Béatrice Viron

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression

Background. The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. Methods. This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1–2 mg/kg per day. Results. At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P =0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P =0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P =0.009), leukopenia (37.3% vs. 9.5%, P <0.001), fever (25.2% vs. 10.1%, P =0.001), herpes simplex (17.9% vs. 5.7%, P =0.001), and thrombocytopenia (11.3% vs. 3.2%, P =0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). Conclusion. Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Fungal Peritonitis in Patients on Peritoneal Dialysis

Fungal peritonitis (FP) is a serious complication of peritoneal dialysis, both in terms of morbidity and mortality. Available data on the effectiveness of fluconazole in eradicating FP without catheter removal are still controversial. We reviewed 20 FP cases that occurred among 325 patients who underwent peritoneal dialysis in our center between January 1984 and January 1992, in order to establish whether a profile of patients at risk of developing FP could be identified and to evaluate the effectiveness of fluconazole in treating FP (7 cases). Age, sex, a particular cause of end-stage renal disease, and the presence of diabetes did not correlate significantly with the development of FP. The risk of FP increased in patients on immunosuppressive treatment. Sixteen of our 20 patients had bacterial peritonitis during the month before they developed FP. Nineteen were treated with antibiotics. Neither the type of bacterial organism isolated during the bacterial peritonitis preceding FP nor modality and duration of antibiotic treatment correlated significantly with the development of FP. Patients who subsequently developed FP were more frequently treated with antibiotics while in hospital (p < 0.001). Candida species accounted for 15 of our 20 FP cases (75%), with Candida albicans being by far the most common isolate. Treatment strategies varied among the 20 patients. The combination of intravenous or intraperitoneal administration of 5-fluorocytosine and oral administration of fluconazole was used in 7 cases: only 1 patient was cured without catheter removal, 1 patient died within the first 4 days of treatment, removal of peritoneal catheter was necessary in the other 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective comparison of the use of sirolimus and cyclosporine in recipients of a kidney from an expanded criteria donor.

A 6-month, open-label, multicenter prospective pilot study was conducted to evaluate the effects of sirolimus (SRL) versus cyclosporine (CsA) in recipients of kidneys from expanded criteria donors. All patients also received antithymocyte globulins induction, mycophenolate mofetil, and steroids. Sixty-nine patients (33 SRL, 36 CsA) were randomized. More patient were withdrawn in the SRL group (16 vs. 6, P<0.01), because of delayed graft function and surgical complications. Delayed graft function tended to be more frequent with SRL than with CsA (45.4% vs. 30.6%, P=0.22). Graft survival was numerically lower in the SRL group (87.5% vs. 97%, P=0.19). At 6 months, there were no significant differences in biopsy-proven acute rejection or calculated creatinine clearance (SRL 12.1% vs. CsA 8.3%; P=0.7 and 44.7±16.6 vs. 41.9±15.2 mL/min; P=0.54 respectively). These results do not support the use of SRL immediately after transplantation in expanded criteria donor recipients.

Didanosine pharmacokinetics in patients with normal and impaired renal function: influence of hemodialysis.

The pharmacokinetics of didanosine were investigated following oral administration of a single 375-mg dose to eight human immunodeficiency virus-seropositive patients with normal renal function and eight human immunodeficiency virus-seropositive uremic patients. In uremic patients, the plasma half-life was longer than that in control patients (respectively, 4.5 +/- 2.2 and 1.6 +/- 0.4 h). The ratio of total plasma clearance to absolute bioavailability was four- to fivefold lower in uremic patients than in patients with normal renal function (respectively, 491 +/- 181 and 2,277 +/- 738 ml/min). Because of the decrease in elimination, concentrations in plasma were higher for uremic patients than for control patients; the maximum concentrations of drug in plasma were, respectively, 3,978 +/- 1,607 and 1,948 +/- 994 ng/ml; the areas under the concentration-time curve were, respectively, 14,050 +/- 4,262 and 3,000 +/- 956 ng.h/ml. Didanosine was removed by hemodialysis with an extraction ratio of 53% +/- 8%, a hemodialysis clearance value of 107 +/- 21 ml/min, and a fractional drug removal during a 4-h dialysis of 20% +/- 8% of the dose. Dosage adjustments are necessary in uremic patients.

Effects of Long-Term Treatment with Recombinant Human Erythropoietin on Physiologic Inhibitors of Coagulation

Recombinant human erythropoietin (rHu-EPO) in the treatment of renal anemia might predispose to an increased risk of thrombotic complications. In an attempt to comprehend the involvement of the physiologic inhibitors of coagulation in this process, we studied 2 groups of hemodialysis patients. Group I included 21 patients receiving a starting dose of 90 IU/kg/week s.c., and group II included 17 patients without rHu-EPO. The following coagulation tests were performed before rHu-EPO treatment, and after 1, 6 and 12 months: prothrombin time; activated partial fistula thromboplastin time; fibrinogen; plasminogen activity; antithrombin III activity; protein C activity; total and free protein S antigens, and C4b binding protein. Only the latter three parameters were changed in group 1, while high baseline levels of protein S antigens were found in both groups. A decrease in total and free protein S was observed within 1 month of treatment. At the 6th month total protein S returned to near pretreatment values, whereas a significant fall in free protein S (p = 0.007) was observed. All three parameters returned to near baseline values by 12 months. These results suggest that protein S activity can be altered at the beginning of EPO therapy, a change that under favoring circumstances might contribute to the thrombotic events reported during the early phase of rHu-EPO treatment.

Failing arteriovenous hemodialysis fistulas: assessment with magnetic resonance angiography.

RATIONALE AND OBJECTIVES The authors sought to evaluate prospectively magnetic resonance angiography (MRA) versus fistulography in the detection and characterization of complications associated with malfunctioning hemodialysis access fistulas (arteriovenous fistulas [AVF]). METHODS Nineteen patients with clinical AVF dysfunction were studied by MRA and fistulography. Data from each study were collected prospectively and analyzed in a blinded manner. RESULTS The main diagnosis was stenosis in eight patients, thrombosis in five patients (mural thrombosis with preserved flow in one), aneurysm without stenosis in two patients, and normal AVF in four patients. A hazy flow void, assumed to be related to turbulence, was observed in normal arterial anastomoses. When flow void was considered as a criterion of stenosis or thrombosis, one false-positive and one false-negative MRA study were determined, yielding a sensitivity and specificity of 92% and 86%, respectively. CONCLUSIONS Magnetic resonance angiography is a feasible and sensitive technique with which to portray suspected malfunctioning hemodialysis access fistulas.

Effect of Recombinant Human Erythropoietin on Nutritional Status and Plasma Lipids in Uremic Patients

Dr. Béatrice Viron, Service de Néphrologie, Hôpital Tenon, 4, rue de la Chine, F-75020 Paris (France) Dear Sir, Improved appetit and food intake have been reported from earlier studies of patients treated with recombinant human erythro-poietin (r-Hu EPO) [1]. An increase in BUN, plasma creatinine and plasma phosphorus values as well as, in some cases, severe hyper-kaliemia were observed in certain series [2]. Contrasting with their generally poor nutritional status [3], plasma lipid abnormalities are common in uremic patients [4], especially those maintained on hemodialysis (HD) or peritoneal dialysis (PD). In those patients, particularly prone to diffuse atherosclerosis [5], any deleterious effect of r-Hu EPO on plasma lipids might question the benefit of correcting anemia with this treatment. However, the effect on plasma lipids of the r-Hu-EPO-induced changes concerning the nutritional behavior of uremic patients had not been assessed yet. We have studied 12 patients, 7 HD (4 males, 3 females, mean age 57) and 5 PD (3 males, 2 females, mean age 70). Plasma lipids were measured together with different reliable parameters of the nutritional status [3], first, before initiating r-Hu EPO, then 6 months from the date of correction of anemia (defined as Hb > 10 g/dl). The following data were collected: body mass index, triceps skin-fold thickness (TST), arm muscle circumference (AMC), serum albumin, prealbumin, transferrin, total cholesterol, triglycerides (Tg), apolipoprotein (Apo) Al, Apo B, retinol-binding protein and acid αΓglycopro-tein. These values were compared to those obtained from 7 HD and 12 PD nonanemic patients, matched for age, sex and duration of maintenance dialysis. Before EPO, Hb was 7.2 ± 0.4 g/dl in the HD and 8.6 ± 0.7 g/dl in the PD patients. The PD patients had decreased serum albumin (2.9 ± 0.4 g/dl), increased Tg (2.3 ± 1.4 mmol/ 1) and Apo B (0.16 ± 0.05 g/dl), whereas only Tg were abnormally high (2.0 ± 1.1 mmol/l) in HD patients. However, anthropometric hallmarks of malnutrition were exclusively found in male HD patients, who had low values of body mass index (20.9 ± 1.0 kg/m2), TST (4.2 ± 1.1 mm) and AMC (22.4 ± 2.7 cm). After 6 months with stable Hb (HD: 10.4 ± 0.8 g/dl; PD: 10.1 ± 0.6 g/dl), only the male HD patients exhibited a significant increase in TST (5.1 ± 1.2 mm; p < O.Ol) and AMC (23.1 ±