Evaluation of clinical and safety outcomes associated with conversion from brand-name to generic tacrolimus in transplant recipients enrolled in an integrated health care system.

STUDY OBJECTIVE: To evaluate clinical and safety outcomes among transplant recipients whose tacrolimus was converted from the brand-name formulation to a generic formulation. DESIGN: Retrospective analysis. DATA SOURCE: Clinical databases and electronic records from a large, integrated health care system in California. PATIENTS: A total of 234 clinically stable, adult transplant recipients (renal, liver, and heart) whose tacrolimus was converted from the brand-name formulation to a generic formulation between October 1, 2010, and December 31, 2010, according to a physician-approved protocol. MEASUREMENTS AND MAIN RESULTS: For each patient, pre- and postconversion tacrolimus trough concentrations and serum creatinine concentrations were analyzed. Data were also collected on the percentage of patients who required dosage titration, drug cost savings, and rates of reversion to brand-name tacrolimus, biopsy-proved acute allograft rejections, and mortality. No significant differences were noted in mean ± SD pre- and postconversion tacrolimus trough levels (6.74 ± 1.61 vs 6.96 ± 2.31 ng/ml, p=0.137) or serum creatinine concentrations (1.33 ± 0.48 vs 1.36 ± 0.82 mg/dl, p=0.302). The mean ± SD percent change in tacrolimus trough concentration was 5.63 ± 32.95%. Thirty-six patients (15.4%) required dosage titration. Six patients (2.6%) reverted back to brand-name tacrolimus. No deaths or acute rejections occurred. Use of the generic product saved each patient an average of $45/month in drug acquisition cost and $26/prescription copayment. CONCLUSION: Clinical experience as well as research data show that use of generic tacrolimus results in trough concentrations that are comparable to the brand-name drug. Given the lack of adverse events reported and the cost savings recognized, conversion from brand-name tacrolimus to generic tacrolimus should be encouraged. Since dosage titration may be required, close therapeutic drug monitoring is recommended.

Trends in maintenance immunosuppressive drugs used in taiwanese kidney transplant recipients: an analysis of the national health insurance research database.

Trends in maintenance immunosuppressive drugs used among Taiwanese kidney transplant recipients have not been reported before. We examined the National Health Insurance Research Database to analyze trends in maintenance immunosuppressive drugs used in Taiwanese kidney transplant recipients for the years 2002-2009. The new case number of kidney transplant recipients ranged from 302 to 673 per year. In 2009, 5276 kidney transplant recipients received immunosuppressive therapy. The 5-year renal graft survival rate of kidney transplant recipients was 93%. In 2009, the most common immunosuppressive therapy among Taiwanese kidney transplant recipients was a triple regimen that included tacrolimus, mycophenolate mofetil, and corticosteroid. There was a significant increase in the use of a tacrolimus-based regimen from 35.1%-58.2%, while the use of cyclosporine decreased from 62.2%-24.8% (P < .05). The percentage of calcineurin inhibitor-free regimen increased from 2.7%-17%. Moreover, the use of Rapamune dramatically increased from 8.2%-22.6% in 2002-2004. However, the percentage of kidney transplant recipients using Rapamune maintained 23 ± 1.6% in 2004-2009. The use of mycophenolic acid remained stable at about 74.9 ± 3.2% in 2002-2009. As predicted, the use of Imuran decreased from 6.9%-3.5%. In summary, although calcineurin inhibitors remained the mainstay of immunosuppressive drugs, these findings suggest a general trends toward individualized regimens and the use of calcineurin inhibitor-free and mammalian target of rapamycin inhibitors-based regimens in Taiwanese kidney transplant recipients.

Preoperative psychological factors predicting graft rejection in patients undergoing kidney transplant: a pilot study.

BACKGROUND: The aim of this study was to investigate whether pretransplant psychological variables included in the CBA 2.0 Primary Scale-fear, personality, obsessive-compulsive symptoms, state and trait anxiety, psychological reactions, and depression-could predict graft rejection among patients undergoing kidney transplantation. METHODS: After ethical committee approval we enrolled 33 consecutive adult patients undergoing kidney transplantation. The inclusion criteria were a stable clinical situation in an out-of-hospital setting; Italian language literacy; a minimum of secondary school-level education, and written informed consent. We excluded patients with a psychotic disturbance, neurocognitive deficit, dementia, serious mental delay (IQ <50), current alcohol or drug abuse, recent ideation or attempted suicide or nonadherence to the therapeutic protocol. Acute and/or chronic graft rejection was diagnosed according to clinical and histopathologic criteria. CBA-2,0 "Primary Scale" series of questionnaires were handed out to patients at the time of the examinations to discrem eligibility for transplantation. Analyses of variance were performed to compare psychological scores among patients with versus without graft rejection. Logistic regression analyses of psychological variables were performed to detect possible predictors for graft rejection. The results of the analysis showed that higher psychoticism scores were able to predict graft rejection (P<.05). RESULTS: The findings of this study suggest that it is mandatory to preoperatively plan an holistic treatment including psychological intervention mainly focused on psychoticism.

Efficacy and safety of thymoglobulin induction as an alternative approach for steroid-free maintenance immunosuppression in pediatric renal transplantation.

BACKGROUND: Given the recent withdrawal of daclizumab (DAC), the safety and efficacy of thymoglobulin (TMG) was tested as an alternative induction agent for steroid-free (SF) immunosuppression in pediatric kidney transplant recipients. METHODS: Thirteen pediatric renal transplant recipients meeting defined high-risk criteria at transplantation were offered TMG induction and SF immunosuppression with maintenance mycophenolate mofetil and tacrolimus between October 2008 and January 2010. Patients were closely monitored at baseline, 3, 6, 9, and 12 months posttransplant for protocol biopsy and clinical outcomes. Outcomes were compared with 13 consecutively transplanted low-risk patients receiving an established DAC-based SF protocol (Sarwal et al., WA, American Transplant Congress 2003). RESULTS: There was a significant trend for overall decrease in the absolute lymphocyte counts in TMG group (F=5.86, mixed model group effect P=0.02), predominately at 3 months compared with DAC group (0.7±0.6 vs. 2.1±1.0, P=0.0004); however, lymphocyte count was recovered and was back to reference range by 6 months in TMG. There was trend toward more subclinical cytomegalovirus (15% vs. 0%) and BK viremia (17% vs. 0%) in the TMG group, with no differences in the incidence of subclinical Epstein Barr virus viremia (23% vs. 31%) or clinical viral disease. Mean graft function was excellent, and with a minimum follow-up of 6 months, there were no episodes of acute rejection. CONCLUSION: TMG seems to be a safe alternative induction strategy in patients for SF immunosuppression in pediatric renal transplantation. Extended follow-up and greater enrollment are necessary to fully explore the impact of TMG dosing on viral replication posttransplantation.

Immunosuppressive agents and bone disease in renal transplant patients with hypercalcemia.

Renal transplantation is the definitive treatment for many metabolic abnormalities of uremic patients, although it is only partially effective for renal osteodystrophy, which may interact with posttransplant renal osteopathy. Osteopenic-osteoporotic syndrome represents, together with fractures secondary to osteoporosis and osteonecrosis, the bone complication most related to renal transplantation. Several factors contribute to the pathogenesis of posttransplantation osteoporosis, particularly immunosuppressive treatment. In this study, we evaluated the prevalence of factors related to posttransplant renal osteopathy and the clinical impact of immunosuppressive protocols. We studied 24 renal transplant recipients with hypercalcemia. Glomerular filtration rate was >50 mL/min. Mean age, time on dialysis, and time from transplantation were 49.6, 5.4, and 6.9 years, respectively. We evaluated serum and urine calcium and phosphorus, calcitonin, parathormone, bone-specific alkaline phosphatase, osteocalcin, urine deoxypyridinoline, telopeptide of type 1 procollagen, 1,25-(OH)(2) and 25-OH vitamin D, parathyroid ultrasound, and computerized bone mineralometry. The combination of sirolimus and steroids resulted in the most disadvantageous outcomes regarding alkaline phosphatase and mineralometry. Calcineurin inhibitors did not significantly influence bone metabolism markers; mycophenolate mofetil evidenced no effect on bone. According to the literature, steroids account for the abnormalities found in our patients and in severe osteopenia. Several factors may contribute to the development of osteoporosis and fractures in transplantation patients, although they are overcome by the prominent effect of steroids. In patients at high risk of osteoporosis, steroid-free therapy should be considered. Everolimus is indicated for diseases with bone loss. Combined therapy with everolimus and mycophenolic acid without cyclosporine and steroids, seemed to be particularly indicated. Prophylactic treatments should be commenced early. No single marker was useful to diagnose posttransplant renal osteopathy. The definitive diagnosis should be made by bone biopsy during transplantation, and noninvasive procedures, such as densitometry and evaluation of biologic markers, may be useful during follow-up.

Treatment with calcimimetics in kidney transplantation.

Graft and patient survival in renal transplantation has increased with better immune suppression treatment, leading to the appearance of new complications such as posttransplant bone disease. After renal transplantation and the recovery of renal function, mineral metabolism disorders secondary to renal failure could be expected to normalize. However, both immediately after transplantation and later, and even with good renal graft function, we see bone disorders associated to renal osteodystrophy, a high incidence of osteopenia, persistent hyperparathyroidism, hypercalcemia, hypophosphoremia, and less commonly, aseptic bone necrosis. The causes potentially responsible for these disorders have basically been identified as different degrees of renal insufficiency in the graft, persistent posttransplant secondary hyperparathyroidism, and negative impact of immunosuppression treatment, particularly corticosteroids. The most important factor in the evolution of metabolic and bone disorders after renal transplantation, however, is pretransplant bone status. Special attention should be paid to other osteoarticular complications such as loss of bone mass and fractures, leading to significant morbidity. In the therapeutic approach to these patients, as well as encouraging physical exercise and advice about diet or other habits, the use of drugs such as calcium and vitamin D supplements, bisphosphonates, and more recently, calcimimetics have made significant improvements in the prevention and treatment of bone-mineral metabolism. It has been shown that calcimimetic agents can control the parathyroid hormone, reduce episodes of hypercalcemia, and improve hypophosphatemia. Their properties have to be assessed in broader studies to establish the basis for their widespread use among renal transplant recipients.

Urinary tract infection caused by extended-spectrum beta-lactamase-producing bacteria in kidney transplant patients.

Urinary tract infection (UTI) is a common complication among kidney transplant patients. UTI caused by multi-resistant extended-spectrum beta-lactamase producing bacteria (ESBL) have largely increased among the hospitalized patient population and especially kidney transplant recipients. We retrospectively studied 83 kidney transplant patients to evaluate the incidence and possible causative conditions of ESBL-related UTI over the last 6 years. ESBL production was determined by the antibiotic susceptibility profile of urine cultures. We compared the incidence in two 3-year periods, 2003-2005 (period 1) and 2006-2008 (period 2). An high incidence of ESBL-related UTI (16.8%) was observed in the posttransplant period performing 31% of the overall UTI incidence, with an increase over the last 3 years from 23.8% to 37.5%. ESBL-related UTI was related to previous episodes of UTI (78.6% vs 29.0%; P < .01) and reoperations (50.0% vs 12.9%; P < .05). We observed a progressively increasing incidence of 13%, 38%, and 45% of ESBL-related UTI among first, second, and third episodes, respectively. Age, gender, HLA mismatches, etiology of chronic kidney disease, diabetes mellitus, acute rejection, induction treatment, and type/level of immunosuppressants were similiar between the groups with or without ESBL-related UTI. We observed a high increased incidence of ESBL-related UTI among kidney transplant recipients, and particularly patients with recurrent UTI.

The yin and yang of B cells in graft rejection and tolerance.

Various lineages of B cells are being increasingly recognized as important players in the etiology and prognosis of both acute and chronic graft rejection. The role of immature, chronically activated B cells, as efficient antigen-presenting cells, supporting recalcitrant cell-mediated graft rejection and late lineage B cells driving humoral rejections, is being increasingly recognized. This review captures the recent literature on this subject and discusses the various roles of the B cell in renal graft rejection and conversely, also in graft tolerance, both in animal and human studies. In addition, novel therapies targeting specific B-cell lineages in graft rejection are also discussed, with a view to developing more targeted therapies for graft rejection.

National Kidney Registry: 213 transplants in three years.

Since its establishment in 2008, the National Kidney Registry has facilitated 213 kidney transplants between unrelated living donors and recipients at 28 transplant centers. Rapid innovations in matching strategies, advanced computer technologies, good communication and an evolving understanding of the processes at participating transplant centers and histocompatibility laboratories are among the factors driving the success of the NKR. Virtual cross match accuracy has improved from 43% to 91% as a result of changes to the HLA typing requirements for potential donors and improved mechanisms to list unacceptable HLA antigens for sensitized patients. A uniform financial agreement among participating centers eliminated a major roadblock to facilitate unbalanced donor kidney exchanges among centers. The NKR transplanted 64% of the patients registered since 2008 and the average waiting time for those transplanted in 2010 was 11 months.

Bortezomib for acute humoral rejection treatment at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City: an update.

The use of bortezomib as a treatment modality of AHR improved and stabilized graft function (clinical response) in the majority of patients. Its use in single dose, even combined with rituximab, does not seem to be useful to obtain a sustained clinical response, or to reduce HLAabs level. The use of 4 doses of bortezomib in days 1, 4, 7, and 10 (1.3 mg/m2 BSA each) plus plasmapheresis produced both a good clinical response and a reduction in DSA. Moving forward, it will be necessary to define the long-term effectiveness of bortezomib and whether rituximab administration is indispensable to achieve this goal. Until now, it is evident that many patients needed retreatment and they were well tolerated.

Combination of everolimus and tacrolimus in kidney transplant patients with intolerance to mycophenolate mofetil/mycophenolic acid.

OBJECTIVE: Most immunosuppressive protocols in de novo renal transplantation include tacrolimus in combination with mycophenolate mofetil/mycophenolic acid (MMF/MPA) and prednisone. A variable percentage of patients show intolerance to MMF/MPA needing a reduction, interruption, or suspension of the drug, thereby exposing the patient to a greater risk of a rejection episode. The association of everolimus and tacrolimus may prove to be an alternative option in such cases. The aim of this study was to present our clinical experience, evaluating the incidence of graft rejection. PATIENTS AND METHODS: We performed a descriptive study of 19 kidney transplant patients from 2001-2008 who were treated with tacrolimus, MMF/MPA, and prednisone and displayed gastrointestinal or hematological adverse events to MMF/MPA, which were addressed with everolimus. We analyzed parameters up to 2 years after the change. RESULTS: The doses and levels of everolimus were increased progressively. At the same time, we decreased the doses and levels of tacrolimus. Renal function remained stable during the period and there was no case of a rejection episode during the 2 years. Only 5 patients (26%) showed side effects which were attributable to everolimus; 36% of patients required starting and/or increasing the erythropoietin dose, 15% required iron supplements, 15% required diuretics, and 31% began or increased treatment with statins. CONCLUSION: Our experience suggested that a combination of tacrolimus and everolimus may be a safe, effective alternative for kidney transplant patients who show intolerance to MMF/MPA.

Treatment with cinacalcet of secondary hyperparathyroidism after renal transplantation.

BACKGROUND: The treatment of posttransplant secondary hyperparathyroidism (SHP) with vitamin D analogues is determined by their effectiveness to reverse hypercalcemia. Calcimimetics inhibit parathyroid hormone (PTH) secretion by modulating the calcium-sensing receptor in the parathyroid gland. Cinacalcet, a calcimimetic drug, has proven its effectiveness for the treatment of SHP among patients in phase V of chronic renal disease. PATIENTS AND METHODS: This retrospective analysis included 48 patients with SHP who were treated with cinacalcet. The initial dose of 30 mg/d could be increased to 180 mg, administering calcitriol also, depending on the serum calcium and PTH levels. The objectives were a PTH level between 75 and 125 pg/mL or a decrease >40%, and a serum calcium level below 10.5 mg/dL. RESULTS: The average PTH at baseline was 244 pg/mL, decreasing to 131 pg/mL at 1 year (P < .01). The average calcium at baseline was 10.1 mg/dL descending to 9.2 mg/dL at 1 year (P < .01). Among patients with hypercalcemia, the calcium decreased from 11 to 9.6 mg/dL at 1 year (P < .01). Seventy percent of patients without hypercalcemia reached the desired value of PTH, and 100% of those with hypercalcemia. Among patients with hypercalcemia, the desired calcium level was reached in 91% of cases. Ten patients developed hypocalcemia. In 3 cases we stopped the treatment with cinacalcet due to digestive intolerance. CONCLUSIONS: Treatment with cinacalcet controlled hyperparathyroidism and hypercalcemia among patients with posttransplant SHP. It was a safe drug, with a low incidence of side effects.

Successful multiple pregnancy (triplets) in a kidney transplant recipient: a case report.

Renal failure generally accompanies an alteration in reproduction function. Even though a renal transplantation does in fact improve this function, there are few cases described in medical literature of multiple pregnancies in transplant patients that ended in a successful manner. In addition, there is a greater incidence of complications such as hypertension, preeclampsia, and premature delivery. This article describes a 31-year-old patient who became pregnant with triplets at 3 years and 6 months after receiving a renal transplant from a cadaver. The patient received treatment with cyclosporine, azathioprine, and prednisolone. During the pregnancy, there was a increase in hypertension, proteinuria, cholestasia gravidic symptoms, and premature delivery. Pregnancy control included evaluation of the fetoplacental unit together with hypertensive management and adjustment of immunosuppressant treatment, especially the cyclosporine dose, seeking to facilitate greater fetal maturity. Three newborns of 840, 860, and 1020 were delivered by cesarean section. The newborns spent 6 to 8 weeks in the neonatal unit and were released without complications. The newborns have presented adequate psychomotor and physical development to date. The triplets are now 4 years old. The transplant recipient has a creatinine clearance of 81 mL/min at 7 years after transplantation.

Clinical application of Cordyceps sinensis on immunosuppressive therapy in renal transplantation.

OBJECTIVE: We sought to explore the adjunctive effects of Cordyceps sinensis (CS) in clinical renal transplantation. MATERIALS AND METHODS: Patients (n = 202) were divided randomly by lottery into a treatment (n = 93) and a control group (n = 109). Patients in the treatment group were treated with CS 1.0 g 3 times a day in addition to the immunosuppressive regimen given to the control group. We compared patient and graft survivals, incidence, time and severity of acute rejection episodes, chronic allograft nephropathy (CAN), hepatotoxicity and nephrotoxicity, biochemistry parameters including indicators of liver and kidney functions, fats, proteinuria, dosages, and whole blood concentrations of cyclosporine (CsA). RESULTS: Patient and graft survival rates, serum creatinine (SCr), and blood urea nitrogen (BUN) were not significantly different between the 2 groups (P > .05). Serum uric acid (UA) and 24-hour urinary total protein (24-hour UTP) were significantly lower in the treatment group than in the control group (P < .05). The incidences (11.83% vs 15.60%) and times to acute renal allograft rejection (23.48 +/- 7.22 vs 22.27 +/- 8.03 days posttransplantation) were not significantly different between the treated and control groups (P > .05). Patients receiving thymoglobulin antirejection therapy (3 cases) were fewer in the heated versus control group (13 cases; P = .014). The incidences of hepatotoxicity and nephrotoxicity in the treated group were 12.90% and 19.35%, significantly lower than 24.77% and 33.94% in the control group, respectively (P < .05). At 2 to 6 months posttransplantation, the CsA dosages in the treated group were significantly lower than those in the control group (P < .05). The whole blood trough CsA concentrations in the treated group were significantly lower than those in the control group at 3 to 6 months posttransplantation (P < .05). The decreasing trends of the 2 aforementioned parameters in the treatment group were approximately linear among treated subjects compared with approximately quadratic in the control group (P < .05). The incidence of CAN in the treated group was 7.53%, which was significantly lower than 18.35% in the control group (P = .024). The 24-hour UTP level in CAN patients within the treated group was significantly lower than the control group after transplantation (P = .045). The differences in total bilirubin, SCr, serum UA, and total cholesterol levels among otherwise normal patients in the treated group were significantly lower than those among the control group (P < .05). CONCLUSIONS: The use of CS may allow decreased dosages and concentrations of CsA causing fewer side effects without an increased risk of acute rejection. In addition, CS with reduced dose CsA may decrease proteinuria and retard CAN progression.

Therapeutic effect of Tripterygium wilfordii on proteinuria associated with sirolimus in renal transplant recipients.

Sirolimus (SRL) is a potent immunosuppressive drug used to prevent acute allograft rejection after renal transplantation. Nevertheless, the occurrence of proteinuria has recently been recognized among patients on SRL-based therapy. The aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii Hook F. (T II) on proteinuria associated with SRL in renal transplant recipients. According to accepting T II, 36 recipients were divided into 2 groups: T II group (n = 21) and valsartan group (n = 15). The T II group was administered 1 mg/kg/d, and the valsartan group, 80 mg twice per day for 12 months. Efficiency was then evaluated. Complete remission: proteinuria decreased by >50%; partial remission: proteinuria decreased by 20% to 50%; ineffective: proteinuria decreased by <20%. Upon 12-month follow-up, the total effective rates in the T II group and the valsartan group were 95.2% and 86.7% (P < .05), respectively. Twenty of 21 patients with proteinuria in the T II group were negative at 3-month follow-up with disappearance of edema. There were some adverse events that had greater incidence rates in the valsartan group compared with the T II group, such as hyperkalemia (26.7% vs 4.8%). We concluded that the application of T II markedly reduced proteinuria associated with SRL in renal transplant patients.

Tripterygium wilfordii hook f increase the blood concentration of tacrolimus.

OBJECTIVE: To observe the influence of the Tripterygium wilfordii Hook F (T II) on the blood concentration of tacrolimus and analyze the impact of this effect. METHOD: Twenty-two renal transplant receipts taking tacrolimus combined with the T II were selected for this study. We analyzed the blood concentrations and the rate of concentration compared with dosage (C/D rate) pre- and postcombination over 6 months. All cases underwent the CYP3A5 genotype test. RESULT: The concentrations of tacrolimus were raised to a certain degree after the combination in all the cases. The first-time elevation differed from 1 week to 4 months. The C/D rate increased by 1.7 to 7.2 times with most evaluated C/D rates ranging from 1.8 to 3.8. The elevated C/D rate of the subgroup of CYP3A5 1/1 and 1/3 (n = 10) contrasted with the 3/3 genotype subgroup (n = 12: 2.99 +/- 1.71 vs 2.55 +/- 1.07; P = .472). The mycophenolate mofetil subgroup (n = 17) was not contrasted to the mizoribine subgroup (n = 5: 2.85 +/- 1.51 vs 2.31 +/- 0.26; P = .498). CONCLUSION: T II considerably increased the blood concentration and the C/D rate of tacrolimus. The degree of increase was probably not related to the CYP3A5 genotype and the combination of immunosuppressive agents.

[Treatment of post-transplant glomerulonephritis]. / Il trattamento delle glomerulonefriti de novo e recidivate come causa di disfunzione cronica del rene trapiantato.

The treatment of recurrent glomerulonephritis (GN) is often empirical. Plasmapheresis has received the largest consensus for the treatment of focal glomerular sclerosis (FGS), whether associated with cyclophosphamide and steroids or not. To be effective, such therapy needs to be started as quickly as possible after the onset of proteinuria, and prolonged for months when recovery is delayed. Plasmapheresis and cyclophosphamide have also been used to treat GNs with glomerular crescents. However, there has been no consensus on the efficacy of such therapy. The recently introduced rituximab is the most innovative drug but also the most experimental. So far, it has been used for the treatment of ANCA-associated vasculitis, FGS and membranous GN, with results that are still under debate. Cyclophosphamide has been used in patients with severe recurrent GN, but the anedoctal cases described prevent us from drawing any firm conclusions. Steroids have been used for the treatment of many recurrent GNs, but yet again, without any standard protocol. They have been used both in children with FGS and in adults with aggressive GN or severe proteinuria. Both ACE inhibitors and angiotensinreceptor blockers have been suggested as first-line therapy in recurrent GN with proteinuria. This therapy is safe and can be even more effective than others. Finally, it must be kept in mind that the addition of immunosuppression in transplant patients can dramatically increase the risk of infective complications. Moreover, recurrent GNs are often associated with chronic allograft diseases that can cause graft worsening independently of any therapy.

Hepatocellular carcinoma following renal transplantation: experience in northern Taiwan.

BACKGROUND: Transitional cell carcinomas (TCC) have been reported to be the most common post-renal transplantation malignancy in Taiwan; they are considered to be related to the use of herbal drugs. However, in 2004, hepatocellular carcinoma (HCC) was the most prevalent malignancy at our institute. We therefore extended our observations through 2006 to include a larger renal transplant cohort. MATERIALS AND METHODS: Patients were given an immunosuppressive regimen consisting of either cyclosporine or FK 506, mycophenolate mofetil, and copticosteroid. Critical diagnostic follow-up procedures were performed trimonthly. Aggressive surgical procedures were performed when operable cancers were found. Immunosuppressants were reduced thereafter to prevent recurrence. RESULTS: Among 663 patients, 55 developed 58 malignancies which were diagnosed after a mean of 70 months posttransplantation. Among these 55 patients, 25 died. HCC accounted for 22 malignancies, followed by 15 cases of TCC, and 8 cases of posttransplantation lymphoproliferative disorder (PTLD). Fifteen known hepatitis B carriers received lamivudine therapy; none had recurrences and only 2 acquired HCC. These 2 patients are still living, whereas the remaining 20 subjects with HCC are deceased. Of the 37 patients who received anti-CD25 induction therapy, none displayed PTLD. CONCLUSIONS: HCC remains the most common post-renal transplantation malignancy in northern Taiwan. The high rates of hepatitis B and C endemic to Taiwan and the prevalence of hepatitis C virus (HCV) genotype 1b infections in northern Taiwan may explain this finding. Frequent alpha-fetoprotein measurements and liver ultrasonograms are recommended for early detection of HCC among Taiwanese renal transplant recipients. Anti-CD25 induction therapy appears to be helpful to prevent the development of PTLD among Taiwanese renal transplant recipients.

Reduction in erythropoietin resistance after conversion from sirolimus to enteric coated mycophenolate sodium.

BACKGROUND: Anemia is a known adverse effect of sirolimus (SRL) therapy. Sirolimus may contribute to anemia by a direct antiproliferative effect or by increasing inflammation, worsening kidney function, or decreasing iron utilization. After observing the need for high dose exogenous erythropoietin dosage in some patients on SRL, we hypothesized that SRL therapy may influence anemia by inducing a state of erythropoietin resistance. METHODS: Twenty-five stable renal transplant patients on maintenance tacrolimus and SRL therapy were enrolled in a prospective trial with conversion from SRL to enteric coated mycophenolate sodium. Measurement of plasma erythropoietin and red cell indices were performed pre- and postconversion. RESULTS: Renal function remained unchanged after conversion. Serum hemoglobin (Hb) increased in 18/21 (86%) of patients after conversion. Endogenous erythropoietin level decreased from a median of 28.3 (11.5-374) to 16.6 (3.1-78.8) mIU/mL, (P<0.001); and the erythropoietin:Hb ratio dropped from 2.7 (0.7-34.3) to 1.2 (0.2-6.7), (P<0.001); indicating less erythropoietin resistance after conversion. Mean corpuscular volume increased after conversion, but transferrin saturation and ferritin did not change. Conversion was complicated by posttransplant erythrocytosis in two patients. DISCUSSION: Conversion from SRL to enteric coated mycophenolate sodium led to an increase in Hb and a decrease in erythropoietin resistance in stable kidney transplant recipients. Increase in Hb seemed to be independent of renal functional changes or changes in iron sequestration.

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.