[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.

Circulating ionized and total magnesium in end-stage kidney disease.

BACKGROUND: Circulating magnesium exists in the ionized state and in the undissociated form, either bound to albumin, or complexed to various anions. Until recently, only the measurement of total plasma magnesium has been possible. Now circulating ionized magnesium can be assessed as well. METHODS: Total and ionized plasma magnesium were determined in 43 patients on maintenance hemodialysis (dialysate composition: calcium 1.75 mmol/l, magnesium 0.75 mmol/l) before a dialysis session and in a group of 23 healthy subjects. RESULTS: The total (1.16 [1.03-1.31] versus 0.81 [0.78-0.89] mmol/l; median and interquartile range) and the ionized (0.71 [0.66-0.78] versus 0.54 [0.53-0.59] mmol/l) plasma magnesium levels were significantly higher (p < 0.01) and the ionized plasma magnesium fraction lower (0.61 [0.58-0.65] versus 0.67 [0.64-0.70]; p < 0.02) in patients than in controls. CONCLUSION: The determination of circulating ionized magnesium using selective electrodes is an attractive method to evaluate extracellular magnesium in kidney disease.

Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.

BACKGROUND: A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. METHODS: Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.

Six-month overnight administration of intraperitoneal amino acids does not improve lean mass.

UNLABELLED: Intraperitoneal administration of 1% amino acid dialysis solution in patients on continuous peritoneal dialysis (CAPD) is associated with improvement in plasma amino acid concentrations and inconsistent results with respect to nitrogen balance. Whether alteration(s) in lean mass and body fat distribution also occur remains controversial. Therefore 18 patients (P), on CAPD for at least 6 months, were assigned in a prospective and controlled fashion to receive overnight either a 1% amino acid (AA-P) or a 1.36% glucose (Glu-P) containing dialysis solution. Body composition was investigated using whole body dual energy X-ray absorptiometry (Hologic QDR 1000/W). In P receiving glucose (n = 9), total body fat mass increased (+1.0 +/- 0.4 kg, mean +/- SEM, p < 0.03), whereas in patients on amino acids (n = 9), it decreased (-0.6 +/- 0.3, p < 0.02). This decrease in fat mass in AA-P was attributable to a decrease in upper body fat (-0.6 +/- 0.2, p < 0.02), whereas in Glu-P, it increased (+0.9 +/- 0.03, p < 0.03). No change in lower body fat was observed in either group. Total body lean mass remained similar in both groups during the six months of study (AA-P: 46.6 +/- 2.9 kg vs 47.0 +/- 3.0 kg, Glu-P 50.8 +/- 3.2 vs 50.1 +/- 2.2 kg baseline vs 6 months, respectively). In AA-P plasma urea concentrations increased from 25 +/- 2 to 34 +/- 3 mmol/l (p < 0.05), whereas plasma bicarbonate concentrations were similar before and after 6 months of therapy in either group. Plasma albumin and transferrin concentrations did not change in either group. Protein catabolic rate increased in AA-P (p < 0.01), whereas K x t/V did not change as a consequence of either therapy. CONCLUSION: Reduction in the amount of glucose in the peritoneal dialysate and the addition of amino acids decreases, whereas continuous dialysis with overnight glucose increases upper body fat over a 6-month period. However, no changes in protein stores were observed with the addition of amino acids. Therefore overnight peritoneal dialysis with amino acids offers minor advantages to protein-malnourished patients on CAPD, but may be of benefit in overweight CAPD patients.

Evidence for preservation of cortical bone mineral density in patients on continuous ambulatory peritoneal dialysis.

It is still unclear whether dialysis modality, i.e., continuous ambulatory peritoneal dialysis (CAPD) versus hemodialysis (HD) specifically affects bone mineral density (BMD). To answer this question, 34 patients on HD and 25 on CAPD were matched for age, sex, height, and body weight with 125 normal subjects. BMD was measured using dual-energy X-ray absorptiometry (DXA; Hologic QDR 1000/W) at the lumbar spine (trabecular bone), the femoral neck (mixed cortical and trabecular bone), the distal tibial diaphysis (cortical bone), and the epiphysis (trabecular bone) in all subjects. No significant difference for blood hemoglobin, albumin, total and ionized calcium, intact parathyroid hormone (PTH) or phosphorus concentrations, as well as for alkaline phosphatase activity, failed renal allograft, prior steroid therapy, prior parathyroidectomy, duration of uremia, or of dialysis was found between patients on HD and those on CAPD. However, the residual daily urine volume and renal function at the time of the absorptiometry were higher in CAPD than in HD patients (p < 0.05) as well as the mean dialysate calcium concentration during dialysis, the blood bicarbonate concentration, and the residual renal function at the initiation of dialysis (p < 0.01, p < 0.05, and p < 0.005, respectively). In contrast, the total dose of calcium carbonate was lower in CAPD than in HD patients (p < 0.01). Results of BMD were expressed as Z scores (the number of standard deviations from the appropriate mean of BMD of 623 healthy subjects adjusted for age and sex). At the lumbar spine, no significant difference with respect to BMD was observed between the three groups. At the femoral neck and tibial epiphysis, HD patients had lower BMD (p < 0.001) than normal controls, whereas no difference was observed between HD and CAPD patients. At tibial diaphysis, patients on HD had lower BMD (p < 0.001) than patients on CAPD and than normal controls, with the values being similar in patients on CAPD and in normal controls. The results remained identical after exact matching of HD (n = 25) and CAPD (n = 25) patients for dialysis duration (1.9 +/- 0.3 and 1.7 +/- 0.3 years, respectively). Multiple regression analysis revealed significant negative correlations between Z scores at the lumbar spine (p < 0.05), femoral neck (p < 0.02), tibial diaphysis (p < 0.005), and tibial epiphysis (p < 0.05) on the one hand and plasma alkaline phosphatase activity on the other. The Z score at tibial diaphysis was also correlated with residual renal function at the initiation of dialysis (p < 0.05). In conclusion, this study provides evidence for the preservation of cortical bone with CAPD as opposed to HD. The higher residual renal function observed in the former treatment modality might account, at least in part, for this finding.

Effect of calcium-channel blockers on calcium-phosphate metabolism in patients with end-stage renal disease.

BACKGROUND: After EDTA-induced hypocalcaemia, healthy volunteers treated with diltiazem display more severe hyperparathyroidism than subjects on felodipine studied under identical conditions. Therefore patients with end-stage renal disease (ESRD) and severe secondary hyperparathyroidism might be particularly sensitive to this side-effect. METHODS: To test this hypothesis, seven patients with ESRD on chronic haemodialysis (3 women and 4 men) with serum levels of intact PTH ranging from 204 to 675 pg/ml were studied both before and during the first 180 min of haemodialysis against a dialysate with low calcium concentration (0.75 mmol/l, n = 6 and 1 mmol/l, n = 1) under the following three experimental conditions: control, felodipine (10 mg/day) and diltiazem (120 mg b.i.d.). RESULTS: At onset of dialysis, plasma phosphorus level was higher on diltiazem (2.03 +/- 0.08 mM) than on felodipine (1.64 +/- 0.10, P < 0.02), and on the latter it was lower than in control condition (1.88 +/- 0.16, P < 0.02). As a probable consequence, blood ionized calcium concentration was lower on diltiazem (1.14 mM +/- 0.02, mean +/- SEM) than on felodipine (1.2 +/- 0.03, P < 0.05) or in control condition (1.17 +/- 0.01, NS). There was a trend for intact PTH to be higher on diltiazem (324 +/- 47 pg/ml) than on felodipine (246 +/- 55) or in control condition (305 +/- 49) and 1,25-dihydroxyvitamin D was higher indeed on diltiazem (6.70 +/- 0.92 pg/ml) than on felodipine (4.75 +/- 0.91, P < 0.02) or control (3.87 +/- 0.62, P < 0.05). Area under the curve PTH over the first 60 min of dialysis was higher by 16 +/- 7% on diltiazem than on felodipine (P < 0.05). CONCLUSIONS: While on diltiazem rather than on felodipine, patients with ESRD display higher plasma phosphorus levels, and slightly aggravate the degree of severity of hyperparathyroidism recorded during haemodialysis against low-calcium dialysate. The long-term effect of this new observation remains to be evaluated.

Impact of time-interval after transplantation and therapy with fibrates on serum cholesterol levels in renal transplant patients.

It is unclear to what extent different immunosuppressive regimens contribute to increased serum cholesterol levels observed in renal transplant patients after prolonged periods of immunosuppression (i.e. 3 and 5 years following kidney grafting). Therefore 2 groups of renal transplant patients were evaluated with respect to serum cholesterol 3 years (n = 103) and 5 years (n = 66) after transplantation: Group 1: prednisone (Pred)/azathioprine (Aza) [3 years (y): n = 52; 5 y: n = 49; mean prednisone dose 12 +/- 1 mg/day]; group 2: cyclosporine A (CsA) alone or in combination with Pred (3 y: n = 51; 5 y: n = 17; prednisone dose 4 +/- 2 mg/day, p < 0.001 vs group 1). The groups were similar with respect to age, sex, body mass index, time interval after transplantation, underlying kidney diseases and concomitant drug therapy. Serum cholesterol levels were persistently higher in patients of group 2 when compared to group 1 (3 years: 7.3 +/- 0.2 vs 6.7 +/- 0.2 mmol/l, p < 0.01; 5 years: 7.5 +/- 0.1 vs 6.6 +/- 0.3 mmol/l, p < 0.01) despite 75% lower daily doses of Pred (p < 0.001) in CsA treated patients (group 2). Before transplantation, patients exhibited a similar distribution of serum cholesterol levels when compared to age, sex and body mass index matched healthy subjects. In contrast 3 and 5 years following transplantation 72% of the patients had serum cholesterol levels above 6.5 mmol/l, whereas in normal subjects, 60% had serum cholesterol levels below 6.5 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of dialysis modality on body composition in patients with end-stage renal disease.

Loss of muscle mass and altered body fat distribution (i.e. increased central fat stores in the presence of normal peripheral fat stores) have been reported in patients on hemodialysis (HD), when compared to normal volunteers. Whether treatment of end-stage renal disease (ESRD) with continuous ambulatory peritoneal dialysis (CAPD) would alter body composition in a different manner than HD is unknown. To answer this question, two groups (n = 11 each) of male patients with ESRD (matched for age, residual renal function, body weight and body height as well as physical activity) were studied. Muscle mass and body fat distribution were assessed using computed tomography. Mid-thigh muscle area, peripheral and central fat stores were similar between the two groups of dialysis patients. In both patient groups muscle mass and fat stores were independent of duration of dialysis, age, daily protein intake and residual renal function. In CAPD-patients mid-thigh muscle area was correlated with plasma albumin (r = 0.56, p < 0.05), while serum cholesterol level was correlated with mediastinal fat area (r = 0.81, p < 0.01). The present results indicate that both treatment modalities of ESRD (HD vs CAPD) result in similar changes of body composition. Despite continuous glucose loading in CAPD-patients, neither central nor peripheral fat stores are increased in these subjects compared with HD treated patients.

[Toxicity of an organic Germanium compound: deleterious consequences of a "natural remedy"]. / Toxizität einer organischen Germanium-Verbindung: Deletäre Folgen eines "Naturheilmittels"

Reports mainly from Japan, recommend germanium (Ge)-containing compounds as "anti-cancer" and "immunostimulatory" remedies. We report on a 25-tear-old woman with stage II HIV disease who consumed a total of 47 g Ge as Ge-lactate-citrate 18%. She developed severe renal insufficiency (creatinine clearance 7 ml/min/1.73 m2, proteinuria 0.28 g/d) and hepatomegaly. Biopsies revealed tubulointerstitial nephropathy with vacuolar degeneration, mainly of distal tubular epithelia, and severe liver steatosis. Tissue Ge content in kidney and liver biopsy specimens was increased 68-and 140 fold respectively. In agreement with previous reports, renal dysfunction persisted 9 months later (creatinine clearance 11 ml/min/1.73 m2).

Serum immunoglobulin levels and natural antibodies to Haemophilus influenzae in hemodialysis patients: evidence for IgG subclass imbalances.

Humoral immune parameters were studied in 13 patients with end-stage renal failure on maintenance hemodialysis. Serum IgA, IgM and IgG concentrations were comparable to control values from 14 healthy blood donors. IgG subclass analysis revealed significantly increased IgG1 levels in the patients when compared to controls (p less than 0.01). In 3 patients, IgG2 deficiency was found, in one case associated with low IgG3 level. Concentrations and subclass composition of naturally occurring antibodies to Haemophilus influenzae type b (Hib) polysaccharide (PS) were measured using an indirect ELISA. In patients IgM and IgG, including IgG1 and IgG2 antibodies to Hib, presented no difference from controls. Subclass analysis of Hib specific IgG antibodies revealed that IgG2 accounted for a substantial amount of the anti-Hib PS antibody response in controls as well as in patients. We conclude that patients on maintenance hemodialysis present imbalances of immunoglobulin levels. However, the antibody response to certain PS antigens could remain unaffected by renal failure.

[Determination of fructosamine in chronic kidney diseases (dialysis-dependent patients)]. / Die Fructosaminbestimmung bei chronischen Nierenerkrankungen (dialysepflichtige Patienten).

The serum fructosamine normal range was confirmed. Correction to protein or albumin did not significantly affect the results. Therefore, correction of fructosamine values from patients with normal protein and albumin values would not improve the clinical significance of fructosamine. Fructosamine concentrations of heparin plasma from non-diabetics also fell within the serum fructosamine normal range. The fructosamine concentration from non-diabetic dialysis patients was significantly higher and more widely distributed than that of the reference collective despite normal blood glucose concentration. Relating fructosamine to protein had no substantial effect, whereas the differences were even increased when fructosamine was related to albumin. On the present stage of knowledge it might be considered to establish a reference interval for dialysis patients. It appears that the fructosamine estimation may then be successfully applied also to dialysis patients. Although dialysis resulted in hemoconcentration, the fructosamine concentration remained virtually unchanged. Referencing both values before and after dialysis to protein or albumin improved the correlation, but substantial differences were introduced as well. However, none of several parameters measured in parallel interfered to a degree which might explain such differences. In order to find a reasonable explanation for these findings further experiments are necessary.

[Home dialysis]. / Heimdialyse.

Home haemodialysis is a good example of life-conserving medical technique performed outside the hospital. Since 1982, CPD has been displacing home haemodialysis as preferred independent dialysis. Nevertheless, for all those unable or unwilling to perform peritoneal dialysis, home haemodialysis continues to offer the advantages of self-treatment with good rehabilitation and excellent quality of life.

[Hemodialysis as kidney replacement therapy]. / Hämodialyse als Nierenersatztherapie.

Haemodialysis is the most frequently used renal replacement therapy and in Europe keeps alive more than 80,000 patients with end-stage renal failure. Three times weekly the patient is connected to the artificial kidney and uraemic toxins are removed using a filter permeable for water and small solutes. This treatment lasts about 3-4 hours and can be performed in hospitals, dialysis centers or in the patient's own home. With haemodialysis, patients can survive for many years with a good quality of life. However, dialysis treatment is time-consuming, there are dietary restrictions, and the patients become increasingly dependent on medical personnel and relatives. It is therefore not surprising that most dialysis patients hope for a kidney transplantation.

[Selective elimination of atherogenic lipoproteins using dextran-sulfate cellulose. Experiences in 2 patients with heterozygote familial hypercholesterolemia]. / Selektive Elimination atherogener Lipoproteine mit Dextransulfat-Cellulose. Erfahrungen bei 2 Patienten mit heterozygoter, familiärer Hypercholesterinämie.

Extracorporeal elimination of atherogenic lipoproteins with dextran-sulfate-cellulose for lowering of plasma cholesterol levels was tested in 2 patients with familial heterozygous hypercholesterolemia (untreated cholesterol values 12.9 +/- 1.5 and 12.5 +/- 1.2 respectively) in a longterm experiment. One patient was treated weekly for a period of 36 weeks and the other at fourteen days' intervals with simultaneous administration of 40 mg/day Simvastatin (synvinolin, MSD) for 8 weeks. The mean reduction in total cholesterol concentration was 41% in the first case and 54% in the second (combination with Simvastatin). The therapy was well tolerated without side effects.

Pharmacokinetics of amoxycillin and clavulanic acid in haemodialysis patients following intravenous administration of Augmentin.

1. Serum concentrations of amoxycillin and clavulanic acid were measured in patients with end-stage renal disease (ESRD) following intravenous administration of 1.2 g Augmentin. Augmentin was administered on a non-dialysis day and 2 h prior to a 4 h dialysis session. 2. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for amoxycillin on the non-dialysis day were 14.4 ml min-1, 19.2 h, 14.9 l and 13.6 h, respectively. 3. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for amoxycillin were 77.1 ml min-1, 91.5 ml min-1, 0.64 and 2.30 h, respectively. 4. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for clavulanic acid on the non-dialysis day were 43.6 ml min-1, 4.4 h, 11.0 l and 3.05 h, respectively. 5. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for clavulanic acid were 92.8 ml min-1, 136 ml min-1, 0.65 and 1.19 h, respectively. 6. The total serum clearance on the non-dialysis day, which represents non-renal clearance, was lower than that in normal subjects for both amoxycillin and clavulanic acid. These data would suggest some degree of hepatic impairment in patients with ESRD.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein changes in familial hypercholesterolemia after extracorporeal immunoadsorption of low density lipoproteins.

The effects of extracorporeal immunoadsorption of LDL on the lipoprotein metabolism in two patients with familial hypercholesterolemia are reported. The immunoadsorbent consisted of F(ab')2 fragments of sheep anti-LDL antibodies, which had been coupled to Sepharose CL 4B. Within a time period of 3 to 3.5 hours a mean reduction of the level of total cholesterol by 76 +/- 4 p. cent could be obtained. The level of LDL cholesterol was reduced by 78 +/- 4 p. cent and the level of apo. B by 84 +/- 5 p. cent. Both LDL and VLDL were bound to the immunoadsorbent, while HDL was predominantly lowered by the plasma-dilution, which was in the order of 20 p. cent. The same was true for other serum proteins, not related to LDL or VLDL. The relative distribution of the different lipoprotein classes was again reached 3 days after the treatment, the initial lipid and apolipoprotein levels two to three weeks after the treatment. In a long-term therapy consisting of 45 treatments with a mean interval of 18 days between two treatments a mean cholesterol lowering of 42 p. cent could be achieved. No adverse effects and no sensitization to be heterologous protein were observed.

Human recombinant erythropoietin in anaemic patients on maintenance haemodialysis. Secondary effects of the increase of haemoglobin.

Twelve anaemic patients on haemodialysis were treated with recombinant human erythropoietin, starting with 72 IU/kg/week. The dose was doubled after 2 weeks until an increase of 2 g/dl of haemoglobin was observed. The effects on various parameters were studied during a 3-month period. Haemoglobin increased from 6.70 +/- 0.74 to 10.49 +/- 1.04 g/dl (mean +/- SD, P less than 0.001), potassium from 5.51 +/- 0.50 to 6.06 +/- 0.65 mmol/l (P less than 0.005), phosphate from 1.78 +/- 0.40 to 2.17 +/- 0.40 mmol/l (P less than 0.001) and the calcium phosphorus product from 4.3 to 5.2 (P less than 0.001). Three patients developed marked periarticular inflammation due to calcified deposits with a high calcium-phosphorus product of 6.8. An increase in arterial blood pressure was observed in three previously well-controlled hypertensive patients, one of whom developed hypertensive encephalopathy. We conclude that recombinant human erythropoietin is very effective in treating the anaemia of end-stage renal failure on haemodialysis. Regular estimations of serum potassium and phosphate are mandatory. In hypertensive individuals a further increase in blood pressure is possible.

Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin.

Amoxicillin and clavulanic acid are prescribed as a fixed drug combination. The purpose of the present study was to assess the influence of various degrees of renal insufficiency (glomerular filtration rate [GFR], less than 5 to greater than 75 ml/min per 1.73 m2) on the pharmacokinetics of amoxicillin and clavulanic acid following oral (500 and 125 mg of amoxicillin and clavulanic acid, respectively) and intravenous (1,000 and 200 mg, respectively) dosing. The volume of distribution and the systemic availability were independent of the renal function, while the total body clearance and the renal and the nonrenal clearance of amoxicillin and clavulanic acid decreased with decreasing renal function. The decrease in the total body clearance was more pronounced for amoxicillin than for clavulanic acid. This explains the increase in the ratio of the area under the plasma concentration versus time curve of amoxicillin to that of clavulanic acid with decreasing glomerular filtration rate after oral dosing; for example for a GFR of 75 ml/min, the ratio of amoxicillin to clavulanic acid was 4.9 +/- 1.2; for a GFR of 35 to 75 ml/min, 5.3 +/- 2.4; for a GFR of 10 to 35 ml/min, 11.9 +/- 5.8; for a GFR of 5 to 10 ml/min, 13.4 +/- 9.1; and for patients on hemodialysis, 14.7 +/- 5.3. Dosage recommendations are suggested which prevent undue accumulations of amoxicillin while maintaining adequate concentrations of clavulanic acid.