Luc Frimat

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.

Impact of nephrology referral on early and midterm outcomes in ESRD: EPidémiologie de l'Insuffisance REnale chronique terminale en Lorraine (EPIREL): results of a 2-year, prospective, community-based study.

BACKGROUND Most studies looking at how the outcome of end-stage renal disease (ESRD) is affected by the timing and quality of the care received before initiation of renal replacement therapy (RRT) are inconclusive. METHODS Five hundred and two adult French patients (age, 62.8 +/- 16 years) receiving their first RRT were enrolled in a 2-year, community-based, prospective study. Subjects were assigned to 1 of 5 groups depending on the time between their first serum creatinine reading above 2 mg/dL (177 micromol/L): chronic renal failure (CRF) and nephrology referral (NR) and RRT. Multivariate logistic regression was used to analyze 90-day survival data, and data concerning long-term survival and inclusion on the waiting list for renal transplantation were analyzed using Cox proportional hazards regression. RESULTS Overall survival rates were 88% at 90 days, 77.2% at 1 year, 65.2% at 2 years, and 54.2% at 3 years. The nephrology referral pattern was associated with age and systolic blood pressure, and independently predicted early death. Compared with group 1 (NR > 12 months), odds ratios (confidence interval 95%) were 2.7 (1.2 to 6.3) for group 2 (NR < or = 12 months or >4 months), 2.8 (1.0 to 8.0) for group 3 (NR < or = 4 months or >1 month), 4.9 (2.2 to 11.0) for group 4 (NR < or = 1 month; CRF > 1 month), and 5.2 (2.2 to 12.3) for group 5 (NR < or = 1 month; CRF < or = 1 month). Independent predictors of death in 90-day survivors were age, cardiac disease with previous episodes of heart failure, vascular disease, low diastolic blood pressure, and group 3 referral pattern. Not being entered on the waiting list for renal transplantation was predicted by age, diabetes, vascular disease, and nonelective first dialysis. CONCLUSION Late nephrology referral is strongly associated with early death. Emergency first dialysis is an independent risk factor for not being placed on the waiting list for transplantation. Among 90-day survivors, referral pattern has little influence on mortality, which is mainly determined by cardiovascular complications at initiation of RRT.

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.

Recent Changes in Therapeutic Approaches and Association with Outcomes among Patients with Secondary Hyperparathyroidism on Chronic Hemodialysis: The DOPPS Study

BACKGROUND AND OBJECTIVES Elevated parathyroid hormone levels may be associated with adverse clinical outcomes in patients on dialysis. After the introduction of practice guidelines suggesting higher parathyroid hormone targets than those previously recommended, changes in parathyroid hormone levels and treatment regimens over time have not been well documented. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using data from the international Dialysis Outcomes and Practice Patterns Study, trends in parathyroid hormone levels and secondary hyperparathyroidism therapies over the past 15 years and the associations between parathyroid hormone and clinical outcomes are reported; 35,655 participants from the Dialysis Outcomes and Practice Patterns Study phases 1-4 (1996-2011) were included. RESULTS Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan, where it remained stable. Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time. Compared with 150-300 pg/ml, in adjusted models, all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio, 1.09; 95% confidence interval, 1.01 to 1.18) and >600 pg/ml (hazard ratio, 1.23; 95% confidence interval, 1.12 to 1.34). Parathyroid hormone >600 pg/ml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations. In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy, very low parathyroid hormone (<50 pg/ml) was associated with mortality (hazard ratio, 1.25; 95% confidence interval, 1.04 to 1.51). CONCLUSIONS In a large international sample of patients on hemodialysis, parathyroid hormone levels increased in most countries, and secondary hyperparathyroidism treatments changed over time. Very low and very high parathyroid hormone levels were associated with adverse outcomes. In the absence of definitive evidence in support of a specific parathyroid hormone target, there is an urgent need for additional research to inform clinical practice.

Effect of end-stage renal disease on the quality of life of older patients.

OBJECTIVES: To assess the effect of chronic renal failure (CRF) on quality of life (QOL).

Association between orthostatic hypotension and cardiovascular risk, cerebrovascular risk, cognitive decline and falls as well as overall mortality: a systematic review and meta-analysis.

Objective: Several studies have suggested that orthostatic hypotension may be an independent predictor of cardiovascular or cerebrovascular risk and all-cause mortality, particularly in a geriatric population. In 1996, a consensus defined orthostatic hypotension as a SBP fall at least 20 mmHg and/or a DBP fall at least 10 mmHg within 3 min of standing. Methods: Pubmed and Cochrane database were searched up to October 2013 in order to identify prospective studies evaluating, in adult populations, the association between orthostatic hypotension as defined by the 1996 consensus and clinical outcome. Meta-regression was performed when sufficient data were available. Results: A total of 28 prospective studies were found eligible for inclusion in this systematic review. Nine prospective studies found an association between orthostatic hypotension and various cardiovascular events such as coronary disease, heart failure, and arrhythmias. No association was found between orthostatic hypotension and the risk for strokes and falls in the majority of the prospective included studies. Insufficient data were available to perform a meta-analysis for strokes and falls. The meta-analysis of seven prospective studies found that orthostatic hypotension is associated with a significant increased risk for overall mortality [pooled hazard ratio in random-effects model = 1.36 (1.13–1.63), P < 0.001)]. Conclusion: This meta-analysis provides evidence that orthostatic hypotension is associated with a 36% increase in the risk of overall mortality. A systematic review of the literature suggests that orthostatic hypotension is also associated with a higher risk for cardiovascular events. Insufficient data are available to enable a precise assessment of the association of orthostatic hypotension with strokes and falls.

Complete robotic‐assistance during laparoscopic living donor nephrectomies: An evaluation of 38 procedures at a single site

Objective:  To evaluate our initial experience with entirely robot‐assisted laparoscopic live donor (RALD) nephrectomies.

Renal involvement in Castleman disease

BACKGROUND Castleman disease (CD), or angiofollicular lymph-node hyperplasia, is an atypical lymphoproliferative disorder with heterogeneous clinical manifestations. Renal involvement in CD has been described in only single-case reports, which have included various types of renal diseases. METHODS Nineteen patients with histologically documented CD and renal biopsies available were included. Clinical features and renal histological findings were reviewed, and the available samples were immunolabelled with anti-vascular endothelial growth factor (VEGF) antibody. RESULTS Nineteen CD cases were identified: 89% were multicentric, and 84% were of the plasma-cell or mixed type. Four cases (21%) were associated with human immunodeficiency virus (HIV) infection. Among HIV-negative patients, two main patterns of renal involvement were found: (i) a small-vessel lesions group (SVL) (60%) with endotheliosis and glomerular double contours in all patients and with superimposed glomerular/arteriolar thrombi or mesangiolysis in most; and (ii) AA amyloidosis (20%). Renal histology was more heterogeneous among HIV-positive patients. Decreases in glomerular VEGF were observed only in some patients with SVL, whereas VEGF staining was normal in all other histological groups. Interestingly, glomerular VEGF loss associated with SVL was correlated with plasma C-reactive protein levels, a marker of CD activity. CONCLUSIONS Small-vessel lesions are the most frequent renal involvement in CD, whereas loss of glomerular VEGF is correlated with CD activity and could have a role in SVL pathophysiology.

Cardiac impact of the arteriovenous fistula after kidney transplantation: a case-controlled, match-paired study

In kidney transplant (KT) recipients, cardiac impact of the persistence of an asymptomatic arteriovenous fistula (AVF) for hemodialysis has not been fully elucidated. Seventy‐six patients (mean age: 49 years) without history of diabetes or cardiovascular disease underwent an echocardiography. Thirty‐eight had a functioning AVF and were match‐paired for age, gender and KT duration. Left ventricular mass index (LVMI) was significantly higher in patients with functioning AVF: 135.1 ± 30.3 vs. 112.4 ± 28 g/m2 (P = 0.001). Exposure to AVF increased the risk of developing high LVH fourfold. Search for a dose‐effect of AVF flow revealed a trend towards increasing LVMI with higher flow: 142.6 ± 30 vs. 126.9 ± 23.9 g/m2 (P = 0.084) (median flow of the population as cut‐off). Other significant changes were observed in left ventricular dimensions: greater end diastole‐ and systole diameters, both larger left and right atria, and left atrium diameter. Our study suggests that, in stable asymptomatic KT patients, functioning AVF has significant impact on cardiac mass, cardiac index and left ventricular dimensions. The effects on morbidity and mortality were to be investigated.

Survival of transplanted and dialysed patients in a French region with focus on outcomes in the elderly

BACKGROUND Impact of kidney transplantation on survival of French end-stage renal disease (ESRD) patients is unknown. METHODS A total of 1495 adults living in the Lorraine region and starting renal replacement therapy from 1997 to 2003 were included. A propensity score (PS) of registration on the renal transplant waiting list was estimated. Patient survival was studied using a time-dependent Cox multivariate regression and a Cox model stratified by PS tertiles. Survival of older patients (> or =60 years) was detailed. RESULTS Survival was associated with age, medical factors and transplantation. The hazard ratio (HR) of death for patients on dialysis compared to transplant recipients was 4.6 (95% CI: 2.9-7.2). The survival analysis stratified by PS was similar to the multivariate Cox model. The survival benefit of transplantation over dialysis persisted among elderly patients [HR: 4.6 (95% CI: 2.2-9.7)]. CONCLUSIONS In a French community-based network, after taking into account comorbidities, transplantation was associated with longer survival even among elderly patients. Age per se should not therefore be considered as a contraindication to renal transplantation. However, elderly patients should be evaluated carefully before registration on the list. Medical guidelines should put forward a standard set of criteria for access to renal transplantation.