Yohan Duny

Effect of TNF inhibitors on lipid profile in rheumatoid arthritis: a systematic review with meta-analysis

Background Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease. Lipid changes related to inflammation have been described in RA. Tumour necrosis factor α (TNFα) inhibitor (TNFi) treatment is effective in controlling inflammation and decreasing the number of cardiovascular events. Objective To assess the change in lipid levels with TNFi treatment in patients with RA by systematic review and meta-analysis. Methods A Medline search was performed for articles published up to March 2011. Reports describing values for total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TGs), atherogenic index (AI) and apolipoprotein B/A (apoB/A) collected before and after TNFi initiation were included. Data were analysed according to short-, mid- and long-term treatment. Statistical analysis of pre–post data was performed by comprehensive meta-analysis. A random effects model was used when there was evidence of heterogeneity. Results The search retrieved 32 articles, of which 13 prospective before/after studies were analysed. Long-term TNFi treatment was associated with increased levels of HDL (+0.27 mmol/l, p<0.0001) and TC (+0.27 mmol/l, p=0.03), whereas LDL levels and AI remained unchanged. After long-term treatment, TG levels increased (+0.28 mmol/l, p<0.001) and apoB/A decreased (−0.3, p<0.0001). Conclusion The presumed cardioprotective effects of TNFi in RA do not seem to be explained by quantitative lipid changes since long-term treatment has no effect on LDL levels or on AI. Increased HDL levels could have some beneficial effects, but this needs to be confirmed by prospective studies with long-term follow-up.

Vitamin D Treatment and Mortality in Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Background/Aims: Hypovitaminosis D has been associated with an increased cardiovascular mortality in the general population and in patients with chronic kidney disease (CKD). Still, whether prescribing vitamin D reduces the risk of mortality in renal patients remains controversial. Methods: We searched PubMed, ClinicalTrials.gov and the Cochrane Library for long-term longitudinal studies comparing vitamin D compounds (25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and synthetic derivatives) to placebo or no treatment in renal patients, and which evaluated mortality, to perform a meta-analysis. Data concerning study quality, population and effect size were extracted independently by two investigators using predefined forms. Results: Fourteen observational studies (194,932 patients) met all eligibility criteria. Most studies were performed in hemodialysis patients and all used calcitriol or synthetic analogues. In a random effects meta-analysis, receiving any vitamin D therapy significantly reduced the risk of all-cause mortality (relative risk 0.73, 95% CI 0.65-0.82). The relative risk of death was 0.72 (95% CI 0.65-0.80) after 3 years of therapy and 0.67 (95% CI 0.45-0.98) after 5 years. In meta-regression, the risk reduction was shown to be greater in patients with higher parathyroid hormone serum levels (p = 0.01). The risk of cardiovascular mortality was also significantly reduced in patients receiving any vitamin D derivative (relative risk 0.63, 95% CI 0.44-0.92). Conclusion: Therapies with 1,25-dihydroxyvitamin D and analogues are associated with reduced mortality in CKD patients, and particularly in those suffering from secondary hyperparathyroidism. These results, based on observational evidence, are supportive of prescribing vitamin D therapies to CKD patients, while respecting good practice guidelines.

Excessive alcohol consumption after liver transplantation impacts on long-term survival, whatever the primary indication

BACKGROUND & AIMS Beyond 5 years, poorer survival, related to alcohol relapse, is observed in patients with liver transplant for alcohol-related liver disease (ALD). However, alcohol consumption has been significantly understudied in non-ALD transplant recipients. We aimed at analyzing the impact of alcohol consumption on long-term survival irrespective of the indication for transplantation. METHODS This observational study included consecutive adult recipients of a primary liver graft between 1991 and 2007 in our hospital, who survived >6 months. Patients without ALD as primary indication, but with a history of excessive alcohol consumption before transplantation, were classified as secondary indication ALD. We studied the impact on survival of excessive consumption of alcohol after transplantation and several other variables. RESULTS The 441 patients had mean follow-up of 81.7 months. Among the 281 patients with excessive alcohol consumption before transplantation, 206 had ALD as primary indication. After transplantation, alcohol consumption was reported by 32.3% of the study population, 43.7% in primary indication ALD, and 24.3% in non-ALD patients. Survival was 82% at 5 years and 49% at 10 years for patients with excessive alcohol relapse, compared with 86% and 75%, respectively, for patients without persistent excessive alcohol relapse. By multivariable analysis, the independent risk factors of death were: excessive alcohol relapse, age >51 years, post-transplantation diabetes mellitus, cyclosporine-based immunosuppression, and non-hepatic cancer. CONCLUSIONS Excessive alcohol consumption has a negative impact on long-term survival after liver transplant, irrespective of the primary indication. Death is mainly due to recurrence of liver disease and non-hepatic cancer.

Treatment of hypertension with renin-angiotensin system inhibitors and renal dysfunction: a systematic review and meta-analysis.

BACKGROUND To determine whether inhibitors of the renin-angiotensin system (RAS) reduce the incidence of renal dysfunction when compared to other antihypertensive treatments in patients with essential hypertension and no pre-existent renal disease. METHODS The search strategy used the Cochrane Library, Medline, previous meta-analyses, and journal reviews. The selection criteria included randomized, controlled trials of antihypertensive drugs that compared a RAS inhibitor with another treatment in essential hypertension. Studies that specifically enrolled only patients with diabetes or renal disease were not included. The quality assessment and data extraction of studies were performed by two independent reviewers. Effects on dichotomous renal outcome (serum creatinine (SCreat) higher than a prespecified value, doubling of SCreat or end-stage renal disease) and secondary continuous marker of renal outcome (change in SCreat) were calculated using Petos method. RESULTS 33,240 patients met the inclusion criteria for studies with a dichotomous outcome and 10,634 patients for studies with a continuous outcome. The mean follow-up was 42 ± 13 months. Patients randomized to RAS inhibitors did not show a significant reduction in the risk of developing renal dysfunction as compared to other antihypertensive strategies (odds ratio = 1.05; 95% confidence interval (CI) 0.89-1.25; P = 0.54). There was no significant difference in change of SCreat between groups (mean difference = 0.0005 mg/dl; 95% CI -0.0068 to 0.0077 mg/dl; P = 0.91). CONCLUSION In patients with essential hypertension and no pre-existent renal disease, prevention of renal dysfunction is not significantly different with RAS inhibitors when compared to other antihypertensive agents.

Incidence of solid organ cancers after liver transplantation: comparison with regional cancer incidence rates and risk factors.

Increased rates of solid organ cancers post‐liver transplantation have been reported, but the contribution of environmental factors and immunosuppressive therapy is not clear. This studys aims were to compare the incidence of de novo solid organ cancers after liver transplantation; identify risk factors independent of immunosuppressive therapy associated with these cancers; and assess the influence of calcineurin inhibitors on the appearance of these cancers.

Tacrolimus and the risk of solid cancers after liver transplant: a dose effect relationship.

Although increased rates of solid organ cancers have been reported following liver transplantation (LT), the impact of quantitative exposure to calcineurin inhibitors (CNI) remains unclear. We have therefore probed the relationship between the development of solid organ cancers following LT and the level of CNI exposure. This prospective single‐center study was conducted between 1995 and 2008 and is based on 247 tacrolimus‐treated liver transplant recipients who survived at least 1 year following surgery. The incidence of cancer was recorded, and the mean blood concentration of tacrolimus (TC) was determined at 1 and 3 years following LT. The study results indicate that 43 (17.4%) patients developed de novo solid cancers. Mean TC during the first year after LT was significantly higher in patients who developed solid organ tumors (10.3 ± 2.1 vs. 7.9 ± 1.9 ng/mL, p < 0.0001). Independent risks factors in multivariate analysis were tobacco consumption before LT (OR = 5.42; 95% CI [1.93–15.2], p = 0.0014) and mean annual TC during the first year after LT (p < 0.0001; OR = 2.01; 95% CI [1.57–2.59], p < 0.0001). Similar effects were observed in 216 patients who received tacrolimus continuously for ≥3 years. It appears therefore that CNI should be used with caution after LT, and that new immunosuppressive therapies could deliver significant clinical benefits in this regard.

Similar patient survival following kidney allograft failure compared with non-transplanted patients

Data from the national French Renal Epidemiology and Information Network (REIN) registry were used to compare survival between transplant recipients under age 65 who resumed dialysis after graft failure during 2007-2009 and transplant-naïve incident dialysis patients matched for age, gender, diabetes mellitus, and year of starting dialysis. Among 911 transplant patients who returned to dialysis, 103 had died by 1 January 2011. Multivariate analysis showed that age over 48 years, coronary artery disease, peripheral artery disease, and inability to walk unassisted were significant predictors of death. In the case-control analysis, the observed mortality rates in 778 transplant failure and 778 transplant-naïve dialysis patients were 11.8 and 10.8%, respectively. Kaplan-Meier estimates of survival after transplant failure vs. the transplant-naïve controls were 95.2 vs. 94.1% at 1 year, 90.3 vs. 88.8% at 2 years, and 84.2 vs. 80.2% at 3 years (log rank P=0.197 overall). Dialysis in transplant failure vs. transplant-naïve patients was not associated with significantly increased mortality. At the start of dialysis, the serum creatinine levels and the rate of unplanned dialysis were significantly lower in transplant failure patients compared with transplant-naïve controls. Thus, in patients under 65 years of age in France, survival of dialysis patients after graft loss is similar to that of incident dialysis patients who have not undergone transplantation.

The use of SDS–PAGE scanning of spent dialysate to assess uraemic toxin removal by dialysis

Background. Uraemic toxins in the 8 to 60 kDa molecular weight range have been attracting increasing attention in dialysis therapy. However, there are no available standardized methods to evaluate their removal. Using new filtering membranes, we evaluated SDS–PAGE of spent dialysate to assess cut-off ranges and removal capacities into dialysate, while also measuring classical markers of dialyser function. Methods. Eighteen dialysis patients were washed out for 2 weeks with FX 100 (Helixone®), followed by randomization to Xevonta Hi 23 (Amembris®) or FX dialysers for 2 weeks, then crossed over for an additional 2 weeks, and finally placed on Xenium 210 (Purema®) for 2 weeks. SDS–PAGE scanning of the removed proteins contained in the spent dialysate was performed during all dialysis sessions. Total mass of urea, creatinine, total proteins, beta 2 microglobulin (β2m), retinol-binding protein (RBP) and albumin were measured. The reduction rates of serum urea, creatinine, β2m, leptin, RBP, alpha 1-antitrypsin, albumin and total proteins were also determined. Results. SDS–PAGE scanning identified four major protein peaks (10–18, 20–22.5, 23–30 and 60–80 kDa molecular weight) and showed clear differences in the amounts of removed proteins between the dialysers, particularly in the 20–22.5, 23–30 and 60–80 kDa ranges. Total mass of removed β2m, RBP and albumin were in agreement with SDS–PAGE, while serum assays showed differing results. Conclusions. SDS–PAGE scanning provided a good characterization of protein patterns in the spent dialysate; it extended and agreed with protein determinations and allowed a better assessment of dialyser performance in removing 10 to 80 kDa molecular weight substances. It also identified differences between the three mainly filtrating polysulfone dialysers that were not detected with blood measurements.

Impact of tobacco and alcohol consumption in patients registered on waiting list on early morbidity following liver transplantation.

BACKGROUND Liver transplantation (LT) is a high-risk surgery associated with postoperative complications. Smoking and drinking are known risk factors of long-term post-LT complications, but their role in early complications is still questioned. PATIENTS AND METHODS We retrieved from our medical files the data of all patients registered for LT and who had had a consultation with a physician specialized in substance abuse. Consumption of alcohol, tobacco, and drugs before and after registration for LT was assessed. RESULTS One hundred and five patients were included. Pre-registration smoking and drinking rates were 75.3 and 69.5%, respectively. Forty-three patients continued smoking and nine continued drinking until LT. Mortality and early morbidity rates were not impacted by smoking or drinking. Active smokers had significantly increased prevalence of bacterial cholangitis in comparison to patients who stopped smoking when registered for LT. CONCLUSION Persistent drinking in patients registered for LT is rare as compared to smoking; however, in our series, smoking until LT was not associated with major risk of early complication, except for cholangitis. This suggests that clinicians should take time to encourage patients to quit smoking and the intervention of a team specialized in substance abuse could be highly beneficial.

Early changes in body weight and blood pressure are associated with mortality in incident dialysis patients

Abstract Background While much research is devoted to identifying novel biomarkers, addressing the prognostic value of routinely measured clinical parameters is of great interest. We studied early blood pressure (BP) and body weight (BW) trajectories in incident haemodialysis patients and their association with all-cause mortality. Methods In a cohort of 357 incident patients, we obtained all records of BP and BW during the first 90 days on dialysis (over 12 800 observations) and analysed trajectories using penalized B-splines and mixed linear regression models. Baseline comorbidities and all-cause mortality (median follow-up: 2.2 years) were obtained from the French Renal Epidemiology and Information Network (REIN) registry, and the association with mortality was assessed by Cox models adjusting for baseline comorbidities. Results During the initial 90 days on dialysis, there were non-linear decreases in BP and BW, with milder slopes after 15 days [systolic BP (SBP)] or 30 days [diastolic BP (DBP) and BW]. SBP or DBP levels at dialysis initiation and changes in BW occurring in the first month or during the following 2 months were significantly associated with survival. In multivariate models adjusting for baseline comorbidities and prescriptions, higher SBP value and BW slopes were independently associated with a lower risk of mortality. Hazard ratios of mortality and 95% confidence intervals were 0.92 (0.85–0.99) for a 10 mmHg higher SBP and 0.76 (0.66–0.88) for a 1 kg/month higher BW change on Days 30–90. Conclusions BW loss in the first weeks on dialysis is a strong and independent predictor of mortality. Low BP is also associated with mortality and is probably the consequence of underlying cardiovascular diseases. These early markers appear to be valuable prognostic factors.