Effect of adding vildagliptin to insulin in haemodialysed patients with type 2 diabetes: The VILDDIAL study, a randomized, multicentre, prospective study.

AIM: To evaluate the effect of adding the dipeptidyl-peptidase-4 inhibitor vildagliptin to insulin on the glycaemic control of patients with type 2 diabetes undergoing haemodialysis. METHODS: Overall, 65 insulin-treated patients with type 2 diabetes undergoing haemodialysis (HbA1c: 7.3% ± 1.1%; age: 70.5 ± 8.5 years) were randomized (1:1) either to receive vildagliptin 50 mg/day in addition to insulin (vildagliptin-insulin group) or to pursue their usual insulin regimen (insulin-only group). Continuous glucose monitoring (CGM) was performed for 48 ± 6 hours at baseline and at week 12. The primary study endpoint was change from baseline in mean interstitial glucose using CGM. The secondary endpoints included other CGM variables and glucose control markers. RESULTS: After 12 weeks, a greater reduction in mean CGM glucose from baseline was observed in the vildagliptin-insulin group compared with the insulin-only group, although the between-treatment difference was not statistically significant (mean difference [CI 95%]: -0.96 mmol/L [-2.09; 0.18] vs. -0.29 mmol/L [-1.29; 0.76], P = 0.32). However, a significant decrease from baseline in HbA1c, glycated albumin and insulin daily doses was observed in the vildagliptin-insulin group versus the insulin-only group (-0.6% [-1.19; -0.1], P < 0.01), in the vildagliptin-insulin group versus no change in the insulin-only group (-130.6 µmol/L [-271; 10.7] vs. +36.2 µmol/L [-164.4; 236.9], P = 0.04 and - 5.9 IU/day [-1.8; 7.1] vs. +1.1 IU/day [-14.5; 16.6], P = 0.01, respectively). There was no significant difference in the percentage of time spent in hypoglycaemia using CGM, occurrence of severe hypoglycaemia or number of adverse events. CONCLUSION: In this study, vildagliptin added to insulin improved glycaemic control with an associated insulin-sparing effect in patients with type 2 diabetes undergoing haemodialysis and was well tolerated.

Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis.

Heparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess non-inferiority of a heparin grafted dialyzer (NCT01318486). A total of 251 maintenance hemodialysis patients at increased risk of hemorrhage were randomly allocated for up to three heparin-free hemodialysis sessions using a heparin-grafted dialyzer or the center standard-of-care consisting of regular saline flushes or pre-dilution. The first heparin-free hemodialysis session was considered successful when there was neither complete occlusion of air traps or dialyzer, nor additional saline flushes, changes of dialyzer or bloodlines, or premature termination. The current standard-of-care resulted in high failure rates (50%). The success rate in the heparin-grafted membrane arm was significantly higher than in the control group (68.5% versus 50.4%), which was consistent for both standard-of-care modalities. The absolute difference between the heparin-grafted membrane and the controls was 18.2%, with a lower bound of the 90% confidence interval equal to plus 7.9%. The hypothesis of the non-inferiority at the minus 15% level was accepted, although superiority at the plus 15% level was not reached. Thus, use of a heparin-grafted membrane is a safe, helpful, and easy-to-use method for heparin-free hemodialysis in patients at increased risk of hemorrhage.

[Focusing on peritoneal dialysis adequacy]. / Adéquation en dialyse péritonéale : mise au point.

The optimal method to assess the adequacy of peritoneal dialysis therapies is controversial. Today, the adequacy must not be considered as a number or a concept assessed only by two parameters (total KT/V urea and total solute clearance) but defined by many more items. In the absence of data, based on theoretical considerations, the reanalysis of the CANUSA study showed that renal kidney function, rather than peritoneal clearance, was associated with improved survival. Residual renal function is considered as a major predictor factor of cardiovascular mortality. Results of this reanalysis were supported by the adequacy data in ADEMEX, EAPOS and ANZDATA studies. Therefore, clinical assessment plays a major role in PD adequacy. The management of fluid balance, the regular monitoring of malnutrition, the control of mineral metabolism and particularly the glucose load, considered as the "corner-stone" of the system, are the main points to be considered in the adequacy of PD patients. The essential goal is to minimize glucose load by glucose-sparing strategies in order to reduce the neoangiogenesis of the peritoneal membrane.

Visit-to-visit blood pressure variability is a strong predictor of cardiovascular events in hemodialysis: insights from FOSIDIAL.

Optimal blood pressure (BP) targets are still controversial in end-stage renal disease. Recent data have highlighted shortcomings of the usual BP hypothesis in other patient populations and emphasized the importance of visit-to-visit variability of BP in predicting cardiovascular events. The Fosinopril in Dialysis Study failed to demonstrate the efficacy of 2-year angiotensin-converting enzyme inhibition with fosinopril versus placebo in 397 hemodialysis patients with left ventricular hypertrophy but provided an opportunity to assess the influence of BP variability on cardiovascular events. The primary end point was the occurrence of a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina, stroke, revascularization, hospitalization for heart failure, and resuscitated cardiac arrest. The variations in BP throughout the 17 visits were assessed by within-patient overall variability of systolic, diastolic, and pulse pressures between adjacent readings, by within-patient overall variability of systolic/diastolic/pulse pressures, and the residual of the linear fit. Compared with our previous predictive model of cardiovascular events occurrence based on stroke, peripheral arterial disease, coronary artery disease, diabetes mellitus, left ventricular mass, and age (which exhibited similar coefficients herein), the percentage of explained variance improved by 30.1% (R(2)=0.141-0.183) when adding the coefficient of variation of within-patient overall variability of systolic BP. Usual BP parameters were neither cardiovascular events predictors nor correlated to BP variability. Visit-to-visit BP variability was extremely high in hemodialysis patients compared with other populations and a major determinant of cardiovascular events. Such assessments should be prioritized for testing prevention strategies in end-stage renal disease.

Formulation of a dry weight bioimpedance index in hemodialysis patients.

Hydration status has a major impact on hemodialysis (HD) patients. Overhydration is related to hypertension, pulmonary and peripheral edema, and other cardiovascular events; while dehydration is related to hypotension, and other severe ischemic symptoms. All result in increased morbidity and mortality. Bioimpedance has been newly developed to measure the amount of water in the body. Several predictive equations were used, taken from demographic and anthropometric data. The purpose of this study was to evaluate the body composition of HD patients and to propose a hydration index. We performed bioimpedance measures with the Tanita TBF-300 scale, which calculates Total Body Water (TBW). The tool was reliable, with good reproducibility. However, we found significant differences between weight variations (dW) and TBW variations (dTBW) during HD sessions. This paper proposes a hydration index (I=dW-dTBW), with the hypothesis that dry weight is reached when I=0, while I>0 or I<0 indicate overhydrated or dehydrated, respectively. In this study, the changes in the index corresponded to the variations in weight and hydration state. We conclude that impedancemetry is a currently available technique that can be used to estimate TBW in HD patients. Although the index has to be improved by complementary studies, it may be a good guide to assess the dry weight achieved.

Impact of free light chain hemodialysis in myeloma cast nephropathy: a case-control study.

New very high permeability dialysis membranes have been developed to enable the clearance of free light chains in myeloma cast nephropathy. These new dialysis techniques, in combination with chemotherapy, should allow improved prognosis in patients with myeloma cast nephropathy. We report a prospective observational study comparing patients who underwent hemodialysis in our center in 2009 for cast nephropathy revealing multiple myeloma vs. patients treated for the same condition during the same period in other centers in our region. The main difference in the management protocols was the use of high cutoff (HCO) membranes in our center. We described the clinical features, the management protocols, and the outcomes as of June 1, 2010. In 2009, five patients were treated for myeloma cast nephropathy with HCO hemodialysis in our center. At 386 ± 100 days follow-up, one patient died, while three of the five patients recovered their renal function, allowing cessation of hemodialysis. During the same period, five patients were treated for myeloma cast nephropathy in other centers in our region. At 398 ± 131 days follow-up, four patients died, and none of the patients recovered renal function, allowing cessation of hemodialysis. In our study, light chain clearance allowed recovery of renal function and cessation of hemodialysis in three of five patients with acute kidney injury secondary to myeloma cast nephropathy. A randomized trial comparing this technique with conventional hemodialysis techniques should be conducted to raise the level of proof for this therapeutic option. The overall prognosis, including quality of life and cost-effectiveness, of HCO hemodialysis should also be examined.

[Segmental arterial mediolysis and renovascular hypertension]. / Médiolyse artérielle segmentaire et HTA rénovasculaire.

Segmental arterial mediolysis (SAM) is a rare nonarteriosclerotic, noninflammatory vascular disease of unknown origin that causes vascular occlusion or massive life-threatening intraabdominal hemorrhages. SAM is an acute disease. The initial injurious phase consist in mediolysis, then evolves in chronic vascular lesions. Diagnostic criteria are histologic, but rarely accessible apart from surgical complications. To our knowledge, there is no recommendation concerning therapy and follow-up of these patients. In our patient, we were interested in the atypical clinical presentation with renovascular hypertension, and the coexistence of acute and chronic vascular lesions that suppose the existence of recurrences in the evolution of this disease. We are interested also in the link that might exist between renal infarct and SAM, SAM's chronic vascular lesions and fibromuscular dysplasia vascular lesions.

[Workload during hemodialysis sessions]. / Description de la charge de soins en séance d'hémodialyse.

In recent years, the population of dialysis patients has become frailer and older. Patients present with more comorbid conditions and experience more complications during their follow-up. The aim of the present study is to describe the workload of the dialysis center during hemodialysis sessions and determine whether comorbidities are associated with increased workload. We conducted a retrospective multicentric study on a sample population of 123 patients selected from a dialysis population within a regional network. We described hospitalizations and HD sessions during a 1-year follow-up. We collected data on 19 prescriptions and events occurring during HD sessions. We described two HD care profiles (easy and difficult) and looked for variables linked with these profiles. We found that age more or equal to 60 years, elevated C-reactive protein and HD catheters are associated with difficult HD care. Surprisingly, apart from heart failure, comorbidities were not linked to greater workload during HD sessions. The development of HD care profiles should be helpful in early detection of frailer patients. This could have concrete applications such as better allocation of human and material resources and better training for the dialysis staff.

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/m(2) (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/m(2) (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.