Outcome of autosomal dominant polycystic kidney disease patients on peritoneal dialysis: a national retrospective study based on two French registries (the French Language Peritoneal Dialysis Registry and the French Renal Epidemiology and Information Network).

Background: Pathological features of autosomal dominant polycystic kidney disease (ADPKD) include enlarged kidney volume, higher frequency of digestive diverticulitis and abdominal wall hernias. Therefore, many nephrologists have concerns about the use of peritoneal dialysis (PD) in ADPKD patients. We aimed to analyse survival and technique failure in ADPKD patients treated with PD. Methods: We conducted two retrospective studies on patients starting dialysis between 2000 and 2010. We used two French registries: the French Renal Epidemiology and Information Network (REIN) and the French language Peritoneal Dialysis Registry (RDPLF). Using the REIN registry, we compared the clinical features and outcomes of ADPKD patients on PD (n = 638) with those of ADPKD patients on haemodialysis (HD) (n = 4653); with the RDPLF registry, those same parameters were determined for ADPKD patients on PD (n = 797) and compared with those of non-ADPKD patients on PD (n = 12 059). Results: A total of 5291 ADPKD patients and 12 059 non-ADPKD patients were included. Analysis of the REIN registry found that ADPKD patients treated with PD represented 10.91% of the ADPKD population. During the study period, PD was used for 11.2% of the non-ADPKD population. Compared with ADPKD patients on HD, ADPKD patients on PD had higher serum albumin levels (38.8 ± 5.3 versus 36.8 ± 5.7 g/dL, P < 0.0001) and were less frequently diabetic (5.31 versus 7.71%, P < 0.03). The use of PD in ADPKD patients was positively associated with the occurrence of a kidney transplantation but not with death [hazard ratio 1.15 (95% confidence interval 0.84-1.58)]. Analysis of the RDPLF registry found that compared with non-ADPKD patients on PD, ADPKD patients on PD were younger and had fewer comorbidities and better survival. ADPKD status was not associated with an increased risk of technique failure or an increased risk of peritonitis. Conclusions: According to our results, PD is proposed to a selected population of ADPKD patients, PD does not have a negative impact on ADPKD patients' overall survival and PD technique failure is not influenced by ADPKD status. Therefore PD is a reasonable option for ADPKD patients.

Modifications to bicarbonate conductivity: A way to increase phosphate removal during hemodialysis? Proof of concept.

Introduction Hyperphosphatemia and cardiovascular mortality are associated particularly with end-stage renal disease. Available therapeutic strategies (i.e., diet restriction, calcium [or not]-based phosphate binders, calcimimetics) are associated with extrarenal blood purification. Compartmentalization of phosphate limits its depuration during hemodialysis. Several studies suggest that plasmatic pH is involved in the mobilization of phosphate from intracellular to extracellular compartments. Consequently, the efficiency of modified bicarbonate conductivity to purify blood phosphate was tested. Methods Ten hemodialysis patients with chronic hyperphosphatemia (>2.1 mmol/L) were included in the two three-sessions-per week periods. Bicarbonate concentration was fixed at 40 mmol/L and 30 mmol/L in the first and second periods, respectively. Phosphate depuration was evaluated by phosphate mobilization clearance (KM ). Findings Although bicarbonatemia was lower during the second period (21.0 ± 2.7 vs. 24.4 ± 3.1 mmol/L, P < 0.01), no difference was observed in phosphatemia (2.4 ± 0.5 vs. 2.3 ± 0.4 mmol/L, P = NS). The in-session variation of phosphate was lower (-1.45 ± 0.42 vs. -1.58 ± 0.44 mmol/L, P < 0.05) and KM was higher during the second period (82.94 ± 38.00 vs. 69.74 ± 24.48 mL/min, P < 0.05). Discussion The decrease of in-session phosphate and the increase in KM reflect phosphate refilling during hemodialysis. Thus, modulation of serum bicarbonate may play a role in controlling the phosphate pool. Even though correcting metabolic acidosis during hemodialysis remains important, alkaline excess can impair phosphate mobilization clearance. Clinical trials are needed to test the efficiency and relevance of a strategy where bicarbonatemia is corrected less at the beginning of sessions.

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.

[Why and how correct calcidiol deficiency in haemodialysis patients?]. / Pourquoi et comment corriger le déficit en calcidiol chez les patients hémodialysés ?

UNLABELLED: The plasma concentration of 25(OH) D - calcidiol - is low in most of stage 5 renal patients. Due to the lack of renal 1alpha-hydroxylase, no supplementation is recommended. However, calcidiol also displays many extraosseous beneficial antiproliferative effects. It may be useful to correct its deficiency in dialysis patients. The efficacy of an oral supplementation for 6 months with ergocalciferol, (Sterogyl), was evaluated in a monocentric cohort of 107 prevalent hemodialysis patients. Plasma levels of 25(OH) D, parathormone, total and ionized calcium, phosphates, were measured at month 0, 3 and 6 in all patients and plasma levels of 1-25(OH) D at month 0 and 6 in 38 patients with the lowest 25(OH) D levels at baseline. Patients were divided into four groups according to their initial 25(OH) D plasma levels and received ergocalciferol supplementation in accordance to the KDOQI Guidelines for stage 3 and 4 renal patients. RESULTS: 101/107 patients display low levels of 25(OH) D at baseline: mean 11.8+/-11.6 microg/l (normal> 30 microg/l). At the end of the initial three months correction period, the plasma levels of 25(OH) D rose significantly. However, only 60% of patients reach a normal plasma concentration of calcidiol with the highest - 600,000UI - ergocalciferol cumulative dosage. At the end of the three months maintenance period, plasma 25(OH) D concentrations fell in all patients. No significant change was observed in parathormone, calcium, phosphates and 1-25(OH) D plasma levels. There was no hypercalcemic episode. CONCLUSION: KDOQI ergocalciferol recommended doses for stages 3 and 4 renal patients did not correct calcidiol deficiency in hemodialysis patients. New prospective studies are required for defining the modalities of an efficient vitamin D supplementation with ergocalciferol or cholecalciferol.

The clinical evaluation of low-dose heparin in haemodialysis: a prospective study using the heparin-coated AN69 ST membrane.

BACKGROUND: The AN69 ST haemodialysis membrane, a new membrane resulting from coating polyethyleneimine upon the polyacrylonitrile surface, binds heparin. In patients at risk of bleeding, a pilot study has demonstrated the efficient anticoagulant effect of this heparin-coated membrane. Study design. In chronic haemodialyzed patients, we evaluated whether this anticoagulant effect can be validated in a controlled, prospective, open study. Pragmatically, we tested the hypothesis of no difference of the massive clotting rate in two groups of patients haemodialyzed either with 50% reduced standard doses of nonfractionated heparin using the heparin-coated AN69 ST or with a full dose of heparin (100%) using another type of dialysis membrane that does not bind heparin. Secondary objectives included evaluation of partial clotting, changes in haemoglobin levels, erythropoietin consumption and dialyzer performances. RESULTS: One hundred and eighty-four patients were elected and 170 finally included in an 18-month follow-up study. They were allocated to one of the two arms of the study. In the heparin-reduced group (n = 85, mean age: 73 +/- 11 years), 12 472 sessions were performed after priming the AN69 ST dialyzer with 2 L of heparinized saline (5000 IU/L heparin) and using 50% reduced doses of previously administered heparin. In the control group with standard heparin (n = 85, mean age: 74 +/- 13 years), 14 154 sessions were analysed (NS), and mean heparin doses were 2718 +/- 1388 and 4800 +/- 1564 IU per session, respectively (P < 0.001). In the heparin-reduced group, massive clotting occurred in 1.4 per 1000 sessions, whereas it occurred in 1.6 per 1000 sessions in the standard heparin group (P < 0.05). Mild to moderate partial clotting in the venous drip chamber and in the dialyzer was evaluated in a subset of patients, on a visual scale. It was more frequent in the experimental group than in the control group (P < 0.001). Platelets, haemoglobin levels, erythropoietin needs and dialyzer performances remained unchanged in both groups. The global mean death rate was 16.8% per year and did not differ significantly between groups. CONCLUSION: The use of the heparin-coated AN69 ST membrane allows a 50% reduction of standard doses of nonfractionated heparin administration for routine haemo- dialysis without increasing the risk of massive clotting of the extracorporeal circuit. This result needs confirmation since massive clotting questions clinical practice and is team dependent.

The renal epidemiology and information network (REIN): a new registry for end-stage renal disease in France.

The French Renal Epidemiology and Information Network (REIN) registry began in 2002 to provide a tool for public health decision support, evaluation and research related to renal replacement therapies (RRT) for end-stage renal disease (ESRD). It relies on a network of nephrologists, epidemiologists, patients and public health representatives, coordinated regionally and nationally. Continuous registration covers all dialysis and transplanted patients. In 2003, 2070 patients started RRT, 7854 were on dialysis and 7294 lived with a functioning graft in seven regions (with a population of 16.5 million people). The overall crude annual incidence rate of RRT for ESRD was 123 per million population (p.m.p.) with significant differences in age-adjusted rates across regions, from 84 [95% confidence interval (CI): 74-94] to 155 [138-172] p.m.p. The principal causes of ESRD were hypertension (21%) and diabetic (20%) nephropathies. Initial treatment for ESRD was peritoneal dialysis for 15% of patients and a pre-emptive graft for 3%. The one-year survival rate was 81% [79-83] in the cohort of 2002-2003 incident patients. As of December 31, 2003, the overall crude prevalence was 898 [884-913] p.m.p, with 5% of patients receiving peritoneal dialysis, 47% on haemodialysis and 48% with a functioning graft. The experience in these seven regions over these two years clearly shows the feasibility of the REIN registry, which is progressively expanding to cover the entire country.

Assessment of the heparin-binding AN69 ST hemodialysis membrane: II. Clinical studies without heparin administration.

Binding polyanionic unfractionated heparin over the modified AN69 polyacrylonitrile membrane, the surface electronegativity of which has been neutralized by polyethyleneimine (AN69-ST), renders the membrane more hemocompatible. This property was tested in two groups of long-term hemodialysis patients. Results were rated as massive or partial clotting of a dialyzer at the end of the session. Group I patients were included in a prospective, cross-over study comparing standard dialysis with hemodialysis without systemic administration of unfractionated heparin (n = 12, 123 sessions). In all instances, priming was made with 2 I saline containing 5,000 IU/l heparin. Only patchy or partial clotting was observed in 11% and 39% of the sessions with standard and heparin-free administration, respectively. Group II patients were included in an open, observational pilot study testing the effects of the heparin-coated membrane, without systemic administration of heparin, in patients at high risk of bleeding (n = 68, 331 sessions). Massive clotting was observed in six sessions only (less than 2%) and normal or slightly patchy dialyzers were found in 88% of the sessions. It is concluded that the dialysis AN69 ST membrane, after adequate priming at bedside, can be used without systemic administration of heparin for hemodialysis in patients at high risk of bleeding.

Optimal anticoagulation strategy in haemodialysis with heparin-coated polyacrylonitrile membrane.

BACKGROUND: Binding of polycationic unfractionated heparin onto the modified AN69 polyacrylonitrile membrane, whose surface electronegativity has been neutralized by layering polyethyleneimine (AN69ST), produces stable coating. We investigated whether the heparin-coated membrane was suitable for regular haemodialysis with low heparin doses. METHODS: Sheep were instrumented for extracorporeal circulation perfusing a dialyser equipped with either the AN69ST or the original AN69 membrane. Dialysis sessions were performed after priming the dialyser with heparinized saline. The session was conducted without systemic administration of heparin. In chronic haemodialysis patients, the AN69ST membrane was tested for safety, clotting and thrombin generation according to protocols of 4-h haemodialysis sessions with tapered heparin doses. The goal was to define optimal heparin requirements with the heparin-coated membrane in the setting of continuous or intermittent administration of heparin. Both unfractionated and low molecular weight heparin (LMWH) (enoxaparin) were tested. RESULTS: In sheep, systemic heparin-free haemodialysis was conducted for 6 h without clotting using the heparin-coated dialyser. In the same conditions, massive clotting was observed within 90 min of dialysis with the native AN69 membrane. In man, through kinetic measurements of activated partial thromboplastin time (APTT), heparin anti-Xa concentration and thrombin-anti-thrombin complexes levels (TAT), significant dialyser clotting was avoided when APTT and anti-Xa concentration at 180 min of dialysis, were maintained at >40 s and >0.2 IU/ml, respectively. With the AN69ST heparin-coated membrane, thrombin generation was reduced then suppressed, as compared with the original AN69, primed in the same conditions. Safety of haemodialysis conducted with the AN69ST heparin-coated membrane and low doses of unfractionated heparin (50% reduction of the reference dose) was validated by a survey of 2590 sessions in 32 patients. Doses of LMWH were also safely reduced by 50%. In addition, haemodialysis without systemic administration of heparin was possible with minor risk of clotting. CONCLUSION: During the rinsing phase, the ionic interactions between the new AN69ST polyacrylonitrile membrane and unfractionated heparin induce stable heparin coating. This allows a significant reduction of systemic anticoagulant requirements without increasing the risk of clotting, both in the experimental setting and in the chronic haemodialysis patients. Further studies are required to assess this advantage in patients with acute renal failure and at risk of bleeding and to reduce the metabolic consequences of long-term treatment with heparin.