Polypill Strategy in Secondary Cardiovascular Prevention.

PURPOSE OF REVIEW: The polypill strategy, originally developed to improve medication adherence, has demonstrated efficacy in improving baseline systolic blood pressures and cholesterol levels in multiple clinical trials. However, the long-term clinical impact of improved major cardiovascular events (MACE) outcomes by the polypill remains uncertain. RECENT FINDINGS: Recent trials with long-term follow-up, which included minority groups and people with low socioeconomic status, have shown non-inferiority with no difference in adverse effects rates for the secondary prevention of MACE. Although the polypill strategy was initially introduced to improve adherence to guideline-directed medical therapy (GDMT) for cardiovascular complications, the strategy has surpassed standard medical treatment for secondary prevention of MACE outcomes. Studies also showed improved medication compliance in underserved populations.

Characteristics of Kidney Transplant Recipients with Prolonged Pre-Transplant Dialysis Duration as Identified by Machine Learning Consensus Clustering: Pathway to Personalized Care.

Longer pre-transplant dialysis duration is known to be associated with worse post-transplant outcomes. Our study aimed to cluster kidney transplant recipients with prolonged dialysis duration before transplant using an unsupervised machine learning approach to better assess heterogeneity within this cohort. We performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in 5092 kidney transplant recipients who had been on dialysis ≥ 10 years prior to transplant in the OPTN/UNOS database from 2010 to 2019. We characterized each assigned cluster and compared the posttransplant outcomes. Overall, the majority of patients with ≥10 years of dialysis duration were black (52%) or Hispanic (25%), with only a small number (17.6%) being moderately sensitized. Within this cohort, three clinically distinct clusters were identified. Cluster 1 patients were younger, non-diabetic and non-sensitized, had a lower body mass index (BMI) and received a kidney transplant from younger donors. Cluster 2 recipients were older, unsensitized and had a higher BMI; they received kidney transplant from older donors. Cluster 3 recipients were more likely to be female with a higher PRA. Compared to cluster 1, cluster 2 had lower 5-year death-censored graft (HR 1.40; 95% CI 1.16-1.71) and patient survival (HR 2.98; 95% CI 2.43-3.68). Clusters 1 and 3 had comparable death-censored graft and patient survival. Unsupervised machine learning was used to characterize kidney transplant recipients with prolonged pre-transplant dialysis into three clinically distinct clusters with variable but good post-transplant outcomes. Despite a dialysis duration ≥ 10 years, excellent outcomes were observed in most recipients, including those with moderate sensitization. A disproportionate number of minority recipients were observed within this cohort, suggesting multifactorial delays in accessing kidney transplantation.

Distinct Phenotypes of Non-Citizen Kidney Transplant Recipients in the United States by Machine Learning Consensus Clustering.

BACKGROUND: Better understanding of the different phenotypes/subgroups of non-U.S. citizen kidney transplant recipients may help the transplant community to identify strategies that improve outcomes among non-U.S. citizen kidney transplant recipients. This study aimed to cluster non-U.S. citizen kidney transplant recipients using an unsupervised machine learning approach; Methods: We conducted a consensus cluster analysis based on recipient-, donor-, and transplant- related characteristics in non-U.S. citizen kidney transplant recipients in the United States from 2010 to 2019 in the OPTN/UNOS database using recipient, donor, and transplant-related characteristics. Each cluster's key characteristics were identified using the standardized mean difference. Post-transplant outcomes were compared among the clusters; Results: Consensus cluster analysis was performed in 11,300 non-U.S. citizen kidney transplant recipients and identified two distinct clusters best representing clinical characteristics. Cluster 1 patients were notable for young age, preemptive kidney transplant or dialysis duration of less than 1 year, working income, private insurance, non-hypertensive donors, and Hispanic living donors with a low number of HLA mismatch. In contrast, cluster 2 patients were characterized by non-ECD deceased donors with KDPI <85%. Consequently, cluster 1 patients had reduced cold ischemia time, lower proportion of machine-perfused kidneys, and lower incidence of delayed graft function after kidney transplant. Cluster 2 had higher 5-year death-censored graft failure (5.2% vs. 9.8%; p < 0.001), patient death (3.4% vs. 11.4%; p < 0.001), but similar one-year acute rejection (4.7% vs. 4.9%; p = 0.63), compared to cluster 1; Conclusions: Machine learning clustering approach successfully identified two clusters among non-U.S. citizen kidney transplant recipients with distinct phenotypes that were associated with different outcomes, including allograft loss and patient survival. These findings underscore the need for individualized care for non-U.S. citizen kidney transplant recipients.

Efficacy and Safety of Plasma Exchange as an Adjunctive Therapy for Rapidly Progressive IgA Nephropathy and Henoch-Schönlein Purpura Nephritis: A Systematic Review.

Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor prognosis despite aggressive immunosuppressive therapy. The utility of plasmapheresis/plasma exchange (PLEX) for IgAN/HSP is not well established. This systematic review aims to assess the efficacy of PLEX for IgAN and HSP patients with RPGN. A literature search was conducted using MEDLINE, EMBASE, and through Cochrane Database from inception through September 2022. Studies that reported outcomes of PLEX in IgAN or HSP patients with RPGN were enrolled. The protocol for this systematic review is registered with PROSPERO (no. CRD42022356411). The researchers systematically reviewed 38 articles (29 case reports and 9 case series articles) with a total of 102 RPGN patients (64 (62.8%) had IgAN and 38 (37.2%) had HSP). The mean age was 25 years and 69% were males. There was no specific PLEX regimen utilized in these studies, but most patients received at least 3 PLEX sessions that were titrated based on the patient's response/kidney recovery. The number of PLEX sessions ranged from 3 to 18, and patients additionally received steroids and immunosuppressive treatment (61.6% of patients received cyclophosphamide). Follow-up time ranged from 1 to 120 months, with the majority being followed for at least 2 months after PLEX. Among IgAN patients treated with PLEX, 42.1% (n = 27/64) achieved remission; 20.3% (n = 13/64) achieved complete remission (CR) and 18.7% (n = 12/64) partial remission (PR). 60.9% (n = 39/64) progressed to end-stage kidney disease (ESKD). Among HSP patients treated with PLEX, 76.3% (n = 29/38) achieved remission; of these, 68.4% (n = 26/38) achieved CR and 7.8% achieved (n = 3/38) PR. 23.6% (n = 9/38) progressed to ESKD. Among kidney transplant patients, 20% (n = 1/5) achieved remission and 80% (n = 4/5) progressed to ESKD. Adjunctive plasmapheresis/plasma exchange with immunosuppressive therapy showed benefits in some HSP patients with RPGN and possible benefits in IgAN patients with RPGN. Future prospective, multi-center, randomized clinical studies are needed to corroborate this systematic review's findings.

Differences between kidney retransplant recipients as identified by machine learning consensus clustering.

BACKGROUND: Our study aimed to characterize kidney retransplant recipients using an unsupervised machine-learning approach. METHODS: We performed consensus cluster analysis based on the recipient-, donor-, and transplant-related characteristics in 17 443 kidney retransplant recipients in the OPTN/UNOS database from 2010 to 2019. We identified each cluster's key characteristics using the standardized mean difference of >.3. We compared the posttransplant outcomes, including death-censored graft failure and patient death among the assigned clusters RESULTS: Consensus cluster analysis identified three distinct clusters of kidney retransplant recipients. Cluster 1 recipients were predominantly white and were less sensitized. They were most likely to receive a living donor kidney transplant and more likely to be preemptive (30%) or need ≤1 year of dialysis (32%). In contrast, cluster 2 recipients were the most sensitized (median PRA 95%). They were more likely to have been on dialysis >1 year, and receive a nationally allocated, low HLA mismatch, standard KDPI deceased donor kidney. Recipients in cluster 3 were more likely to be minorities (37% Black; 15% Hispanic). They were moderately sensitized with a median PRA of 87% and were also most likely to have been on dialysis >1 year. They received locally allocated high HLA mismatch kidneys from standard KDPI deceased donors. Thymoglobulin was the most commonly used induction agent for all three clusters. Cluster 1 had the most favorable patient and graft survival, while cluster 3 had the worst patient and graft survival. CONCLUSION: The use of an unsupervised machine learning approach characterized kidney retransplant recipients into three clinically distinct clusters with differing posttransplant outcomes. Recipients with moderate allosensitization, such as those represented in cluster 3, are perhaps more disadvantaged in the kidney retransplantation process. Potential opportunities for improvement specific to these re-transplant recipients include working to improve opportunities to improve access to living donor kidney transplantation, living donor paired exchange and identifying strategies for better HLA matching.

Characteristics of Kidney Recipients of High Kidney Donor Profile Index Kidneys as Identified by Machine Learning Consensus Clustering.

Background: Our study aimed to characterize kidney transplant recipients who received high kidney donor profile index (KDPI) kidneys using unsupervised machine learning approach. Methods: We used the OPTN/UNOS database from 2010 to 2019 to perform consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in 8935 kidney transplant recipients from deceased donors with KDPI ≥ 85%. We identified each cluster's key characteristics using the standardized mean difference of >0.3. We compared the posttransplant outcomes among the assigned clusters. Results: Consensus cluster analysis identified 6 clinically distinct clusters of kidney transplant recipients from donors with high KDPI. Cluster 1 was characterized by young, black, hypertensive, non-diabetic patients who were on dialysis for more than 3 years before receiving kidney transplant from black donors; cluster 2 by elderly, white, non-diabetic patients who had preemptive kidney transplant or were on dialysis less than 3 years before receiving kidney transplant from older white donors; cluster 3 by young, non-diabetic, retransplant patients; cluster 4 by young, non-obese, non-diabetic patients who received dual kidney transplant from pediatric, black, non-hypertensive non-ECD deceased donors; cluster 5 by low number of HLA mismatch; cluster 6 by diabetes mellitus. Cluster 4 had the best patient survival, whereas cluster 3 had the worst patient survival. Cluster 2 had the best death-censored graft survival, whereas cluster 4 and cluster 3 had the worst death-censored graft survival at 1 and 5 years, respectively. Cluster 2 and cluster 4 had the best overall graft survival at 1 and 5 years, respectively, whereas cluster 3 had the worst overall graft survival. Conclusions: Unsupervised machine learning approach kidney transplant recipients from donors with high KDPI based on their pattern of clinical characteristics into 6 clinically distinct clusters.

Distinct Phenotypes of Kidney Transplant Recipients in the United States with Limited Functional Status as Identified through Machine Learning Consensus Clustering.

Background: There have been concerns regarding increased perioperative mortality, length of hospital stay, and rates of graft loss in kidney transplant recipients with functional limitations. The application of machine learning consensus clustering approach may provide a novel understanding of unique phenotypes of functionally limited kidney transplant recipients with distinct outcomes in order to identify strategies to improve outcomes. Methods: Consensus cluster analysis was performed based on recipient-, donor-, and transplant-related characteristics in 3205 functionally limited kidney transplant recipients (Karnofsky Performance Scale (KPS) < 40% at transplant) in the OPTN/UNOS database from 2010 to 2019. Each cluster's key characteristics were identified using the standardized mean difference. Posttransplant outcomes, including death-censored graft failure, patient death, and acute allograft rejection were compared among the clusters Results: Consensus cluster analysis identified two distinct clusters that best represented the clinical characteristics of kidney transplant recipients with limited functional status prior to transplant. Cluster 1 patients were older in age and were more likely to receive deceased donor kidney transplant with a higher number of HLA mismatches. In contrast, cluster 2 patients were younger, had shorter dialysis duration, were more likely to be retransplants, and were more likely to receive living donor kidney transplants from HLA mismatched donors. As such, cluster 2 recipients had a higher PRA, less cold ischemia time, and lower proportion of machine-perfused kidneys. Despite having a low KPS, 5-year patient survival was 79.1 and 83.9% for clusters 1 and 2; 5-year death-censored graft survival was 86.9 and 91.9%. Cluster 1 had lower death-censored graft survival and patient survival but higher acute rejection, compared to cluster 2. Conclusion: Our study used an unsupervised machine learning approach to characterize kidney transplant recipients with limited functional status into two clinically distinct clusters with differing posttransplant outcomes.

Feature Importance of Acute Rejection among Black Kidney Transplant Recipients by Utilizing Random Forest Analysis: An Analysis of the UNOS Database.

Background: Black kidney transplant recipients have worse allograft outcomes compared to White recipients. The feature importance and feature interaction network analysis framework of machine learning random forest (RF) analysis may provide an understanding of RF structures to design strategies to prevent acute rejection among Black recipients. Methods: We conducted tree-based RF feature importance of Black kidney transplant recipients in United States from 2015 to 2019 in the UNOS database using the number of nodes, accuracy decrease, gini decrease, times_a_root, p value, and mean minimal depth. Feature interaction analysis was also performed to evaluate the most frequent occurrences in the RF classification run between correlated and uncorrelated pairs. Results: A total of 22,687 Black kidney transplant recipients were eligible for analysis. Of these, 1330 (6%) had acute rejection within 1 year after kidney transplant. Important variables in the RF models for acute rejection among Black kidney transplant recipients included recipient age, ESKD etiology, PRA, cold ischemia time, donor age, HLA DR mismatch, BMI, serum albumin, degree of HLA mismatch, education level, and dialysis duration. The three most frequent interactions consisted of two numerical variables, including recipient age:donor age, recipient age:serum albumin, and recipient age:BMI, respectively. Conclusions: The application of tree-based RF feature importance and feature interaction network analysis framework identified recipient age, ESKD etiology, PRA, cold ischemia time, donor age, HLA DR mismatch, BMI, serum albumin, degree of HLA mismatch, education level, and dialysis duration as important variables in the RF models for acute rejection among Black kidney transplant recipients in the United States.