Impact of hypovitaminosis D and alfacalcidol therapy on survival of hemodialysis patients: results from the French ARNOS study.

BACKGROUND: In chronic kidney disease and dialysis patients, vitamin D deficiency is associated with mortality. In some observational studies, calcitriol analogue therapy was associated with a better survival rate in hemodialysis (HD) patients. The aim of this study was to determine the relationship between serum 25-hydroxyvitamin D (25-OHD) levels and alfacalcidol therapy with HD patients' outcomes. METHODS: We measured baseline 25-OHD levels using a cross-sectional analysis in 648 HD prevalent patients from the regional ARNOS French cohort. A 42-month survival analysis was applied according to serum 25-OHD level and calcitriol analogue therapy. RESULTS: The prevalence of 25-OHD insufficiency <30 ng/ml was high (73%), with only 22% taking native vitamin D supplementation. A baseline 25-OHD level above the median value (18 ng/ml) was associated with lower all-cause mortality [hazard ratio (HR), 0.73 (0.5-0.96); p = 0.02] after adjustment for age, gender, dialysis vintage, calcemia, phosphatemia, cardiovascular disease, and diabetes. Only in monovariate analysis was low-dose oral alfacalcidol therapy associated with a better survival rate in patients with and without 25-OHD deficiency [HR, 0.7 (0.5-0.92); p = 0.05]. CONCLUSIONS: Our study shows that, among prevalent HD patients, low 25-OHD levels affect mortality. Alfacalcidol therapy, especially in small doses, may provide compensation, but this needs to be further confirmed using prospective controlled studies comparing native and active vitamin D compounds.

Association between very low PTH levels and poor survival rates in haemodialysis patients: results from the French ARNOS cohort.

INTRODUCTION: A very low parathyroid hormone (PTH) level (VLPL) is associated with an increased risk of adynamic bone disease, vascular calcification, and mortality in haemodialysis (HD) patients. The aim of the study was to assess the frequency, the associated factors, and the prognosis of non-surgical VLPL in a cohort of prevalent HD patients. METHODS: In July 2005, a cross-sectional study was performed on the French ARNOS cohort in 1,348 prevalent HD patients from 24 dialysis centres in the Rhône-Alpes area. Patients with a baseline intact PTH level <50 pg/ml (VLPL, Group 1) and ≥ 50 pg/ml (Group 2) were compared and a 42-month survival analysis was performed. Patients with prevalent or incident parathyroidectomy were excluded. RESULTS: We studied 1,138 prevalent HD patients. As compared to patients of Group 2 (n = 1,019), patients with VLPL (Group 1, n = 119) had lower serum albumin levels (34.5 ± 5 vs. 36.4 ± 5 g/l, p < 0.0001), less protein intake (nPCR 0.99 ± 0.28 vs. 1.1 ± 0.28 g/kg/day, p = 0.01), higher calcaemia (2.30 ± 0.2 vs. 2.26 ± 0.2 mmol/l, p = 0.01) and were more frequently treated with calcium carbonate (67 vs. 54%, p < 0.001). Patients with VLPL had a higher mortality rate (HR: 1.4 (1.07-1.8), p = 0.006) after adjustment for age, gender, diabetes, and dialysis vintage. The odds ratios of mortality for patients with VLPL remained higher in all calcaemia and serum albumin quartiles. Only 3/119 patients in Group 1 did not receive any PTH-lowering therapies (i.e. calcium carbonate (67%), alfacalcidol (38%), cinacalcet (10.1%), and dialysate calcium ≥ 1.5 mmol/l (94%)). CONCLUSION: In this observational French cohort, VLPL was observed in 10% of prevalent HD patients and was associated with poor survival rates. An inadequate therapeutic strategy could be responsible for this observation. The real consequences of this iatrogenic adynamic bone disease remain hypothetical, but it may be related to the risk of developing vascular calcification. It is hypothesized that a more adequate strategy, using fewer PTH-lowering therapies in cases of VLPL, may help in improving the poor prognosis.

[Mesenteric ischemia in hemodialyzed patients]. / L'ischémie mésentérique chez le sujet dialysé.

OBJECTIVES: Mesenteric ischemia is uncommon in the general population but is frequently encountered in chronic hemodialysis patients. We present here four cases which occurred in our unit within one year while only six cases had been observed in the preceding twenty years. OBSERVATIONS: Four chronic hemodialysis patients (age: 57 to 76 years) with renal failure due to diffuse atheromatous disease, presented non-occlusive mesenteric ischemia. One patient died and one underwent resection of the colon. For the final two patients, prophylactic therapy was initiated. DISCUSSION: Mesenteric ischemia is a severe condition which appears to occur more frequently in end-stage renal disease. In the chronic hemodialysis patient excessive ultrafiltration or a too rapid filtration rate can favor ischemia. Prophylactic measures must be taken at the first sign of ischemia, especially since clinical and biological features of mesenteric ischemia remain largely non-specific.

[Twenty one years of hemodialysis in a patient with primary hyperoxaluria]. / Vingt et un ans d'hémodialyse chez un patient atteint d'hyperoxalurie primitive.

We report a male patient with primary hyperoxaluria from childhood who survived more than 21 years on conventional haemodialysis. Despite the severity of his bone disease, he was married and actively employed up until 2 years before his death. His condition really worsened a few months before his death. He presented with only renal and bone involvement and had hardly any cardiovascular complications, that was probably a reason for his prolonged survival. Such an evolution is very unusual and we speculate that the length of haemodialysis sessions in addition to the large surface of the membrane probably contributed to such an outcome. During the time period on HD, anemia was transiently controlled by recombinant erythropoietin despite oxalate involvement of the marrow. He was refused a liver-kidney transplant and died from malnourishment at 43 years of age. To our knowledge, such an outcome has not yet been reported. It shows that careful prolonged hemodialysis sessions should be helped in admet patients without severe cardiovascular involvement.

[Ophthalmologic manifestations of dialysis. Retrospective study on 81 patients]. / Manifestations ophtalmologiques du dialysé. Etude rétrospective sur 81 patients.

In this work, we looked at the results of a retrospective study carried out in our unit on the ocular manifestations in the dialysed chronic renal failure patient. Eighty-one of our 189 patients had an ophtalmic examination. Thirty-six showed a retinopathy, 26 suffered from a corneoconjunctival alterations, 19 from a cataract, 6 a vascular thrombosis, 4 a glaucoma and one motor-ocular paralysis. There was no significant difference for age and sex between the 81 patients and the group of 108 who did not have an ophtalmic examination. But this difference was positive for duration of time on dialysis (p = 0.01). There is a correlation between the presence of a cataract and the age of the patients (p = 0.01). There was no link between the different types of ophtalmic problems on the one hand, and the age, sex, time on dialysis, type of dialysis, original nephropathy, hypertensive history or anterior renal transplantation on the other hand.

[Aggravation of anemia in a hypertensive hemodialysis patient by captopril treatment]. / Aggravation de l'anémie chez un sujet hémodialysé hypertendu par un traitement au captopril.

We report here the case of an hypertensive chronic hemodialysis patient treated by captopril. Captopril treatment has been effective in normalizing blood pressure but induced a severe anemia necessitating frequent transfusions. Captopril withdrawal eliminated transfusion needs.

[What are the prerequisites for establishing a peritoneal dialysis treatment? (Training center, the place of private practice nurses, the administrative structure of management)]. / Quels sont les pré-requis à la mise en place d'un traitement par dialyse péritonéale? (Le centre de formation, la place des infirmiers libéraux, les structures administratives de gestion).

In spite of the same quality of results in term of five year survival by peritoneal dialysis (PD) compared to hemodialysis (HD), this method of renal substitutive therapy is concerning no more than 7% ESRF patients in France. What structural inadaptations could account for such striking differences between the two modalities? We present here the results of a French multi-center survey and our proposal for improving the actual tendency. Nonante PD centers were included representing a total number of 1592 patients, among them 90% were on continuous ambulatory peritoneal dialysis. We could observe a predominant proportion of public district services and non-profit associations. Sixty per cent of PD units were part of hemodialysis centers and 20% were totally independent. Patient mean age was very old, with limited autonomy, necessitating frequent visits of liberal nurses for 57% patients. We suggest to reinforce the role of non-profit making associations and to reorganize the existing centers on two levels in term of facilities, personal services and on functional modalities according to the number of treated patients.

[Atypical pleural effusion secondary to transdiaphragmatic communication. Apropos of two cases: a chylothorax and a hydrothorax]. / Epanchement pleural atypique par communication transdiaphragmatique. A propos de deux cas: un chylothorax et un hydrothorax.

We report two cases of pleural effusion in which a subdiaphragmatic cause was noted. In both cases it was necessary to obliterate a defect in the diaphragm via a thoracic incision. In one case, a left chylothorax occurred in a patient with hepatic cirrhosis. In this case, it was postulated that the normal lymphatic pathway through the right hemidiaphragm could have been stopped by pleural sequelae from right lobectomy. In the other case, a right pleural effusion occurred after peritoneal dialysis. It is a well known pathological entity: the structural defect can be observed by separation of collagen bundles in the tendinous diaphragm. This type of pleuro-peritoneal communication is well known in women suffering from menstrual pneumothorax or in patients treated by peritoneal dialysis.

[Atypical pleural effusion by transdiaphragmatic communication. Apropos of two cases: chylothorax and hydrothorax]. / Epanchement pleural atypique par communication transdiaphragmatique. A propos de deux cas: un chylothorax et un hydrothorax.

We report two cases of pleural effusion in which a subdiaphragmatic cause was noted. In both cases it was necessary to obliterate a defect in the diaphragm via a thoracic incision. In one case, a left chylothorax occurred in a patient with hepatic cirrhosis. In this case, it was postulated that the normal lymphatic pathway through the right hemidiaphragm could have been stopped by pleural sequelae from right lobectomy. In the other case, a right pleural effusion occurred after peritoneal dialysis. It is a well known pathological entity: the structural defect can be observed by separation of collagen bundles in the tendinous diaphragm. This type of pleuro-peritoneal communication is well known in women suffering from menstrual pneumothorax or in patients treated by peritoneal dialysis.

[Short- (1 session) and long-term (6 months) course of the serum level of zinc in 33 hemodialysis patients]. / Evolution du taux sérique du zinc à court (1 séance) et moyen terme (6 mois) chez 33 hémodialysés.

In patients with chronic renal insufficiency undergoing hemodialysis, the seric zinc level was significantly lower than in normal subjects. In 7 patients this was even more marked prior to their first hemodialysis session. Following hemodialysis this level increased, but by comparing the zinc level to that of the binding proteins it could be seen that this result was a reflection of the hemo-concentration phenomenon. During hemodialysis there was no change in the zinc level of dialysate. Finally, a significant increase in the seric level of the 7 new patients was noted after 6 months of hemodialysis treatment. This increase reached the mean level observed in the 26 other patients who had been undergoing hemodialysis from between 8 and 87 months, but pre-dialysis normalization of seric zinc levels was not attained. The reasons for this increase in the 7 recently hemodialysed patients receiving no zinc treatment are discussed.

[Enoxaparin in the prevention of thrombosis of extracorporeal circulation during dialysis of patients with chronic renal failure]. / L'enoxaparine dans la prévention de la thrombose du circuit extracorporel de dialyse des insuffisants rénaux chroniques.

Chronic renal failure patients under haemodialysis are exposed to two dangers: haemorrhage and clotting of the extracorporeal circulation circuit. This problem can be solved by using low molecular weight heparins. Two studies were conducted to evaluate the effectiveness and safety of a low molecular weight heparin: enoxaparin. The first study, which involved 42 chronic renal failure patients under haemodialysis without any particular risk, enabled the optimum dosage (1 mg/kg bodyweight) to be determined. The second study, which concerned 46 patients at high risk of haemorrhage who received enoxaparin 0.5 mg/kg or 0.75 mg/kg depending on the vascular approach, confirmed that enoxaparin was highly effective (clotting of the extracorporeal circuit in only 0.6 p. 100 of the cases) and well tolerated (bleeding in only 0.2 p. 100 of the cases).

Acute anaphylactoid reactions during hemodialysis in France.

A retrospective survey of anaphylactoid reactions during dialysis in France was conducted. In 52 of 112 hemodialysis units surveyed 111 patients who had suffered one or more anaphylactoid reactions during dialysis were identified. According to the Hamilton/Adkinson classification, in 31 patients reactions were minor, in 54 patients moderate, and in 26 patients severe. Four patients died of their reactions. A preponderance of reactions (75 and 11%) occurred with cuprammonium cellulose hollow-fiber and plate dialyzers, respectively. Severe dialyzer reactions were found to occur more frequently after the long (weekend) interdialytic interval. In an in vitro study, six brands of cuprammonium cellulose hollow-fiber dialyzers were rinsed with water and the eluates analyzed by size exclusion chromatography for contaminant particles. Substantial variation in the amount of extractable material was found between dialyzers of different brands, despite the fact that all dialyzers used membranes from the same manufacturer. Previous data by others has suggested that this extractable material is a derivative of cellulose. Results of our epidemiologic survey in France are similar to those previously reported in the United States and suggest an increased incidence of dialyzer reactions with ethylene oxide-sterilized cuprammonium cellulose dialyzers. The presence of cellulose-derived particles in the rinsing fluid of such dialyzers and the possible increased incidence of reactions after the long (weekend) interdialytic interval suggest that allergy to cellulose-derived particles eluted from cellulosic dialyzers may contribute to dialyzer hypersensitivity reactions.

[The use of enoxaparine for anticoagulation in extracorporeal circulation in hemodialysis at high risk for hemorrhage]. / Utilisation de l'énoxaparine pour l'anticoagulation du circuit extracorporel des hémodialyses à haut risque hémorragique.

After evaluation of efficacy of a low molecular weight heparin (LMWH), enoxaparine (Lovenox), in patients on continuous hemodialysis without a particular known hemorrhagic risk, this same LMWH was administered during 493 dialysis sessions to 46 patients presenting various degrees of risk of hemorrhage. Lower doses of 0.5 mg/kg or 0.75 mg/kg as bolus injections were administered at the start of the 4 or 5 hourly session. Clotting in the extracorporeal circulation (ECC) was noted in 0.6% treatments, the product being effective in all other sessions. Only one case of bleeding can be imputed to the LMWH injected during hemodialysis (0.2% of sessions). Although an open trial, the superiority of enoxaparine both for antithrombotic activity in ECC, and its simple management, as well as the small number of hemorrhages noted, has led to the routine use of this method in all patients at hemorrhagic risk.

Evaluation and tolerance of a new polycarbonate membrane in elderly patients. Preliminary results.

We studied the performance and tolerance of a new capillary hemodialyzer using a polycarbonate membrane (Gambrane PCD 1000) in a group of 5 elderly patients (mean age 68 years). The ultrafiltration coefficient is 6 (justifying the monitoring control of weight loss) and clearances for small molecules are comparable with cellulosic membranes. A good tolerance during 300 sessions was observed; nevertheless, an important neutropenia was noted in 2 out of 5 patients. The complement activation measured by the dosage of the C3a Desarg fraction existed in all the patients, reaching an average 6 times the initial level compared to 40 times for Cuprophan. Complement activation and neutropenia are considerably reduced by the reuse of the hemodialyzer as it was described for the cellulosic membranes.

Mechanisms of hypersensitivity reactions during hemodialysis.

We suggest that many severe hypersensitivity reactions during dialysis are IgE mediated (classical anaphylaxis). Besides ETO there must be other substances involved which are not extractable from the dialyzer (e.g. heparin). Some severe reactions are not explained by high IgE levels in the serum. However, in vitro complement activation gives no indication of an anaphylatoxin mediated reaction mechanism, at least in the severe cases of hypersensitivity.