Relationship between decline in estimated or measured glomerular filtration rate and 16-year postrenal transplant outcome.

BACKGROUND: Glomerular filtration rate (GFR) decline ≥30% over 2 years can substitute for the conventional 'doubling of serum creatinine' to predict end-stage renal disease in patients with native kidneys. While chronic kidney disease trajectory is less predictable in transplanted patients, recent data have suggested that similar GFR decline might be an acceptable surrogate for long-term transplant outcome. We sought (i) to confirm the prognostic value of an early GFR decline in kidney transplant recipients and (ii) to determine whether using direct measurement of GFR with inulin improves the performance of this surrogate. METHODS: We retrospectively analysed all recipients transplanted between 1989 and 2000 in our centre, with inulin-measured and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-estimated GFR at 1 and 5 years post-transplant, and evaluated the performance [time-dependent area under the receiver operating characteristic curve (ROC AUC) and subdistribution hazard ratio (sdHR) with competing risk model] of GFR change to predict graft failure and all-cause mortality. RESULTS: Out of 417 kidney transplant recipients, 116 patients had lost their graft and 77 had died 16 years after transplantation. While being significantly associated with graft failure [sdHR = 2.37 (95% confidence interval 1.47-3.83)], CKD-EPI-GFR decline ≥30% failed to appropriately predict long-term graft survival (C-statistics of 0.63). Concordance between inulin-GFR and CKD-EPI-GFR to detect similar GFR change was only 53%. Inulin-GFR change was, however, not a better predictor (C-statistics of 0.59). Comparable results were observed for mortality. CONCLUSIONS: Our data suggest that early GFR decline is a poor surrogate for long-term transplant outcome, even when change in GFR is directly measured by a reference method.

Medication burden and inappropriate prescription risk among elderly with advanced chronic kidney disease.

BACKGROUND: Elderly patients with chronic kidney disease (CKD) frequently present comorbidities that put them at risk of polypharmacy and medication-related problems. This study aims to describe the overall medication profile of patients aged ≥75 years with advanced CKD from a multicenter French study and specifically the renally (RIMs) and potentially inappropriate-for-the-elderly medications (PIMs) that they take. METHODS: This is a cross-sectional analysis of medication profiles of individuals aged ≥75 years with eGFR < 20 ml/min/1.73 m2 followed by a nephrologist, who collected their active prescriptions at the study inclusion visit. Medication profiles were first analyzed according to route of administration, therapeutic classification. Second, patients were classified according to their risk of potential medication-related problems, based on whether the prescription was a RIM or a PIM. RIMs and PIMs have been defined according to renal appropriateness guidelines and to Beer's criteria in the elderly. RIMs were subclassified by 4 types of category: (a) contraindication; (b) dose modification is recommended based on creatinine clearance (CrCl); (c) dose modification based on CrCl is not recommended but a maximum daily dose is mentioned, (d) no specific recommendations based on CrCl: "use with caution", "avoid in severe impairment", "careful monitoring of dose is required" "reduce the dose". RESULTS: We collected 5196 individual medication prescriptions for 556 patients, for a median of 9 daily medications [7-11]. Antihypertensive agents, antithrombotics, and antianemics were the classes most frequently prescribed. Moreover, 77.0% of patients had at least 1 medication classified as a RIM. They accounted 31.3% of the drugs prescribed and 9.25% was contraindicated drugs. At least 1 PIM was taken by 57.6 and 45.5% of patients had at least one medication classified as RIM and PIM. The prescriptions most frequently requiring reassessment due to potential adverse effects were for proton pump inhibitors and allopurinol. The PIMs for which deprescription is especially important in this population are rilmenidine, long-term benzodiazepines, and anticholinergic drugs such as hydroxyzine. CONCLUSION: We showed potential drug-related problems in elderly patients with advanced CKD. Healthcare providers must reassess each medication prescribed for this population, particularly the specific medications identified here. TRIAL REGISTRATION: NCT02910908.

Treatment plans and outcomes in elderly patients reaching advanced chronic kidney disease.

Background: Elderly patients with advanced chronic kidney disease require accurate outcome descriptions to make treatment decisions. Methods: The PSPA [Parcours de soins des personnes âgées (Treatment pathways for elderly patients)] prospective multicentre cohort study included 573 such patients with a median age of 82 [interquartile range (IQR) 79-86] years and a median estimated glomerular filtration rate of 14 (IQR 11-17) mL/min/1.73 m2 and studied their 5-year outcomes according to the dialysis component of their treatment plans. Results: Mean follow-up for the overall cohort was 34.5 ± 21 months and the 5-year survival rate was 27%. During follow-up, 288 (50%) patients started dialysis and 237 (42%) died before dialysis. At baseline, the four possible dialysis plans were dialysis when needed (38%), stable without mention of a dialysis plan (40%) and dialysis specifically excluded by the patient's (9%) or nephrologist's decision (12%). These baseline plans were associated with death and dialysis start. Follow-up plans were those decided during the study period: dialysis when needed for 47%, stable without mention of a dialysis plan for 20% and dialysis excluded at any time for 32%. For the subgroup of patients who started dialysis, those whose follow-up plan was dialysis started under better conditions than those who had stable or no dialysis follow-up plans before starting. However, survival afterwards did not differ significantly. Conclusions: These findings indicate that nephrology care should accommodate changes over time in older patients' treatment preferences and plans concerning dialysis. These changes are associated with whether, when and how these patients initiate dialysis but are not necessarily associated with post-dialysis survival.

Efficiency of delivery observed treatment in hemodialysis patients: the example of the native vitamin D therapy.

INTRODUCTION: Adherence to therapy is a relevant challenge in chronic hemodialysis patients. The directly observed therapy (DOT) could be an effective method to increase adherence for specific therapies. We aimed to study the performance of DOT versus home medication. We follow the impact of providing native vitamin D directly by the nurse after a dialysis session on the 25-hydroxyvitamin [25(OH)D] concentrations. METHODS: In this observational study, we included 38 dialysis patients treated by stable dosage of cholecalciferol. DOT was implemented in December 2010. We considered the concentrations of 25-OH vitamin D three times before (T1 = June 2010, T2 = July 2010 and T3 = September 2010) and three times after the modification of prescription (T4 = February 2011, T5 = March 2011 and T6 = April 2011). RESULTS: Median age was 72 [62; 79] years and 48 % were diabetics. Mean body mass index was 26 ± 5 kg/m(2) and median dialysis vintage was 20 [8; 46] months. The patients were compared to themselves. Before DOT, median concentrations of 25(OH)D were 27 (14-36), 23 (17-31), 31 (22-38) ng/mL at T1, T2 and T3, respectively. When DOT was effective, the concentrations significantly increased to 34 (28-44), 35 (29-41), 39 (32-47) ng/mL at T4, T5 and T6, respectively. Before DOT, 19 patients (50 %) reached the target of 30 ng/mL. After DOT, 29 patients (76 %) reached the target concentration of 30 ng/mL. CONCLUSIONS: In hemodialysis patients, DOT is both simple and effective to increase the therapeutic impact to native vitamin D.

A simple clinical tool to inform the decision-making process to refer elderly incident dialysis patients for kidney transplant evaluation.

Patients over the age of 70 constitute the fastest growing segment of the ESKD population worldwide, but most of them are not considered candidates for kidney transplantation (KT). We have developed a simple clinical screening score to identify incident elderly dialysis patients over 70 years with an acceptable long-term prognosis to identify those patients most suitable for KT evaluation. From the French national prospective registry, a logistic regression was used to develop a risk score of mortality within 3 years in a derivation cohort (years 2002-06) and validated in a separate cohort (years 2007-08). Of the 9305 patients in the derivation cohort, the points assigned for the score were: male (1pt); age (75-80); 2pts), (80-85; 5pts), 85 and over (9pts); diabetes (2pts); intermittent hemodialysis (2pt); peripheral vascular disease stage III-IV (5pts); congestive heart failure stages I-II (2pts), III-IV (4pts); dysrhythmia (2pts); chronic respiratory disease (2pts); active malignancy (5pts); severe behavioral disorder (6pts); cardiovascular disease (1pt); mobility (needs assistance for transfers (4pt), totally dependent (9pts)); BMI (21-25; 1pt), BMI (<21; 3pts); and temporary central vascular catheter (3pts). In the 7947 patient validation cohort, the probability of patients being alive within 3 years was around 70% for the lowest risk score quintile (0-6 pts) representing about 20% of incident patients. Thus, our tool identified a subgroup of patients to help nephrologists select individuals who, despite their age, could be suitable candidates for KT evaluation.

Determinants and changes associated with aldosterone breakthrough after angiotensin II receptor blockade in patients with type 2 diabetes with overt nephropathy.

BACKGROUND AND OBJECTIVES: Inhibition of the renin-angiotensin-aldosterone system decreases proteinuria and slows estimated GFR decline in patients with type 2 diabetes mellitus with overt nephropathy. Serum aldosterone levels may increase during renin-angiotensin-aldosterone system blockade. The determinants and consequences of this aldosterone breakthrough remain unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examined the incidence, determinants, and changes associated with aldosterone breakthrough in a posthoc analysis of a randomized study that compared the effect of two angiotensin II receptor blockers in patients with type 2 diabetes mellitus with overt nephropathy. RESULTS: Of 567 of 860 participants included in this posthoc analysis, 28% of participants developed aldosterone breakthrough, which was defined by an increase greater than 10% over baseline values of serum aldosterone levels after 1 year of angiotensin II receptor blocker treatment. Factors independently associated with aldosterone breakthrough at 1 year were lower serum aldosterone and potassium levels at baseline, higher decreases in sodium intake, systolic BP, and estimated GFR from baseline to 1 year, and use of losartan versus telmisartan. Aldosterone breakthrough at 6 months was not sustained at 1 year in 69% of cases, and it did not predict estimated GFR decrease and proteinuria increase between 6 months and 1 year. CONCLUSIONS: Aldosterone breakthrough is a frequent event 1 year after initiating renin-angiotensin-aldosterone system blockade, particularly in participants exposed to intensive lowering of BP with sodium depletion and short-acting angiotensin II receptor blockers. Short-term serum aldosterone level increases at 6 months are not associated with negative kidney outcomes between 6 months and 1 year.

Patients' preferences regarding choice of end-stage renal disease treatment options.

BACKGROUND: Dialysis registries have reported a low take-up of home treatment. The aim of our study was to report patients' preferred treatment options for end-stage renal disease (ESRD) after information delivery, patients' characteristics by treatment preference, and the reasons for differences between treatment preference and the treatment delivered. METHODS: A prospective cohort study on patients seen in our nephrology department between January 2009 and June 2011 included all patients with chronic kidney disease (GFR <20 ml/min/1.73 m(2)) and incident dialysis patients who received an information program about ESRD treatment options. RESULTS: 228 patients received information delivery and either expressed a preference for a given renal replacement therapy (peritoneal dialysis, PD: 42%; hemodialysis, HD: 33%), remained undecided (20%) or expressed reluctance to undergo renal replacement therapy (5%). Multivariate analysis revealed that compared to HD preference, patients preferring PD were older (OR 1.02, 95% CI 1.0-1.04), had a lower BMI (OR 0.9, 95% CI 0.87-0.98) and were more likely to have been informed before rather than after starting dialysis (OR 3.4, 95% CI 1.5-7.4); home treatment was the main reason given for preferring PD. Undecided patients were mainly women and the majority were eventually treated by HD. Reluctant patients were the oldest (OR 1.12, 95% CI 1.02-1.22) and were rarely treated by dialysis. Only 24% of patients informed before and 8% of patients informed after starting dialysis were ultimately treated with PD. Reasons for a mismatch between dialysis modality preference and treatment delivered were equally distributed between medical and nonmedical. CONCLUSION: Patients should be systematically informed before starting dialysis, patients' preferences should be taken into account before organizing dialysis and all treatment modalities should be available in all centers.

[Description of characteristics, therapy and outcome of patients older than 75 years presenting with severe renal insufficiency (eGFR below 20 mL/min/1.73 m(2): pilot study]. / Description des caractéristiques, des projets de soins et du devenir des patients de plus 75ans présentant une insuffisance rénale sévère (DFGe≤20mL/min/1,73m(2)) : phase pilote du projet PSPA.

In France, the incidence of dialysis patients is increasing in people over 75 years and represents 40% of incident patients. In these elderly patients with many comorbidities, the benefit of dialysis in terms of survival and quality of life remains controversial. Using data from REIN, determinants of early mortality were identified and a prognostic score was provided. This approach must now be adapted to elderly with end stage renal failure (ESRF) not on dialysis for which we have little data on their clinical characteristics, therapeutic projects and outcome. We report the results of a pilot study and the prospective study protocol that resulted. In four French nephrology department, 76 patients were studied with a mean age of 83 ± 5 years, with a MDRD estimated GFR (abbreviated MDRD) of 16 ± 4 mL/min/1.73 m(2). These patients were different from the population on dialysis recorded in REIN. This pilot study has shown the feasibility of a prospective study on a larger scale, which aims to build a valuable tool for decision making in elderly patients with ESRF not yet on dialysis.

[Focusing on the steps to follow to initiate a clinical research project]. / Mise au point sur les démarches à suivre pour initier un projet de recherche clinique.

Texts governing clinical research are regularly revised in French law. The knowledge of administrative procedures to enable studies should be available to all interested clinicians. University hospitals are privileged with dedicated structures providing methodological and administrative support but which are sometimes ignored or underutilized. In this paper, we propose to define the categories of clinical research, their respective administrative framework and the steps and documents required for their realization in France. Finally, we specify some rules to follow in order to enable the communication of scientific results in international journals.