms of damage induced by HF, transcriptional profiles of kidney biopsies from Pima Indians with type 2 diabetes with or without early-stage diabetic kidney disease (DKD) were grouped into two HF categories based on annual iothalamate GFR measurements. Twenty-six participants with a peak GFR measurement within two years of biopsy were categorized as the HF group, and 26 in whom biopsy preceded peak GFR by >2 years were considered pre-HF. The HF group had higher hemoglobin A1c, higher urine albumin-to-creatinine ratio, increased glomerular basement membrane width and lower podocyte density compared to the pre-HF group. A glomerular 1240-gene transcriptional signature identified in the HF group was enriched for endothelial stress response signaling genes, including from endothelin-1, tec-kinase and TGF-β1 pathways, with the majority of the transcripts mapped to endothelial and inflammatory cell clusters in kidney single cell transcriptional data. This analysis reveals molecular pathomechanisms contributing to development of HF and early DKD and involving putative ligand-receptor pairs and downstream intracellular targets linked to cellular crosstalk between endothelial and mesangial cells.

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Section: Discussionsupporting

confidence: 88%

Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

Stefansson

Nair

Melsom

et al. 2021

Preprint

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“…The lack of association of the studied polymorphism with diabetic nephropathy is difficult to explain in the light of the links between renalase and kidney disease widely described in the literature. Concentrations of renalase in serum are significantly higher in patients with chronic kidney disease (CKD) than in control group and are elevated in the increasing stage of renal failure [31][32][33]. Zbroch et al described a significant inverse correlation between the serum renalase and residual renal function [34].…”

Section: Discussionmentioning

confidence: 99%

Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus

et al. 2021

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Aims Renalase (RNLS) is an enzyme with monoamine oxidase activity that metabolizes circulating catecholamines. The RNLS gene Asp37Glu missense polymorphism (rs2296545) has been associated with hypertension, cardiac hypertrophy and dysfunction, and stroke. The purpose of our study was to investigate the potential involvement of this polymorphism in the microvascular complications of type 2 diabetes (T2DM). Methods In this case–control study, the polymorphism was genotyped in 860 patients with T2DM and 400 healthy controls. The genotype and allele distribution was compared in subgroups of patients: with diabetic nephropathy (DN+) (n = 405) versus DN− (independently of the presence of DR) and, similarly, patients with diabetic retinopathy (DR+) (n = 328) versus DR− (independently of the presence of DN). Results No significant association was detected between analyzed polymorphism and DN. In contrast, the retinopathy subgroup showed a significantly higher frequency of G allele (OR 1.4, 95% CI 1.16–1.72, p = 0.0005) and GG genotype (OR 1.86, 95% CI 1.26–2.75, p = 0.001) than DR− patients. The effect of RNLS Glu37Asp polymorphism on DR remained significant after adjustments for age, gender, BMI, and duration of T2DM (p = 0.005). Conclusions This is the first study to investigate RNLS gene polymorphism in microvascular complications of T2DM. The results suggest that RNLS rs2296545 SNP might be considered a risk factor for diabetic retinopathy in T2DM patients. This can provide new insight into the role of renalase gene in the pathophysiology of microvascular complications of diabetes.

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“…Li et al have indicated increased renalase serum levels in CKD patients, which correlated with increased levels of endotelin, a hormone involved in pathogenesis of cardiovascular diseases [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Renalase in Haemodialysis Patients with Chronic Kidney Disease

Wiśniewska

Serwin

Dziedziejko

et al. 2021

JCM

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Chronic kidney disease (CKD) is an inflammatory disease leading to kidney insufficiency and uremia. Renalase is a novel flavoprotein with enzymatic activities. Previous studies have shown that chronic kidney disease may influence renalase serum levels. Renalase metabolises catecholamines and therefore may be involved in the pathogenesis of hypertension and other diseases of the circulatory system. In this study, we examined renalase levels in serum, erythrocytes and urine from haemodialysis CKD patients. The study enrolled 77 haemodialysis CKD patients and 30 healthy subjects with normal kidney function as the control group. Renalase serum and urine concentrations in CKD patients were significantly increased when compared with control subjects (185.5 ± 64.3 vs. 19.6 ± 5.0 ng/mL; p < 0.00001 and 207.1 ± 60.5 vs. 141.6 ± 41.3 ng/mL; p = 0.00040, respectively). In contrast, renalase levels in erythrocytes were significantly lower in CKD patients when compared with control subjects (176.5 ± 60.9 vs. 233.2 ± 83.1 ng/mL; p = 0.00096). Plasma levels of dopamine, adrenaline and noradrenaline were also significantly lower in CKD patients when compared with controls. Conclusions: Increased serum and urine concentrations of renalase in haemodialysis CKD patients are likely related to compensatory production in extrarenal organs as a result of changes in the cardiovascular system and hypertension. The decreased plasma concentrations of catecholamines may be due to their increased degradation by plasma renalase. Decreased renalase levels in erythrocytes may be probably due to lower renalase synthesis by the kidneys in CKD. The results indicate the presence of renalase in erythrocytes.

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Synergistic effect of renalase and chronic kidney disease on endothelin-1 in patients with coronary artery disease ‒ a cross-sectional study

Cited by 15 publications

References 51 publications

Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus

Renalase in Haemodialysis Patients with Chronic Kidney Disease

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