[Factors determining the choice of a modality of treatment by dialysis: a study of nine dialysis centers]. / Facteurs déterminant le choix d'une modalité de traitement par dialyse: une enquête dans neuf centres de dialyse.

BACKGROUND: The objective of this cross-sectional study in a population of 1472 dialysis patients was to identify the main factors involved in the choice of a specific option for dialysis therapy, taking into account three different types of criteria such as medical dependence (DM), nurse care requirement (SI) and independence for dialysis therapy (CA). METHODS: Each patient has been analysed, independently of present treatment modality, according to the above three criteria, namely DM, SI and CA. For each type of parameter, patients have been allocated to one of three levels, each level being established to evaluate whether dialytic treatment should be undertaken as hospital centre dialysis (HDC) or in a facility off the hospital. Level 3 of any one category corresponded to the inability of doing haemodialysis at home (HHD) or in self-care unit (AD). Level 2 included patients who could be treated in AD or by peritoneal dialysis (PD) with the assistance of a nurse. CAPD or HHD were considered as potential treatment modalities only in patients qualifying for level 1 of each criterion. RESULTS: In the patient population as a whole, the following treatment options were observed: HHD 3.6%, CAPD 6%, PD 1.8%, AD 16.3% and HDC 72.2%. For medical dependence (DM) there was a relatively even distribution for the three levels in six centres. In contrast, two centres were characterized by a predominance of DM level 3. Differences in DM levels between centres were greatly reduced when considering separately only those patients who were actually treated by CAPD, HDC and AD. SI levels were more uniformly distributed within all centres, and this was true for HCD and AD patients. When considering CA levels in HDC patients, a large predominance of CA level 3 was observed in all centres whereas CA level 1 was nearly in existent. CONCLUSION: The major finding of this study was that the inability or the refusal of dialysis patients to participate at treatment, independently of medical condition and nurse care requirement, was the main factor in the choice of hospital centre dialysis.

Distinct HLA class II alleles determine antibody response to vaccination with hepatitis B surface antigen.

Major histocompatibility complex (MHC) determinants control antibody production in response to protein antigens. Vaccination with hepatitis B surface antigen (HBsAg) frequently fails in hemodialyzed patients, but the genetic factors that modulate humoral responsiveness are poorly characterized. We studied the distribution of HLA class II alleles in 415 hemodialyzed Caucasian patients who received a full course of HBsAg vaccination, using class II oligotyping after genomic amplification of the DRB1 and DQB1 loci. Phenotype frequencies were compared in 114 non responders (anti-HBs antibodies < or = 10 SI units/liter), 301 responders (anti-HBs antibodies > 10 units/liter) and 471 healthy controls. DRB1*01 (DR1) and DRB1*15 (DR15) frequencies were lower in nonresponders than in responders and controls (DR1, 12.3% vs. 22.9% and 24.8%, respectively; DR15, 14% vs. 22.9% and 25.1%), while DRB1*03 (DR3) and DRB1*14 (DR14) frequencies were higher (DR3, 32.5% vs. 16.6% and 25.3%, respectively; DR14, 9.6% vs. 3% and 6.6%). Overall, 44.5% of DR3 or DR14 patients were nonresponders, compared to 18.1% of DR1 or DR15 patients (P = 0.0001). In conclusion the humoral response to HBsAg vaccine is influenced by class II allelic variants, which differ in their capacity to bind and present peptides to T lymphocytes.

Pregnancy in women with impaired renal function.

The outcome and consequences of pregnancy in women with impaired renal function are still debated. To assess the benefit of recent advances in coordinated obstetrical and nephrologic management, we analyzed fetal and maternal outcome of 43 pregnancies in 30 women with various types of primary renal disease and moderate to severe renal failure at conception defined by serum creatinine concentration (Scr) ranging from 0.11 to 0.49 mmol/l. All pregnancies took place during the 20-year period from 1975 through 1994 and were prospectively followed jointly by our Nephrology Unit and Obstetric and Neonatology Units of University Hospitals. Of the 43 pregnancies (45 fetuses), 13 ended in fetal death (including 5 first-trimester abortions and 8 fetal deaths beyond the 20th gestational week). There were 32 live births, a success rate of 82% not considering first-trimester abortions. Successful pregnancies were significantly more frequent in the last decade than in the preceding one (91 vs 65%, p = 0.05). Overall live birth rate was higher in pregnancies started with Scr < 0.20 mmol/l than in those with Scr > 0.20 mmol/l (80% vs 53%, p = 0.02). The upper preconception Scr value associated with a successful fetal outcome was 0.27 mmol/l. Hypertension was the major factor of fetal prognosis, as the relative risk of fetal loss was 10.6 times higher when hypertension was present at conception or early in pregnancy than when blood pressure was spontaneously normal or well-controlled by therapy. An accelerated course toward end-stage renal failure was observed in 7 patients (23%), all of whom had severe hypertension and heavy proteinuria at conception. We conclude that fetal outcome in patients with impaired renal function has been improved in recent years, due to advances in obstetrics and neonatology, improved blood pressure control and close co-operation between nephrologists and obstetricians, but that a risk of fetal loss and of accelerated deterioration of maternal renal disease still persists when Ccr at conception is lower than 25-30 ml/ min/1.73 m2.

Pregnancy in women with reflux nephropathy.

Reflux nephropathy is one of the most prevalent renal diseases and a leading cause of chronic renal failure in women-of childbearing age. To evaluate the issue and possible complications of pregnancy in women with reflux nephropathy, we retrospectively analyzed fetal and maternal outcome in 158 women who had 375 pregnancies between 1965 and 1994. The overall fetal death rate was 10.2% and tended to decrease in the 1985 to 1994 decade as compared to the preceding period (8.4% vs. 12.6%). The relative risk of fetal death was 4.8 times greater hypertension was present at conception than in normotensive patients. Fetal death rate was also higher in patients with impaired renal function that in those with serum creatinine < 0.11 mmol/liter at conception (36.7% vs. 7.7%, P < 0.0001). Urinary tract infection accounted for frequent morbidity but seldom resulted in fetal mortality. Maternal renal disease was unaffected by pregnancy, excepted for 4 of the 21 patients with pre-existing renal failure who exhibited an irreversibly accelerated course after pregnancy. We conclude that pregnancy is essentially successful and uneventful in patients diagnosed with reflux nephropathy who have normal blood pressure and preserved renal function, whereas the fetal prognosis is more compromised and there is a risk of accelerated progression of maternal renal disease when serum creatinine concentration is in excess of 0.22 mmol/ liter. This suggests that women with reflux nephropathy should preferably conceive before having reached that stage of renal failure.

Dialysis clearance of buflomedil in hemodialysed patients.

Buflomedil (CAS 55837-25-7, Fonzylane) is a peripherally vasoactive drug which improves nutritional blood flow in ischaemic tissue of patients with peripheral vascular disease by the way of an increase of perfusion in the microcirculation. Ten hemodialysed patients with chronic renal failure treated with intravenous infusion of 400 mg of buflomedil during 4 h of dialysis were included in the first study. This study was carried out to determine the dialysis plasma clearance and the amount of drug dialysed during the first intravenous administration of buflomedil. The dialysis clearance calculated from the amount recovered in dialysate was (mean +/- SD) 25.4 +/- 25.6 ml/min. The drug recovery resulting from hemodialysis represented a small fraction of the dose (< or = 5%). A second study was carried out to determine the accumulation of buflomedil in chronic hemodialysed patient. The drug concentration were measured before and at the end (4 h) of the infusion of buflomedil in six other patients maintained on intermittent hemodialysis (3 per week) for 4 weeks. The average Cmin and Cmax were stable during the 12 successive dialyses (mean +/- SD intervals were between 0.36 +/- 0.53 and 0.66 +/- 0.79 microgram/ml for Cmin and between 5.15 +/- 2.19 and 7.37 +/- 1.76 micrograms/ml for Cmax), showing no trend of accumulation of buflomedil. These results agree with the pharmacokinetics of the drug which is mainly metabolised in the liver and has a low renal clearance. Dialysis is unable to modify significantly the plasma concentration of the drug in regularly dialysed patients.

Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationships with activation markers of T cells, B cells, and monocytes.

Patients with end-stage renal disease present an immunodeficiency that paradoxically coexists with activation of most immunocompetent cells, and the roles of chronic uremia and maintenance dialysis are poorly understood. We determined circulating levels of IL-1 beta and IL-1Ra, TNF-alpha and its soluble receptors (TNF-sR55 and TNF-sR75), and activation markers of T cells (soluble CD25), B cells (soluble CD23), and monocytes (neopterin) in a large cohort of undialyzed patients at various stages of chronic renal failure and in dialyzed patients on maintenance hemodialysis or chronic peritoneal dialysis. The progression of uremia was associated with a gradual increase in soluble CD25, CD23, and especially neopterin levels. Although IL-1 beta could not be detected, IL-1Ra levels were significantly increased from the earliest stage of renal failure. Plasma levels of TNF-alpha, TNF-sR55, and TNF-sR75 progressed with the severity of renal failure and correlated with soluble CD25, CD23, and neopterin levels, whereas IL-1Ra levels correlated exclusively with TNF-sR55 levels. Compared with undialyzed patients, levels of IL-1 beta were higher in patients on maintenance hemodialysis, whereas those of IL-1Ra were lower and decreased further at the end of dialysis sessions. In contrast, both TNF-sR55 and TNF-sR75 levels were significantly higher than in undialyzed patients and increased further at the end of dialysis sessions in the absence of an increase of TNF-alpha. Such an imbalance between cytokines and their inhibitors may play a pivotal role in the multifaceted process of immune dysfunction.

Evaluation in patients with Alport syndrome of knowledge of the disease and attitudes toward prenatal diagnosis.

Cloning of the COL4A5 gene has now made possible prenatal testing for Alport syndrome with X-linked dominant inheritance. We interviewed 27 females and 24 males with Alport syndrome to evaluate their knowledge of the disease and its transmission, and their attitudes to prenatal testing. Twenty-two males and 8 females were on renal replacement therapy. In all cases transmission was compatible with X-linked disease. Only 59% of the interviewees (74% of women, 42% of men) knew that gender was the major determinant in progression of the disease. Knowledge of the mode of inheritance was adequate in only 25%, in both sexes. Seventy percent of the participants (78% of women, 63% of men) would use prenatal testing. Of the women in favor of prenatal diagnosis, 67% and 39% would terminate pregnancy in the case of an affected male or female fetus, respectively. Of the men in favor of prenatal diagnosis, 53% would consider termination of an affected fetus. In summary, a majority would use prenatal testing, but only one or two thirds of them wished to use selective abortion. As in other inherited disorders, there is a discrepancy between the demand for prenatal diagnosis and the decision to terminate pregnancy. Most of the participants who would terminate a pregnancy had, however, little knowledge of the clinical and genetic aspects of Alport syndrome on which to base such a decision. An important aspect of genetic counselling is to assist consultants in reaching a decision regarding future reproductive behaviour which is appropriate to their situation. This study underlines the need to improve education and counselling to assure appropriate use of prenatal testing.

[One-year treatment of 43 chronic hemodialysis patients with recombinant human erythropoietin]. / Traitement pendant un an de 43 malades hémodialysés chroniques par l'érythropoïétine recombinante humaine.

Twenty men and 23 women aged from 18 to 65 years, who had been under maintenance haemodialysis for 2 to 16 years and whose haematocrit had been below 30 percent for at least 3 months received recombinant human erythropoietin intravenously at the end of each session for one year. Anaemia was corrected in all patients, the delay in response to each dosage variation being about 4 weeks. The necessary maintenance dosage ranged from 96 to 240 u/kg/week. The number of leucocytes increased significantly until the 4th month, from 5880 +/- 1760 to 6600 +/- 1920 per cubic mm (P less than 0.01). During treatment, pre-dialysis blood creatinine concentrations and potassium and phosphate levels rose, while blood calcium levels fell significantly from 2.45 +/- 0.16 to 2.36 +/- 0.19 mmol/l (P less than 0.01). A nonsignificant increase in systolic and diastolic pressures was also observed, from 129 +/- 16 to 134 +/- 18 mmHg (P = 0.06) and from 75 +/- 9 to 78 +/- 10 mmHg (P = 0.07) respectively. Eight patients (18 percent) required antihypertensive drugs or a higher dose of those previously prescribed. There were 7 cases of vascular thrombosis on pre-existing stenosis, and the dosage of heparin during dialysis had to be increased in most patients. This study confirms that erythropoietin plays a major role in the genesis of the anaemia associated with renal failure. The absence of severe complications in this series was probably due to the criteria of inclusion in the study.

[Treatment of anemia in chronic hemodialysis patients with recombinant human erythropoietin: long-term results in 15 patients]. / Correction de l'anémie des hémodialysés chroniques par l'érythropoïétine recombinante humaine: résultats à long terme sur quinze malades.

Recombinant human erythropoietin (rHu-EPO) was given during 12 to 20 months in 15 long term haemodialysis anaemic (mean Hb: 6.6 +/- 1 g/dl) patients who required no blood transfusion. Patients over 65, or with severe arterial disease or with uncontrolled hypertension were not included in this trial. Correction of anaemia (mean Hb 12.1 +/- 0.6 g/dl) was achieved in all patients and maintained all along the study. An improved sense of wellbeing and increased exercise tolerance were reported by all patients. Appropriate maintenance dosage of rHu-EPO was 74 +/- 6 U/kg i.v. twice weekly. High dose oral and/or intravenous iron therapy was necessary in the absence of previous marked iron overload. One retinal venous thrombosis was the sole severe side-effect encountered. A slight but significant increase of blood pressure was observed with the need of intensifying previous anti-hypertensive therapy in one patient and of starting one in one another. Fine adjustment of the dry weight was necessary to maintain blood pressure in the normal range. Heparin requirements increased in the majority of patients because of hollow fibre clotting but there was no evidence of decreased efficacy of dialysis. In two patients clotting of arteriovenous fistula was not obviously related to the rHu-EPO treatment.

Kinetics of erythropoiesis in dialysis patients receiving recombinant erythropoietin treatment.

In eleven patients with uraemia on intermittent haemodialysis treatment, recombinant human erythropoietin (rHuEpo) was used at a dosage schedule of 100 IU/kg bodyweight thrice weekly. Erythrokinetic studies (blood volume, RBC survival and iron kinetics) were performed in nine cases before and after 6 months of treatment. The remaining two patients had only RBC and plasma volume determinations before and after treatment. Although total blood volume remained unchanged, RBC volume was increased in all cases. Red cell loss was not modified, and quantitative improvement of RBC production was noted in all cases. No qualitative defect of erythroid maturation or release was observed in the treated patients. In conclusion, rHuEpo treatment improves the anaemia of haemodialysis patients by normalising circulating RBC volume only through an increase in red cell production.

Cortical v trabecular bone aluminum in dialyzed patients.

Differences among measurement of cortical and trabecular bone aluminum (AI) have been observed. Furthermore, its relationship to bone histology has been variable. In order to clarify these points, we have evaluated measurements of bone AI in relation to the source of AI and bone lesion in 25 hemodialysis patients. All patients were dialyzed in the same unit since commencement of dialysis and treated by the same physician. Age of the patients ranged from 29 to 66 years; mean duration of dialysis was 6.6 +/- 3.5 years. Dialysate water has been treated by reverse osmosis since 1980. Bone biopsy was performed in all patients after double tetracycline labeling. AI was measured biochemically in cortical bone (bCAI) and histochemically in trabecular (TAI) and cortical bone (CAI). Mean serum AI (36 +/- 21 micrograms/L) and bCAI (59 +/- 44 micrograms/g) were increased. There were significant correlations between: cortical AI and (1) serum AI (r = 0.71, p less than 0.001); (2) duration of dialysis with softened water (AI content, 55 +/- 21 micrograms/L, r = 0.65, P less than 0.001) but not with total duration of dialysis; and (3) AI ingested since commencement of dialysis (r = 0.57, P less than 0.01). Trabecular AI was not correlated with any of these parameters. None of cortical AI measurements were correlated with bone formation rates (BFR), osteoblastic surfaces (ObS), and resorption surfaces (RS) determined on trabecular bone. However, trabecular AI was inversely correlated with BFR (P less than 0.01) and ObS (P less than 0.05). Serum parathyroid hormone (PTH) was positively correlated with BFR (P less than 0.001) and RS (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Factors predictive of perinatal outcome in pregnancies complicated by hypertension.

Perinatal outcome and various indicators of perinatal risk were analyzed in a prospective study of 268 pregnant women with hypertension. Poor perinatal outcome was defined by stillbirth (n = 13), neonatal death (n = 2), and in surviving babies, by birth before 32 weeks or a birthweight below 1500 g (n = 13). In multivariate analysis, proteinuria and onset of hypertension between the 27th and 36th weeks of amenorrhea were the only two independent indicators of poor outcome (relative risks of 4.0 and 3.7, p less than 0.001 and p less than 0.01 respectively). Both these indicators were more frequent in mothers with no history of pre-pregnancy hypertension.

Cholangiocellular carcinoma in polycystic kidney and liver disease.

Cholangiocellular carcinoma developed in two uremic patients with polycystic kidney and liver disease, who had been treated with intermittent hemodialysis for one and nine years. In one case, in situ transformation of the liver cyst epithelium into cholangiocellular carcinoma could be demonstrated. The incidence of cholangiocellular carcinoma in patients undergoing long-term dialysis for polycystic kidney and liver disease, however, has yet to be determined.