Living and deceased organ donation should be financially neutral acts.

The supply of organs­particularly kidneys­donated by living and deceased donors falls short of the number of patients added annually to transplant waiting lists in the United States. To remedy this problem, a number of prominent physicians, ethicists, economists and others have mounted a campaign to suspend the prohibitions in the National Organ Transplant Act of 1984 (NOTA) on the buying and selling of organs. The argument that providing financial benefits would incentivize enough people to part with a kidney (or a portion of a liver) to clear the waiting lists is flawed. This commentary marshals arguments against the claim that the shortage of donor organs would best be overcome by providing financial incentives for donation. We can increase the number of organs available for transplantation by removing all financial disincentives that deter unpaid living or deceased kidney donation. These disincentives include a range of burdens, such as the costs of travel and lodging for medical evaluation and surgery, lost wages, and the expense of dependent care during the period of organ removal and recuperation. Organ donation should remain an act that is financially neutral for donors, neither imposing financial burdens nor enriching them monetarily.

Consensus conference on best practices in live kidney donation: recommendations to optimize education, access, and care.

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation.

Organ transplantation for nonresidents of the United States: a policy for transparency.

A policy proposal relating to transplantation of deceased donor organs into nonresidents of the United States was jointly sponsored by the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) International Relations and Ethics Committees and approved by the OPTN/UNOS Board in June 2012. The proposal followed prior acceptance by the Board of the definitions of "travel for transplantation" and "transplant tourism" and the introduction in March 2012 of revised data collection categories for transplant candidates who are neither citizens nor residents. The most important aspect of the new policy concerns replacement of the previous so-called "5% rule" with the review of all residency and citizenship data and the preparation of a public annual report. The new policy does not prohibit organ transplantation in nonresidents. However, the policy and public data report will ensure transparency and support transplant center responsibility to account for their practices. Since the adoption of the policy, the first 19 months of data show that less than 1% of new deceased donor waitlist additions and less than 1% of transplantation recipients were non-US citizen/nonresidents candidates who traveled to the United States for purposes of transplantation. By adopting this policy, the US transplant community promotes public trust and serves as an example to the international transplant community.

Chain transplantation: initial experience of a large multicenter program.

We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross-matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O-patients receiving a transplant (n = 90) was greater than the number of blood type O-non-directed donors (n = 32) initiating chains. We have 1-year follow up on the first 100 transplants. The mean 1-year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.

Simultaneous liver-kidney transplantation summit: current state and future directions.

Although previous consensus recommendations have helped define patients who would benefit from simultaneous liver-kidney transplantation (SLK), there is a current need to reassess published guidelines for SLK because of continuing increase in proportion of liver transplant candidates with renal dysfunction and ongoing donor organ shortage. The purpose of this consensus meeting was to critically evaluate published and registry data regarding patient and renal outcomes following liver transplantation alone or SLK in liver transplant recipients with renal dysfunction. Modifications to the current guidelines for SLK and a research agenda were proposed.

The use of executed prisoners as a source of organ transplants in China must stop.

Internationally accepted ethical standards are unequivocal in their prohibition of the use of organs recovered from executed prisoners: yet this practice continues in China despite indications that Ministry of Health officials intend to end this abhorrent practice. Recently published articles on this topic emphasize the medical complications that result from liver transplantation from executed 'donors' but scant attention is given to the source of the organs, raising concern that the transplant community may be becoming inured to unacceptable practice. Strategies to influence positive change in organ donation practice in China by the international transplant community are discussed. They include an absolutist policy whereby no clinical data from China is deemed acceptable until unacceptable donation practices end, and an incremental policy whereby clinical data is carefully evaluated for acceptability. The relative advantages and drawbacks of these strategies are discussed together with some practical suggestions for response available to individuals and the transplant community.

Associations of body mass index and weight loss with mortality in transplant-waitlisted maintenance hemodialysis patients.

A body mass index (BMI) below morbid obesity range is often a requirement for kidney transplant wait-listing, but data linking BMI changes to mortality during the waitlist period are lacking. By linking the 6-year (7/2001-6/2007) national databases of a large dialysis organization and the Scientific Registry of Transplant Recipients, we identified 14 632 waitlisted hemodialysis patients without kidney transplantation. Time-dependent survival models examined the mortality predictability of 13-week-averaged BMI, pretransplant serum creatinine as a muscle mass surrogate and their changes over time. The patients were on average 52 ± 13 years old, 40% women and had a BMI of 26.9 ± 6.3 kg/m². Each kg/m² increase of BMI was associated with a death hazard ratio (HR) of 0.96 (95%CI: 0.95-0.97). Compared to the lowest creatinine quintile, the 4th and 5th quintiles had death HRs of 0.75 (0.66-0.86) and 0.57 (0.49-0.66), respectively. Compared to minimal (< ± 1 kg) weight change over 6 months, those with 3 kg- < 5 kg and ≥ 5 kg weight loss had death HRs of 1.31 (1.14-1.52) and 1.51 (1.30-1.75), respectively. Similar associations were observed with creatinine changes over time. Transplant-waitlisted hemodialysis patients with lower BMI or muscle mass and/or unintentional weight or muscle loss have higher mortality in this observational study. Impact of intentional weight change remains unclear.

Disparities in the utilization of live donor renal transplantation.

Despite universal payer coverage with Medicare, sociodemographic disparities confound the care of patients with renal failure. We sought to determine whether adults who realize access to kidney transplantation suffer inequities in the utilization of live donor renal transplantation (LDRT). We identified adults undergoing primary renal transplantation in 2004-2006 from the United Network for Organ Sharing (UNOS). We modeled receipt of live versus deceased donor renal transplant on multilevel multivariate models that examined recipient, center and UNOS region-specific covariates. Among 41 090 adult recipients identified, 39% underwent LDRT. On multivariate analysis, older recipients (OR 0.62, 95% CI 0.56-0.68 for 50-59 year-olds vs. 18-39 year-old recipients), those of African American ethnicity (OR 0.54, 95% CI 0.50-0.59 vs. whites) and of lower socioeconomic status (OR 0.72, 95% CI 0.67-0.79 for high school-educated vs. college-educated recipients; OR 0.78, 95% CI 0.71-0.87 for lowest vs. highest income quartile) had lower odds of LDRT. These characteristics accounted for 14.2% of the variation in LDRT, more than recipient clinical variables, transplant center characteristics and UNOS region level variation. We identified significant racial and socioeconomic disparities in the utilization of LDRT. Educational initiatives and dissemination of processes that enable increased utilization of LDRT may address these disparities.

Asynchronous, out-of-sequence, transcontinental chain kidney transplantation: a novel concept.

The organ donor shortage has been the most important hindrance in getting listed patients transplanted. Living kidney donors who are incompatible with their intended recipients are an untapped resource for expanding the donor pool through participation in transplant exchanges. Chain transplantation takes this concept further, with the potential to benefit even more recipients. We describe the first asynchronous, out of sequence transplant chain that was initiated by transcontinental shipment of an altruistic donor kidney 1 week after that recipient's incompatible donor had already donated his kidney to the next recipient in the chain. The altruistic donor kidney was transported from New York to Los Angeles and functioned immediately after transplantation. Our modified-sequence asynchronous transplant chain (MATCH) enabled eight recipients, at four different institutions, to benefit from the generosity of one altruistic donor and warrants further exploration as a promising step toward addressing the organ donor shortage.

Military antishock trousers. Effect on hemodialysis-induced hypotension.

To evaluate the effect of military antishock trousers (MAST) on hemodialysis-induced hypotension, we observed seven patients undergoing maintenance hemodialysis treatment. We saw each patient on two separate occasions during four-hour hemodialysis treatments. On one occasion , we inflated the MAST to a pressure of 45 mm Hg over the lower extremities and 15 mm Hg over the abdomen; on the second occasion, the MAST were not inflated. Blood pressure was recorded at 15-minute intervals. We found no significant difference between the mean arterial pressure with MAST inflation and that in the control studies. The weight losses during the two studies were also similar. We suggest that, despite their reported efficacy in post-trauma hypotension, MAST are not effective in managing dialysis-induced hypotension.

Catecholamine responses to central volume expansion produced by head-out water immersion and saline infusion.

To delineate plasma catecholamine responses to central volume expansion, four salt-replete healthy adults were subjected to 4 h of thermoneutral head-out water immersion (WI) and infusion of 2 liters normal saline (SI) over 4 h on two separate occasions. Each study was preceded and followed by a control hour. Both of these maneuvers resulted in significant increases in urinary sodium excretion and suppression of PRA and plasma aldosterone levels. During WI studies, plasma norepinephrine levels fell steadily from a prestudy value of 453 +/- 74 pg/ml to a nadir of 254 +/- 71 pg/ml (P less than 0.05) during the fourth immersion hour. In response to SI, plasma norepinephrine fell steadily from a prestudy level of 328 +/- 56 pg/ml to a nadir of 261 +/- 47 pg/ml during the fourth hour of infusion. Plasma dopamine levels rose and epinephrine levels were unchanged in response to WI as well as SI. When the mean urinary sodium excretion was plotted against the mean dopamine to norepinephrine ratio, there was a direct relationship in WI studies (r = 0.90) as well as SI studies (r = 0.92). These data suggest that plasma norepinephrine levels fall and plasma dopamine levels rise in response to volume expansion. These data also suggest that relative concentrations of dopamine vs those of norepinephrine may have a role in mediating natriuresis in response to volume expansion.

Cyclosporine microemulsion- and mycophenolate mofetil-related lymphoid aggregates are not associated with acute rejection.

BACKGROUND: Microemulsion cyclosporine, mycophenolate mofetil, and prednisone have become a common immunosuppressive protocol in renal transplantation. We identified lymphocytic infiltrates in transplant fine-needle aspirates and core biopsies from patients on this regimen without acute rejection clinically or by standardized morphological criteria and investigated this inflammatory response. METHODS: Twenty-eight aspirates from 21 patients were included and assessed in the standard fashion. Nine core biopsies showing interstitial lymphocytic infiltration were evaluated with antibodies against CD3, CD4, CD8, CD20, CD30, CD56, KP1, and epithelial membrane antigen (EMA). Aspirates and biopsies were assessed for tubular cell major histocompatibility complex (MHC) class II antigen and for gamma-interferon (gamma-IFN), interleukin-4 (IL-4), and IL-10 mRNAs by reverse transcription-polymerase chain reaction. RESULTS: Fifteen aspirates showed immune activation solely due to mature lymphocytes and monocytes; 13 had no immune activation. All aspirates were negative for MHC class II antigens. Of 6 activated aspirates assessed for gamma-IFN mRNA, 5 were negative. All 21 patients had similar clinical characteristics and recovered renal function without rejection treatment. The core biopsies had lymphocytes in 5-30% of the interstitium. The cells were 70-85% CD3+, with 50-85% CD4+, 3-10% KP1+, and rare cells CD56+. No T-cell activation was present (EMA- and CD30-). Seven biopsies were assessed and were negative for gamma-IFN mRNA; only one biopsy had weakly positive MHC class II staining. Two activated aspirates were negative for IL-4 and IL-10 mRNA, while three biopsies each contained IL-4 and IL-10 mRNAs. CONCLUSIONS: Inactive interstitial lymphoid infiltrates are frequent in patients on this drug regimen and should not be interpreted as acute rejection, particularly in aspirate samples. These lymphocytes may play a role in long-term allograft acceptance.

Gamma-interferon gene expression in human renal allograft fine-needle aspirates.

Cytokines appear to play a major role in acute transplant rejection (AR); however, the specific cytokines initiating AR are not known. To investigate gamma-interferon messenger RNA (mRNA) as a key factor in AR induction, we performed reverse transcription-polymerase chain reaction (RT-PCR) on renal allograft fine-needle aspirates (FNA). Fifteen FNA from 15 patients were processed and interpreted in the standard fashion, the percent of tubular cells with MHC class II expression (DR) quantitated, and aliquots of FNA obtained for RT-PCR. RT-PCR was performed with primers to gamma-IFN with cyclophylin and insulin primers as controls. Retrospective clinical diagnoses were made for each FNA sample. Following RT-PCR, all FNA and FNAs from control normal and AR nephrectomy specimens had cyclophylin present, and in the 9 samples tested insulin was absent. Five patients had AR clinically and by FNA criteria; all 5 had elevated DR and gamma-IFN mRNA present in FNA. Five patients had tubular necrosis or cyclosporine toxicity clinically, and FNA without immune activation or elevated DR and negative gamma-IFN mRNA. Two patients had immune activation by FNA with elevated DR; both FNA expressed gamma-IFN mRNA by Southern blot, one only weakly, and both patients subsequently developed clinical AR. Two patients had recently treated AR, one with persistent DR elevation without-immune activation and negative gamma-IFN mRNA in FNAs. This study demonstrates that RT-PCR can be performed with renal allograft FNA samples. The findings suggest intragraft gamma-IFN mRNA expression occurs in active AR preceding clinical AR, thus defining incipient AR. Detection of gamma-IFN mRNA may offer an early diagnostic tool for detection of AR.

The evaluation of candidates for renal transplantation. The current practice of U.S. transplant centers.

The criteria for acceptance of candidates for renal transplantation varies throughout the United States. The Patient Care and Education Committee of the American Society of Transplant Physicians conducted a survey of all U.S. centers that participate in the United Network for Organ Sharing (UNOS) concerning their evaluation of adult candidates for kidney transplantation. The response to each question was examined according to the specialty of the individual who filled out the questionnaire, as well as the type of transplant center (university or private) and the size of the center. The response rate to the survey was 81% (147/182). We found the following: (1) university-based and larger centers accepted more medically complicated patients; (2) 83% noted that attendance to dialysis was an important indicator of compliance after transplantation; (3) 79% did not require preoperative blood transfusions for cadaver kidney recipients; (4) 66% set no specific upper age limit for transplantation; (5) 56% excluded patients with chronic active hepatitis in the setting of hepatitis B antigenemia; (6) 50% had no specific policy for evaluating hepatitis C antibody-positive patients, while 54% excluded the use of hepatitis C antibody-positive donors, and (7) 15% obtained coronary angiography on all diabetic patients. U.S. transplant centers have a heterogeneous approach to the evaluation of patients for renal transplantation, particularly in the areas of viral hepatitis, cardiovascular disease, and noncompliance. University-based centers and centers that perform a larger number of transplants accept more medically complicated patients.

Angiotensin-converting enzyme inhibition in the treatment of renal transplant erythrocytosis. Clinical experience and observation of mechanism.

Recent observations indicate that angiotensin-converting enzyme (ACE) inhibition corrects renal transplant erythrocytosis (RTE). The mechanism for this association is not known. We examined the effect of ACE inhibition on hematocrit, erythropoietin (EPO), and renin substrate. ACE inhibition has been reported to suppress renin substrate, which is known to stimulate EPO and erythropoiesis. In 15 patients with RTE, hematocrit dropped from 52.8 +/- 0.6 (SEM) to 45.8 +/- 1.4% after 8 weeks of treatment with Enalapril, 2.5-20 mg/day. Serum EPO (normal range: 9-30 mU/ml) was high in one, normal in seven, and low in seven patients. ACE inhibition reduced EPO in patients with initial high or normal levels but induced no change in patients with initial low levels. ACE inhibition had no significant effect on renin substrate. In one patient who rejected his first graft, erythrocytosis recurred following a second, successful transplant. Treatment was discontinued because of cough in two patients and symptomatic drop in blood pressure in one patient. We conclude RTE is not caused by hypererythropoietinemia. In patients with normal circulating EPO, erythrocytosis may result from an increase sensitivity to EPO, and ACE inhibition lowered hematocrit by further reduction of this hormone. However, the finding of erythrocytosis in half our patients with suppressed EPO, suggests the participation of non-EPO-mediated mechanism(s). The recurrence of RTE in a patient after a second transplant raises the additional possibility of patient-specific factors in the pathogenesis of this disorder. In contrast to other reports, we documented side-effects (cough, hypotension) in three (20%) of our patients. Our clinical experience, coupled with prior reports of spontaneous resolution of RTE in some patients, suggests that intermittent courses of ACE-inhibition may be the optimal strategy in the use of this form of therapy for RTE.

Interleukin-12 mRNA levels in renal allograft fine-needle aspirates do not correlate with acute transplant rejection.

TH1 cytokines, including gamma-interferon (IFN), are critical in the initiation and progression of allograft rejection. As interleukin (IL)-12 up-regulates gamma-IFN, we assessed the role of IL-12 in human transplant rejection. Twenty renal allograft fine-needle aspirates from 19 patients were obtained, evaluated in the standard fashion, and assessed for gamma-IFN and IL-12p40 subunit mRNA levels using nested reverse transcriptase polymerase chain reaction. Ten aspirates demonstrated acute rejection by clinical criteria, and 9 of the 10 aspirates contained gamma-IFN while only 3 demonstrated IL-12; there were no distinguishing characteristics for these 3 patients with regard to therapy, or time of onset and severity of rejection. Seven patients without clinical or morphologic rejection failed to demonstrate gamma-IFN or IL-12. Three patients had discrepant findings; there was no morphologic rejection, yet all 3 patients contained gamma-IFN and 1 patient demonstrated rejection on subsequent biopsy. However, only 1 aspirate exhibited IL-12 and this patient had no documented subsequent rejection. This study confirms the association of gamma-IFN mRNA with acute rejection. In contrast, IL-12 mRNA does not appear to play a key role early in the rejection process.

Pentoxifylline does not prevent the cytokine-induced first dose reaction following OKT3--a randomized, double-blind placebo-controlled study.

The use of OKT3 as an immunosuppressive agent is accompanied by increased cytokine production and constellation of side effects collectively termed cytokine release syndrome (CRS). Pentoxifylline (PTF) inhibits synthesis of some cytokines, and has been shown to attenuate CRS when administered before OKT3. In this double-blinded, placebo-controlled study, 46 renal allograft recipients were randomized to receive either PTF (800 mg q 8 hr for at least 24 h) p.o. or placebo, along with methylprednisolone (7 mg/kg), diphenhydramine, and acetaminophen, prior to beginning OKT3 as therapy for acute rejection. Patients were observed, and symptoms scored semiquantitatively. Despite the presence of therapeutic PTF levels (721 +/- 726 ng/ml), the frequency and severity of side effects (fever, chills, headache, neurocortical symptoms, dyspnea, nausea, vomiting, diarrhea) did not differ between treatment groups. Likewise PTF did not affect renal function or immunologic response to OKT3, with similar graft and patient survival in both groups. Plasma levels of TNF alpha, IFN gamma, IL-6, and IL-8 increased as predicted following OKT3 administration, without significant differences between PTF and placebo groups. In this controlled, multicenter trial, pretreatment with oral PTF was ineffective in attenuating OKT3-related CRS in renal allograft recipients.

Evaluation of living renal donors. The current practice of US transplant centers.

To examine practice patterns regarding how living donors are evaluated and selected in the U.S., a survey was sent to all 231 United Network of Organ Sharing (UNOS)-approved transplant centers. Respondents from 75% of centers completed the questionnaire, all of whom utilize living donors for renal transplantation. Although the use of living-unrelated donors is also widely accepted (in 92% of centers), only 31% of responding centers performed such transplants in 1992, indicating a discrepancy between acceptance and actual practice. Morbidity (0.23%) and mortality (0.03%) of kidney donation continue to be low. The long-term risk of renal insufficiency in kidney donors appears to be similar to, or lower than, that in the general population. There is substantial variability in how potential donors are evaluated and what they are told regarding the risk involved in renal donation. There is also variability in exclusion criteria such as the acceptance of older donors (> 55 years old); those with borderline-to-mild hypertension, and those with borderline low glomerular filtration rate. Larger centers tended to be less rigid in their exclusion criteria compared with smaller centers. While our results indicate widespread acceptance and use of living donors, they also highlight the need for future studies to examine the efficacy of tests used in the evaluation process and to determine the long-term risks of renal donation.

A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. A report of the Tacrolimus Kidney Transplantation Rescue Study Group.

A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection. Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81%) had previously received at least one course of antilymphocyte antibody as rejection therapy. One-year follow-up was available in 93% of patients. Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78% of patients, stabilization in 11%, and progressive deterioration in 11%. The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine < or = mg/dl, 3%; 3.1-5 mg/dl, 16% (P < 0.04); > 5 mg/dl, 23% (P < 0.02). Twelve-month (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93% and 75%. Graft loss occurred in 19 patients (25%) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients (14%), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients. Antilymphocyte antibody therapy was not used to treat recurrent rejection. Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15%), including cytomegalovirus infection in three patients (4%). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0 +/- 9.9 ng/ml at day 7 of tacrolimus therapy and 9.4 +/- 5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18% of patients for rejection (11% for progressive, unrelenting rejection, and 7% for recurrent rejection). Tacrolimus therapy was discontinued in 8% of patients due to adverse events. In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good long-term renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection.

Cyclosporine and tacrolimus-associated thrombotic microangiopathy.

The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA.