Faculty Bibliography

BACKGROUND:Management of patients on the kidney transplant waitlist lacks oversight, and transplant centers can delist candidates without consequence. To better understand between-center differences in waitlist management, we examined delisting rates and mortality after delisting within 3 years of removal from the kidney transplant waitlist. STUDY DESIGN:This is a retrospective cohort study using data from the Scientific Registry of Transplant Recipients of adults listed for deceased donor kidney transplant in 2015 and followed until the end of 2018. Patients of interest were those delisted for reasons other than transplant, death, or transfer. Centers were excluded if they had fewer than 20 waitlisted patients per year. We calculated probability of delisting and death after delisting using multivariable competing risk models. RESULTS:During follow-up, 14.2% of patients were delisted. The median probability of delisting within 3 years, adjusted for center-level variability, was 7.0% (interquartile range [IQR]: 3.9% to 10.6%). Median probability of death was 58.2% (IQR: 40% to 73.4%). There was no meaningful correlation between probability of delisting and death (τ = -0.05, p = 0.34). CONCLUSIONS:There is significant variability in the rate of death after delisting across kidney transplant centers. Likelihood of transplant is extremely important to candidates, and improved data collection efforts are needed to inform whether current delisting practices are successfully removing patients who could not meaningfully benefit from transplant, or whether certain populations may benefit from remaining on the list and maintaining eligibility.

Kidney transplant centers set organ offer filters enabling all candidates at their center to be bypassed during allocation of deceased donor kidneys from the UNOS Organ Center. These filters aim to increase allocation efficiency by preemptively screening out offers unlikely to be accepted. National data were used to compare filter settings of 175 centers in 2007 and in 2019. We examined characteristics of centers whose settings became increasingly restrictive over time, and associations between filter settings and organ offer acceptance. Overall, centers became more open to receiving offers over time, from a median 62% of filters open to receiving national offers in 2007 to 73% in 2019. Intravenous drug use filter settings changed most, from 63 to 153 willing centers. Centers with more open filter settings had higher transplant volume and offer acceptance ratios across all risk categories despite preemptively screening out fewer offers compared to centers with less open settings, but similar transplant rates. There was significant geographic heterogeneity in the distribution of centers with more open filter settings. Current center bypass filters may impact patients' access to transplantation without achieving their full potential for improving allocation efficiency.

INTRODUCTION/UNASSIGNED:The utility of kidney procurement biopsies is controversial. Understanding the current landscape of how clinicians obtain and use biopsies in organ evaluation may help inform consensus-building efforts. METHODS/UNASSIGNED:An electronic survey was distributed to clinicians at US kidney transplant programs (April 22, 2021-June 30, 2021) to evaluate donor biopsy indications, frequency, processing and interpretation, and impact of findings on practices. RESULTS/UNASSIGNED:Responses from staff involved in organ acceptance (73% surgeons, 20% nephrologists, 6% coordinators) at 95 transplant centers were analyzed, representing 40% of US transplant centers and 50% of recent deceased donor kidney transplant volume. More than a third of centers (35%) reported obtaining procurement biopsies on most-to-all kidneys. Most clinicians decided when to biopsy jointly with the Organ Procurement Organization (OPO) (82%) based on formal criteria for the decision (72%), although 41% reported having requested a biopsy outside of the criteria. Most respondents used a semiquantitative scoring system for interpretation (57%). Many respondents reported rarely or never having access to renal specialty pathologists (37%) or to telepathology (59%). Most respondents reported that a favorable biopsy result would encourage them to accept a "marginal" donor kidney (72%); nearly half (46%) indicated that an unfavorable biopsy result would lead to decline of a standard criteria kidney. CONCLUSION/UNASSIGNED:Procurement biopsies are commonly used in organ acceptance decisions despite inconsistent access to experienced renal pathologists and heterogeneous approaches to criteria, scoring, and interpretation. Ongoing study and consensus building are needed to direct procurement biopsy practice toward increasing organ utilization and reducing allocation inefficiency.

Although there is a shortage of kidneys available for transplantation, many transplantable kidneys are not procured or are discarded after procurement. We investigated whether local market competition and/or organ availability impact kidney procurement/utilization. We calculated the Herfindahl-Hirschman Index (HHI) for deceased donor kidney transplants (2015-2019) for 58 US donation service areas (DSAs) and defined 4 groups: HHI ≤ 0.32 (high competition), HHI = 0.33-0.51 (medium), HHI = 0.53-0.99 (low), and HHI = 1 (monopoly). We calculated organ availability for each DSA as the number kidneys procured per incident waitlisted candidate, grouped as: <0.42, 0.42-0.69, >0.69. Characteristics of procured organs were similar across groups. In adjusted logistic regression, the HHI group was inconsistently associated with composite export/discard (reference: high competition; medium: OR 1.16, 95% CI 1.11-1.20; low 1.01, 0.96-1.06; monopoly 1.19, 1.13-1.26) and increasing organ availability was associated with export/discard (reference: availability <0.42; 0.42-0.69: OR 1.35, 95% CI 1.30-1.40; >0.69: OR 1.83, 95% CI 1.73-1.93). When analyzing each endpoint separately, lower competition was associated with higher export and only market monopoly was weakly associated with lower discard, whereas higher organ availability was associated with export and discard. These results indicate that local organ utilization is more strongly influenced by the relative intensity of the organ shortage than by market competition between centers.

PURPOSE OF REVIEW:Low-level evidence and opinion-based clinical practice guidelines highlight the substantial uncertainty in the practice patterns of hyperphosphatemia management in patients with chronic kidney disease (CKD). This manuscript reviews the evidence for the choice of phosphate binders and its impact on clinical outcomes. RECENT FINDINGS:Phosphate binders are among the most common medications prescribed for patients on dialysis. Clinical practice guidelines recommend lowering phosphate levels toward normal range and restricting calcium-based binders in all CKD patients. There is substantial gap in the evidence underlying these recommendations with lack of any placebo-controlled, randomized trials showing survival benefits for any class of phosphate-binders. Despite the lack of evidence for specific phosphate target or if lowering phosphate improves survival, use of phosphate binders has remained central strategy in approach to hyperphosphatemia. Use of binders has added to the cost and contributed significant pill burden. Restriction of calcium-based binders to avoid positive calcium balance and consequent vascular calcification risk has a physiological rationale and weight of observational studies. SUMMARY:There is currently no conclusive evidence that definitively guides the choice of any specific binders for management of hyperphosphatemia in patients with CKD. Use of noncalcium-based binders has a theoretical advantage in restricting total calcium intake to decrease the risk of vascular calcification but no proven benefits for mortality.

Deceased donor kidney allocation follows a ranked match-run of potential recipients. Organ procurement organizations (OPOs) are permitted to deviate from the mandated match-run in exceptional circumstances. Using match-run data for all deceased donor kidney transplants (Ktx) in the US between 2015 and 2019, we identified 1544 kidneys transplanted from 933 donors with an OPO-initiated allocation exception. Most OPOs (55/58) used this process at least once, but 3 OPOs performed 64% of the exceptions and just 2 transplant centers received 25% of allocation exception Ktx. At 2 of 3 outlier OPOs these transplants increased 136% and 141% between 2015 and 2019 compared to only a 35% increase in all Ktx. Allocation exception donors had less favorable characteristics (median KDPI 70, 41% with history of hypertension), but only 29% had KDPI ≥ 85% and the majority did not meet the traditional threshold for marginal kidneys. Allocation exception kidneys went to larger centers with higher offer acceptance ratios and to recipients with 2 fewer priority points-equivalent to 2 less years of waiting time. OPO-initiated exceptions for kidney allocation are growing increasingly frequent and more concentrated at a few outlier centers. Increasing pressure to improve organ utilization risks increasing out-of-sequence allocations, potentially exacerbating disparities in access to transplantation.

To evaluate the role of circulating dd-cfDNA in allograft surveillance in immunologically high-risk patients, a retrospective cross-sectional study of 261 kidney transplant recipients who underwent outpatient allograft biopsy at our center between September 2020 and August 2021 was performed. Of the 236 dd-cfDNA results included, 37 samples were obtained at the time of a surveillance biopsy in sensitized recipients and 199 at the time of a clinically indicated biopsy. The median serum creatinine at the time of the biopsy was 1.3 mg/dl and 2.1 mg/dl for surveillance biopsies and clinically indicated biopsies, respectively (P < .001). Rejection was diagnosed in 27% of surveillance biopsies and 29% of clinically indicated biopsies. Among surveillance biopsies, sensitivity and specificity to detect rejection were 0% and 89%, respectively, and among clinically indicated biopsies they were 28% and 96%, respectively. The sensitivity and specificity to detect antibody-mediated rejection were 0% and 91% among surveillance biopsies and 50% and 94% among clinically indicated biopsies. Nine biopsies without rejection findings had corresponding dd-cfDNA of ≥1%. Our data does not support dd-cfDNA as a biomarker for kidney allograft rejection, even in immunologically high-risk patients in the absence of graft dysfunction.