Phenotypic subtypes of fibrotic hypersensitivity pneumonitis identified by machine learning consensus clustering analysis.

BACKGROUND: Patients with fibrotic hypersensitivity pneumonitis (f-HP) have varied clinical and radiologic presentations whose associated phenotypic outcomes have not been previously described. We conducted a study to evaluate mortality and lung transplant (LT) outcomes among clinical clusters of f-HP as characterized by an unsupervised machine learning approach. METHODS: Consensus cluster analysis was performed on a retrospective cohort of f-HP patients diagnosed according to recent international guideline. Demographics, antigen exposure, radiologic, histopathologic, and pulmonary function findings along with comorbidities were included in the cluster analysis. Cox proportional-hazards regression was used to assess mortality or LT risk as a combined outcome for each cluster. RESULTS: Three distinct clusters were identified among 336 f-HP patients. Cluster 1 (n = 158, 47%) was characterized by mild restriction on pulmonary function testing (PFT). Cluster 2 (n = 46, 14%) was characterized by younger age, lower BMI, and a higher proportion of identifiable causative antigens with baseline obstructive physiology. Cluster 3 (n = 132, 39%) was characterized by moderate to severe restriction. When compared to cluster 1, mortality or LT risk was lower in cluster 2 (hazard ratio (HR) of 0.42; 95% CI, 0.21-0.82; P = 0.01) and higher in cluster 3 (HR of 1.76; 95% CI, 1.24-2.48; P = 0.001). CONCLUSIONS: Three distinct phenotypes of f-HP with unique mortality or transplant outcomes were found using unsupervised cluster analysis, highlighting improved mortality in fibrotic patients with obstructive physiology and identifiable antigens.

Association of Proton Pump Inhibitor Use and Immune Checkpoint Inhibitor Mediated Acute Kidney Injury: A Meta-Analysis and a Review of Related Outcomes.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, they pose the risk of immune-related adverse events, including ICI-mediated acute kidney injury (ICI-AKI). Recent studies have implicated proton pump inhibitors (PPIs) as potential contributors to ICI-AKI development. This meta-analysis examines the association between PPI use and ICI-AKI, exploring a potential modifiable risk factor in ICI therapy, while also reviewing the possible outcomes of ICI-AKI. METHODS: We conducted a comprehensive systematic review and meta-analysis of observational studies, assessing the risk of ICI-AKI in cancer patients concurrently using PPIs and potential outcomes. Odds ratios (ORs) were pooled using random-effects models. Subgroup analyses and sensitivity analyses were performed to evaluate heterogeneity and potential biases. RESULTS: A total of 14 studies involving 12,694 patients were included. In total, we analyzed 639 patients with all-cause AKI and 779 patients with ICI-AKI. The pooled OR for the overall incidence of AKI from all-cause was 1.57 (95% Confidence Interval (CI), 1.02 to 2.40) among patients on PPIs. Specifically, the risk of ICI-AKI associated with PPI use was significantly higher, with a pooled OR of 1.84 (95% CI 1.16 to 2.90). This indicates approximately 84% higher likelihood of developing ICI-AKI with concurrent use of PPIs. Additionally, among patients with ICI-AKI, 67% had complete or partial recovery of renal function, 32% progressed to chronic kidney disease (CKD) and about 36% died during a follow-up period of at least 3 months. CONCLUSION: This meta-analysis highlights the importance of cautious PPI prescription in cancer patients undergoing ICI therapy. Clinicians are advised to evaluate the risks and benefits of PPI use and consider alternative therapies when feasible.

Re-assessing prolonged cold ischemia time in kidney transplantation through machine learning consensus clustering.

BACKGROUND: We aimed to cluster deceased donor kidney transplant recipients with prolonged cold ischemia time (CIT) using an unsupervised machine learning approach. METHODS: We performed consensus cluster analysis on 11 615 deceased donor kidney transplant patients with CIT exceeding 24 h using OPTN/UNOS data from 2015 to 2019. Cluster characteristics of clinical significance were identified, and post-transplant outcomes were compared. RESULTS: Consensus cluster analysis identified two clinically distinct clusters. Cluster 1 was characterized by young, non-diabetic patients who received kidney transplants from young, non-hypertensive, non-ECD deceased donors with lower KDPI scores. In contrast, the patients in cluster 2 were older and more likely to have diabetes. Cluster 2 recipients were more likely to receive transplants from older donors with a higher KDPI. There was lower use of machine perfusion in Cluster 1 and incrementally longer CIT in Cluster 2. Cluster 2 had a higher incidence of delayed graft function (42% vs. 29%), and lower 1-year patient (95% vs. 98%) and death-censored (95% vs. 97%) graft survival compared to Cluster 1. CONCLUSIONS: Unsupervised machine learning characterized deceased donor kidney transplant recipients with prolonged CIT into two clusters with differing outcomes. Although Cluster 1 had more favorable recipient and donor characteristics and better survival, the outcomes observed in Cluster 2 were also satisfactory. Overall, both clusters demonstrated good survival suggesting opportunities for transplant centers to incrementally increase CIT.

Efficacy of Therapeutic Apheresis for Cryoglobulinemic Vasculitis Patients with Renal Involvement: A Systematic Review.

INTRODUCTION: Therapeutic apheresis (TA) is commonly used for cryoglobulinemic vasculitis (CV) patients, but its efficacy remains uncertain. This systematic review aimed to assess the efficacy of different TA modalities, such as plasma exchange (PE), plasmapheresis (PP), and cryofiltration (CF), in treating CV patients with renal involvement. METHODS: Literature search of MEDLINE, EMBASE, and Cochrane Databases was conducted up to December 2022. Studies that reported the outcomes of TA in adult CV patients with renal involvement were assessed. The protocol for this systematic review has been registered with PROSPERO (No. CRD42023417727). The quality of each study was evaluated by the investigators using the validated methodological index for non-randomized studies (minors) quality score. RESULTS: 154 patients who encountered 170 episodes of serious events necessitating TA were evaluated across 76 studies. Among them, 51% were males, with a mean age ranging from 49 to 58 years. The CV types included 15 type I, 97 type II, and 13 type III, while the remaining patients exhibited mixed (n = 17) or undetermined CV types (n = 12). Among the treatment modalities, PE, PP, and CF were performed in 85 (56%), 52 (34%), and 17 patients (11%), respectively, with no identical protocol for TA treatment. The overall response rate for TA was 78%, with response rates of 84%, 77%, and 75% observed in type I, II, and III patients respectively. Most patients received steroids, immunosuppressants, and treatment targeting the underlying causative disease. The overall long-term renal outcome rate was 77%, with type I, II, and III patients experiencing response rates of 89%, 76%, and 90%, respectively. The renal outcomes in patients receiving PE, PP, and CF were comparable, with rates of 78%, 76%, and 81%, respectively. CONCLUSIONS: This study presents compelling evidence that combination of TA with other treatments, especially immunosuppressive therapy, is a successful strategy for effectively managing severe renal involvement in CV patients. Among the TA modalities studied, including PE, PP, and CF, all demonstrated efficacy, with PE being the most frequently employed approach.

Evaluating ChatGPT's Accuracy in Responding to Patient Education Questions on Acute Kidney Injury and Continuous Renal Replacement Therapy.

INTRODUCTION: Acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) are critical areas in nephrology. The effectiveness of ChatGPT in simpler, patient education-oriented questions has not been thoroughly assessed. This study evaluates the proficiency of ChatGPT 4.0 in responding to such questions, subjected to various linguistic alterations. METHODS: Eighty-nine questions were sourced from the Mayo Clinic Handbook for educating patients on AKI and CRRT. These questions were categorized as original, paraphrased with different interrogative adverbs, paraphrased resulting in incomplete sentences, and paraphrased containing misspelled words. Two nephrologists verified the questions for medical accuracy. A χ2 test was conducted to ascertain notable discrepancies in ChatGPT 4.0's performance across these formats. RESULTS: ChatGPT provided notable accuracy in handling a variety of question formats for patient education in AKI and CRRT. Across all question types, ChatGPT demonstrated an accuracy of 97% for both original and adverb-altered questions and 98% for questions with incomplete sentences or misspellings. Specifically for AKI-related questions, the accuracy was consistently maintained at 97% for all versions. In the subset of CRRT-related questions, the tool achieved a 96% accuracy for original and adverb-altered questions, and this increased to 98% for questions with incomplete sentences or misspellings. The statistical analysis revealed no significant difference in performance across these varied question types (p value: 1.00 for AKI and 1.00 for CRRT), and there was no notable disparity between the artificial intelligence (AI)'s responses to AKI and CRRT questions (p value: 0.71). CONCLUSION: ChatGPT 4.0 demonstrates consistent and high accuracy in interpreting and responding to queries related to AKI and CRRT, irrespective of linguistic modifications. These findings suggest that ChatGPT 4.0 has the potential to be a reliable support tool in the delivery of patient education, by accurately providing information across a range of question formats. Further research is needed to explore the direct impact of AI-generated responses on patient understanding and education outcomes.

Assessing the impact of continuous positive airway pressure therapy on clinical outcomes in interstitial lung disease patients with coexisting obstructive sleep apnea: a systematic review.

PURPOSE: Interstitial lung disease (ILD) often coexists with obstructive sleep apnea (OSA), contributing to increased morbidity and mortality. However, the effectiveness of continuous positive airway pressure (CPAP) therapy in this population remains unclear. We conducted a systematic review to evaluate CPAP therapy's impact on clinical outcomes in patients with ILD and comorbid OSA. METHODS: Following PRISMA guidelines, we systematically searched multiple databases for studies assessing CPAP therapy's effects on ILD exacerbation, hospitalization, quality of life, and mortality in ILD-OSA patients. Studies were selected based on predefined inclusion criteria, and their quality was assessed using the Newcastle-Ottawa quality scale. RESULTS: Among 485 articles screened, 82 underwent full review, with four observational studies meeting inclusion criteria. CPAP therapy demonstrated potential benefits in improving quality of life and reducing ILD exacerbations in ILD-OSA patients. However, its impact on mortality was inconclusive due to variability in study definitions and methodology. CONCLUSION: CPAP therapy may improve outcomes in ILD-OSA patients, particularly in terms of quality of life and ILD exacerbations. Nonetheless, further research with standardized definitions and rigorous methodology is needed to confirm its efficacy, particularly regarding mortality outcome.

Outpatient Antibiotic Use is Not Associated with an Increased Risk of First-Time Symptomatic Kidney Stones.

SIGNIFICANCE STATEMENT: Antibiotics modify human microbiomes and may contribute to kidney stone risk. In a population-based case-control study using 1247 chart-validated first-time symptomatic kidney stone formers and 4024 age- and sex-matched controls, the risk of kidney stones was transiently higher during the first year after antibiotic use. However, this risk was no longer evident after adjustment for comorbidities and excluding participants with prior urinary symptoms. Findings were consistent across antibiotic classes and the number of antibiotic courses received. This suggests that antibiotics are not important risk factors of kidney stones. Rather, kidney stones when they initially cause urinary symptoms are under-recognized, resulting in antibiotic use before a formal diagnosis of kidney stones ( i.e. , reverse causality). BACKGROUND: Antibiotics modify gastrointestinal and urinary microbiomes, which may contribute to kidney stone formation. This study examined whether an increased risk of a first-time symptomatic kidney stone episode follows antibiotic use. METHODS: A population-based case-control study surveyed 1247 chart-validated first-time symptomatic kidney stone formers with a documented obstructing or passed stone (cases) in Olmsted County, Minnesota, from 2008 to 2013 and 4024 age- and sex-matched controls. All prescriptions for outpatient oral antibiotic use within 5 years before the onset of symptomatic stone for the cases and their matched controls were identified. Conditional logistic regression estimated the odds ratio (OR) of a first-time symptomatic kidney stone across time after antibiotic use. Analyses were also performed after excluding cases and controls with prior urinary tract infection or hematuria because urinary symptoms resulting in antibiotic prescription could have been warranted because of undiagnosed kidney stones. RESULTS: The risk of a symptomatic kidney stone was only increased during the 1-year period after antibiotic use (unadjusted OR, 1.31; P = 0.001), and this risk was attenuated after adjustment for comorbidities (OR, 1.16; P = 0.08). After excluding cases and controls with prior urinary symptoms, there was no increased risk of a symptomatic kidney stone during the 1-year period after antibiotic use (unadjusted OR, 1.04; P = 0.70). Findings were consistent across antibiotic classes and the number of antibiotic courses received. CONCLUSIONS: The increased risk of a first-time symptomatic kidney stone with antibiotic use seems largely due to both comorbidities and prescription of antibiotics for urinary symptoms. Under-recognition of kidney stones that initially cause urinary symptoms resulting in antibiotic use may explain much of the perceived stone risk with antibiotics ( i.e. , reverse causality).

Perspectives on AI-based recommendations for mask-wearing and COVID-19 vaccination for transplant recipients in the post-COVID-19 era.

In the aftermath of the COVID-19 pandemic, the ongoing necessity for preventive measures such as mask-wearing and vaccination remains particularly critical for organ transplant recipients, a group highly susceptible to infections due to immunosuppressive therapy. Given that many individuals nowadays increasingly utilize Artificial Intelligence (AI), understanding AI perspectives is important. Thus, this study utilizes AI, specifically ChatGPT 4.0, to assess its perspectives in offering precise health recommendations for mask-wearing and COVID-19 vaccination tailored to this vulnerable population. Through a series of scenarios reflecting diverse environmental settings and health statuses in December 2023, we evaluated the AI's responses to gauge its precision, adaptability, and potential biases in advising high-risk patient groups. Our findings reveal that ChatGPT 4.0 consistently recommends mask-wearing in crowded and indoor environments for transplant recipients, underscoring their elevated risk. In contrast, for settings with fewer transmission risks, such as outdoor areas where social distancing is possible, the AI suggests that mask-wearing might be less imperative. Regarding vaccination guidance, the AI strongly advocates for the COVID-19 vaccine across most scenarios for kidney transplant recipients. However, it recommends a personalized consultation with healthcare providers in cases where patients express concerns about vaccine-related side effects, demonstrating an ability to adapt recommendations based on individual health considerations. While this study provides valuable insights into the current AI perspective on these important topics, it is crucial to note that the findings do not directly reflect or influence health policy. Nevertheless, given the increasing utilization of AI in various domains, understanding AI's viewpoints on such critical matters is essential for informed decision-making and future research.

Integrating Retrieval-Augmented Generation with Large Language Models in Nephrology: Advancing Practical Applications.

The integration of large language models (LLMs) into healthcare, particularly in nephrology, represents a significant advancement in applying advanced technology to patient care, medical research, and education. These advanced models have progressed from simple text processors to tools capable of deep language understanding, offering innovative ways to handle health-related data, thus improving medical practice efficiency and effectiveness. A significant challenge in medical applications of LLMs is their imperfect accuracy and/or tendency to produce hallucinations-outputs that are factually incorrect or irrelevant. This issue is particularly critical in healthcare, where precision is essential, as inaccuracies can undermine the reliability of these models in crucial decision-making processes. To overcome these challenges, various strategies have been developed. One such strategy is prompt engineering, like the chain-of-thought approach, which directs LLMs towards more accurate responses by breaking down the problem into intermediate steps or reasoning sequences. Another one is the retrieval-augmented generation (RAG) strategy, which helps address hallucinations by integrating external data, enhancing output accuracy and relevance. Hence, RAG is favored for tasks requiring up-to-date, comprehensive information, such as in clinical decision making or educational applications. In this article, we showcase the creation of a specialized ChatGPT model integrated with a RAG system, tailored to align with the KDIGO 2023 guidelines for chronic kidney disease. This example demonstrates its potential in providing specialized, accurate medical advice, marking a step towards more reliable and efficient nephrology practices.

Chain of Thought Utilization in Large Language Models and Application in Nephrology.

Chain-of-thought prompting enhances the abilities of large language models (LLMs) significantly. It not only makes these models more specific and context-aware but also impacts the wider field of artificial intelligence (AI). This approach broadens the usability of AI, increases its efficiency, and aligns it more closely with human thinking and decision-making processes. As we improve this method, it is set to become a key element in the future of AI, adding more purpose, precision, and ethical consideration to these technologies. In medicine, the chain-of-thought prompting is especially beneficial. Its capacity to handle complex information, its logical and sequential reasoning, and its suitability for ethically and context-sensitive situations make it an invaluable tool for healthcare professionals. Its role in enhancing medical care and research is expected to grow as we further develop and use this technique. Chain-of-thought prompting bridges the gap between AI's traditionally obscure decision-making process and the clear, accountable standards required in healthcare. It does this by emulating a reasoning style familiar to medical professionals, fitting well into their existing practices and ethical codes. While solving AI transparency is a complex challenge, the chain-of-thought approach is a significant step toward making AI more comprehensible and trustworthy in medicine. This review focuses on understanding the workings of LLMs, particularly how chain-of-thought prompting can be adapted for nephrology's unique requirements. It also aims to thoroughly examine the ethical aspects, clarity, and future possibilities, offering an in-depth view of the exciting convergence of these areas.

Sex differences in clinical characteristics, management, and outcomes in patients admitted for ventricular tachycardia: 2016-2018.

INTRODUCTION: The concurrent data on sex disparities in VT management and outcomes have remained unclear. Therefore, our objective was to determine the impact of sex on ventricular tachycardia (VT) management and outcomes in patients admitted with VT, dervied from the US National Inpatient Sample database (NIS). METHODS: We used data from the US NIS to identify hospitalized adult patients who were admitted with VT between 2016 and 2018. Regression analysis was conducted to evaluate the impact of sex on VT management, in-hospital mortality, complications, length of stay, and hospitalization costs. RESULTS: Of the database, a total of 146 070 patients, who were primarily hospitalized for VT, were approximated. Among these, women comprised 25.5%; they were significantly younger and had fewer comorbidities. Of procedural aspects, women were less likely to receive an angiogram, mechanical support, implantable cardioverter-defibrillator implantation, and VT ablation compared to men. Notably, women were associated with higher do-not-resuscitate rates and in-hospital cardiac arrests than men. No differences in in-hospital mortality and cardiogenic shock were observed between men and women (p > .05). Length of stay was significantly longer for women, while no differences in hospital costs were observed in both sexes. CONCLUSION: Significant sex disparities in management and outcomes were observed in admitted patients with VT. Our results reflect the need for further studies to explore factors causing such diversities.

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.

Nuclear Magnetic Resonance Metabolomic Profiling and Urine Chemistries in Incident Kidney Stone Formers Compared with Controls.

BACKGROUND: The urine metabolites and chemistries that contribute to kidney stone formation are not fully understood. This study examined differences between the urine metabolic and chemistries profiles of first-time stone formers and controls. METHODS: High-resolution 1H-nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was performed in 24-hour urine samples from a prospective cohort of 418 first-time symptomatic kidney stone formers and 440 controls. In total, 48 NMR-quantified metabolites in addition to 12 standard urine chemistries were assayed. Analysis of covariance was used to determine the association of stone former status with urine metabolites or chemistries after adjusting for age and sex and correcting for the false discovery rate. Gradient-boosted machine methods with nested cross-validation were applied to predict stone former status. RESULTS: Among the standard urine chemistries, stone formers had lower urine oxalate and potassium and higher urine calcium, phosphate, and creatinine. Among NMR urine metabolites, stone formers had lower hippuric acid, trigonelline, 2-furoylglycine, imidazole, and citrate and higher creatine and alanine. A cross-validated model using urine chemistries, age, and sex yielded a mean AUC of 0.76 (95% CI, 0.73 to 0.79). A cross-validated model using urine chemistries, NMR-quantified metabolites, age, and sex did not meaningfully improve the discrimination (mean AUC, 0.78; 95% CI, 0.75 to 0.81). In this combined model, among the top ten discriminating features, four were urine chemistries and six NMR-quantified metabolites. CONCLUSIONS: Although NMR-quantified metabolites did not improve discrimination, several urine metabolic profiles were identified that may improve understanding of kidney stone pathogenesis.

Peer-reviewed visuals and auditory - isn't it time to incorporate?

A remarkable opportunity emerges amidst the dynamic evolution of medical education, one that could fundamentally alter how healthcare professionals gain and share knowledge. The concept of incorporating a structured, peer-reviewed video and audio section, as well as a dedicated submission portal, into the medical journals symbolizes a revolutionary advance. This addition has the potential to not only improve the educational experiences of the journal's audience, but also to create a more accessible forum for the exchange of knowledge and citation. In this article, we explore the compelling potential of introducing structured videos and podcasts into the domain of medical literature, as well as the promising implications for revamping medical practitioners' learning strategies.

Efficacy of extracorporeal plasma therapy for adult native kidney patients with Primary FSGS: a Systematic review.

PURPOSE: This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis (LDL-A), and lymphocytapheresis (LCAP) for adult native kidney patients with primary focal segmental glomerulosclerosis (FSGS). METHODS: A literature search was conducted using MEDLINE, EMBASE and Cochrane Databases through August 2022. Studies that reported outcomes of EPT in adult native kidneys with primary FSGS were enrolled. RESULTS: 18 studies with 104 therapy-resistant or refractory primary native FSGS patients were identified. Overall EPT response rate was 56%, with long-term benefit of 46%. Of the 101 non-hemodialysis (HD) patients, 54% achieved remission, with 30% complete remission (CR) and 23% partial remission (PR). Of 31 patients with PE, response rate was 65%; CR and PR rates were 27% and 37% in 30 non-HD patients. Of 61 patients with LDL-A, the response rate was 54%; CR and PR rates were 41% and 3% in 29 non-HD patients. Of 10 patients with IA, response rate was 40%. Of 2 patients with LCAP, 1 achieved CR, and one developed renal failure. All 3 HD patients showed increase in urine output and gradual decrease in urine protein excretion following PE (n = 1) or LDL-A (n = 2). 2 of 3 HD patients ultimately discontinued dialysis. CONCLUSION: EPT with immunosuppressive therapy showed benefit in some patients with refractory primary FSGS, and PE appeared to have a higher response rate.

Distinct clinical profiles and post-transplant outcomes among kidney transplant recipients with lower education levels: uncovering patterns through machine learning clustering.

BACKGROUND: Educational attainment significantly influences post-transplant outcomes in kidney transplant patients. However, research on specific attributes of lower-educated subgroups remains underexplored. This study utilized unsupervised machine learning to segment kidney transplant recipients based on education, further analyzing the relationship between these segments and post-transplant results. METHODS: Using the OPTN/UNOS 2017-2019 data, consensus clustering was applied to 20,474 kidney transplant recipients, all below a college/university educational threshold. The analysis concentrated on recipient, donor, and transplant features, aiming to discern pivotal attributes for each cluster and compare post-transplant results. RESULTS: Four distinct clusters emerged. Cluster 1 comprised younger, non-diabetic, first-time recipients from non-hypertensive younger donors. Cluster 2 predominantly included white patients receiving their first-time kidney transplant either preemptively or within three years, mainly from living donors. Cluster 3 included younger re-transplant recipients, marked by elevated PRA, fewer HLA mismatches. In contrast, Cluster 4 captured older, diabetic patients transplanted after prolonged dialysis duration, primarily from lower-grade donors. Interestingly, Cluster 2 showcased the most favorable post-transplant outcomes. Conversely, Clusters 1, 3, and 4 revealed heightened risks for graft failure and mortality in comparison. CONCLUSIONS: Through unsupervised machine learning, this study proficiently categorized kidney recipients with lesser education into four distinct clusters. Notably, the standout performance of Cluster 2 provides invaluable insights, underscoring the necessity for adept risk assessment and tailored transplant strategies, potentially elevating care standards for this patient cohort.

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.

Sodium Thiosulfate for Calciphylaxis Treatment in Patients on Peritoneal Dialysis: A Systematic Review.

Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in hemodialysis (HD) patients. A systematic literature search was conducted using Ovid MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, and EBM Reviews-Cochrane Database of Systematic Reviews to identify reported cases of PD patients with calciphylaxis who received STS. The search covered the inception of the databases through August 2022. Across 19 articles, this review identified 30 PD patients with calciphylaxis who received STS. These included 15 case reports, 2 case series, and 2 cohort studies. The administration routes and doses varied depending on the study. For intravenous (IV) administration (n = 18), STS doses ranged from 3.2 g twice daily to 25 g three times weekly for 5 weeks to 8 months. Outcomes included 44% of patients experiencing successful wound healing, 6% discontinuing STS due to adverse effects, 67% transitioning to HD, and 50% dying from calciphylaxis complications. For intraperitoneal (IP) administration (n = 5), STS doses ranged from 12.5 to 25 g three to four times weekly for 12 h to 3 months. Results showed 80% of patients achieving successful wound healing, 80% discontinuing STS due to adverse effects, 40% transitioning to HD, and 20% dying from IP STS-related chemical peritonitis. In cases where patients switched from IV to IP STS (n = 3), doses ranged from 12.5 to 25 g two to three times weekly for 2.5 to 5 months. Among them, 67% experienced successful wound healing, while 33% died from sepsis. Two cases utilized oral STS at a dose of 1500 mg twice daily for 6 and 11 months, resulting in successful wound healing without adverse effects or need for HD. However, one patient (50%) died due to small bowel obstruction. This systematic review provides an overview of STS treatment for PD patients with calciphylaxis. Although successful treatment cases exist, adverse effects were significant. Further research, including larger clinical studies and pharmacokinetic data, is necessary to establish the optimal route, dose, and efficacy of STS in PD patients.

Differences between Very Highly Sensitized Kidney Transplant Recipients as Identified by Machine Learning Consensus Clustering.

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.

Antigen identification and avoidance on outcomes in fibrotic hypersensitivity pneumonitis.

BACKGROUND: Suspected causative antigens may be unidentified in 30-50% of patients with fibrotic hypersensitivity pneumonitis (f-HP). It is unclear whether antigen identification and avoidance in this setting offer any additional clinical benefit. We hypothesised that antigen identification and avoidance may improve the clinical course of patients with fibrotic disease. METHODS: Patients meeting recent international practice guidance for f-HP diagnosis evaluated at Mayo Clinic Rochester from January 2005 to December 2018 were included. Causative antigen and antigen avoidance were specifically defined and ascertained through review of the medical records. Cox proportional-hazards regression was performed to assess antigen identification and avoidance as predictors of either all-cause mortality or lung transplantation. RESULTS: 377 patients were included. Of these, suspected causative antigen was identified in 225 (60%). Identification of a suspected antigen (adjusted hazard ratio (HR) 0.69, 95% CI 0.48-0.99; p=0.04) and subsequent antigen avoidance (adjusted HR 0.47, 95% CI 0.31-0.71; p<0.001) were associated with decreased all-cause mortality and transplantation. Both those with suspected antigen identification but nonavoidance and those with unidentifiable antigen had increased risk of all-cause mortality or transplantation (adjusted HR 2.22, 95% CI 1.34-3.69; p=0.002 versus adjusted HR 2.09, 95% CI 1.34-3.26; p=0.001, respectively). Exposure to avian antigen was associated with better outcome compared to other antigen subtypes (adjusted HR 0.63, 95% CI 0.43-0.93; p=0.02). CONCLUSION: Our findings suggest that antigen identification and antigen avoidance remain relevant even in patients with fibrotic disease, where both appear to be associated with improved outcomes.