Short‐term adverse effects of early subclinical allograft inflammation in kidney transplant recipients with a rapid steroid withdrawal protocol

The impact of subclinical inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3‐month biopsy. A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3‐months posttransplant. Among those with stable allograft function at 3 months, 200 biopsies that did not meet the Banff criteria for acute rejection were identified. These were Group I: No Inflammation (NI, n = 71) and Group II: Subclinical Inflammation (SCI, n = 129). We evaluated differences in kidney function at 24‐months and allograft histology score at 12‐month biopsy. SCI patients had a higher serum creatinine (1.6 ± 0.7 vs 1.38 ± 0.45; P = .02) at 24‐months posttransplant, and at last follow‐up at a mean of 42.5 months (1.69 ± 0.9 vs 1.46 ± 0.5 mg/dL; P = .027). The allograft chronicity score (ci + ct + cg + cv) at 12‐months posttransplant was higher in the SCI group (2.4 ± 1.35 vs 1.9 ± 1.2; P = .02). The incidence of subsequent rejections within the first year in SCI and NI groups was 24% vs 10%, respectively (P = .015). De novo donor‐specific antibody within 12 months was more prevalent in the SCI group (12/129 vs 1/71, P = .03). SCI is likely not a benign finding and may have long‐term implications for kidney allograft function.     

Response to treatment and long‐term outcomes in kidney transplant recipients with acute T cell–mediated rejection

The recent recognition of complex and chronic phenotypes of T cell–mediated rejection (TCMR) has fostered the need to better evaluate the response of acute TCMR—a condition previously considered to lack relevant consequences for allograft survival—to the standard of care. In a prospective cohort of kidney recipients (n = 256) with biopsy‐proven acute TCMR receiving corticosteroids, we investigated clinical, histological, and immunological phenotypes at the time of acute TCMR diagnosis and 3 months posttreatment. Independent posttreatment determinants of allograft loss included the glomerular filtration rate (GFR) (HR = 0.94; 95% CI = 0.92‐0.96; P < .001), proteinuria (HR = 1.40; 95% CI = 1.10‐1.79; P = .007), time since transplantation (HR = 1.02; 95% CI = 1.00‐1.03; P = .016), peritubular capillaritis (HR = 2.27; 95% CI = 1.13‐4.55; P = .022), interstitial inflammation in sclerotic cortical parenchyma (i‐IF/TA) (HR = 1.87; 95% CI = 1.08‐3.25; P = .025), and donor‐specific anti‐HLA antibodies (DSAs) (HR = 2.67; 95% CI = 1.46‐4.88; P = .001). Prognostic value was improved using a composite evaluation of response to treatment versus clinical parameters only (cNRI = 0.68; 95% CI = 0.41‐0.95; P < .001). A classification tree for allograft loss identified five patterns of response to treatment based on the posttreatment GFR, i‐IF/TA, and anti‐HLA DSAs (cross‐validated accuracy = 0.80). Compared with responders (n = 155, 60.5%), nonresponders (n = 101, 39.5%) had a higher incidence of de novo DSAs, antibody‐mediated rejection, and allograft loss at 10 years (P < .001 for all comparisons). Thus, clinical, histological, and immunological assessment of response to treatment of acute TCMR revealed different profiles of the response to treatment with distinct outcomes.     

Inferior long‐term allograft and patient outcomes among recipients of offspring living donor kidneys

While offspring‐to‐parent living donor kidney transplantations may represent an ideal donor–recipient combination to optimize long‐term transplantation outcomes, the sex‐specific long‐term success of these transplantations remains unclear. We hypothesize that allograft and recipient survivals in offspring‐to‐parent living donor kidney transplantation differ between men and women due to donor‐specific alloimmunization during pregnancy. We retrospectively analyzed long‐term allograft and patient survival among men and women who received an offspring living donor kidney compared with those who received other haplotype‐matched living donor kidneys. Based on multivariable Cox proportional hazards modeling of Organ Procurement and Transplantation Network data from 2001 to 2015, we found that both men and women who received offspring living donor kidneys had significantly increased mortality compared with recipients who received nonoffspring living donor kidneys. While male recipients of any living donor kidney had greater risk of mortality and allograft failure than female recipients, there was no significant difference in all‐cause allograft failure or mortality in male versus female recipients of offspring living donor kidney transplantations. Our analysis demonstrated no significant interaction between recipient sex and donor offspring status. We conclude that nonoffspring living donors should be considered whenever feasible for both men and women with multiple donor options.     

Impact of ureteral stricture and treatment choice on long‐term graft survival in kidney transplantation

We aimed to evaluate the influence of urological complications occurring within the first year after kidney transplantation on long‐term patient and graft outcomes, and sought to examine the impact of the management approach of ureteral strictures on long‐term graft function. We collected data on urological complications occurring within the first year posttransplant. Graft survivals, patient survival, and rejection rates were compared between recipients with and without urological complications. Male gender of the recipient, delayed graft function, and donor age were found to be significant risk factors for urological complications after kidney transplantation (P < .05). Death censored graft survival analysis showed that only ureteral strictures had a negative impact on long‐term graft survival (P = .0009) compared to other complications. Death censored graft survival was significantly shorter in kidney recipients managed initially with minimally invasive approach when compared to the recipients with no stricture (P = .001). However, graft survival was not statistically different in patients managed initially with open surgery (P = .47). Ureteral strictures following kidney transplantation appear to be strongly negatively correlated with long‐term graft survival. Our analysis suggests that kidney recipients with ureteral stricture should be managed initially with open surgery, with better long‐term graft survival.     

Posttransplant muscle mass measured by urinary creatinine excretion rate predicts long‐term outcomes after liver transplantation

Long‐term survival in orthotopic liver transplant (OLT) recipients remains impaired because of many contributing factors, including a low pretransplant muscle mass (or sarcopenia). However, influence of posttransplant muscle mass on survival is currently unknown. We hypothesized that posttransplant urinary creatinine excretion rate (CER), an established noninvasive marker of total body muscle mass, is associated with long‐term survival after OLT. In a single‐center cohort study of 382 adult OLT recipients, mean ± standard deviation CER at 1 year posttransplantation was 13.3 ± 3.7 mmol/24 h in men and 9.4 ± 2.6 mmol/24 h in women. During median follow‐up for 9.8 y (interquartile range 6.4‐15.0 y), 104 (27.2%) OLT recipients died and 44 (11.5%) developed graft failure. In Cox regression analyses, as continuous variable, low CER was associated with increased risk for mortality (HR = 0.43, 95% CI: 0.26‐0.71, P = .001) and graft failure (HR = 0.42, 95% CI: 0.20‐0.90, P = .03), independent of age, sex, and body surface area. Similarly, OLT recipients in the lowest tertile had an increased risk for mortality (HR = 2.69; 95% CI: 1.47‐4.91, P = .001) and graft failure (HR = 2.77, 95% CI: 1.04‐7.39, P = .04), compared to OLT recipients in the highest tertile. We conclude that 1 year posttransplant low total body muscle mass is associated with long‐term risk of mortality and graft failure in OLT recipients.     

History of posttraumatic stress disorder and outcomes after kidney transplantation

A history of posttraumatic stress disorder (PTSD), if uncontrolled, represents a contraindication for kidney transplantation. However, no previous large study has assessed the association between pretransplant history of PTSD and posttransplantation outcomes. We examined 4479 US veterans who had undergone transplantation. The diagnosis of history of PTSD was based on a validated algorithm. Measured covariates were used to create a matched cohort (n = 560). Associations between pretransplant PTSD and death with functioning graft, all‐cause death, and graft loss were examined in survival models. Posttransplant medication nonadherence was assessed using proportion of days covered (PDC). From among 4479 veterans, 282 (6.3%) had a history of PTSD. The mean age ± standard deviation (SD) of the cohort at baseline was 61 ± 11 years, 91% were male, and 66% and 28% of patients were white and African American, respectively. Compared to patients without a history of PTSD, patients with a history of PTSD had a similar risk of death with a functioning graft (subhazard ratio [SHR] 0.97, 95% confidence interval [CI] 0.61‐1.54), all‐cause death (1.05, 0.69‐1.58), and graft loss (1.09, 0.53‐2.26). Moreover, there was no difference in immunosuppressive drug PDC in patients with and without a history of PTSD (PDC: 98 ± 4% vs 99 ± 3%, P = .733 for tacrolimus; PDC: 99 ± 4% vs 98 ± 7%, P = .369 for mycophenolic acid). A history of PTSD in US veterans with end‐stage renal disease should not on its own preclude a veteran from being considered for transplantation.     

Antihypertensive pharmacotherapy and long‐term outcomes in pediatric kidney transplantation

Hypertension (HTN) is common in pediatric recipients following kidney transplantation (KT). We retrospectively assessed the impact of HTN on long‐term (>10‐yr) outcomes in pediatric KT recipients (aged < 18 yr) at our center. Two hundred and ninety‐three pediatric KT recipients (83% living donor [LD]) with graft survival (GS) for ≥5 yr were studied. HTN was defined by antihypertensive medication use at five yr post‐KT. One hundred and sixty (55%) recipients did not have HTN, and 133 (45%) had HTN at five yr post‐KT. There were no differences in actuarial patient survival between cohorts. Actuarial GS at 15 and 20 yr was 68% and 53% for recipients without HTN, and 53% and 33% for recipients with HTN (p = 0.006). Among LD recipients using one antihypertensive, GS at 15 yr was 100% for those using an angiotensin‐converting enzyme inhibitor (ACEI) and 44% for those not using an ACEI (p = 0.04). Among these recipients, HTN treated with no ACEI was a significant risk factor for graft failure at >5 yr (hazard ratio [HR] = 2.5, p = 0.02), but HTN treated with an ACEI was not (HR = 0.6, p = 0.7). HTN at five yr post‐KT is associated with poorer long‐term GS in pediatric recipients, but ACEI therapy may enable better outcomes and should be studied further.     

Utility of protocol kidney biopsies for de novo donor‐specific antibodies

There is limited information about the role of protocol kidney biopsies for de novo donor‐specific antibodies (dnDSA) in kidney transplant recipients, especially in those with stable graft function. We initiated a routine posttransplant DSA monitoring and surveillance biopsy program for dnDSA since 2014. We identified 45 kidney transplant recipients with dnDSA detected between January 2014 and February 2017 who underwent kidney biopsy within 60 days of detection of dnDSA. Twenty‐nine (64%) had stable graft function and 16 (36%) had impaired graft function at the time of dnDSA detection. Even in the group with stable graft function, we found a high rate of rejection (53%) on biopsy. Eighty‐eight percent of patients with impaired graft function had rejection. Those patients with impaired graft function had significantly lower estimated glomerular filtration rate at 12 months postbiopsy and at last follow‐up. Those with impaired graft function had more graft failures; however, this result was not statistically significant. The high rate of asymptomatic rejection, and the fact that outcomes in asymptomatic patients are poor, is in support of the utility of surveillance biopsies in patients with dnDSA.     

The combination of area under the curve and percentage change in estimated glomerular filtration rate predicts long‐term outcome of kidney transplants

The development of surrogate markers for long‐term outcomes of kidney transplant (KT) is a focus of attention. We examined the possibility of using a combination of the area under the curve of estimated glomerular filtration rate (eGFR) for 2 years (AUC_eGFR2yrs) and percent change in eGFR between 1 and 2 years after KT (% change_eGFR1/2yr) as a surrogate marker. We compared the predictive power of death‐censored graft failure with various combinations. The combination of >2% vs ≤2% for % change_eGFR1/2yr and >1300 vs ≤1300 mL/min/month for AUC_eGFR2yr had the highest Harrell C‐index (0.647; 95% confidence interval [95% CI], 0.604‐0.690). The death‐censored graft survival rate of the group with ≤2% change_eGFR1/2yr and ≤1300 mL/min/month AUC_eGFR2yr was significantly lower than those of other groups. The AUC/% change eGFR had comparable predictive power to the previously identified marker ≥30% decline in eGFR between years 1 and 3 after KT (≤?30% change_eGFR1/3yr) (Harrell's C‐index = 0.645 [95% CI 0.628‐0.662] for ≤?30% change_eGFR1/3yr). The proposed combination might be useful as a surrogate marker in KT trials because it requires a shorter surveillance period than the established marker while having comparable predictive power.     

Development and outcomes of de novo donor‐specific antibodies in low,moderate, and high immunological risk kidney transplant recipients

De novo donor‐specific antibodies (dnDSA) play an important role in antibody‐mediated rejection (ABMR) and graft failure, yet their development in kidney transplant recipients (KTx) of higher immunological risk has not been characterized. We prospectively determined the incidence of dnDSA at 3 and 12 months posttransplant and assessed their associations with outcomes in recipients stratified by low, moderate, and high immunological risk. Adult KTx were screened for DSA pretransplant, months 3 and 12 posttransplant, and when clinically indicated. Outcomes included incidence of dnDSA, death‐censored graft survival (DCGS), and ABMR. Of 371 recipients, 154 (42%) were transplanted across a pretransplant DSA that became undetectable by 12 months posttransplant in 78% of cases. dnDSA were detected in 16% (95% confidence interval [CI]: 12‐20%) by 3 months and 23% (95% CI: 18‐29%) by 12 months posttransplant. Incidence at 12 months was higher in the moderate (30%) and high‐risk groups (29%) compared to the low‐risk group (16%). dnDSA were associated with an increased risk of ABMR (hazard ratio [HR] 2.2; 95% CI: 1.1‐4.4; P = .04) but were not an independent risk factor for DCGS. In conclusion, dnDSA were more frequent in transplant recipients of higher immune risk and associated with an increased risk of ABMR.     

Relationship between antithymocyte globulin,T cell phenotypes,and clinical outcomes in pediatric kidney transplantation

Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Pediatric Transplant (IMPACT) study, we compared T cell phenotypes after ATG or non-ATG induction. We examined the effects of ATG on the early clinical outcomes of alloimmune events (development of de novo donor specific antibody and/or biopsy proven rejection) and infection events (viremia/viral infections). Long-term patient and graft outcomes were examined using the Scientific Registry of Transplant Recipients. After ATG induction, although absolute counts of CD4 and CD8 T cells were lower, patients had higher percentages of CD4 and CD8 memory T cells with a concomitant decrease in frequency of naïve T cells compared to non-ATG induction. In adjusted and unadjusted models, ATG induction was associated with increased early event-free survival, with no difference in long-term patient or allograft survival. Decreased CD4⁺ naïve and increased CD4⁺ effector memory T cell frequencies were associated with improved clinical outcomes. Though immunologic parameters are drastically altered with ATG induction, long-term clinical benefits remain unclear in pediatric patients.     

Isolated v‐lesion in kidney transplant recipients: Characteristics,association with DSA,and histological follow‐up

Isolated v‐lesion (IvL) represents a rare and challenging situation in renal allograft biopsies because it is unknown whether IvL truly represents rejection, antibody‐ or T cell–mediated, or not. This multicentric retrospective study describes the clinicopathological features of IvL with an emphasis on the donor‐specific antibody (DSA) status, histological follow‐up, and graft survival. Inclusion criteria were the presence of v‐lesion with minimal interstitial (i ≤ 1) and microvascular inflammation (g + ptc≤1). C4d‐positive biopsies were excluded. We retrospectively found 33 IvL biopsies in 33 patients, mainly performed in the early posttransplantation period (median time 27 days) and clinically indicated in 66.7%. A minority of recipients (5/33, 15.2%) had DSA at the time of biopsy. IvL was treated by anti‐rejection therapy in 21 cases (63.6%), whereas 12 (36.4%) were untreated. Seventy percent of untreated patients and 66% of treated patients showed favorable histological evolution on subsequent biopsy. Kidney graft survival in IvL was significantly higher than in a matched cohort of antibody‐mediated rejection with arteritis. In conclusion, IvL is not primarily antibody‐mediated and may show a favorable evolution. The heterogeneity of IvL pathophysiology on early biopsies should prompt DSA testing as well as close clinical and histological follow‐up in all patients with IvL.     

Economic analysis of screening for subclinical rejection in kidney transplantation using protocol biopsies and noninvasive biomarkers

Subclinical rejection (SCR) screening in kidney transplantation (KT) using protocol biopsies and noninvasive biomarkers has not been evaluated from an economic perspective. We assessed cost-effectiveness from the health sector perspective of SCR screening in the first year after KT using a Markov model that compared no screening with screening using protocol biopsy or biomarker at 3 months, 12 months, 3 and 12 months, or 3, 6, and 12 months. We used 12% subclinical cellular rejection and 3% subclinical antibody-mediated rejection (SC-ABMR) for the base-case cohort. Results favored 1-time screening at peak SCR incidence rather than repeated screening. Screening 2 or 3 times was favored only with age <35 years and with high SC-ABMR incidence. Compared to biomarkers, protocol biopsy yielded more quality-adjusted life years (QALYs) at lower cost. A 12-month biopsy cost $13 318/QALY for the base-case cohort. Screening for cellular rejection in the absence of SC-ABMR was less cost effective with 12-month biopsy costing $46 370/QALY. Screening was less cost effective in patients >60 years. Using biomarker twice or thrice was cost effective only if biomarker cost was <$700. In conclusion, in KT, screening for SCR more than once during the first year is not economically reasonable. Screening with protocol biopsy was favored over biomarkers.     

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.     

Protocol biopsies after kidney transplantation

Numerous studies have investigated features of allograft injury in renal biopsies obtained in stable kidney transplants. Evaluation of protocol biopsies has revealed a considerably high prevalence of subclinical acute rejection (SAR) and chronic allograft nephropathy (CAN) already in early phases after transplantation. The meanwhile well-established association of SAR and CAN in protocol biopsy with long-term allograft failure and the finding of superior allograft outcome after treatment of SAR in a randomized prospective study may point to clinical relevance of this procedure. In this review, potential benefits and risks associated with kidney allograft biopsy in stable renal transplant recipients are discussed.     

Long‐term outcomes of eculizumab‐treated positive crossmatch recipients: Allograft survival,histologic findings,and natural history of the donor‐specific antibodies

We aimed to determine the long‐term outcomes of eculizumab‐treated, positive crossmatch (+XM) kidney transplant recipients compared with +XM and age‐matched negative crossmatch (?XM) controls. We performed an observational retrospective study and examined allograft survival, histologic findings, long‐term B‐cell flow cytometric XM (BFXM), and allograft‐loss–associated factors. The mean (SD) posttransplant follow‐up was 6.3 (2.5) years in the eculizumab group; 7.6 (3.5), +XM control group; 7.9 (2.5), ?XM control group. The overall and death‐censored allograft survival rates were similar in +XM groups (P = .73, P = .48) but reduced compared with ?XM control patients (P < .001, P < .001). In the eculizumab‐treated group, 57.9% (11/19) of the allografts had chronic antibody‐mediated rejection, but death‐censored allograft survival was 76.6%, 5 years; 75.4%, 7 years. Baseline IgG3 positivity and BFXM ≥300 were associated with allograft loss. C1q positivity was also associated with allograft loss but did not reach statistical significance. Donor‐specific antibodies appeared to decrease in eculizumab‐treated patients. After excluding patients with posttransplant plasmapheresis, 42.3% (9/21) had negative BFXMs; 31.8% (7/22), completely negative single‐antigen beads 1 year posttransplant. Eculizumab‐treated +XM patients had reduced allograft survival compared with ?XM controls but similar survival to +XM controls. BFXM and complement‐activating donor‐specific antibodies (by IgG3 and C1q testing) may be used for risk stratification in +XM transplantation.     

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.     

Long‐term outcome of renal transplantation from octogenarian donors: A multicenter controlled study

To assess whether biopsy‐guided selection of kidneys from very old brain‐dead donors enables more successful transplantations, the authors of this multicenter, observational study compared graft survival between 37 recipients of 1 or 2 histologically evaluated kidneys from donors older than 80 years and 198 reference‐recipients of non–histologically evaluated single grafts from donors aged 60 years and younger (transplantation period: 2006‐2013 at 3 Italian centers). During a median (interquartile range) of 25 (13‐42) months, 2 recipients (5.4%) and 10 reference‐recipients (5.1%) required dialysis (crude and donor age‐ and sex‐adjusted hazard ratio [95% confidence interval] 1.55 [0.34‐7.12], P = .576 and 1.41 [0.10‐19.54], P = .798, respectively). Shared frailty analyses confirmed similar outcomes in a 1:2 propensity score study comparing recipients with 74 reference‐recipients matched by center, year, donor, and recipient sex and age. Serum creatinine was similar across groups during 84‐month follow‐up. Recipients had remarkably shorter waiting times than did reference‐recipients and matched reference‐recipients (7.5 [4.0‐19.5] vs 36 [19‐56] and 40 [24‐56] months, respectively, P < .0001 for both comparisons). Mean (± SD) kidney donor risk index was 2.57 ± 0.32 in recipients vs 1.09 ± 0.24 and 1.14 ± 0.24 in reference‐recipients and matched reference‐recipients (P < .0001 for both comparisons). Adverse events were similar across groups. Biopsy‐guided allocation of kidneys from octogenarian donors permits further expansion of the donor organ pool and faster access to a kidney transplant, without increasing the risk of premature graft failure.     

Comparing outcomes of third and fourth kidney transplantation in older and younger patients

Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18–64 years) and older (≥65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p < .001) which remained significant after adjustment (aHR = 3.21, 95% CI: 2.59–3.99). Similar patterns were noted in the 4KT cohort. When compared with waitlisted patients, 3KT and 4KT are associated with a lower risk of mortality; aHR = 0.37, 95% CI: 0.33–0.41 and aHR = 0.31, 95% CI: 0.24–0.41, respectively. This survival benefit did not differ by recipient age (younger vs. older, p for interaction = 3KT: .49 and 4KT: .58). In the largest cohort described to date, we report that there is a survival benefit of 3KT and 4KT even among older patients. Although a highly selected cohort, our results support improving access to 3KT and 4KT.     

A donor risk index for graft loss in pediatric living donor kidney transplantation

Pediatric kidney transplant candidates often have multiple potential living donors (LDs); no evidence‐based tool exists to compare potential LDs, or to decide between marginal LDs and deceased donor (DD) kidney transplantation (KT). We developed a pediatric living kidney donor profile index (P‐LKDPI) on the same scale as the DD KDPI by using Cox regression to model the risk of all‐cause graft loss as a function of living donor characteristics and DD KDPI. HLA‐B mismatch (adjusted hazard ratio [aHR] per mismatch = _1.041.27_1.55), HLA‐DR mismatch (aHR per mismatch = _1.021.23_1.49), ABO incompatibility (aHR = _1.203.26_8.81), donor systolic blood pressure (aHR per 10 mm Hg = _1.011.07_1.18), and donor estimated GFR (eGFR; aHR per 10 mL/min/1.73 m² = _0.880.94_0.99) were associated with graft loss after LDKT. Median (interquartile range [IQR]) P‐LKDPI was ?25 (?56 to 12). 68% of donors had P‐LKDPI <0 (less risk than any DD kidney) and 25% of donors had P‐LKDPI >14 (more risk than median DD kidney among pediatric KT recipients during the study period). Strata of LDKT recipients of kidneys with higher P‐LKDPI had a higher cumulative incidence of graft loss (39% at 10 years for P‐LDKPI ≥20, 28% for 20> P‐LKDPI ≥?20, 23% for ?20 > P‐LKDPI ≥?60, 19% for P‐LKDPI <?60 [log rank P < .001]). The P‐LKDPI can aid in organ selection for pediatric KT recipients by allowing comparison of potential LD and DD kidneys.