Global Trends in Kidney Stone Awareness: A Time Series Analysis from 2004-2023.

BACKGROUND: Despite the prevalence and incidence of kidney stones progressively increasing worldwide, public awareness of this condition remains unclear. Understanding trends of awareness can assist healthcare professionals and policymakers in planning and implementing targeted health interventions. This study investigated online search interest in "kidney stone" by analyzing Google Trends, focusing on stationarity of the trends and predicting future trends. METHODS: We performed time series analysis on worldwide Google monthly search data from January 2004 to November 2023. The Augmented Dickey-Fuller (ADF) test was used to assess the stationarity of the data, with a p-value below 0.05 indicating stationarity. Time series forecasting was performed using the autoregressive integrated moving average to predict future trends. RESULTS: The highest search interest for "kidney stone" (score 100) was in August 2022, while the lowest was in December 2007 (score 36). As of November 2023, search interest remained high, at 92. The ADF test was significant (p = 0.023), confirming data stationarity. The time series forecasting projected continued high public interest, likely reflecting ongoing concern and awareness. Notably, diverse regions such as Iran, the Philippines, Ecuador, the United States, and Nepal showed significant interest, suggesting widespread awareness of nephrolithiasis. CONCLUSION: This study highlighted that "kidney stone" is a consistently relevant health issue globally. The increase and stationarity of search trends, the forecasted sustained interest, and diverse regional interest emphasize the need for collaborative research and educational initiatives. This study's analysis serves as a valuable tool for shaping future healthcare policies and research directions in addressing nephrolithiasis related health challenges.

Empowering inclusivity: improving readability of living kidney donation information with ChatGPT.

Background: Addressing disparities in living kidney donation requires making information accessible across literacy levels, especially important given that the average American adult reads at an 8th-grade level. This study evaluated the effectiveness of ChatGPT, an advanced AI language model, in simplifying living kidney donation information to an 8th-grade reading level or below. Methods: We used ChatGPT versions 3.5 and 4.0 to modify 27 questions and answers from Donate Life America, a key resource on living kidney donation. We measured the readability of both original and modified texts using the Flesch-Kincaid formula. A paired t-test was conducted to assess changes in readability levels, and a statistical comparison between the two ChatGPT versions was performed. Results: Originally, the FAQs had an average reading level of 9.6 ± 1.9. Post-modification, ChatGPT 3.5 achieved an average readability level of 7.72 ± 1.85, while ChatGPT 4.0 reached 4.30 ± 1.71, both with a p-value <0.001 indicating significant reduction. ChatGPT 3.5 made 59.26% of answers readable below 8th-grade level, whereas ChatGPT 4.0 did so for 96.30% of the texts. The grade level range for modified answers was 3.4-11.3 for ChatGPT 3.5 and 1-8.1 for ChatGPT 4.0. Conclusion: Both ChatGPT 3.5 and 4.0 effectively lowered the readability grade levels of complex medical information, with ChatGPT 4.0 being more effective. This suggests ChatGPT's potential role in promoting diversity and equity in living kidney donation, indicating scope for further refinement in making medical information more accessible.

The impact of induction therapy on the risk of posttransplant lymphoproliferative disorder in adult kidney transplant recipients with donor-recipient serological Epstein-Barr virus mismatch.

Posttransplant lymphoproliferative disorder (PTLD) poses a significant concern in Epstein-Barr virus (EBV)-negative patients transplanted from EBV-positive donors (EBV R-/D+). Previous studies investigating the association between different induction agents and PTLD in these patients have yielded conflicting results. Using the Organ Procurement and Transplant Network database, we identified EBV R-/D+ patients >18 years of age who underwent kidney-alone transplants between 2016 and 2022 and compared the risk of PTLD with rabbit antithymocyte globulin (ATG), basiliximab, and alemtuzumab inductions. Among the 6620 patients included, 64.0% received ATG, 23.4% received basiliximab, and 12.6% received alemtuzumab. The overall incidence of PTLD was 2.5% over a median follow-up period of 2.9 years. Multivariable analysis demonstrated that the risk of PTLD was significantly higher with ATG and alemtuzumab compared with basiliximab (adjusted subdistribution hazard ratio [aSHR] = 1.98, 95% confidence interval [CI] 1.29-3.04, P = .002 for ATG and aSHR = 1.80, 95% CI 1.04-3.11, P = .04 for alemtuzumab). However, PTLD risk was comparable between ATG and alemtuzumab inductions (aSHR = 1.13, 95% CI 0.72-1.77, P = .61). Therefore, the risk of PTLD must be taken into consideration when selecting the most appropriate induction therapy for this patient population.

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.

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.

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.

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.

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.

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.

Distinct phenotypes of kidney transplant recipients aged 80 years or older in the USA by machine learning consensus clustering.

Objectives: This study aimed to identify distinct clusters of very elderly kidney transplant recipients aged ≥80 and assess clinical outcomes among these unique clusters. Design: Cohort study with machine learning (ML) consensus clustering approach. Setting and participants: All very elderly (age ≥80 at time of transplant) kidney transplant recipients in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database database from 2010 to 2019. Main outcome measures: Distinct clusters of very elderly kidney transplant recipients and their post-transplant outcomes including death-censored graft failure, overall mortality and acute allograft rejection among the assigned clusters. Results: Consensus cluster analysis was performed in 419 very elderly kidney transplant and identified three distinct clusters that best represented the clinical characteristics of very elderly kidney transplant recipients. Recipients in cluster 1 received standard Kidney Donor Profile Index (KDPI) non-extended criteria donor (ECD) kidneys from deceased donors. Recipients in cluster 2 received kidneys from older, hypertensive ECD deceased donors with a KDPI score ≥85%. Kidneys for cluster 2 patients had longer cold ischaemia time and the highest use of machine perfusion. Recipients in clusters 1 and 2 were more likely to be on dialysis at the time of transplant (88.3%, 89.4%). Recipients in cluster 3 were more likely to be preemptive (39%) or had a dialysis duration less than 1 year (24%). These recipients received living donor kidney transplants. Cluster 3 had the most favourable post-transplant outcomes. Compared with cluster 3, cluster 1 had comparable survival but higher death-censored graft failure, while cluster 2 had lower patient survival, higher death-censored graft failure and more acute rejection. Conclusions: Our study used an unsupervised ML approach to cluster very elderly kidney transplant recipients into three clinically unique clusters with distinct post-transplant outcomes. These findings from an ML clustering approach provide additional understanding towards individualised medicine and opportunities to improve care for very elderly kidney transplant recipients.

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.

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.

Distinct Subtypes of Hepatorenal Syndrome and Associated Outcomes as Identified by Machine Learning Consensus Clustering.

BACKGROUND: The utilization of multi-dimensional patient data to subtype hepatorenal syndrome (HRS) can individualize patient care. Machine learning (ML) consensus clustering may identify HRS subgroups with unique clinical profiles. In this study, we aim to identify clinically meaningful clusters of hospitalized patients for HRS using an unsupervised ML clustering approach. METHODS: Consensus clustering analysis was performed based on patient characteristics in 5564 patients primarily admitted for HRS in the National Inpatient Sample from 2003-2014 to identify clinically distinct HRS subgroups. We applied standardized mean difference to evaluate key subgroup features, and compared in-hospital mortality between assigned clusters. RESULTS: The algorithm revealed four best distinct HRS subgroups based on patient characteristics. Cluster 1 patients (n = 1617) were older, and more likely to have non-alcoholic fatty liver disease, cardiovascular comorbidities, hypertension, and diabetes. Cluster 2 patients (n = 1577) were younger and more likely to have hepatitis C, and less likely to have acute liver failure. Cluster 3 patients (n = 642) were younger, and more likely to have non-elective admission, acetaminophen overdose, acute liver failure, to develop in-hospital medical complications and organ system failure, and to require supporting therapies, including renal replacement therapy, and mechanical ventilation. Cluster 4 patients (n = 1728) were younger, and more likely to have alcoholic cirrhosis and to smoke. Thirty-three percent of patients died in hospital. In-hospital mortality was higher in cluster 1 (OR 1.53; 95% CI 1.31-1.79) and cluster 3 (OR 7.03; 95% CI 5.73-8.62), compared to cluster 2, while cluster 4 had comparable in-hospital mortality (OR 1.13; 95% CI 0.97-1.32). CONCLUSIONS: Consensus clustering analysis provides the pattern of clinical characteristics and clinically distinct HRS phenotypes with different outcomes.

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.

Periodic limb movements during sleep and risk of hypertension: A systematic review.

BACKGROUND: Several studies suggest an association between periodic limb movements during sleep (PLMS) and hypertension; however, a systematic evaluation of this relationship is lacking. METHODS: We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio, comparing the risk of hypertension in persons with PLMS (defined by the level of periodic limb movements per hour of sleep depended on individual studies) versus those without PLMS. After assessing heterogeneity and bias, the pooled risk ratio and 95% confidence intervals (CIs) were determined using a random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Out of 572 potentially relevant articles, six eligible studies were included in the data analysis. Studies (6 cross-sectional) included 8949 participants. The statistical heterogeneity of this study was insignificant, with an I2 of 0%. A funnel plot and Egger's regression asymmetry test showed no publication bias with P-value ≥0.05. The pooled risk ratio of hypertension in patients with PLMS was 1.26 (95% CI, 1.12-1.41). CONCLUSIONS: Our analysis demonstrates an increased hypertension risk among patients with PLMS. Prospective or interventional studies are needed to confirm this association.

Association of hypochloremia with mortality among patients requiring continuous renal replacement therapy.

BACKGROUND: Serum chloride derangement is common in critically ill patients requiring continuous renal replacement therapy (CRRT). We aimed to assess the association between serum chloride levels before and during CRRT with mortality. METHODS: This is a retrospective cohort study of critically ill patients receiving CRRT for acute kidney injury from December 2006 through November 2015 in a tertiary referral hospital in the United States. We used logistic regression to assess serum chloride before and mean serum chloride during CRRT as predictors for 90 days mortality after CRRT initiation. The normal reference range for serum chloride was 99-108 mmol/L. RESULTS: Of 1282 eligible patients, 25%, 50%, and 25% had hypochloremia, normochloremia, and hyperchloremia, respectively. The adjusted odds ratio for 90 days mortality in patients with hypochloremia before CRRT was 1.82 (95% CI 1.29-2.55). During CRRT, 4%, 70%, 26% of patients had mean serum chloride in the hypochloremia, normochloremia, and hyperchloremia range, respectively. The adjusted odds ratio for 90 days mortality in patients with mean serum chloride during CRRT in the hypochloremia range was 2.96 (95% CI 1.43-6.12). Hyperchloremia before and during CRRT was not associated with mortality. The greater serum chloride range during CRRT was associated with increased mortality (OR 1.29; 95% CI 1.13-1.47 per 5 mmol/L increase). CONCLUSION: Hypochloremia before and during CRRT is associated with higher mortality.

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.