Kaplan, Bruce

Patients with failed renal allografts have associated increased morbidity and mortality. The individualization of immunosuppression taper is the key element in managing these patients to avoid graft intolerance and sensitization while balancing the risk of continued immunosuppression. Most patients with uncomplicated chronic allograft failure do not require allograft nephrectomy (AN), and there is no clear evidence that it improves outcomes. The AN procedure is associated with variable morbidity and mortality. It is reserved mainly for early technical graft failure or in symptomatic cases associated with allograft infection, malignancy, or graft intolerance syndrome. It may also be considered in those who cannot tolerate immunosuppression and are at high risk for graft intolerance. AN has been associated with an increased risk of sensitization due to inflammatory response from surgery, immunosuppression withdrawal with allograft failure, and retained endovascular tissue. Although it is presumed that for-cause AN after transplant failure is associated with sensitization, it remains unclear whether elective AN in patients who remain on immunotherapy may prevent sensitization. The current practice of immunosuppression taper has not been shown to prevent sensitization or increase infection risk, but current literature is limited by selection bias and the absence of medication adherence data. We discuss the management of failed allografts based on retransplant candidacy, wait times, risk of graft intolerance syndrome, and immunosuppression side effects. Many unanswered questions remain, and future prospective randomized trials are needed to help guide evidence-based management.

AbstractThe OPTN/UNOS utilizes the calculated estimated posttransplant survival (EPTS) score as the measure of post‐kidney transplant survival to guide allocation of deceased donor kidney transplantation. This score does not include any metric of functional capacity. Peak oxygen uptake (VO2peak), is an established predictor of survival among both the general and diseased populations. We assessed the association and discriminative capacity of VO2peak and that of EPTS score and all‐cause mortality post‐kidney transplant. Additionally, we assessed the “mortality risk” lower VO2peak conferred on those patients with low EPTS score. Among a cohort of 293 transplant recipients with at least 3‐years post‐transplant follow‐up, the median VO2peak was 15.0 ml/Kg/min. Lower pre‐transplant VO2peak and higher EPTS score conferred higher risk of post‐transplant mortality. Among the cohort of “low‐risk” patients (patients with EPTS score < 50) those with lower VO2peak had significantly higher risk of mortality (log rank p = 0.045). In fact, the mortality risk among those with low‐EPTS (< 50) and low VO2peak < 12 ml/Kg/min was equivalent to those with high EPTS (> 80) score. We concluded functional capacity as defined by VO2peak is an important reflection of post‐transplant survival. VO2peak is able to identify those with low EPTS who have similar survival to that of high EPTS phenotype.

Background. The study aims is to use the fragility index (FI) to examine the strength of evidence of randomized controlled trials (RCTs) published in the last decade on kidney transplantation. Methods. We searched MEDLINE for studies on kidney transplantation. We included the RCTs that compared 2 groups with 1:1 randomization and reported significant P values (<0.05) for a dichotomous outcome and were published in the top 10 transplant journals. We calculated the FI; a calculation used to determine the minimum number of subjects needed to change from a nonevent to an event to make the study results nonsignificant (P ≥ 0.05). Results. Fifty-seven RCTs met our inclusion criteria. The median sample size was 100 participants in each arm, the median number of events was 16 (interquartile range, 8–30) in the intervention group. Among the included trials, 79% were industry-funded, 93% involved medications, and the majority were open label. The median FI was 3 (interquartile range, 1–11). In 43% of the trials, the number of patients reported lost to follow-up was higher than or equal to the FI. Only 4% of the RCTs imputed a value for the missing dichotomous outcome. Furthermore, the median number of subjects who discontinued the trial because of adverse effects was 21, which was greater than the FI in 60% of the RCTs. Conclusions. The arbitrary classification of results into “significant” and “nonsignificant” based on P value <0.05 should perhaps be interpreted with the help of other statistical parameters and FI is one of them.

Background. Participant withdrawal from clinical trials occurs for various reasons, predominantly adverse effects or intervention inefficacy. Because these missing participant data can have implications for the validity, reproducibility, and generalizability of study results, when conducting a systematic review, it is important to collect and appropriately analyze missing data information to assess its effects on the robustness of the study results. Methods. In this methodologic survey of missing participant data reporting and handling in systematic reviews, we included meta-analyses that provided pooled estimates of at least 1 dichotomous intervention outcome of a randomized controlled trial performed in adult kidney transplant subjects. Results. Eighty-three systematic reviews (17 Cochrane and 66 non-Cochrane reviews) met the inclusion criteria. The most common intervention was drugs (80%), with the majority involving immunosuppressant drugs 55% (n = 46), followed by surgery in 14% (n = 12). The median follow-up duration was 12 months (maximum, 240 mo). Intention-to-treat or modified intention-to-treat analysis was reported in 24% (n = 20) of the reviews (76% of Cochrane and 10% of non-Cochrane). Overall, the majority of systematic reviews did not quantify (90% [n = 60] non-Cochrane and 29% [n = 5] Cochrane) or include the reasons for missing participant data (88% [n = 58] non-Cochrane and 24% [n = 4] Cochrane). Eleven percent (n = 9) handled missing participant data, 5% (n = 4) justified the analytical method(s) used to handle it, and 2% (n = 2) performed a sensitivity analysis for it. Conclusions. Systematic reviews of kidney transplantation provide inadequate information on missing participant data and usually do not handle or discuss the associated risk of bias with it.

Background. Underutilization of marginal-quality kidneys for transplantation produced ideas of expediting kidney placement for populations with decreased opportunities of receiving transplants. Such policies can be less efficacious for specific individuals and should be scrutinized until the decision-making for accepting marginal-quality organs, which has relied on experiential judgment, is better understood at the individual level. There exist rigorous tools promoting personalized decisions with useful and objective information. Methods. This article introduces a decision-tree methodology that analyzes a patient’s dilemma: to accept a kidney offer now or reject it. The methodology calculates the survival benefit of accepting a kidney given a certain quality now and the survival benefit of rejecting it. Survival benefit calculation accounts for patients’ and donors’ characteristics and transplant centers’ and organ procurement organizations’ performances and incorporates patients’ perceived transplant and dialysis utilities. Valuations of rejecting an offer are contingent on future opportunities and subject to uncertainty in the timing of successive kidney offers and their quality and donor characteristics. Results. The decision tree was applied to a realistic patient profile as a demonstration. The tool was tested on 1000 deceased-donor kidney offers in 2016. Evaluating up to 1 year of future offers, the tool attains 61% accuracy, with transplant utility of 1.0 and dialysis utility of 0.5. The accuracy reveals potential bias in kidney offer acceptance/rejection at transplant centers. Conclusions. The decision-tree tool presented could aid personalized transplant decision-making in the future by providing patients with calculated, individualized survival benefits between accepting and rejecting a kidney offer.

Background Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO 2peak ), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. Methods and Results We outlined a pre–renal transplant screening algorithm to incorporate VO 2peak testing among a population of asymptomatic high‐risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO 2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO 2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all‐cause mortality. We report a high (>90%) negative predictive value, indicating that VO 2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all‐cause mortality. However, lower VO 2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. Conclusions We conclude that incorporating an objective measure of cardiorespiratory fitness with VO 2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher‐risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.