Kidney Replacement Therapy Research Articles

Drug-Related Pyroglutamic Acidosis: Systematic Literature Review.

Background: Inborn errors of glutathione metabolism may cause high anion gap metabolic acidosis due to pyroglutamic acid accumulation. Since 1988, cases of this acidosis have been reported in individuals without these defects. Methods: Given the poorly characterized predisposing factors, presentation, management, and prognosis of acquired pyroglutamic acidosis, we conducted a systematic review using the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar databases. Results: A total of 131 cases were found. Most patients were females (79%), adults (92%) aged 51 years or older (66%) with pre-existing conditions (74%) such as undernutrition, alcohol-use disorder, or kidney disease, and had an ongoing infection (69%). The clinical features included diminished consciousness (60%), Kussmaul breathing (56%), and nausea or vomiting (27%). At least 92% of patients were on paracetamol therapy for >10 days at an appropriate dose, 32% on a β-lactamase-resistant penicillin, and 2.3% on vigabatrin. Besides severe anion gap acidosis, patients also presented with hypokalemia (24%) and kidney function deterioration (41%). Management involved discontinuing the offending drug (100%), bicarbonate (63%), acetylcysteine (42%), and acute kidney replacement therapy (18%). The fatality rate was 18%, which was higher without acetylcysteine (24%) compared to with it (11%). Conclusions: Acquired pyroglutamic acidosis is a rare, potentially fatal metabolic derangement, which usually occurs after paracetamol use, frequently combined with a β-lactamase-resistant penicillin or vigabatrin. This condition predominantly affects adults, especially women with factors like undernutrition, alcohol-use disorder, or kidney disease, often during infection. Increased awareness of this rare condition is necessary.

Acute kidney injury in coronavirus disease: a comparative study of the two waves in Brazil.

Magalhães et al. demonstrated that the incidence of acute kidney injury was high in hospitalized patients with COVID-19 and that the second wave was associated with greater severity; however, the mortality rates were similar between the two periods. This may reflect both the effectiveness of vaccines and the constant learning that frontline professionals gained throughout the pandemic to provide greater support to their patients. ◼ Renal involvement was frequent in patients with COVID-19 and related to worse outcomes. ◼ Diuretic use, mechanical ventilation, proteinuria, hematuria, age, and creatine phosphokinase and D-dimer levels were risk factors for acute kidney injury. ◼ Acute kidney injury, mechanical ventilation, elevated SOFA Score, and elevated ATN-ISS were associated with mortality. ◼ The second wave was associated with greater severity; however, the mortality rates were similar between the two periods. ◼ This may reflect the effectiveness of vaccines and the constant learning that frontline professionals gained throughout the pandemic. This study aimed to evaluate the incidence of acute kidney injury in hospitalized Brazilian patients with COVID-19 and identify the risk factors associated with its development and prognosis during the two waves of the disease. We performed a prospective cohort study of hospitalized patients with COVID-19 at a public university hospital in São Paulo from March 2020 to May 2021. Of 887 patients hospitalized with COVID-19, 54.6% were admitted to the intensive care unit. The incidence of acute kidney injury was 48.1%, and the overall mortality rate was 38.9%. Acute kidney replacement therapy was indicated for 58.8% of the patients. The factors associated with acute kidney injury were diuretic use (odds ratio [OR] 2.2, 95%CI= 1.2-4.1, p=0.01), mechanical ventilation (OR= 12.9, 95%CI= 4.3-38.2, p<0.0001), hematuria(OR= 2.02, 95%CI= 1.1-3.5, p<0.0001), chronic kidney disease (OR= 2.6, 95%CI= 1.2-5.5, p=0.009), age (OR= 1.03, 95%CI= 1.01-1.07, p=0.02), and elevated creatine phosphokinase (OR= 1.02, 95%CI= 1.01-1.07, p=0.02) and D-dimer levels (OR= 1.01, 95%CI= 1.01-1.09, p<0.0001). Mortality was higher among those with acute kidney injury (OR= 1.12, 95%CI= 1.02-2.05, p=0.01), elevated Sequential Organ Failure Assessment Scores (OR= 1.35, 95%CI= 1.1-1.6, p=0.007), elevated Acute Tubular Necrosis-Injury Severity Score (ATN-ISS; (OR= 96.4, 95%CI= 4.8-203.1, p<0.0001), and who received mechanical ventilation (OR= 12.9, 95%CI= 4.3-38.2, p<0.0001). During the second wave, the number of cases requiring mechanical ventilation (OR= 1.57, 95%CI= 1.01-2.3, p=0.026), with proteinuria (OR= 1.44, 95%CI= 1.01-2.1, p=0.04), and with higher ATN-ISS Scores (OR= 40.9, 95%CI= 1.7-48.1, p=0.04) was higher than that during the first wave. Acute kidney injury was frequent in hospitalized patients with COVID-19, and the second wave was associated with greater severity. However, mortality rates were similar between the two periods, which may reflect both the effectiveness of vaccines and the constant learning that frontline professionals gained throughout the pandemic to provide greater support to their patients. RBR-62y3h7.

Challenges and Potential Solutions for Cycloserine Dosing in Patients With Sepsis Undergoing Continuous Renal Replacement Therapy

Continuous kidney replacement therapy (CRRT) is a special form of dialysis, which has more significant advantages than traditional intermittent hemodialysis in treating critically ill patients. The impact of CRRT and disease complexity on drug clearance in critically ill patients has been reported in several studies, nevertheless, the pharmacokinetic changes of cycloserine in patients with sepsis undergoing CRRT have not been reported. Here, we report a case of a 52-year-old man with septic shock and severe multidrug-resistant tuberculosis who underwent anti-TB therapy. The patient's anti-TB regimen included linezolid, clofazimine, cycloserine, and bedaquiline. Following continuous administration for 14 days, the patient was treated with CRRT due to acid-base imbalance and acute renal failure. Blood samples were collected at 0, 2, 4, 6, 10, and 12 hours following cycloserine administration (CRRT was initiated two hours after administration). Changes in plasma concentration of cycloserine before and after the CRRT were measured. The peak concentration of cycloserine was 39.93 mg/L with a trough concentration of 7.90 mg/L, and the AUC0-12h was 294.36 mg•h/L. These findings firstly suggested that the pharmacokinetics of cycloserine may be influenced by sepsis and CRRT therapy, and cycloserine doses may need to be increased during CRRT therapy in patients with sepsis.

Cognitive impairment in patients on dialysis: can we prevent it?

Chronic kidney disease (CKD) is among the leading causes of morbidity and mortality as it affects more than 10% of the global adult population. Cognitive impairment has a positive correlation with the stage of CKD. It has been recorded in more than half of CKD patients undergoing kidney replacement therapy. The assessment of cognitive function in dialysis patients presents challenges due to various patient limitations. Such a common debilitating comorbidity of CKD has no approved treatment option, highlighting the importance of preventive measures and screening modalities. Erythropoietin therapy, exercise training, cognitive stimulation or behavioral therapies, alterations in dialysis frequency, dialysate cooling and kidney transplantation have been proposed as potential preventive and/or therapeutic options with variable efficiency at a clinical level. Regular screening, such as yearly, for cognitive impairment in maintenance dialysis patients is not only beneficial for timely and accurate diagnosis but also crucial for effective management and improved patient care. However, current practices face challenges, including the absence of validated tools specific for kidney failure and complications arising from patient conditions.

Diagnostic and Prognostic Utilities of Pancreatic Stone Protein in Patients with Suspected Sepsis.

Background/Objectives: Pancreatic stone protein (PSP) is an emerging biomarker of sepsis that is secreted from pancreas sensing remote organ damages. We explored the diagnostic and prognostic utilities of PSP in patients with suspected sepsis. Methods: In a total of 285 patients (suspected sepsis, n = 148; sepsis, n = 137), we compared PSP with procalcitonin (PCT) and sequential organ failure assessment (SOFA) score. Sepsis diagnoses were explored using receiver operating characteristic curve analyses with area under the curves (AUCs). Clinical outcomes (in-hospital mortality, 30-day mortality, and kidney replacement therapy [KRT]) were explored using the Kaplan-Meier method and a multivariate analysis with hazard ratio (HR). Results: PCT and PSP were comparable for sepsis diagnosis (AUC = 0.71-0.72, p < 0.001). The sepsis proportion was significantly higher when both biomarkers increased than when either one or both biomarkers did not increase (89.0% vs. 21.3-47.7%, p < 0.001). Each biomarker quartile (Q1-Q4) differed significantly according to their SOFA score (all p < 0.001). Compared with Q1, the Q2-Q4 groups showed worse clinical outcomes (p = 0.002-0.041). Both biomarkers added to the SOFA score showed higher HRs than the SOFA score alone (3.3-9.6 vs. 2.8-4.2, p < 0.001-0.011), with nearly 2.5-fold higher HR (9.6 vs. 4.2) for predicting KRT. Conclusions: Although PCT and PSP did not independently predict clinical outcomes in the multivariate analysis, PSP demonstrated diagnostic and prognostic utilities in patients with suspected sepsis, especially for predicting kidney dysfunction. PSP, alone or in combination with PCT, would be a valuable tool that can be added to clinical assessments.

The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) Trial

Intravenous fluids are an essential part of treatment in sepsis, but there remains clinical equipoise on which type of crystalloid fluids to use in sepsis. A previously reported sepsis subphenotype (ie, group D) has demonstrated a substantial mortality benefit from balanced crystalloids compared with normal saline. To test the hypothesis that targeting balanced crystalloids to patients with group D sepsis through an electronic health record (EHR) alert will reduce 30-day inpatient mortality. The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) trial is a parallel-group, multihospital, single-blind, pragmatic randomized clinical trial to be conducted at 6 hospitals in the Emory Healthcare system. Patients with suspicion of group D infection in whom a clinician initiates an order for normal saline in the emergency department (ED) or intensive care unit (ICU) will be randomized to usual care and intervention arms. An EHR alert that appears in the ED and ICUs to nudge clinicians to use balanced crystalloids instead of normal saline. The primary outcome is 30-day inpatient mortality. Secondary outcomes are ICU admission, in-hospital mortality, receipt of vasoactive drugs, receipt of new kidney replacement therapy, and receipt of mechanical ventilation (vasoactive drugs, kidney replacement therapy, and mechanical ventilation are counted if they occur after randomization and within the 30-day study period). Intention-to-treat analysis will be conducted. The PRECISE trial may be one of the first precision medicine trials of crystalloid fluids in sepsis. Using routine vital signs (temperature, heart rate, respiratory rate, and blood pressure), available even in low-resource settings, a validated machine learning algorithm will prospectively identify and enroll patients with group D sepsis who may have a substantial mortality reduction from used of balanced crystalloids compared with normal saline. On finalizing participant enrollment and analyzing the data, the study's findings will be shared with the public through publication in a peer-reviewed journal. With use of a validated machine learning algorithm, precision resuscitation in sepsis could fundamentally redefine international standards for intravenous fluid resuscitation. ClinicalTrials.gov Identifier: NCT06253585.

Correlation of bilirubin and toxic bile acids in critically ill patients with cholestatic liver dysfunction and adsorber application

Bilirubin is one of the most frequently used laboratory values to monitor critically ill patients with cholestatic liver dysfunction. Besides bilirubin, toxic bile acids (TBAs), which may cause severe organ damage, are typically elevated. A correlation between both parameters seems plausible, but data are lacking. The aim was to investigate whether there is a correlation between bilirubin and TBAs in patients’ blood and whether a compareable reduction can be observed during the use of the adsorber CytoSorb (CS). As part of the Cyto-SOLVE study (NCT04913298), 16 critically ill patients with cholestatic liver dysfunction, bilirubin concentration > 10 mg/dl, continuous kidney replacement therapy and CS-application were investigated. Bilirubin and TBA concentrations were measured from arterial blood at defined time points (before start, after 6 and 12 h). Relative reduction (RR) was calculated using the formula\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:{\\boldsymbol{RR}}\\:{\\boldsymbol{\\left(\\%\\right)}}=\\frac{{\\boldsymbol{concentration\\left(pre-post\\right)}}}{{\\boldsymbol{concentration\\left(pre\\right)}}}*{\\boldsymbol{100}}$$\\end{document}. A moderate to high correlation between bilirubin and TBA concentration at all defined timepoints (rstart=0.64, p = 0.008; r6h = 0.85, p < 0.001, r12h = 0.72, p = 0.002) was observed. In the first six hours of CS-application, a significant elimination of TBA (median TBA: 30.8→20.1µmol/l, p < 0.001) and bilirubin (median bilirubin: 17.1→11.9 mg/dl, p < 0.001) was observed. The median RR after 6 h was 26.1% and 39.8% for bilirubin and TBA, respectively. No further reduction was observed after 12 h (RRbilirubin: – 0.6%, RRTBA: 1.8%). There was an at least moderate correlation between bilirubin and TBA in patients with cholestatic liver dysfunction. Therefore, bilirubin seems to be a suitable surrogate parameter for TBA elimination during CytoSorb application.

Comprehensive biomarker assessment for predicting severe acute kidney injury and need of kidney replacement therapy in liver transplantation patients

Background Renal dysfunction is a common complication following liver transplantation (LT). This study aimed to determine whether a comprehensive assessment of kidney function using nineteen serum and urinary biomarkers (BMs) within the first 48 h post-LT could enhance the prediction of severe acute kidney injury (AKI) and the need of kidney replacement therapy (KRT) during the first postoperative week. Methods Blood and urine (U) samples were collected during the pre- and postoperative periods. Nineteen BMs were evaluated to assess kidney health in the first 48 h after LT. Classification and regression tree (CART) cross-validation identified key predictors to determine the best BM combination for predicting outcomes. Results Among 100 LT patients, 36 developed severe AKI, and 34 required KRT within the first postoperative week. Preoperative assessment of U neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP) predicted the need for KRT with 75% accuracy. The combined assessment of U osmolality (OSM), U kidney injury molecule 1 (KIM-1), and tissue inhibitor of metalloproteinase (TIMP-1) within 48 h post-LT predicted severe AKI with 80% accuracy. U-OSM alone, measured within 48 h post-LT, had an accuracy of 83% for predicting KRT need, outperforming any BM combination. Conclusions Combined BM analysis can accurately predict severe AKI and KRT needs in the perioperative period of LT. U-OSM alone proved to be an effective tool for monitoring the risk of severe AKI, available in most centers. Further studies are needed to assess its impact on AKI progression postoperatively. Registered at Clinical Trials (clinicaltrials.gov) in March 24th, 2014 by title ‘Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)’ and identifier NCT02095431.

Kynurenine Pathway after Kidney Transplantation: Friend or Foe?

Kidney transplantation significantly improves the survival of patients with end-stage kidney disease (ESKD) compared to other forms of kidney replacement therapy. However, kidney transplant recipients' outcomes are not fully satisfactory due to increased risk of cardiovascular diseases, infections, and malignancies. Immune-related complications remain the biggest challenge in the management of kidney graft recipients. Despite the broad spectrum of immunosuppressive agents available and more detailed methods used to monitor their effectiveness, chronic allograft nephropathy remains the most common cause of kidney graft rejection. The kynurenine (KYN) pathway is the main route of tryptophan (Trp) degradation, resulting in the production of a plethora of substances with ambiguous properties. Conversion of Trp to KYN by the enzyme indoleamine 2,3-dioxygenase (IDO) is the rate-limiting step determining the formation of the next agents from the KYN pathway. IDO activity, as well as the production of subsequent metabolites of the pathway, is highly dependent on the balance between pro- and anti-inflammatory conditions. Moreover, KYN pathway products themselves possess immunomodulating properties, e.g., modify the activity of IDO and control other immune-related processes. KYN metabolites were widely studied in neurological disorders but recently gained the attention of researchers in the context of immune-mediated diseases. Evidence that this route of Trp degradation may represent a peripheral tolerogenic pathway with significant implications for transplantation further fueled this interest. Our review aimed to present recent knowledge about the role of the KYN pathway in the pathogenesis, diagnosis, monitoring, and treatment of kidney transplant recipients' complications.

Low-Protein Diets, Malnutrition, and Bone Metabolism in Chronic Kidney Disease.

Chronic kidney disease (CKD) has a high prevalence worldwide, with increasing incidence in low- and middle-income countries, and is associated with high morbidity and mortality, particularly from cardiovascular disease. Protein-restricted diets are one of the most widely used non-pharmacological approaches to slow the progression of CKD and prevent associated metabolic abnormalities. However, some concerns have been raised about the long-term safety of these diets, particularly with regard to patients' nutritional status and bone and mineral disorders. Therefore, the aim of this article is to review the most recent scientific evidence on the relevance of using protein-restricted diets (with or without keto-analogue supplementation) and, in particular, their relationships with malnutrition and mineral and bone disorders in people with CKD without kidney replacement therapies. Although protein-restricted diets, especially when supplemented with keto-analogues and highly personalized and monitored, do not appear to be associated with malnutrition, research on their effects on bone and mineral disorders is scarce, deserving further investigation.

Bioimpedance-Guided Fluid Removal in Continuous Kidney Replacement Therapy: The VENUS Randomized Clinical Trial.

Ultrafiltration with continuous kidney replacement therapy (CKRT) can be used to manage fluid balance in critically ill patients with acute kidney injury (AKI). We aimed to assess whether bioimpedance analysis (BIA)-guided volume management was more efficacious than conventional management for achieving estimated euvolemia (e-euvolemia) in CKRT-treated patients. In a multi-center randomized controlled trial from July 2017 to July 2020, the patients with AKI requiring CKRT were eligible if the weight at the start of CKRT had increased by ≥5% compared to the weight at the time of admission, or total body water (TBW)/ height (H)2 ≥13 L/m2. We randomly assigned 208 patients to the control (conventional fluid management; N=103) and intervention groups (BIA-guided fluid management; N=105). Primary outcome was the proportion of attaining e-euvolemia seven days post-randomization. E-euvolemia was defined as the difference between TBW/H2 D7 and D0 was <-2.1 L/m2, or when TBW/H2 measured on D7 was <13 L/m2. The 28-, 60-, and 90-day mortality rate were secondary outcomes. The primary outcome occurred in 34 patients in the intervention group and 27 in the control group (47% versus 41%; P=0.50). The mean value of TBW/H2 measured on D7 was the same at 13.9 L/m2 in both groups. The differences between TBW/H2 D7 and D0 were -1.13 L/m2 in the intervention group and -1.08 L/m2 in the control group (P=0.84). Patients in the intervention group had a significantly higher proportion of reaching e-euvolemia on D1 than those in the control group (13% versus 4%, P=0.02). Adverse events did not differ significantly between the groups. BIA-guided volume management did not affect the proportion of reaching the estimated euvolemia at seven days of the start of CKRT. ClinicalTrials.gov, ID: NCT03330626 (Registered on 6 November 2017; Seven study participants were retrospectively registered; nonetheless, IRB approval of each institution was completed before study participant registration).

In-Center Hemodialysis Experiences Among Latinx Adults: A Qualitative Study

Latinx individuals are more likely to start and remain receiving in-center hemodialysis, over home dialysis, than non-Latinx White individuals. The objective of our study was to understand the drivers of sustained in-center dialysis and deterrents of switching to home dialysis use for Latinx individuals receiving in-center dialysis. This qualitative study used semistructured one-on-one interviews. Latinx adults receiving in-center hemodialysis therapy at 2 urban dialysis clinics in Denver, Colorado between November 2021 and March2023. In-center hemodialysis, Latinx ethnicity. Qualitative. Interviews were analyzed with thematic analysis using inductive coding. Theoretical framework development used principles of grounded theory. In total, 25 Latinx adults (10 [40%] female and 15 [60%] male) receiving in-center hemodialysis therapy participated. One theme demonstrated that Latinx individuals experienced hardship with in-center dialysis but used Latinx values to persevere: Psychosocial resilience using Latinx cultural values (faith and spiritual coping, belief in predestination and acceptance, optimism and positive attitude toward treatment, and positive relationships with health care professionals and peers). Two themes illustrate barriers to starting or switching to home dialysis: Insufficient knowledge of kidney replacement therapy (lack of awareness of kidney disease, lack of preparation for dialysis) and Barriers to patient-centered decision making in dialysis treatment (lack of peer perspective toguide dialysis decision making, fear and apprehension of home dialysis, lack of socioemotional support, perception of housing issues). Most participants were from the same geographic area and country of origin, and some may have been uninsured because of immigration status. As Latinx people are less likely to be treated with home dialysis modalities, this study offers important context as to what factors drove sustained in-center dialysis use for this population. Coping mechanisms that promoted resilience with in-center dialysis treatment motivated individuals to remain on in-center hemodialysis, and positive dialysis relationships in the dialysis center strengthened this experience. Switching to home dialysis is hindered by lack of knowledge as well as lack of patient-centered dialysis decision making. Understanding the drivers of sustained in-center hemodialysis use for Latinx individuals is important for future efforts at improving patient-centered education, framing conversations around modality choice, and care for this population.

Association between pre-heart transplant kidney function and post-transplant outcomes in Black and White adults.

It remains unknown whether estimated glomerular filtration rate (eGFR) using the refit Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without a term for race is associated with mortality and the need for kidney replacement therapy (KRT) differentially between Black and White heart transplant recipients. We studied 25,900 adults included in the Scientific Registry of Transplant Recipients. We classified recipients into six categories of eGFR (< 30, 30 to < 45, 45 to < 60, 60 to < 90, 90 to < 120, ≥ 120ml/min/1.73 m2) using the race-neutral CKD-EPI refit equation, and assessed survival with multivariable adjusted Cox proportional hazards regression. The association between pre-transplant race-neutral eGFR and mortality varied by race (Pinteraction = 0.006). Compared to White patients with an eGFR of 90-120ml/min/1.73 m2, the mortality rates were 57% (95% CI 1.25, 1.98), 29% (95% CI 1.11, 1.51), 34% (95% CI 1.19, 1.52), and 19% (95% CI 1.06, 1.33) higher in Black patients with an eGFR less than 30, 30-45, 45-60, and 60-90ml/min/1.73m2, respectively; and 53% (95% CI 1.28, 1.82), 49% (95% CI 1.33, 1.66), and 23% (95% CI 1.11, 1.35) higher among White patients with an eGFR less than 30, 30-45, and 45-60ml/min/1.73 m2, respectively. The association between pre-transplant eGFR and the need for KRT during follow-up was similar between Black and White patients (Pinteraction = 0.57). Worsening pre-transplant eGFR using the new race-neutral CKD-EPI refit equation was associated with a higher rate of post-heart transplant mortality and KRT in Black and White recipients. The racial disparity in post-heart transplant mortality was narrower in the setting of severe kidney dysfunction.

Automated peritoneal dialysis versus continuous ambulatory peritoneal dialysis for people with kidney failure.

Peritoneal dialysis (PD) is a home-based kidney replacement therapy (KRT) performed in people with kidney failure. PD can be performed by manual filling and draining of the abdominal cavity, i.e. continuous ambulatory PD (CAPD), or using a device connected to the PD catheter that is programmed to perform PD exchanges, i.e. automated PD (APD). APD is considered to have several advantages over CAPD, such as a lower incidence of peritonitis, fewer mechanical complications, and greater psychosocial acceptability. Acknowledging the increasing uptake of APD in incident and prevalent patients undergoing PD, it is important to re-evaluate the evidence on the comparative clinical and patient-reported outcomes of APD compared to CAPD. This is an update of a Cochrane review published in 2007. To compare clinical and patient-reported outcomes of APD to CAPD in people with kidney failure. In this update, we searched the Cochrane Kidney and Transplant Register of Studies until 29 August 2024. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. Randomised controlled trials (RCTs) comparing APD with CAPD in adults (≥ 18 years) with kidney failure. Two authors independently screened the search results and extracted data. Data synthesis was performed using random-effects meta-analyses, expressing effect estimates as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data and mean differences (MD) with 95% CIs for continuous data. Certainty in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Two RCTs (131 randomised people) comparing APD with CAPD were included in this update. One RCT had a follow-up of six months, and one RCT had a follow-up of 24 months. The risk of bias in the included studies was mostly low, except for the high risk of performance bias for subjective outcomes. The evidence is very uncertain about the effect of APD compared to CAPD on death, hospitalisations, PD-related peritonitis, change of dialysis modality, residual kidney function, health-related quality of life (HRQoL), overhydration, blood pressure, exit-site infections, tunnel infections, mechanical complications, PD catheter removal, or dialysis adequacy measures. These results were largely based on low to very low certainty evidence; hence, caution is warranted when drawing conclusions. Insufficient evidence exists to decide between APD and CAPD in kidney failure patients with regard to clinical and patient-reported outcomes. Therefore, current evidence is insufficient as a guide for clinical practice. Given that the sample sizes of existing studies are generally small with insufficient follow-up, there is a need for large-scale, multicentre studies. Future research should focus on possible differences between APD and CAPD in residual kidney function, euvolaemia, and patient-reported outcomes such as HRQoL, symptoms, patient satisfaction and life participation.

Evaluation and Management of Kidney Dysfunction in Advanced Heart Failure: A Scientific Statement From the American Heart Association.

Early identification of kidney dysfunction in patients with advanced heart failure is crucial for timely interventions. In addition to elevations in serum creatinine, kidney dysfunction encompasses inadequate maintenance of sodium and volume homeostasis, retention of uremic solutes, and disrupted endocrine functions. Hemodynamic derangements and maladaptive neurohormonal upregulations contribute to fluctuations in kidney indices and electrolytes that may recover with guideline-directed medical therapy. Quantifying the extent of underlying irreversible intrinsic kidney disease is crucial in predicting whether optimization of congestion and guideline-directed medical therapy can stabilize kidney function. This scientific statement focuses on clinical management of patients experiencing kidney dysfunction through the trajectory of advanced heart failure, with specific focus on (1) the conceptual framework for appropriate evaluation of kidney dysfunction within the context of clinical trajectories in advanced heart failure, including in the consideration of advanced heart failure therapies; (2) preoperative, perioperative, and postoperative approaches to evaluation and management of kidney disease for advanced surgical therapies (durable left ventricular assist device/heart transplantation) and kidney replacement therapies; and (3) the key concepts in palliative care and decision-making processes unique to individuals with concomitant advanced heart failure and kidney disease.

Effective management of necrotizing crescentic glomerulonephritis using an aggressive combination therapy including avacopan in a patient double-seropositive for anti-GBM antibodies and ANCA: a case report.

The prognosis of anti-glomerular basement membrane (anti-GBM) nephritis, often accompanied by the presence of antineutrophil cytoplasmic antibodies (ANCA), is poor, and even with aggressive therapeutic approaches, kidney replacement therapy (KRT) is typically required. Here, we present a case of necrotizing crescentic glomerulonephritis in a patient double-seropositive for anti-GBM antibodies and ANCA who successfully achieved dialysis independence following aggressive treatment, including avacopan. The patient was a 77-year-old woman with rapidly progressive glomerulonephritis and double seropositivity for myeloperoxidase-ANCA and anti-GBM antibodies. A kidney biopsy revealed diffuse cellular crescents with necrosis and immunoglobin (Ig)G1 and IgG3 positivity on immunofluorescence staining, leading to a histological diagnosis of anti-glomerular basement membrane nephritis. Our treatment approach involved a novel combination of glucocorticoids, rituximab, low-dose cyclophosphamide, and plasma exchange complemented by avacopan. Temporary hemodialysis was required, and the patient successfully discontinued dialysis after 12 sessions despite a poor histological prognosis. This case underscores the significance of considering aggressive therapeutic strategies, including avacopan, for severe anti-GBM nephritis, even in the absence of lung involvement, to avert the need for KRT.

Homelessness and Risk of End-Stage Kidney Disease and Death in Veterans With Chronic Kidney Disease

Adults experiencing homelessness in the US face numerous challenges, including the management of chronic kidney disease (CKD). The extent of a potentially greater risk of adverse health outcomes in the population with CKD experiencing homelessness has not been adequately explored. To evaluate the association between a history of homelessness and the risk of end-stage kidney disease (ESKD) and death among veterans with incident CKD. This retrospective cohort study was conducted between January 1, 2005, and December 31, 2017. Participants included veterans aged 18 years and older with incident stage 3 to 5 CKD utilizing the Veterans Health Administration health care network in the US. Patients were followed-up through December 31, 2018, for the occurrence of ESKD and death. Analyses were performed from September 2022 to October 2023. History of homelessness, based on utilization of homeless services in the Veterans Health Administration or International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Homelessness was measured during the 2-year baseline period prior to the index date of incident CKD. The primary outcomes were ESKD, based on initiation of kidney replacement therapy, and all-cause death. Adjusted hazard ratios (HRs) were calculated to compare veterans with a history of homelessness with those without a history of homelessness. Among 836 361 veterans, the largest proportion were aged 65 to 74 years (274 371 veterans [32.8%]) or 75 to 84 years (270 890 veterans [32.4%]), and 809 584 (96.8%) were male. A total of 26 037 veterans (3.1%) developed ESKD, and 359 991 (43.0%) died. Compared with veterans who had not experienced homelessness, those with a history of homelessness showed a significantly greater risk of ESKD (adjusted HR, 1.15; 95% CI, 1.10-1.20). A greater risk of all-cause death was also observed (HR, 1.48; 95% CI, 1.46-1.50). After further adjustment for body mass index, comorbidities, and medication use, results were attenuated for all-cause death (HR, 1.09; 95% CI, 1.07-1.11) and were no longer significant for ESKD (HR, 1.04; 95% CI, 0.99-1.09). In this cohort study of veterans with incident stage 3 to 5 CKD, a history of homelessness was significantly associated with a greater risk of ESKD and death, underscoring the role of housing as a social determinant of health.

Estimates of eskd risk and timely kidney replacement therapy education

BackgroundKidney replacement therapy (KRT) needs preparation and its timing is difficult to predict. Nephrologists’ predictions of kidney failure risk tend to be more pessimistic than the Kidney Failure Risk Equation (KFRE) predictions. We aimed to explore how physicians’ risk estimate related to referral to KRT education, vs. the objective calculated KFRE.MethodsProspective observational study of data collected in chronic kidney disease (CKD) clinics of the Veterans Affairs Medical Center San Diego and the University of California, San Diego. The study included 257 participants who were aged 18 years or older, English speaking, prevalent CKD clinic patients, with estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2 (MDRD equation). The exposure consisted of end stage kidney disease (ESKD) risk predictions. Nephrologists’ kidney failure risk estimations were assessed: “On a scale of 0–100%, without using any estimating equations, give your best estimate of the risk that this patient will need dialysis or a kidney transplant in 2 years.” KFRE was calculated using age, sex, eGFR, serum bicarbonate, albumin, calcium, phosphorus, urine albumin/creatinine ratio. The outcomes were the pattern of referral to KRT education (within 90 days of initial visit) and kidney failure evaluated by chart review. The population was divided into groups either by nephrologists’ predictions or by KFRE. Referral to KRT education was examined by group and sensitivity and specificity were calculated based on whether participants reached kidney failure at 2 years.ResultsA fifth were referred for education by 90 days of enrollment. Low risk patients by both estimates had low referral rates. In those with nephrologists’ predictions ≥ 15% (n = 137), sensitivity was 71% and specificity 76%. In those with KFRE ≥ 15% (n = 55), sensitivity was 85% and specificity 41%.ConclusionsAlthough nephrologists tend to overestimate patients’ kidney failure risk, they do not appear to act on this overestimation, as the rates of KRT education referrals are lower than expected when a nephrologist identifies a patient as high risk.Clinical Trial NumberNot applicable

Race- and Ethnicity-Related Disparities in Predialysis Nephrology Care, Kidney Disease Education, and Home Dialysis Utilization.

Pre-dialysis nephrology care and kidney replacement therapy (KRT)-directed education (KDE) are essential for incident home dialysis use. However, there are substantial disparities in these care parameters among patients with advanced CKD. The impact of these disparities on home dialysis underuse has not been examined. We analyzed the 2021 US Renal Database System to identify all adult kidney failure patients with over six months of pre-dialysis Medicare coverage initiating their first-ever dialysis between 2010 and 2019. We used a mediation analysis to dissect the attributable influence of disparities in pre-dialysis nephrology care and KDE on incident home dialysis use. Additionally, we conducted sensitivity analyses using graded levels of mediators and sustained impact on home dialysis outcomes. We identified 464,310 Medicare recipients: 428,301 using incenter hemodialysis and 35,416 using home dialysis as their first-ever dialysis modality during the study period. Compared to non-Hispanic White patients (n=294,914), adjusted odds ratio (95% confidence intervals) for receiving pre-dialysis nephrology care, KDE service, and incident home dialysis were 0.62(0.61, 0.64), 0.58(0.52, 0.63) and 0.76(0.73, 0.79) respectively among Hispanic individuals (n=49,734), and 0.74(0.73, 0.76), 0.84(0.79, 0.89), and 0.63(95%CI:0.61, 0.65) respectively among Black individuals (n=98,992). Mediation analyses showed that compared to non-Hispanic White individuals, lack of nephrology care explained 30% and 14% of incident home dialysis underuse among Hispanic and Black individuals, respectively (p<0.001). Sensitivity analyses using a longer duration of nephrology care and KDE services and the sustained impact on home dialysis underuse through the first-year post-kidney failure showed congruent and consolidating findings. Disparities in pre-dialysis nephrology care were significantly associated with lower home dialysis among Hispanic and Black individuals.

Denovo glomerulonephritis associated with IgA anti-GBM alloantibodies after kidney transplantation in Alport syndrome: A case report with diagnostic implications

Alport syndrome (AS) is a hereditary disorder caused by pathogenic variants in COL4A3, COL4A4, or COL4A5 genes expressing α3, α4, and α5 chains of basement membrane type IV collagen (COL4). The triple-helical α3α4α5(IV) protomer is a major component of the mature glomerular basement membrane (GBM) whose defective formation in AS leads to structural GBM disruption and kidney dysfunction, often resulting in kidney replacement therapy. A genetically intact renal graft exposes the immune system to a non-tolerized α3α4α5(IV) component and an alloimmune response eventually ensues. So far, only IgG alloantibodies reacting against COL4 have been reported in AS alloimmune responses. Here, we report alloimmune glomerulonephritis mediated by IgA antibodies against the non-collagenous C-terminal domain 1 of the α5(IV) chain in a patient with autosomal recessive AS following a second kidney transplantation. The patient presented a not previously described biallelic variant in the COL4A4 gene. Immunological, diagnostic, and clinical implications are discussed.