Treatment Of Renal Transplant Recipients Research Articles

Atorvastatin improves endothelial function in renal-transplant recipients.

Hyperlipidaemia and endothelial dysfunction are common features in cyclosporin A (CsA)-treated renal transplant recipients. Endothelial dysfunction may contribute to the risk of premature atherosclerosis and cardiovascular death in these patients. A beneficial effect of statin therapy beyond cholesterol lowering may be an improvement of endothelial function. The present study was designed to assess the effect of atorvastatin on serum lipids and endothelial function in CsA treated renal transplant recipients. This pilot study was an open trial of 4 weeks atorvastatin (10 mg per day) treatment in renal transplant recipients (n=22). All patients received a CsA- and prednisolone-based immunosuppressive regimen. Endothelial function was assessed in the forearm skin microvasculature by acetylcholine stimulation and laser Doppler flowmetry, before and after atorvastatin treatment. Serum lipids, plasma endothelin-1 (ET-1), nitric oxide (NO), and von Willebrand factor (vWF) were also measured. Both total and LDL cholesterol were significantly reduced by 26.8 +/- 8.4 and 41.5 +/- 11.0% respectively, after 4 weeks of treatment. Endothelial function was significantly improved during atorvastatin treatment, area under the flux versus time curve (AUC)(ACh) was 538 +/- 362 AU x min before and 682 +/- 276 AU x min after treatment (P=0.042). Plasma NO levels also showed a borderline significant increase from 49 +/- 30 to 57 +/- 37 micromol/l during the treatment period (P=0.051), though plasma ET-1 (0.37+/-0.08 vs 0.37+/-0.12 fmol/ml) and vW (196+/-57 vs 197+/-37%) were unchanged. Atorvastatin lowered serum cholesterol significantly and improved endothelial function in renal transplant recipients after 4 weeks of treatment. Plasma NO levels were increased during atorvastatin treatment, indicating a possible endothelial protective effect through an "endothelial-NO pathway".

Induction immunosuppression with interleukin-2 receptor antibodies (basiliximab and daclizumab) in renal transplant recipients

KIDNEY transplantation is the treatment of choice for patients with end-stage renal disease. Acute rejection (AR) episodes are still a major problem in renal transplant recipients (RTR), predisposing them for chronic allograft dysfunction and graft loss. The search for more specific immunosuppressive agents to prolong graft survival has recently led us to focus on anti-interleukin (IL)-2 receptor antibodies (anti-IL-2Rab) in induction therapy. Two anti-IL-2 Rab are now approved for clinical use. They are biologically engineered to contain more human gene regions and fewer murine-derived regions. These are basiliximab (Simulect; Novartis, Basel, Switzerland) and daclizumab (Zenapax; Hoffman-La Roche, Switzerland). Reports of successful clinical trials of these agents in induction treatment of RTR is already available in the literature. These authors found anti IL-2 Rab useful for prevention of AR episodes and reported good tolerability. This paper reports on a prospective study of use of basiliximab (Simulect) and daclizumab (Zenapax) in induction immunosuppression in mismatched first renal transplants in our unit.

Strategies to reduce or replace steroid dosing

Basiliximab is widely used in clinical practice for initial immunosuppressive treatment of renal transplant recipients, seeking to reduce the incidence of acute rejection episodes without adverse events. This retrospective study included 123 renal allograft recipients transplanted at a single center. All were followed for longer than 1 year after transplantation and treated with calcineurin inhibitor and steroid (methylprednisolone) for prophylactic immunosuppression, but basiliximab and mycophenolate mofetil were optional. We compared the outcomes of renal transplant recipients who were versus treated were not with basiliximab as initial immunosuppressive therapy. Basiliximab was used for initial immunosuppression in 42 patients. Their maintenance immunosuppressive treatment included triple (n = 44) or double (n = 79) regimens, including a calcineurin inhibitor (cyclosporine [n = 87] or tacrolimus [n = 36]), methylprednisolone with or without mycophenolate mofetil. Twenty-six (21.1%) patients had a rejection episode within 1 year after transplantation and 22 (17.9%) had infections. Within the first year after transplantation the patients who were treated with basiliximab showed fewer rejection episodes (n = 6, 14.3%) than the patients without this therapy (n = 20, 24.7%), which was not statistically significant (P = .245). However, basiliximab significantly affected the occurrence of rejection episodes among the double immunosuppressive regimen group (P = .006), but not the triple regimen group (P = .098) without an impact on infection episodes (P value of double, triple = .291, .414) within 1 year after transplantation. We concluded that basiliximab was more useful for the recipients treated with double immunosuppression with a calcineurin inhibitor and steroid than for those on a triple regimen including mycophenolate mofetil.

DIETARY VERSUS HMG-Co REDUCTASE INHIBITOR TREATMENT OF HYPERLIPIDEMIA IN RENAL TRANSPLANT RECIPIENTS - PROSPECTIVE, RANDOMIZED STUDY.

652 The aim of this study was to compare efficacy and safety of lipid -lowering diet with HMG-Co reductase inhibitor treatment in renal transplant recipients (TxR) with hyperlipidemia (HL). Despite wide agreement on the serious risks and on the need for aggressive treatment of HL, no consensus has yet been reached on the best management of HL in transplant population. This is because some investigators have found that the diet alone is inadequate, while others point out to the side effects of lipid-lowering drugs. We prospectively studied 30 TxR (21 males and 9 females, aged 24-57 yrs.) presenting with HL at 3-6 mos. after renal transplantation. All patients were immunosuppressed with csa-aza-pred and had stable renal function, no proteinuria or liver dysfunction. The patients were prospectively randomized in 3 groups of 10 pts. each: 1.control-C which received routine dietary recommendations, 2.diet-D which received detailed lipid-lowering diet and was under close supervision of the dietitian, and 3.medication-M which received 10 mg/day of Simvastatin (5pts.) or 20 mg/day of Fluvastatin (5 pts.). All patients were followed up for 3 mos., with monthly physical examinations and biochemical and lipid profile studies. Patients diet and caloric intake were recorded using RECALL questionnaires filled by pts. twice a week. The results are shown in table 1.:TableAt the end of follow up and up to the present no adverse effects or changes in hepatic or renal function were observed in group with medications. Conclusions: in this study HMG-Co reductase inhibitors were found effective and significantly superior to diet in lowering total and HDL cholesterol and in restoration of more favorable LDL/HDL ratio. Post-transplant HL was found generally to be more resistant to dietary treatment, which was effective only in reduction of body weight. These findings, together with demonstrated safety of HMG-Co reductase inhibitors, suggest that these agents may be recommended as first line treatment of post-transplant hyperlipidemia.

Spontaneous tendon rupture after ofloxacin treatment in renal transplant recipients on high-dose corticosteroids

<h2>Abstract</h2> Acute tendon rupture without any history of trauma, a rare complication occurring mainly in metabolic diseases, is increasingly reported after treatment with fluoroquinolones. We report here on the occurrence of Achilles tendinitis and Achilles tendon rupture after ofloxacin treatment for uncomplicated urinary tract infection in four patients receiving high-dose corticosteroid treatment after renal organ transplantation and compare them with a control group without this complication. Patients experiencing tendon rupture had been on regular dialysis treatment for 54.5 ± 39.5 months before receiving cadaveric kidney transplants. All had secondary hyperparathyroidism, with parathyroid hormone levels ranging from 247 to 707 ng/L, had low or normal serum phosphate levels (1.21 to 2.69 mg/dL), and had moderately elevated alkaline phosphatase levels (75 to 285 U/L). Tendon ruptures occurred at a median of 49 days after organ transplantation and 15.3 ± 9.6 days after initiation of quinolone treatment. Mean time of treatment was 5 days. All patients received triple-regimen immunosuppression consisting of methylprednisolone, cyclosporin A, and mycophenolate mofetil. Transplant function was stable, and none had experienced transplant rejection. Mean ingestion of prednisolone ranged from 6 to 16 mg/d, and mycophenolate mofetil from 1 to 2 g/d; cyclosporin A serum levels were 208 ± 76 μg/L. After kidney transplantation, spontaneous large tendon rupture after quinolone treatment is deleterious during the early posttransplantion phase. Secondary risk factors are high-dose corticosteroid treatment and history of secondary hyperparathyroidism. Quinolones should be restricted for treatment of severe urinary tract infection only, which failed to respond to other antibiotic regimens in the early posttransplantation period after kidney transplantation under high-dose corticosteroid treatment.

T-Cell Acute Lymphoblastic Leukemia After Renal Transplantation in Childhood

Lymphoproliferative disorders in solid organ recipients are usually of B-cell type and have rarely been described in childhood. This study describes the development of T-cell acute lymphoblastic leukemia (ALL) in a child occurring 6 years after renal transplantation. An 11-year-old boy had received a renal allograft from his father at 5 years of age. He was receiving imuran, prednisone, and cyclosporin A prophylaxis for graft rejection after transplant until T-cell ALL was diagnosed. Although an acute Epstein-Barr virus (EBV) infection was noted at the time of diagnosis, the EBV genome was not detected by Southern blot analysis and polymerase chain reaction (PCR) in the leukemic cells. A large mediastinal mass and malignant pleural effusion were noted at diagnosis. Leukemic cells of his bone marrow and pleural fluid expressed T-cell antigens with unique cytogenetic features, including add(1)(p36.1), del(11)(q14), and monosomy 7. EBV serology was consistent with a recent infection but EBV genome was not detected by Southern blot and PCR analysis in his leukemic cells. Human T-lymphotropic virus-I (HTLV-I) antibody titer was negative. He has been on chemotherapy for 9 months, maintaining his first remission. Malignancies developing after renal transplantations are usually lymphoproliferative disorders and of B-cell origin. In the majority of these patients, EBV plays an etiologic role. Although adult T-cell leukemia developing during immunosuppressive treatment in renal transplant recipients has been reported, T-cell leukemia after transplant in pediatric patients has not been reported to date. This case is unique in terms of the patient's age, the T-cell immunophenotype, the cytogenetic features, and the absence of an EBV genome within the leukemic cells despite an acute EBV infection before diagnosis.

Mycophenolate mofetil, ATG, and cyclosporine in the induction treatment of renal transplant recipients minimizes the incidence of acute rejection episodes

Mycophenolate mofetil, ATG, and cyclosporine in the induction treatment of renal transplant recipients minimizes the incidence of acute rejection episodes

A bright future for renal transplant therapy

Immunosuppressive antibody therapy has been available since the 1960s, but it is only recently that such therapy has been used more widely. A number of exciting new antibody agents are poised to enter the market and it is likely that their use will increase in the near future. The potential role of these agents in the treatment of renal transplant recipients was discussed at the 32nd Annual Midyear Clinical Meeting of the American Society of Health Systems Pharmacists [Atlanta, US; December 1997].

Pharmacokinetic Cyclosporine A profiles under long-term neoral treatment in renal transplant recipients: Does fat intake still matter?

Pharmacokinetic Cyclosporine A profiles under long-term neoral treatment in renal transplant recipients: Does fat intake still matter?

Growth-hormone treatment of renal transplant recipients: The National Cooperative Growth Study experience—A report of the National Cooperative Growth Study and the North American Pediatric Renal Transplant Cooperative Study

Objective: To evaluate growth response and renal allograft measures after recombinant human growth-hormone (GH) treatment in pediatric renal transplant recipients. Study design: Data on GH-treated children in the National Cooperative Growth Study (NCGS) database were linked to the database of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Data were analyzed for growth rate, graft survival, graft function, acute rejection, and adverse events. Data on 2390 transplant recipients in the NAPRTCS who had at least 24 months of graft function were used in the comparisons. Results: Fifty-nine patients were treated with GH after renal transplantation. One-year growth data were available for 42 of these; 2-year, for 31; and 3-year, for 13. Growth velocity increased from 2.47 ± 1.83 cm/yr to 7.17 ± 2.97 cm/yr after 1 year. Year-2 and -3 growth rates were 5.93 ± 2.29 cm/yr and 6.31 ± 2.32 cm/yr. Height standard deviation score immediately after transplantation was –3.26 ± 1.44 and at the initiation of GH was –3.59 ± 1.15; it increased to –3.18 ± 1.06 at year 1 and to –3.15 ± 0.92 at year 2 and was –3.31 ± 1.00 at year 3. Five-year graft survival was 80% in the GH cohort and 85% in the NAPRTCS cohort. Acute rejection ratio was 1.44 and 1.43 episodes per patient in the GH and NAPRTCS cohorts, respectively. Calculated creatinine clearance at 5 years was 68 and 63 ml/min per 1.73 m 2, respectively. Conclusions: Growth hormone increases growth velocity for up to 3 years without an apparent decrease in graft survival or renal function, and no relation between GH therapy and acute rejection is seen. A randomized, prospective study to evaluate further the safety and efficacy of this promising therapy is required.

Treatment of hyperlipidemia in renal transplant recipients.

Treatment of hyperlipidemia in renal transplant recipients.

Fibrinolysis and serotonin under cyclosporine a treatment in renal transplant recipients

Cyclosporine A (CyA), a potent immunosuppressive drug, has been used in renal transplant recipients with increasing frequency since 1982. Despite its efficacy, CyA therapy has been associated with an increased incidence of thromboembolic complications. This has been attributed to increased thromboxane production, reduced prostacyclin synthesis and increased platelet aggregability. The coagulation system is also altered in CyA-treated patients and some of these changes would favor thrombosis. Increased fibrinogen and FVII:C levels have also been associated with an enhanced risk of thrombosis. In contrast, CyA therapy was reported to increase the levels of antithrombin III and protein C, two proteins known to protect against venous thromboembolism. However, the possible effect of CyA on the fibrinolytic system has not been thoroughly investigated and rather confusing data have been reported concerning both enhancement and suppression of fibrinolysis. Serotonin (5-hydroxytryptamine, 5-HT) may play a role in hemostasis and platelet/vessel wall interactions. It may facilitate platelet thrombus formation by potentiating the aggregatory response to other agents such as ADP, collagen or epinephrine and by causing vasoconstriction. Taking all these data into consideration we have measured some fibrinolytic parameters, whole blood and plasma serotonin concentration in cyclosporine A- and non-cyclosporine A-treated kidney transplant recipients.

Increased Serum Erythropoietin Level during Azathioprine Treatment in Renal Transplant Recipients

One hundred and six renal transplant patients were studied. During the first 12 months after renal transplantation all patients were treated with cyclosporine (Cy) and prednisone. At 12 months after transplantation the patients were randomly allocated to either conventional treatment with azathioprine (Az) and prednisone (group Az) or to continued treatment with Cy and prednisone (group Cy). Serum erythropoietin (s-EPO), glomerular filtration rate (GFR) and hematocrit (Hct) were measured at 12, 18 and 24 months after transplantation. s-EPO rose in the group Az from 19 U/l (mean) at 12 months to 28 U/l (p < 0.01) at 18 months and remained elevated at 24 months at 29 U/l compared with baseline level and with healthy subjects without anemia 18 U/l (p < 0.01). There was no significant change in s-EPO in group Cy during the study. The Hct in the two groups was not significantly different. GFR was the same in the two groups at 12 months and after 24 months. In conclusion, a switch from Cy to Az 1 year after renal transplantation results in a sustained rise in s-EPO which may in part represent a compensatory phenomenon to bone marrow suppression.

Variations in envelope sites during corticosteroid treatment of renal transplant recipients evaluated by radiological measurements on metacarpal bone

Variations in envelope sites during corticosteroid treatment of renal transplant recipients evaluated by radiological measurements on metacarpal bone