The living donor evaluation as a life-saving event.

BACKGROUND: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem. While these problems may preclude donation, they may be lifesaving, as they are likely to be diagnosed and treated before the donor develops symptoms. PATIENTS AND METHODS: We looked at the incidence of occult cancer and other previously undiagnosed medical problems including renal disease, diabetes, hypertension, cardiac disease, and hepatitis C, in individuals volunteering to become a kidney donor at our center who proceeded with the evaluation between January 1, 1996 and May 31, 2011. RESULTS: Of 4088 potential donors, 19 (.46%) were discovered to have an unsuspected cancer, and 286 (7%) were found to have a previously undiagnosed medical problem. CONCLUSIONS: The living donor evaluation may lead to the early diagnosis of a life-threatening illness. This should be considered as one of the potential benefits of living donation.

The Abdominal Transplant Surgery Workforce: Current state and future trends.

Transplant surgical workforce concerns have arisen in the last 5 years as reflected in challenges securing job opportunities for new fellows. The present survey was designed by the ASTS Membership and Workforce Committee to describe the current practice characteristics of transplant centers in order to estimate changes in the workforce. The survey questionnaire requested information about the transplant programs, the transplant surgeons involved in the program, and the estimated changes in the staffing of the program over the next 3 years. Seventy-one transplant centers responded from a total of 235 identified and queried (30.2% response rate), with median responding centers per UNOS region of 7 (IQR 4.5-8.5). The recruitment outlook for the next 3 years forecasts a positive inflow of surgeons at a 2:1 rate (incoming:leaving). The new female transplant workforce within the responding cohort has increased from 3.7% in 1980 to 18.4% in 2010. Currently, 13.1% of practicing US transplant surgeons in this survey are female which is higher than many other surgical specialties. This report represents the most up-to-date view into the abdominal transplant surgical workforce. The positive job recruitment outlook for transplant surgeons and the narrowing gender gap are new findings from this study.

The development of practice guidelines for independent living donor advocates.

The practice recommendations discussed here are based on the findings of the national survey as well as the opinions of the authors. The recommendations that are proposed here are not exhaustive and are aspirational in intent and are likely to evolve with time. Practice guidelines are recommended for legal and regulatory issues (e.g., state or federal laws), consumer or public benefit (e.g., improving service delivery, avoiding harm to the patient, decreasing disparities in underserved or vulnerable populations), and for professional guidance (e.g., new role, professional risk management issues, advances in practice). Without such practice guidelines, donors, and indirectly the candidates, may be at increased risk for possible bias or undue harm.

Prevention of poor psychosocial outcomes in living organ donors: from description to theory-driven intervention development and initial feasibility testing.

CONTEXT: Although some living donors experience psychological, somatic, and interpersonal difficulties after donation, interventions to prevent such outcomes have not been developed or evaluated. OBJECTIVE: To (1) summarize empirical evidence on psychosocial outcomes after donation, (2) describe a theoretical framework to guide development of an intervention to prevent poor outcomes, and (3) describe development and initial evaluation of feasibility and acceptability of the intervention. METHODS: Based on a narrative literature review suggesting that individuals ambivalent about donation are at risk for poor psychosocial outcomes after donation, the intervention targeted this risk factor. Intervention structure and content drew on motivational interviewing principles in order to assist prospective donors to resolve ambivalence. Data were collected on donors' characteristics at our institution to determine whether they constituted a representative population in which to evaluate the intervention. Study participants were then recruited to assess the feasibility and acceptability of the intervention. They were required to have scores greater than 0 on the Simmons Ambivalence Scale (indicating at least some ambivalence about donation). RESULTS: Our population was similar to the national living donor population on most demographic and donation-related characteristics. Eight individuals who had been approved to donate either a kidney or liver segment were enrolled for pilot testing of the intervention. All successfully completed the 2-session telephone-based intervention before scheduled donation surgery. Participants' ratings of acceptability and satisfaction were high. Open-ended comments indicated that the intervention addressed participants' thoughts and concerns about the decision to donate. CONCLUSIONS: The intervention is feasible, acceptable, and appears relevant to donor concerns. A clinical trial to evaluate the efficacy of the intervention is warranted.

Rates and correlates of health maintenance behaviors after living kidney donation.

CONTEXT AND OBJECTIVE: Donating a kidney may provide an opportunity for donors to reevaluate their health maintenance behaviors (eg, regular exercise, smoking cessation, medical checkups). Although the effect of donation on donors' health, quality of life, and financial outcomes has received growing attention, no studies have examined whether donation is related to changes in health maintenance behaviors. The study aims were to (1) describe and compare kidney donors' health maintenance behaviors before and after donation, and (2) determine the correlates of health maintenance behaviors after donation. DESIGN, SETTING, PARTICIPANTS AND MEASURES: We conducted a telephone-interview study with 85 randomly selected laparoscopic kidney donors in a major US transplant center to assess health behaviors before and after donation, postdonation characteristics (eg, quality of life, postsurgical pain), and demographics. RESULTS: Sample demographics included a median age of 48 years; 55% were female, 82% were white, 71% were married, and 52% were college graduates. Few health behaviors changed significantly from before to after donation. Only the rate of medical checkups increased after donation (P< .001). Logistic regression was used to examine the association of demographics and postdonation characteristics with postdonation health maintenance behaviors, after adjusting for predonation behavior. Older age, higher income, less postsurgical pain, and better physical functioning were associated with more exercise after donation. Longer time since donation was associated with a higher prevalence of obesity. CONCLUSIONS: These results may help identify donors who are at greater risk for poor health maintenance behaviors after donation and suggest areas of health behavior that should be the focus of education sessions before donation.

Systematic review: hepatitis C viraemic allografts to hepatitis C-negative recipients in solid organ transplantation.

BACKGROUND: Given the success of direct-acting antivirals (DAAs) in treating hepatitis C (HCV), interest is growing in utilizing solid organs from allografts with active HCV to expand donor availability. AIM: To review post-transplant outcomes and patient survival in HCV-negative recipients receiving solid organ transplants (SOT) from viraemic, that is, HCV+/NAT+ (nucleic acid testing) allografts. METHODS: A literature search was conducted on PubMed and EMBASE from 01/01/2007 to 4/17/2021 for articles matching eligibility criteria. Two authors independently screened titles and abstracts. Disagreements were solved by a third independent reviewer. Methodological quality assessment was done using a modified Newcastle-Ottawa scale (NOS). Data synthesis was done qualitatively using median, ranges and percentages. RESULTS: Thirty-five studies were included (or 852 SOTs): 343 kidney, 233 heart, 204 liver, and 72 lung transplants from viraemic allografts. Of the recipients eligible for sustained virological response at 12 weeks (SVR12) calculation, 100% achieved cure from HCV. No deaths/graft failures were reported to be related to HCV transmission. Seven SOT recipients had viral relapse, with all seven patients treated successfully. Four patients developed fibrosing cholestatic hepatitis with complete resolution post-treatment. CONCLUSIONS: Transplanting viraemic organs into uninfected individuals can become the standard of care for patients who do not have contraindications to DAAs.

HMG-CoA reductase inhibitors in kidney transplant recipients receiving tacrolimus: statins not associated with improved patient or graft survival.

BACKGROUND: The beneficial effects of early statin use in kidney transplant recipients, especially those on tacrolimus-based immunosuppression, are not well established. We evaluated the predictors of statin use following kidney transplantation and examined its association with patient and allograft survival. METHODS: We examined 615 consecutive patients who underwent kidney transplant at our institution between January 1998 and January 2002. Statin use was assessed at baseline and 3, 6, 9, and 12 months following kidney transplant. Patients were followed for allograft and patient survival. RESULTS: 36% of the 615 kidney transplant recipients were treated with statin treatment. Statin use increased over the course of the study period. Older age, elevated body mass index, higher triglyceride levels, hypercholesterolemia, diabetes, history of myocardial infarction were associated with higher rates of statin use; elevated alkaline phosphatase levels and CMV IgG seropositivity were associated with less statin use. Older age, elevated BMI and hypercholesterolemia remained significant predictors of increased statin use after accounting for covariates using multiple regression. The early use of statins was not associated with improvements in unadjusted patient survival [HR 0.99; 95%CI 0.72-1.37] or graft survival [HR 0.97; 95% CI 0.76-1.24]. The risks of death and graft survival were not consistently reduced with exposure to statin using either adjusted models or propensity scores in Cox Proportional Hazards models. CONCLUSIONS: In a kidney transplant population primarily receiving tacrolimus-based immunosuppression, early statin use was not associated with significantly improved graft or patient survival.

The significance of renal C4d staining in patients with BK viruria, viremia, and nephropathy.

Peritubular capillary C4d staining in allograft kidney is an important criterion for antibody-mediated rejection. Whether BK virus infection can result in complement activation is not known. We studied 113 renal allograft biopsies from 52 recipients with a history of BK virus activation. The samples were classified into four groups according to the concurrent detection of BK virus DNA in urine, plasma, and/or biopsy: BK-negative (n=37), viruria (n=53), viremia (n=7), and nephropathy (n=16) groups. The histological semiquantitative peritubular capillary C4d scores in the viremia (0.3+/-0.8) and BK nephropathy (0.6+/-0.9) groups were lower than those in the BK-negative group (1.2+/-1.1, P=0.05 and P=0.06, respectively) and the viruria group (1.2+/-1.1, P=0.04 and P=0.06, respectively). Diffuse or focal peritubular capillary C4d staining was present in 9/76 (12%) and 14/76 (19%) of all samples with concurrent BK virus reactivation (viruria, viremia, and nephropathy). The diagnosis of antibody-mediated rejection could be established in 7/9 (78%) and 5/14 (36%) of these samples, respectively. Diffuse tubular basement membrane C4d staining was restricted to BK nephropathy cases (4/16, 25%). Semiquantitative tubular basement membrane C4d scores were higher in BK nephropathy (1.2+/-1.3) compared with BK-negative (0.05+/-0.3, P=0.017) and viruria (0.0+/-0.0, P=0.008) groups. Bowman's capsule C4d staining was more frequent in BK nephropathy (5/16) compared with the aforementioned groups (2/36 (P=0.023) and 4/51 (P=0.03), respectively). Within the BK nephropathy group, samples with tubular basement membrane stain had more infected tubular epithelial cells (12.1+/-7.6% vs 4.4+/-5.0%, P=0.03) and a trend toward higher interstitial inflammation scores. In conclusion, peritubular capillary C4d staining remains a valid marker for the diagnosis of antibody-mediated rejection in the presence of concurrent BK virus infection. A subset of biopsies with BK nephropathy shows tubular basement membrane C4d staining, which correlates with marked viral cytopathic effect.

Outcomes of Deceased Donor Kidney Transplantation Using Expanded Criteria Donor Kidneys Following Pulsatile Preservation.

Aim We compared the outcomes of transplanting expanded criteria donor (ECD) kidneys undergoing machine perfusion (MP) versus cold storage (CS). Material and methods Data on all expanded criteria deceased donor kidney transplants performed at the University of Pittsburgh Medical Center from January 2003 through December 2012 were collected from an in-house electronic repository. There were 78 patients in the MP group and 101 patients in the CS group. The majority of the ECD kidneys were imported from other organ procurement organizations: 69 of 73 in the MP group (94.5%, 5 from unknown sources); and 90 of 99 in the CS group (91%), 2 from an unknown source). Most of the patients in the MP group (77 of 78) received a combination of MP and static CS. MP was performed just prior to transplantation in all MP patients. We used descriptive statistics to characterize our sample. We used logistic regression analysis to model the binary outcome of delayed graft function (DGF; i.e., "yes/no") and Cox (proportional hazard) regression to model time until graft failure. The Kaplan-Meier product-limit method was used to estimate survival curves for graft and patient survival. Results A total of 179 transplants were done from ECD donors (MP, 78; CS, 101). The mean static cold storage time was 14 ± 4.1 hours and the mean machine perfusion time was 11.2 ± 6.3 hours in the MP group. The donor creatinine was higher (1.3 ± 0.6 mg/dl vs. 1.2 ± 0.4 mg/dl, p = 0.01) and the cold ischemia time was longer (28.9 ± 10 hours vs. 24 ± 7.9 hours, p = 0.0003) in the MP patients. There were no differences between the two groups in DGF rate (20.8% [MP] vs. 25.8% [CS], p = 0.46), six-year patient survival (74% [MP] vs. 63.2% [CS], p = 0.11), graft survival (64.3% [MP] vs. 51.5% [CS], p = 0.22), and serum creatinine levels (1.5 mg/dl vs. 1.5 mg/dl) on univariate analysis. On unadjusted analysis, MP subjects without DGF had longer graft survival compared to CS subjects with DGF (p < 0.0032) and MP subjects with DGF (p < 0.0005). MP subjects without DGF had longer death-censored graft survival compared to CS subjects with DGF (p < 0.0077) and MP subjects with DGF (p < 0.0016). However, on regression analysis, MP subjects had longer graft survival than CS subjects when DGF was not present. MP subjects without DGF had longer patient survival compared to CS subjects with DGF (p < 0.0289), on unadjusted analysis. MP subjects had a reduced risk of graft failure (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.17, 0.68) and death-censored graft failure (HR, 0.44; 95% CI, 0.19, 1.00), compared to CS subjects when DGF was not present. Conclusions Reduction of DGF rates for imported ECD kidneys is vital to optimize outcomes and increase their utilization. One strategy to decrease DGF rates may be to reduce static CS time during transportation, by utilizing a portable kidney perfusion machine.

Clinical significance of the distribution of C4d deposits in different anatomic compartments of the allograft kidney.

Diffuse C4d deposition in peritubular capillaries is a well-recognized marker of antibody-mediated rejection. The significance of staining patterns that are focal or affect non-peritubular capillary compartments is less well defined. Paired frozen section and paraffin-embedded tissue stains were performed in 52 kidney allograft biopsies, and correlated with clinicopathologic parameters. Diffuse peritubular capillary C4d deposits were more often seen in frozen sections (22/52, 43% frozen tissue vs 10/52, 19% paraffin-embedded tissue), whereas focal staining was observed more frequently within paraffin sections (13/52, 25% paraffin-embedded tissue vs 7/52, 14% frozen tissue). In biopsies taken from patients with a history of donor-specific antibodies, diffuse, focal and negative peritubular capillary C4d staining patterns were seen in 11/14 (79%), 1/14 (7%) and 2/14 (14%) of frozen biopsies vs 5/14 (36%), 6/14 (43%) and 3/14 (21%) of paraffin-embedded biopsies. Transplant glomerulopathy score in paraffin-embedded biopsies was higher in specimens with vs without glomerular basement membrane C4d staining (1.5+/-0.8 vs 1.0+/-0.6, P=0.03). Tubular basement membrane staining was present in 4% paraffin-embedded and 48% frozen specimens independent of tubular atrophy. Arteriolar hyalinosis score in paraffin-embedded specimens was higher in biopsies with vs those without arteriolar C4d deposits (1.3+/-0.9 vs 0.9+/-0.8, P=0.04). Arterial staining was unrelated to the degree of intimal thickening. In conclusion, peritubular capillary deposits correlate well with circulating donor-specific antibody. For paraffin-embedded tissue, combining the results of focal and diffuse staining allows a diagnostic sensitivity comparable to diffuse staining in frozen tissue. Finally, C4d deposits preferentially in lesions of chronic transplant glomerulopathy and arteriolar hyalinosis.

Alemtuzumab preconditioning with tacrolimus monotherapy-the impact of serial monitoring for donor-specific antibody.

BACKGROUND: Antibody preconditioning with tacrolimus monotherapy has allowed many renal allograft recipients to be maintained on spaced weaning. METHODS: Of 279 renal allograft recipients transplanted between March 2003 and December 2004, 222 (80%) had spaced weaning (i.e., reduction of tacrolimus monotherapy dosing to every other day, three times a week, twice a week, or once a week) attempted. Routine monitoring for donor-specific antibody (DSA) was begun in September 2004. Mean follow-up is 34+/-6.5 months after transplantation and 26+/-8.1 months after the initiation of spaced weaning. RESULTS: One hundred and twenty-two (44%) patients remained on spaced weaning. One- and 2-year actual patient/graft survival was 99%/99%, and 97%/96%. Fifty-six (20%) patients experienced acute rejection after initiation of spaced weaning. One- and 2-year actual patient/graft survival was 100%/98%, and 94%/78%. Forty-two (15%) patients with stable renal function had spaced weaning stopped because of the development of DSA, which disappeared in 17 (40%). One- and 2-year actual patient and graft survival was 100% and 100%. CONCLUSION: Adult renal transplant recipients who are able to be maintained on spaced weaning have excellent outcomes. Patients with stable renal function who have reversal of weaning because of the development of DSA also have excellent outcomes. Routine monitoring for DSA may allow patients to avoid late rejection after spaced weaning.

Measurements of global cell-mediated immunity in renal transplant recipients with BK virus reactivation.

The Cylex ImmuKnow Test (Cylex, Columbia, MD) measures immune cell function (ICF) and is based on the amount of adenosine triphosphate (ATP) released when T cells are stimulated by phytohemagglutinin. This preliminary study sought to determine if ICF measurements can be used to stratify kidney transplant recipients according to the risk for developing BK virus infection. ICF measurements were done in 15 samples from 8 patients with BK viremia, 38 samples from 25 patients with BK viruria, and 243 samples from 148 patients with no BK viruria or viremia. The mean+/-SD amounts of ATP released in these 3 groups were 102.9+/-58.6, 227.2+/-146.4, and 231.8+/-150.8 ng/mL, respectively (P= .002, viremia vs all other samples). Within the viruria group, lower ICF values were associated with higher urinary viral load (P= .037). These results show that a decreased ICF test result correlates with active viral replication in kidney transplant recipients.

Cold heparinized lactated Ringers with procaine (HeLP) preservation fluid in 266 living donor kidney transplantations.

Since the 1960s simple inexpensive cold lactated Ringers with additives has been used for short-term cold preservation of kidneys from living donors. We performed 266 living donor kidney transplantations from January 22, 2003 to October 30, 2006. Donor allografts were recovered laparoscopically and flushed with cold heparin, lactated Ringer's and procaine (HeLP) solution. Warm and cold ischemic times were typically <45 min and <90 min, respectively. The mean follow up was 21.6+/-12.2 months. There was no delayed graft function. Actuarial 1-year patient and graft survival were 98.6% and 98.1%, respectively. The creatinine at 1 year was 1.46+/-0.51 mg/dL. The cumulative incidences of acute cellular rejection at 6, 12, 18, and 24 months were 3.0%, 7.1%, 10.2%, and 11.7%. There were no identifiable side effects attributed to the HeLP solution. This study documents the effectiveness of cold HeLP as a flushing and short-term preservation fluid for living donor kidney transplantation with excellent results and significant cost benefit because of its low cost.

Renal transplantation in children managed with lymphocyte depleting agents and low-dose maintenance tacrolimus monotherapy.

OBJECTIVE: Describe the safety and efficacy of antithymocyte globulin or alemtuzumab preconditioning, steroid avoidance and reduced calcineurin inhibitor (CNI) immunosuppression in 34 children undergoing renal transplantation. METHODS: ATG (n=8) or alemtuzumab (n=26) were infused at the time of transplantation. This was followed by low-dose twice a day tacrolimus monotherapy with consolidation to once daily dosing by 6 months and once every other day dosing by 12 months. Follow-up ranged from 0.5-2.9 years (mean 1.33 years), with a minimum of 6 months. RESULTS: Both ATG and alemtuzumab were well tolerated. Lymphopenia occurred routinely and resolved after 3-6 months. Acute cellular rejection occurred in 9%; it was related to medical nonadherence in two patients and resulted in one graft loss at 1.5 years. Important adverse events included transient neutropenia in 10 children (none with serious infection), and autoimmune hemolytic anemia in two (resolved with a steroid course in both and conversion to sirolimus in one). Estimated glomerular filtration rate (e-GFR) was stable and averaged 88 mL/min/1.73 m2 at latest follow-up. Fifteen preadolescents had a greater increase in height Z-score at 1 year (1.3 vs. 0.5, P=0.001), and a higher e-GFR (94.8+/-21 vs. 76.6+/-20 ml/min/1.73 m2, P<0.05), when compared to case-matched historical controls who were weaned off steroids by 6 months after transplantation and received twice daily tacrolimus monotherapy. CONCLUSION: This simple regimen appears safe, has a low risk for acute cellular rejection or other adverse effects, and is associated with excellent growth and renal function. Such a regimen may also improve compliance and limit CNI nephrotoxicity.

Alemtuzumab induction and tacrolimus monotherapy in pancreas transplantation: One- and two-year outcomes.

BACKGROUND: Alemtuzumab (Campath-1H) induction with tacrolimus monotherapy has been shown to provide effective immunosuppression for kidney, liver, lung, and small bowel transplantation. This drug combination was evaluated in pancreas transplant recipients. METHODS: Sixty consecutive pancreas transplants (30 simultaneous pancreas-kidney, 20 pancreas after kidney, and 10 pancreas alone) were carried out under this protocol between July 2003 to January 2005. The mean follow-up was 22 months (range 17-33). RESULTS: One-year patient, pancreas, and kidney allograft survival were 95%, 93%, and 90%, respectively. With 22 months follow-up, patient, pancreas, and kidney survival were 94%, 89%, and 87%, respectively. The rejection rate was 30% (18/60), with four patients (7%) experiencing steroid-resistant rejection. Major infection occurred in three (5%) patients resulting in two (3.3%) deaths from disseminated histoplasmosis and a herpes virus infection. One patient with cryptococcal meningitis was successfully treated. Seven (11.7%) patients experienced cytomegalovirus infection, all of whom responded to treatment with ganciclovir. One (1.7%) case of polymorphic posttransplant lymphoproliferative disease was seen, which regressed with a temporary discontinuation of tacrolimus and high-dose ganciclovir. The mean serum creatinine of the 30 simultaneous pancreas-kidney transplants at one year posttransplant was 1.37+/-0.33 mg/ml. The preexisting creatinine in pancreas after kidney transplants was not adversely affected by this immunosuppressive protocol. CONCLUSION: A single dose of perioperative alemtuzumab followed by daily tacrolimus monotherapy provides effective immunosuppression for pancreas transplantation, but the optimal use of this drug combination is not yet clear.

Pancreas transplantation under alemtuzumab (Campath-1H) and tacrolimus: Correlation between low T-cell responses and infection.

BACKGROUND: Alemtuzumab induction and tacrolimus-based immunosuppression has been effective in pancreas transplantation. Despite the encouraging results of this minimalistic approach to immunosuppression, infection still remains a significant cause of morbidity. The Cylex ImmuKnow [corrected] assay was used in this study to compare pancreas recipient clinical states (stable, rejection, infection) with T cell responses. METHODS: Blood samples were taken from pancreas recipients pretransplant and at approximately three-month intervals posttransplant for analysis of T cell responses. When possible, T cell responses were also quantified during changes in clinical status (infection or rejection). RESULTS: A range between 100-300 ng/ml adenosine triphosphate (ATP) was found in stable patients (mean 194+/-123, n = 51) with good graft function and no infection or rejection. A low T cell response was highly correlated with infectious states. The fourteen patients with infections/posttransplant lymphoproliferative disease had a mean ATP of 48 ng/ml. Risk hazard analysis showed that patients with ATP levels <100 ng/ml were four to seven times more susceptible to infection compared to stable patients. Four patients with rejection showed a T cell response of 550 ng/ml ATP, which was statistically significant compared to stable patients, although the sampling numbers (9) were too small to be conclusive. CONCLUSION: The Cylex ImmuKnow [corrected] assay is a valuable tool to more precisely modulate immunosuppression in pancreas transplant patients. In particular, the assay is extremely useful in detecting overly immunosuppressed patients vulnerable to infections.

Immunosuppressive preconditioning or induction regimens : evidence to date.

The success of solid organ transplantation has been directly related to the development of immunosuppressive drug therapies. Preconditioning or induction therapy was developed to reduce early immunological and nonimmunological renal injury, with the goal of increasing long-term graft survival. However, the routine induction of immunological tolerance to solid organ allograft is currently not achievable because of the morbidity and mortality related to the immunosuppressive regimens themselves. The different therapeutic preconditioning or induction agents and their associated effects on cellular rejection, graft survival outcomes and the need for multiagent post-transplant maintenance therapy are reviewed.

Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with Thymoglobulin or Campath.

BACKGROUND: Multiple drug immunosuppression has allowed the near elimination of rejection, but without commensurate improvements in longterm graft survival and at the cost of quality of life. We have suggested that transplantation outcomes can be improved by modifying the timing and dosage of immunosuppression to facilitate natural mechanisms of alloengraftment and acquired tolerance. STUDY DESIGN: Two therapeutic principles were applied for kidney transplantation: pretransplant recipient conditioning with antilymphoid antibody preparations (Thymoglobulin [Sangstat] or Campath [ILEX Pharmaceuticals]), and minimal posttransplant immunosuppression with tacrolimus monotherapy including "spaced weaning" of maintenance doses when possible. The results in Thymoglobulin- (n = 101) and Campath-pretreated renal transplantation recipients (n = 90) were compared with those in 152 conventionally immunosuppressed recipients in the immediately preceding era. RESULTS: Spaced weaning was attempted in more than 90% of the kidney transplant recipients after pretreatment with both lymphoid-depleting agents, and is currently in effect in two-thirds of the survivors. Although there was a much higher rate of acute rejection in the Thymoglobulin-pretreated recipients than in either the Campath-pretreated or historic control recipients, patient and graft survival in both lymphoid depletion groups is at least equivalent to that of historic control patients. In the Thymoglobulin-conditioned patients for whom followups are now 24 to 40 months, chronic allograft nephropathy (CAN) progressed at the same rate as in historic control patients. Selected patients on weaning developed donor-specific nonreactivity. CONCLUSIONS: After lymphoid depletion, kidney transplantation can be readily accomplished under minimal immunosuppression with less dependence on late maintenance immunosuppression and a better quality of life. Campath was the more effective agent for pretreatment. Guidelines for spaced weaning need additional refinement.

Living-related donor renal transplantation in HIV+ recipients using alemtuzumab preconditioning and steroid-free tacrolimus monotherapy: a single center preliminary experience.

BACKGROUND: End-stage renal disease (ESRD) is an increasing problem in patients infected with the human immunodeficiency virus (HIV). The use of highly active antiretroviral therapy (HAART) has decreased the morbidity associated with HIV and has prompted renewed interest in renal transplantation. METHODS: We performed four cases of deceased donor renal transplantation in HIV+ recipients and three cases where laparoscopic live donor nephrectomy (LLDN) was utilized to obtain the kidney for transplantation into living-related HIV+ recipients. In the four deceased donor cases, conventional tacrolimus-based immunosuppression, without antibody induction was used. In the three living-related cases, the immunosuppressive regimen was based on two principles: recipient pretreatment and minimal posttransplant immunosuppression. Alemtuzumab 30 mg (Campath 1-H) was used for preconditioning followed by low-dose tacrolimus monotherapy. RESULTS: Of the four deceased donor cases, one patient continues to have good graft function, and another is not yet on dialysis but has significant graft dysfunction. Rejection was observed in three patients (75%). Infectious complications occurred in one patient (25%), all non-acquired immunodeficiency syndrome (AIDs) defining. In the three living-related cases, all had good graft function, and none have experienced acute rejection. HIV viral loads remain undetectable. CD4 counts are slowly recovering. No infectious or surgical complications occurred. There were no deaths in either group. CONCLUSIONS: These data suggest that living-related donor renal transplantation with steroid-free tacrolimus monotherapy in a "tolerogenic" regimen can be efficacious. However, long-term follow-up is needed to confirm this observation.