The First International Seminars on Renal Epidemiology held in Paris, France, in May 2012.

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1 The First International Seminars on Renal Epidemiology held in Paris, France, in May The organization committee : Dr Cécile Couchoud (registre REIN, Agence de la biomédecine, Saint- Denis La Plaine, France), Dr Olivier Moranne (Département de Néphrologie, Département de Santé Publique, Centre hospitalo-universitaire, Nice, France), Pr Cécile Vigneau (Département de Néphrologie, Centre hospitalo-universitaire, Rennes, France), Dr Emmanuel Villar (Département de Néphrologie, Centre Hospitalier St Joseph St Luc, Lyon, France) This two day symposium aims to become the biennial meeting that gathers together Nephrologists and Epidemiologists involved in renal epidemiology around the world. The subject of this first seminar was to show how epidemiology may help nephrologists in their decision. During 7 sessions of oral communications, many questions were debated. Each time, methodological aspects and cutting edge results were discussed. The first day started with a session devoted to the chronic kidney disease in the general population. Luc Frimat 1 (France) did a review on the various biases that should be avoid in prevalent studies. In the definition of the patients for a study, it is necessary to control for indication bias and to take into account potential bias due to the stage of the disease. The Neyman bias occurs when one try to estimate the risk of a disease or death on the basis of data collected at a given time point in survivors rather than on data gathered in a group of incident cases. In survival studies, the competing risks between events should be analyzed. His communication was the opportunity to underline the dynamics of renal epidemiology in France. Nathalie Ebert 2 (Germany) presented the first results of the Berliner Initiative Studie that concerns epidemiology of chronic kidney disease in a sample of elderly people over 70 years, selected by randomization in the general population. This study aims to measure incidence of renal disease and to develop new tools for the evaluation 1

2 the renal function in this population. Stephen McDonald 3 (Australia) presented data about end-stage renal disease in Aboriginal Australians. Indigenous are characterize by a higher incidence of ESRD but now stabilized, more diabetic nephropathies, higher peritonitis on peritoneal dialysis and lower access to transplantation and poorer graft survival. Remoteness and socioeconomically factors are important predictors of these differences. The prognosis of patients with CKD was discussed during the second session. Olivier Moranne (France) presented results of a study assessing the association between GFR slope and risk of mortality in transplant kidney recipients. This association has been reported in general population with native kidney. This single center study evaluated incident survivors at one year post kidney transplant between 1990 and 2000 yrs and found a graded and significant association between GFR slope decrease after one year and risk of mortality. These results deserve further interventional trials evaluating strategies of graft protection according to their ability to slow the decline of GFR along with their impact on long term mortality. Christophe Mariat 4 (France) et Christine White 5;6 (Canada) discussed Kidney function as a common surrogate endpoint in Kidney Transplantation. They discussed the dosage of Cystatin C such as a better GFR marker and prognosis factor than Serum Creatinine in Kidney transplantation. However they point out the lack of data showing that Cystatin C has a clinical benefit to predict graft failure and mortality. Bénédicte Stengel 7 (France) presented an overview of the results from the Three-City population-based study. This study is a multicentric prospective cohort including more than 8000 patients over 65 yrs old from general population in France. In this population, mean age is 74±5 yrs with 60% women. Subjects were followed up at least 7 years. This study underlined the prevalence of CKD in this population: 28% CKD stages 1 to 4 and 21% stages 3-4. It showed the mean annual estimated GFR (egfr) decline (- 1.5 ml/min/1.73m2), a significant increased risk of cardio-vascular mortality with egfr < 60 ml/min/1.73m2, a significant increased risk of all-cause mortality with egfr < 45 ml/min/1.73m2 vs [75-90 ml/min/1.73m2], a 2

3 significant association between egfr slope > -4 ml/min/1.73m2/yr and a cognitive decline (estimated with MMSE) and finally the increased risk of inappropriate drug use and mortality in community-dwelling elderly with impaired kidney function (i.e egfr< 60 ml/min/1.73m2). Lastly William McClellan 8;9 (USA) presented an overview about morbidity and prognosis of elderly with CKD. He noted the increased prevalence of CKD in the general population, the high proportion of the elderly (> 70 years), but the rates of CKD complications was not significantly different between age group. The risk of death outweighs the risk of care for dialysis in patients over 75 years with an egfr <60 ml/min/1.73m2. And finally he presented recent results of the study REGARDS who showed a link between GFR stage and mortality risk persisting regardless of age group. The second day started with a session on the optimization of renal health care organization. Cécile Couchoud 10;11 (France) presented a data model that describes treatment course of patients with ESRD. This tool has two advantages. It improves the understanding of our administrative partners on the dynamic underlying process and the interpretation of static indicators like the rate of patients with peritoneal dialysis among dialysis patients. It also allows simulations of possible change in practices. Impact of each scenario may be quantified in terms of life expectancy, cost and number of transfers between treatment modalities. Fergus Caskey 12 (United Kingdom) presented the results of the EVEREST Study. This international study aims to analyze the non-medical determinants (macro-economic indicators, renal care organization ) that may explain differences in ESRD incidences, survival or dialysis modality mix among 46 countries. Mark Marshall 13 (New-Zealand), based on an example on home hemodialysis and mortality, showed the advantages of structural models. They allow adjusting for time-varying co-morbidity that is both affected by previous modality exposure while also affecting subsequent modality choice. Another session addressed the issue of support for the elderly with CKD. Aine Burns 14;15 (United Kingdom) presented her experience in the conservative treatment in the elderly with CKD stage 5 3

4 (10% of their patients). She detailed the studies of Murtagh FE (London) who described the complexity of the symptoms of CKD stage 5 because of their overlap with the geriatric syndrome, the description of the functional trajectory of elderly with CKD stage 5 in the last year life, the criteria to choose conservative treatment (i.e. without dialysis support) such as lower incidence of hospitalization and probably a moderate loss of quantity of life compared to dialysis treatment in patients with comorbidities. Finally she spoke of the need to establish a unit for decision making with patients, families and physician to plan therapeutic project. Moranne Olivier (France) presented the PSPA study that is a French multicentric prospective cohort evaluating the prognosis of patients aged over 75 years followed by a nephrologist with an egfr below 20 ml/ min/1.73m2 without dialysis. He described the characteristics at baseline of the population (mean age of 82 ± 5 years, 57% of men, a mean MDRD of 13.5 ± 4 ml/min/1.73m2 and the therapeutic projects defined by the referent Nephrologist). Follow-up of the cohort is planned for 4 years with the aim to define the trajectory associated with better prognosis and more specifically identification of the elderly patient who can benefit from dialysis. Indeed some recent English monocentric retrospective studies discuss the benefit/risk balance of dialysis in the elderly with comorbidities. Kitty Jager 19;20 (Netherlands) presented the EQUAL study that is a multicenter International (5 European countries) prospective cohort planed to include 3500 patients over 65 years followed by nephrologists with an egfr 20 ml/min/1.73m2. The multiple objectives of this study are: identifying the good time to start dialysis depending on renal function and symptoms of uremia, defining the estimator of renal function that informs the best of the good time to initiate dialysis and how the decision process of the physician with the patient leads to the choice of therapeutic project. Finally the study will evaluate the prognosis related to the stage of renal function and symptoms to initiate dialysis. The pilot study is underway. Elke Schäffner 21 (Germany) presented the results of her study comparing European (European Senior Transplant (EST)) and American (UNOS) programs of access to renal transplantation 4

5 on prognosis in the elderly. The EST model expand the donor pool for patients older than 65 yrs with extension criteria including graft for cadaveric specimens age> 60 or > 50 years with 2 criteria including hypertension, creatinine> 1.5 mg / dl, a stroke as cause of death and also the living donor transplant. Comparison of practices between Europe and USA found that donor in Europe were more likely to be older than 70 years, to have diabetes or high blood pressure and finally higher graft survival in patients over 65 years. However, this graft survival difference would relate the problem of the cost of drugs associated with poor compliance. Finally the implementation of this program in 2002 in Europe is associated with an increased number of transplant recipients over 65 years with a decrease in the cold ischemic time. The evaluation of chronic kidney disease treatment was discussed in the fifth session. Based on the example of daily haemodialysis, Gihad Nesrallah 22 (Canada) illustrated the difficulty to evaluate new practices. The clinical trial published by the FHN group was not conclusive. A study of the International Quotidian Registry (IQDR) shows a lower survival for those patients, that may be explain by preferential use of this technique in high-risk patients. A new clinical trial in high-risk patients may be discussed. René Ecochard 23 (France) illustrated the advantage of latent trajectories to take into account the diversity of evolution of renal function after cardiac transplantation in a randomized control trial. Sahar Bayat 24 (France) studied the medical and non-medical factors associated with listing on the waiting list of a cohort of adult patients starting a renal replacement therapy. Age, comorbidities, gender, ownership of dialysis facility are associated to the access on the list. At the regional level, density of general practitioners and specialists and number of grafts implanted are related to list registration while other Socioeconomic or Health care supply indicators are not. Thierry Lobbedez 25;26 (France) discussed the advantage of assisted peritoneal dialysis. The analysis of the impact of assistance on the transfer tot hemodialysis took into account the competing risks of death, renal transplantation and recovery of renal function. In a study based on the data of 5

6 the RDPLF, assisted peritoneal dialysis was associated with a lower transfer to hemodialysis and renal transplantation and a higher mortality rate. Various factors of confusion like patients clinical characteristics and the center experience may explain these associations. The sixth session dealt with renal transplantation benefit evaluation. Christian Jacquelinet 27 (France) presented the advantages of simulation to evaluate a procedure when randomization is not possible. Based on the example of liver transplantation, the steps of simulation, of construction of a score to allocate renal transplant and its evaluation have been discussed and illustrated. Franck Assogaba (France) presented the results of his study on the proper effect of type 2 diabetes on death and too sick patients delisting among renal transplant candidates. A model with competing risk of renal transplantation has shown that type 2 diabetes per se is not associated with both delisting and kidney transplantation when the other factors are taken into account. Jean-Baptiste Beuscart 28 (France) illustrated the complexity of taking into account the access on the waiting list in survival analysis on dialysis. A stratification based on registration seems to be the more reasonable approach. Jérome Harambat 29 (France) analyzed the variations in pediatric transplantation practices and access to transplantation between European countries. Efforts could be made for both living donation policy and offering kidneys to children first. Six submitted abstracts were the object of a session of short oral communications. Living kidney donation is subject to significant unexplained relationship differences amongst ethnic minorities. There is a need to understand these differences, and develop a strategy to increase donation rates in ethnic minorities especially from male spouses (Rishi Pruthi, United Kingdom). Diabetes as primary renal disease is associated with an increased risk of death following transplant failure (Lynsey Webb, United Kingdom). Many Belgian dialysis patients display a relatively limited autonomy and a high care-dependency. Moreover, this frailty seems to independently reinforce the known detrimental effects of classical medical co-morbidity on quality of life in these patients (Wim Lemahieu, 6

7 Belgium). Use of acute PD, having a responsive dialysis access service, being able to provide dialysis education to late presenting patients and providing home visits were all found to be associated with higher rate of incident patients on home dialysis. Social deprivation and proximity to a renal unit were associated with lower rates of home dialysis (Clare Castledine, United Kingdom). Based on the analyzed data a survival prognosis can be given for every patient group stratified for age, primary renal disease and status at 90 days after the start of renal replacement therapy (Aline Hemke, The Netherlands). Over the last years, the rate of patients starting as late referral decreased gradually but late referral seems to be inevitable for some patients. Poor outcome of late referral patients persists even after surviving the first year of dialysis. (Johan De Meester, Belgium). Seven posters were display. Cost per shift hemodialysis contracts are associated with higher renal replacement therapy incidence rates even after adjustment for the level of need for dialysis. Difficulty accommodating new patients was associated with lower RRT incidence rates raising the possibility of unmet need for dialysis in areas where it is most difficult to accommodate patients into HD slots (Clare Castledine, United-Kingdom). Many patients in the UK commence dialysis after transplant failure with suboptimal laboratory measures. Many patients are not listed for retransplantation, which may reflect comorbidities accrued during graft function or centre variation in access to transplantation (Lynsey Webb, United Kingdom). Worse specification of outcomes and lower homogeneity of outcomes were observed in nephrology as compared to rheumatology trials, reducing the ability to perform adequate meta-analyses from these trials. The absence of nephrology guidelines such as OMERACT in rheumatology may explain the observed differences (B Sautenet, France). The association of kidney disease complications with kidney function differed by age, but most of these associations were not modified by the presence of albuminuria. These results suggest that most kidney disease-associated abnormalities mainly reflect the physiologic effects of reduced kidney function (L Plantinga, United-States of America). 7

8 The study of the epidemiological profile of hemodialysis patients encourages to develop other means of substitution of renal failure and to improve our strategy to prevent chronic kidney disease (B. Bouterfas, Algeria). The renal prognosis of acute renal failure is often favorable (B. Bouterfas, Algeria). An exploratory study enabled to reduce the prevalence of the hypertension (R.Elharraqui, Morocco). The vesico-ureteral reflux after renal transplantation remains a surgical complication still little known because of the absence of its systematic research (R.Elharraqui, Morocco). Reference List 1. Villar E, Frimat L, Ecochard R, Labeeuw M. [Specificities of the methodology of survival analysis in dialysis patients]. Nephrol Ther 2008; 4: Schaeffner ES, van der Giet M, Gaedeke J et al. The Berlin initiative study: the methodology of exploring kidney function in the elderly by combining a longitudinal and cross-sectional approach. Eur J Epidemiol 2010; 25: McDonald S. Incidence and treatment of ESRD among indigenous peoples of Australasia. Clin Nephrol 2010; 74 Suppl 1: S28-S31 4. Mariat C, Maillard N, Phayphet M et al. Estimated glomerular filtration rate as an end point in kidney transplant trial: where do we stand? Nephrol Dial Transplant 2008; 23: White CA, Siegal D, Akbari A, Knoll GA. Use of kidney function end points in kidney transplant trials: a systematic review. Am J Kidney Dis 2010; 56: White CA, Akbari A, Doucette S et al. Effect of clinical variables and immunosuppression on serum cystatin C and beta-trace protein in kidney transplant recipients. Am J Kidney Dis 2009; 54: Stengel B, Metzger M, Froissart M et al. Epidemiology and prognostic significance of chronic kidney disease in the elderly--the Three-City prospective cohort study. Nephrol Dial Transplant 2011; 26:

9 8. Muntner P, Bowling CB, Gao L et al. Age-specific association of reduced estimated glomerular filtration rate and albuminuria with all-cause mortality. Clin J Am Soc Nephrol 2011; 6: McClellan WM, Flanders WD. Risk factors for progressive chronic kidney disease. J Am Soc Nephrol 2003; 14: S65-S Couchoud C, Guihenneuc C, Bayer F, Lemaitre V, Brunet P, Stengel B. Medical practice patterns and socio-economic factors may explain geographical variation of end-stage renal disease incidence. Nephrol Dial Transplant 2012; 27: Couchoud C, Stengel B, Landais P et al. The renal epidemiology and information network (REIN): a new registry for end-stage renal disease in France. Nephrol Dial Transplant 2006; 21: Caskey F, Stel V, Elliot R et al. The EVEREST Study: an international collaboration. Nephrol Dial Transplant Plus 2010; 3: Marshall MR, Hawley CM, Kerr PG et al. Home hemodialysis and mortality risk in Australian and New Zealand populations. Am J Kidney Dis 2011; 58: Burns A, Carson R. Maximum conservative management: a worthwhile treatment for elderly patients with renal failure who choose not to undergo dialysis. J Palliat Med 2007; 10: Burns A, Davenport A. Maximum conservative management for patients with chronic kidney disease stage 5. Hemodial Int 2010; 14 Suppl 1: S32-S Couchoud C, Labeeuw M, Moranne O et al. A clinical score to predict 6-month prognosis in elderly patients starting dialysis for end-stage renal disease. Nephrol Dial Transplant 2009; 24: Moranne O, Couchoud C, Vigneau C, and collaborators. Characteristics and treatment course of patients older than 75 years, reaching end stage renal failure in France. The PSPA study. Journal of Gerontology 2012; 18. Moranne O, Couchoud C, Kolko-Labadens A, Allot V, Fafin C, Vigneau C. Description of characteristics, therapeutic project and outcome of patients older than 75 years with egfr below 20 ml/min/1.73m 2 : PSPA pilot study. Nephrol Ther 2012; 19. Kramer A, Stel V, Zoccali C et al. An update on renal replacement therapy in Europe: ERA-EDTA Registry data from 1997 to Nephrol Dial Transplant 2009; 24: van de Luijtgaarden MW, Noordzij M, Stel VS et al. Effects of comorbid and demographic factors on dialysis modality choice and related patient survival in Europe. Nephrol Dial Transplant 2011; 26: Schaeffner ES, Rose C, Gill JS. Access to kidney transplantation among the elderly in the United States: a glass half full, not half empty. Clin J Am Soc Nephrol 2010; 5:

10 22. Nesrallah GE, Suri RS, Moist LM et al. International Quotidian Dialysis Registry: annual report Hemodial Int 2009; 13: Bastard M, Fall MB, Laniece I et al. Revisiting long-term adherence to highly active antiretroviral therapy in Senegal using latent class analysis. J Acquir Immune Defic Syndr 2011; 57: Bayat S, Frimat L, Thilly N, Loos C, Briancon S, Kessler M. Medical and non-medical determinants of access to renal transplant waiting list in a French community-based network of care. Nephrol Dial Transplant 2006; 21: Lobbedez T, Moldovan R, Lecame M, Hurault de LB, El HW, Ryckelynck JP. Assisted peritoneal dialysis. Experience in a French renal department. Perit Dial Int 2006; 26: Lobbedez T, Verger C, Ryckelynck JP, Fabre E, Evans D. Is assisted peritoneal dialysis associated with technique survival when competing events are considered? Clin J Am Soc Nephrol 2012; 7: Jacquelinet C, Audry B, Golbreich C et al. Changing kidney allocation policy in France: the value of simulation. AMIA Annu Symp Proc 2006; Beuscart JB, Pagniez D, Boulanger E et al. Overestimation of the probability of death on peritoneal dialysis by the Kaplan-Meier method: advantages of a competing risks approach. BMC Nephrol 2012; 13: Harambat J, van Stralen KJ, Kim JJ, Tizard EJ. Epidemiology of chronic kidney disease in children. Pediatr Nephrol 2011; 10