Circulating miRNAs and Vascular Injury Markers Associate with Cardiovascular Function in Older Patients Reaching End-Stage Kidney Disease

The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from ‘The Cognitive decline in Older Patients with End stage renal disease’ (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology.

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Association of cardiovascular structure and function with cerebrovascular changes and cognitive function in older patients with end-stage renal disease

Aging ◽

10.18632/aging.102696 ◽

2020 ◽

Vol 12 (2) ◽

pp. 1496-1511 ◽

Cited By ~ 1

Author(s):

Laurien E. Zijlstra ◽

Stella Trompet ◽

J. Wouter Jukema ◽

Lucia J. M. Kroft ◽

Jeroen de Bresser ◽

...

Keyword(s):

Cognitive Function ◽

Renal Disease ◽

End Stage Renal Disease ◽

Older Patients ◽

Structure And Function ◽

Cardiovascular Structure ◽

Stage Renal Disease ◽

End Stage ◽

And Function

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Health-related quality of life and symptoms of conservative care versus dialysis in patients with end-stage kidney disease: a systematic review

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa078 ◽

2020 ◽

Cited By ~ 1

Author(s):

Wouter R Verberne ◽

Iris D van den Wittenboer ◽

Carlijn G N Voorend ◽

Alferso C Abrahams ◽

Marjolijn van Buren ◽

...

Keyword(s):

Kidney Disease ◽

Older Patients ◽

Health Related Quality ◽

End Stage Kidney Disease ◽

Conservative Care ◽

Patient Reported ◽

Related Quality ◽

Health Related ◽

End Stage

Abstract Background Non-dialytic conservative care (CC) has been proposed as a viable alternative to maintenance dialysis for selected older patients to treat end-stage kidney disease (ESKD). This systematic review compares both treatment pathways on health-related quality of life (HRQoL) and symptoms, which are major outcomes for patients and clinicians when deciding on preferred treatment. Methods We searched PubMed, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus and PsycINFO from inception to 1 October 2019 for studies comparing patient-reported HRQoL outcomes or symptoms between patients who chose either CC or dialysis for ESKD. Results Eleven observational cohort studies were identified comprising 1718 patients overall. There were no randomized controlled trials. Studies were susceptible to selection bias and confounding. In most studies, patients who chose CC were older and had more comorbidities and worse functional status than patients who chose dialysis. Results were broadly consistent across studies, despite considerable clinical and methodological heterogeneity. Patient-reported physical health outcomes and symptoms appeared to be worse in patients who chose CC compared with patients who chose dialysis but had not yet started, but similar compared with patients on dialysis. Mental health outcomes were similar between patients who chose CC or dialysis, including before and after dialysis start. In patients who chose dialysis, the burden of kidney disease and impact on daily life increased after dialysis start. Conclusions The available data, while heterogeneous, suggest that in selected older patients, CC has the potential to achieve similar HRQoL and symptoms compared with a dialysis pathway. High-quality prospective studies are needed to confirm these provisional findings.

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Can quality of life be improved for the increasing numbers of older patients with end-stage kidney disease?

Expert Review of Pharmacoeconomics & Outcomes Research ◽

10.1586/erp.10.78 ◽

2010 ◽

Vol 10 (6) ◽

pp. 661-666 ◽

Cited By ~ 10

Author(s):

Edwina A Brown

Keyword(s):

Quality Of Life ◽

Kidney Disease ◽

Older Patients ◽

End Stage Kidney Disease ◽

End Stage

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A randomized pilot study comparing graft-first to fistula-first strategies in older patients with incident end-stage kidney disease: Clinical rationale and study design

Contemporary Clinical Trials Communications ◽

10.1016/j.conctc.2019.100357 ◽

2019 ◽

Vol 14 ◽

pp. 100357 ◽

Cited By ~ 2

Author(s):

Mariana Murea ◽

Randolph L. Geary ◽

Matthew S. Edwards ◽

Shahriar Moossavi ◽

Ross P. Davis ◽

...

Keyword(s):

Pilot Study ◽

Kidney Disease ◽

Study Design ◽

Older Patients ◽

End Stage Kidney Disease ◽

End Stage

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Comprehensive Search for Novel Circulating miRNAs and Axon Guidance Pathway Proteins Associated with Risk of End Stage Kidney Disease in Diabetes

Journal of the American Society of Nephrology ◽

10.1681/asn.2021010105 ◽

2021 ◽

pp. ASN.2021010105

Author(s):

Eiichiro Satake ◽

Pierre-Jean Saulnier ◽

Hiroki Kobayashi ◽

Manoj Gupta ◽

Helen Looker ◽

...

Keyword(s):

Kidney Disease ◽

Axon Guidance ◽

Diabetic Kidney Disease ◽

Umbilical Vein ◽

Micro Rna ◽

Circulating Mirnas ◽

End Stage Kidney Disease ◽

Diabetic Kidney ◽

End Stage ◽

Circulating Levels

Background Mechanisms underlying the progression of diabetic kidney disease to end-stage kidney disease (ESKD) are not fully understood. Methods We performed global micro-RNA (miRNA) analysis in plasma in two cohorts encompassing 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease and targeted proteomics analysis in plasma in four cohorts encompassing 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsies from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. Results In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, miR-328-3p), which were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins—most notably EFNA4 and EPHA2—were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsies. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. Conclusions This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition.

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