Postdonation Anemia in Living Kidney Donors.

BACKGROUND: The effect of nephrectomy on development of anemia in living kidney donation has not been well studied. We hypothesized that the remaining kidney volume and function after donation are determinants of hemoglobin (Hb) concentration and postdonation anemia (PDA). METHODS: We studied 398 living kidney donors (LKDs) who donated from January 2001 to December 2013. Demographic variables, hematologic variables, renal mass, and renal function were investigated as factors associated with PDA with the use of univariate and multivariable logistical regression analysis. Renal mass was determined from kidney volume measured with the use of computerized tomographic scans. RESULTS: Prevalence of PDA in LKDs was 11.8% at a median follow-up time of 601 days. In univariate analyses, PDA was more prevalent in women than in men (72% vs 28%; P = .048). Age and race were not associated factors. Kidney volume was lower in donors with PDA than in those without PDA (326 ± 52 mL vs 368 ± 70 mL; P < .001). Donors with and without PDA had similar predonation and postdonation glomerular filtration rates. In the multivariable logistic regression analysis, total kidney volume and predonation anemia remained as independent factors associated with PDA. CONCLUSIONS: PDA is prevalent after living kidney donation, with donor kidney volume and predonation hemoglobin levels being independent determinants for PDA.

Association of Candidate Removals From the Kidney Transplant Waiting List and Center Performance Oversight.

Approximately 59 000 kidney transplant candidates have been removed from the waiting list since 2000 for reasons other than transplantation, death, or transfers. Prior studies indicate that low-performance (LP) center evaluations by the Scientific Registry of Transplant Recipients (SRTR) are associated with reductions in transplant volume. There is limited information to determine whether performance oversight impacts waitlist management. We used national SRTR data to evaluate outcomes of 315 796 candidates on the kidney transplant waiting list (2007-2014). Compared to centers without LP, rates of waitlist removal (WLR) were higher at centers with LP evaluations (44.6/1000 follow-up years, 95% confidence interval [CI] 44.0, 45.1 versus 68.0/1000 follow-up years, 95% CI 66.6, 69.4), respectively, which was consistent after risk adjustment (adjusted hazard ratio [AHR] = 1.59, 95% CI 1.55, 1.63). Candidate mortality following waitlist removal was lower at LP centers (AHR = 0.90, 95% CI 0.87, 0.94). Analyses limited to LP centers indicated a significant increase in WLR (+28.6 removals/1000 follow-up years, p < 0.001), a decrease in transplant rates (-11.9/1000 follow-up years, p < 0.001) and a decrease in mortality after removal (-67.5 deaths/1000 follow-up years, p < 0.001) following LP evaluation. There is a significant association between LP evaluations and transplant center processes of care for waitlisted candidates. Further understanding is needed to determine the impact of performance oversight on transplant center quality of care and patient outcomes.

Estimated GFR for Living Kidney Donor Evaluation.

All living kidney donor candidates undergo evaluation of GFR. Guidelines recommend measured GFR (mGFR), using either an endogenous filtration marker or creatinine clearance, rather than estimated GFR (eGFR), but measurement methods are difficult, time consuming and costly. We investigated whether GFR estimated from serum creatinine (eGFRcr) with or without sequential cystatin C is sufficiently accurate to identify donor candidates with high probability that mGFR is above or below thresholds for clinical decision making. We combined the pretest probability for mGFR thresholds <60, <70, ≥80, and ≥90 mL/min per 1.73 m(2) based on demographic characteristics (from the National Health and Nutrition Examination Survey) with test performance of eGFR (categorical likelihood ratios from the Chronic Kidney Disease Epidemiology Collaboration) to compute posttest probabilities. Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation eGFRcr high enough to ensure ≥95% probability that predonation mGFR was ≥90 mL/min per 1.73 m(2) , suggesting that mGFR may not be necessary in a large proportion of donor candidates. We developed a Web-based application to compute the probability, based on eGFR, that mGFR for a donor candidate is above or below a range of thresholds useful in living donor evaluation and selection.

Interferon Gamma ELISPOT Testing as a Risk-Stratifying Biomarker for Kidney Transplant Injury: Results From the CTOT-01 Multicenter Study.

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.

Critical Factors Associated With Missing Follow-Up Data for Living Kidney Donors in the United States.

Follow-up care for living kidney donors is an important responsibility of the transplant community. Prior reports indicate incomplete donor follow-up information, which may reflect both donor and transplant center factors. New UNOS regulations require reporting of donor follow-up information by centers for 2 years. We utilized national SRTR data to evaluate donor and center-level factors associated with completed follow-up for donors 2008-2012 (n = 30 026) using multivariable hierarchical logistic models. We compared center follow-up compliance based on current UNOS standards using adjusted and unadjusted models. Complete follow-up at 6, 12, and 24 months was 67%, 60%, and 50% for clinical and 51%, 40%, and 30% for laboratory data, respectively, but have improved over time. Donor risk factors for missing laboratory data included younger age 18-34 (adjusted odds ratio [AOR] = 2.03, 1.58-2.60), black race (AOR = 1.17, 1.05-1.30), lack of insurance (AOR = 1.25, 1.15-1.36), lower educational attainment (AOR = 1.19, 1.06-1.34), >500 miles to center (AOR = 1.78, 1.60-1.98), and centers performing >40 living donor transplants/year (AOR = 2.20, 1.21-3.98). Risk-adjustment moderately shifted classification of center compliance with UNOS standards. There is substantial missing donor follow-up with marked variation by donor characteristics and centers. Although follow-up has improved over time, targeted efforts are needed for donors with selected characteristics and at centers with higher living donor volume. Adding adjustment for donor factors to policies regulating follow-up may function to provide more balanced evaluation of center efforts.

Effect of dialysis initiation for preemptively listed candidates in the revised kidney allocation policy.

The new allocation policy for deceased donor kidneys in the United States is expected to begin in late 2014. As part of this policy, prioritization to the highest quality deceased donor kidneys is dependent on candidate's estimated posttransplant survival (EPTS) score. In particular, candidates with low (≤20%) EPTS (indicating better estimated survival) will have greater access to donor offers. We evaluated the effect of dialysis initiation on preemptively listed candidates' EPTS score. Using current estimates, approximately 10% (n = 19,406) of candidates placed on the waiting list between 2008 and 2013 were listed preemptively and would have qualified for top 20% status. These patients were more likely younger, female, Caucasian and nondiabetic compared to other candidates. Among nondiabetic preemptively listed candidates, dialysis initiation decreases EPTS score (indicating better estimated survival and higher allocation priority) for approximately 5 months. In contrast, diabetic patients' EPTS score significantly increases (approximately 6%) immediately upon dialysis initiation. Our results reveal a counterintuitive aberration in the EPTS formula, which is important for decision making regarding organ selection and timing of dialysis initiation in the new allocation system. Revision of the EPTS formula should be considered to address these findings and further understanding of the impact of the new allocation system on candidates' prognosis is important.

IL-15 induces alloreactive CD28(-) memory CD8 T cell proliferation and CTLA4-Ig resistant memory CD8 T cell activation.

The presence of CD28(-) memory CD8 T cells in the peripheral blood of renal transplant patients is a risk factor for graft rejection and resistance to CTLA-4Ig induction therapy. In vitro analyses have indicated poor alloantigen-induced CD28(-) memory CD8 T cell proliferation, raising questions about mechanisms mediating their clonal expansion in kidney grafts to mediate injury. Candidate proliferative cytokines were tested for synergy with alloantigen in stimulating CD28(-) memory CD8 T cell proliferation. Addition of IL-15, but not IL-2 or IL-7, to co-cultures of CD28(-) or CD28(+) memory CD8 T cells and allogeneic B cells rescued proliferation of the CD28(-) and enhanced CD28(+) memory T cell proliferation. Proliferating CD28(-) memory CD8 T cells produced high amounts of interferon gamma and tumor necrosis factor alpha and expressed higher levels of the cytolytic marker CD107a than CD28(+) memory CD8 T cells. CTLA-4Ig inhibited alloantigen-induced proliferation of CD28(+) memory CD8 T cell proliferation but had no effect on alloantigen plus IL-15-induced proliferation of either CD28(-) or CD28(+) memory CD8 T cells. These results indicate the ability of IL-15, a cytokine produced by renal epithelial during inflammation, to provoke CD28(-) memory CD8 T cell proliferation and to confer memory CD8 T cell resistance to CTLA-4Ig-mediated costimulation blockade.

Risk factors for retransplant kidney recipients: relisting and outcomes from patients' primary transplant.

As of November 2013, 14.5% of the waitlist for a donor kidney comprised patients awaiting a retransplant. We performed a retrospective cohort study of 11,698 adult solitary kidney recipients using national Scientific Registry of Transplant Recipients data transplanted between 2002 and 2011. The aim was to investigate whether outcomes from patients' initial transplants are significant risk factors for patients' repeat transplants or for likelihood of relisting after a failed primary transplant. Retransplant recipients were more likely to be treated for acute rejection [adjusted odds ratio (AOR), 95% confidence interval (CI) = 1.26 (1.07-1.48), p = 0.0053] or hospitalized (AOR = 1.19, 95% CI 1.08-1.31, p = 0.0005) within a year of retransplantation if these outcomes were experienced within a year of primary transplant. Delayed graft function following primary transplants was associated with 35% increased likelihood of recurrence (AOR = 1.35, 95% CI = 1.18-1.54, p < 0.0001). An increase in 1-year GFR after primary transplant was associated with GFR 1 year postretransplant (ß = 6.82, p < 0.0001), and retransplant graft failure was inversely associated with 1-year primary transplant GFR (adjusted hazard ratio = 0.74, 95% CI = 0.71-0.76 per 10 mL/min/1.73 m(2) ). A decreased likelihood for relisting was associated with hospitalization and higher GFR following primary transplantation. The increasing numbers of individuals requiring retransplants highlights the importance of incorporating prior transplant outcomes data to better inform relisting decisions and prognosticating retransplant outcomes.

Prominent impact of community risk factors on kidney transplant candidate processes and outcomes.

Numerous factors impact patients' health beyond traditional clinical characteristics. We evaluated the association of risk factors in kidney transplant patients' communities with outcomes prior to transplantation. The primary exposure variable was a community risk score (range 0-40) derived from multiple databases and defined by factors including prevalence of comorbidities, access and quality of healthcare, self-reported physical and mental health and socioeconomic status for each U.S. county. We merged data with the Scientific Registry of Transplant Recipients (SRTR) and utilized risk-adjusted models to evaluate effects of community risk for adult candidates listed 2004-2010 (n = 209 198). Patients in highest risk communities were associated with increased mortality (adjusted hazard ratio [AHR] = 1.22, 1.16-1.28), decreased likelihood of living donor transplantation (adjusted odds ratio [AOR] = 0.90, 0.85-0.94), increased waitlist removal for health deterioration (AHR = 1.36, 1.22-1.51), decreased likelihood of preemptive listing (AOR = 0.85, 0.81-0.88), increased likelihood of inactive listing (AOR = 1.49, 1.43-1.55) and increased likelihood of listing for expanded criteria donor kidneys (AHR = 1.19, 1.15-1.24). Associations persisted with adjustment for rural-urban location; furthermore the independent effects of rural-urban location were largely eliminated with adjustment for community risk. Average community risk varied widely by region and transplant center (median = 21, range 5-37). Community risks are powerful factors associated with processes of care and outcomes for transplant candidates and may be important considerations for developing effective interventions and measuring quality of care of transplant centers.

Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for kidney transplant injury.

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.

Association of metabolic syndrome with kidney function and histology in living kidney donors.

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.

The prognostic value of kidney transplant center report cards.

SRTR report cards provide the basis for quality measurement of US transplant centers. There is limited data evaluating the prognostic value of report cards, informing whether they are predictive of prospective patient outcomes. Using national SRTR data, we simulated report cards and calculated standardized mortality ratios (SMR) for kidney transplant centers over five distinct eras. We ranked centers based on SMR and evaluated outcomes for patients transplanted the year following reports. Recipients transplanted at the 50th, 100th and 200th ranked centers had 18% (AHR = 1.18, 1.13-1.22), 38% (AHR = 1.38, 1.28-1.49) and 91% (AHR = 1.91, 1.64-2.21) increased hazard for 1-year mortality relative to recipients at the top-ranked center. Risks were attenuated but remained significant for long-term outcomes. Patients transplanted at centers meeting low-performance criteria in the prior period had 40% (AHR = 1.40, 1.22-1.68) elevated hazard for 1-year mortality in the prospective period. Centers' SMR from the report card was highly predictive (c-statistics > 0.77) for prospective center SMRs and there was significant correlation between centers' SMR from the report card period and the year following (ρ = 0.57, p < 0.001). Although results do not mitigate potential biases of report cards for measuring quality, they do indicate strong prognostic value for future outcomes. Findings also highlight that outcomes are associated with center ranking across a continuum rather than solely at performance margins.

The impact of deceased donor kidney risk significantly varies by recipient characteristics.

As of May 2012, over 92 000 patients were awaiting a solitary kidney transplant in the United States and new waitlist registrations have been rising for over a decade. The decreasing availability of donor organs makes it imperative that organ allocation be as efficient and effective as possible. We performed a retrospective cohort study of adult recipients in the United States (n=109 392) using Scientific Registry of Transplant Recipients data. The primary aim was to evaluate the interaction of donor risk with recipient characteristics on posttransplant outcomes. Donor quality (based on kidney donor risk index [KDRI]) had significant interactions by race, primary diagnosis and age. The hazard of KDRI on overall graft loss in non-African Americans was 2.16 (95%CI 2.08-2.25) versus 1.85 (95%CI 1.75-1.95) in African Americans (p<0.0001), 2.16 (95%CI 2.08-2.24) in nondiabetics versus 1.84 (95%CI 1.74-1.94) in diabetics (p<0.0001), and 2.22 (95%CI 2.13-2.32) in recipients<60 years versus 1.83 (95%CI 1.74-1.92) in recipients≥60 (p<0.0001). The relative hazard for diabetics at KDRI=0.5 was 1.49 but at KDRI=2.0 the hazard was significantly attenuated to 1.17; among African Americans the respective risks were 1.50 and 1.17 and among recipients 60 and over, it was between 1.64 and 1.22. These findings are critical considerations for informed decision-making for transplant candidates.

The association of center performance evaluations and kidney transplant volume in the United States.

Report cards evaluating transplant center performance have received significant attention in recent years corresponding with the Centers for Medicare and Medicaid Services issue of the 2007 Conditions of Participation. Our primary aim was to evaluate the association of report card evaluations with transplant center volume. We utilized data from the Scientific Registry of Transplant Recipients (SRTR) along with six consecutive program-specific reports from January 2007 to July 2009 for adult kidney transplant centers. Among 203 centers, 46 (23%) were low performing (LP) with statistically significantly lower than expected 1-year graft or patient survival at least once during the study period. Among LP centers, there was a mean decline in transplant volume of 22.4 cases compared to a mean increase of 7.8 transplants among other centers (p = 0.001). Changes in volume between LP and other centers were significant for living, standard and expanded criteria deceased donor (ECD) transplants. LPs had a reduction in use of donors with extended cold ischemia time (p = 0.04) and private pay recipients (p = 0.03). Centers without low performance evaluations were more likely to increase the proportion of overall transplants that were ECDs relative to other centers (p = 0.04). Findings indicate a significant association between reduced kidney transplant volume and low performance report card evaluations.

Evaluation of alloreactivity in kidney transplant recipients treated with antithymocyte globulin versus IL-2 receptor blocker.

Induction therapy is used in kidney transplantation to inhibit the activation of donor-reactive T cells which are detrimental to transplant outcomes. The choice of induction therapy is decided based on perceived immunological risk rather than by direct measurement of donor T-cell reactivity. We hypothesized that immune cellular alloreactivity pretransplantation can be quantified and that blocking versus depleting therapies have differential effects on the level of donor and third-party cellular alloreactivity. We studied 31 kidney transplant recipients treated with either antithymocyte globulin (ATG) or an IL-2 receptor blocker. We tested pre- and posttransplant peripheral blood cells by flow cytometry to characterize T-cell populations and by IFN-γ ELISPOT assays to assess the level of cellular alloreactivity. CD8(+) T cells were more resistant to depletion by ATG than CD4(+) T cells. Posttransplantation, frequencies of donor-reactive T cells were markedly decreased in the ATG-treated group but not in the IL-2 receptor blocker group, whereas the frequencies of third-party alloreactivity remained nearly equivalent. In conclusion, when ATG is used, marked and prolonged donor hyporesponsiveness with minimal effects on nondonor responses is observed. In contrast, induction with the IL-2 receptor blocker is less effective at diminishing donor T-cell reactivity.

Living donor kidney transplantation: an update on evaluation and medical implications of donation.

As the number of potential transplant recipient candidates increases with a relatively fixed number of organ donors, waitlists for kidney donation continue to grow. The disparity has forced physicians to reconsider prospective living organ candidates who are advanced in age with some degree of illness burden as a viable option for donation. The 2004 Amsterdam Forum was established to create consensus guidelines for donor evaluation. The primary goal of the evaluation of the prospective living donor is to risk stratify disease burden to ensure the safety of the donor. This article underscores some of the most contentious aspects of living donor evaluation such as metabolic derangements, donor age, donor gender and kidney function among others. Outcomes of the allograft and recipient are reviewed in the context of these medical conditions. The evaluation of the prospective living donor requires that he/she has agreed to proceed with donation after obtaining informed consent which can only be acquired by understanding all the short and long term complications and risks associated with kidney donation. This review will discuss the immediate surgical complications and long-term implications. There may be additional risk for female donors who are at childbearing age and plan to start a family. However, living kidney donation is the best treatment option available for patients with end stage renal disease and it is a safe procedure for the donor after careful medical consideration in each particular case is given.

25-OH-vitamin D deficiency and cellular alloimmunity as measured by panel of reactive T cell testing in dialysis patients.

Primed antidonor alloreactive T cells are detrimental to transplant outcome, but factors that impact the strength of this immune response prior to transplantation are unknown. We tested peripheral blood mononuclear cells from dialysis patients, against panels of allogeneic, primary B-cell lines in a newly standardized IFNγ ELISPOT panel of reactive T cell (PRT) assay. Results were correlated with known alloantibody-sensitizing events and other clinical parameters. As 25-OH-vitamin D deficiency is associated with enhanced cellular immunity, is common in dialysis patients and is correctable, we assessed the relationship between serum 25-OH-vitamin D and the PRT. Using independent test and validation cohorts we found that low serum levels of 25-OH-vitamin D (<26 ng/mL) correlated with high-PRT values (in the upper 50th percentile, OR 0.02, p = 0.01) independent of age, sex, race, previous transplant, transfusion, pregnancy, time on dialysis, panel of reactive antibody, iPTH, and treatment with 1,25-OH-vitamin D. The data provide a potential mechanism for the possible relationship between vitamin D deficiency and poor posttransplant outcome, and support studies to test the impact of 25-OH-vitamin D repletion on alloimmunity and allograft injury in kidney transplant candidates.

Marked variation of the association of ESRD duration before and after wait listing on kidney transplant outcomes.

Numerous studies report a strong association between pretransplant end-stage renal disease (ESRD) duration and diminished transplant outcomes. However, cumulative waiting time may reflect distinct phases and processes related to patients' physiological condition as well as pre-existing morbidity and access to care. The relative impact of pre- and postlisting ESRD durations on transplant outcomes is unknown. We examined the impact of these intervals from a national cohort of kidney transplant recipients from 1999 to 2008 (n = 112,249). Primary factors explaining prelisting ESRD duration were insurance and race, while primary factors explaining postlisting ESRD duration were blood type, PRA% and variation between centers. Extended time from ESRD to waitlisting had significant dose-response association with overall graft loss (AHR = 1.26 for deceased donors [DD], AHR = 1.32 for living donors [LD], p values < 0.001). Contrarily, time from waitlisting (after ESRD) to transplantation had negligible effects (p = 0.10[DD], p = 0.57[LD]). There were significant associations between pre- and postlisting ESRD time with posttransplant patient survival, however prelisting time had over sixfold greater effect. Prelisting ESRD time predominately explains the association of waiting time with transplant outcomes suggesting that factors associated with this interval should be prioritized for interventions and allocation policy. The degree to which the effect of prelisting ESRD time is a proxy for comorbid conditions, socioeconomic status or access to care requires further study.

Conversion to sirolimus with calcineurin inhibitor elimination vs. dose minimization and renal outcome in heart and lung transplant recipients.

Sirolimus (SRL) has been used as an alternative immunosuppressant strategy to allow either dose minimization or complete withdrawal of calcineurin inhibitors (CNI) therapy to improve renal outcome. One hundred thirty-one heart and 55 lung transplant patients were converted from a CNI to SRL based immunosuppression, with CNI elimination in 25 patients, and dose reduction in 161 patients. Fifty-six (28%) patients died and 65 (33%) patients had a 25% or more decline in estimated glomerular filtration rate (eGFR) during a median follow-up of 18 months. The three groups (SRL only group n = 25; SRL + tacrolimus n = 94; SRL + cyclosporine n = 67) had an initial improvement in estimated glomerular filtration rate (p = 0.05), with subsequent similar slow decline in mean eGFR (repeated measures ANOVA, p = 0.96). After controlling for important potential confounding variables, the three groups had similar renal outcome (p = 0.40) and overall survival (p = 0.45). In conclusion, the benefits of CNI withdrawal vs. minimization as part of SRL-based regimens are similar with regard to renal outcomes and patient survival.