Miao, Jing

Background and Objectives: The aim of our study was to categorize very highly sensitized kidney transplant recipients with pre-transplant panel reactive antibody (PRA) ≥ 98% using an unsupervised machine learning approach as clinical outcomes for this population are inferior, despite receiving increased allocation priority. Identifying subgroups with higher risks for inferior outcomes is essential to guide individualized management strategies for these vulnerable recipients. Materials and Methods: To achieve this, we analyzed the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database from 2010 to 2019 and performed consensus cluster analysis based on the recipient-, donor-, and transplant-related characteristics in 7458 kidney transplant patients with pre-transplant PRA ≥ 98%. The key characteristics of each cluster were identified by calculating the standardized mean difference. The post-transplant outcomes were compared between the assigned clusters. Results: We identified two distinct clusters and compared the post-transplant outcomes among the assigned clusters of very highly sensitized kidney transplant patients. Cluster 1 patients were younger (median age 45 years), male predominant, and more likely to have previously undergone a kidney transplant, but had less diabetic kidney disease. Cluster 2 recipients were older (median 54 years), female predominant, and more likely to be undergoing a first-time transplant. While patient survival was comparable between the two clusters, cluster 1 had lower death-censored graft survival and higher acute rejection compared to cluster 2. Conclusions: The unsupervised machine learning approach categorized very highly sensitized kidney transplant patients into two clinically distinct clusters with differing post-transplant outcomes. A better understanding of these clinically distinct subgroups may assist the transplant community in developing individualized care strategies and improving the outcomes for very highly sensitized kidney transplant patients.

ABSTRACT Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and outcomes, leading to an expanding use in millions of patients worldwide. However, they can cause a spectrum of immune-related adverse events (irAEs). Essentially, any organs can be affected by irAEs, which have emerged as therapy-limiting side effects. In the kidneys, ICI-associated acute interstitial nephritis (ICI-AIN) leads to acute kidney injury (AKI) in 2%–5% of patients on ICI therapy. AKI associated with ICI therapy pathologically presents with AIN in nearly 90% of the cases, but the pathophysiology of ICI-AIN remains to be defined. The generation of autoreactive T cells in patients receiving AIN-inducible drugs, such as proton pump inhibitors (PPIs), is one of the leading theories, supported by a higher incidence of ICI-AIN in patients on these AIN-inducible drugs. In this review, we will discuss our understanding of the incidence, potential pathophysiological mechanisms, clinical presentations, risk factors, diagnosis, and management of PPI-related AIN and its interaction with ICI therapy.

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.

Background: The Mediterranean, Dietary Approach to Stop Hypertension (DASH), and plant-based diets may provide cardiovascular benefit to the general population. However, data on their effect on end stage kidney disease (ESKD) patients are limited. This systematic review aims to assess the impact of Mediterranean, DASH, and plant-based diets on outcomes among ESKD patients. Methods: A literature review was conducted in EMBASE, MEDLINE, and Cochrane databases from inception through September 2022 to identify studies that assess the clinical outcomes of Mediterranean, DASH, or plant-based diets on ESKD patients on hemodialysis (HD) or peritoneal dialysis (PD). Effect estimates from the individual studies were derived utilizing the random-effect, generic inverse variance approach of DerSimonian and Laird. Results: Seven studies with 9400 ESKD patients (8395 HD and 1005 PD) met the eligibility criteria and were included in the data analysis. Pooled odds ratios (ORs) of mortality for ESKD patients who adhered to the Mediterranean versus plant-based diet were 0.49 (95% CI: 0.07–3.54; two studies, I2 = 67%) and 0.87 (95% CI: 0.75–1.01; two studies, I2 = 0%), respectively. Data on mortality for ESKD patients on a DASH diet were limited to one study with an OR of 1.00 (95% CI: 0.89–1.12). The pooled OR of cardiovascular mortality among ESKD patients who adhered to a plant-based diet was 0.86 (95% CI: 0.68–1.08; two studies, I2 = 0%), compared to those who did not. Data on cardiovascular mortality among those with Mediterranean and DASH diet were limited to one study with ORs of 1.14 (95% CI: 0.90–1.43) and 1.19 (95% CI: 0.99–1.43), respectively. Mediterranean diet adherence was found to be associated with reduced risk of left ventricular hypertrophy (LVH) with an OR of 0.82 (95% CI: 0.68–0.99) in a study including 127 ESKD patients. The risk of hyperkalemia was not significant among those with a plant-based diet with an OR of 1.00 (95% CI: 0.94–1.07) in a study including 150 ESKD patients. Conclusions: While our systematic review demonstrated no significant associations of Mediterranean, DASH, and plant-based diets with reduced all-cause mortality or cardiovascular mortality, there was also no evidence that suggested harmful effects of these diets to ESKD patients.