Renal function decline in older men and women with advanced chronic kidney disease-results from the EQUAL study

Introduction. Understanding the mechanisms underlying the differences in renal decline between men and women may improve sex-specific clinical monitoring and management. To this end, we aimed to compare the slope of renal function decline in older men and women in chronic kidney disease (CKD) Stages 4 and 5, taking into account informative censoring related to the sex-specific risks of mortality and dialysis initiation.Methods. The European QUALity Study on treatment in advanced CKD (EQUAL) study is an observational prospective cohort study in Stages 4 and 5 CKD patients >= 65years not on dialysis. Data on clinical and demographic patient characteristics were collected between April 2012 and December 2018. Estimated glomerular filtration rate (eGFR) was calculated using the CKD Epidemiology Collaboration equation. eGFR trajectory by sex was modelled using linear mixed models, and joint models were applied to deal with informative censoring.Results. We included 7801 eGFR measurements in 1682 patients over a total of 2911years of follow-up. Renal function declined by 14.0% [95% confidence interval (CI) 12.9-15.1%] on average each year. Renal function declined faster in men (16.2%/year, 95% CI 15.9-17.1%) compared with women (9.6%/year, 95% CI 6.3-12.1%), which remained largely unchanged after accounting for various mediators and for informative censoring due to mortality and dialysis initiation. Diabetes was identified as an important determinant of renal decline specifically in women.Conclusion. In conclusion, renal function declines faster in men compared with women, which remained similar after adjustment for mediators and despite a higher risk of informative censoring in men. We demonstrate a disproportional negative impact of diabetes specifically in women.Clinical epidemiolog

Timing of dialysis initiation to reduce mortality and cardiovascular events in advanced chronic kidney disease: nationwide cohort study

OBJECTIVE To identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease.DESIGNNationwide observational cohort study.SETTINGNational Swedish Renal Registry of patients referred to nephrologists.PARTICIPANTSPatients had a baseline eGFR between 10 and 20 mL/min/1.73 m(2) and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017.MAIN OUTCOME MEASURESThe strict design criteria of a clinical trial were mimicked by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias. A dynamic marginal structural model was used to estimate adjusted hazard ratios and absolute risks for five year all cause mortality and major adverse cardiovascular events (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) for 15 dialysis initiation strategies with eGFR values between 4 and 19 mL/min/1.73 m(2) in increments of 1 mL/min/1.73 m(2). An eGFR between 6 and 7 mL/min/1.73 m(2) (eGFR(6-7)) was taken as the reference.RESULTSAmong 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m(2)), 3822 started dialysis, 4160 died, and 2446 had a major adverse cardiovascular event. A parabolic relation was observed for mortality, with the lowest risk for eGFR(15-16). Compared with dialysis initiation at eGFR(6-7), initiation at eGFR(15-16) was associated with a 5.1% (95% confidence interval 2.5% to 6.9%) lower absolute five year mortality risk and 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.89 (95% confidence interval 0.87 to 0.92) and 0.94 (0.91 to 0.98), respectively. This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up. However, dialysis would need to be started four years earlier. When emulating the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR(10-14)v eGFR(5-7)) and the achieved eGFRs in IDEAL (eGFR(7-10)v eGFR(5-7)), hazard ratios for all cause mortality were 0.96 (0.94 to 0.99) and 0.97 (0.94 to 1.00), respectively, which are congruent with the findings of the randomised IDEAL trial.CONCLUSIONSVery early initiation of dialysis was associated with a modest reduction in mortality and cardiovascular events. For most patients, such a reduction may not outweigh the burden of a substantially longer period spent on dialysis.Clinical epidemiolog

Kidney function and symptom development over time in elderly patients with advanced chronic kidney disease: results of the EQUAL cohort study

Background. Initiation of renal replacement therapy often results from a combination of kidney function deterioration and symptoms related to chronic kidney disease (CKD) progression. We investigated the association between kidney function decline and symptom development in patients with advanced CKD.Methods. In the European Quality study on treatment in advanced CKD (EQUAL study), a European prospective cohort study, patients with advanced CKD aged >= 65 years and a kidney function that dropped <20 mL/min/1.73 m(2) were followed for 1 year. Linear mixed-effects models were used to assess the association between kidney function decline and symptom development. The sum score for symptom number ranged from 0 to 33 and for overall symptom severity from 0 to 165, using the Dialysis Symptom Index.Results. At least one kidney function estimate with symptom number or overall symptom severity was available for 1109 and 1019 patients, respectively. The mean (95% confidence interval) annual kidney function decline was 1.70 (1.32; 2.08) mL/min/1.73 m(2). The mean overall increase in symptom number and severity was 0.73 (0.28; 1.19) and 2.93 (1.34; 4.52) per year, respectively. A cross-sectional association between the level of kidney function and symptoms was lacking. Furthermore, kidney function at cohort entry was not associated with symptom development. However, each mL/min/1.73 m(2) of annual kidney function decline was associated with an extra annual increase of 0.23 (0.07; 0.39) in the number of symptoms and 0.87 (0.35; 1.40) in overall symptom severity.Conclusions. A faster kidney function decline was associated with a steeper increase in both symptom number and severity. Considering the modest association, our results seem to suggest that repeated thorough assessment of symptom development during outpatient clinic visits, in addition to the monitoring of kidney function decline, is important for clinical decision-making.Clinical epidemiolog

Reply to 'Depression and clinical outcomes in CKD: do anti-depressants play a role? (EQUAL Study)'

Nephrolog

Health-related quality-of-life trajectories over time in older men and women with advanced chronic kidney disease

Background and objectives The effect of sex on longitudinal health-related quality of life remains unknown in CKD. Here we assess differences in the sex-specific evolution of health-related quality of life in older men and women with advanced CKD.Design, setting, participants, & measurements The European Quality Study on Treatment in Advanced Chronic Kidney Disease is a European observational prospective cohort study in referred patients with CKD and an incident eGFR = 65 years of age not on dialysis. Health-related quality of life was measured using the 36-Item Short Form Survey at 3- to 6-month intervals between April 2012 and September 2020, providing Physical Component Summary and Mental Component Summary scores. Trajectories were modeled by sex using linear mixed models, and sex differences in health-related quality-of-life slope were explored. Results We included 5345 health-related quality-of-life measurements in 1421 participants. At baseline, women had considerably lower mean Physical Component Summary (42) and Mental Component Summary (60) compared with men (Physical Component Summary: 55; Mental Component Summary: 69; P < 0.001). However, during follow-up, Physical Component Summary and Mental Component Summary scores declined approximately twice as fast in men (Physical Component Summary: 2.5 per year; 95% confidence interval, 1.8 to 3.1; Mental Component Summary: 2.7 per year; 95% confidence interval, 2.0 to 3.4) compared with in women (Physical Component Summary: 1.1 per year; 95% confidence interval, 0.1 to 2.0; Mental Component Summary: 1.6 per year; 95% confidence interval, 0.7 to 2.6). This difference was partly attenuated after adjusting for important covariates, notably eGFR decline. Higher serum phosphate, lower hemoglobin, and the presence of preexisting diabetes were associated with lower Physical Component Summary and Mental Component Summary scores in men but to a lesser extent in women. Conclusions Among older men and women with advanced CKD, women had lower health-related quality of life at baseline, but men experienced a more rapid decline in health-related quality of life over time.Clinical epidemiolog

International prescribing patterns and polypharmacy in older people with advanced chronic kidney disease: results from the European Quality study

Background. People with chronic kidney disease (CKD) are at high risk of polypharmacy. However, no previous study has investigated international prescribing patterns in this group. This article aims to examine prescribing and polypharmacy patterns among older people with advanced CKD across the countries involved in the European Quality (EQUAL) study.Methods. The EQUAL study is an international prospective cohort study of patients >= 65 years of age with advanced CKD. Baseline demographic, clinical and medication data were analysed and reported descriptively. Polypharmacy was defined as >= 5 medications and hyperpolypharmacy as >= 10. Univariable and multivariable linear regressions were used to determine associations between country and the number of prescribed medications. Univariable and multivariable logistic regression were used to determine associations between country and hyperpolypharmacy.Results. Of the 1317 participants from five European countries, 91% were experiencing polypharmacy and 43% were experiencing hyperpolypharmacy. Cardiovascular medications were the most prescribed medications (mean 3.5 per person). There were international differences in prescribing, with significantly greater hyperpolypharmacy in Germany {odds ratio (OR) 2.75 [95% confidence interval (CI) 1.73-4.37]; P < 0.001, reference group UK}, the Netherlands [OR 1.91 (95% CI 1.32-2.76); P = 0.001] and Italy [OR 1.57 (95% CI 1.15-2.15); P = 0.004]. People in Poland experienced the least hyperpolypharmacy [OR 0.39 (95% CI 0.17-0.87); P = 0.021].Conclusions. Hyperpolypharmacy is common among older people with advanced CKD, with significant international differences in the number of medications prescribed. Practice variation may represent a lack of consensus regarding appropriate prescribing for this high-risk group for whom pharmacological treatment has great potential for harm as well as benefit.Clinical epidemiolog

Patient-reported measures and lifestyle are associated with deterioration in nutritional status in CKD stage 4-5: the EQUAL cohort study

Objective: The aim of this study was to explore the changes in nutritional status before dialysis initiation and to identify modifiable risk factors of nutritional status decline in older adults with advanced renal disease.& nbsp;Design and Methods: The European Quality Study on treatment in advanced chronic kidney disease (EQUAL) is a prospective, observational cohort study involving six European countries. We included 1,103 adults > 65 years with incident estimated glomerular filtration rate = 2 points). The proportion of patients with low SGA (<= 5) increased every 6 months. Those who dropped in SGA also declined in estimated glomerular filtration rate and mental health score. Every 10 points decrease in physical function score increased the odds of decline in SGA by 23%. Lower physical function score at baseline, gastrointestinal symptoms, and smoking were risk factors for impaired nutritional status. There was an interaction between diabetes and physical function on SGA decline.& nbsp;Conclusions: Nutritional status deteriorated in more than one-third of the study participants during the first year of follow-up. Lower patient-reported physical function, more gastrointestinal symptoms, and current smoking were associated with decline in nutritional status. (C)& nbsp;2021 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.Clinical epidemiolog

Renal replacement therapy in Europe : A summary of the 2013 ERA-EDTA Registry Annual Report with a focus on diabetes mellitus

Publisher Copyright: © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.Background: This article provides a summary of the 2013 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at http://www.era-edta-reg.org), with a focus on patients with diabetes mellitus (DM) as the cause of end-stage renal disease (ESRD). Methods: In 2015, the ERA-EDTA Registry received data on renal replacement therapy (RRT) for ESRD from 49 national or regional renal registries in 34 countries in Europe and bordering the Mediterranean Sea. Individual patient datawere provided by 31 registries, while 18 registries provided aggregated data. The total population covered by the participating registries comprised 650 million people. Results: In total, 72 933 patients started RRT for ESRD within the countries and regions reporting to the ERA-EDTA Registry, resulting in an overall incidence of 112 per million population (pmp). The overall prevalence on 31 December 2013was 738 pmp (n = 478 990). Patients with DM as the cause of ESRD comprised 24% of the incident RRT patients (26 pmp) and 17% of the prevalent RRT patients (122 pmp).Whencompared with the USA, the incidence of patients starting RRTpmpsecondary toDMin Europe was five times lower and the incidence of RRT due to other causes of ESRD was two times lower. Overall, 19 426 kidney transplants were performed (30 pmp). The 5-year adjusted survival for all RRT patients was 60.9% [95% confidence interval (CI) 60.5-61.3] and 50.6% (95% CI 49.9-51.2) for patients with DM as the cause of ESRD.publishersversionPeer reviewe

Socio-economic status, ethnicity and geographical variations in acceptance rates for renal replacement therapy in England and Wales: an ecological study

BackgroundIt is not known to what extent the reported regional variations in renal replacement therapy (RRT) acceptance rates in England and Wales are due to differences in the socio-demographic characteristics of the population.MethodsThe authors calculated age–gender indirectly standardised RRT rates in 2007 for Primary Care Trusts (PCT)/Local Health Boards (LHB) in England and Wales and Government Office Regions (GOR) in England. Multivariable Poisson regression was used to examine the regional variations in the age–gender standardised RRT rates before and after adjustment for area deprivation (Townsend index) and the proportion of non-white people living in an area.ResultsIncreasing deprivation of PCT/LHB was associated with higher RRT acceptance rates. RRT rates were higher in PCTs with a greater proportion of non-white people in England (correlation coefficient 0.60, p&lt;0.001) but not in Wales. There were variations in the age–gender standardised RRT rates between PCT/LHBs in England and Wales. Adjusting for deprivation and the proportion of non-white people attenuated the high RRT rate ratio observed in London and West Midlands, but the RRT acceptance rate ratio (95% CI) remained higher in Wales 1.38 (1.22 to 1.57) and lower in North West England 0.82 (0.74 to 0.93) and Yorkshire and Humberside 0.86 (0.77 to 0.98).ConclusionsThis study highlights that RRT acceptance rates are positively associated with social deprivation and the proportion of non-white people in a PCT/LHB, but regional variations in RRT acceptance rates still persist despite taking these into account. Further study is required to understand the extent to which these differences reflect variation in underlying need or provision of care

The EQUAL study: a European study in chronic kidney disease stage 4 patients

Clinical epidemiolog