Cécile Couchoud

A clinical score to predict 6-month prognosis in elderly patients starting dialysis for end-stage renal disease.

AIM The aim of this study was to develop and validate a prognostic score for 6-month mortality in elderly patients starting dialysis for end-stage renal disease. METHODS Using data from the French Rein registry, we developed a prognostic score in a training sample of 2500 patients aged 75 years or older who started dialysis between 2002 and 2006, which we validated in a similar sample of 1642 patients. Multivariate logistic regression with 500 bootstrap samples allowed us to select risk factors from 19 demographic and baseline clinical variables. RESULTS The overall 6-month mortality was 19%. Age was not associated with early mortality. Nine risk factors were selected and points assigned for the score were as follows: body mass index <18.5 kg/m2 (2 points), diabetes (1), congestive heart failure stages III to IV (2), peripheral vascular disease stages III to IV (2), dysrhythmia (1), active malignancy (1), severe behavioural disorder (2), total dependency for transfers (3) and unplanned dialysis (2). The median score was 2. Mortality rates ranged from 8% in the lowest risk group (0 point) to 70% in the highest risk group (> or =9 points) and 17% in the median group (2 points). Seventeen percent of all deaths occurred after withdrawal from dialysis, ranging from 0% for a score of 0-1 to 15% for a score of 7 or higher. CONCLUSIONS This simple clinical score effectively predicts short-term prognosis among elderly patients starting dialysis. It should help to illuminate clinical decision making, but cannot be used to withhold dialysis. It ought to only be used by nephrologists to facilitate the discussion with the patients and their families.

Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.

Age and comorbidity may explain the paradoxical association of an early dialysis start with poor survival

Starting patients on dialysis early has been increasing in incidence in several countries. However, some studies have questioned its utility, finding a counter-intuitive effect of increased mortality when dialysis was started at a higher estimated glomerular filtration rate (eGFR). To examine this issue in more detail we measured mortality hazard ratios associated with Modification of Diet in Renal Disease eGFR at dialysis initiation for 11,685 patients from the French REIN Registry, with sequential adjustment for a number of covariates. The eGFR was analyzed both quantitatively by 5-ml/min per 1.73 m(2) increments and by demi-decile (i.e., 5 percentiles of the distribution); the 15th demi-decile, including values around 10 ml/min per 1.73 m(2), was our reference point. The patients more likely to begin dialysis at a higher eGFR were older male patients; had diabetes, cardiovascular diseases, or low body mass index and level of albuminemia; or were started with peritoneal dialysis. During a median follow-up of 21.9 months, 3945 patients died. The 2-year crude survival decreased from 79 to 46%, with increasing eGFR from less than 5 to over 20 ml/min per 1.73 m(2). Each 5-ml/min/1.73 m(2) increase in eGFR was associated with a 40% increase in crude mortality risk, which weakened to 9%, but remained statistically significant after adjusting for the above covariates. Analysis by demi-decile showed only the highest to be at significantly higher risk. Hence we found that age and patient condition strongly determine the decision to start dialysis and may explain most of the inverse association between eGFR and survival.

Cytomegalovirus prophylaxis with antiviral agents in solid organ transplantation : a meta-analysis.

BACKGROUND The aim of this meta-analysis was to assess the efficacy of antiviral agents to prevent, in solid organ transplant recipients, cytomegalovirus infection and symptomatic disease and to decrease the incidence of acute rejection, graft loss, and death. METHODS Of the studies identified, 13 met the following inclusion criteria: prospective randomized study, in adults or pediatric recipients of a solid organ transplant, where one group in the study received a prophylactic treatment with acyclovir and/or ganciclovir begun before the cytomegalovirus infection and a control group was not treated or receive placebo. RESULTS Prophylactic treatment was found to be associated with a significant decrease of cytomegalovirus disease compared with placebo or no treatment, using the logarithm of relative risk method (relative risk=0.50; 95% confidence interval, 0.40-0.62; P-value for chi-square association <0.001). Prophylactic treatment decreased also the rate of cytomegalovirus infection (relative risk=0.74; 95% confidence interval, 0.62-0.88; P<0.001). Our analysis failed to show a significant decrease of graft loss, acute rejection, and death in the prophylactic treatment group. Subgroup analysis based on the type of antiviral agent (acyclovir or ganciclovir) and on the type of organ (kidney or liver) gave comparable results. CONCLUSION The use of antiviral agents for the prevention of cytomegalovirus disease and cytomegalovirus infection in solid organ transplantation is supported by this meta-analysis.

Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe: prevalence and survival-an analysis of data from the ERA-EDTA Registry.

BACKGROUND Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common renal disease requiring renal replacement therapy (RRT). Still, there are few epidemiological data on the prevalence of, and survival on RRT for ADPKD. METHODS This study used data from the ERA-EDTA Registry on RRT prevalence and survival on RRT in 12 European countries with 208 million inhabitants. We studied four 5-year periods (1991-2010). Survival analysis was performed by the Kaplan-Meier method and by Cox proportional hazards regression. RESULTS From the first to the last study period, the prevalence of RRT for ADPKD increased from 56.8 to 91.1 per million population (pmp). The percentage of prevalent RRT patients with ADPKD remained fairly stable at 9.8%. Two-year survival of ADPKD patients on RRT (adjusted for age, sex and country) increased significantly from 89.0 to 92.8%, and was higher than for non-ADPKD subjects. Improved survival was noted for all RRT modalities: haemodialysis [adjusted hazard ratio for mortality during the last versus first time period 0.75 (95% confidence interval 0.61-0.91), peritoneal dialysis 0.55 (0.38-0.80) and transplantation 0.52 (0.32-0.74)]. Cardiovascular mortality as a proportion of total mortality on RRT decreased more in ADPKD patients (from 53 to 29%), than in non-ADPKD patients (from 44 to 35%). Of note, the incidence rate of RRT for ADPKD remained relatively stable at 7.6 versus 8.3 pmp from the first to the last study period, which will be discussed in detail in a separate study. CONCLUSIONS In ADPKD patients on RRT, survival has improved markedly, especially due to a decrease in cardiovascular mortality. This has led to a considerable increase in the number of ADPKD patients being treated with RRT.

Clinical Practice Guideline on management of patients with diabetes and chronic kidney disease stage 3b or higher (eGFR <45 mL/min)

Diabetes mellitus is becoming increasingly prevalent and is considered a rapidly growing concern for healthcare systems. Besides the cardiovascular complications, diabetes mellitus is associated with chronic kidney disease (CKD). CKD in patients with diabetes can be caused by true diabetic nephropathy, but can also be caused indirectly by diabetes, e.g. due to polyneuropathic bladder dysfunction, increased incidence of relapsing urinary tract infections or macrovascular angiopathy. However, many patients who develop CKD due to a cause other than diabetes will develop ormay already have diabetes mellitus. Finally, many drugs that are used for management of CKDs, e.g. corticosteroids or calcineurin inhibitors, can cause diabetes. Despite the strong interplay between diabetes and CKD, the management of patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) remains problematic. Many guidance-providing documents have been produced on the management of patients with diabetes to prevent or delay the progression to CKD, mostly defined as the presence of microand macro-albuminuria. However, none of these documents specifically deal with the management of patients with CKD stage 3b or higher (eGFR <45 mL/min). There is a paucity of well-designed, prospective studies in this population, as many studies exclude either patients with diabetes, or with CKD stage 3b or higher (eGFR <45 mL/min), or both. This limits the evidence base to these approaches. In addition, due to some new developments in this area, the advisory board of ERBP decided that a guideline on the management of patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) was needed and timely:

The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry

BACKGROUND This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe. METHODS Eighteen national or regional renal registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry between 1998 and 2011 were included. Incidence and prevalence time trends between 2001 and 2011 were studied with Joinpoint and Poisson regression. Patient and kidney allograft survival and COD between 1998 and 2011 were analysed using Kaplan-Meier and competing risk methods and Cox regression. RESULTS From 2001 to 2008, the adjusted incidence of RRT rose by 1.1% (95% CI: 0.6, 1.7) annually to 131 per million population (pmp). During 2008-2011, the adjusted incidence fell by 2.2% (95% CI: -4.2, -0.2) annually to 125 pmp. This decline occurred predominantly in patients aged 45-64 years, 65-74 years and in the primary renal diseases diabetes mellitus type 1 and 2, renovascular disease and glomerulonephritis. Between 2001 and 2011, the overall adjusted prevalence increased from 724 to 1032 pmp (+3.3% annually, 95% CI: 2.8, 3.8). The adjusted 5-year patient survival on RRT improved between 1998-2002 and 2003-2007 [adjusted hazard ratio (HRa) 0.85, 95% CI: 0.84, 0.86]. Comparing these time periods, the risk of cardiovascular deaths fell by 25% (HRa 0.75, 95% CI: 0.74, 0.77). However the risk of malignant death rose by 9% (HRa 1.09, 95% CI: 1.03, 1.16) in patients ≥65 years. CONCLUSION This European study shows a declining RRT incidence, particularly in patients aged 45-64 years, 65-74 years and secondary to diabetic nephropathy. Encouragingly, the adjusted RRT patient survival continues to improve. The risk of cardiovascular death has decreased, though the risk of death from malignancy has increased in the older population.

A new approach for measuring gender disparity in access to renal transplantation waiting lists.

Background Gender inequity in access to renal transplantation waiting lists, in favor of men, has long since been demonstrated in a number of studies. Discrepancies between the results of the available studies might be explained by different analytical approaches or different national contexts. In this study we analyzed French end-stage renal disease registry data using a novel model to determine whether the female gender is associated with a lower probability of being listed on the transplant waiting list or with a longer time from dialysis start until registration, or both. Methods The effect of gender on access to the national renal transplantation waiting list was assessed in 9497 men and 5386 women aged 18 to 74 years who started dialysis between 2002 and 2009. We used a semiparametric regression cure model adjusted for age, work status, and 11 comorbidities or disabilities. Results Women were younger and less likely to work or have associated comorbidities. At the study endpoint, 33.8% of the men and 34.1% of the women were placed on the renal transplantation waiting list. After taking potential confounders into account, our model shows that women demonstrated a lower probability of being registered on the national transplant waiting list (odds ratio=0.69; 95% confidence interval, 0.62–0.78) and a longer time from dialysis start to registration (hazard ratio=0.89; 95% confidence interval, 0.84–0.95) than men. This disparity affects predominantly older women who do not work or have diabetes and is more pronounced in some geographic areas. Conclusions These poorly understood gender-based inequities require further consideration.

Development of a risk stratification algorithm to improve patient-centered care and decision making for incident elderly patients with end-stage renal disease.

A significant number of elderly patients die during their first 3 months of dialysis. Because dialysis can impair the quality of both life and death, a personalized care plan based on both early prognosis and patient choices is required. We developed a prognostic screening tool to identify older patients in need of specific care based on a multidisciplinary approach. Our study included 24,348 patients aged 75 years and older from the French national renal epidemiology and information network (REIN) registry who began dialysis between 1 January 2005 and 30 September 2012. Our primary outcome was overall mortality during the first 3 months of renal replacement therapy. Multivariate logistic regression was used to construct a scoring system in a random half of the cohort (training set). This score, which included age, gender, specific comorbidities, albumin levels, and mobility, was then applied to the other half (validation set). In all, 2548 patients died during the first 3 months after dialysis initiation, 22% after dialysis withdrawal. Three risk groups were identified: low risk (score under 12 points, 3-month expected mortality under 20%), intermediate risk (score from 12 to 16, mortality between 20 and 40%, 9.5% of patients) and high risk (score 17 or more, mortality over 40%, 2.5% of patients). We developed a decision-making process that classifies patients according to their risk of early death in view of their potentially imminent need for supportive care or treatment.

Trends in dialysis modality choice and related patient survival in the ERA-EDTA Registry over a 20-year period.

BACKGROUND Although previous studies suggest similar patient survival for peritoneal dialysis (PD) and haemodialysis (HD), PD use has decreased worldwide. We aimed to study trends in the choice of first dialysis modality and relate these to variation in patient and technique survival and kidney transplant rates in Europe over the last 20 years. METHODS We used data from 196 076 patients within the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry who started renal replacement therapy (RRT) between 1993 and 2012. Trends in the incidence rate and prevalence on Day 91 after commencing RRT were quantified with Joinpoint regression. Crude and adjusted hazard ratios (HRs) for 5-year dialysis patient and technique survival were calculated using Cox regression. Analyses were repeated using propensity score matching to control for confounding by indication. RESULTS PD prevalence dropped since 2007 and HD prevalence stabilized since 2009. Incidence rates of PD and HD decreased from 2000 and 2009, respectively, while the incidence of kidney transplantation increased from 1993 onwards. Similar 5-year patient survival for PD versus HD patients was found in 1993-97 [adjusted HR: 1.02, 95% confidence interval (95% CI): 0.98-1.06], while survival was higher for PD patients in 2003-07 (HR: 0.91, 95% CI: 0.88-0.95). Both PD (HR: 0.95, 95% CI: 0.91-1.00) and HD technique survival (HR: 0.93, 95% CI: 0.87-0.99) improved in 2003-07 compared with 1993-97. CONCLUSIONS Although initiating RRT on PD was associated with favourable patient survival when compared with starting on HD treatment, PD was often not selected as initial dialysis modality. Over time, we observed a significant decline in PD use and a stabilization in HD use. These observations were explained by the lower incidence rate of PD and HD and the increase in pre-emptive transplantation.