Cyclosporine microemulsion formulation (sigmasporin microral) effect as first-line immunosuppressant on renal functions at 3 years.

BACKGROUND: Cyclosporine (CsA) remains a mainstay of immunosuppressive maintenance regimens in developing countries, but its effects on long-term kidney allograft survival are still unclear. Our aim was to assess a generic microemulsion CsA (Sigmasporin) for long-term impact on graft function and patient survival among stable renal transplant patients. METHODS: Over a 36-month period, patients with transplantations from >6 months earlier were maintained on CsA doses of 2-8 mg/kg/d to keep C(2) within the recommended therapeutic range. We assessed 25 efficacy and tolerability parameters of scheduled intervals. RESULTS: Twenty-seven patients (9 female, 18 male) from 6 centers in 4 Middle-Eastern countries were enrolled between 2004 and 2009. Their average age was 35.1 ± 9.8 years, body mass index ranged from 15.7 to 41.2 kg/m(2), and average time from transplantation was 2.2 ± 1.6 years. Within the 36-month observation period the CsA dose was reduced by 17.3% from 2.89 ± 0.88 mg/kg/d to achieve C(2) levels of 600-1000 ng/mL. After 36 months the glomerular filtration rate declined by 8.2% from an overall baseline mean of 72.7 ± 23.5 mL/min/1.73 m(2). It improved in 11.1% of patients and remained unchanged in 44.4%. No new cases of hypertension or diabetes mellitus were reported, and there was 1 case of borderline hyperlipidemia. Graft functions were stable, apart from 2 incidences of CsA nephrotoxicity. Both graft and patient 3-year survival rates were 100%. CONCLUSIONS: On a 3-year basis, Sigmasporin Microral was effective to maintain stable renal functions in kidney transplant patients, with safety and tolerability profiles similar to those reported in the international literature.

It takes time after bilateral nephrectomy for better control of resistant hypertension in renal transplant patients.

UNLABELLED: Severe resistant hypertension in end-stage renal disease patients has traditionally been an indication for bilateral nephrectomy (BN) before kidney transplantation. Nevertheless the influence of BN on successful control of hypertension has not been well documented. We sought to clarify the effect of BN on blood pressure patterns and control in renal transplant patients. MATERIALS AND METHODS: We retrospectively reviewed 28 patients who underwent BN between November 2003 and May 2009 before or after kidney transplantation. Nineteen of them were under treatment with 4 or 5 antihypertensives according to the international guide lines; they had BN for resistant hypertension. They were considered as group 1 (G1). Nine patients operated for indications other than resistant hypertension; they constitute group 2 (G2) and considered as a control group. All patients received triple immunosuppression according to our local protocol. BN was done either before, simultaneously or after transplantation. Antihypertensives were recorded before and after BN. We evaluated our patients at 3 months, 1 year, and 3 years. Acute rejection episodes and calcinurein nephrotoxicity were reported. RESULTS: In G1, the mean age was 30.2 years (range, 10-62). In G2, the mean age was 33.6 years (range, 11-61). Before BN, G1 patients used antihypertensive drugs (3.6 +/- 1.05 drugs per day; mean +/- SD), which was significantly higher than in G2 patients (2.0 +/- 1.65 drugs per day; P = .02). Three months after BN, G1 patients used 2.6 + 0.9 drugs per day, with gradual reduction in number of antihypertensives to 1.4 +/- 1.3 drugs per day at 3 years (P = .008). In G2, there was reduction in antihypertensive drug number per day, which was insignificant during the follow-up period. No difference was noted between G1 and G2 drug administered after BN. We conclude that BN is effective to help blood pressure control, in resistant hypertension in renal transplant patients, but it starts to show up 3 months after surgery, and continues to work for a year and more.

Six-month clinical outcome of cyclosporine microemulsion formulation (Sigmasporin Microral) in stable renal transplant patients previously maintained on sandimmun neoral.

The trial objective was to investigate the feasibility and safety of conversion to a generic microemulsion cyclosporine in stable renal transplant patients premaintained on Neoral. We enrolled 75 patients from seven centers in five Middle Eastern countries monitored them for 6 months after conversion to Sigmasporin Microral. Readings at 0, 0.5, 1, 2, 3, 4.5, and 6 months included cyclosporine blood level, serum creatinine, liver enzymes, lipid profile, blood sugar, blood pressure and adverse events. Patients included 54 men and 21 women of mean age 38.9 +/- 10.7 years at 30.3 +/- 29.3 months post-transplantation maintained on Sigmasporin Microral dose of 2.8 +/- 1.0 mg/kg per day; they were observed to be stable throughout the study period as reflected by the therapeutic blood C0 level of 181.6 +/- 102.1 and C2 of 759.2 +/- 384.4. Their absorption profile as represented by C2/C0 was 4.9 +/- 2.8, and C2/cyclosporine dose of 282.3 +/- 128.8. An average serum creatinine level of 116.1 +/- 29.5 micromol/L denoted stable graft function and their liver enzymes did not change during the study. No new-onset cases of hypertension, diabetes mellitus, or hyperlipidemia were reported among the patients. Graft function was stable for all patients, except for two incidences of mild acute rejection and two of mild cyclosporine nephrotoxicity; graft and patient survival rates were both 100%. Results of this 6-month study showed that Sigmasporin Microral was effective to maintain stable renal function in kidney transplant patients converted from Neoral with similar safety and tolerability profiles as those reported in the literature.

Therapeutic equivalence and mg:mg switch ability of a generic cyclosporine microemulsion formulation (Sigmasporin Microral) in stable renal transplant patients maintained on Sandimmun Neoral.

We tested a hypothesized pharmacokinetic difference between the reference (Sandimmun Neoral) and test (Sigmasporin Microral) products to prove therapeutic equivalence in an open, multiple fixed dose, one-way crossover, multicenter, and multinational study over a period of 29 days. Forty two stable renal transplant recipients maintained on Sandimmun Neoral were enrolled. Whole blood was collected at day 14 of the study at 0, 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after reference dosing and the same schedule was repeated at day 29 after switching on an mg:mg basis to the test product at day 15 of the study. Analysis of variance was performed for the pharmacokinetic parameters (area under the curve [AUC]0-12, maximum concentration [Cmax]) of cyclosporine using log-transformed values. Tolerability was assessed by vital signs, adverse events, and laboratory investigations. The 90% confidence interval (CI) test for the Ln-transformed, pharmacokinetic parameters was all within the US Food and Drug Administration acceptable range of 80% to 125%, as Ln area under the steady-state curve (AUCss) was within the range of 92.56 to 103.55 and Ln Cmax was within the range of 85.73 to 103.58; the same also applied for AUC0-4, which may be considered the area of greatest inter- and intra-patient variability. Furthermore, in line with the newly adopted recommendations of the Expert Advisory Committee on Bioavailability and Bioequivalence of Health Canada, the 90% CI for AUCss was within the narrow range of 90% to 112%. No significant difference in tolerability was recorded between the two products. Sigmasporin Microral (Julphar) was found to be bioequivalent and clinically interchangeable on an mg:mg basis with Sandimmun Neoral (Novartis).

Postrenal transplantation urologic complications.

OBJECTIVES: We sought to explore the incidence, risk factors, clinical presentation, management options, and outcomes of post renal transplant urologic complications. PATIENTS AND METHODS: Between November 1993 and December 2005, we performed 646 renal transplantation procedures in 373 males and 273 females, of whom 81 were children. Kidney grafts were obtained from 461 living and 185 cadaveric donors. The medical records were retrospectively reviewed for urologic complications. Affected patients presented clinically with impaired kidney function: the diagnosis was confirmed by ultrasound scanning, isotope renal scanning, magnetic resonance urography, and/or antegrade urography. Ureteric stricture was managed by percutaneous antegrade ureteric dilatation and stenting, or by surgical reconstruction. Urine leak was treated by prolonged bladder drainage or surgical reconstruction. Renal stones were treated with extracorporeal shockwave lithotripsy. RESULTS: Urologic complications were detected in 31 recipients (4.8%), including 21 males and 10 females, among whom 4 were children. They had received kidney grafts from 19 living and 12 cadaveric donors. Urologic complications were ureteric strictures in 15 (2.58%), urine leaks in 15 (2.58%), and ureteric stone in 1 (0.17%) recipients. There was no graft loss to urologic complications. CONCLUSIONS: The incidence of post-kidney transplant urologic complications was 4.8%. They were more common among male recipients and after cadaveric kidney transplantation. Although ureteric stricture presented late posttransplantation and was more common among children (4.23%), urine leak presented early and was more common in the elderly (4.69%). All urologic complications were successfully managed, with no graft loss.

Kuwait experience in laparoscopic donor nephrectomy: first 80 cases.

INTRODUCTION: Laparoscopic donor nephrectomy (LDN) has been adopted rapidly as it offers less postoperative pain, early recovery, and better cosmetic results compared with the open approach. This prospective study investigated the results of the first 80 LDN performed between May 2005 and May 2006, with regard to donor morbidity and effect on graft function. PATIENTS AND METHODS: LDN was attempted in 80 donors by one surgical team. Donors included 68 men and 12 women, ages 22 to 53 years, with body mass indices of 17.9 to 42.4. According to computed tomographic angiography, left nephrectomy was planned in 75 donors and right nephrectomy in 5. RESULTS: LDN was completed successfully in 74 (92.5%) and converted to open in 6 (7.5%) secondary to technical difficulties and operative bleeding. The mean operating time for LDN was 186.16 minutes (range, 95-260 minutes). Mean warm ischemia time (WIT) was 5.7 minutes (range 2-16 minutes). Mean hospital stay was 5.28 days (range, 3-14 days). Two donors (2.5%) were reexplored for postoperative bleeding. Renal function in all donors was satisfactory within 3 months of surgery. Immediate diuresis occurred in 76 (95%) recipients. Acute cellular rejection was diagnosed in 1 recipient. No association was observed between WIT, graft function, development of acute tubular necrosis (ATN), or rejection. Plasma creatinine normalization was clearly associated with donor age. CONCLUSIONS: LDN was found to be a safe procedure with low postoperative morbidity and short recovery time for donors. It can potentially increase the donor pool.

Renal transplantation in children.

OBJECTIVE: Renal transplantation is the preferred method for the treatment of children in end-stage renal disease (ESRD). In this retrospective study, we analyzed the results at our center. PATIENTS AND METHODS: Between November 1993 and June 2006, 86 children (50 boys and 36 girls) received organs from 50 living donors (LDTx) and 36 cadaveric donors (CDTx). Twenty children were <10 years. In addition to ESRD, some patients had one or more other high-risk factors, eg, abnormal lower urinary tract in 36 recipients (42%). The procedure was a preemptive transplantation in 28, and a retransplantation in 9 recipients. Induction immunosuppression used either antithymocyte globulin (43 cases) or anti-interleukin-2 receptor antibodies (20 cases). RESULTS: Patients were followed for 6 to 150 months. There were 24 surgical complications (28%), 26 acute rejection episodes (33%), and 17 of systemic bacterial or viral infections. Two recipients died at 1 and 21 months. The 14 grafts were lost at 1 day to 87 months. The 1- and 10-year actuarial survival rates were 99% and 98%, respectively, for the recipients, and 88% and 84%, respectively, for the grafts. The 10-year actuarial graft survival rates were 98% in LDTx and 64% in CDTx; 86% in recipients >10 years old and 75% in recipients <10 years old. Abnormal urinary tract, pretransplantation dialysis, and transplant number showed no effect on graft survival. All pediatric recipients with functioning grafts are fully rehabilitated. CONCLUSION: Renal transplantation is the preferred method of treatment for children in ESRD. Higher graft survival rates were achieved in older children and following LDTx.

Oral valgancyclovir versus intravenous gancyclovir for cytomegalovirus prophylaxis in kidney transplant recipients.

BACKGROUND: Prophylaxis against cytomegalovirus (CMV) is a regular practice in organ transplantation. Oral valgancyclovir appears to be an interesting alternative to the usual intravenous form. PATIENTS AND METHODS: We prospectively compared the response of intravenous gancyclovir for 2 weeks (GAN; n=41) to oral valgancyclovir for 2 weeks (VAL2w; n=23) or 3 months (VAL3m; n=46) in kidney transplant recipients receiving induction immunosuppression. CMV antigenemia assay and/or polymerase chain reaction (PCR) were used for viral detection. Patients were followed for a minimum of 6 months posttransplantation. SPSS software was used for statistical analysis using a cutoff of significance as P<.05. RESULTS: There was no statistical difference in the demographic features among the study groups. However, human leukocyte antigen (HLA) match was better in the VAL3m group and the patients of this group received less ATG induction immunosuppression (41.3%) compared with the GAN group (100%). The incidence of acute rejection was not different among the study groups. There was a higher incidence of fever with positive CMV tests in the VAL2w group (P=.035) compared with the other groups, while leukopenia with a negative CMV test was significantly higher in the VAL3m group (P=.04). The incidence of CMV disease was higher in the VAL2w group (30.4%) compared with the GAN group (14.6%) or the VAL3m group (8.7%). Renal function was significantly worse in the VAL2w group at 3 and 6 months (P=.011 and .02, respectively). CONCLUSIONS: Three months oral valgancyclovir prophylaxis for CMV was a more effective regimen compared with intravenous gancyclovir for 2 weeks. Shorter courses were associated with a higher incidence of CMV infection and poorer graft function. Leukopenia observed in patients receiving valgancyclovir may be a drug-related side effect.

Hyperinfection strongyloidiasis: an anticipated outbreak in kidney transplant recipients in Kuwait.

BACKGROUND: Hyperinfection strongyloidiasis is a potentially fatal syndrome associated with conditions of depressed host cellular immunity. A high degree of suspicion is required to detect cases early and thereby avoid a fatal outcome. PATIENTS AND METHODS: Three consecutive cadaveric kidney transplant recipients died within 2 months from hyperinfections with strongyloides. All members of the transplant team were involved in a campaign to localize the source of infection, identify and treat affected patients, and provide adequate prophylaxis to other transplant recipients. We reviewed cadaveric donor files and screened 61 hospital personnel, 27 hospital inpatients, and the 87 hospital outpatients transplanted in a year's time before that event for a possible source. The screening test included analysis of fresh stool samples on 3 consecutive days for strongyloides larvae. The anti-helminthic drug albendazol was administered to all patients during screening. They were followed for possible development of the disease during the infectivity period. RESULTS: The first 2 recipients received their kidneys from 1 cadaveric donor, while the third received it from a different donor. Both donors came from areas endemic for strongyloidiasis. The 3 recipients were on tacrolimus-based immunosuppression. The twin recipient of the second kidney was on cyclosporine and did not manifest a disease. All stool samples taken for screening were negative for the infective larvae. None of the other recipients developed the disease. CONCLUSIONS: Cadaveric donors were the possible source for this outbreak. Cyclosporine probably has a protective effect against strongyloides. In our setting, screening of cadaveric donors for strongyloides is mandatory before accepting them for donation, and oral prophylaxis is required for all recipients.

Outcome of renal allografts with multiple arteries.

BACKGROUND: Renal allograft transplantation with multiple arteries (MRA) was always avoided as much as possible as it is technically demanding and carries a higher MSK for complications. This was a single-center study to explore the graft outcomes of kidney transplantation with MRA. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 35 patients who received kidney grafts with MRA for the surgical technique, surgical complications, graft function, and graft survival. The results were compared with those achieved in recipients of kidney grafts with a single renal artery (SRA). RESULTS: Of 35 grafts, there were 2 renal arteries in 30 grafts, and 3 renal arteries in 5 grafts. In the MRA group, there were 7 instances of surgical complications, the mean serum creatinine levels were 122, 139, and 156 micromol/L at 1 month, 1 year, and 5 years, respectively, and the actuarial graft survival rates were 94.3%, 88.6%, and 83% at 1, 5, and 10 years, respectively. In the SRA group, there were 56 instances of surgical complications, the mean serum creatinine levels were 115, 121, and 141 micromol/L at 1 month, 1 year, and 5 years, respectively, and the actuarial graft survival rates were 93.7%, 88.1%, and 84.4% at 1, 5, and 10 years, respectively. CONCLUSION: Although transplantation of MRA grafts might carry a relatively higher risk for complications, it is justified because it gives results comparable with those achieved in SRA.

Renal allograft venous thrombosis is salvageable.

BACKGROUND: Renal vein thrombosis (RVT) is an uncommon but serious complication. It usually occurs early after surgery. While compression of the renal vein is the most common cause, early rejection and hemostatic defects are other known causes. The symptoms are nonspecific and diagnosis is often delayed. Ultrasonography and renal isotope scan findings may resemble acute rejection or acute tubular necrosis. PATIENTS AND METHODS: We retrospectively reviewed the records of 684 recipients who were transplated between November 1993 and May 2006. The diagnosis of RVT was suspected by an unexplained drop in urine output, rise in serum creatinine, or hematuria, and confirmed by Doppler ultrasound and isotope scanning. Urgent exploration was performed in all suspected cases. RESULTS: Seven incidences of biopsy-proven RVT were encountered, including 3 associated with hematoma and 1 with rejection. Four grafts were from cadaveric donors. Three grafts were salvaged. CONCLUSIONS: The incidence of RVT in the present series was 1%. All cases developed in the first 2 weeks after transplantation. It was more common in adults, in female recipients, and in cadaveric grafts. Early diagnosis and intervention were the keys to salvage.

Lymphedema: an unusual complication of sirolimus therapy.

INTRODUCTION: Lymphedema is an increasingly observed complication of sirolimus (SIR) therapy. In this report, we describe four renal recipients with SIR-induced lymphedema of varying severity. CASES REPORTS: Patient 1, a 38-year-old man developed lymphedema of the left upper limb after being exposed to SIR for 30 months (mean daily Rapamune dose, 3 mg; trough level, 10-18 ng/mL). Venography and duplex ultrasound were normal. Lymphangiography was showed delayed lymphatic drainage. SIR was replaced with Prograf with significant improvement in the lymphedema over the next 6 months. Patient 2, a 26-year-old woman, developed lymphedema of the left lower limb at 24 months after starting SIR (mean daily dose, 3 mg; trough level, 10-15 ng/mL). Lymphangiography showed delayed drainage of lymphatics in the left lower limb. The patient was shifted to Prograf and there was some improvement over the next 4 months. Patient 3, a 28-year-old man, developed lymphedema of the left upper limb at 24 months after the start of SIR (mean daily dose, 2 mg, trough level, 6-15 ng/mL). Lymphangiography showed evidence of lymphatic obstruction. SIR was changed to cyclosporine with only mild improvement in lymphedema over the next 6 months. Patient 4, a 46-year-old man, developed lymphedema of the right upper limb at 7 months after starting SIR (mean daily dose, 6 mg; trough level, 10-16 ng/mL). Lymphangiography showed complete blockage of the lymphatic channels. SIR was changed to cyclosporine and there was mild improvement in lymphedema over the next 8 to 10 months. CONCLUSION: The exact mechanism of SIR-induced lymphedema is unknown. The absence of other demonstrable etiologies and spontaneous improvement after discontinuation of SIR suggest that this drug was the responsible factor in these four patients. It occurred 7 to 30 months after transplantation. This is the fourth such report in the literature to the best of our knowledge.

Single daily dose administration of cyclosporine in renal transplant recipients.

Cyclosporine (CsA) microemulsion has been the mainstay immunosuppressive agent for renal transplant recipients for years. A single daily dosing of cyclosporine (SD) is rarely used. The objective of this study was to evaluate the efficacy of SD versus twice daily dosing of CsA. Retrospective evaluation of SD use was conducted for 44 renal transplant recipients for 12 months (study group). Equal numbers of matched recipients were selected for age, sex, HLA mismatch, donor type, and immunosuppressive regimen (control group). We measured CsA trough (C0) and peak (C2) blood levels, 12-hour CsA profile, and the area under the concentration-time curve (AUC). There were significant differences in C0, C2, and calculated AUC after shifting to SD. In the study group, the mean AUC was 4619 ng/mL/h before versus 6567 ng/mL/h after shifting to SD (P=.004). This became more therapeutic and identical to the mean AUC in the control group, which was 6551 ng/mL/h. Total daily CsA dose was significantly lower in the study group compared with the control group (P<.0001). A significantly higher incidence of hepatitis was observed among the study group (P=.011). There were significantly fewer adverse effects in patients in the study group than the control group. There were no significant differences in graft and patient outcomes between the groups. We concluded that CsA dose should be individualized in renal transplant recipients especially if they have viral hepatitis. SD has the advantage of decreasing dosage and CsA-related adverse effects while maintaining optimal graft function.

De novo Crohn's disease in a renal transplant recipient.

The prevalence of inflammatory bowel disease (IBD) after renal transplantation is affected by the immune tolerance and the modality of immunosuppression. Mycophenolate mofetil (MMF) may have a promoting effect on the development of posttransplantation erosive enterocolitis and a Crohn's disease-like pattern of colitis. We have presented a 40-year-old man with end-stage renal disease due to chronic glomerulonephritis who commenced hemodialysis for 2 months before receipt of a live unrelated renal transplant. He developed early posttransplantation diabetes mellitus and an anti graft rejection episode, which responded to a methylprednisolone pulse and OKT3 treatment. His immunosuppressive regimen included prednisolone, MMF, and tacrolimus. Three years after transplantation, he developed mild constitutional symptoms, mouth ulcerations, and chronic intermittent bloody diarrhea. Colonoscopy showed active segmental colitis with aphthous ulcers, involving the proximal descending colon and the splenic flexure. Colonic biopsies showed distended and branched crypts in the ascending colon, moderate active chronic colitis with regenerative atypia, skipping appearance, and ulceration in the splenic flexure and descending colon. The edematous crypts were associated with ulcerations in the sigmoid colon and rectum. The features were highly suggestive of Crohn's disease. He was successfully treated with high-dose steroids and 5-aminosalicylic acid. Subsequently, he developed chronic transplant glomerulopathy and restarted hemodialysis. We concluded that de novo Crohn's disease may develop in renal transplant recipients despite immunosuppressive therapy especially with MMF immunosuppression.

Lymphocele following renal transplantation.

We attempt in this retrospective study to evaluate the incidence, clinical presentations, and outcome of lymphocele in renal transplant recipients. 528 patients (313 males and 215 females) have received renal allografts from 384 living and 144 cadaveric donors. Diagnosis of lymphocele was made basically by ultrasound examination, and symptomatic collections were drained either percutaneously or into the peritoneal cavity. There were 50 (9.5%) instances of lymphocele encountered between 2 weeks and 6 months after transplantation. The lymphocele presented clinically predominantly as a single pelvi-abdominal swelling in 28 (56%) cases or as a swelling associated with manifestations of utereric and/or venous compression in 18 (36%) cases, and it was more common after cadaveric transplantation. All the cases of lymphocele were successfully treated with no graft loss. Lymphocele is an uncommon complication after renal transplantation, and is formed during the early post transplantation period. If not treated, it could seriously affect the kidney function. Intraperitoneal drainage is the most effective method for the treatment of symptomatic lymphocele.

Results in 158 consecutive cadaveric renal transplantations.

OBJECTIVES: We investigated the outcome of deceased donor kidney transplantations performed in a single center in a developing country. MATERIALS AND METHODS: A total of 158 patients (69 male and 89 female patients, including 32 children) received kidney grafts obtained from deceased donors between March 1996 and October 2004. Cadaveric renal grafts were transplanted after a cold ischemia time of 4 to 24 hours (mean, 12.5 hours). Retransplantation was performed in 19 recipients. Induction immunosuppression was achieved with antithymocyte globulin. The diagnosis of acute graft rejection was based on histopathological findings. RESULTS: Primary graft function was observed in 77% of cases. Posttransplantation complications were: surgical (n = 60; 38%), systemic bacterial and viral infections (n = 33; 21%), acute rejection (n = 47; 30%), and malignancy (n = 2; 1.3%). Seventeen recipients died with a functioning graft, and 23 more grafts were lost. The 7-year actuarial survival rates were 89% and 75% for recipients and grafts, respectively. CONCLUSIONS: The kidney transplantation program in Kuwait is steadily growing. Kidney grafts obtained from deceased donors contributed 28% of the transplantation activity and were associated with a high rate of primary function. Overall actuarial recipient and graft survival rates were comparable to those reported by larger centers.

The area under the concentration-time curve versus trough and peak blood level monitoring in renal transplant recipients on cyclosporine.

OBJECTIVE: The area under the concentration-time curve of cyclosporine microemulsion is the best measure of the absorption and beneficial effects in renal transplant recipients. We sought to determine the best method of monitoring cyclosporine levels in these patients. METHODS: Prospective evaluation of peak cyclosporine blood levels and area under the curve monitoring were performed for 1 year in 65 renal transplant recipients (study group). Cyclosporine trough levels and peak cyclosporine blood levels were correlated with the calculated area under the curve. Cyclosporine trough levels were monitored in equal numbers of matched controls. RESULTS: There were no significant differences in the incidence of acute rejection, cyclosporine nephrotoxicity, proteinuria, serum creatinine levels, or graft and patient outcomes between the groups (P = .1). Peak cyclosporine blood levels guided by calculating the area under the curve were found to be 27% to 32% lower than previously reported. The correlation coefficient was <70% for cyclosporine trough levels (P < .02) and >90% for peak cyclosporine blood levels (P < .001) when related to the calculated area under the curve. The calculated area under the curve was approximately 6000 ng/mL/h following transplantation, gradually decreasing to approximately 3000 ng/mL/h at 1 year. Both appeared to the acceptable therapeutic values. CONCLUSION: Calculating the area under the curve using trough and peak blood levels versus using isolated readings for either of these levels alone is the most effective method of monitoring cyclosporine in recipients undergoing renal transplant.

Single daily dose administration of cyclosporine in renal transplant recipients: a preliminary report.

INTRODUCTION: Cyclosporine microemulsion has been the mainstay immunosuppressive agent in renal transplantation for years. Since single daily dosing of cyclosporine is rarely used, the objective of this investigation was to evaluate the efficacy of a single daily dose versus twice daily dosing of cyclosporine in renal transplant recipients. METHODS: Retrospective evaluation of single-dose cyclosporine use was conducted for 15 renal transplant recipients for 12 months (study group). Equal numbers of matched renal transplant recipients were selected for age, sex, human leukocyte antigen mismatch, donor type, and immunosuppressive regimen (control group). Cyclosporine trough level and peak cyclosporine blood levels, 12-hour cyclosporine profile, and the area under the concentration-time curve were measured. RESULTS: There was a significant difference in cyclosporine peak blood level and calculated area under the curve after shifting to single-dose cyclosporine (P = .001). In the study group, the mean area under the curve was significantly below the average therapeutic range before (3154 ng/mL/ho) versus 5532 ng/mL/h after shifting to the single-dose regimen (which was therapeutic). This value was 5749 ng/mL/h in the control group. Total daily cyclosporine dose was lower in the study group when compared with the control group at 6 and 12 months (P = .01). There were significantly fewer adverse effects in patients in the study group than in patients in the control group. CONCLUSION: We conclude that although cyclosporine dose should be individualized in renal transplant recipients, a single dose of cyclosporine has the added advantage of decreasing dosages and cyclosporine-related adverse effects while maintaining optimal graft function.

Early acute rejection episodes in renal transplantation in relation to immunosuppression protocols: an audit of 100 cases.

INTRODUCTION: Early acute rejection episodes (ARE) have deleterious effects on graft outcomes. The incidence of ARE in the first 3 months has been reported to be <20%. In a recent audit of ARE among 100 renal transplants, we observed the rates to be high (30%). We retrospectively collected details of donor type, induction therapy, immunosuppression medications, drug levels, HLA mismatches, acute tubular necrosis (ATN), and delayed graft function (DGF) to correlate with ARE and response to therapy. RESULTS: Thirty rejection episodes occurred after a mean period of 14.3 days after transplantation. Ninety-one patients had induction treatment with either antithymocyte globulin (ATG) or interleukin 2 receptor antibodies (IL2 Rab). The drugs included cyclosporine, mycophenolate, sirolimus, azathioprine, and prednisolone in these patients. There was no significant difference in ARE among the different drug protocols (30.7%-35.2%). Subjects with 4 or more HLA mismatches displayed more ARE (40.3%) compared with those with 3 or less (23%). Subjects with ATN or DGF immediately posttransplantation had a higher incidence of ARE (39.2%) than those without them (26.3%). Deceased donor recipients had a higher episode of ARE (45.1%) compared with live related donor recipients (25%). On stratifying the known risk factors for ARE, subjects with no risk factors had the least (22.2%) ARE compared with those with one (32.5%) or two (47.6%) risk factors. Subjects who failed to achieve adequate cyclosporine (C2) levels showed significantly higher rates of ARE (86.9%) than those with adequate or higher levels (8.6%). CONCLUSION: Higher HLA mismatches, DGF, deceased donor, and failure to achieve adequate cyclosporine levels were observed to be major risk factors for the development of ARE.

Safety of caspofungin for treating invasive nasal sinus aspergillosis in a kidney transplant recipient.

INTRODUCTION: Invasive fungal sinusitis is a rare but often fatal infection in immunocompromised patients. Aggressive antifungal treatment is mandatory, but is not without risk. Caspofungin, an antifungal agent that is a member of the echinocandin family, an inhibitor of glucan synthesis in the fungal wall, is active against Aspergillus and Candidae infections. Although it works on the fungal wall, it does not affect mammalian cells; hence, its toxicity is minimal. CASE SUMMARY: This report describes a case of invasive Aspergillus sinusitis in a kidney transplant recipient with diabetes mellitus. The infection involved the apex of the right orbit causing optic nerve compression. The patient was treated with transnasal endoscopic decompression of the optic nerve and intravenous AmBisome (liposomal amphotericin B) for 2 weeks without clinical improvement. The combination of caspofungin and AmBisome administered for another 2 weeks yielded partial improvement. The AmBisome had to be discontinued due to deterioration of renal and hepatic function, but the patient completed a further 7-week course of caspofungin alone. Retro-orbital biopsy confirmed a complete response to treatment; the patient's renal and hepatic function returned to normal. CONCLUSION: This case indicates that caspofungin is effective to treat invasive Aspergillus sinusitis in kidney transplant recipients. This agent is well tolerated and safe with respect to renal and hepatic function.