RESUMEN
BACKGROUND: The cardiovascular and metabolic benefits of physical activity have been studied at length, however, data on the association between physical fitness and progression to kidney disease is lacking. We aimed to identify the association between cardiorespiratory fitness and development of chronic kidney disease (CKD) among the healthy population. METHODS: We retrospectively investigated 11,579 healthy self-referred subjects who underwent annual medical screening. All subjects had an estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73 m2, no known kidney disease, hematuria or proteinuria, and were free of diabetes or cardiovascular disease at baseline. All participants completed a maximal exercise test, and were categorized into low and high cardiorespiratory fitness groups based on age- and gender-specific quintiles. The primary end point was the development of significant CKD defined as eGFR below 45 ml/min/1.73 m2 during follow-up. RESULTS: Median follow-up was 7.6 years, and the participants' median age was 50 ± 8 years. Baseline creatinine and eGFR were 1.02 mg/dl and 81 ml/min/1.73 m2, respectively. During follow-up, 81 (0.6%) participants developed CKD, and the cumulative probability was significantly higher among the low fitness group (HR = 2.41, p = 0.001). The effect of physical fitness on the risk to develop CKD remained significant after adjusting for age, gender, baseline creatinine and other cardiovascular risk factors. CONCLUSION: Cardiorespiratory fitness is an independent risk factor inversely associated with development of CKD.
RESUMEN
Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities. Methods: Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated. Result: In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012-2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft.
RESUMEN
BACKGROUND: Chronological and biological age correlate with DNA methylation levels at specific sites in the genome. Linear combinations of multiple methylation sites, termed epigenetic clocks, can inform us the chronological age and predict multiple health-related outcomes. However, why some sites correlating with lifespan, healthspan, or specific medical conditions remain poorly understood. Kidney fibrosis is the common pathway for chronic kidney disease, which affects 10% of European and US populations. RESULTS: Here we identify epigenetic clocks and methylation sites that correlate with kidney function. Moreover, we identify methylation sites that have a unique methylation signature in the kidney. Methylation levels in majority of these sites correlate with kidney state and function. When kidney function deteriorates, all of these sites regress toward the common methylation pattern observed in other tissues. Interestingly, while the majority of sites are less methylated in the kidney and become more methylated with loss of function, a fraction of the sites are highly methylated in the kidney and become less methylated when kidney function declines. These methylation sites are enriched for specific transcription-factor binding sites. In a large subset of sites, changes in methylation patterns are accompanied by changes in gene expression in kidneys of chronic kidney disease patients. CONCLUSIONS: These results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines. However, this information loss is not random, but guided toward a baseline that is dependent on the genomic loci. SIGNIFICANCE STATEMENT: DNA methylation at specific sites accurately reflects chronological and biological age. We identify sites that have a unique methylation pattern in the kidney. Methylation levels in the majority of these sites correlate with kidney state and function. Moreover, when kidney function deteriorates, all of these sites regress toward the common methylation pattern observed in other tissues. Thus, the unique methylation signature of the kidney is degraded, and epigenetic information is lost, when kidney disease progresses. These methylation sites are enriched for specific and methylation-sensitive transcription-factor binding sites, and associated genes show disease-dependent changes in expression. These results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines.