Transplant social worker and donor financial assistance to increase living donor kidney transplants among African Americans: The TALKS Study,a randomized comparative effectiveness trial

Lack of donors hinders living donor kidney transplantation (LDKT) for African Americans. We studied the effectiveness of a transplant social worker intervention (TALK SWI) alone or paired with living donor financial assistance to activate African Americans’ potential living kidney donors. African Americans (N = 300) on the transplant waiting list were randomly assigned to usual care; TALK SWI; or TALK SWI plus Living Donor Financial Assistance. We quantified differences in live kidney donor activation (composite rate of live donor inquiries, completed new live donor evaluations, or live kidney donation) after 12 months. Participants’ mean age was 52 years, 56% were male, and 43% had annual household income less than $40,000. Most previously pursued LDKT. Participants were highly satisfied with TALK social workers, but they rarely utilized Financial Assistance. After 12 months, few (n = 39, 13%) participants had a new donor activation event (35 [12%] new donor inquiries; 17 [6%] new donor evaluations; 4 [1%] LDKT). There were no group differences in donor activation events (subdistribution hazard ratio [95% CI]: 1.09 [0.51–2.30] for TALK SWI and 0.92 [0.42–2.02] for TALK SWI plus Financial Assistance compared to Usual Care, p = 91). Alternative interventions to increase LDKT for African Americans on the waiting list may be needed. Trial registration: ClinicalTrials.gov (NCT02369354).     

Epidemiology of end‐stage renal failure among twins and diagnosis,management, and current outcomes of kidney transplantation between identical twins

The aim of the study is to provide a comprehensive overview of identical twin kidney transplantation in the modern era. We provide epidemiologic trends in the US twin population from 1959 to 2000, current methods to identify zygosity, outcomes for identical twin transplants, and a comprehensive management strategy for identical twin kidney transplantation. By 2019, we project that 433 010 dizygotic and monozygotic twins will be alive and at risk for developing ESRF. Monozygosity between a donor‐recipient pair can be confirmed by concordance in sex, blood type, and HLA antigen match with precision testing using 13/17 Short Tandem Repeat sequencing to a likelihood of nearly 100%. Among identical twin transplants from 2001 to 2017, excellent patient and kidney graft survival rates were noted. Approximately 50% of kidney transplant recipients of identical twins transplant did not receive maintenance immunosuppression, and no differences in graft survival were noted among patients with and without immunosuppression at 6 and 12 months (P = .8 and .7). Patients with glomerulonephritis as the cause of ESRF had lower graft survival (P = .06) suggesting that recurrent glomerulonephritis as a likely cause of graft loss among these recipients.     

Impact of kidney transplantation on sleep apnea severity: A prospective polysomnographic study

Fluid overload has been associated with a high prevalence of sleep apnea (SA) in patients with end‐stage kidney disease (ESKD). In this prospective study, we hypothesized that improvement in kidney function and hydration status after kidney transplantation (Tx) may result in an improvement in SA severity. A total of 196 patients on the kidney Tx waiting list were screened for SA using home nocturnal polysomnography (PSG) to measure the apnea‐hypopnea index (AHI) and underwent bioimpedance to assess body composition. Of 88 participants (44.9%) with SA (AHI ≥ 15/h), 42 were reassessed 6 months post‐Tx and were compared with 27 control patients. There was a significant, but small, post‐Tx improvement in AHI (from 44.2 ± 24.3 to 34.7 ± 20.9/h, P = .02) that significantly correlated with a reduction in fluid overload (from 1.8 ± 2.0 to 1.2 ± 1.2 L, P = .02) and body water (from 54.9% to 51.6%, P = .003). A post‐Tx increase in body fat mass (from 26% to 30%, P = .003) possibly blunted the beneficial impact of kidney Tx on SA. All parameters remained unchanged in the control group. In conclusion, SA is a frequent condition in ESKD patients and partially improved by kidney Tx. We suggest that SA should be systematically assessed before and after kidney Tx. ClinicalTrials.gov Identifier: NCT02020642.     

Posttransplant recurrence of calcium oxalate crystals in patients with primary hyperoxaluria: Incidence,risk factors,and effect on renal allograft function

Primary hyperoxaluria (PH) is a metabolic defect that results in oxalate overproduction by the liver and leads to kidney failure due to oxalate nephropathy. As oxalate tissue stores are mobilized after transplantation, the transplanted kidney is at risk of recurrent disease. We evaluated surveillance kidney transplant biopsies for recurrent calcium oxalate (CaOx) deposits in 37 kidney transplants (29 simultaneous kidney and liver [K/L] transplants and eight kidney alone [K]) in 36 PH patients and 62 comparison transplants. Median follow-up posttransplant was 9.2 years (IQR: [5.3, 15.1]). The recurrence of CaOx crystals in surveillance biopsies in PH at any time posttransplant was 46% overall (41% in K/L, 62% in K). Higher CaOx crystal index (which accounted for biopsy sample size) was associated with higher plasma and urine oxalate following transplant (p < .01 and p < .02, respectively). There was a trend toward higher graft failure among PH patients with CaOx crystals on surveillance biopsies compared with those without (HR 4.43 [0.88, 22.35], p = .07). CaOx crystal deposition is frequent in kidney transplants in PH patients. The avoidance of high plasma oxalate and reduction of CaOx crystallization may decrease the risk of recurrent oxalate nephropathy following kidney transplantation in patients with PH. This study was approved by the IRB at Mayo Clinic.     

Long‐term outcomes in patients with obesity and renal disease after sleeve gastrectomy

Morbid obesity is a barrier to kidney transplant in patients with end‐stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (SG) is an increasingly considered intervention, but the safety and long‐term outcomes are uncertain. We reviewed prospectively collected data on patients with ESRD and chronic kidney disease (CKD) undergoing SG from 2011 to 2018. There were 198 patients with ESRD and 45 patients with CKD (stages 1‐4) who met National Institutes of Health guidelines for bariatric surgery and underwent SG; 72% and 48% achieved a body mass index of ≤ 40 and ≤ 35 kg/m², respectively. The mean percentages of total weight loss and excess weight loss were 18.9 ± 10.8% and 38.2 ± 20.3%, respectively. SG reduced hypertension (85.8% vs 52.1%), decreased antihypertensive medication use (1.6 vs 1.0) (P < .01 each), and reduced incidence of diabetes (59.6% vs 32.5%, P < .01). Of the 71 patients with ESRD who achieved a body mass index of ≤ 40 kg/m², 45 were waitlisted and received a kidney transplant, whereas 10 remain on the waitlist. Mortality rate after SG was 1.8 per 100 patient‐years, compared with 7.3 for non‐SG. Patients with stage 3a or 3b CKD exhibited improved glomerular filtration rate (43.5 vs 58.4 mL/min, P = .01). In conclusion, SG safely improves transplant candidacy while providing significant, sustainable effects on weight loss, reducing medical comorbidities, and possibly improving renal function in stage 3 patients.     

Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R² 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.     

Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial

Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-γ ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E−) were randomized to LI (n = 48) or SOC (n = 53), E+ received the same SOC. Six- and 12-month BPAR rates were higher among LI than SOC/E− (4/35 [13%] vs. 1/43 [2%], p = .15 and 12/48 [25%] vs. 6/53 [11.3%], p = .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per-protocol analyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E− patients, notably E−/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p = .043). Eplet mismatch also predicted anti-class-I (p = .05) and anti-DQ (p < .001) de novo DSA. Adverse events were similar, but E−/LI developed fewer viral infections, particularly polyoma-virus-associated nephropathy (p = .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation.     

The Novel Application of Genomic Profiling Assays to Shorten Inactive Status for Potential Kidney Transplant Recipients With Breast Cancer

The concern about cancer recurrence has traditionally resulted in delaying kidney transplantation for 2–5 years after a cancer diagnosis in patients who are otherwise eligible for transplant. This period of inactive status to observe the tumor biology can result in significant morbidity and decreased quality of life for patients with end‐stage renal disease (ESRD). We reported the novel application of genomic profiling assays in breast cancer to identify low‐risk cancers in two patients with ESRD who were able to have the mandatory inactive status eliminated prior to kidney transplantation.     

Simultaneous robotic kidney transplantation and bariatric surgery for morbidly obese patients with end-stage renal failure

Patients with obesity have limited access to kidney transplantation, mainly due to an increased incidence of surgical complications, which could be reduced with selective use of robotic-assisted surgery. This prospective randomized controlled trial compares the safety and efficacy of combining robotic sleeve gastrectomy and robotic-assisted kidney transplant to robotic kidney transplant alone in candidates with class II or III obesity. Twenty candidates were recruited, 11 were randomized to the robotic sleeve gastrectomy and robotic-assisted kidney transplant group and 9 to the robotic kidney transplant group. At 12-month follow-up, change in body mass index was –8.76 ± 1.82 in the robotic sleeve gastrectomy and robotic-assisted kidney transplant group compared to 1.70 ± 2.30 in the robotic kidney transplant group (P = .0041). Estimated glomerular filtration rate, serum creatinine, readmission rates, and graft failure rates up to 12 months were not different between the two groups. Length of surgery was longer in the robotic sleeve gastrectomy and robotic-assisted kidney transplant group (405 minutes vs. 269 minutes, p = .00304) without increase in estimated blood loss (120 ml vs. 117 ml, p = .908) or incidence of surgical complications. Combined robotic-assisted kidney transplant and sleeve gastrectomy is safe and effective compared to robotic-assisted kidney transplant alone.     

Increasing access to renal transplantation in India through our single‐center kidney paired donation program: a model for the developing world to prevent commercial transplantation

Because access to transplantation with HLA‐desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end‐stage renal disease (ESRD) patient in India. We present a government and institutional ethical review board approved study of 56 ESRD patients [25 two‐way and 2 three‐way pairs] who consented to participate in KPD transplantation at our center in 2013, performed to avoid blood group incompatibility (n = 52) or positive cross‐match (n = 4). All patients had anatomic, functional, and immunologically comparable donors. The waiting time in KPD was short as compared to deceased donor transplantation. Laparoscopic donor nephrectomy was performed in 54 donors. Donor relationships were spousal (n = 40), parental (n = 13), others (n = 3), with median HLA match of 1. Graft survival was 97.5%. Three patients died with functioning graft. 16% had biopsy‐proven acute rejection. Mean serum creatinine was 1.2 mg/dl at 0.73 ± 0.32 months follow‐up. KPD is a viable, legal, and rapidly growing modality for facilitating LDRT for patients who are incompatible with their healthy, willing living donor. To our knowledge, this is the largest single‐center report from India.     

Outcomes in Pancreas Transplantation With Exocrine Drainage Through a Duodenoduodenostomy Versus Duodenojejunostomy

Until recently, pancreas transplantation has mostly been performed with exocrine drainage via duodenojejunostomy (DJ). Since 2012, DJ was substituted with duodenoduodenostomy (DD) in our hospital, allowing endoscopic access for biopsies. This study assessed safety profiles with DD versus DJ procedures and clinical outcomes with the DD technique in pancreas transplantation. DD patients (n = 117; 62 simultaneous pancreas–kidney [SPK_DD] and 55 pancreas transplantation alone [PTA_DD] with median follow‐up 2.2 years) were compared with DJ patients (n = 179; 167 SPK_DJ and 12 PTA_DJ) transplanted in the period 1998–2012 (pre‐DD era). Postoperative bleeding and pancreas graft vein thrombosis requiring relaparotomy occurred in 17% and 9% of DD patients versus 10% (p = 0.077) and 6% (p = 0.21) in DJ patients, respectively. Pancreas graft rejection rates were still higher in PTA_DD patients versus SPK_DD patients (p = 0.003). Hazard ratio (HR) for graft loss was 2.25 (95% CI 1.00, 5.05; p = 0.049) in PTA_DD versus SPK_DD recipients. In conclusion, compared with the DJ procedure, the DD procedure did not reduce postoperative surgical complications requiring relaparatomy or improve clinical outcomes after pancreas transplantation despite serial pancreatic biopsies for rejection surveillance. It remains to be seen whether better rejection monitoring in DD patients translates into improved long‐term pancreas graft survival.     

Immune responses following tocilizumab therapy to desensitize HLA-sensitized kidney transplant candidates

Kidney transplant candidates (KTCs) who are HLA highly sensitized (calculated panel-reactive alloantibodies >95%) have poor access to deceased kidney transplantation. In this single-center prospective study, 13 highly sensitized desensitization-naïve KTCs received IV tocilizumab (8 mg/kg) every 4 weeks. We evaluated tolerability as well as immune responses, that is, T cell, B cell, T follicular helper (Tfh) subsets, blood cytokines (IL-6, soluble IL-6 receptor-sIL-6R-, IL-21), blood chemokines (CXCL10, CXCL13), and anti-HLA alloantibodies. Tocilizumab treatment was well-tolerated except in one patient who presented spondylodiscitis, raising a note of caution. Regarding immune parameters, there were no significant changes of percentages of lymphocyte subsets, that is, CD3⁺, CD3⁺/CD4⁺, CD3⁺/CD8⁺ T cells, and NK cells. This was also the case for Tfh cell subsets, B cells, mature B cells, plasma cells, pre-germinal center (GC) B cells, and post-GC B cells, whereas we observed a significant increase in naïve B cells (p = .02) and a significant decrease in plasmablasts (p = .046) over the tocilizumab treatment course. CXCL10, CXCL13, IL-21, total IgG, IgA, and IgM levels did not significantly change during tocilizumab therapy; conversely, there was a significant increase in IL-6 levels (p = .03) and a huge increase in sIL-6R (p = .00004). There was a marginal effect on anti-HLA alloantibodies (class I and class II). To conclude in highly sensitized KTCs, tocilizumab as a monotherapy limited B cell maturation; however, it had almost no effect on anti-HLA alloantibodies.     

Transplantation for pulmonary arterial hypertension with congenital heart disease: Impact on outcomes of the current therapeutic approach including a high-priority allocation program

Patients with end-stage pulmonary arterial hypertension due to congenital heart disease have limited access to heart-lung transplantation or double-lung transplantation. We aimed to assess the effects of a high-priority allocation program established in France in 2007. We conducted a retrospective study to compare waitlist and posttransplantation outcomes before versus after implementation of the high-priority allocation program. We included 67 consecutive patients (mean age at listing, 33.2 ± 10.5 years) with pulmonary arterial hypertension due to congenital heart disease listed for heart-lung transplantation or double-lung transplantation from 1997 to 2016. At one month, the incidences of transplantation and death before transplantation were 3.5% and 24.6% in 1997–2006, 4.8% and 4.9% for patients on the regular list in 2007–2016, and 41.2% and 7.4% for patients listed under the high-priority allocation program (p < .001 and p = .0001, respectively). Overall survival was higher in patients listed in 2007–2016 (84.2% and 61.2% at 1 and 10 years vs. 36.8% and 22.1%, p = .0001). Increased incidence of transplantation, decreased waiting list mortality, and improved early and long-term outcomes were observed in patients with pulmonary arterial hypertension due to congenital heart disease listed for transplantation in the recent era, characterized by implementation of a high-priority allocation program.     

COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients

The COVID-19 pandemic has brought unprecedented challenges to the transplant community. The reduction in transplantation volume during this time is partly due to concerns over potentially increased susceptibility and worsened outcomes of COVID-19 in immunosuppressed recipients. The consequences of COVID-19 on patients waitlisted for kidney transplantation, however, have not previously been characterized. We studied 56 waitlisted patients and 80 kidney transplant recipients diagnosed with COVID-19 between March 13 and May 20, 2020. Despite similar demographics and burden of comorbidities between waitlisted and transplant patients, waitlisted patients were more likely to require hospitalization (82% vs. 65%, P = .03) and were at a higher risk of mortality (34% vs. 16%, P = .02). Intubation was required in one third of hospitalized patients in each group, and portended a very poor prognosis. The vast majority of patients who died were male (84% waitlist, 100% transplant). Multivariate analysis demonstrated waitlist status, age, and male sex were independently associated with mortality. COVID-19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk. Understanding the impact of COVID-19 on waitlist patients in comparison to transplant recipients may aid centers in weighing the risks and benefits of transplantation in the setting of ongoing COVID-19.     

Oxalate retinopathy is irreversible despite early combined liver‐kidney transplantation in primary hyperoxaluria type 1

In primary hyperoxaluria type 1 (PH1), systemic oxalate deposition (oxalosis) in end‐stage renal disease (ESRD) is associated with high morbidity and mortality, particularly in children with infantile oxalosis (IO). Combined liver and kidney transplantation (CLKT) is the only curative treatment option in these patients. After CLKT, systemic oxalosis decreases continuously, although only insufficient data are available regarding oxalate retinopathy (ROx), leading to severe visual impairment. We analyzed long‐term follow‐up data of ROx in 13 patients undergoing CLKT for PH1 at our center between 1998 and 2018. Age at transplantation was 1.3‐14.2 years, including nine patients with IO. We performed visual acuity testing, slit lamp investigation, funduscopy, fundus photography, and spectral‐domain optical coherence tomography (SD‐OCT) imaging. Severe (grade 2‐4) ROx was present in all nine children with IO but not in the four patients developing ESRD in adolescence. A significant negative correlation was found between age at onset of ESRD and grade of ROx (r = ?0.66; P < .001). Notably, follow‐up assessment after CLKT demonstrated no regression of ROx after a median of 5.3 years (range 0.6‐14). The data show that despite early CLKT in IO, ROx is irreversible and the concomitant visual deterioration occurs prior to transplantation.     

Transplant trends in Mexico during the COVID-19 pandemic: Disparities within healthcare sectors

Healthcare systems worldwide were challenged during the COVID-19 pandemic. In Mexico, the public hospitals that perform most transplants were adapted to provide care for COVID-19 patients. Using a nationwide database, we describe the first report of the impact of COVID-19 and related transplantation healthcare policies in a middle-income country by comparing statistics before and during the pandemic (pre-COVID: March 2019–February 2020 vs. COVID era: March 2020–February 2021) and by type of institution (public vs. private). The global reduction in transplantation was higher in public institutions compared with private institutions, 89% versus 62%, respectively, p < .001. When analyzing by organ, kidney transplantation decreased by 89% at public versus 57% at private, p < .001; cornea by 88% at public versus 64% at private, p < .001; liver by 88% at public versus 35% at private, p < .001; and heart by 88% in public versus 67% at private institutions, p = .4. The COVID-19 pandemic along with the implemented health policies were associated with a decrease in donations, waiting list additions, and a decrease in transplantation, particularly at public institutions, which care for the most vulnerable.     

Recipient Outcomes Following Transplantation of Allografts From Live Kidney Donors Who Subsequently Developed End‐Stage Renal Disease

Live kidney donors have an increased risk of end‐stage renal disease (ESRD) compared with nondonors; however, it is unknown whether undetected, subclinical kidney disease exists at donation that subsequently contributes to this risk. To indirectly test this hypothesis, the authors followed the donated kidneys, by comparing the outcomes of 257 recipients whose donors subsequently developed ESRD with a matched cohort whose donors remained ESRD free. The compared recipients were matched on donor (age, sex, race/ethnicity, donor–recipient relationship), transplant (HLA mismatch, peak panel‐reactive antibody, previous transplantation, year of transplantation), and recipient (age, sex, race/ethnicity, body mass index, cause of ESRD, and time on dialysis) risk factors. Median recipient follow‐up was 12.5 years (interquartile range 7.4–17.9, maximum 20 years). Recipients of allografts from donors who developed ESRD had increased death‐censored graft loss (74% versus 56% at 20 years; adjusted hazard ratio [aHR] 1.7; 95% confidence interval [CI] 1.5–2.0; p < 0.001) and mortality (61% versus 46% at 20 years; aHR 1.5; 95% CI 1.2–1.8; p < 0.001) compared with matched recipients of allografts from donors who did not develop ESRD. This association was similar among related, spousal, and unrelated nonspousal donors. These findings support a novel view of the mechanisms underlying donor ESRD: that of pre‐donation kidney disease. However, biopsy data may be required to confirm this hypothesis.     

Opinions of African American adults about the use of apolipoprotein L1 (ApoL1) genetic testing in living kidney donation and transplantation

Apolipoprotein L1 (ApoL1) predictive genetic testing for kidney disease, and its emerging role in transplantation, remains controversial as it may exacerbate underlying disparities among African Americans (AAs) at increased risk. We conducted an online simulation among AAs (N = 585) about interest in ApoL1 testing and its cofactors, under 2 scenarios: as a potential living donor (PLD), and as a patient awaiting transplantation. Most respondents (61%) expressed high interest in genetic testing as a PLD: age ≥35 years (adjusted odds ratio [aOR], 1.75; 95% confidence interval [CI], 1.18, 2.60, P = .01), AA identity (aOR, 1.67; 95% CI, 1.02, 2.72, P = .04), perceived kidney disease risk following donation (aOR, 1.68; 95% CI, 1.03, 2.73, P = .03), interest in genetics (aOR, 2.89; 95% CI, 1.95, 4.29, P = .001), and genetics self-efficacy (aOR, 2.38; 95% CI, 1.54, 3.67, P = .001) were positively associated with ApoL1 test interest. If awaiting transplantation, most (89%) believed that ApoL1 testing should be done on AA deceased donors, and older age (aOR, 1.85; 95% CI, 1.03, 3.32, P = .04) and greater interest in genetics (aOR, 2.61; 95% CI, 1.41, 4.81, P = .002) were associated with interest in testing deceased donors. Findings highlight strong support for ApoL1 testing in AAs and the need to examine such opinions among PLDs and transplant patients to enhance patient education efforts.     

Positive flow cytometry crossmatch with discrepant antibody testing results following COVID-19 vaccination

The impact of COVID-19 vaccination on the alloimmunity of transplant candidates is unknown. We report a case of positive B cell flow cytometry crossmatch in a patient waiting for second kidney transplantation, 37 days after receiving the COVID-19 vaccine. The preliminary crossmatch, using sample collected before COVID-19 vaccination, was negative. The antibodies to mismatched donor HLA-DR7 were detected only with multi-antigen beads but not with single-antigen beads, excluding possible prozone effects in solid-phase antibody assays. The crossmatches were positive with HLA-DR7–positive surrogates (n = 2) while negative with HLA-DR7–negative surrogates (n = 3), which confirms the HLA-DR7 alloreactivity. The antigen configurations on B lymphocytes are similar to that on the multi-antigen beads while distinct from the single-antigen beads. HLA-DR7 was the repeating mismatched antigen with the failing first kidney allograft. The newly emerged antibody to HLA-DR7 probably is the consequence of bystander activation of memory response by the COVID-19 vaccination. This case highlights the importance of verifying allo-sensitization history and utilizing multiple assays, including cell-based crossmatch and solid-phase assays with multi-antigens. COVID-19 immunization may deserve special attention when assessing the immunological risk before and after organ transplantation.     

Quantifying lead time bias when estimating patient survival in preemptive living kidney donor transplantation

Preemptive kidney transplantation is the preferred initial renal replacement therapy, by avoiding dialysis and reportedly maximizing patient survival. Lead time bias may account for some or all of the observed survival advantage, but the impact of this has not been quantified. Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included adult recipients of living donor kidney transplants during 1998‐2017. Patients were transplanted preemptively (n = 1435) or after receiving up to 6 months of dialysis (n = 712). We created a matched cohort using propensity scores, and accounted for lead time (dialysis and estimated predialysis) using left‐truncated Cox models with the primary outcome of patient survival. The median eGFR at transplantation was 6.9 mL/min per 1.73 m² in the non‐pre‐emptive, and 9.6 mL/min per 1.73 m² in the preemptive group. In the matched cohort (n = 1398), preemptive transplantation was not associated with a survival advantage hazard ratio (HR) for preemptive vs non‐pre‐emptive 1.12 (95% confidence interval [CI] 0.79‐1.61). Accounting for lead time moved the point estimates toward a survival disadvantage for preemptive transplantation (eg, HR assuming 4 mL/min per 1.73 m²/year eGFR decline, 1.21 [0.85, 1.73]), but in all cases the 95% CIs crossed 1. The optimal timing of preemptive living donor kidney transplantation requires further study.