[Medical and economic evaluation of new peritoneal dialysis solutions]. / Evaluation médico-économique des nouvelles solutions en dialyse péritonéale.

Conventional peritoneal dialysis solutions are mostly bioincompatible in relationship with a low pH, a high glucose and glucose degradation products (GDP) concentrations inducing anatomical and functional peritoneal membrane alterations. Use of icodextrin solution instead of glucose hypertonic solution preserves peritoneal membrane minimizing glucose exposure and its peritoneal absorption. Physiological fluids with a neutral pH and less GDP seem to have a positive effect on residual renal function which declines more slowly when they are early prescribed, before highly damaged and sclerotic kidneys. Preliminary data show that patients and technique survivals are better when physiological solutions are used either for diabetic and non diabetic patients. However, these new solutions do not improve peritonitis rates except for bicarbonate solutions but this fact must still be confirmed by other studies. In spite of a higher cost, physiological solutions must be proposed mainly for patients with a low comorbidity index and a high life expectancy.

A trial comparing local pain after subcutaneous injection of epoetin-beta versus darbepoetin-alpha in healthy volunteers.

BACKGROUND: The aim of this study was to compare local pain experienced with subcutaneous (s.c.) injection of epoetin-beta vs. darbepoetin-alpha. METHODS: 40 healthy volunteers were enrolled into this single-blind, crossover study. After receiving an injection of placebo, individuals were randomized to receive s.c. injections of epoetin-beta 6,000 IU (0.3 ml) or darbepoetin-alpha 30 mg (0.3 ml), with a 1-week washout period between injections. Local pain was evaluated using a Visual Analog Scale (VAS) and a 6-item Verbal Rating Scale (VRS) immediately after (T0) and 1 h after injection (T1). RESULTS: The respective mean (standard deviation) and median (range) VAS values at T0 were 1.2 (1.7) and 0.5 (0.0 - 6.9) for epoetin-beta vs. 2.8 (2.4) and 1.9 (0.0 - 9.0) for darbepoetin-alpha (p < 0.0001). At T0, VRS scores demonstrated that 51% of individuals experienced no pain after epoetin- injection compared with 16% of those receiving darbepoetin-alpha. The percentage of individuals perceiving moderate or important pain was significantly greater with darbepoetin-alpha (38%) compared with epoetin-beta (5%, p = 0.0005) and placebo (14%). Pain evaluation at T1 showed no difference between treatment groups. Local tolerance was excellent except for a small hematoma with epoetin- at T1 and with darbepoetin-alpha at T0 which persisted at T1. CONCLUSION: In healthy volunteers, s.c. injection of epoetin-beta was significantly less painful than with darbepoetin-alpha and comparable with placebo. No significant pain was apparent at T1 in any group.

French peritoneal dialysis registry (RDPLF): outline and main results.

The Registre de Dialyse Péritonéale de Langue Française (RDPLF Registry) is a non-profit association that has been set up to assist physicians and nurses in evaluating their practical experience and results regarding peritoneal dialysis (PD). Five French-speaking and two Spanish-speaking countries have participated in this initiative (which includes 21 000 patients). In France, 82% of all PD patients are included in the registry and the main results for the period from 1995 to January 2006 form the basis of this report: of 11 744 incident patients with a median age of 71 years, 21.5% were over 80 years of age and 56% were not able to perform PD treatment at home without assistance. Eighty-six percent of the latter group received external assistance from a private nurse and 14% were aided by their family. The overall average rate of peritonitis was one episode every 29 months. The probability of being peritonitis-free appeared to be better for patients on automated PD (59.4% at 2 year) than for those on continuous ambulatory PD (55.3%), but this finding requires further validation. The average waiting time before transplantation was about 2 years. In patients who had undergone transplantation, the peritonitis rate was one episode per 42 months before transplantation compared to one episode per 29 months for patients who had not received a transplant. Eighty-three percent of patients had a hemoglobin level greater than 11 g%. Catheter survival was 92% at 2 years post-insertion and 85% at 5 years, with 94% being implanted by experienced surgeons. In conclusion, the RDPLF results demonstrate that PD may be successfully prescribed for older patients who receive assistance either from their family or from a nurse. Further, a larger number of younger patients should also be prescribed this technique in France. Patients eligible for transplantation and on short-term PD have the lowest risk of developing peritonitis; PD before transplantation may help prolong residual renal function, and initial treatment by PD may also help to preserve vascular access for the future.

The evolution of weight and body composition in renal transplant recipients: Two-year longitudinal study.

UNLABELLED: Previous series have reported weight gain after kidney transplantation. However few studies have investigated the body composition after kidney transplantation, particularly during longitudinal follow-up. In this prospective study, we assessed the changes in body composition after kidney transplantation. We also analyzed the effect of steroid withdrawal from the immunosuppressive regimen on weight gain and body composition. METHODS: Thirty-eight cadaveric kidney transplant recipients were followed for 2 years posttransplant. Total and segmental body composition were measured by dual energy X-ray absorptiometry (DEXA) at the time of transplantation as well as 3, 6, 12, and 24 months later. RESULTS: In 28 patients (group A), prednisone was stopped by month 6, whereas, in 10 patients (group B), it was continued throughout the study. In the overall patient group, there were no significant changes in body weight. However, a trend to increased weight was observed in group B. In this group, patients showed an early increase in total body fat with a central accumulation of fat mass that was maintained during the follow-up period. On the other hand, total lean mass increased significantly in group A but did not change significantly in group B. CONCLUSION: In summary, overall the group showed no major changes in body weight during the 2 years after transplantation. Steroid withdrawal in kidney transplant recipients may have a significant positive effect on body composition.

Pharmacokinetics of mycophenolic acid in kidney transplant patients receiving sirolimus versus cyclosporine.

INTRODUCTION: Mycophenolic acid (MPA) pharmacokinetics exhibit large variability in transplant recipients and may be altered due to concurrent immunosuppressants. Little is known about the influence of sirolimus (SRL) on MPA pharmacokinetics in kidney transplant patients. METHODS: We studied the areas under concentration-time curves (AUC) for MPA in 15 patients receiving immunosuppression combining SRL with mycophenolate mofetil (MMF). The pharmacokinetic measurements were performed in all patients using three MMF dosing regimens (0.5 g twice a day, 0.75 g twice a day, 1 g twice a day). Similar blood AUC profiles were also sampled from 12 patients treated with a fixed dose of MMF 1 g twice a day and cyclosporine (CsA). MPA was measured using HPLC; the AUC0-12 of MPA was determined by the trapezoidal method using four sampling time points: C0, C1, C3, C5. RESULTS: While patients on SRL were receiving 0.75 g MMF twice a day, mean AUC0-12 and C0 values of MPA were comparable to those of patients receiving CsA and 1 g MMF twice a day (54.1 +/- 17.6 and 3 +/- 1.87 vs 51.7 +/- 16.7 mg.h/L and 2.76 +/- 1.57 mg/L, respectively). On the other hand, 0.5 g MMF twice a day with SRL therapy resulted in AUC0-12 and C0 values of MPA of 32.3 +/- 12.6 mg.h/L and 2.32 +/- 1.72 mg/L, respectively, whereas, 1 g MMF twice a day with SRL resulted in AUC0-12 and C0 values of MPA of 70.9 +/- 19.3 mg.h/L and 4.7 +/- 2.44 mg/L, respectively. CONCLUSIONS: These findings demonstrate that MPA exposure in the presence of SRL is higher than that with CsA. It appears that the MMF dose should be reduced to 0.75 g twice a day in patients receiving SRL to obtain AUC0-12 of MPA levels comparable to that in patients treated with CsA and MMF 1 g twice a day.

Factors predicting the long-term success of maintenance cyclosporine monotherapy after kidney transplantation.

BACKGROUND: The theoretical aim of maintenance cyclosporine monotherapy (mCsA) after kidney transplantation is to reduce the incidence of the metabolic complications of corticosteroids and to minimize the adverse effects of excessive long-term immunosuppression. This study was performed in low-immunological-risk cadaveric kidney transplant recipients to evaluate the risks and benefits of mCsA and the long-term graft survival, and to determine the factors predicting success of this policy. METHODS: The multicenter retrospective study was conducted in 329 Caucasian patients receiving mCsA out of 728 first cadaveric kidney transplant recipients. The inclusion criteria were: HLA antibodies < or =25%, serum creatinine <200 micromol/L, and no rejection or only one rejection episode. At the end of the study, we compared the group of patients successfully treated with mCsA (successful group) with those requiring additional immunosuppressive agents (unsuccessful mCsA group). RESULTS: Overall patient and graft survival rates for the 728 first cadaveric graft were 92% and 64%, respectively, at 8 years. Out of 329 patients enrolled in mCsA, 240 were maintained on this treatment and 89 were withdrawn (3 deaths, 18 graft losses, 68 functional grafts). The 8-year graft survival in the 329 enrolled mCsA patients was 84%, 95% in the successful mCsA group, and 70% in the unsuccessful mCsA group. Multivariate analysis showed that the factors predicting success of mCsA were: donor age <40 years (P = 0.001), serum creatinine at mCsA initiation <125 micromol/L (P = 0.02), no rejection episode before mCsA initiation (P = 0.005), and glomerulopathy as the primary renal disease (P = 0.001). CONCLUSION: Numerous kidney transplant recipients with a low immunological risk and good and stable renal function may benefit from discontinuation of prednisone and azathioprine in order to reduce the complications related to these drugs. This therapeutic approach had no adverse impact on the overall long-term graft survival for "low risk" and successful patients.

Clinical pharmacokinetics of fluconazole.

Fluconazole was recently developed for the treatment of superficial and systemic fungal infections. Triazole groups and insertion of 2 fluoride atoms increase the polarity and hydrosolubility of the drug, allowing it to be used in a parenteral form. Bioassay methods using Candida pseudotropicalis as a test organism were the first techniques used for the determination of fluconazole in body fluids. Gas chromatographic and high performance liquid chromatographic methods were later developed with better accuracy and sensitivity. Prediction of efficacious concentrations in patients from the minimum inhibitory concentrations in vitro seems to be uncertain because of low efficacy of the drug on some yeasts in vitro compared with efficacy in vivo in animal models. Oral forms (capsule and solution) are quickly absorbed and bioavailability is nearly complete (about 90%). Plasma protein binding is low (11 to 12%) and fluconazole circulates as active drug. Distribution is extensive throughout the tissues and allows the treatment of a variety of systemic fungal infections. The average elimination half-life (t1/2) of 31.6 +/- 4.9h is long, with a minimum of 6 days needed to reach steady-state; thus, a loading dose (equal to double the maintenance dose) is recommended. The metabolism of fluconazole is not qualitatively or quantitatively significant. The main route of elimination is renal. The mean +/- SD (calculated from published data) total and renal clearance values are 19.5 +/- 4.7 and 14.7 +/- 3.7 ml/min (1.17 +/- 0.28 and 0.88 +/- 0.22 L/h), respectively. Concentrations of fluconazole in blood after administration of single doses correlated well with the administered dose. There was very little interassay variation between the data reported in literature. Concentrations in blood after multiple doses also exhibit little variation and the accumulation factor was between 2.1 and 2.8. Fluconazole was found in many body fluids, especially in cerebrospinal fluid and dialysis fluid, allowing the treatment of systemic fungal infections such as coccidioidal meningitis and fungal peritonitis. Concentrations of 1 to 3 mg/L and 20 mg/L are the extreme values expected in clinical practice. In renal insufficiency the fluconazole t1/2 is longer, requiring dosage adjustment in relation to creatinine clearance. In continuous ambulatory peritoneal dialysis a 150mg dose in a 2L dialysis solution every 2 days has been proposed. In haemodialysis, a dose of 100 or 200mg should be given at the end of each dialysis session. Neither old age nor irradiation affect fluconazole pharmacokinetics, but the t1/2 was shorter in children.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical pharmacokinetics of ketoprofen after single intravenous administration as a bolus or infusion.

The pharmacokinetics of ketoprofen were evaluated in 29 patients suffering from acute renal colic following a single intravenous administration as a bolus or short infusion (1.5 and 2 hours), and after a loading dose and a 24-hour infusion. Serum concentrations of ketoprofen were measured by high pressure liquid chromatography. The mean (+/- SD) values of clinical parameters were as follows: distribution half-life = 0.34 +/- 0.19 h; elimination half-life = 2.05 +/- 0.58 h; kel = 0.968 +/- 0.282 h-1; k21 = 0.943 +/- 0.425 h-1; k12 = 1.004 +/- 0.708 h-1; volume of central compartment = 5.58 +/- 1.67L; volume of tissue compartment = 5.14 +/- 2.12L; plasma clearance = 5.10 +/- 1.14L/h. These results concur with previously published data obtained after oral or intramuscular administration. According to clinical observations, administration of a ketoprofen bolus suppressed pain within 5 to 30 minutes; the administration of a loading dose and a 24-hour infusion is almost never followed by a recurrence of pain, and this regimen was proposed as the dosage schedule of ketoprofen to treat renal colic.

Pharmacokinetics of fluconazole in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of fluconazole given orally (100 mg) or intraperitoneally (50 and 150 mg) were determined in 15 patients with chronic renal failure who were undergoing continuous ambulatory peritoneal dialysis. The half-life (72 to 85 hours) was intermediate between values obtained in healthy volunteers and in patients with renal insufficiency studied during an interhaemodialysis period. The peritoneal clearance, 0.26 to 0.33 L/h, led to an 18% recovery of administered drug in the dialysates after 48 hours. The peritoneal absorption was slow (time to peak plasma concentration 7 hours) but the peritoneal bioavailability was excellent at 87 +/- 5%. The mean concentrations of fluconazole up to 24 hours were 770 and 1900 micrograms/L after single intraperitoneal doses of 50 and 150 mg, respectively. The volume of distribution (40 to 60 L) did not differ from that determined in patients with normal renal function. In the case of fungal peritonitis essentially attributed to Candida spp., a 6-hour intraperitoneal infusion of fluconazole 150 mg every 2 days appears to be a good regimen to rapidly exceed minimum inhibitory concentrations and treat infection without risk of systemic dissemination of fungi or toxicity.

Pharmacokinetics of rilmenidine in patients with chronic renal insufficiency and in hemodialysis patients.

The pharmacokinetics of rilmenidine (1 mg orally) was studied in 3 groups of patients with stable chronic renal insufficiency. This was an open, single-blind study following a single administration, and after 15 days of treatment. Group 1 included 11 patients with a creatinine clearance between 15 and 80 mL/min. Group 2 included 17 patients with a creatinine clearance < 15 mL/min. Group III included 10 hemodialysis patients. In patients with chronic renal failure, total plasma clearance and renal clearance of rilmenidine decreased; terminal half-life was 30-42 hours, which is clearly longer than previous values achieved in healthy volunteers. After repeated administration (1 mg daily in group 1, 1 mg every other day in group 2, 1 mg at the end of each dialysis session in group 3), the area under the curve was significantly increased, corresponding to drug accumulation. The steady state was reached after 6 days in patients in group 1 and after 8 days in patients in group 2. The pharmacokinetics of rilmenidine was linear since the terminal elimination half-life and renal clearance were not significantly different after single and repeated administration of rilmenidine. A positive correlation was found between rilmenidine total plasma clearance and creatinine clearance, and between rilmenidine renal clearance and creatinine clearance. Mean rilmenidine hemodialysance was 85 mL/min, that is, 26% of the rilmenidine renal clearance value achieved in healthy volunteers (330 mL/min). Thus, the following dosage schedule can be proposed. In patients whose creatinine clearance ranges between 15 and 80 mL/min, a 1 mg dose every day can be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of fluconazole in biological fluids by capillary column gas chromatography with a nitrogen detector.

Fluconazole concentrations in biological fluids were determined by high-performance gas chromatography. A simple extraction procedure with chloroform, under basic conditions and after the addition of UK-47,265 as the internal standard and with no evaporation stage, was carried out prior to analysis. A solid injector and a 15-m capillary column, coated with a nonpolar phase and connected to a nitrogen-selective detector that afforded an excellent selectivity and sensitivity, constituted the gas chromatographic system. The duration of each analysis was less than 4 min and the minimum detectable serum concentration was 50 ng/mL. In five patients undergoing chronic peritoneal dialysis, the mean serum concentrations +/- SD at 1, 6, and 48 h after the intraperitoneal administration of a single dose of fluconazole were, respectively, 325 +/- 75, 928 +/- 159, and 607 +/- 80 ng/mL.

Pharmacokinetics of piperacillin in patients on peritoneal dialysis with and without peritonitis.

The pharmacokinetics of piperacillin given intravenously (1 or 2 g) to nine patients with chronic renal failure and undergoing continuous ambulatory peritoneal dialysis was intermediate between values obtained in healthy volunteers and in patients with renal insufficiency studied between dialyses: half-life, 2.4 h; total clearance, 100 mL/min; urinary or peritoneal clearance, 3 mL/min. The intraperitoneal administration of piperacillin in dialysis fluid (400 mg or 1 g to five patients) increased the half-life (6 to 7 h) and decreased the volume of distribution of about two thirds. In both instances, the area under the curve was well correlated with dosage. The absorption of piperacillin by an inflamed peritoneum in eight patients suffering from peritonitis and treated with 400 mg, 1 g, or 2 g, was increased and returned to normal concurrently with care. Consequently, the recommended dosage is intravenous administration of 2 g of piperacillin every 8 h or intraperitoneal administration of 1 g every 6 h in the dialysate. With such conditions, serum concentrations greater than minimal inhibitory concentrations and sufficient to avoid dissemination of piperacillin-susceptible organisms without risk of accumulation are obtained.

Peritoneal ultrafiltration and refractory congestive heart failure.

This prospective nonrandomized study enrolled 16 patients with congestive heart failure [NYHA (New York Heart Association) III and IV] refractory to a maximal well-tolerated drug therapy. The aims were to evaluate if peritoneal ultrafiltration (PUF) could improve clinical conditions and to determine morbidity secondary to resistant congestive heart failure (RCHF) and PUF. There were 16 patients (12 male, 4 female) with a mean age of 65.4 years (56-81 years) and follow-up of 15.6 months (4-33 months). Thirteen patients had RCHF without end-stage renal disease. Patients were classified as NYHA class IV (n = 11) or class III (n = 5). One anuric patient had been on previous hemodialysis and switched to APD. PUF was obtained with a 2-L hypertonic dialysis solution, once a day (n = 7) or every 2 days (n = 4). Clinical improvement was obtained for all the patients. Weight decreased from 72.2 to 66.7 kg with a weekly ultrafiltration of 3.74 L (2.2-6.5 L). Sodium removal was 79 mmol/day (urinary 43%, peritoneal transport 57%). During the follow-up period, 2 patients received a cardiac transplant since 7 died due to cardiac reasons. Mean hospitalization time was 4.4 and 1.20 per patient per day before and after PUF, respectively. Hospitalization was in keeping with either RCHF (36%), dialysis complications (16%), or miscellaneous causes (48%). Our experience showed that a functional improvement and a better quality of life were achieved for all these patients with a low rate of hospitalization.

[Hypercalcemic sarcoidosis and primary hyperparathyroidism disclosed by renal insufficiency]. / Sarcoïdose hypercalcémique et hyperparathyroïdie primaire révélées par une insuffisance rénale.

Primary hyperparathyroidism and sarcoidosis were found in one patient with hypercalcemia and renal failure. Cervicotomy disclosed a parathyroid adenoma and renal biopsy demonstrated interstitial nephropathy. Association of sarcoidosis with hyperparathyroidism, if not fortuitous, has not yet been clearly established.

[Requirements for the successful implementation of unity of care: study of a computer-assisted dispensation of pharmaceuticals]. / Les conditions du succès de l'informatisation de l'unité de soins: à propos d'un logiciel de dispensation pharmaceutique.

PURPOSE: Even though computerized workstations bring undisputed benefits in nursing units, introducing them is still hard when most of the staff members have to share the workstation. We took advantage of the implementation of the drug prescription software SAUPHIX in a nephrology department to better define the encountered difficulties. The workstation described in this paper is shared by physicians who enter their prescriptions (proprietary names, doses, routes of administration), nurses who use dosage schedules for drug administration, and the chemist who has authority to control prescription orders. METHODS: Six months after the implementation of the workstation, physicians and nurses had to fill out an anonymous questionnaire aimed at assessing each function of the software. RESULTS: Prescriptions proved to be more accurate and legible, while management of drugs was more precise. However, interns complained that entering data was time consuming. Furthermore, they raised objections to control of prescription orders. Nurses criticized dosage schedules, the primary reason being that they had to change their practice. The convenience of notebooks was questioned by both physicians and nurses who would have preferred a greater number of desktop computers at their disposition. CONCLUSION: The implementation of a computerized workstation requires information, diplomacy and negotiations to obtain real implication of the staff. Tasks and schedules must be specified for everybody. The system has to be carefully customized, according to the requirement of the unit. Computers must be properly chosen and allocated in sufficient number. Finally, appropriate preparation, staff training and follow-up of the computerized system are essential.

[AA amyloidosis complicating sarcoidosis]. / Amylose AA compliquant une sarcoïdose.

INTRODUCTION: Amyloidosis combined with sarcoidosis has been very rarely described. EXEGESIS: We report the case of a 72-year-old man presenting with sarcoidosis and amyloidosis AA. The association of peripheral and retroperitoneal adenopathies accompanied by loss of weight and histopathological results conducted to the diagnosis of sarcoidosis, excluding other causes. Corticosteroid therapy led to a decrease in clinical manifestations and after 2 years, clinical signs of amyloidosis have not progressed. CONCLUSION: According to results previously described in the literature and the description of the present case, we conclude that sarcoidosis can be complicated by amyloidosis AA, the presence of which may justify corticosteroid therapy.

[Visceral leishmaniasis of favourable course in a patient with renal transplantation]. / Leishmaniose viscérale d'évolution favorable chez un transplanté rénal.

The authors report a case of non fatal visceral leishmaniasis in a renal transplant recipient and underline the fact that immunosuppressive treatments facilitate the occurrence of this disease. In patients with fever, pancytopenia and spleen enlargement, it is capital to inquire whether they have sojourned in a country where leishmaniasis is endemic. The diagnosis is then confirmed by bone marrow examination. Treatment rests on antimony derivatives, but these must be handled with caution in immunocompromised patients.

[Polymorphism of light-chain deposition disease. Apropos of 3 cases]. / Polymorphisme de la maladie des dépôts de chaînes légères. A propos de trois observations.

Three cases of light chain deposition disease are reported. The condition was associated with monoclonal dysglobulinaemia in two cases and with amyloidosis in one case. This, and the different course of the disease in these three patients, illustrates the need for an early histological diagnosis, using immunofluorescence with monospecific anti-light chain sera.

[Nephropathies caused by interferon alpha: apropos of 2 cases]. / Néphropathies secondaires aux interférons alpha: à propos de deux observations.

Two cases reports of interferon alpha-associated nephropathy are reported. The first observation is a membranoproliferative glomerulonephritis and the second a renal microangiopathy. The different cases in the literature are reviewed and the pathophysiology is discussed.

[Captopril treatment of severe arterial hypertension in pregnancy]. / Traitement par captopril de l'hypertension artérielle sévère au cours de la grossesse.

The authors report three cases where captopril was used in pregnancy. This was shown to be more useful in cases of essential hypertension than in toxaemia. There was no bad side effect from the use of Captopril. It did not alter the fetal growth once the hypertension was well controlled. Using it together with other anti-hypertensives has to be thought out very carefully and it has to be used with great care. The state of the newborns at birth was satisfactory. Follow-up was without complications except for one case where was a persistent ductus. Whether captopril had any role to play in this is uncertain. Although these results are good, captopril should not be used as first choice treatment in hypertension.