Assessing a pharmacist-run anaemia educational programme for patients with chronic renal insufficiency.

OBJECTIVE: Assessment of a pharmacist-run anaemia educational programme for patients with chronic renal insufficiency. SETTING: Nephrology Department, Grenoble Hospital, France. METHOD: A 12-week prospective study, using a before-after intervention design. Included in the study were predialysis outpatients with a haemoglobin level < 10 g/dl, de novo EPO prescription; judged qualified by the nephrologist for self-injections; accepting self-injections. The intervention was a single one-hour individual session between the pharmacist and the patient to target (1) medical and therapeutic information; (2) information on the device, a pen used with a cartridge of beta epoietin; (3) training with the pen; and (4) self-injection of the first dose by the patient, in front of the pharmacist. Main outcome measures were knowledge (7-item questionnaire); handling skills (observation) and Quality of Life (1 Likert scale on apprehension towards self-injections and 3 Linear Analog Scales on energy, daily activities, and general well-being); compliance (self-report on self-administered injections) and haemoglobin level. RESULTS: Ten patients were followed for 3 months after intervention. The evolution of the knowledge was positive but not statistically significant after the programme (80% of good answers before; 93% 3 months later). Concerning the patients' skills, difficulties with the pen were important at inclusion, (1) to reset the pen into zero position (2.8 tries/patient +/- 1.8); (2) to insert a new cartridge (1.9 +/- 1.1); and (3) to take air out of the cartridge (2.3 +/- 1.2). After the session, results were satisfactory, since 3 months later, all patients were still on self-injections. QoL improved significantly over the study period respectively on energy, daily activities, and general well-being. The mean level of compliance remained above 90% at 3 months for 8 out of 10 patients. Patients reached the haemoglobin target value of 11 g/dl during the second month of treatment. CONCLUSION: A tailored educational programme conducted by a pharmacist is beneficial for anaemia patients with chronic renal insufficiency. The programme seems to result in a high level of compliance, leading to an optimal haemoglobin level within two months.

A case of arthritis caused by cytomegalovirus after kidney transplantation.

Cytomegalovirus (CMV) is the leading cause of infectious complications after organ transplantation. We report the case of a 55-year-old renal transplant recipient who presented with CMV infection 2 months after transplantation. During oral ganciclovir treatment (5 weeks after interruption of intravenous ganciclovir), he experienced a sharp pain in the right shoulder. Examination was normal, but CMV antigenemia remained positive with 30 cells/300,000. He underwent a shoulder puncture, which confirmed the presence of CMV in the articular fluid after evaluation by polymerase chain reaction gene amplification. The patient recovered from his arthritis of the shoulder, and antigenemia became negative after 3 weeks of parenteral ganciclovir. We describe a CMV arthritis that occurred despite a curative treatment for CMV disease, and comment on the pathogenesis of this infection, the pharmalogical failure, and dosing or treatment duration.

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.

Urinary F2-isoprostanes formation in kidney transplantation.

BACKGROUND: Oxygen free-radical mediated lipid peroxidation has been implicated in many diseases such as chronic renal failure, hemodialysis and chronic kidney transplant rejection. However, insight into the role of free radical generation in kidney transplantation has been constrained by the limitations of current indexes of oxidant stress in vivo. Isoprostaglandin F2alpha type-III (iPF2alpha-III, formerly known as 8-iso-prostaglandin F2alpha) is emerging as a reliable marker of oxidant stress in vivo. The purpose of our study was to investigate iPF2alpha-III formation as an index of lipid peroxidation in the 5 d following kidney transplantation. METHODS: Urinary iPF2alpha-III measurements were performed by enzyme immunoassay from day I to 5 in 11 patients undergoing kidney transplantation. Results were compared with 11 healthy volunteers matched in sex, age and cigarette smoking. RESULTS: Urinary excretion of iPF2alpha-III at day 1 did not significantly differ between control and transplant group (111 +/- 17 vs. 92 +/- 10 pM/ mM creatinine, respectively, NS). Urinary iPF2alpha-III levels did not differ between day 1 to 5, and were not correlated to cold ischaemia time. CONCLUSION: Our study shows no evidence of enhanced lipid peroxidation in the first 5 d following kidney transplantation.

Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients.

INTRODUCTION: A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) in a triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar (approximately 40%) with a trend for better renal function with sirolimus. METHODS: In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n = 40) or CsA (n = 38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured. RESULTS: At 12 months, graft survival (92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11, P = 0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often. DISCUSSION: Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection.

[Economic contribution of mofetil mycofenolate as preventive immunosuppressive treatment after renal transplantation from cadaver]. / Apport économique du mycophénolate mofétil comme traitement immunosuppresseur prophylactique après transplantation rénale de cadavre.

OBJECTIVES: The economic impact resulting from the clinical consequences of immunosuppressive strategy using mycophenolate mofetil in new renal transplant recipients was conducted considering the viewpoint of the health insurance system. METHODS: The analysis was based on the results of three controlled randomized double-blind clinical trials comparing mycophenolate mofetil with placebo or azathioprine in 1003 out of 1493 included patients respectively. Health care costs associated with each event were determined by 7 French experts in renal transplantation working in six different hospitals. Direct cumulative costs for each strategy were compared. RESULTS: The studies demonstrated a difference in the incidence of acute rejection and treatment failures whatever the cause. The three trials showed that, compared with current strategies, use of mycophynolate mofetil in the immunosuppression protocol generated a 19 to 38% cost reduction during the 6 months after transplantation. Cost reduction resulted from lower incidence of acute rejection and the subsequent nephrectomics and dialysis sessions. The sensitivity analysis on the most important cost factors-cost of hospitalization per day and number of hospitalization days-confirmed strength of the results. CONCLUSION: Use of mycophenolate mofetil in the immunosuppressive prophylaxis protocol after renal transplantation allows a reduction in the direct costs during the 6 months following transplantation.

[Hematotoxicity caused by azathioprine genetically determined and aggravated by xanthine oxidase deficiency in a patient following renal transplantation]. / Hématotoxicité de l'azathioprine à déterminisme génétique aggravée par un déficit en xanthine oxydase chez une transplantée rénale.

Azathioprine is an immunosuppressor used with ciclosporin and corticosteroids after organ transplantation. Azathioprine is rapidly transformed into 6-mercaptopurine which in turn is metabolized by three competitive pathways: a) intracellular hypoxanthine guanine phosphoribosyl transferase leads to 6-thioguanine nucleotides which can damage chromosome DNA; b) thiopurine methyltransferase produces inactive methylated derivatives; c) xanthine oxidase produces thiouric acid. Due to inter-individual variations in the later two pathways, azathioprine dose must be adapted to each patient. A 48-year-old female patient underwent renal transplantation in 1994 and was given immunosuppressive therapy combining thymoglobulins, azathioprine and ciclosporin. Severe leukopenia (< 3000/mm3) occurred on day 5 requiring withdrawal of azathioprine. Known hypouricaemia (< 50 mumol/l) suggested xanthine oxidase deficiency. Laboratory results confirmed xanthine oxidase deficiency and also revealed reduced thiopurine methyltransferase activity (14.9 pmol/h/mg Hb). Azathioprine toxicity was confirmed by regression of the leukopenia after withdrawal and recurrence at rechallenge. Xanthine oxidase deficiency occurs in 2% of the general population. Reduced thiopurine methyltransferase activity affects 11% of the population. The combined presence of these two genetic anomalies led to early and sudden intolerance to azathioprine and emphasize the need to develop new immunosuppressor agents degraded by other metabolic pathways.

Beneficial effect of one HLA haplo- or semi-identical transfusion versus three untyped blood units on alloimmunization and acute rejection episodes in first renal allograft recipients.

Acute allograft rejection is the major risk factor of renal function decline and graft loss. Beside histocompatibility matches and pharmacological immunosuppression, blood transfusion is empirically used to detect responder subjects and to induce immune tolerance. Alloimmunization associated with blood transfusions readily detected by anti-HLA antibodies could induce acute vascular rejection episodes during the early period after grafting. Our open prospective study was aimed at analyzing the 1 year follow-up of 105 successive first cadaver renal transplant recipients according to the transfusion protocol as assessed by anti-HLA antibody production, acute rejection episodes, and graft survival. Our conventional transfusion protocol involved 3 nonphenotyped blood transfusions set up at least 20 days before grafting in a control cohort (group A) and was compared with a single pretransplant HLA haplo- or semi-identical blood transfusion in a successive group of patients (group B). Our results suggest that both protocols were associated with similar 1-year graft survivals (> 96% in both groups) and number of patients experiencing rejection episodes (20.7% in group A; 9.6% in group B; P NS). HLA haplo- or semi-identical transfusion was significantly beneficial in naive patients without previous alloantigen contact by pregnancy or blood transfusions during dialysis. Naive patients in group B did not develop post-transfusion anti-HLA antibodies compared to naive patients in group A (16.6%; P < 0.001), and they experienced significantly less acute rejection episodes (2.7%) compared to group A naive patients (20.8%; P = 0.02).

[Influence of kidney procurement techniques on urologic and vascular complications of the transplantation]. / Influence des techniques de prélèvement de rein sur les complications urologiques et vasculaires de la transplantation.

Surgical complications of renal transplantation, rejection and infectious diseases are factors contributing to poor renal graft survival. Factors directly concerning the donor can be involved in graft failure: age, medical history, causes of donor brain death. Urologic or arterial anatomic variations are often the source of difficult surgical conditions during renal transplantation. Technical errors during graft procurement must be avoided such as excess of traction or coagulation. Failure in perfusion preservation. As few renal grafts are available, it is thus essential to obtain optimal conditions to avoid failure in cadaver donor graft linked to technical errors during organ procurement.

[Multiorgan procurement (MPO). Who? How? What results?]. / Le prélèvement multi-organe (PMO). Qui? Comment? Quels résultats?

Between 1985 and 1988, 156 organs were harvested using a multiorgan procurement technique (MPO) in the Urology Dept of Grenoble University Hospital (50 MOP). All the organs transplanted either in Grenoble or in other centers have been followed up after transplantation to try to appreciate their value and function. The surgical procedure is described, and results, organ by organ, are given. The conclusion is that the MOP technique is perfectly usable and reliable without jeopardizing any of the transplanted organs.

[Mixed cryoglobulinemia with necrotizing angiitis. Apropos of 2 cases]. / Cryoglobulinémies mixtes avec angéites nécrosantes. A propos de deux observations.

Out of a series of 26 personal cases, 2 cases of mixed IgM-IgG cryoglobulinemia, one type II the other type III, are reported because they were associated with histologically proven necrotizing vasculitis. In both cases the numerous symptoms were due to renal damage (the vasculitis was discovered in the kidney) and to peripheral neuropathy. One of the patients died; the other had severely deteriorated general condition and required substitution hemodialysis. Cases of vasculitis associated with mixed cryoglobulinemia have often been published, but there are few reports mentioning necrotizing vasculitis; a search in the literature yielded only 9 cases. This small number does not mean that mixed cryoglobulinemia should not be listed among the causes of necrotizing vasculitis, but it makes it difficult to extract those specific features that would enable to predict which case of mixed cryoglobulinemia is associated or not with necrotizing vasculitis.