Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes.

BACKGROUND: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.

Managing highly sensitized renal transplant candidates in the era of kidney paired donation and the new kidney allocation system: Is there still a role for desensitization?

Kidney paired donation (KPD) and the new kidney allocation system (KAS) in the United States have led to improved transplantation rates for highly sensitized candidates. We aimed to assess the potential need for other approaches to improve the transplantation rate of highly sensitized candidates such as desensitization. Using the UNOS STAR file, we analyzed transplant rates in a prevalent active waiting-list cohort as of June 1, 2016, followed for 1 year. The overall transplantation rate was 18.9% (11 129/58769). However, only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% (ie. 100%), only 2.5% of transplants were from living donors (13 total, 7 from KPD). Nearly 4 years after KAS (6/30/2018), 1791 actively wait-listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time. Thus, despite KPD and KAS, many sensitized candidates have not been transplanted even with prolonged waiting time. We conclude that candidates with a CPRA ≥ 99.9% and sensitized candidates with an incompatible living donor and prolonged waiting time may benefit from desensitization to improve their ability to receive a transplant.

Deep Learning-Based Histopathologic Assessment of Kidney Tissue.

BACKGROUND: The development of deep neural networks is facilitating more advanced digital analysis of histopathologic images. We trained a convolutional neural network for multiclass segmentation of digitized kidney tissue sections stained with periodic acid-Schiff (PAS). METHODS: We trained the network using multiclass annotations from 40 whole-slide images of stained kidney transplant biopsies and applied it to four independent data sets. We assessed multiclass segmentation performance by calculating Dice coefficients for ten tissue classes on ten transplant biopsies from the Radboud University Medical Center in Nijmegen, The Netherlands, and on ten transplant biopsies from an external center for validation. We also fully segmented 15 nephrectomy samples and calculated the network's glomerular detection rates and compared network-based measures with visually scored histologic components (Banff classification) in 82 kidney transplant biopsies. RESULTS: The weighted mean Dice coefficients of all classes were 0.80 and 0.84 in ten kidney transplant biopsies from the Radboud center and the external center, respectively. The best segmented class was "glomeruli" in both data sets (Dice coefficients, 0.95 and 0.94, respectively), followed by "tubuli combined" and "interstitium." The network detected 92.7% of all glomeruli in nephrectomy samples, with 10.4% false positives. In whole transplant biopsies, the mean intraclass correlation coefficient for glomerular counting performed by pathologists versus the network was 0.94. We found significant correlations between visually scored histologic components and network-based measures. CONCLUSIONS: This study presents the first convolutional neural network for multiclass segmentation of PAS-stained nephrectomy samples and transplant biopsies. Our network may have utility for quantitative studies involving kidney histopathology across centers and provide opportunities for deep learning applications in routine diagnostics.

Reassessing Preemptive Kidney Transplantation in the United States: Are We Making Progress?

BACKGROUND: Preemptive kidney transplantation (preKT) is associated with higher patient survival, improved quality of life, and lower costs. However, only a minority of patients receives preKT. The aim of this study was to examine changes over the past decade in rates of preKT, focusing on living donor kidney transplantation (LDKT) and specifically recipients who underwent kidney transplantation within 1 year of initiating dialysis. METHODS: Using United Network of Organ Sharing data, we examined retrospectively all kidney transplant candidates (n = 369 103) and recipients (n = 141 254) from 2003 to 2012 in the United States focusing on LDKT (n = 47 108). Predictors of preKT were examined, and patient and graft survival were compared for preKT, pretransplant dialysis less than 1 year, and pretransplant dialysis recipients of 1 year or longer. RESULTS: PreKT occurred in only 17% of recipients overall and 31% of LDKT recipients. Medicare patients (odds ratio [OR], 0.29; 95% confidence interval [95% CI], 0.28-0.31), diabetics (OR, 0.75; 95% CI, 0.69-0.80), and minorities (Hispanics OR, 0.62; 95% CI, 0.57-0.68 and African Americans OR, 0.58; 95% CI, 0.53-0.63) were less likely to receive preKT. Dialysis recipients for less than 1 year comprised 30% of nonpreemptive LDKT. Dialysis recipients of less than 1 year had similar patient survival to preKT (5 years: preKT, 94%; dialysis < 1 year, 94%; dialysis ≥ 1 year, 89%; P < 0.01), but decreased death-censored graft survival (5 years: preKT, 93%; dialysis < 1 year, 89%; and dialysis ≥ 1 year, 89%; P < 0.01). CONCLUSIONS: PreKT remains an unrealized goal for the majority of recipients. Medicare patients, diabetics, and minorities are less likely to receive preKT. Almost one third of nonpreemptive LDKT recipients were dialyzed for less than 1 year, highlighting an important target for improvement.

Using implantation biopsies as a surrogate to evaluate selection criteria for living kidney donors.

BACKGROUND: The acceptance criteria used for living kidney donors are largely theoretical, as they are not clearly linked to outcomes. The goal of this study was to use implantation biopsies as a surrogate outcome marker to evaluate our living kidney donor selection criteria. METHODS: One thousand six hundred sequential living kidney donor biopsies were performed between 2001 and 2011. Implantation biopsies were assessed by dedicated renal pathologists according to the Banff criteria. Biopsies with any chronic score of 2 or higher were deemed to have moderate to severe changes (MSC). RESULTS: MSC was present in 4% (n=65) of implantation biopsies and occurred across a wide range of age and other demographics. By multivariate analysis, donor age (odds ratio [95% confidence interval], 1.060 [1.035-1.086]; P<0.0001) and donor systolic blood pressure (SBP) (odds ratio [95% confidence interval], 1.022 [1.006-1.037]; P=0.0060) were associated with MSC. Donor gender, body mass index, diastolic blood pressure, glomerular filtration rate, and urinary microalbuminuria were not. MSC was further increased in donors older than 60 years with SBP>140 (30% [7 of 23]) and donors older than 60 years with SBP>140 and glomerular filtration rate above the 25th percentile (42.8% [3 of 7]). In donors younger than 60 years, combining factors did not show an increased prevalence of MSC. At follow-up, renal function was similar in donors with and without MSC. CONCLUSIONS: MSC occurred sporadically in donors with varied characteristics. Although we did not detect patterns to support specific changes in our acceptance criteria, certain subgroups of donors might benefit from close follow-up.

Desensitization in the era of kidney paired donation: the Mayo Foundation 3-site experience.

Sensitized renal allograft candidates face significant barriers to transplantation. While several options exist, including: kidney paired donation (KPD), desensitization, or pursuing a deceased donor kidney transplant, it is unclear from existing data what is the appropriate protocol for an individual patient. In this study, we seek to devise a balance between waiting for a paired donor and combining desensitization with KPD.

ABO incompatible kidney transplantation.

PURPOSE OF REVIEW: Although ABO incompatible kidney transplantation is increasingly recognized as effective, the procedure is still evolving. The purpose of this review is to summarize recent advances in this area. RECENT FINDINGS: Short to intermediate-term outcome appears good, although long-term results are still preliminary. Pretransplant risk stratification based on antidonor antibody titer may be of limited value. Splenectomy, previously reported to be an important component of ABO incompatible transplantation, appears to be avoidable under many circumstances. The wider implementation of A2 blood group incompatible transplantation shortens waiting time for deceased donor transplantation of blood group B recipients without significantly disadvantaging others. The diagnosis of acute humoral rejection has become clearer following the recognition that C4d deposition commonly occurs in well functioning ABO incompatible allografts. The long-term implications of acute humoral rejection appear substantial even following successful acute therapy, with a significant percentage of patients developing chronic humoral rejection manifested as transplant glomerulopathy. Finally, although ABO incompatible transplantation entails increased expense, when compared with maintenance dialysis and taking into account the health related quality of life benefits of a successful transplant, it is clearly cost effective. SUMMARY: ABO incompatible kidney transplantation is an effective therapy, and will become more widely implemented in the future.

The rationale for the new deceased donor pancreas allocation schema.

BACKGROUND: To ensure the continued success of whole organ pancreas and islet transplantation, deceased donor pancreas allocation policy must continue to evolve. METHODS: To assess the existing system, the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing Kidney and Pancreas Transplant Committee retrospectively analyzed the disposition and outcomes of deceased donor pancreata in the United States between January 1, 2000 and December 31, 2003. RESULTS: During the time period studied, consent was obtained but the pancreas was not recovered in 48% (11,820) of organ donors. The most common reasons given for nonrecovery were poor quality of the pancreas and difficulty in placement. Of whole organ pancreata that were transplanted, 90% were from donors with a body mass index (BMI) 50 years (P=0.04), and there were trends toward lower graft survival with donor BMI >30 (P=0.06) and increasing cold-ischemia time. CONCLUSIONS: Based on these data, the OPTN adopted a new allocation algorithm in which pancreata from donors >30 kg/m or >50 years of age are, unless accepted for a local whole organ pancreas transplant candidate, preferentially allocated for islet transplantation. These data also suggest that many good quality pancreata are not procured, emphasizing the need for improved communication and cooperation between organ procurement organizations and pancreas and islet transplant programs.

Comparison of low versus high tacrolimus levels in kidney transplantation: assessment of efficacy by protocol biopsies.

BACKGROUND: The use of calcineurin inhibitors is generally guided by drug blood levels. However, those levels are chosen based on clinical experience, lacking adequate titration studies. METHODS: In these analyses, we compared clinical and histologic endpoints in two groups of kidney transplant recipients: in the first (HiTAC, January 2000 to June 2002, n=245) tacrolimus levels were significantly higher than in the second (LoTAC, July 2002 to September 2004, n=330). This change in drug levels (15% reduction) was made in an attempt to reduce the incidence of polyoma virus nephropathy (PVAN). Other immunosuppressive medications were unchanged during these two time periods. RESULTS: The recipient and donor demographics were not statistically different between the two groups. Compared to HiTAC, at one year posttransplant LoTAC had: 1) lower incidence of PVAN (10.5% vs. 2.5%, P<0.0001); 2) lower fasting glucose levels; 3) higher iothalamate glomerular filtration rate (52+/-19 vs. 59+/-17 ml/min/m, P<0.0001); and 4) on protocol one-year biopsies, lower incidence and severity of interstitial fibrosis (67% vs. 45%, P=0.003) and tubular atrophy (82% vs., 66%, P=0.01). The incidence and severity of acute rejection episodes was similar between both groups (7.8% versus 7.6%). CONCLUSIONS: Modest reductions in tacrolimus exposure early posttransplant are associated with significant beneficial effects for the patient and the allograft without an increased immunologic risk.

Complications, resource utilization, and cost of ABO-incompatible living donor kidney transplantation.

BACKGROUND: The transplantation of living donor renal allografts across blood group barriers requires protocols to reduce and maintain anti-blood group antibody at safe levels. These protocols lead to an increase in resource utilization and cost of transplantation and may result in increased complications. METHODS: In this retrospective study, we compared 40 ABO-incompatible to 77 matching ABO-compatible living donor renal allografts with respect to complications, resource utilization, and cost from day -14 to 90 days after transplantation. RESULTS: Overall, surgery-related complications and resource utilization were increased in the ABO-incompatible group, primarily due to the desensitization protocol and antibody-mediated rejection. In the absence of rejection, the mean number of complications was similar for both groups. ABO-incompatible kidney transplantation was approximately 38,000 US dollars more expensive than ABO-compatible transplants, but was cost effective when compared to maintaining the patient on dialysis while waiting for a blood group compatible deceased donor kidney. Actuarial graft and patient survival was similar in the two groups. CONCLUSIONS: We conclude that ABO-incompatible living donor kidney transplantation is a viable option for patients whose only donor is blood group incompatible despite the additional resource utilization and cost of therapy.