Thierry Krummel

Oral antidiabetics use among diabetic type 2 patients with chronic kidney disease. Do nephrologists take account of recommendations

BACKGROUND There is an increasing prevalence of diabetes type 2 and chronic kidney disease, challenging appropriate prescribing of oral anti-diabetic drugs (OADs). METHODS We have described the practice patterns of 13 nephrologists in 4 centers, in a cohort of 301 consecutive adult type 2 diabetic patients. Among oral anti-diabetic prescriptions, we have detailed drugs dosage for each subject, with 3 different formulae for estimating glomerular filtration rate (GFR) and its adequation according to the latest ERBP recommendations (2015). As individuals were mostly obese in this work, we also compare adequacy rates using both standard indexed CKD-EPI formula and CKD-EPI formula de-indexed from body surface area. RESULTS Using the CKD-EPI formula as the reference method for estimating GFR, 53.5% of patients were outside the recommendations, mostly for metformin (30% of the whole cohort) and for sitagliptin (17.9% of the whole cohort). With Cockcroft and Gault formula, 38.2% of persons were outside recommendations and 45.9% (p<0.001) with CKD-EPI de-indexed. Among individuals consulting a nephrologist for the first time (n=90), 61.1% were outside recommendations (p=0.1). Among those persons under diabetologist supervision (n=103), 63.1% were outside recommendations (p=0.09), and were taking significantly more often metformin and insulin. CONCLUSION We have found a substantial number of inadequate OAD prescriptions in type 2 diabetic patients with chronic kidney disease. The proportion of individuals outside guidelines was strongly affected by the method used for estimating GFR and by the type of practice, i.e., specialists versus general practitioners.

Clinical Potentials of Adsorptive Dialysis Membranes

and proteins to a surface, but without actually penetrating the surface. This process depends mostly upon the internal pore structure and the hydrophobic properties of the dialysis membrane. So far, the potential survival benefit of adsorption has not been examined. There is, however, a growing body of evidence suggesting improvement on removal of AGEs, homocysteine and erythropoiesis inhibitors or increased response to vaccination [3, 4] . In this supplemental issue of Blood Purification , several reviews discuss the potential clinical benefits of dialysis membranes with high adsorptive properties. Renal insufficiency is a frequent complication of multiple myeloma which may affect up to 50% of patients, 15–20% of them developing acute renal failure and 10% of these patients later becoming dialysis dependent. A substantial proportion of patients develop a distinct form of renal failure (cast nephropathy) due to high concentrations of monoclonal free light chains (FLC) in the plasma and hence in the urine, leading to precipitation and aggregation with uromodulin to form tubular casts. In these patients, early removal of circulating FLC is of paramount importance to recover a normal renal function. In conjunction with bortezomib-based chemotherapy, extracorporeal removal of FLC may be achieved with plasma exchanges or more recently by haemodialysis using highpermeability filters with a very high cutoff (HCO), close to 55 kDa, thus potentially capable of removing κ and λ Haemodialysis for chronic renal failure encompasses 3 different biophysical processes, namely dialysis, convection and adsorption. The relative part of each process varies largely according to the chemical and pore structure of membranes, electrostatic charges and hydrophobic properties. Dialysis of small molecules along a concentration gradient has been the cornerstone of haemodialysis therapy during the last decades. However, using an index of solute clearance, the HEMO study failed to show a benefit on mortality when equilibrated KT/V urea was increased from 1.05 to 1.45 per session, suggesting that most of the diffusive exchanges are obtained during a classic 4to 5-hour dialysis session [1] . Larger (middle-molecular-weight uraemic toxins) molecules or protein-bound molecules can be mostly cleared from plasma using haemodiafiltration, i.e. convection with a large volume of generally >20 litres per session. The CONTRAST study has recently examined the potential clinical benefits associated with haemodiafiltration versus standard conventional low-flux dialysis. This trial failed to show any substantial benefit on mortality with haemodiafiltration treatment despite achieving significant improvement on several intermediate end points (β2-microglobulin, etc.) [2] . Adsorption is the accumulation and adhesion of molecules, ions or larger particles including macromolecules Published online: May 3, 2013

Haemodialysis in patients treated with oral anticoagulant: should we heparinize?

BACKGROUND Anticoagulation for the haemodialysis circuit in patients treated with oral anticoagulation poses additional haemorrhagic risk. The few available data suggest that tapering or even stopping heparinization is feasible and the HeprAN membrane with grafted heparin was developed to decrease heparin dose. The objective of our study was to evaluate the need for additional anticoagulation in patients on long-term oral anticoagulation, according to the type of membrane used. METHODS This is a prospective, randomized, crossover bifactorial trial in haemodialysed patients on oral anticoagulation. Each patient had four haemodialysis sessions with two different membranes [HeprAN or polysulphone (PS)] and with or without enoxaparin. Clinical coagulation was evaluated by the need for premature ending and by a visual score (Janssen scale). Coagulation activation markers were also measured: d-dimers, prothrombin fragments 1 + 2, thrombin-antithrombin complexes, tissue factor pathway inhibitor and platelet factor-4. RESULTS Ten patients were included (M/F = 4/6, mean age 63 ± 15 years). None of the 40 sessions ended prematurely. The clotting scores were similar with or without enoxaparin (dialyser: 1.49 ± 0.19 versus 1.53 ± 0.17, P = 0.97; bubble trap: 0.75 ± 0.19 versus 0.78 ± 0.22, P = 0.62) and with the polysulphone or the HeprAN membrane (dialyser: 1.54 ± 0.20 versus 1.47 ± 0.16, P = 0.65; bubble trap: 0.74 ± 0.22 versus 0.79 ± 0.19, P = 0.58). There was no significant difference in coagulation activation markers between dialysis modalities; however, dialysis efficacy was significantly greater with the PS membrane (1.58 ± 0.07 versus 1.43 ± 0.06, P = 0.02). CONCLUSIONS These results suggest that haemodialysis without additional anticoagulation is possible in patients with oral anticoagulation. The HeprAN membrane did not provide any additional benefit compared with a PS membrane.

The Relationship of NT-proBNP and Dialysis Parameters with Outcome of Incident Haemodialysis Patients: Results from the Membrane Permeability Outcome Study

Background/Aims: The association of raised levels of natriuretic peptides with elevated risk of mortality was investigated in the present analysis of the Membrane Permeability Outcome study. Methods: N-terminal probrain type natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis patients, randomised to either high-flux or low-flux. Characteristics of patients with NT-proBNP levels below or above the median were descriptively analysed and survival analysis was performed. Results: Median NT-proBNP value was 2,124 pg/ml, with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival probability was lowest in patients with both a history of cardiovascular disease and NT-proBNP values above the median (p < 0.001). A multivariate Cox proportional hazard model showed interaction between presence of cardiovascular diseases and NT-proBNP levels above the median. Conclusions: NT-proBNP is an independent predictor of mortality also in incident haemodialysis patients. Lower concentrations associated with high-flux dialysis suggest a possible biological link to improved survival in this group.

Diagnostic précoce de l’insuffisance rénale

Resume Le depistage de l’insuffisance renale chronique et la quantification de la filtration glomerulaire reposent classiquement sur des methodes qui ne sont pas applicables a l’echelle des populations. L’utilisation d’equations permettant d’estimer le debit de filtration glomerulaire a partir d’un minimum de donnees (marqueurs seriques et donnees anthropomorphiques) constitue une avancee considerable pour la problematique du depistage. Les equations proposees, MDRD en particulier, sont performantes pour la quantification de la fonction renale chez des patients ayant une nephropathie connue et un DFG compris entre 10 et 60 ml/min.1,73 m2. Ces equations ont cependant une precision insuffisante pour le depistage et la quantification de la fonction renale chez des individus presumes sains avec un DFG normal. Cet article passe en revue les avantages et les faiblesses des equations actuellement utilisees et aborde quelques consequences sur le depistage dans la population generale.

Les promesses de la néphroprotection à l’épreuve des faits

Clinical studies of the last 15 years have shown the benefit of pharmacological interventions on the progression of chronic kidney disease, confirming the concept of nephroprotection. Pharmacological blockade of the renin angiotensin system remains the cornerstone of the nephroprotective treatment but the benefits and limitations are now better defined. The RAS blockers are all the more efficient than the proteinuria is abundant and nephroprotection is obtained in proportion to the reduction in proteinuria. Combinations of ACEI+ARA are not validated and their use should be considered only under the supervision of a specialist when optimal monotherapy has failed. The target blood pressure has been the subject of recent controversies, particularly in type 2 diabetic patients with nephropathy. The target should be individualized based on the main risk, renal or cardiovascular. Recent maneuvers have also shown a nephroprotective effect, including the correction of metabolic acidosis with sodium bicarbonate.

Survival advantage of planned haemodialysis over peritoneal dialysis: a cohort study

Background Previous studies comparing the outcomes in haemodialysis (HD) with those in peritoneal dialysis (PD) have yielded conflicting results. Methods The aim of the study was to compare the survival of planned HD versus PD patients in a cohort of adult incident patients who started renal replacement therapy (RRT) between 2006 and 2008 in the nationwide REIN registry (Réseau Epidémiologie et Information en Néphrologie). Patients who started RRT in emergency or stopped RRT within 2 months were excluded. Adjusted Cox models, propensity score matching and marginal structural models (MSMs) were used to compensate for the lack of randomization and provide causal inference from longitudinal data with time-dependent treatments and confounders including transplant censorship, modality change over time and time-varying covariates. Results Among a total of 13 767 dialysis patients, 13% were on PD at initiation of RRT and 87% were on HD. The median survival times were 53.5 months or 4.45 years and 38.6 months or 3.21 years for patients starting on HD and PD, respectively. Regardless of the model used, there was a consistent advantage in terms of survival for HD patients: hazard ratio (HR) 0.76 [95% confidence interval (95% CI) 0.69-0.84] with the Cox model using propensity score; HR 0.67 (95% CI 0.62-0.73) in the Cox model with censorship for each treatment change; and HR 0.82 (95% CI 0.69-0.97) with MSMs. However, MSMs tended to reduce the survival gap between PD and HD patients. Conclusion This large cohort study using various statistical methods to minimize the bias appears to demonstrate a better survival in planned HD than in PD.

Les recommandations des néphrologues sont peu suivies par les médecins traitants. L’exemple de la vaccination contre l’hépatite B

The relationship between specialist physician and primary care physician (PCP) has been poorly evaluated in France. We have studied the application of a specialists recommendation by the PCP. Vaccination against hepatitis B in patients with chronic renal failure was the follow-up marker. After consultation, the nephrologist wrote in his report to the PCP that the vaccination was recommended. At the next nephrological consultation, the patient was asked if the PCP had proposed vaccination. The clinical, biological characteristics and history of the patients were recorded as well as number and location of the PCP consultations. Five nephrology centers recruited 315 patients. In 61.6% (194/315) of the cases, the vaccination was not proposed by the PCP. Only the estimated GFR (lowest in vaccinated patients, 29.5 vs. 34.5mL/min/1.73m2), the delay between the two consultations of the nephrologist (shorter in vaccinated patients, 18.7 vs. 22.9 weeks) and the nephrologists practice center (17.5 to 52% vaccination rate) are statistically significant in univariate analysis. In multivariate analysis, only the center effect persists. The lack of vaccination was argued by a letter from the PCP in 2 cases (1%). In the absence of a direct questioning of the PCP, the reasons for not following the recommendation remain unexplained. Overall, the recommendation of the nephrologist was little followed. Our study can contribute to the reflection on the shared follow-up of patients suffering from chronic diseases.

Psychotropic Drug Use in Recreational Scuba Divers and its Effect on Severe Narcosis

Recreational scuba diving is no longer reserved for young healthy individuals, and as a result, medical drug consumption is on the rise in the diving population. Due to the possible potentiation of nitrogen narcosis by psychotropic drugs, the latter are hence discouraged and are subject to contraindications for practice. However, there are no available experimental data to support this theoretical assumption. The objective of this study is to investigate whether psychotropic drug users are more at risk of severe narcosis. An online survey was sent to the licensed divers from the East of France registered with the French Underwater Federation. Divers were surveyed regarding their consumption of psychotropic drugs, the occurrence of nitrogen narcosis as well as their respective divers curriculum vitae.1 608 divers responded to the survey of which 15.2% confirmed having used psychotropic drugs and 7.8% since they became divers. Overall, 40.0% and 5.5% experienced severe and critical narcosis. In multivariate analysis, neither severe nor critical narcosis was associated with psychotropic drug use (OR 0.97 [0.59-1.57] and 0.76 [0.29-2.00], respectively).In conclusion, despite the recommendations, a significant proportion of divers use psychotropic drugs but do not seem to be more prone to severe narcosis.

Traitement pharmacologique de l'HTA en hémodialyse

Resume Les patients dialyses qui restent hypertendus malgre l’obtention du poids sec necessitent un traitement antihypertenseur pharmacologique. Il y a peu d’essais d’intervention chez ce type de patients si bien qu’il est difficile de savoir si le benefice cardiovasculaire du traitement est lie a la baisse tensionnelle en soi ou a des proprietes specifiques de classe ou de molecules. Cet article passe en revue les differentes classes de medicaments antihypertenseurs et leurs avantages et inconvenients. En pratique la prescription depend essentiellement des donnees pharmacocinetiques et surtout des indications privilegiees pour des complications cardiovasculaires associees a l’hypertension.