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's 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.

BK polyomavirus genotypes in renal transplant recipients in the United States: A meta-analysis.

BACKGROUND: In the United States, increasing ethnic diversity has been apparent. However, the epidemiology and trends of BKV genotypes remain unclear. This meta-analysis was conducted with the aim to assess the prevalence of BKV genotypes among kidney transplant (KTx) recipients in the United States. METHODS: A comprehensive literature review was conducted through October 2018 utilizing MEDLINE, Embase, and Cochrane Database to identify studies that reported the prevalence of BKV subtypes and/or subgroups in KTx recipients in the United States. Pooled prevalence rates were combined using random effects, generic inverse variance method. The protocol for this study is registered with PROSPERO (no. CRD42019134582). RESULTS: A total of eight observational studies with a total of 193 samples (urine, blood, and kidney tissues) from 188 BKV-infected KTX recipients were enrolled. Overall, the pooled estimated prevalence rates of BKV subtypes were 72.2% (95% confidence of interval [CI]: 62.7-80.0%) for subtype I, 6.8% (95% CI: 2.5-16.9%) for subtype II, 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 metaregression analysis demonstrated a significant positive correlation between year of study and the prevalence of BKV subtype I (slopes = +0.1023, P = .01), there were no significant correlations between year of study and percentages of BKV subtype II-IV (P > .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 Ia, 30.6% (95% CI: 17.7-47.5%) for subgroup Ib1, 47.7% (95% CI: 35.8-59.9%) for subgroup Ib2, and 4.1% (95% CI:1.2-13.3%) for subgroup Ic, respectively. CONCLUSION: BKV subtype I is the most prevalent subtype among KTx recipients in the United States and its prevalence seems to increasing overtime. Subgroup Ib2 is the most common subgroup among BKV subtype I.

Incidence and Mortality of Renal Cell Carcinoma after Kidney Transplantation: A Meta-Analysis.

BACKGROUND: The incidence and mortality of renal cell carcinoma (RCC) after kidney transplantation (KTx) remain unclear. This study's aims were (1) to investigate the pooled incidence/incidence trends, and (2) to assess the mortality/mortality trends in KTx patients with RCC. METHODS: A literature search was conducted using the MEDLINE, EMBASE and Cochrane databases from inception through October 2018. Studies that reported the incidence or mortality of RCC among kidney transplant recipients were included. The pooled incidence and 95% CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO; no. CRD42018108994. RESULTS: A total of 22 observational studies with a total of 320,190 KTx patients were enrolled. Overall, the pooled estimated incidence of RCC after KTx was 0.7% (95% CI: 0.5-0.8%, I2 = 93%). While the pooled estimated incidence of de novo RCC in the native kidney was 0.7% (95% CI: 0.6-0.9%, I2 = 88%), the pooled estimated incidence of RCC in the allograft kidney was 0.2% (95% CI: 0.1-0.4%, I2 = 64%). The pooled estimated mortality rate in KTx recipients with RCC was 15.0% (95% CI: 7.4-28.1%, I2 = 80%) at a mean follow-up time of 42 months after RCC diagnosis. While meta-regression analysis showed a significant negative correlation between year of study and incidence of de novo RCC post-KTx (slopes = -0.05, P = 0.01), there were no significant correlations between the year of study and mortality of patients with RCC (P = 0.50). Egger's regression asymmetry test was performed and showed no publication bias in all analyses. CONCLUSIONS: The overall estimated incidence of RCC after KTX was 0.7%. Although there has been a potential decrease in the incidence of RCC post-KTx, mortality in KTx patients with RCC has not decreased over time.

Is Remote Ischemic Conditioning of Benefit to Patients Undergoing Kidney Transplantation?

Renal ischemia-reperfusion injury (IRI), an inevitable event during kidney transplantation procedure, can result in delayed graft function or even primary nonfunction. In addition to strategies to limit IRI such as advancements in organ allocation systems and preservation of organs, and reduction in cold and warm ischemia time, remote ischemic conditioning (RIC) has attracted much attention in recent years. With promising findings and data suggesting a potential benefit of RIC in animal kidney transplantation models, a few clinical trials have investigated the use of RIC in human kidney transplantation. Unfortunately, the findings from these investigations have been inconclusive due to a number of factors such as diverse time points of RIC, limited sample size, and complexity of kidney transplant patients. This brief commentary aims to discuss the effects of RIC on clinical outcomes and proinflammatory cytokines in patients undergoing kidney transplantation.

Reactivation of BK polyomavirus during pregnancy, vertical transmission, and clinical significance: A meta-analysis.

BACKGROUND: Studies have shown conflicting results on the prevalence and the risks of BK reactivation among pregnant women. In addition, the prevalence of vertical transmission and its clinical significance during pregnancy are not well studied. OBJECTIVES: The study's aims were (1) to investigate the prevalence, and (2) to assess the risk of BK Polyomavirus reactivation and its clinical significance in pregnant women and fetuses. STUDY DESIGN: A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through May 31, 2017. We included studies that reported prevalence, relative risks, odds ratios, or hazard ratios of BK Polyomavirus reactivation during pregnancy. Pooled odds ratios (ORs) and 95% CI were calculated using a random-effect model. The protocol for this study is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017063919). RESULTS: 17 observational studies with a total of 2553 pregnant women were enrolled. The estimated prevalence of BK seropositivity and BK in urine (viruria) among pregnant women were 79.2% (95%CI: 69.6%-86.4%) and 18.9% (95%CI: 10.4%-31.8%). When compared to non-pregnant women, the pooled ORs of BK seropositivity and BK viruria in pregnant women were 1.84 (95%CI: 1.05-3.22) and 6.02 (95%CI: 2.43-14.92), respectively. The estimated prevalence of positive BK-specific IgM antibody in cord blood was 4.9% (95%CI: 0.5%-36.2%). The data on the fetal effects of BK virus were limited. Although BK was detected in fetal organs, available data suggested no association between BK infection and adverse consequences such as miscarriage during pregnancy or childhood malignancy. CONCLUSION: Our meta-analysis demonstrates a significantly increased risk of BK Polyomavirus reactivation during pregnancy. Although vertical transmission can occur with an overall estimated prevalence of 4.9%, there are currently no data suggesting harm to pregnant women and fetuses from BK Polyomavirus.