The ERA Registry Annual Report 2021: a summary

[EN] 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.The ERA Registry is funded by the European Renal Association (ERA). This article was written by B.A. Boerstra et al. on behalf of the ERA Registry, which is an official body of the ERA. P.B. reports payments from AstraZeneca and Takeda. S.B. reports consulting fees from GSK, Bayer, and AstraZeneca. A.C.A. reports payments from Diaverum Spain. F.J. reports payments from AstraZeneca, Boehringer Ingelheim, Servier, and Merck; and support for attending meetings and/or travel from Servier, AstraZeneca, Pfizer, and Fresenius. J.M. reports receiving support for attending meetings and/or travel from CSL Vifor. M.F.S.-R. reports receiving consulting fees from Baxter, Fresenius, and Nipro; payments from Baxter and Fresenius; and support for attending meetings and/or travel from Vifor, Fresenius, and Palex. I.Z. reports consulting fees from Astellas, Pharma, and Bayer; and payments from AstraZeneca, Bayer, Behringer Ingelheim, Norameda, and Swixx Biopharma. A.O. reports receiving grants from Sanofi; and consultancy or speaker fees or travel support from Advicciene, Astellas Pharma, AstraZeneca, Amicus, Amgen, Boehringer Ingelheim, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Menarini, Mundipharma, Kyowa Kirin, Lilly, Alexion, Freeline, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex, and Vifor Fresenius Medical Care Renal Pharma. K.J.J. reports receiving funds from ERA during the conduct of the study and grants from ESPN. V.S.S. reports receiving funds from ERA.Boerstra, BA.; Boenink, R.; Astley, ME.; Bonthuis, M.; Elhafeez, SA.; Arribas Monzón, F.; Asberg, A.... (2024). The ERA Registry Annual Report 2021: a summary. Clinical Kidney Journal. 17(2). https://doi.org/10.1093/ckj/sfad28117

The ERA Registry Annual Report 2021:a summary

BackgroundThe 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.MethodsData 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.ResultsIn 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

Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

The Peritoneal Membrane—A Potential Mediator of Fibrosis and Inflammation among Heart Failure Patients on Peritoneal Dialysis

Peritoneal dialysis is a feasible, cost-effective, home-based treatment of renal replacement therapy, based on the dialytic properties of the peritoneal membrane. As compared with hemodialysis, peritoneal dialysis is cheaper, survival rate is similar, residual kidney function is better preserved, fluid and solutes are removed more gradually and continuously leading to minimal impact on hemodynamics, and risks related to a vascular access are avoided. Those features of peritoneal dialysis are useful to treat refractory congestive heart failure patients with fluid overload. It was shown that in such patients, peritoneal dialysis improves functional status and quality of life, reduces hospitalization rate, and may decrease mortality rate. High levels of serum proinflammatory cytokines and fibrosis markers, among other factors, play an important part in congestive heart failure pathogenesis and progression. We demonstrated that those levels decreased following peritoneal dialysis treatment in refractory congestive heart failure patients. The exact mechanism of beneficial effect of peritoneal dialysis in refractory congestive heart failure is currently unknown. Maintenance of fluid balance, leading to resetting of neurohumoral activation towards a more physiological condition, reduced remodeling due to the decrease in mechanical pressure on the heart, decreased inflammatory cytokine levels and oxidative stress, and a potential impact on uremic toxins could play a role in this regard. In this paper, we describe the unique characteristics of the peritoneal membrane, principals of peritoneal dialysis and its role in heart failure patients

Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression

Abstract 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

Human Kidney Tubule-Specific Gene Expression Based Dissection of Chronic Kidney Disease Traits

Chronic kidney disease (CKD) has diverse phenotypic manifestations including structural (such as fibrosis) and functional (such as glomerular filtration rate and albuminuria) alterations. Gene expression profiling has recently gained popularity as an important new tool for precision medicine approaches. Here we used unbiased and directed approaches to understand how gene expression captures different CKD manifestations in patients with diabetic and hypertensive CKD. Transcriptome data from ninety-five microdissected human kidney samples with a range of demographics, functional and structural changes were used for the primary analysis. Data obtained from 41 samples were available for validation. Using the unbiased Weighted Gene Co-Expression Network Analysis (WGCNA) we identified 16 co-expressed gene modules. We found that modules that strongly correlated with eGFR primarily encoded genes with metabolic functions. Gene groups that mainly encoded T-cell receptor and collagen pathways, showed the strongest correlation with fibrosis level, suggesting that these two phenotypic manifestations might have different underlying mechanisms. Linear regression models were then used to identify genes whose expression showed significant correlation with either structural (fibrosis) or functional (eGFR) manifestation and mostly corroborated the WGCNA findings. We concluded that gene expression is a very sensitive sensor of fibrosis, as the expression of 1654 genes correlated with fibrosis even after adjusting to eGFR and other clinical parameters. The association between GFR and gene expression was mostly mediated by fibrosis. In conclusion, our transcriptome-based CKD trait dissection analysis suggests that the association between gene expression and renal function is mediated by structural changes and that there may be differences in pathways that lead to decline in kidney function and the development of fibrosis, respectively