Use of Machine Learning Consensus Clustering to Identify Distinct Subtypes of Black Kidney Transplant Recipients and Associated Outcomes

Importance: Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups. Objective: To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach. Design, Setting, and Participants: This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster\u27s key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021. Exposure: Machine learning consensus clustering approach. Main Outcomes and Measures: Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant. Results: Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4. Conclusions and Relevance: In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups

Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000–2019 UNOS/OPTN Database

Background: Lower patient survival has been observed in sickle cell disease (SCD) patients who go on to receive a kidney transplant. This study aimed to assess the post-transplant outcomes of SCD kidney transplant recipients in the contemporary era. Methods: We used the OPTN/UNOS database to identify first-time kidney transplant recipients from 2010 through 2019. We compared patient and allograft survival between recipients with SCD (n = 105) vs. all other diagnoses (non-SCD, n = 146,325) as the reported cause of end-stage kidney disease. We examined whether post-transplant outcomes improved among SCD in the recent era (2010–2019), compared to the early era (2000–2009). Results: After adjusting for differences in baseline characteristics, SCD was significantly associated with lower patient survival (HR 2.87; 95% CI 1.75–4.68) and death-censored graft survival (HR 1.98; 95% CI 1.30–3.01), compared to non-SCD recipients. The lower patient survival and death-censored graft survival in SCD recipients were consistently observed in comparison to outcomes of recipients with diabetes, glomerular disease, and hypertension as the cause of end-stage kidney disease. There was no significant difference in death censored graft survival (HR 0.99; 95% CI 0.51–1.73, p = 0.98) and patient survival (HR 0.93; 95% CI 0.50–1.74, p = 0.82) of SCD recipients in the recent versus early era. Conclusions: Patient and allograft survival in SCD kidney recipients were worse than recipients with other diagnoses. Overall SCD patient and allograft outcomes in the recent era did not improve from the early era. The findings of our study should not discourage kidney transplantation for ESKD patients with SCD due to a known survival benefit of transplantation compared with remaining on dialysis. Urgent future studies are needed to identify strategies to improve patient and allograft survival in SCD kidney recipients. In addition, it may be reasonable to assign risk adjustment for SCD patients

Epidemiology of Parvovirus B19 and Anemia Among Kidney Transplant Recipients

Purpose: Persistent anemia has been described in kidney transplant (KTX) recipients with Parvovirus B19 virus infection. However, epidemiology of Parvovirus B19 and Parvovirus B19-related anemia after KTx remains unclear. The study\u27s aims were 1) to investigate the frequency of Parvovirus B19 infection and 2) to assess the incidence of Parvovirus B19-related anemia in KTx recipients. Methods: Aliterature search for studies that reported the occurrence rate of Parvo-virus B19 infection and/or seroprevalence of Parvovirus B19 inKTx recipientswas conducted using Medline, Embase, and Cochrane Database from inception through October 2018. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Results: 15 observational studies with a total of 1, 757 KTx patients were enrolled. Overall, the pooled estimated seroprevalence of Parvovirus B19 IgG was 87. 4% (950/oCI: 64. 4°/\u3c, 96. 4%). The pooled estimated occurrence rate of positive Parvovirus B19 DNA in the first year after KTx was 9. 7% (95%CI: 4. 7°/\u3c, 18. 9%). Sensitivity analysis excluding a study (that solely included KTx patients with anemia) was performed, and showed the pooled estimated occurrence rate of positive Parvovirus B19DNAafterKTxof8. 6%(95%CI: 4. 0%-17. 6%). Meta-regression analysis demonstrated no significant correlations between the year of study and occurrence rate of positive Parvovirus B19 DNA (P = 0. 93). Among KTx recipients with positive Parvovirus B19 DNA, the pooled estimated incidence rates of anemia and severe anemiawere37. 6o/o(95o/oCL25. 8o/o-51. 1o/o)and22. 3o/o(7. 1o/\u3c, 51. 9o/o), respectively. Egger\u27s regression asymmetry test was perforated and showed no publication bias in all analyses. Conclusions: Parvovirus B19 infection occurs mostly within the first year post-transplant. The overall estimated occurrence of positive Parvovirus Bl 9 DNA after KTX is 9. 70/0. The estimated incidence of anemia among KTx recipients with positive Parvovirus B19 DNA is 21. 6%. Parvovirus B 19 should be ruled out in cases of persistent anemia after transplant. [Figure Presented]

Polyomavirus Genotypes in Renal Transplant Recipients in the United States

Purpose: BK Polyomavirus (BKV) subtypes and subgroups present uneven geo-graphical distribution, suggesting a potential relationship with ethnicity. In the United States where there is a definite racial and ethnic diversity, the epidemiology of BKV genotypes remains unclear. This meta-analysis was conducted with the aim to assess BKV genotypes among kidney transplant (KTX) recipients. Methods: A comprehensive literature review was conducted utilizing MEDLINE. Embase and Cochrane Database through October 2018 to identify all studies that reported BKV subtypes and/or subgroups in KTx recipients in the United States. Effect estimates from each individual study were extracted and combined using random-effect, generic inverse variance method of DerSimoman and Laird. Results: 8 observational studies with a total of 193 samples (urine, blood, and kidney tissues) from 188 BKV-mfected KTx recipients in the United States were enrolled. The study years ranged from 2001 to 2016. Overall, the pooled estimated percentages of BKV subtypes were 72. 2% (95%CI: 62. 7%-80. 0%) for subtype I, 6. 8%(95%CI: 2. 5%-16. 9%)forsubtypeII, 8. 3% (95%CI: 4. 4%-15. 1%)for subtype III, and 16. 1% (95%CI: 10. 4%-24. 2%) for subtype IV, respectively. While meta-regression analysis demonstrated a significant positive correlation between year of study and the percentage of BKV subtype I (slopes =+0. 1023, P =0. 01), there were no significant correlations between year of study and percentages of BKV subtype II-IV (P \u3e0. 05). Among KTx recipients with BKV subtype I, the pooled estimated percentages of BKV subgroups were 22. 4% (95%CI: 13. 7%-34. 5%) for subgroup la, 30. 6% (95%CI: 17. 7%-47. 5%)for subgroup Ibl, 47. 7% (95%CI: 35. 8%-59. 9%) for subgroup Ib2, and 4. 1% (95%CI: 1. 2%-13. 3%) for subgroup Ic, respectively. Conclusions: BKV subtype I is the most prevalent subtype among KTx recipients in the United States and its percentage seems to increase overtime. Subgroup Ib2 is the most common among BKV subtype I. Further analysis is needed to assess the effect of BKV genotype on the clinical course of BK viremia in KTx

Zero-mismatch deceased-donor kidney versus simultaneous pancreas-kidney transplantation.

BackgroundPatients with type 1 diabetes mellitus (T1DM) and end-stage renal disease may receive a simultaneous pancreas-kidney (SPK), living-donor kidney (LDK), or deceased-donor kidney (DDK) with possible pancreas after kidney transplantation. SPK is associated with superior patient and kidney graft survival compared with DDK, whereas SPK and LDK have comparable outcomes. It is unclear whether SPK and LDK offer a survival benefit over zero-mismatch (0MM) DDK. In this study, we compared the outcomes of T1DM recipients using data from the Organ Procurement and Transplant Network/United Network for Organ Sharing.MethodsAdult (≥18 years) first-time transplant recipients with T1DM waitlisted for SPK and transplanted from 1995 to 2010 were included in this study. Patient and death-censored kidney graft survival were compared between 0MMDDK (n=228), mismatched (MM) DDK (n=964), 0MMSPK (n=215), MMSPK (n=11951), 2 haplotype identical (2hap) LDK (n=205), and non-2hapLDK (n=1719) recipients. Multivariate analysis was performed using stepwise Cox proportional hazards models.ResultsAt 7 years, patient and death-censored graft survival of 0MMDDK recipients (85% and 81%, respectively) were not statistically different from that of 0MMSPK (81% and 85%; log-rank P value vs. 0MMDDK, 0.17 and 0.48, respectively) and 2hapLDK recipients (89% and 86%; log-rank P value vs. 0MMDDK, 0.34 and 0.18, respectively). Among all groups, MMDDK showed the worst patient survival (71%; log-rank P value vs. 0MMDDK, 0.001)ConclusionPatient and kidney graft survival of 0MMDDK recipients were comparable to both SPK and LDK recipients. These findings suggest that T1DM patients awaiting SPK may consider accepting a 0MMDDK if an offer is available