scholarly journals P0070ARE BIOMARKERS OF AGEING IN THE FORM OF TELOMERE LENGTH AND/OR THE DNA METHYLATION STATUS ASSOCIATED WITH FRAILTY PHENOTYPE IN PATIENTS WITH END STAGE KIDNEY DISEASE ON DIALYSIS?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Vasantha Muthuppalaniappan ◽  
Kieran McCafferty ◽  
Muhammad Yaqoob
Keyword(s):  
Dna Methylation ◽  
Kidney Disease ◽  
Telomere Length ◽  
Biological Age ◽  
Chronological Age ◽  
Dialysis Patients ◽  
End Stage Kidney Disease ◽  
Frailty Phenotype ◽  
Cpg Sites ◽  
End Stage

Abstract Background and Aims There appears to be an accelerated ageing process seen among patients with end stage kidney disease. They often exhibit prematurely aged phenotypes which include frailty, sarcopenia and protein energy wasting. These phenotypes are associated with increased morbidity and mortality. The exact reason for premature ageing in this cohort is poorly understood. We hypothesised that biomarkers of cellular senescence and biological age may be associated with phenotypes of ageing observed in dialysis patients; in particular the frailty phenotype. Both telomere length (TL) and DNA methylation (DNAm) status have been recognised as predictors of biological age. The aim of the study was to investigate the relationship between TL and DNAm status with frailty phenotype among patients on dialysis. Method This was a single centre prospective observational study among eligible haemodialysis (HD) and peritoneal dialysis (PD) patients as per the inclusion and exclusion criteria. All recruited patients had their DNA extracted from peripheral leucocytes and frailty was measured by using the Fried Frailty Phenotype criteria. Extracted DNA was used to measure TL by quantitate polymerase chain reaction according to the modified Cawthon protocol. DNAm status was measured by sodium bisulphite conversion with targeted sequencing of 48 CpG sites. All baseline demographic data were obtained from electronic patient record. Results Between the period of December 2015 to July 2018, 239 dialysis (125 HD, 114 PD) patients were recruited. The age range of the study recruits were 23 to 83 years of age with a mean age of 54.3 years. There were 44 and 43 females in the HD and PD group respectively. All patients had TL measured and 228 patients (118 in HD, 110 in PD) had DNAm status measured successfully. Frailty assessments at baseline were completed in 213 patients (110 in HD, 103 in PD). A decrease in mean TL (p<0.001) and increased mean DNAm age (p<0.001) was observed in the frail group. TL and DNAm status were significantly associated with frailty in a univariate analysis, p=0.010 and p=0.014 respectively but only TL remained significant in a multivariate analysis to predict frailty, p=0.018. Increased frailty was observed in dialysis patients with shorter TL which remained significant following multivariate logistic regression analysis. A receiver operating characteristic curve analysis demonstrated that TL was a significant predictor of frailty, p<0.001 with an area under the curve of 0.64. A decrease of TL by one standard deviation was associated with a 52.2% increase risk of frailty when adjusted for age and gender in this dialysis cohort. Conclusion The study supports the hypothesis that TL; a biomarker of ageing is better associated with frailty, an ageing phenotype in comparison to DNAm status in dialysis patients. This is the first study to show a significant association between TL and frailty status in the dialysis patients. DNAm status is derived from an individual’s chronological age and may not be the best surrogate for chronological age. Therefore, to use this measure seems rather counter intuitive as the incorporation of chronological age might mask clinically significant associations that exist when the DNAm status is considered in isolation. These findings provide a preliminary proof of concept validation that TL is associated with frailty and may provide the basis of future research. The use of targeted methylation CpG sites may be a better predictor of frailty in this cohort which is an area that has sparked an interest.

Arrhythmias in dialysis patients

2021 ◽  
Vol 4 (57) ◽  
pp. 8-11
Author(s):  
Szymon Warwas ◽  
Marta Jagosz ◽  
Beata Średniawa ◽  
Michał Mazurek ◽  
Ewa Jędrzejczyk-Patej
Keyword(s):  
Cardiovascular Diseases ◽  
Sudden Cardiac Death ◽  
Kidney Disease ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Dialysis Patients ◽  
End Stage Kidney Disease ◽  
Common Cause ◽  
Conduction Disturbances ◽  
End Stage

The most common cause of death among dialysis patients with end-stage kidney disease are cardiovascular diseases. It is estimated that 18-27% of all deaths in dialysis patients are sudden cardiac deaths due to arrhythmias and conduction disturbances. The most common arrhythmias in dialysis patients, often leading to sudden death, are not ventricular arrhythmias but bradyarrhythmias. The article below discusses the most common arrhythmias in dialysis patients and methods of preventing sudden cardiac death in this group of patients.

scholarly journals Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease

2020 ◽  
Author(s):  
Laura J Smyth ◽  
Jill Kilner ◽  
Viji Nair ◽  
Hongbo Liu ◽  
Eoin Brennan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Gene Annotation ◽  
Repeated Testing ◽  
End Stage Kidney Disease ◽  
Diabetic Kidney ◽  
Long Duration ◽  
End Stage ◽  
Methylation Patterns

A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), which is the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina's Infinium MethylationEPIC BeadChip arrays (n=862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p≤x10-8 and fold change ±2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. Top-ranked genes within which several dmCpGs were located and supported by in silico functional data, and replication where possible, include; AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9, and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation. Epigenetic alterations provide a dynamic link between an individual's genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals, has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.

scholarly journals Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes: analysis from the Hong Kong Diabetes Register

Diabetologia ◽  
2021 ◽  
Author(s):  
Feifei Cheng ◽  
Andrea O. Luk ◽  
Hongjiang Wu ◽  
Claudia H. T. Tam ◽  
Cadmon K. P. Lim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hong Kong ◽  
Kidney Disease ◽  
Telomere Length ◽  
Rapid Decline ◽  
End Stage Kidney Disease ◽  
End Stage ◽  
Diabetes Register

Abstract Aims/hypothesis Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes. Methods We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. Results In this cohort (mean ± SD age 54.3 ± 12.6 years) followed up for 14.1 ± 5.3 years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 ± 1.2 vs 4.7 ± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024). Conclusions/interpretation rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes. Graphical abstract

scholarly journals Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease: an exploratory study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
L. J. Smyth ◽  
J. Kilner ◽  
V. Nair ◽  
H. Liu ◽  
E. Brennan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Gene Annotation ◽  
Repeated Testing ◽  
End Stage Kidney Disease ◽  
Diabetic Kidney ◽  
Long Duration ◽  
End Stage ◽  
Methylation Patterns

Abstract Background A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina’s Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10–8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. Results Top-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation. Conclusions Epigenetic alterations provide a dynamic link between an individual’s genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.

scholarly journals Dysfunction of natural killer cells in end-stage kidney disease on hemodialysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Kei Nagai
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Number ◽  
Dialysis Patients ◽  
End Stage Kidney Disease ◽  
Activating Receptors ◽  
End Stage

AbstractNatural killer (NK) cells are known to play an important role in defense against infection and tumors. Although there is no clear consensus, most studies have shown that the number and cytotoxicity of NK cells decreases in end-stage kidney disease (ESKD) patients undergoing hemodialysis. Uremic patients chronically suffer from oxidative stress, which could be responsible for downregulation of the activating receptors on NK cells and modulation of ligand expression for activating receptors. Theoretically, the reduced number of NK cells and decreased function might increase susceptibility to viral infections and cancer development in patients with ESKD. There is emerging evidence that NK cell numbers may be an outcome predictor in renal transplantation; however, the clinical significance of NK cell dysfunction in dialysis patients requires clarification. In this review, I describe NK cell number, cytotoxic activity, and activating mechanisms in the context of uremia and oxidative stress, which is anticipated to assist in elucidating the mechanisms underlying immunodeficiency in dialysis patients.

scholarly journals Epidemiology of COVID-19 Infection in Hospitalized End-Stage Kidney Disease Patients in a Predominantly African-American Population

2021 ◽  
pp. 1-9
Author(s):  
José E. Navarrete ◽  
David C. Tong ◽  
Jason Cobb ◽  
Frederic F. Rahbari-Oskoui ◽  
Darya Hosein ◽  
...  
Keyword(s):  
African American ◽  
Kidney Disease ◽  
Peripheral Vascular ◽  
C Reactive Protein ◽  
Dialysis Patients ◽  
End Stage Kidney Disease ◽  
Reactive Protein ◽  
History Of ◽  
End Stage ◽  
D Dimer

<b><i>Background:</i></b> End-stage kidney disease patients on dialysis are particularly susceptible to COVID-19 infection due to comorbidities, age, and logistic constraints of dialysis making social distancing difficult. We describe our experience with hospitalized dialysis patients with COVID-19 and factors associated with mortality. <b><i>Methods:</i></b> From March 1, 2020, to May 31, 2020, all dialysis patients admitted to 4 Emory Hospitals and tested for COVID-19 were identified. Sociodemographic information and clinical and laboratory data were obtained from the medical record. Death was defined as an in-hospital death or transfer to hospice for end-of-life care. Patients were followed until discharge or death. <b><i>Results:</i></b> Sixty-four dialysis patients with COVID-19 were identified. Eighty-four percent were African-American. The median age was 64 years, and 59% were males. Four patients were on peritoneal dialysis, and 60 were on hemodialysis for a median time of 3.8 years, while 31% were obese. Fever (72%), cough (61%), and diarrhea (22%) were the most common symptoms at presentation. Thirty-three percent required admission to intensive care unit, and 23% required mechanical ventilation. The median length of stay was 10 days, while 11 patients (17%) died during hospitalization and 17% were discharged to a temporary rehabilitation facility. Age &#x3e;65 years (RR 13.7, CI: 1.9–100.7), C-reactive protein &#x3e;100 mg/dL (RR 8.3, CI: 1.1–60.4), peak D-dimer &#x3e;3,000 ng/mL (RR 4.3, CI: 1.03–18.2), bilirubin &#x3e;1 mg/dL (RR 3.9, CI: 1.5–10.4), and history of peripheral vascular disease (RR 3.2, CI: 1.2–9.1) were associated with mortality. Dialysis COVID-19-infected patients were more likely to develop thromboembolic complications than those without COVID-19 (RR 3.7, CI: 1.3–10.1). <b><i>Conclusion:</i></b> In a predominantly African-American population, the mortality of end-stage kidney disease patients admitted with COVID-19 infection was 17%. Age, C-reactive protein, D-dimer, bilirubin, and history of peripheral vascular disease were associated with worse survival.

scholarly journals Frailty Prevalence in Younger End-Stage Kidney Disease Patients Undergoing Dialysis and Transplantation

2020 ◽  
Vol 51 (7) ◽  
pp. 501-510
Author(s):  
Nadia M. Chu ◽  
Xiaomeng Chen ◽  
Silas P. Norman ◽  
Jessica Fitzpatrick ◽  
Stephen M. Sozio ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Age Groups ◽  
Wald Test ◽  
Community Dwelling ◽  
End Stage Kidney Disease ◽  
Frailty Phenotype ◽  
Younger Adults ◽  
Younger Patients ◽  
End Stage ◽  
Community Dwelling Older Adults

Background: Frailty, originally characterized in community-dwelling older adults, is increasingly being studied and implemented for adult patients with end-stage kidney disease (ESKD) of all ages (>18 years). Frailty prevalence and manifestation are unclear in younger adults (18–64 years) with ESKD; differences likely exist based on whether the patients are treated with hemodialysis (HD) or kidney transplantation (KT). Methods: We leveraged 3 cohorts: 378 adults initiating HD (2008–2012), 4,304 adult KT candidates (2009–2019), and 1,396 KT recipients (2008–2019). The frailty phenotype was measured within 6 months of dialysis initiation, at KT evaluation, and KT admission. Prevalence of frailty and its components was estimated by age (≥65 vs. <65 years). A Wald test for interactions was used to test whether risk factors for frailty differed by age. Results: In all 3 cohorts, frailty prevalence was higher among older than younger adults (HD: 71.4 vs. 47.3%; candidates: 25.4 vs. 18.8%; recipients: 20.8 vs. 14.3%). In all cohorts, older patients were more likely to have slowness and weakness but less likely to report exhaustion. Among candidates, older age (odds ratio [OR] = 1.79, 95% CI: 1.47–2.17), non-Hispanic black race (OR = 1.30, 95% CI: 1.08–1.57), and dialysis type (HD vs. no dialysis: OR = 2.06, 95% CI: 1.61–2.64; peritoneal dialysis vs. no dialysis: OR = 1.78, 95% CI: 1.28–2.48) were associated with frailty prevalence, but sex and Hispanic ethnicity were not. These associations did not differ by age (pinteractions > 0.1). Similar results were observed for recipients and HD patients. Conclusions: Although frailty prevalence increases with age, younger patients have a high burden. Clinicians caring for this vulnerable population should recognize that younger patients may experience frailty and screen all age groups.

scholarly journals Why and how should we promote home dialysis for patients with end-stage kidney disease during and after the coronavirus 2019 disease pandemic? A French perspective

2021 ◽  
Author(s):  
Guy Rostoker ◽  
Belkacem Issad ◽  
Hafedh Fessi ◽  
Ziad A. Massy
Keyword(s):  
Kidney Disease ◽  
Scientific Data ◽  
Dialysis Patients ◽  
End Stage Kidney Disease ◽  
Health Crisis ◽  
Home Dialysis ◽  
Objective Information ◽  
Home Haemodialysis ◽  
Renal Replacement Therapies ◽  
End Stage

AbstractThe health crisis induced by the pandemic of coronavirus 2019 disease (COVID-19) has had a major impact on dialysis patients in France. The incidence of infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first wave of the COVID-19 epidemic was 3.3% among dialysis patients—13 times higher than in the general population. The corresponding mortality rate was high, reaching 21%. As of 19th April, 2021, the cumulative prevalence of SARS-CoV-2 infection in French dialysis patients was 14%. Convergent scientific data from France, Italy, the United Kingdom and Canada show that home dialysis reduces the risk of SARS-CoV-2 infection by a factor of at least two. Unfortunately, home dialysis in France is not sufficiently developed: the proportion of dialysis patients being treated at home is only 7%. The obstacles to the provision of home care for patients with end-stage kidney disease in France include (i) an unfavourable pricing policy for home haemodialysis and nurse visits for assisted peritoneal dialysis (PD), (ii) insufficient training in home dialysis for nephrologists, (iii) the small number of administrative authorizations for home dialysis programs, and (iv) a lack of structured, objective information on renal replacement therapies for patients with advanced chronic kidney disease (CKD). We propose a number of pragmatic initiatives that could be simultaneously enacted to improve the situation in three areas: (i) the provision of objective information on renal replacement therapies for patients with advanced CKD, (ii) wider authorization of home dialysis networks and (iii) price increases in favour of home dialysis procedures.

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