[Management of renal anemia in patients with chronic kidney disease: the role of the general practitioner]. / Prise en charge de l'anémie chez les patients atteints de maladie renale chronique: rôle du médecin gênéraliste.

The prevalence of chronic kidney disease (CKD) is high and diabetic nephropathy is a leading cause of CKD. One of the most common complications of CKD is anemia, the frequency and severity of which increase as kidney failure progresses. Renal anemia is primarily caused by reduced renal erythropoietin production. It can also be associated with iron deficiency caused by reduced iron absorption, occult blood loss and impaired iron mobilization. This work provides an overview of the management of renal anemia with focus on intravenous iron therapy, which is more effective than oral iron administration in CKD due to reduced iron absorption.

[Treatment of anemia in chronic renal failure (predialysis)]. / Die Behandlung der Anämie bei chronischer Niereninsuffizienz (Prädialyse).

The treatment of renal anaemia with human recombinant erythropoietin (r-hu-EPO) in predialysis patients requires a close collaboration between the general practitioner and the nephrologist. This therapeutic option, along with other measures as part of the management of patients with renal insufficiency, is aimed at slowing down the progression of the kidney failure and at maintaining the patient in the best possible metabolic conditions. This paper summarises the benefits and risks of r-hu-EPO administered in renal insufficiency. The practical guidelines for the r-hu-EPO administration should help to assure an optimal and cost-effective utilization of the treatment.

Effects of oral calcitriol on bone mineral density in patients with end-stage renal failure.

Evolution of bone mineral density (BMD) at various skeletal sites and the influence of calcitriol on BMD are still poorly documented in patients with terminal renal failure. Using dual photon absorptiometry, we investigated the changes in BMD at the levels of lumbar spine, femoral neck and midfemoral shaft in 21 patients with end-stage renal failure (ESRF) treated with calcitriol (mean dosage +/- SEM: 0.21 +/- 0.02 microgram/day) and compared them to 25 patients with ESRF but not treated with calcitriol (control group) over a period of 20.3 +/- 1.5 and 17.2 +/- 1.2 months, respectively. Lumbar spine BMD increased by 7.7 +/- 3.2%/year in the treated group and decreased by 2.5 +/- 1.3%/year in the control group (P < 0.005). Femoral shaft BMD increased more in treated than in control group (+ 6.7 +/- 2.3 vs. + 1.4 +/- 2.0%/year; P < 0.05) and femoral neck BMD remained stable. PTH levels increased by 92 +/- 121 and 1033 +/- 254 pmol/year (P < 0.01) in the treated group and the controls, respectively. Osteocalcin changes were -2.7 +/- 3.7 and +20.1 +/- 11.7 micrograms/liter (P < 0.05) per year in the same groups. These results indicate that low doses of oral calcitriol in patients with end-stage renal failure were associated with an increase in BMD at the levels of lumbar spine and femoral shaft, and with a stabilization of serum PTH and osteocalcin concentrations.

Effects of dialysate composition during hemodialysis on left ventricular function.

To determine the effects of dialysate composition during hemodialysis on left ventricular systolic and diastolic function, 12 patients treated by chronic hemodialysis (mean age 40.8 +/- 2.7 years), without overt heart disease, were studied by Doppler-echocardiography successively before and after acetate hemodialysis (AHD), bicarbonate hemodialysis (BHD), and acetate-free biofiltration (AFB). The three types of hemodialysis resulted in a comparable decrease of the body weight. Mean arterial blood pressure decreased by 5 mm Hg (NS), 8 mm Hg (NS) and 10 mm Hg (P < 0.05) during AHD, BHD and AFB, respectively. There was a significant increase of the heart rate and the shortening fraction of the left ventricular diameter after AHD, but not after BHD and AFB. Mean total systemic resistance increased by 20% after AHD, 18% after BHD and by 7% after AFB (all changes NS). During each type of hemodialysis there was a significant reduction of the peak velocity of the early diastolic rapid filling wave (peak E) without change of the peak filling velocity during atrial contraction (peak A). During AHD and BHD the pressure half-time of the early filling phase (TP/2) increased, and the velocity-integral of the early diastolic filling phase (E-area) decreased. However, TP/2 and E-area did not change significantly after AFB.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of altered loading conditions during haemodialysis on left ventricular filling pattern.

Changes in the circulating volume associated with haemodialysis result in modification of left ventricular loading conditions. To determine the influence of haemodialysis on Doppler indices of left ventricular filling, 12 patients (mean age 40.8 +/- 2.7 (SEM) years) with renal insufficiency but without overt heart disease were studied by Doppler-echocardiography immediately before and after haemodialysis. Haemodialysis resulted in a decrease in body weight from 68.0 +/- 3.8 kg to 65.0 +/- 3.7 kg (P < 0.01). Heart rate and blood pressure did not change significantly during haemodialysis. Left ventricular diastolic dimension (M-mode) decreased from 53.5 +/- 1.1 mm to 49.5 +/- 1.9 mm (P < 0.05), whereas the shortening fraction did not change. Haemodialysis elicited marked changes in the early diastolic rapid filling wave (E wave) recorded by pulsed Doppler at the level of the mitral annulus. Peak velocity of the early rapid filling phase (peak E) decreased significantly from 95.3 +/- 8.2 cm.s-1 to 63.0 +/- 5.7 cm.s-1 (P < 0.001) and mid-diastolic deceleration of transmitral velocity decreased from 437.3 +/- 54.2 cm.s-2 to 239.7 +/- 54.4 cm.s-2 (P < 0.01). The peak filling velocity during atrial contraction (peak A) did not change (79.7 +/- 6.3 cm.s-1 vs 74.1 +/- 4.7 cm.s-1; P = NS). The ratio peak E/peak A decreased from 1.19 +/- 0.06 to 0.85 +/- 0.04 (P < 0.01) during haemodialysis. The results provide further evidence for the pronounced preload-dependence of Doppler indices of left ventricular diastolic function.

Bone mineral density in patients with end-stage renal failure.

Renal osteodystrophy is a well-recognized complication of chronic renal failure (CRF) and is associated with a marked morbidity. Bone mineral density (BMD) has been shown to be the best predictor of fracture risk in different circumstances. In this cross-sectional study, we measured BMD using dual photon absorptiometry at three skeletal sites of functional importance such as the lumbar spine (LS), the femoral shaft (FS) and the femoral neck (FN) in 106 patients with end-stage renal failure (11 predialysis patients and 95 patients on maintenance dialysis). These skeletal sites are characterized by various relative amounts of trabecular and cortical bone. The results indicate that decreased bone mass was detectable in all skeletal sites before the beginning of dialysis and that BMD was negatively related to dialysis duration in LS and FS. Nevertheless, the deleterious effects of renal osteodystrophy were more pronounced at the FS level, where cortical bone is predominant. A separate analysis of BMD in both sexes revealed that females presented a more important bone loss in both cortical and trabecular bone than males. We did not find any significant difference in BMD at the three measured sites between patients on continuous ambulatory peritoneal dialysis and on regular hemodialysis. This study emphasizes the need to pay more attention to the prevention of bone loss in patients on CRF before the start of dialysis therapy, and to the fact that the female population might display a more pronounced susceptibility to bone loss.

Safety and efficacy of recombinant human erythropoietin treatment of anaemia associated with multiple myeloma in haemodialysed patients.

Recombinant human erythropoietin (rHuEpo) was used to treat the anaemia of four haemodialysed patients (3 males, 1 female) with advanced multiple myeloma; the type of serum M component was IgG kappa in all cases. During the 6-month period preceding rHuEpo therapy the patients received multiple blood transfusions (range 4-22 units of packed red cells per patient). After the first month of treatment haematocrit increased from 23 +/- 3 (SD) to 32 +/- 4% and during the last 3 months the maintenance dose of rHuEpo was 143 +/- 37 U/kg per week to achieve a mean haematocrit of 35 +/- 1%. After introduction of rHuEpo, blood transfusions were no longer required and the patients reported an improvement in wellbeing. No apparent worsening of multiple myeloma has been observed over the treatment period ranging from 5 to 34 months (cumulative duration of treatment 55 months). Anti-hypertensive therapy was started in one case and increased in two patients. We conclude that rHuEpo appears to be effective and safe in treating anaemia associated with multiple myeloma in patients requiring haemodialysis.

Traumatic rupture of the urinary tract in a patient presenting nephrogenic diabetes insipidus associated with hydronephrosis and chronic renal failure: case report and review of the literature.

We report the case of a 34-year-old Japanese man suffering from a nephrogenic diabetes insipidus (NDI) associated with bilateral hydronephrosis, hydroureters and enlarged trabeculated bladder without obstruction. He also presented with chronic renal failure which has rarely occurred in similar cases. The patient was admitted after a traumatic rupture of the left urinary tract which had never been described until now in NDI. He was treated successfully by transient peritoneal and vesical drainages. This paper focuses on the very rare complication of chronic renal failure secondary to hydronephrosis in cases of NDI. The literature of this association is reviewed.

Hemostatic disturbances induced by two hollow-fiber hemodialysis membranes.

The effects on hemostasis of two high-flux membranes in hollow-fiber configuration, polyamide (PAM) and polyacrylonitrile (AN69), were analyzed in a cross-over study involving ten chronic hemodialyzed patients. Blood samples were obtained at arterial and venous sites of the extracorporeal circuit before dialysis and at 15, 30 and 180 min. Primary hemostasis: PAM induced an early significant drop in platelet counts, but at 180 min there was no longer any difference between membranes. Beta-thromboglobulin release by PAM was significantly higher at all time points. Coagulation: thrombin-antithrombin III complexes (TAT) and fibrinopeptide A increased significantly, the highest values being found with AN69. With both membranes the arterio-venous differences in TAT levels were negative throughout the sessions. Fibrinolysis: no significant differences were observed. In conclusion, both membranes induced hemostatic changes. Although these two hollow-fiber dialyzers look relatively similar, the changes observed were different, polyamide acting mainly on primary hemostasis and polyacrylonitrile on coagulation.

[Kidney retransplantation: results and prognostic factors]. / Retransplantation rénale: résultats et facteurs de pronostic.

48 non primary renal transplants were performed in 40 recipients during the 1973-1990 period in our institution (40 second grafts, 6 third grafts and 1 four and fifth grafts). Despite poor HLA matching our second graft survival rates compare favorably with others (80% and 70%, 1 and 5 year graft survival rates). The type of immunosuppression (including ciclosporine A or not) and the duration of the first graft had an influence on the outcome of second grafts. Our experience with repeated retransplantation is limited, but graft survival appears to be poor: most of the grafts were rejected within 2 years (or less). However patient survival was not affected by overimmunosuppression following multiple grafts.

[Comparison of the efficacy and tolerance of recombinant human erythropoietin between intravenous and subcutaneous administration in chronic hemodialysis. Prospective multicenter study]. / Comparaison de l'efficacité et de la tolérance de l'érythropoïétine humaine recombinante entre l'administration intra-veineuse et sous-cutanée en hémodialyse chronique. Etude prospective multicentrique.

The efficacy and tolerance of intravenous and subcutaneous administrations of recombinant human erythropoietin (r-HuEPO) have been compared in 50 maintenance hemodialysis patients. A 2 month course of intravenous r-HuEPO given at stable dosage was followed by a 6 month course of subcutaneous r-Hu EPO. We reduced r-HuEPO dosage by 50% when starting subcutaneous administration and regularly adapted the dosage to achieve hematocrit levels between 30 and 35%. At the end of the study, mean r-HuEPO dosage was 82 +/- 8 (mean +/- SEM) IU/kg/week, which represented 70 +/- 7% of intravenous r-HuEPO dosage. Mean hematocrit value was 32.9 +/- 0.5% when starting subcutaneous administration and also at the end of this study. Arterial blood pressure remained stable over the whole trial period as did most biological blood tests which were not influenced by the route of administration. In 98% of cases, patients expressed either pain-free (50%) or slight to moderate pain (48%) at the injection site. This trial confirms a substantial dosage economy when using r-HuEPO by subcutaneous route rather than by intravenous route. Moreover, objective and subjective tolerance was excellent on r-HuEPO subcutaneous administration.

Renal retransplantation in Switzerland: poor HLA matching of first and subsequent allografts does not appear to affect overall graft survival.

In Switzerland graft survival after primary renal transplantation can be considered as satisfactory, although our current policy does not favour HLA compatibility except for acute rejectors or sensitized patients. This low level of HLA matching could result in increased sensitization and affect subsequent graft survival. A total of 318 non-primary renal transplants were performed in 293 recipients during the period 1981-1990. Of these, 271 were second transplants, 40 were third transplants and seven were fourth or fifth transplants. Survival rates at 1, 2 and 5 years were 75%, 68% and 60% for second grafts, and 72%, 60% and 54% for third grafts, respectively. Results after multiple grafts were poor, but our experience was limited. The number of sensitized patients (peak PRA > 50%) awaiting retransplantation slightly increased (51 to 69), but decreased as a proportion (72% to 66%). Our policy of relying only marginally on HLA compatibility does not appear to have affected our results adversely.

Fibrin deposition and adaptive changes in glomerular procoagulant and fibrinolytic activities in rat renoprival nephropathy.

To investigate the mechanisms which may influence fibrin deposition in the remnant kidney, glomerular morphology and the haemostatic properties of isolated glomeruli were assessed in two groups of rats, 30 days after surgical removal of three-quarters of the total renal parenchyma, and compared to glomeruli in sham-operated controls. One group was given the thromboxane synthetase inhibitor OKY 046 and the other was not. Fibrin deposition occurred in about 20% of glomeruli, of which 4% exhibited segmental necrotizing lesions. Concomitantly, glomerular procoagulant activity dropped to 40% of the control level and glomerular fibrinolytic activity rose to 120-130% of this level. Inhibition of thromboxane synthesis did not affect fibrin deposition, glomerular haemostasis or the development of renal insufficiency. In an additional group of unilaterally nephrectomized rats, procoagulant activity also markedly decreased in the remaining kidney. These results indicate that in the rat remnant kidney, alterations in glomerular haemostatic properties tend to have antithrombotic effects which seem to constitute an adaptive reaction by an autacoid system to glomerular fibrin deposition.

Plasma exchange and immunosuppression for rapidly progressive glomerulonephritis: prognosis and complications.

Rapidly progressive glomerulonephritis frequently leads to death or dialysis. In 21 cases treated by plasma exchange and immunosuppression we observed seven deaths, with 12 others progressing to chronic renal failure within 3 months. Patients who died were older than those who survived (57.5 +/- 17.7 vs 40.5 +/- 16.5 years, mean +/- SD, P = 0.05), but had similar clinical symptoms (hypertension, haematuria, proteinuria, extrarenal signs) and biochemical presentation (initial creatininaemia). They required the same degree of haemodialysis, of plasma exchanges and of bolus methylprednisolone. The causes of death were infection (three cases), cardiac arrhythmia (two cases) and gastrointestinal bleeding (two cases). Among the 14 remaining patients, only two recovered normal renal function. Twelve had chronic renal failure, six of them requiring chronic dialysis or transplantation. Severe renal failure at entry and anuria were more frequently observed in patients whose renal function did not improve during treatment. Plasma exchange and steroid bolus infusions also seemed to have a beneficial effect on renal function.