Challenges in the management of the kidney allograft: from decline to failure: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

In March 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a virtual Controversies Conference to address the important but rarely examined phase during which the kidney transplant is failing or has failed. In addition to discussing the definition of a failing allograft, 4 broad areas were considered in the context of a declining functioning graft: prognosis and kidney failure trajectory; immunosuppression strategies; management of medical and psychological complications, and patient factors; and choice of kidney replacement therapy or supportive care following graft loss. Identifying and paying special attention to individuals with failing allografts was felt to be important in order to prepare patients psychologically, manage immunosuppression, address complications, prepare for dialysis and/or retransplantation, and transition to supportive care. Accurate prognostication tools, although not yet widely available, were embraced as necessary to define allograft survival trajectories and the likelihood of allograft failure. The decision of whether to withdraw or continue immunosuppression after allograft failure was deemed to be based most appropriately on risk-benefit analysis and likelihood of retransplantation within a few months. Psychological preparation and support was identified as a critical factor in patient adjustment to graft failure, as was early communication. Several models of care were noted that enabled a medically supportive transition back to dialysis or retransplantation. Emphasis was placed on the importance of dialysis-access readiness before initiation of dialysis, in order to avoid use of central venous catheters. The centrality of the patient to all management decisions and discussions was deemed to be paramount. Patient "activation," which can be defined as engaged agency, was seen as the most effective way to achieve success. Unresolved controversies, gaps in knowledge, and areas for research were also stressed in the conference deliberations.

The windows of opportunity.

Models to predict survival after kidney transplantation have been developed, which have assisted clinicians in the selection of patients suitable for kidney transplant wait-listing. However, these models have ignored the competing problem of delisting and wait-list mortality, which are equally important in the decision-making process for determining transplant suitability. This commentary focuses on a newly introduced concept that integrates and quantifies the probability of wait-list survival versus receiving a deceased donor kidney transplant.

The differential impact of size mismatch in live versus deceased donor kidney transplant.

BACKGROUND: The impact of weight mismatch between donors and recipients (D-R) undergoing living-donor kidney transplant (LDKT) versus weight-matched deceased donor kidney transplant (DDKT) is not established. AIM: To determine whether absolute weight mismatch between D-R affects graft survival following LDKT and how this relates to graft outcomes with DDKT when D-R are weight matched. MATERIALS & METHODS: We used multivariable Cox proportional hazards models and the Scientific Registry of Transplant Recipients to determine the association of weight-mismatched D-R (>50 kg, 30-50 kg or 10-30 kg ((D < R); (D > R) and <10 kg (D = R)) with death-censored graft failure in US LDKT recipients from 2006 to 2017. We also explored outcomes relative to weight-matched DDKT and finally, the impact of combined D-R weight-sex mismatch. RESULTS: In LDKT, the risk of graft loss was highest in the setting of D < R (HR 1.28, 95% CI 1.05-1.56 for >50 kg difference relative to D = R); however, this was still lower risk than weight-matched DDKT. D-R sex and combined weight-sex mismatch were only important for male recipients (HR 1.47, 95% CI 1.27-1.71 for a male recipient >30 kg larger than their female donor, relative to weight-matched male donor-male recipient). This remained superior to weight-sex-matched DDKT however. CONCLUSION: D-R weight-sex mismatch is important in LDKT; however, graft survival remains superior to proceeding with matched DDKT. Optimizing D-R matching in LDKT could be facilitated through a national kidney-paired donation registry. LDKT weight-sex mismatch should not be deferred in favor of DDKT.

Referral for Kidney Transplantation in Canadian Provinces.

BACKGROUND: Patient referral to a transplant facility, a prerequisite for dialysis-treated patients to access kidney transplantation in Canada, is a subjective process that is not recorded in national dialysis or transplant registries. Patients who may benefit from transplant may not be referred. METHODS: In this observational study, we prospectively identified referrals for kidney transplant in adult patients between June 2010 and May 2013 in 12 transplant centers, and linked these data to information on incident dialysis patients in a national registry. RESULTS: Among 13,184 patients initiating chronic dialysis, the cumulative incidence of referral for transplant was 17.3%, 24.0%, and 26.8% at 1, 2, and 3 years after dialysis initiation, respectively; the rate of transplant referral was 15.8 per 100 patient-years (95% confidence interval, 15.1 to 16.4). Transplant referral varied more than three-fold between provinces, but it was not associated with the rate of deceased organ donation or median waiting time for transplant in individual provinces. In a multivariable model, factors associated with a lower likelihood of referral included older patient age, female sex, diabetes-related ESKD, higher comorbid disease burden, longer durations (>12.0 months) of predialysis care, and receiving dialysis at a location >100 km from a transplant center. Median household income and non-Caucasian race were not associated with a lower likelihood of referral. CONCLUSIONS: Referral rates for transplantation varied widely between Canadian provinces but were not lower among patients of non-Caucasian race or with lower socioeconomic status. Standardization of transplantation referral practices and ongoing national reporting of referral may decrease disparities in patient access to kidney transplant.

A contemporary description of patients' estimated blood losses from diagnostic phlebotomy in a census of hospital episodes from a Canadian tertiary care center.

BACKGROUND: Phlebotomy for diagnostic testing is among the commonest hospital procedures, but hospital-wide surveys of all inpatients characterizing blood draw volumes have not been published. The objectives were to characterize the daily blood volumes drawn for diagnostic testing from patients discharged from a Canadian tertiary care center, describe the daily distributions of phlebotomy volumes across service locations, and describe changes in hemoglobin (Hb) and transfusion across service locations. STUDY DESIGN AND METHODS: Data were obtained on all patients discharged between 2012 and 2014 using linked discharge abstract and laboratory data. Cumulative daily blood volume and draw frequency were reported by service and days since admission. Changes in Hb and red blood cell (RBC) transfusion rates were reported for nontransfused and transfused patients. RESULTS: Data were included on 59,715 subjects. Mean daily estimated blood loss varied from 8.5 ± 6.5 mL/day onward to 27.2 ± 20.0 mL/day in the intensive care unit (ICU; p < 0.001). Phlebotomy volumes were highest on the first day of admission and declined thereafter (p < 0.001). For nontransfused individuals in the first week of admission, Hb levels decreased by the highest percentage in the ICU. The rate of RBC unit transfusion was highest in the ICU (232.4 units/1000 patient-days; 95% confidence interval, 225.8-239.2; p < 0.0001 compared with all other locations). CONCLUSION: Considerable variation was observed in estimated blood loss due to diagnostic phlebotomy across different services within one teaching hospital. Thi information is foundational for planning interventions to minimize estimated blood loss from phlebotomy.

Burden of Emergency Medical Services Usage by Dialysis Patients.

BACKGROUND: Patients receiving chronic dialysis often require emergent and inpatient care; however, only a minimal amount is known about their out-of-hospital/inter-hospital use of Emergency Medical Services (EMS). The purpose of this study was to describe the utilization of EMS in a cohort of dialysis patients. METHODS: We analyzed a cohort of adult (≥18 years) chronic dialysis patients within the Nova Scotia Health Authority Central Zone Renal Program who initiated chronic dialysis between January 1, 2009 and June 30, 2013 (last follow up July 1, 2015). Dialysis patient data was linked to regional EMS data. Requests for EMS, including encounter type, day of the week, and patient characteristics were described. RESULTS: The cohort consisted of 468 patients of whom 79% (N = 361) had an EMS encounter. There were a total of 8,774 EMS encounters for the entire cohort. Patients who had an EMS encounter tended to be older (64 ± 14 years), compared to those without an encounter (55 ± 16 years, P < 0.001) and also had a higher burden of comorbidity. Transfers (including those between facilities) accounted for 89% of all encounters (N = 7,826), followed by emergency department (ED) transports (N = 749, 9%). Overall, 79% of all non-transfers underwent transport to the ED. For patients receiving thrice weekly in-center hemodialysis, the highest EMS utilization for ED transport occurred on the first hemodialysis day after the long dialysis break (22%, P < 0.01). The lowest proportion of ED transports occurred on the day after hemodialysis day 3. CONCLUSION: Utilization of EMS services by dialysis patients is considerable, particularly for transfers. This highlights a potential area to be targeted for reducing resource utilization. Calls requiring transport to the ED occurred most often on Mondays and Tuesdays, the day after the long-dialysis break, and may represent a time of heightened risk for in-center hemodialysis patients.

Frailty in end-stage renal disease: comparing patient, caregiver, and clinician perspectives.

BACKGROUND: Frailty is associated with poor outcomes for patients on dialysis and is traditionally measured using tools that assess physical impairment. Alternate measurement tools highlight cognitive and functional domains, requiring clinician, patient, and/or caregiver input. In this study, we compared frailty measures for incident dialysis patients that incorporate patient, clinician, and caregiver perspectives with an aim to contrast the measured prevalence of frailty using tools derived from different conceptual frameworks. METHODS: A prospective cohort study of incident dialysis patients was conducted between February 2014 and June 2015. Frailty was assessed at dialysis onset using: 1) modified definition of Fried Phenotype (Dialysis Morbidity Mortality Study definition, DMMS); 2) Clinical Frailty Scale (CFS); 3) Frailty Assessment Care Planning Tool (provides CFS grading, FACT-CFS); and 4) Frailty Index (FI). Measures were compared via correlation and sensitivity/specificity analyses. RESULTS: A total of 98 patients participated (mean age of 61 ± 14 years). Participants were primarily Caucasian (91%), male (58%), and the majority started on hemodialysis (83%). The median score for both the CFS and FACT-CFS was 4 (interquartile range of 3-5). The mean FI score was 0.31 (standard deviation ± 0.16). The DMMS identified 78% of patients as frail. The FACT-CFS demonstrated highest correlation (r = 0.71) with the FI, while the DMMS was most sensitive (97%, 100%) and a CFS ≥ 5 most specific (100%, 77%) at corresponding FI cutoff values (>0.21, >0.45). CONCLUSIONS: Frailty assessments of incident dialysis patients that include clinician, caregiver and patient perspectives have moderate to strong correlation with the FI. At specified FI cutoff values, the FACT-CFS and DMMS are highly sensitive measures of frailty. The CFS and FACT-CFS may represent viable alternative screening tools in dialysis patients.

Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation.

Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000-2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10-to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99-1.15), 1.13 (1.06-1.22), 1.17 (1.09-1.26), 1.20 (1.12-1.30), and 1.23 (1.15-1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study.

Incidence, etiology, and significance of acute kidney injury in the early post-kidney transplant period.

Little is known about the incidence, causes, and significance of acute kidney injury (AKI) in the early transplant period. This study used a definition as >26 µmol/L increase in creatinine within 48 h or >50% increase over a period >48 h. In 326 adult consecutive recipients of a solitary kidney transplant from 2006 to 2014 followed at this center, 21% developed AKI within the first six months. Most etiologies were CNI toxicity (33%) or unknown (26%), whereas acute rejection accounted for 17% and urinary tract obstruction for 10%. Those with AKI had a significantly lower glomerular filtration rate (GFR) at one-yr post-transplant (adjusted beta coefficient -5.5 mL/min/1.73 m(2) , 95% CI: -10.4, -0.7, p = 0.025) in a multivariable linear regression model. However, the AKI definition missed 6 of 19 episodes of acute rejection and 4 of 10 episodes of urinary tract obstruction. When acute rejection (including those that did not satisfy AKI criteria) was included in the model, other causes of AKI were not significantly associated with GFR at year 1. Although AKI, using current criteria, is likely to be a significant predictor of later outcomes, important causes are missed and the criteria are not sensitive for clinical decision-making.

Predicting 5-year risk of kidney transplant failure: a prediction instrument using data available at 1 year posttransplantation.

BACKGROUND: Accurate prediction of kidney transplant failure remains imperfect. The objective of this study was to develop and validate risk scores predicting 5-year transplant failure, based on data available 12 months posttransplantation. STUDY DESIGN: Development and then independent multicenter validation of risk scores predicting death-censored and overall transplant failure. SETTING & PARTICIPANTS: Outcomes of kidney transplant recipients (n=651) alive with transplant function 12 months posttransplantation in Birmingham, United Kingdom, were used to develop models predicting transplant failure risk 5 years posttransplantation. The resulting risk scores were evaluated for prognostic utility (discrimination, calibration, and risk reclassification) in independent cohorts from Tours, France (n=736); Leeds, United Kingdom (n=787); and Halifax, Canada (n=475). PREDICTORS: Weighted regression coefficients for baseline and 12-month demographic and clinical predictor characteristics. OUTCOMES: Death-censored and overall transplant failure 5 years posttransplantation. MEASUREMENTS: Baseline data and time to transplant failure. RESULTS: Following model development, variables included in separate scores for death-censored and overall transplant failure included recipient age, sex, and race; acute rejection; transplant function; serum albumin level; and proteinuria. In the validation cohorts, these scores showed good to excellent discrimination for death-censored transplant failure (C statistics, 0.78-0.90) and moderate to good discrimination for overall transplant failure (C statistics, 0.75-0.81). Both scores demonstrated good calibration (Hosmer-Lemeshow P>0.05 in all cohorts). Compared with estimated glomerular filtration rate in isolation, application of the scores resulted in statistically significant and clinically relevant risk reclassification for death-censored transplant failure (net reclassification improvement [NRI], 36.1%-83.0%; all P<0.001) and overall transplant failure (NRI, 38.7%-53.5%; all P<0.001). Compared with the previously described US Renal Data System-based risk calculator, significant and relevant risk reclassification for overall transplant failure was seen (NRI, 30.0%; P<0.001). LIMITATIONS: Validation is required in further populations. CONCLUSIONS: These validated risk scores may be of prognostic utility in kidney transplantation, accurately identifying at-risk transplants, and informing clinicians and patients.

The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation.

BK polyomavirus (BKPyV) remains a significant challenge after kidney transplantation. International experts reviewed current evidence and updated recommendations according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Risk factors for BKPyV-DNAemia and biopsy-proven BKPyV-nephropathy include recipient older age, male sex, donor BKPyV-viruria, BKPyV-seropositive donor/-seronegative recipient, tacrolimus, acute rejection, and higher steroid exposure. To facilitate early intervention with limited allograft damage, all kidney transplant recipients should be screened monthly for plasma BKPyV-DNAemia loads until month 9, then every 3 mo until 2 y posttransplant (3 y for children). In resource-limited settings, urine cytology screening at similar time points can exclude BKPyV-nephropathy, and testing for plasma BKPyV-DNAemia when decoy cells are detectable. For patients with BKPyV-DNAemia loads persisting >1000 copies/mL, or exceeding 10 000 copies/mL (or equivalent), or with biopsy-proven BKPyV-nephropathy, immunosuppression should be reduced according to predefined steps targeting antiproliferative drugs, calcineurin inhibitors, or both. In adults without graft dysfunction, kidney allograft biopsy is not required unless the immunological risk is high. For children with persisting BKPyV-DNAemia, allograft biopsy may be considered even without graft dysfunction. Allograft biopsies should be interpreted in the context of all clinical and laboratory findings, including plasma BKPyV-DNAemia. Immunohistochemistry is preferred for diagnosing biopsy-proven BKPyV-nephropathy. Routine screening using the proposed strategies is cost-effective, improves clinical outcomes and quality of life. Kidney retransplantation subsequent to BKPyV-nephropathy is feasible in otherwise eligible recipients if BKPyV-DNAemia is undetectable; routine graft nephrectomy is not recommended. Current studies do not support the usage of leflunomide, cidofovir, quinolones, or IVIGs. Patients considered for experimental treatments (antivirals, vaccines, neutralizing antibodies, and adoptive T cells) should be enrolled in clinical trials.

The Impact of Combined Warm and Cold Ischemia Time on Post-transplant Outcomes.

Background: Prolonged warm ischemia time (WIT) and cold ischemia time (CIT) are independently associated with post-transplant graft failure; their combined impact has not been previously studied. We explored the effect of combined WIT/CIT on all-cause graft failure following kidney transplantation. Methods: The Scientific Registry of Transplant Recipients was used to identify kidney transplant recipients from January 2000 to March 2015 (after which WIT was no longer separately reported), and patients were followed until September 2017. A combined WIT/CIT variable (excluding extreme values) was separately derived for live and deceased donor recipients using cubic splines; for live donor recipients, the reference group was WIT 10 to <23 minutes and CIT >0 to <0.42 hours, and for deceased donor recipients the WIT was 10 to <25 minutes and CIT 1 to <7.75 hours. The adjusted association between combined WIT/CIT and all-cause graft failure (including death) was analyzed using Cox regression. Secondary outcomes included delayed graft function (DGF). Results: A total of 137 125 recipients were included. For live donor recipients, patients with prolonged WIT/CIT (60 to ≤120 minutes/3.04 to ≤24 hours) had the highest adjusted hazard ratio (HR) for graft failure (HR = 1.61, 95% confidence interval [CI] = 1.14-2.29 relative to the reference group). For deceased donor recipients, a WIT/CIT of 63 to ≤120 minutes/28 to ≤48 hours was associated with an adjusted HR of 1.35 (95% CI = 1.16-1.58). Prolonged WIT/CIT was also associated with DGF for both groups although the impact was more driven by CIT. Conclusions: Combined WIT/CIT is associated with graft loss following transplantation. Acknowledging that these are separate variables with different determinants, we emphasize the importance of capturing WIT and CIT independently. Furthermore, efforts to reduce WIT and CIT should be prioritized.

Contexte: La période prolongée d'ischémie à chaud (WIT­warm ischemia time) et la période prolongée d'ischémie à froid (CIT­cold ischemia time) ont été associées de façon indépendante à une défaillance du greffon post-transplantation, mais leur effet combiné n'a jamais été étudié. Nous avons examiné l'effet combiné WIT/CIT sur la défaillance du greffon toutes causes confondues après une transplantation rénale. Méthodologie: Le Scientific Registry of Transplant Recipients a été utilisé pour identifier les receveurs d'une greffe de rein entre janvier 2000 et mars 2015 (date après laquelle la WIT n'a plus été rapportée séparément). Les patients ont été suivis jusqu'en septembre 2017. Une variable combinée WIT/CIT (excluant les valeurs extrêmes) a été dérivée de façon isolée pour les donneurs vivants et les donneurs décédés à l'aide d'une fonction spline cubique. La WIT du groupe référence pour les donneurs vivants se situait entre 10 et <23 minutes, et la CIT entre 0 et <0,42 heure; pour les donneurs décédés, la WIT se situait entre 10 et <25 minutes, et la CIT entre 1 et <7,75 heures. L'association corrigée entre une combinaison WIT/CIT et la défaillance du greffon toutes causes confondues (y compris le décès) a été analysée à l'aide de la régression de Cox. Les résultats secondaires incluaient une reprise retardée de la fonction du greffon (RRFG). Résultats: Un total de 137 125 receveurs d'un rein a été inclus. Dans le groupe des receveurs d'un organe provenant d'un donneur vivant, les patients avec une WIT/CIT prolongée (60 à ≤120 minutes/3,04 à ≤24 heures) présentaient un risque relatif corrigé plus élevé de défaillance du greffon (RRc: 1,61; IC 95 %: 1,14-2,29) par rapport au groupe de référence. Dans le groupe des receveurs d'un organe provenant d'un donneur décédé, une combinaison WIT/CIT de 63 à ≤120 minutes/28 à ≤48 heures a été associée à un RRc de 1,35 (IC 95 %: 1,16-1,58). La WIT/CIT prolongée a également été associée à une RRFG pour les deux groupes, bien que cet effet ait été davantage influencé par la CIT. Conclusion: La combinaison WIT/CIT est associée à la perte du greffon après la transplantation. Sachant qu'il s'agit de variables distinctes avec des déterminants différents, nous soulignons l'importance de rapporter la WIT et la CIT de façon indépendante. Qui plus est, les efforts visant à réduire la WIT et la CIT devraient être prioritaires.

Limits to intensified mycophenolate mofetil dosing in kidney transplantation.

BACKGROUND: Studies have shown that achieving adequate exposure of mycophenolic acid (MPA) early post transplant is associated with less acute rejection in kidney recipients. Intensified dosing with the equivalent of mycophenolate mofetil (MMF) 3 g daily in tacrolimus-treated patients has been shown to increase exposure however about 15% remain below the lower therapeutic threshold of MPA area under the curve (AUC) of 30 mg · hr⁻¹ · L⁻¹ early post transplant. A post hoc analysis of this study showed that a target MPA AUC >40 mg · hr⁻¹ · L⁻¹ was most effective. The primary objective of this study was to determine whether 4 g daily of MMF would result in a greater proportion achieving adequate MPA exposure. MATERIALS AND METHODS: MMF 4 g daily was used in tacrolimus treated de novo kidney transplant recipients. A 3-point limited sample strategy was used to measure MPA AUC on days 5 and 14. Doses were adjusted at day 5 if exposure was high. RESULTS: In 30 patients, the mean AUC was 63 ± 28 mg · hr⁻¹ · L⁻¹ on day 5, with 13% (4/30) ≤ 30 mg · hr⁻¹ · L⁻¹ and 57% (17/30) >60 mg · hr⁻¹ · L⁻¹. The target MPA AUC was <40 mg · hr⁻¹ · L⁻¹ in 23% (7/30). Three patients developed gastrointestinal toxicity and required dose changes. Acute rejection occurred in only 2 patients (grade 1A and 2B) within 3 months (day 5 MPA AUCs were 29.9 and 33 mg · hr⁻¹ · L⁻¹. On day 14 the mean AUC was 46 ± 17 mg · hr⁻¹ · L⁻¹. Many were on MMF doses >2 g daily (8 on 3 g and 9 on 4 g daily). CONCLUSION: Compared to MMF 3 g daily, 4 g daily dose not result in a greater proportion adequately exposed. Rejections were few and occurred in the lower MPA exposed recipients. More than 50% of patients needed doses of MMF >2 g daily for 2 weeks to avoid underexposure. If intensified MPA dosing is considered, exceeding 3 g daily in tacrolimus-treated patients provides no added benefit.

The impact of an "acute dialysis start" on the mortality attributed to the use of central venous catheters: a retrospective cohort study.

BACKGROUND: Central venous catheters (CVCs) are associated with early mortality in dialysis patients. However, some patients progress to end stage renal disease after an acute illness, prior to reaching an estimated glomerular filtration rate (eGFR) at which one would expect to establish alternative access (fistula/peritoneal dialysis catheter). The purpose of this study was to determine if exclusion of this "acute start" patient group alters the association between CVCs and mortality. METHODS: We conducted a retrospective cohort study of 406 incident dialysis patients from 1 Jan 2006 to 31 Dec 2009. Patients were classified as acute starts if 1) the eGFR was >25 ml/min/1.73 m2, ≤ 3 months prior to dialysis initiation and declined after an acute event (n = 45), or 2) in those without prior eGFR measurements, there was no supporting evidence of chronic kidney disease on history or imaging (n = 12). Remaining patients were classified as chronic start (n = 349). RESULTS: 98 % and 52 % of acute and chronic starts initiated dialysis with a CVC. There were 148 deaths. The adjusted mortality hazard ratio (HR) for acute vs. chronic start patients was 1.84, (95 % CI [1.19-2.85]). The adjusted mortality HR for patients dialyzing with a CVC compared to alternative access was 1.19 (95 % CI [0.80-1.77]). After excluding acute start patients, the adjusted HR fell to 1.03 (95 % CI [0.67-1.57]). CONCLUSIONS: A significant proportion of early dialysis mortality occurs after an acute start. Exclusion of this population attenuates the mortality risk associated with CVCs.

Comparing the Net Benefits of Adult Deceased Donor Kidney Transplantation for a Patient on the Preemptive Waiting List vs a Patient Receiving Dialysis.

Importance: Preemptive kidney transplantation is the preferred treatment for end-stage kidney disease. However, deceased donor (DD) kidneys are limited, and the net benefit of allocating kidneys to a preemptively waitlisted patient rather than to a patient receiving dialysis is unclear. Objective: To estimate the net benefit and costs of allocating kidneys to preemptively waitlisted patients vs those receiving dialysis. Design, Setting, and Participants: This medical decision analytical model used data from the 2020 US Renal Data System to calculate patient survival among waitlisted patients who received a DD kidney transplant. Four patients were simulated, with similar characteristics: (1) a patient on the preemptive waiting list receiving a DD transplant, (2) a patient on the preemptive waiting list never receiving a transplant, (3) a waitlisted patient already receiving dialysis (dialysis vintage <1 year) receiving a transplant, and (4) a waitlisted patient already receiving dialysis (dialysis vintage <1 year) never receiving a transplant. Annual probability of initiating dialysis (for patients 1 and 2) and duration of dialysis (for patients 3 and 4) were varied in sensitivity analyses. Exposures: Allocating a DD kidney to a patient on the preemptive waiting list vs the same kidney to a patient receiving dialysis for less than 1 year, with similar recipient characteristics. Main Outcomes and Measures: Differences in projected quality-adjusted life-years (QALYs) and total costs. Results: In a simulated patient with a mean start age of 50 years (range, 30-64 years), the patient receiving a preemptive DD transplantation experienced 10.58 (95% CI, 10.36-10.80) QALYs, and the patient on the preemptive waiting list never transplanted experienced 6.83 (95% CI, 6.67-6.99) QALYs. The patient receiving DD transplantation after less than 1 year of dialysis experienced 10.33 (95% CI, 10.21-10.55) QALYs, and the patient receiving dialysis who remained on the waiting list experienced 6.20 (95% CI, 6.04-6.36) QALYs; allocating a DD kidney to the preemptive patient added 3.75 (95% CI, 3.57-3.93) QALYs, whereas allocating the kidney to the patient already receiving dialysis added 4.13 (95% CI, 3.92-4.31) QALYs. While the estimated posttransplant survival was longest for the preemptive transplant recipient, preferentially allocating the kidney to the preemptive patient results in 0.39 (95% CI, 0.49-0.29) fewer QALYs. The net cost of preemptive transplantation was $54 100 (95% CI, $44 100-$64 100) more than transplantation to a waitlisted patient. If the rate of transitioning to dialysis was 20 (rather than 33) events per 100 patient waiting list-years, the net QALYs were -0.67 (95% CI, -0.78 to -0.56). If the patient was receiving dialysis for 3 to 4 years (vs <1 year) the net benefit was not significantly different; however, net costs were considerably higher for the preemptive option. Conclusions and Relevance: In this decision analytic model study, although allocating DD kidneys to patients preemptively was the best option from a patient perspective, allocating DD kidneys to patients receiving dialysis was a better use of a scare resource from a societal perspective.

Optimal Sequencing of Deceased Donor and Live Donor Kidney Transplant Among Pediatric Patients With Kidney Failure.

Importance: In the US, live donor (LD) kidney transplant rates have decreased in pediatric recipients. Pediatric patients with kidney failure will likely need more than 1 kidney transplant during their lifetime, but the optimal sequence of transplant (ie, deceased donor [DD] followed by LD or vice versa) is not known. Objective: To determine whether pediatric recipients should first receive a DD allograft followed by an LD allograft (DD-LD sequence) or an LD allograft followed by a DD allograft (LD-DD sequence). Design, Setting, and Participants: This decision analytical model examined US pediatric patients with kidney failure included in the US Renal Data System 2019 Report who were waiting for a kidney transplant, received a transplant, or experienced graft failure. Interventions: Kidney transplant sequences of LD-DD vs DD-LD. Main Outcomes and Measures: Difference in projected life-years between the 2 sequence options. Results: Among patients included in the analysis, the LD-DD sequence provided more net life-years in those 5 years of age (1.82 [95% CI, 0.87-2.77]) and 20 years of age (2.23 [95% CI, 1.31-3.15]) compared with the DD-LD sequence. The net outcomes in patients 10 years of age (0.36 [95% CI, -0.51 to 1.23] additional life-years) and 15 years of age (0.64 [95% CI, -0.15 to 1.39] additional life-years) were not significantly different. However, for those aged 10 years, an LD-DD sequence was favored if eligibility for a second transplant was low (2.09 [95% CI, 1.20-2.98] additional life-years) or if the LD was no longer available (2.32 [95% CI, 1.52-3.12] additional life-years). For those aged 15 years, the LD-DD sequence was favored if the eligibility for a second transplant was low (1.84 [95% CI, 0.96-2.72] additional life-years) or if the LD was no longer available (2.49 [95% CI, 1.77-3.27] additional life-years). Access to multiple DD transplants did not compensate for missing the LD opportunity. Conclusions and Relevance: These findings suggest that the decreased use of LD kidney transplants in pediatric recipients during the past 2 decades should be scrutinized. Given the uncertainty of future recipient eligibility for retransplant and future availability of an LD transplant, the LD-DD sequence is likely the better option. This strategy of an LD transplant first would not only benefit pediatric recipients but allow DD kidneys to be used by others who do not have an LD option.

The Role of Donor Sex in Females Undergoing Repeat Kidney Transplant: Does Prior Donor Sex Matter?

Female recipients of male donor kidneys are at increased risk for graft failure because of the HY antigen effect. However, whether prior transplant with a male donor impacts subsequent transplant outcomes is unknown. Therefore, the purpose of this study was to determine whether prior male-current male donor sex is associated with an increased risk of graft failure in female recipients. Methods: We performed a cohort study of adult female recipients undergoing a second kidney transplant (2000-2017), identified using the Scientific Registry of Transplant Recipients. Using multivariable Cox models, we analyzed the risk of death-censored graft loss (DCGL) if the second transplant was from a male versus female kidney donor, conditional on donor sex at the time of the first transplant. In a secondary analysis, we stratified results by recipient age (>50 or ≤50 y) at the time of retransplant. Results: Of 5594 repeat kidney transplants, 1397 (25.0%) developed DCGL. Overall, there was no association between first and second donor sex pairing and DCGL. A prior and current female donor (FD1FD2) posed a higher risk for DCGL in recipients aged >50 y at second transplant (hazard ratio,≤0.67, confidence interval 0.46-0.98, for all other donor combinations), but posed a lower risk if aged ≤50 y at retransplant (hazard ratio, ≥1.37, confidence interval 1.04-1.80, for all other donor combinations). Conclusions: Overall, past-current donor sex pairing was not associated with DCGL in female recipients undergoing second kidney transplant; however, the risk with a past and current female donor was increased in older, and decreased in younger, female recipients at retransplant.

Economic Evaluation of Screening for Polyomavirus Infection in Kidney Transplant Recipients: A Cost-Utility Analysis.

Screening for polyomavirus infection after kidney transplantation is recommended by clinical practice guidelines, but cost-effectiveness of this strategy is uncertain. The aim of this study was to estimate the incremental costs and benefits of routine screening for polyomavirus infection compared with no screening in kidney transplant recipients. Methods: Probabilistic Markov models were constructed to compare the health and economic benefits of routine screening for polyomavirus infection using real-time polymerase chain reaction assay. A series of 1-way and probabilistic sensitivity analyses were conducted to define the most influential variables in the model. Results: Monthly screening for 6 mo followed by 3 monthly screenings until 12 mo after transplant was dominant (lower costs and improved outcomes). Compared with no screening, the incremental benefits of screening were 0.294 life-years saved and 0.232 quality-adjusted life-years saved. Total savings from screening were $6986 Australian dollars ($5057 US dollars). The cost-effectiveness ratios were most sensitive to the costs of transplantation and dialysis, age of transplantation, prevalence of viremia, and probability of death in patients with a history of polyomavirus-associated nephropathy. Probabilistic sensitivity analysis indicated that screening (compared with no screening) was the dominant strategy across all plausible ranges of transition probabilities. Conclusions: Screening for polyomavirus infections 1 year following transplantation appears to save money, improves survival, and improves quality of life in kidney transplant recipients.

Disparities in Access to Preemptive Repeat Kidney Transplant: Still Missing the Mark?

Background: The need for repeat transplant due to failing kidney allografts is increasing over time. The benefit of preemptive kidney retransplant (PKre-T) is controversial. Marginalized populations are less likely to undergo their first transplant preemptively; however, whether inequities exist for those undergoing PKre-T is unknown. Methods: We performed a cohort study of adult patients undergoing live and deceased kidney transplant in the United States from 2000 to 2018 identified using the Scientific Registry of Transplant Recipients, and we identified patients with first preemptive kidney transplant (PKT) and PKre-T. In the primary analysis, a multivariable logistic regression was used to identify independent predictors of PKre-T. In secondary analyses, multivariable Cox models were used to determine the association of PKre-T with death-censored and all-cause graft loss. Results: In total, 4910 (15.5%) patients underwent PKre-T, and 43,293 (19.1%) underwent first PKT. Inequities in access to PKre-T persisted (OR, 0.49; 95% CI, 0.44 to 0.55 for unemployed versus full time; OR, 1.61; 95% CI, 1.14 to 2.25 for graduate school versus not completing high school; OR, 0.61; 95% CI, 0.52 to 0.70 for Black versus White race); 7.1% of all transplanted Black patients received PKre-T versus 17.4% of White patients. Women were more likely to undergo PKre-T than men (OR, 1.42; 95% CI, 1.29 to 1.57). PKre-T was associated with superior graft survival relative to retransplant after a period of dialysis (HR, 0.73; 95% CI, 0.67 to 0.80 for all-cause graft failure; HR, 0.72; 95% CI, 0.65 to 0.81 for death-censored graft loss). Conclusions: Despite improved patient and graft survival, inequities in access to PKre-T persist. Patients with lower education, patients with reduced employment status, patients of Black race, and men are less likely to receive PKre-T.