RESUMEN
The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.
Asunto(s)
Hepatitis C/transmisión , Trasplante de Órganos , Donantes de Tejidos , Viremia/transmisión , Hepacivirus/fisiología , Hepatitis C/virología , Humanos , Sociedades Médicas , Viremia/virologíaRESUMEN
We hypothesized that de novo donor-specific antibody (DSA) causes complement-dependent endothelial cell injury in kidney transplants, as assessed by expression of endothelial cell-associated transcripts (ENDATs), that may be attenuated through complement inhibition. In total, 15 participants (five control, 10 treatment) with DSA and deteriorating renal function were enrolled. The treatment group received 6 mo of eculizumab followed by 6 mo of observation, whereas controls were observed. The primary end point was percentage change in estimated GFR (eGFR) trajectory over the treatment period. The treatment group had an improved eGFR trajectory versus control, based on our predetermined two-sided 0.10 significance level (p = 0.09). Within-subject analysis of treated participants at 6-mo intervals did not show significant change (p = 0.60). Modeling C1q status showed that C1q-positive patients had significantly higher mean eGFR than patients with negative C1q (p = 0.04). Biopsies revealed elevated renal ENDATs in most participants, but ENDATs were not reduced with complement inhibition. Our data suggest that eculizumab treatment may stabilize kidney function in patients with chronic persistent DSA based on our pilot a priori significance threshold. ENDAT expression predicative of acute humoral injury is not reduced with complement inhibition in this chronic setting. Further studies will be necessary to determine which patients may benefit from eculizumab.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Isoanticuerpos/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Adolescente , Adulto , Anciano , Enfermedad Crónica , Complemento C5/antagonistas & inhibidores , Inactivadores del Complemento/uso terapéutico , Intervención Educativa Precoz , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Supervivencia de Injerto/inmunología , Humanos , Pruebas de Función Renal , Donadores Vivos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Pronóstico , Factores de Riesgo , Donantes de Tejidos , Receptores de Trasplantes , Adulto JovenRESUMEN
Thirteen percent of individuals of African ancestry express two variant copies of the gene encoding apolipoprotein 1 (APOL1) that has been associated with an increased risk of end-stage renal disease (ESRD) in the general population. Limited studies suggest that the survival of transplanted kidneys from donors expressing two APOL1 risk alleles is inferior to that of kidneys from donors with zero or one risk allele. In living kidney donation, two case reports describe donors expressing two APOL1 risk alleles who developed ESRD. Given the potential impact of APOL1 variants on the utility and safety of kidney transplantation and living kidney donation, the American Society of Transplantation convened a meeting with the goals of summarizing the current state of knowledge with respect to transplantation and APOL1, identifying knowledge gaps and studies to address these gaps, and considering approaches to integrating APOL1 into clinical practice. The authors recognize that current data are not sufficient to support traditional evidence-based guidelines but also recognize that it may require several years to generate the necessary data. Thus, approaches as to how APOL1 might currently be integrated into the clinical decision-making process were considered. This report summarizes the group's deliberations.
Asunto(s)
Apolipoproteína L1/genética , Toma de Decisiones Clínicas , Variación Genética , Fallo Renal Crónico/diagnóstico , Trasplante de Riñón , Pautas de la Práctica en Medicina/normas , Congresos como Asunto , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/genéticaRESUMEN
Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome. Belatacept, an inhibitor of T cell costimulatory protein CTLA-4 has been used in immunosuppression strategies aimed at minimization of CNI. Here we report the first case of treatment of CNI-associated TMA/hemolytic uremic syndrome with withdrawal of tacrolimus and initiation of both belatacept and eculizumab. The case describes a favorable clinical course for both graft and patient, and is accompanied by a review of the literature.
Asunto(s)
Abatacept/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inhibidores de la Calcineurina/efectos adversos , Inmunosupresores/uso terapéutico , Microangiopatías Trombóticas/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/complicaciones , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Plasmaféresis/efectos adversos , Complicaciones Posoperatorias/inducido químicamente , Microangiopatías Trombóticas/inducido químicamente , Adulto JovenRESUMEN
Transplant professionals recognize that the long-term follow-up of living organ donors is a priority, yet there has been no implemented solution to this problem. This critical gap is essential, because the transplant field is now emphasizing living donation as a means to address the organ shortage. We detail our living donor initiative, which sets several priorities we recognize as fundamental to persons who have donated organs at our transplant center. This intervention attempts to mitigate the donor and center factors that are known to contribute to the lack of long-term follow-up. Beyond that, our goals are aimed at providing ongoing engagement, wellness, clinical data accrual, laboratory follow-up, and social support for our living donors, in continuity. Our ultimate goal is to nurture the development of local living donor community networks by providing social engagement for current and past donors, which also serves as a platform for greater population education on the societal importance of living donation. This initiative is based on joint recognition by our transplant team and our hospital leadership that supporting the long-term welfare of living donors is essential to accomplishing the goal of expanding living donor transplantation. The transplant team and hospital missions are aligned, and both contribute resources to the initiative.
Asunto(s)
Continuidad de la Atención al Paciente/normas , Atención a la Salud/normas , Donadores Vivos , Trasplante de Órganos , Calidad de Vida , Obtención de Tejidos y Órganos , Humanos , PronósticoRESUMEN
After over a decade of discussion, analysis, and consensus-building, a new kidney allocation system (KAS) was implemented on December 4, 2014. Key goals included improving longevity matching between donor kidneys and recipients and broadening access for historically disadvantaged subpopulations, in particular highly sensitized patients and those with an extended duration on dialysis but delayed referral for transplantation. To evaluate the early impact of KAS, we compared Organ Procurement and Transplantation Network data 1 year before versus after implementation. The distribution of transplants across many recipient characteristics has changed markedly and suggests that in many ways the new policy is achieving its goals. Transplants in which the donor and recipient age differed by more than 30 years declined by 23%. Initial, sharp increases in transplants were observed for Calculated Panel-Reactive Antibody 99-100% recipients and recipients with at least 10 years on dialysis, with a subsequent tapering of transplants to these groups suggesting bolus effects. Although KAS has arguably increased fairness in allocation, the potential costs of broadening access must be considered. Kidneys are more often being shipped over long distances, leading to increased cold ischemic times. Delayed graft function rates have increased, but 6-month graft survival rates have not changed significantly.
Asunto(s)
Funcionamiento Retardado del Injerto/epidemiología , Selección de Donante , Implementación de Plan de Salud , Trasplante de Riñón , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Obtención de Tejidos y Órganos/métodos , Adolescente , Adulto , Anciano , Cadáver , Niño , Preescolar , Femenino , Regulación Gubernamental , Supervivencia de Injerto , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Estados Unidos/epidemiología , Adulto JovenAsunto(s)
Altruismo , Donadores Vivos , Comercio , Humanos , Trasplante de Riñón , Obtención de Tejidos y ÓrganosRESUMEN
The introduction of the Mayo End-Stage Liver Disease score into the Organ Procurement and Transplantation Network (OPTN) deceased donor liver allocation policy in 2002 has led to a significant increase in the number of simultaneous liver-kidney transplants in the United States. Despite multiple attempts, clinical science has not been able to reliably predict which liver candidates with renal insufficiency will recover renal function or need a concurrent kidney transplant. The problem facing the transplant community is that currently there are almost no medical criteria for candidacy for simultaneous liver-kidney allocation in the United States, and this lack of standardized rules and medical eligibility criteria for kidney allocation with a liver is counter to OPTN's Final Rule. Moreover, almost 50% of simultaneous liver-kidney organs come from a donor with a kidney donor profile index of ≤0.35. The kidneys from these donors could otherwise be allocated to pediatric recipients, young adults or prior organ donors. This paper presents the new OPTN and United Network of Organ Sharing simultaneous liver-kidney allocation policy, provides the supporting evidence and explains the rationale on which the policy was based.
Asunto(s)
Política de Salud , Trasplante de Riñón/estadística & datos numéricos , Trasplante de Hígado/estadística & datos numéricos , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adulto , Anciano , Selección de Donante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Obtención de Tejidos y Órganos/organización & administración , Listas de EsperaRESUMEN
Recent studies have highlighted the need for better understanding of the long-term health outcomes of living donors. Barriers to establishment of a dedicated long-term donor follow-up data system in the United States include infrastructure costs and donor retention. We propose providing all previous and future living donors with a lifelong health insurance benefit for the primary purpose of facilitating acquisition of health information after donation as an alternative to establishment of a dedicated donor follow-up data system. Donors would consent to allow collection and analysis of their medical data, and continuation of insurance coverage would require completion of regular health assessments. The extension of health insurance would be analogous to the established practice of paying people for participation in a research study and would provide a mechanism to engage donors in a new paradigm of postdonation care in which donors are actively involved in their own health maintenance. Rather than acting as an inducement for donation, providing donors with the ability to easily contribute information about their health status represents a practical strategy to acquire the long-term medical information necessary to better inform future generations of living kidney donors.
Asunto(s)
Atención a la Salud/normas , Seguro de Salud , Donadores Vivos/psicología , Obtención de Tejidos y Órganos , Humanos , Trasplante de Riñón , Motivación , Estados UnidosRESUMEN
Previous studies suggest that quantifying donor-reactive memory T cells prior to kidney transplantation by interferon gamma enzyme-linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation-01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6- or 12-month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell-depleting, rabbit anti-thymocyte globulin (ATG). Within the no-ATG subset, IFNγELISPOT(neg) subjects had higher 6- and 12-month eGFRs than IFNγELISPOT(pos) subjects, independent of biopsy-proven AR, peak PRA, human leukocyte antigen mismatches, African-American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor-reactive memory T cells.
Asunto(s)
Biomarcadores/análisis , Ensayo de Inmunoadsorción Enzimática/métodos , Rechazo de Injerto/diagnóstico , Interferón gamma/análisis , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias , Adulto , Animales , Suero Antilinfocítico/inmunología , Niño , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Conejos , Factores de Riesgo , Donantes de TejidosRESUMEN
We sought to assess how written informed consent practices for candidate living kidney donors have changed over the last 5 years and to assess compliance with Centers for Medicare and Medicaid (CMS) and Organ Procurement and Transplantation Network (OPTN) regulations that took effect in 2007. We requested evaluation consent forms from US centers that performed >5 living kidney transplants during the prior year (n = 184). We received 148 consent forms; each was reviewed for information provided and inclusion of CMS- and OPTN-required elements. We found that nearly all transplant centers now obtain written consent for living kidney donor evaluation. However, most centers' evaluation consent forms do not include all CMS and OPTN requirements. Multiple items balancing donor and recipient interests and confidentiality were omitted. In addition, information about payment for routine follow-up care, complications related to surgery and other health problems following surgery were highly variable and frequently ambiguous. As centers revise their consent forms to address the 2013 OPTN policies, our findings may help them identify areas of potential deficiency. We propose that UNOS develop a uniform donor evaluation consent form to improve the clarity, consistency and efficiency of living donor consent.
Asunto(s)
Adhesión a Directriz/estadística & datos numéricos , Política de Salud , Consentimiento Informado/legislación & jurisprudencia , Trasplante de Riñón/ética , Donadores Vivos/ética , Guías de Práctica Clínica como Asunto , Obtención de Tejidos y Órganos/organización & administración , Formularios de Consentimiento , Selección de Donante , Estudios de Seguimiento , Humanos , Consentimiento Informado/ética , Trasplante de Riñón/psicología , Donadores Vivos/psicología , Medicare , Pronóstico , Estados UnidosRESUMEN
Noninvasive biomarkers are needed to assess immune risk and ultimately guide therapeutic decision-making following kidney transplantation. A requisite step toward these goals is validation of markers that diagnose and/or predict relevant transplant endpoints. The Clinical Trials in Organ Transplantation-01 protocol is a multicenter observational study of biomarkers in 280 adult and pediatric first kidney transplant recipients. We compared and validated urinary mRNAs and proteins as biomarkers to diagnose biopsy-proven acute rejection (AR) and stratify patients into groups based on risk for developing AR or progressive renal dysfunction. Among markers tested for diagnosing AR, urinary CXCL9 mRNA (odds ratio [OR] 2.77, positive predictive value [PPV] 61.5%, negative predictive value [NPV] 83%) and CXCL9 protein (OR 3.40, PPV 67.6%, NPV 92%) were the most robust. Low urinary CXCL9 protein in 6-month posttransplant urines obtained from stable allograft recipients classified individuals least likely to develop future AR or a decrement in estimated glomerular filtration rate between 6 and 24 months (92.5-99.3% NPV). Our results support using urinary CXCL9 for clinical decision-making following kidney transplantation. In the context of acute dysfunction, low values can rule out infectious/immunological causes of injury. Absent urinary CXCL9 at 6 months posttransplant defines a subgroup at low risk for incipient immune injury.
Asunto(s)
Lesión Renal Aguda/orina , Biomarcadores/orina , Quimiocina CXCL9/orina , Rechazo de Injerto/orina , Trasplante de Riñón , Lesión Renal Aguda/cirugía , Adulto , Biomarcadores/sangre , Quimiocina CXCL9/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Humanos , Pruebas de Función Renal , Masculino , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
Combined liver kidney transplantation (LKT) can be successfully performed on patients with liver and renal failure; however, outcomes are inferior to liver transplantation alone (OLT). Our aim was to determine the indications for and outcome of LKT and whether patients with longer wait times required more frequent LKT versus OLT alone. We included 18/93 adults who underwent LKT from August 2007 to August 2010 for hepatitis C virus (HCV, n = 7), alcohol (n = 5), nonalcoholic steatohepatitis (n = 2), primary biliary sclerosis, polycystic kidney disease with liver involvement, hepatic adenomatosis, and ischemic hepatitis. Eleven were originally listed for LKT and 7 required listing for-kidney transplantation while awaiting OLT. Eight were on dialysis when first listed and 10 had a low glomerular filtration rate or known kidney disease. The mean calculated Model for End-Stage Liver Disease (MELD) score for LKT was 31.2 ± 3.54. Seven had hepatocellular carcinoma in explants. Two patients had acute cellular kidney rejection that responded to treatment. Recurrence of HCV was documented in 5 patients within 6 months of LKT; 2/5 received HCV therapy (interferon and ribavirin) without renal allograft rejection. One-year liver graft/patient survival was 94% after LKT. One patient died at 6 months post LKT due to severe HCV recurrence. Last mean serum creatinine level was 1.35 ± 0.28 mg/dL for LKT patients. LKT is a safe procedure with favorable outcomes even in patients with a high MELD score. Transplantation of patients with a high MELD score due to regional variations in organ allocation results in additional use of kidneys by OLT patients. Improved organ allocation algorithms in OLT would help to reduce combined transplants, sparing more kidneys.
Asunto(s)
Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Riñón , Trasplante de Hígado , Insuficiencia Renal/cirugía , Adolescente , Adulto , Anciano , Connecticut , Enfermedad Hepática en Estado Terminal/complicaciones , Humanos , Persona de Mediana Edad , Insuficiencia Renal/complicaciones , Resultado del Tratamiento , Adulto JovenRESUMEN
Multidetector computed tomography (MDCT) angiography is a reliable technique for assessing pre-operative renal anatomy in living kidney donors. The method has largely evolved into protocols that eliminate dedicated venous phase and instead utilize a combined arterial/venous phase to delineate arterial and venous anatomy simultaneously. Despite adoption of this protocol, there has been no study to assess its accuracy. To assess whether or not MDCT angiography compares favorably to intra-operative findings, 102 donors underwent MDCT angiography without a dedicated venous phase with surgical interpretation of renal anatomy. Anatomical variants included multiple arteries (12%), multiple veins (7%), early arterial bifurcation (13%), late venous confluence (5%), circumaortic renal veins (5%), retroaortic vein (1%), and ureteral duplication (2%). The sensitivity and specificity of multiple arterial anomalies were 100% and 97%, respectively. The sensitivity and specificity of multiple venous anomalies were 92% and 98%, respectively. The most common discrepancy was noted exclusively in the interpretation of right venous anatomy as it pertained to the renal vein/vena cava confluence (3%). MDCT angiography using a combined arterial/venous contrast-enhanced phase provides suitable depiction of renal donor anatomy. Careful consideration should be given when planning a right donor nephrectomy whether the radiographic interpretation is suggestive of a late confluence.
Asunto(s)
Angiografía/métodos , Supervivencia de Injerto , Trasplante de Riñón/diagnóstico por imagen , Donadores Vivos , Arteria Renal/diagnóstico por imagen , Venas Renales/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Humanos , Cuidados Preoperatorios , Pronóstico , Arteria Renal/anatomía & histología , Venas Renales/anatomía & histología , Sensibilidad y EspecificidadRESUMEN
Angiotensin II converting enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) are frequently avoided as treatment for hypertension in the early posttransplant period (0 to 90 days) for fear of nephrotoxicity. The following retrospective study was designed to explore the safety of these drugs in the early posttransplant period and determine appropriate clinical criteria for starting these medications. The records of all adult renal transplants performed between January 1997 and December 2000 (N = 290) were reviewed. All patients started on ACE or ARB for treatment of hypertension within 90 days of their transplant were included in the analysis (n = 17). Controls (n = 19) were patients who were treated with a calcium channel blocker (CCB) for hypertension. Cases and controls were matched for gender and type of transplant, living or cadaver. Patients were considered to be enrolled whey they met the following criteria: hypertension, serum creatinine < or =3.0 mg/dL, or falling 1 mg/dL/d and serum potassium < or =5.5 mEq/L. Exclusion criteria were coexistent pancreas transplant, anaphylaxis to ACE, and use of ACE or ARB for treatment of posttransplant erythrocytosis. There were no differences between cases and controls in hemoglobin or serum potassium concentrations or calculated glomerular filtration rate at 3, 6, and 9 months. In renal transplant patients with reasonable allograft function, administration of ACE and ARB to treat hypertension in the early posttransplant period appears to be well tolerated and not associated with excess hyperkalemia, anemia, or acute renal dysfunction.
Asunto(s)
Bloqueadores del Receptor Tipo 2 de Angiotensina II , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Trasplante de Riñón/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Potasio/sangre , Estudios Retrospectivos , Seguridad , Trasplante HomólogoRESUMEN
Everolimus is a derivative of sirolimus, a macrocyclic lactone, originally isolated from Streptomyces hygroscopicus. Both everolimus and sirolimus have a similar mechanism of action, exerting potent inhibition of growth factor-induced proliferation of lymphocytes, as well as other hematopoietic and nonhematopoietic cells of mesenchymal origin. Each agent complexes with the FK506 binding protein 12 to inhibit cyclin dependent kinase(s), collectively termed the target of rapamycin (TOR), causing G1-S phase cell cycle arrest. Safety and efficacy have been documented in large-scale, blinded, randomized, international clinical renal and cardiac transplant trials. Everolimus is more hydrophilic, exhibits a shorter elimination half-life (approximately 30 hours), and demonstrates greater relative bioavailability compared to sirolimus. However, similar to the calcineurin inhibitors and sirolimus, everolimus is biotransformed by the cytochrome P450, 3A4 isozyme. Also similar to sirolimus, clinical experiences identified biologically relevant side effects including hyperlipidemia and exacerbation of cyclosporine (CsA)-associated nephrotoxicity. However, also similar to sirolimus, accumulating evidence suggests that the hyperlipidemia can be controlled and the CsA-associated renal effects appear reduced with a low incidence of acute rejection when everolimus is administered in combination with reduced CsA doses. The experience using everolimus in cardiac transplantation has also provided potentially important insights into the consequences of antiproliferative effects on vascular smooth muscle cells and fibroblasts where reduction in intimal expansion was identified by intravascular coronary ultrasound examination among those patients receiving everolimus. Therefore, available results suggest that the introduction of everolimus as the newest TOR inhibitor should enhance therapeutic options for immunosuppression after organ transplantation.
Asunto(s)
Inmunosupresores/uso terapéutico , Sirolimus/análogos & derivados , Sirolimus/uso terapéutico , Inmunología del Trasplante , Ensayos Clínicos Fase I como Asunto , Everolimus , Humanos , Inmunosupresores/toxicidad , Sirolimus/toxicidadRESUMEN
Sirolimus (SRL), a fermentation product of Streptomyces hygroscopicus, complexes with the FKBP12 to inhibit cyclin dependent kinase(s), collectively termed the target of rapamycin (TOR), causing G(1)-S phase cell cycle arrest. Safety and efficacy have been documented in clinical renal transplantation, but concerns were raised due to important biologically relevant side effects. Hyperlipidemia was identified, beginning with early clinical experiences, and the unexpected findings that SRL may exacerbate CsA associated nephrotoxicity was observed during the pivotal phase III studies. This report details results of our experience using SRL (target trough concentration, 10-15 ng/mL) with low dose CsA (target trough concentration, 50-100 ng/mL), seeking to determine whether this approach might provide effective immunosuppression while reducing associated nephrotoxicity. Among 121 renal transplant recipients, 62 received the SRL based regimen and 59 received MMF with all patients receiving CsA and prednisone. Similar to earlier clinical experiences, hematopoeitic abnormalities and hyperlipidemia were observed among patients who received SRL, and those abnormalities were readily controlled. However, unlike observations from the phase III SRL studies, renal function was not adversely affected. These findings support the growing body of evidence indicating that SRL based immunosuppression in combination low dose calcineurin inhibitors and corticosteroids is safe, efficacious, and without associated renal toxicity.