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.

Oral sub-chronic toxicity of fingerroot (Boesenbergia rotunda) rhizome extract formulation in Wistar rats.

Background: Boesenbergia rotunda (fingerroot) rhizome extract contains two major bioactive components, panduratin A and pinostrobin. In our previous study, we found the anti-inflammatory effects of the fingerroot extract against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in golden Syrian hamsters. In the present study, we evaluated the sub-chronic toxicity of a fingerroot extract formulation over 90 consecutive days of oral administration. Methods: We enhanced the water solubility of a fingerroot extract by formulating it with cyclodextrin, containing panduratin A (29% w/w) and pinostrobin (32% w/w). This formulation was administered to male and female Wistar rats at doses of 25, 50, or 100 mg/kg/day for a duration of 90 days. Additionally, two recovery groups, comprising a control group and a high-dose group, were designated for a 14-day observation period to assess the persistence and reversibility of potential adverse effects. Throughout the experiment, we performed clinical and health observations, followed by hematological testing, clinical biochemistry analysis, necropsy examination, and histopathological evaluation at the end of the experiment. Results: The administration of the fingerroot extract formulation at doses of 25, 50, or 100 mg/kg/day did not result in mortality or clinical signs of toxicity. No clinically significant findings were associated with the oral administration of the fingerroot extract formulation. Conclusion: The fingerroot extract formulation showed no serious adverse effects at doses up to 100 mg/kg/day in Wistar rats under the experimental condition. Consequently, the No Observed Adverse Effect Level (NOAEL) was considered to be 100 mg/kg/day. This finding contributes significance for future developments involving fingerroot extract in herbal medicinal products targeting chronic inflammation.

Safety and efficacy of glucagon-like peptide-1 receptor agonists among kidney transplant recipients: a systematic review and meta-analysis.

Background: Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis aims to evaluate the safety and efficacy of GLP-1RAs in this population. Methods: A comprehensive literature search was conducted in the MEDLINE, Embase and Cochrane databases from inception through May 2023. Clinical trials and observational studies that reported on the safety or efficacy outcomes of GLP-1RAs in adult KTRs were included. Kidney graft function, glycaemic and metabolic parameters, weight, cardiovascular outcomes and adverse events were evaluated. Outcome measures used for analysis included pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean difference (SMD) or mean difference (MD) with 95% CI for continuous outcomes. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023426190). Results: Nine cohort studies with a total of 338 KTRs were included. The median follow-up was 12 months (interquartile range 6-23). While treatment with GLP-1RAs did not yield a significant change in estimated glomerular filtration rate [SMD -0.07 ml/min/1.73 m2 (95% CI -0.64-0.50)] or creatinine [SMD -0.08 mg/dl (95% CI -0.44-0.28)], they were associated with a significant decrease in urine protein:creatinine ratio [SMD -0.47 (95% CI -0.77 to -0.18)] and haemoglobin A1c levels [MD -0.85% (95% CI -1.41 to -0.28)]. Total daily insulin dose, weight and body mass index also decreased significantly. Tacrolimus levels remained stable [MD -0.43 ng/ml (95% CI -0.99 to 0.13)]. Side effects were primarily nausea and vomiting (17.6%), diarrhoea (7.6%) and injection site pain (5.4%). Conclusions: GLP-1RAs are effective in reducing proteinuria, improving glycaemic control and supporting weight loss in KTRs, without altering tacrolimus levels. Gastrointestinal symptoms are the main side effects.

Sub-chronic oral toxicity of a water-soluble extract of Centella asiatica (Centell-S) in Wistar rats.

BACKGROUND: Centell-S, a water-soluble extract from Centella asiatica, is predominantly composed of madecassoside and asiaticoside, exceeding 80% w/w. Pursuing its development as an herbal medicinal product, Centell-S underwent sub-chronic toxicity assessment adhering to OECD GLP 408 standards. METHODS: In a study involving 100 Wistar rats, varying doses of Centell-S (50, 200, or 800 mg/kg/day) or a vehicle control were administered orally over 90 days. To evaluate Centell-S's safety profile, assessments included clinical observations, health examinations, clinical biochemistry analyses, and detailed anatomical pathology evaluations were conducted. RESULTS: Over the 90 days of treatment, the administration of Centell-S did not lead to any fatalities in the test animals. Clinical observations did not reveal any signs indicative of toxic effects. Notably, an increase in total white blood cell and lymphocyte counts was observed in both sexes, yet these levels returned to normal following a two-week discontinuation period post-treatment. CONCLUSIONS: Under the specific conditions of the OECD GLP 408, Repeated Dose 90-day Oral Toxicity Study in Rodents, the no observed adverse effect level (NOAEL) of Centell-S was 800 mg/kg/day. These findings are promising for the continued development of Centell-S as a phytopharmaceutical for clinical applications.

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.

Safety and Efficacy of GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus with Advanced and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Background and Objectives: Limited evidence exists regarding the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Thus, we conducted a systematic review and meta-analysis to assess the safety and efficacy of GLP-1RAs in T2DM patients with advanced CKD and ESKD. Materials and Methods: We performed a systematic literature search in MEDLINE, EMBASE, and Cochrane database until 25 October 2023. Included were clinical trials and cohort studies reporting outcomes of GLP-1RAs in adult patients with T2DM and advanced CKD. Outcome measures encompassed mortality, cardiovascular parameters, blood glucose, and weight. Safety was assessed for adverse events. The differences in effects were expressed as odds ratios with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference or standardized mean difference (SMD) with 95% confidence intervals for continuous outcomes. The Risk of Bias In Non-randomized Studies-of Interventions (ROBIN-I) tool was used in cohort and non-randomized controlled studies, and the Cochrane Risk of Bias (RoB 2) tool was used in randomized controlled trials (RCTs). The review protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023398452) and received no external funding. Results: Eight studies (five trials and three cohort studies) consisting of 27,639 patients were included in this meta-analysis. No difference was observed in one-year mortality. However, GLP-1RAs significantly reduced cardiothoracic ratio (SMD of -1.2%; 95% CI -2.0, -0.4) and pro-BNP (SMD -335.9 pmol/L; 95% CI -438.9, -232.8). There was no significant decrease in systolic blood pressure. Moreover, GLP-1RAs significantly reduced mean blood glucose (SMD -1.1 mg/dL; 95% CI -1.8, -0.3) and increased weight loss (SMD -2.2 kg; 95% CI -2.9, -1.5). In terms of safety, GLP-1RAs were associated with a 3.8- and 35.7-time higher risk of nausea and vomiting, respectively, but were not significantly associated with a higher risk of hypoglycemia. Conclusions: Despite the limited number of studies in each analysis, our study provides evidence supporting the safety and efficacy of GLP-1RAs among T2DM patients with advanced CKD and ESKD. While gastrointestinal side effects may occur, GLP-1RAs demonstrate significant improvements in blood glucose control, weight reduction, and potential benefit in cardiovascular outcomes.

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.

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.

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.

Potential drug-drug interactions of frequently prescribed medications in long COVID detected by two electronic databases.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a wide range of acute and chronic complications including long COVID, a well-known chronic sequela. Long COVID often necessitates long-term treatment, which may lead to an increased potential for drug-drug interactions (DDIs). The objective of this study was to assess potential DDIs among frequently prescribed medications in long COVID by using two electronic databases. Sixty frequently prescribed agents were selected from Thailand's National List of Essential Medicine 2022 for potential DDI analysis by Micromedex and Drugs.com. From these databases, 488 potential DDIs were identified. There were 271 and 434 DDI pairs based on Micromedex and Drugs.com, respectively. Among these DDIs, 77 pairs were labeled as contraindicated or major by both databases. The most common mechanisms for these serious interactions are cytochrome P450 (CYP) inhibition (45%), CYP induction (19%), and QT interval prolongation (7.8%). Based on Fleiss' kappa (0.073), there was only slight agreement of the DDI severity classifications between these two databases. In conclusion, a large number of potential DDIs were detected among frequently prescribed medications for long COVID. Health care providers should be aware of these DDIs, particularly those that are deemed as contraindicated or major. These DDIs are most likely to cause significant adverse events in patients with long COVID because polypharmacy is common.

AI-Powered Renal Diet Support: Performance of ChatGPT, Bard AI, and Bing Chat.

Patients with chronic kidney disease (CKD) necessitate specialized renal diets to prevent complications such as hyperkalemia and hyperphosphatemia. A comprehensive assessment of food components is pivotal, yet burdensome for healthcare providers. With evolving artificial intelligence (AI) technology, models such as ChatGPT, Bard AI, and Bing Chat can be instrumental in educating patients and assisting professionals. To gauge the efficacy of different AI models in discerning potassium and phosphorus content in foods, four AI models-ChatGPT 3.5, ChatGPT 4, Bard AI, and Bing Chat-were evaluated. A total of 240 food items, curated from the Mayo Clinic Renal Diet Handbook for CKD patients, were input into each model. These items were characterized by their potassium (149 items) and phosphorus (91 items) content. Each model was tasked to categorize the items into high or low potassium and high phosphorus content. The results were juxtaposed with the Mayo Clinic Renal Diet Handbook's recommendations. The concordance between repeated sessions was also evaluated to assess model consistency. Among the models tested, ChatGPT 4 displayed superior performance in identifying potassium content, correctly classifying 81% of the foods. It accurately discerned 60% of low potassium and 99% of high potassium foods. In comparison, ChatGPT 3.5 exhibited a 66% accuracy rate. Bard AI and Bing Chat models had an accuracy rate of 79% and 81%, respectively. Regarding phosphorus content, Bard AI stood out with a flawless 100% accuracy rate. ChatGPT 3.5 and Bing Chat recognized 85% and 89% of the high phosphorus foods correctly, while ChatGPT 4 registered a 77% accuracy rate. Emerging AI models manifest a diverse range of accuracy in discerning potassium and phosphorus content in foods suitable for CKD patients. ChatGPT 4, in particular, showed a marked improvement over its predecessor, especially in detecting potassium content. The Bard AI model exhibited exceptional precision for phosphorus identification. This study underscores the potential of AI models as efficient tools in renal dietary planning, though refinements are warranted for optimal utility.

Safety and Efficacy of Vaptans in the Treatment of Hyponatremia from Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): A Systematic Review and Meta-Analysis.

The utilization of vasopressin receptor antagonists, known as vaptans, in the management of hyponatremia among patients afflicted with the syndrome of inappropriate antidiuretic hormone (SIADH) remains a contentious subject. This meta-analysis aimed to evaluate the safety and efficacy of vaptans for treating chronic hyponatremia in adult SIADH patients. Clinical trials and observational studies were identified by a systematic search using MEDLINE, EMBASE, and Cochrane Database from inception through September 2022. The inclusion criteria were the studies that reported vaptans' safety or efficacy outcomes compared to placebo or standard therapies. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD 42022357307). Five studies were identified, comprising three RCTs and two cohort studies, enrolling a total of 1840 participants. Regarding short-term efficacy on days 4-5, vaptans exhibited a significant increase in serum sodium concentration from the baseline in comparison to the control group, with a weighted mean difference of 4.77 mmol/L (95% CI, 3.57, 5.96; I2 = 34%). In terms of safety outcomes, the pooled incidence rates of overcorrection were 13.1% (95% CI 4.3, 33.6; I2 = 92%) in the vaptans group and 3.3% (95% CI 1.6, 6.6; I2 = 27%) in the control group. Despite the higher correction rate linked to vaptans, with an OR of 5.72 (95% CI 3.38, 9.70; I2 = 0%), no cases of osmotic demyelination syndrome were observed. Our meta-analysis comprehensively summarizes the efficacy and effect size of vaptans in managing SIADH. While vaptans effectively raise the serum sodium concentration compared to placebo/fluid restriction, clinicians should exercise caution regarding the potential for overcorrection.

Examining the Validity of ChatGPT in Identifying Relevant Nephrology Literature: Findings and Implications.

Literature reviews are valuable for summarizing and evaluating the available evidence in various medical fields, including nephrology. However, identifying and exploring the potential sources requires focus and time devoted to literature searching for clinicians and researchers. ChatGPT is a novel artificial intelligence (AI) large language model (LLM) renowned for its exceptional ability to generate human-like responses across various tasks. However, whether ChatGPT can effectively assist medical professionals in identifying relevant literature is unclear. Therefore, this study aimed to assess the effectiveness of ChatGPT in identifying references to literature reviews in nephrology. We keyed the prompt "Please provide the references in Vancouver style and their links in recent literature on… name of the topic" into ChatGPT-3.5 (03/23 Version). We selected all the results provided by ChatGPT and assessed them for existence, relevance, and author/link correctness. We recorded each resource's citations, authors, title, journal name, publication year, digital object identifier (DOI), and link. The relevance and correctness of each resource were verified by searching on Google Scholar. Of the total 610 references in the nephrology literature, only 378 (62%) of the references provided by ChatGPT existed, while 31% were fabricated, and 7% of citations were incomplete references. Notably, only 122 (20%) of references were authentic. Additionally, 256 (68%) of the links in the references were found to be incorrect, and the DOI was inaccurate in 206 (54%) of the references. Moreover, among those with a link provided, the link was correct in only 20% of cases, and 3% of the references were irrelevant. Notably, an analysis of specific topics in electrolyte, hemodialysis, and kidney stones found that >60% of the references were inaccurate or misleading, with less reliable authorship and links provided by ChatGPT. Based on our findings, the use of ChatGPT as a sole resource for identifying references to literature reviews in nephrology is not recommended. Future studies could explore ways to improve AI language models' performance in identifying relevant nephrology literature.

Ethical Implications of Chatbot Utilization in Nephrology.

This comprehensive critical review critically examines the ethical implications associated with integrating chatbots into nephrology, aiming to identify concerns, propose policies, and offer potential solutions. Acknowledging the transformative potential of chatbots in healthcare, responsible implementation guided by ethical considerations is of the utmost importance. The review underscores the significance of establishing robust guidelines for data collection, storage, and sharing to safeguard privacy and ensure data security. Future research should prioritize defining appropriate levels of data access, exploring anonymization techniques, and implementing encryption methods. Transparent data usage practices and obtaining informed consent are fundamental ethical considerations. Effective security measures, including encryption technologies and secure data transmission protocols, are indispensable for maintaining the confidentiality and integrity of patient data. To address potential biases and discrimination, the review suggests regular algorithm reviews, diversity strategies, and ongoing monitoring. Enhancing the clarity of chatbot capabilities, developing user-friendly interfaces, and establishing explicit consent procedures are essential for informed consent. Striking a balance between automation and human intervention is vital to preserve the doctor-patient relationship. Cultural sensitivity and multilingual support should be considered through chatbot training. To ensure ethical chatbot utilization in nephrology, it is imperative to prioritize the development of comprehensive ethical frameworks encompassing data handling, security, bias mitigation, informed consent, and collaboration. Continuous research and innovation in this field are crucial for maximizing the potential of chatbot technology and ultimately improving patient outcomes.

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.

Contrast-Induced Encephalopathy in Patients with Chronic Kidney Disease and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Background: Contrast-induced encephalopathy (CIE) is an infrequent but serious neurological condition that occurs shortly after the administration of contrast during endovascular and angiography procedures. Patients suffering from chronic kidney disease (CKD) or end-stage kidney disease (ESKD) are considered to be at a higher risk of contrast medium neurotoxicity, due to the delayed elimination of the contrast medium. However, the occurrence and characteristics of CIE in CKD/ESKD patients have not been extensively investigated. Methods: We conducted a comprehensive literature search, utilizing databases such as MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, up to September 2022. The purpose was to identify documented cases of CIE among patients with CKD or ESKD. Employing a random-effects model, we calculated the pooled incidence and odds ratio (OR) of CIE in CKD/ESKD patients. Results: Our search yielded a total of eleven articles, comprising nine case reports and two observational studies. Among these studies, 2 CKD patients and 12 ESKD patients with CIE were identified. The majority of the CKD/ESKD patients with CIE (93%) had undergone intra-arterial contrast media and/or endovascular procedures to diagnose acute cerebrovascular disease, coronary artery disease, and peripheral artery disease. The male-to-female ratio was 64%, and the median age was 63 years (with an interquartile range of 55 to 68 years). In the two observational studies, the incidence of CIE was found to be 6.8% in CKD patients and 37.5% in ESKD patients, resulting in a pooled incidence of 16.4% (95% CI, 2.4%-60.7%) among the CKD/ESKD patients. Notably, CKD and ESKD were significantly associated with an increased risk of CIE, with ORs of 5.77 (95% CI, 1.37-24.3) and 223.5 (95% CI, 30.44-1641.01), respectively. The overall pooled OR for CIE in CKD/ESKD patients was 32.9 (95% CI, 0.89-1226.44). Although dialysis prior to contrast exposure did not prevent CIE, approximately 92% of CIE cases experienced recovery after undergoing dialysis following contrast exposure. However, the effectiveness of dialysis on CIE recovery remained uncertain, as there was no control group for comparison. Conclusions: In summary, our study indicates an association between CIE and CKD/ESKD. While patients with CIE showed signs of recovery after dialysis, further investigations are necessary, especially considering the lack of a control group, which made the effects of dialysis on CIE recovery uncertain.

Differences between Kidney Transplant Recipients from Deceased Donors with Diabetes Mellitus as Identified by Machine Learning Consensus Clustering.

Clinical outcomes of deceased donor kidney transplants coming from diabetic donors currently remain inconsistent, possibly due to high heterogeneities in this population. Our study aimed to cluster recipients of diabetic deceased donor kidney transplants using an unsupervised machine learning approach in order to identify subgroups with high risk of inferior outcomes and potential variables associated with these outcomes. Consensus cluster analysis was performed based on recipient-, donor-, and transplant-related characteristics in 7876 recipients of diabetic deceased donor kidney transplants from 2010 to 2019 in the OPTN/UNOS database. We determined the important characteristics of each assigned cluster and compared the post-transplant outcomes between the clusters. Consensus cluster analysis identified three clinically distinct clusters. Recipients in cluster 1 (n = 2903) were characterized by oldest age (64 ± 8 years), highest rate of comorbid diabetes mellitus (55%). They were more likely to receive kidney allografts from donors that were older (58 ± 6.3 years), had hypertension (89%), met expanded criteria donor (ECD) status (78%), had a high rate of cerebrovascular death (63%), and carried a high kidney donor profile index (KDPI). Recipients in cluster 2 (n = 687) were younger (49 ± 13 years) and all were re-transplant patients with higher panel reactive antibodies (PRA) (88 [IQR 46, 98]) who received kidneys from younger (44 ± 11 years), non-ECD deceased donors (88%) with low numbers of HLA mismatch (4 [IQR 2, 5]). The cluster 3 cohort was characterized by first-time kidney transplant recipients (100%) who received kidney allografts from younger (42 ± 11 years), non-ECD deceased donors (98%). Compared to cluster 3, cluster 1 had higher incidence of primary non-function, delayed graft function, patient death and death-censored graft failure, whereas cluster 2 had higher incidence of delayed graft function and death-censored graft failure but comparable primary non-function and patient death. An unsupervised machine learning approach characterized diabetic donor kidney transplant patients into three clinically distinct clusters with differing outcomes. Our data highlight opportunities to improve utilization of high KDPI kidneys coming from diabetic donors in recipients with survival-limiting comorbidities such as those observed in cluster 1.

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.

The use of continuous positive airway pressure in COPD-OSA overlap syndrome: A systematic review.

BACKGROUND: The co-occurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), known as COPD-OSA overlap syndrome, increases morbidity and mortality. The effectiveness of continuous positive airway pressure (CPAP) therapy, a commonly used treatment for OSA, in this patient population remains uncertain. Therefore, we conducted a systematic review to evaluate the efficacy of CPAP therapy in improving clinical outcomes. METHODS: We conducted a comprehensive systematic review to identify studies that evaluated the impact of CPAP therapy on COPD exacerbation, hospitalization, and mortality in patients with COPD-OSA overlap syndrome. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Statement and assessed the quality of each study using the Newcastle-Ottawa quality scale. RESULTS: From the initial 3184 articles identified, we reviewed 365 and included five in the systematic review. Our findings revealed that CPAP therapy improved clinical outcomes, including COPD exacerbation, COPD related hospitalization, and mortality in patients with COPD-OSA overlap syndrome. However, the definition of COPD and OSA varied across studies, and the definition of CPAP usage was not consistent. CONCLUSION: Our systematic review suggests that CPAP therapy is effective in improving outcomes in patients with COPD-OSA overlap syndrome. Nonetheless, further research is required to establish the efficacy of CPAP therapy by standardizing the definition of COPD, OSA, and CPAP usage.

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.