[Switch of methoxy-polyethylene-glycol-epoetin beta to darbepoetin alfa in 263 dialysis patients]. / Étude de la conversion du méthoxypolyéthylèneglycol-époétine bêta vers la darbépoétine alfa chez 263 patients hémodialysés.

In early 2012, due to national supply disruption, the methoxy-polyethylene glycol-epoetin beta (CERA) was no longer available and has been replaced by darbepoetin alfa (DA) in all dialysis patients. Official recommendations for the replacement of one by the other is missing or unclear. On this occasion, we wanted to examine how the shift from CERA to DA was done in terms of dose conversion factor and the other factors that could have influenced the dose of DA prescribed (hemoglobin, patient weight, dose of CERA). This retrospective multicenter open conducted in six dialysis centers in Alsace is the first large study (n=263) that evaluated the switch from CERA to DA in all chronic hemodialysis patients. We found that the instantaneous ratio of dose adjustment is close to 1 and that nephrologists are mainly based on the dose of CERA for determining the DA dose, before hemoglobin and weight. However, establishing a true dose-response ratio between the two molecules requires a long term prospective study.

Influence of dialysis on the glucose profile in patients with diabetes: usefulness of continuous glucose monitoring.

We sought to investigate the impact of dialysis on glucose profiles of diabetic patients using continuous glucose monitoring (CGM). The study included 33 hemodialyzed patients with diabetes (14 females and 19 males; mean age: 66±8 years; patients with type 2 diabetes: 30; mean duration of dialysis: 3.8±2.6 years) who were under insulin treatment. After a run-in period, CGM was performed for 48 h, including a dialysis session. Three CGM sessions were proposed for each patient over a 3-month period. CGM results were analyzed during and after dialysis at 6 different time points. Moreover, data were analyzed in 7 different day periods according to meals. Of the 99 CGM available, 21 were excluded because of technical issues or patient refusal. The CGM results indicated that mean glucose values (7.5±2.5 mmol/l vs. 9.4±1.9 mmol/l; p<0.001) and variability indices (p<0.001) were lower, whereas the frequency of hypoglycemia (4.4±9.6% vs. 2.1±7.9%; p<0.001) was higher during hemodialysis sessions. Significant differences were observed in glucose values only before and 2 h after breakfast (p<0.001). Compared with other day periods, glucose values were lower during the second half of the night and higher before and after dinner (p<0.001). In summary, CGM allows the identification of a particular glucose profile in hemodialyzed diabetic patients. CGM seems feasible and clinically useful for the analysis of glucose profiles in this group of patients.

[Survival and mortality in ESRD patients]. / Survie et mortalité des patients en IRCT.

This chapter provides a set of indicators on survival, life expectancy and causes of death of patients in chronic renal failure treated by dialysis or transplantation beginning a first replacement therapy between 2002 and 2011. Age strongly influences survival on dialysis. Thus, one year survival of patients under age 65 is over 90%. After 5 years, among patients over 85 years, it is more than 15%. The presence of diabetes or one or more cardiovascular comorbidities also significantly worse patient survival. In terms of trend, we do not find significant improvement in the 2-year survival between patients in the cohort 2006-2007 and the 2008-2009 cohort. Cardiovascular diseases account for 27% of causes of death to infectious diseases (12%) and cancer (10%). Life expectancy of patients is highly dependent on their treatment. Thus, a transplant patient aged 30 has a life expectancy of 41 years versus 23 years for a dialysis patient. Transplant patients have a mortality rate much lower than those of dialysis patients. Thus, between 60 and 69 years, for 1000 patients in dialysis in 2011, 127 died within the year. For 1000 patients of the same age, who have a functioning kidney transplant, 24 died within the year.

Familial membranous glomerulopathy, toxic exposure and/or genetic sensibility?

Membranous nephropathy rarely occurs as a familial disease. We report two siblings (brother and sister) who presented with nephrotic syndrome and many vascular complications. HLA identities and potential toxic exposure may be concurring in these cases.

Chronic lymphocytic leukemia: a hazardous condition before kidney transplantation.

Long-term survival of patients with chronic lymphocytic leukemia (CLL) is over 10 years, and such patients are thus potential kidney recipients in the case of superimposed end-stage renal disease. However, the renal and patient outcome in this condition is unknown. We report the charts of four patients with CLL who were engrafted in France with a deceased-donor kidney and underwent routine triple immunosuppressive therapy. The results show that these patients developed severe infectious episodes (fatal in one case) and tumoral complications including rapid progression of CLL in two cases. Moreover, the graft may be infiltrated and damaged by monoclonal B cells: one patient lost his graft 14 months after transplantation. Various therapeutic options (modifications of the immunosuppressive regimen, anti-CD20 antibodies, irradiation of the graft) showed little (if any) efficacy. Therefore, we believe that CLL is a too hazardous condition to envisage solid organ transplantation with a routine immunosuppressive regimen, and we propose a more appropriate approach.

[Preanalytical variability of parathyroid hormone measurement in dialysis patients; application to Elecsys 2010 (Roche) automate]. / Variabilité préanalytique du dosage de la parathormone chez le patient dialysé; application à l'automate Elecsys 2010 (Roche).

The working group PTH-Vitamin D of the SFBC recently underlined the great intertechnic variability of parathormone (PTH) assays. At the same time, the data of the literature showed an impact of the preanalytic stage, significant and variable according to the automat used. We worked on the automat Roche Elecsys. On quickly centrifuged and decanted samples, the small difference in results between serum and plasma EDTA (6%) is compatible with an indifferent use of the two samples for dialysed patients. The reputation of greater stability on plasma EDTA seems primarily based on studies after decantation of plasma. The extension to a non decanted sample, maintained on primary tube for deferred shipping to the laboratory would require verification. Concerning the serum, on tube with serum separator, after early centrifugation, we checked the stability of the PTH measurement for a delay lower than or equal to 4 hours. For an extrahospital structure of dialysis, in the conditions of an early and an on site centrifugation, this delay allows to defer the transport of the primary closed tube to the laboratory. Contrary to plasma EDTA, the serum also allows simultaneous measurements of other parameters used for the care of the dialysed patients.

[Assessement of home blood pressure with a monitor including MAM technology: comparison with the standard monitor]. / Relevé d'automesure utilisant un autotensiomètre incluant la technologie MAM: avec la méthode de référence.

OBJECTIVES: To compare two periods of three days of home blood pressure monitoring (HBPM) using two different monitors with one including MAM (microlife average mode) technology. METHODS: In 152 hypertensive subjects referred to hypertension specialists, a self-measurement of blood pressure was performed sequentially with an Omron M6 (arm cuff, A/A, BHS validation) or Microlife BP-3AC1 with the MAM technology. Each patient recorded home blood pressure during two periods of 3 days with 3 measures in the morning and 3 in the evening. Order for use of each monitor was randomised. BP values were reported on a standardized document. RESULTS: In this population, aged 60 +/- 14 years, with 57% of men and a mean blood pressure of 150 +/- 21/84 +/- 21 mmHg, the home blood pressure values were 141.5 +/- 18.7/79.9 +/- 9.6 mmHg with the OMRON monitor and 138.2 +/- 17.1/79.9 +/- 10.1 mmHg with the Microlife monitor. Values between the two monitors differed about 5 mmHg for the mean SBP and about 2.8 mmHg for the mean DBP. The mean HBPM values does not differ between the two methods for more than 2.5 mmHg, 5 mmHg, 10 mmHg and 15 mmHg in 29%, 49%, 80% and 90% for SBP and in 42%, 76%, 94% and 98% for DBP respectively. CONCLUSIONS: For most of patients, mean SBP/DBP obtained with home blood pressure Measurement during three days are comparable when using monitor operated with MAM technology or not.

[Diagnostic approach prior to the onset of chronic renal insufficiency]. / Démarche diagnostique devant une insuffisance rénale chronique débutante.

Chronic nephropathies are usually asymptomatic and should therefore be systematically depisted, especially in "high risk" patients. These subgroups of patients have been relatively well defined as subjects with hypertension, diabetes and ageing. A plasma creatinine concentration of 150 mumol/L can easily diagnose chronic renal failure with an absolute specificity (100% of the subjects do have a glomerular filtration rate beneath 80 mL/min). This threshold however is too high as some patients may already exhibit a significant reduction in renal function. "Corrected" creatinine, i.e., computing creatinine clearance using the Cockcroft's formula allows a more reliable estimation of glomerular filtration rate. The long term prognosis of chronic renal failure is far from good. The progression rate is higher in patients with persistent hypertension and heavy proteinuria that are themselves amenable to symptomatic therapies. Timely nephrologic referral is a warrant of optimal care.

Comparison of cystatin C versus creatinine for detection of mild renal failure.

AIM: Serum cystatin C (SCyst) has been proposed as a novel indicator of GFR. PATIENTS AND METHODS: We compared SCyst, serum creatinine (SCreat) and Cockcroft and Gault's estimated clearance (CCG) using inulin clearance (Cin) as gold standard. 140 subjects (161 samples; aged 39 +/- 14; male/female: 79/82) underwent simultaneous measurements. RESULTS: A highly significant correlation r = 0.70, 0.74, 0.77 (p < 0.0001) was found between 1/SCyst, 1/SCreat, C(CG), respectively, and Cin. Receiver-operating characteristic (ROC) analysis was performed on SCyst, SCreat and C(CG) using a Cin cut-off of 90 ml/min/1.73 m2. Best fit for SCyst was 0.90 mg/l with a sensitivity of 75% and a specificity of 92%. The area under the ROC curve was not significantly greater for SCreat or C(CG) than for SCyst (p = 0.91,0.13, respectively). When relationship between Cin and SCyst was plotted, experimental data deviated from the theoretical model, suggesting that cystatin C may not be solely filtered. Additional patients were selected in our database on the basis of discordant SCreat/GFR values: false negative (n = 46 samples, 31 patients) and false positive (n = 16 samples, 9 patients). In this highly selected subgroup, 38% of the SCreat false positive had normal SCyst values and 48% of the false negative SCreat had abnormally elevated SCyst. CONCLUSION: This study suggests that SCyst is not more sensitive than SCreat or C(CG) for detecting renal failure, however, SCyst could be proposed as a confirmatory test for patients with elevated SCreat.

Blood pressure, diabetes and diabetic nephropathy.

Despite multiple evidence-based data that diabetic nephropathy is largely preventable and its progression slowed by currently available interventions diabetic patients are often undertreated, especially for the lowering of blood pressure. Recent studies, (HOT Syst-Eur, SHEP, UKPDS, CAPPP, ABCD, HOPE) have confirmed the efficiency of intensively treated blood pressure in reducing morbidity-mortality in this group of patients at high risk. Low blood pressure targets are mandatory, but may not be that easy to achieve, especially in the presence of renal failure. Early prescription of a combination of antihypertensive drugs is often neccessary. Thus, the clinical question relates to the best combination of drugs. Most studies in hypertensive diabetic patients have dealt with 3 classes of antihypertensives drugs: diuretics, beta-blockers and ACE-inhibitors. Diuretics are one of the most efficient hypotensive drugs available for treatment of hypertension in diabetic patients. Their use must be encouraged early in the stepped approach since diabetes is usually associated with mid-volume expansion due to hyperinsulinism and hyperadrenergic state. In spite of the proven benefit of beta-blockers in diabetic patients, these drugs are largely underused. The indications for selective beta-blockers should probably be broadened for most diabetic patients in primary prevention. Beta-blockers are essential in secondary prevention for patients with coronary artery disease and hypertension. ACE-inhibitors are now more and more widely prescribed in diabetic patients at all stages of hypertension and nephropathy, but paradoxally their use has not been validated in Type 2 diabetic nephropathy. When the desired blood pressure target is obtained, cardiovascular outcome and probably also progression of diabetic nephropathy are significantly improved independently of a specific drug. Early combination therapy, including ACE-inhibitors, diuretics and beta-blockers, should be promptly proposed to all hypertensive diabetic patients to achieve low blood pressure and prevent high cardiovascular burden and progression of nephropathy.

[Antihypertensive treatment in type II diabetes and diabetic nephropathy]. / Traitement antihypertenseur du diabète et de la néphropathie diabétique de type II.

Hypertension is very prevalent in patients with type II diabetes. Beside increasing the cardiovascular risk, hypertension has several deleterious effects on the kidney: hypertension promotes the development of diabetic nephropathy, the progression from microalbuminuria to overt diabetic nephropathy and progression to end stage renal disease. In this review, we analyze systematically the benefit of antihypertensive therapy in patients with type II diabetes, with either normo-albuminuria, microalbuminuria or overt nephropathy. General considerations are developed about the general use of antihypertensive drugs in this population. An approach based on the prevention of the global or absolute cardiovascular risk is further recommended due to the very high cardiovascular burden in this diabetic patients.

Prediction of colloid osmotic pressure in renal patients.

BACKGROUND: Colloid osmotic pressure (COP) plays a major role in transcapillary fluid shift, including in the glomerular capillary. However, COP is generally estimated by quadratic equations derived from total plasma protein and/or albumin concentrations. The aim of this study was to assess the accuracy of such equations, and to determine the potential role of liver-derived non-albumin proteins in the maintenance of COP, especially in patients presenting a nephrotic syndrome. METHODS: COP was directly assessed with an osmometer in 170 patients (347 samples), and the results compared with calculated COP, using 4 previously published formulas [Brenner 1972, Canaan-Kühl 1993, Landis-Pappenheimer 1963, Navar 1977]. RESULTS: The 4 calculated COP values were strongly correlated with measured COP (range r = 0.88 - 0.96). However, in absolute terms, measured COP differed significantly from each of the 4 calculated mean values of COP (p < 0.001). Fibrinogen exerted per se a weak oncotic effect as measured in vitro. However, fibrinogen was highly related to albumin and presumably reflected the oncotic effect of other liver-derived non-albumin proteins. Inclusion of albumin and fibrinogen in a linear model provided an excellent fit for predicted COP with a highly significant correlation (r = 0.96, p < 0.001) over a wide range of COP values. The predicted equation was: COP(mmHg) = 6.89 x (albumin + fibrinogen) (g/dl) - 5.68. CONCLUSION: None of the 4 most commonly used formulas correctly predicted COP, and direct measurement of COP is still preferable for research studies. The introduction of fibrinogen into the formula estimating COP leads to higher accuracy, and therefore represents a more convenient model for routine evaluation.

[Value of the analysis of pulmonary venous flow in the evaluation of hemodynamics in dialysed patients]. / De l'intérêt de l'analyse du flux veineux pulmonaire dans l'estimation d'un état hémodynamique. Exemple de la dialyse.

The aim of this study was to assess the value of analysis of pulmonary venous flow in the evaluation of the haemodynamic status of patients with chronic renal failure with normal left ventricular function, treated by haemodialysis. Pulmonary venous flow was recorded immediately before and after haemodialysis in 27 patients with chronic renal failure and a mean age of 44 years. Three groups of patients were defined according to the change in mitral E/A ratio: Group I (E/A < 1 before and after dialysis), Group II (E/A > 1 before and < 1 after dialysis) and Group III (E/A > 1 before and after dialysis). There was a significant difference between these subgroups before dialysis with respect to age, S, D, VTI S, Total VTI, VTI S/Total (p < 0.05). However, because the values overlapped, only a VTI S/Total ratio greater than 59% differentiated patients in Group II from those in group III (p < 0.05). After dialysis, the change in S/D and VTI S/Total ratios increased in Groups I and II and decreased in Group III. The authors concluded that 63% of patients without LV dysfunction on haemodialysis have abnormalities of relaxation which are latent in 47% of cases due to increased filling pressures diagnosed by a VTI S/Total ratio > 59% or simply because the patients are over 50 year old.

[Antihypertensive treatment in type 1 diabetes and diabetic nephropathy]. / Traitement antihypertenseur du diabète et de la néphropathie diabétique de type 1.

In diabetic patient, hypertension is a major factor contributing to both cardiovascular morbidity-mortality and progression toward renal impairment. This review analyzes studies from the literature regarding the benefits of antihypertensive treatment at every stage of type 1 diabetes and diabetic nephropathy.

Cardiovascular morbidity and endothelial dysfunction in chronic haemodialysis patients: is homocyst(e)ine the missing link?

BACKGROUND: Haemodialysis patients exhibit an excessive burden of atherothrombotic disease, which is not explained adequately by traditional risk factors. Hyperhomocyst(e)inaemia, a consistent finding in uraemic patients, is now widely recognized as an independent risk factor for vascular disease. The aim of this study was to examine the hypothesis that hyperhomocyst(e)inaemia is associated with cardiovascular complications in dialysed patients. METHODS: In a cohort of 63 stable chronic haemodialysis patients, we examined the causal relationship between hyperhomocyst(e)inaemia and vascular endothelial and haemostatic function. All their markers were determined before and after an 8-week course of a 10 mg per day oral folate supplementation, a manoeuvre known to decrease hyperhomocyst(e)inaemia in uraemic patients. RESULTS: History of at least one cardiovascular atherothrombotic event was present in 47.6% of the haemodialysed patients, and radiographic evidence of vascular calcifications in 70%. Hyperhomocyst(e)inaemia was found in all patients, averaging 3.5-fold the upper limit of normal values (P<0.001), despite the lack of clinical and biological evidence of malnutrition. Fibrinogen, von Willebrand factor and plasminogen activator inhibitor type 1, but not endothelin 1, were significantly higher in haemodialysis patients than in controls. After adjustment for all variables, past history of cardiovascular events was independently associated with higher levels of homocyst(e)inaemia only (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01-1.12; P<0.026). The presence of aortic calcifications was independently and significantly associated with age (OR 1.37; 95% CI 1.07-1.75; P<0.025), homocyst(e)inaemia (OR 1.14; 95% CI 1.02-1.27; P<0.05) and fibrinogen concentration only (OR 9.74; 95% CI 1.25-75.2; P<0.05). None of the endothelial haemostatic factors was, however, related to homocyst(e)ine levels. Mid-term folate supplementation decreased plasma homocyst(e)ine levels significantly without achieving normal values. No significant change of endothelial-haemostatic markers was observed, however, despite the drop in plasma homocyst(e)ine. CONCLUSIONS: Hyperhomocyst(e)inaemia is associated with increased cardiovascular risk in haemodialysis patients. Folate supplementation was partially effective in lowering hyperhomocyst(e)inaemia, but its usefulness in terms of reduction in cardiovascular morbidity and mortality remains to be determined in prospective trials.

Abysmal prognosis of patients with type 2 diabetes entering dialysis.

INTRODUCTION: The importance of non-insulin-dependent diabetes mellitus (type II diabetes) as a leading cause of end-stage renal disease is now widely recognized. The purpose of this study was to assess life-prognosis and its predictors in a cohort of patients newly entering dialysis. MATERIAL AND METHODS: Eighty-four consecutive type II diabetes patients (40% of all patients) starting dialysis between 01/01/95 and 31/12/96 were studied retrospectively, focusing on clinical data at inception and life-prognosis after a mean follow-up of 211 days. Patients were divided into three groups, according to onset of renal failure: acute 11% (9/84), chronic 61% (51/84) and acutely aggravated chronic renal failure 28% (25/84). RESULTS: Patients (mean age 67 years) had long-standing diabetes (mean duration approximately 15 years), heavy proteinuria (approximately 3 g/24h) and diabetic retinopathy (67%). The average creatinine clearance (Cockcroft's formula) was 13 ml/min. Cardiovascular diseases were highly prevalent at the start of dialysis: history of myocardial infarction (26%), angina (36%) and acute left ventricular dysfunction (67%). More than 80% of the patients underwent the first session dialysis under emergency conditions, a situation in part related to late referral to the nephrology division (63% for chronic patients). A great majority of the patients were overhydrated when starting dialysis, as evidenced by the average weight loss of 6 kg, during the first month of dialysis, required to reach dry weight. Nearly 64% of the patients presented high blood pressure (> 140/90 mmHg) when starting dialysis despite antihypertensive therapy (mean: 2.3 drugs). The outcome of this type II diabetes population was dramatic: 32% (27/84) died after a mean follow-up of 211 days, mostly from cardiovascular diseases. The rate of recovery of renal function was low in both the acute and the acutely aggravated renal failure group (30% and 24%, respectively). Of note, iatrogenic nephrotoxic agents accounted for renal function impairment in nearly 30% of patients. CONCLUSION: Our observational study illustrates the high burden of cardiovascular diseases contrasting with sub-optimal cardiovascular therapeutic interventions in type II diabetes patients entering dialysis. Factors aggravating renal failure were mainly iatrogenic, and therefore largely avoidable. Late referral generally implied a poor clinical condition at the start of dialysis.