Factors That Influence Delayed Graft Function in Kidney Transplants: A Single-Center Paired Kidney Analysis.

BACKGROUND: The risk factors associated with delayed graft function (DGF) and its impact in kidney transplant (KTx) outcomes remains controversial; it is possible that donor renal characteristics influence the initial graft function in KTx. OBJECTIVE: Evaluate risk factors associated with DGF and its impact in KTx outcomes. METHODS: One hundred six mate KTx mate recipients performed in a single center were grouped according to the presence or absence of DGF. RESULTS: Donors were predominantly men (58%); 70% were standard criteria type, with a mean Kidney Donor Profile Index (KDPI) of 62% ± 28%, median age of 42 ± 15 and presenting hospitalization time of 6 ± 5 days. KTx recipients presented an overall DGF rate of 82%, lasting 12 ± 7 days. Pairs presenting DGF were older than pairs without DGF (P = .008), while cold ischemia time (CIT) was significantly shorter in the group without DGF compared to those presenting DGF (P = .003). The KDPI of the KTx pairs was significantly higher in pairs with DGF versus without DGF (P = .04). No statistically significant differences in 1 year allograft and patient survival were observed. Recipient age (odds ratio = 6.3, confidence interval = 1.5-25.8; P = .009) and CIT (odds ratio = 4.6, confidence interval = 1.2-17.7; P = .002) were significantly associated with DGF. CONCLUSION: This study suggests that recipient age, cold ischemic time, and KDPI are factors associated with DGF. In addition, DGF had no impact on 1-year renal function, allograft, and patient survival. In the transplant conditions of our country, Brazil, CIT seems to represent an important variable to be managed, and the aim should be to reduce this factor as much as possible.

Zika Virus Infection and Solid Organ Transplantation: A New Challenge.

Public health concerns exist surrounding the epidemic of the Zika virus (ZIKV) and the rapid growth of transplantation in developing countries, including endemic zones of active arbovirus transmission, as well as travel to such regions by potential organ donors and recipients. Few data exist regarding the clinical characteristics of ZIKV infection in immunocompromised hosts. Laboratory screening protocols for transplantation to differentiate ZIKV infections from other endemic viral diseases and for the detection of possible donor-derived infection have not been stated. The diagnosis of ZIKV infection remains a challenge, fueled by the lack of standardized commercially available diagnostic tests and validated reference diagnostic laboratories, as well as the limited duration of ZIKV viremia. In this small series, ZIKV infection in renal and liver recipients presented without rash, conjunctivitis, or neurological symptoms, and with abnormal graft function, thrombocytopenia, and bacterial superinfection. We report the first case series of ZIKV infection in solid organ recipients, with a description of clinical and laboratory features and therapeutic management.

Randomized Trial of Machine Perfusion Versus Cold Storage in Recipients of Deceased Donor Kidney Transplants With High Incidence of Delayed Graft Function

BACKGROUND: This study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF). METHODS: In this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals. RESULTS: Mean cold ischemia time was high but not different between the 2 groups (25.6 ± 6.6 hours vs 25.05 ± 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 ± 19.9 mL/min per 1.73 m2 vs 49.0 ± 26.9 mL/min per 1.73 m2; P = 0.262) and 1 year (48.3 ± 19.8 mL/min per 1.73 m2 vs 54.4 ± 28.6 mL/min per 1.73 m2; P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed...

Collaborative Brazilian Pediatric Renal Transplant Registry (CoBrazPed-RTx): A Report From 2004 to 2013.

BACKGROUND: The Collaborative Brazilian Pediatric Renal Transplant Registry started in 2004 as a multicenter initiative aiming to analyze, report, and share the results of pediatric kidney transplantation in Brazil. Data from all pediatric kidney transplants performed between January 2004 and December 2013 were recorded electronically and periodically updated. All patients under 18 years old from the participating centers were enrolled. Demographic data, etiology of chronic kidney disease, and patient and graft survival were analyzed. From a total of 2443 pediatric kidney transplants performed in Brazil during the study period, we report data from 1751 pediatric renal transplants performed in 13 centers enrolled in the collaborative study. Median age at transplantation was 12.4 years, and most of recipients were male (56%). The most common underlying renal etiologies were obstructive uropathy (31%) and glomerulopathy (26%). METHODS: According to donor source, 1155 (66%) of transplants were performed with deceased donors (DD). Initial immunosuppression consisted mainly of tacrolimus, mycophenolate, steroids, and induction therapy with anti-IL-2R antibodies. RESULTS: One-year graft survival (death-censored) was 93% and 90% (log rank test, P < .01), respectively, for living donor (LD) and DD. Graft losses (15%) were most frequently caused by vascular thrombosis, chronic allograft nephropathy, death with functioning kidney, acute rejection, and recurrent renal disease. Recipients of DD had 2.02 (95% confidence interval: 1.14-3.59) times the hazard of graft loss compared with those of LD (P = .015). Patient survival rates at 1 and 5 years were 98% and 97% for LD and 97% and 93% for DD, respectively. The mortality rate was 3.8%, mainly as the result of infection and cardiovascular disease. CONCLUSIONS: The results of this collaborative pediatric transplant study are comparable to international registries. Our effort has been able to maintain an exchange of information, both among the participating centers and with other international registries.

Clinical and histopathologic comparative analysis between kidney transplant recipients from expanded-criteria donors and standard-criteria donors.

Owing to the disparity between the supply of kidney donors and demand, the use of organs from older deceased donors was initiated in recent years. The potentially poor outcome of these grafts is a major concern. This retrospective study compares graft and patient 1-year survivals between recipients from expanded-criteria donors (ECD; n = 30) and standard-criteria donors (SCD; n = 104). Rates of delayed graft function (DGF), acute rejection (AR), and chronic injury in the pre-implantation biopsy were also assessed. Increasing donor age was associated with increased rates of DGF, and DGF correlated with AR. Cold ischemia time >30 hours was associated with worse graft outcomes. Induction with Simulect correlated with better patient survival compared with Timoglobulina. Chronic injury pre-implantation biopsy correlated with worse renal function, but graft survival was similar. Death-censored graft survival at 1 year was 90% and patient survival 82%, and these were similar in ECD and SCD recipients. Selection of transplant candidates for ECD kidneys must be performed with caution. One-year graft survival was similar to that of SCD kidneys, but kidney function was worse during the same period. This may result in poorer graft survival over longer follow-up.

Families who previously refused organ donation would agree to donate in a new situation: a cross-sectional study.

BACKGROUND: The limited supply of organs restricts the number of transplantations. Studying the families who refuse donation may help to increase the number of transplantations. METHODS: This descriptive cross-sectional study used a questionnaire to obtain information from 61 family members who had refused to donate organs from January 1997 to December 2004. The exclusion criterion was donor death less than 1 year from the study. The mean age of subjects was 41 ± 12.7 years (range, 18 to 79 years) with 66% women. RESULTS: More than half (36 of 69; 52%) of the families who refused donation would agree to donate in a new situation. The primary reasons for refusing donation were: disagreement among family members (25 of 128; 19%), lack of knowledge regarding the deceased's wishes (22 of 128; 17%), and previous request from the deceased not to be a donor (17 of 128; 13%). The most frequent suggestions to increase organ donation were to provide families with more information (43 of 149; 29%), initiate contact among the families (36 of 149; 24%), and involve a trusted physician (30 of 149; 20%). CONCLUSION: Most family members who refused organ donation changed their minds and would agree to donate in a few situation. Most of the reasons for refusing to donate reflected a lack of information and discussion on the topic.

Repairing the chronic damaged kidney: the role of regenerative medicine.

The increasing number of patients who suffer from chronic kidney diseases combined with the organ shortage have directed the attention of researchers to new alternatives in the fields of regenerative medicine including cell-based therapies and tissue bioengineering. This review of renal regenerative medicine addresses the mechanisms of action by stem cells to regenerate or repair chronically damaged renal tissue, alternative routes for their delivery, the role of biomaterials in tissue engineering, and the potential therapeutic effects of combining cell therapy with biomaterials. Despite the promise of ongoing work for therapy of chronic renal failure, caution is required as a large gap still exists between scientific knowledge and clinical translation for safe, effective stem cell-based therapies.

The emerging role of Brazil in clinical trial conduct for transplantation.

Brazil is a country with over 190 000 000 inhabitants and a health system composed of a large public, government managed system. Between 1999 and 2010 the number of deceased donors increased by 161%, from 3.8 to 9.9 pmp, and the number of solid organ transplants increased by 121%, from 2891 to 6402. This growth was a consequence of the creation of a well-organized national transplant program. Government funding, decentralization and educational investment in transplant coordinators and related professional were decisive. In 2009 Brazil was the second largest country in the absolute number of kidney transplants (n = 4259). There are significant region disparities in performance which are mainly due to the development status. Improvements in transplant and research regulations resulted in an increasing participation of Brazilian transplant centers in multicenter trials, reaching over 44 studies during the last 11 years. Brazilian centers have been involved in clinical trials using everolimus, sirolimus, fingolimod, mycophenolate mofetyl, mycophenolate sodium, tacrolimus modified-release, sotrastaurin, belatacept, JAK3 inhibitor CP690,550 and valganciclovir. The still increasing number of transplants performed every year along with more efficient regulatory and sanitary analysis, organized clinical research programs and reduction in region performance disparities will eventually increase even more the participation of Brazil in trials worldwide.

Nonsurgical periodontal therapy combined with laser and photodynamic therapies for periodontal disease in immunosuppressed rats.

BACKGROUND: Periodontal disease is often associated with systemic diseases and is characterized by destruction of the tissues supporting the teeth. Patients using immunosuppressive drugs such as tacrolimus are among those who suffer from tissue destruction. OBJECTIVE: We sought to evaluate the effects of laser and photodynamic therapies (PDT; nonsurgical) as an adjunct to scaling and rootplaning (SRP) in the treatment of corona-induced periodontitis in rats immunosuppressed with tacrolimus (Prograf). MATERIALS AND METHODS: The animals were divided into 5 groups. Each groups had 6 rats. Group I, the control group, received only saline solution throughout the study period of 42 days and did not receive periodontal treatment; group II received saline solution and SRP; group III received tacrolimus (1 mg/kg per day) and was treated with SRP; group IV animals were treated identically to group III and then administered laser treatment; and in group V, the animals were treated identically to group III and then administered PDT. RESULTS: Statistical analysis indicated decreased bone loss with the progression of time (P = .035). There was no difference between the bone loss associated with the types of treatment administered to groups I, II, and III (P > .9) or groups IV and V (P > .6). The analysis also indicated that immunosuppression was not a bone loss-determining factor. CONCLUSION: Laser and PDT therapies were effective as an adjunctive treatment to SRP in reducing bone loss caused by experimental periodontitis induced in animals being treated systemically with tacrolimus.

Individualizing early use of sirolimus in renal transplantation.

One of the main goals in the current care of kidney transplant recipients is to extend long-term graft survival. Efficacious immunosuppressive agents devoid of nephrotoxicity are needed. In human clinical transplantation, sirolimus combined with other immunosuppressive drugs has proven to be a powerful immunosuppressant capable of preventing acute graft rejection, as well as of improving renal function, renal histology, and graft survival when compared with immunosuppressive regimens that include calcineurin inhibitors. The valuable experience gained through many clinical studies allows clinicians to plan sirolimus use. We present a review of the clinical experience and literature review on the use of sirolimus in the first 12 months posttransplantation.

Comparison of the safety and efficacy of cyclosporine minimization versus cyclosporine elimination in de novo renal allograft patients receiving sirolimus.

The safety and efficacy of concentration-controlled use of sirolimus (SRL) and cyclosporine (CsA) followed by CsA minimization (CsAm) or elimination (CsAe) beginning at week 13 was compared in a phase 4, open-label, randomized (1:1) trial of renal transplant recipients enrolled between March 2004 and November 2005. The primary endpoint was renal function, measured at 12 months using the Nankivell formula, in patients remaining on therapy. Though a total enrollment of 140 patients in each group was planned to provide an 80% power to detect a difference in means, only 207 subjects were enrolled in this study. Demographic characteristics were similar between groups, with 98.1% recipients of first grafts, 69.1% from living donors, and 7.2% diabetics. At 12 months, there were no differences in renal function (61.08 vs 65.24 mL/min, P = .132); incidence of biopsy-confirmed acute rejection (14.3% vs 22.5%, P = .152); and patient (89.5% vs 92.2%, P = .632), graft (87.6% vs 88.2%, P = .999), and death-censored graft (98.1% vs 94.1%, P = .166) survivals between CsAm and CsAe groups, respectively. There were no differences in the overall rate of study-drug discontinuation (32.4% vs 36.3%, P = .562) but more patients discontinued because of lack of efficacy/graft loss in the CsAe group (4.8% vs 14.7%, P = .018). This study was underpowered to demonstrate the superiority of one regimen over the other. In summary, SRL immunotherapy combined with CsA minimization or elimination showed comparative safety and efficacy. Both regimens offer potential treatment options for de novo renal allograft recipients.

Corticosteroid reduction with tacrolimus (CORRETA) TRIAL: a prospective Brazilian multicenter, randomized trial of early corticosteroid reduction versus regular corticosteroid dosage maintenance on a tacrolimus (Prograf) and mycophenolate mofetil (Cellcept) immunosuppression regimen in kidney transplant recipients: interim analysis.

Corticosteroids are a cornerstone of immunosuppressive therapy in renal transplantation despite their side effects and morbidity. Newer immunosuppressive agents may be more effective to allow corticosteroid sparing. An interim analysis of 60 completed out of 100 planned primary kidney transplant recipients is presented. All patients on tacrolimus (Prograf) and MMF (Cellcept) were randomized into two groups following a 1:1 distribution for early steroid reduction at posttransplant day 7 (G1; n = 31) versus to long-term maintenance steroids (G2; n = 29). Primary efficacy endpoints were composite endpoint of death, graft loss, or severe acute rejection at 6 and 12 months follow-up. Safety evaluation included severity and frequency of diabetes mellitus, hypertension, hyperlipidemia, leukopenia, infection, malignancy, and severe adverse events. Mean age was 39.1 years, with 45.0% males and 66.7% Caucasians. African-Americans were 25.8% in G1 and 27.6% in G2. One death occurred in each group, as well as one case of severe (Banff III) rejection in G1 (P = 1.00). The incidence of rejection episodes between groups was not significant, namely, 41.9% in G1 and 20.7% in G2 (P = .077). There were no differences between groups concerning mean, systolic and diastolic blood pressure, HbA1c, or creatinine at 12 months. This interim analysis showed no evidence of an increased risk of poorer performance among the early steroid reduction or safety differences in kidney transplant recipients versus a regular dosage steroid group of patients. Further analysis of the complete study data is underway.

Influence of UDP-glucuronosyltransferase polymorphisms on mycophenolate mofetil-induced side effects in kidney transplant patients.

Mycophenolate mofetil (MMF) is an immunosuppressive prodrug approved for use in transplantation. Its active metabolite, mycophenolic acid, is mainly metabolized by UDP-glucuronosyltransferase (UGT) enzymes. In this study, we retrospectively analyzed 74 kidney transplant patients who had been prescribed MMF as part of their immunosuppression regimen. Polymorphisms in UGT1A8 (-999C > T, codon 255A > G, codon 277G > A) were correlated with the occurrence of side effects, such as diarrhea, blood disorders, and infections. The infectious episodes were more frequently observed among individuals receiving MMF (2 g/d) who carryied the variant UGT1A8 codon 277A (P = .031), the haplotype UGT1A8H5 (-999C/codon 55A/codon 277A; P = .02), and the diplotype UGT1A8H2/H5 (-999CC/codon 255AA/codon 277GA; P = .015). The molecular data from this study suggest that UGT polymorphisms may be a factor influencing clinical outcomes among patients receiving MMF for transplant therapy; however, larger studies are warranted.

Role of glutathione s-transferase polymorphisms and chronic allograft dysfunction.

Polymorphisms within genes encoding glutathione S-transferases (GSTs) may affect responses against damage induced by oxidative stress and therefore play a role to prevent chronic allograft dysfunction (CAD). In the present study, we estimated the frequencies of GSTM1- and GSTT1-null genotypes among 227 renal transplant recipients seeking to establish an association with CAD. Patients persistently displaying serum creatinine (sCr) values < or = 1.5 mg/dL, measured creatinine clearances (CLcr) > or = 50 mL/min/1.73 m(2), and 24-hour proteinuria < or = 500 mg were classified as normal graft function (NF; n = 107). In contrast, the CAD group (n = 120) presented sCr > 1.5 mg/dL, CLcr < 50 mL/min/1.73 m(2), and proteinuria > 500 mg. The GSTM1 and GSTT1 polymorphisms were evaluated by the multiplex polymerase chain reaction. The frequencies of GSTT1-null genotypes in NF and CAD cohorts were 15% and 24.2%, respectively (P = .057), while GSTM1-null genotypes in the same groups of patients were 44% and 46.7% (P = .389). A combination of null genotypes for GSTT1 and GSTM1 was observed in 9.2% of patients with CAD and in 5.6% of those with NF (P = .449). This study did not show an association of either GSTT1- and GSTM1-null genotypes with CAD. It is likely that development and progression of CAD are determined by a combination of complex genetic traits resulting from the interplay of several genes rather than a single gene.

Report of initial experience in small bowel transplantation at São José do Rio Preto Medical School Hospital.

Intestinal failure is the patient's inability to maintain hydroelectric and nutritional support by the digestive route, arising from massive enterectomy or diseases in which the bowel is incapable of adequately absorbing fluids and nutrients. Patients with intestinal failure associated with short bowel syndrome (SBS) and with other functional diseases with malabsorption or with total parenteral nutrition-related complications (recurrent sepsis and thrombosis of one or more deep venous accesses) are candidates for small bowel transplantation (SBT), which can be an isolated small bowel, a combined liver and small bowel, or a multivisceral graft. At our institution, three isolated SBTs were performed as our initial experience with this transplant.

Effect of whole bone marrow cell infusion in the progression of experimental chronic renal failure.

INTRODUCTION: The therapeutic potential of adult stem cells for the treatment of chronic diseases is becoming increasingly evident over the last few years. In the present study, we sought to assess whether the infusion of bone marrow-derived mononuclear cells (MoSCs) and mesenchymal cells (MSCs) could reduce/stabilize the rate of progression of chronic renal failure (CRF) in rats. METHODS: We used the 5/6 renal mass reduction model to induce chronic renal failure in male Wistar rats. Renal function was assessed by measurements of serum creatinine (sCr), creatinine clearance (Clcr), and 24-hour proteinuria at baseline as well as 60 and 120 days after surgery. MoSCs and MSCs obtained from bone marrow aspirates were separated by the Ficoll-Hypaque method. After a 12- to 14-day culture, 1.5 x 10(6) MSCs and the same number of MoSCs were injected into the renal parenchyma of the remanant kidney of rats with CRF on the day of surgery. RESULTS: Among the control group, at day 120, the results were sCr = 1.31 +/- 0.5 mg/dL, Clcr = 0.64 +/- 0.35 mL/min, and proteinuria = 140.0 +/- 57.7 mg/24 h. Rats treated with MoSCs at day 120 had sCr = 0.81 +/- 0.20 mg/dL, Clcr = 1.05 +/- 0.26 mL/min, and proteinuria = 61 +/- 46.5 mg/24 h, while rats injected with MSCs had sCr = 0.95 +/- 0.1 mg/dL, Clcr = 0.68 +/- 0.24 mL/min, and proteinuria = 119.2 +/- 50.0 mg/24 h. Analysis of the progression to CRF showed that the treatment significantly reduced the rate of decline in Clcr after treatment with MoSc: control: -0.0049 +/- 0.0024 mL/min/d versus MSC: - 0.0013 +/- 0.0017 mL/min/d versus MoSC: +0.0002 +/- 0.0016 mL/min/d (P = .017). Proteinuria tended to be lower among the treated groups. Histological scores of chronic damage were not different, but distinct patterns of chronic lesions were observed among treated rats. CONCLUSION: Our results showed that progression of CRF in rats could be slowed/stabilized by intrarenal parenchymal injection of MoSCs. A trend toward reduction in the progression rate of CRF was also observed with injection of MSCs.

Effect of folate, vitamin B6, and vitamin B12 intake and MTHFR C677T polymorphism on homocysteine concentrations of renal transplant recipients.

Plasma hyperhomocysteinemia (HHcy) is considered a risk factor for chronic allograft dysfunction (CAD), the main cause of functional loss in transplant recipients. Genetic polymorphisms that alter enzymes involved in homocysteine (Hcy) metabolism, such as methylenetetrahydrofolate reductase (MTHFR), and vitamin deficiency can result in HHcy. The objectives of this study were to investigate the relationship between HHcy and CAD development, and to evaluate the effect of intake of folate and vitamins B6 and B12 as well as MTHFR C677T polymorphism on Hcy concentrations. Ninety-eight renal transplant recipients including 48 showing CAD and 50 with normal renal function (NRF), were included in this cross-sectional study. Peripheral blood samples were collected for plasma Hcy quantification by liquid chromatography/sequential mass spectrometry (LC-MS/MS), and for MTHFR polymorphism analysis using polymerase chain reaction-restriction fragment length polymorphism. Dietary intake was evaluated using a nutritional questionnaire. HHcy (P=.002) and higher mean concentrations of Hcy (P=.029) were associated with CAD. An association was observed between HHcy and 677T variant allele in the CAD group (P=.0005). There was no correlation between Hcy concentration and folate, vitamin B6 or vitamin B12 intake in the CAD group. However, a negative correlation was observed between Hcy concentration and folate intake (P=.043), and also between Hcy concentration and vitamin B6 intake (P=.030) in the NRF group. According to our study, HHcy is associated with CAD development. In patients with CAD, MTHFR polymorphism seems to have a greater effect on the Hcy concentration than the vitamin intake. Increased folate and vitamin B6 intakes seem to reduce Hcy concentrations among transplant recipients with NRF, and could contribute to reducing the risk of CAD development.

Combination of angiotensin-converting enzyme and methylenetetrahydrofolate reductase gene polymorphisms as determinant risk factors for chronic allograft dysfunction.

OBJECTIVE: The aim of this study was to investigate the frequency of gene angiotensin-converting enzyme insertion/deletion (ACE I/D) and methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) variants, as well as to evaluate the plasma homocysteine concentrations in 217 patients who underwent renal transplantation at least 12 months prior to define risk factors for chronic allograft dysfunction. METHODS: The presence of the polymorphism ACE deletion was assessed by polymerase chain reaction (PCR) analysis. MTHFR polymorphisms were determined by PCR and restriction fragment length polymorphism (RFPL) techniques. The restriction enzymes were Hinf I and Mbo II for MTHFR variants C677T and A1298C, respectively. Plasma homocysteine concentrations were measured by liquid chromatography-tandem mass spectrometry (LS-MS/MS). RESULTS: Hyperhomocysteinemias were more common in patients with chronic allograft dysfunction (P = .004). No statistically significant differences were observed between the allelic and genotypic distributions of MTHFR and ACE polymorphisms. An effective risk factor was found when the polymorphisms of the ACE and MTHFR genes and hyperhomocysteinemia were associated (odds ratio 2.51; 95% confidence interval 1.19-5.28). In conclusion, our study identified that the presence of hyperhomocysteinemia in combination with unfavorable genotypes contributes to an increased risk for development of chronic allograft dysfunction.

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable maintenance renal transplant patients: pooled results from three international, multicenter studies.

BACKGROUND: Mycophenolate mofetil (MMF) is effective in renal transplant patients but concerns remain over its gastrointestinal (GI) tolerability. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed with the intention of improving mycophenolic acid-related GI tolerability. METHODS: Data were pooled in a planned analysis of three subprotocols of the myfortic Prospective Multicenter Study (myPROMS). In a 6-month study, efficacy and safety of converting stable renal transplant recipients from MMF to a bioequivalent dose of EC-MPS for mycophenolic acid exposure were evaluated. Treatment efficacy was recorded and graft function was assessed by measuring serum creatinine and estimating creatinine clearance. Adverse events (AEs) and infections were monitored and the incidence of EC-MPS dose changes was recorded. RESULTS: A total of 588 patients were recruited, 564 (96%) of whom completed the study. The rate of treatment failure (defined as biopsy-proven acute rejection, graft loss, or death) was 1.9%, with no episodes of graft loss and only one death reported during the study. Renal function remained stable throughout the trial. EC-MPS was well tolerated; the majority of AEs were mild or moderate in severity. Dose reductions or interruptions were required by 6.3% and 1.9% of patients, respectively. Gastrointestinal AEs occurred in 138 patients (23.5%). The rate of dose adjustment as a result of a GI AE was 2.2%. CONCLUSIONS: Equimolar conversion from MMF to EC-MPS in maintenance renal transplant patients was safe and maintained efficacy.