Advanced Chronic Kidney Disease Research Articles

Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease.

The potential influence of hyperuricemia on the genesis and progression of chronic kidney disease (CKD) remains controversial. In general, the correlation between blood levels of uric acid (UA) and the rate of progression of CKD is considered to be modest, if any, and the results of relevant trials oriented to disclose the effect of urate-lowering therapies on this outcome have been disappointing. Urinary excretion rates of UA could reflect more accurately the potential consequences of urate-related kidney injury. Using a cross-sectional design, we investigated the correlation between different estimators of the rates of urinary excretion of UA (total 24-hour excretion, mean urinary concentration, renal clearance and fractional excretion)(main study variables), on one side, and urinary levels of selected biomarkers of kidney injury and CKD progression (DKK3, KIM1, NGAL, interleukin 1b and MCP)(main outcome variables), in 120 patients with advanced CKD (mean glomerular filtration rate 21.5 mL/minute). We took into consideration essential demographic, clinical and analytic variables with a potential confounding effect on the explored correlations (control variables). Spearman's rho correlation and nonlinear generalized additive regression models (GAM) with p-splines smoothers were used for statistical analysis. Multivariate analysis disclosed independent correlations between urinary UA concentrations, clearances and fractional excretion rates (but not plasma UA or total 24-hour excretion rates of UA), on one side, and the scrutinized markers. These correlations were more consistent for DKK3 and NGAL than for the other biomarkers. Glomerular filtration rate, proteinuria and treatment with statins or RAA axis antagonists were other independent correlates of the main outcome variables. Our results support the hypothesis that urinary excretion rates of UA may represent a more accurate marker of UA-related kidney injury than plasma levels of this metabolite, in patients with advanced stages of CKD. Further, longitudinal studies will be necessary, to disclose the clinical significance of these findings.

Nephrology nurse practitioner model of care for chronic kidney disease: Lessons learned and informing future healthcare delivery

Background: Chronic kidney disease (CKD) affects more than 10% of the Australian adult population. It is a progressive disease that involves multiple physiological systems and is associated with several comorbid conditions, making it particularly burdensome on patients and the healthcare system. Alternative models of healthcare delivery are required to slow the progression to kidney failure. Aim: To describe the characteristics, patient profiles, and health outcomes of patients with CKD attending a nephrology nurse practitioner-led clinic. Design: Longitudinal health-service exploratory design. Methods: Following ethics approval, data were extracted from a chronic kidney disease registry for all consenting patients who attended a nephrology nurse practitioner-led clinic. Data were analysed descriptively. Results: Over the study period, 253 patients (122 male and 131 female) attended the clinic. The mean age was 70.27 ± 10.48 years, and at baseline most had either chronic kidney disease grade 3A (32.8%) or 3B (41.5%). For the majority of those who remained in the clinic, kidney function remained stable or slightly improved. A large proportion were within recommended target ranges for systolic (85.6%) and diastolic (98%) blood pressure although many had high BMI (mean 31.99 ± 6.47) and HbA1c (57.1%). Conclusion: The nephrology nurse practitioner-led clinic demonstrated effectiveness in addressing CKD targets for patients and provides an opportunity to transform traditional primary and specialist healthcare delivery. What is already known about the topic? Early intervention in chronic kidney disease (CKD) can slow or halt the progression of the disease, reducing long-term burden and healthcare costs. An integrated model of care including primary and specialist providers is considered optimal for the early detection and treatment of CKD. An integrated nephrology nurse practitioner model is an emerging model of care for CKD patients. However, studies investigating the cost-effectiveness, efficacy, and characteristics of this model compared to specialist or primary care in Australia are lacking. What this paper adds: This paper describes the characteristics and outcomes of a nephrology nurse practitioner-led outpatient clinic embedded within a multidisciplinary model of care. The majority of patients who remained in nephrology nurse practitioner care maintained recommended CKD targets. The findings provide evidence that nephrology nurse practitioners are able to manage patients with less advanced CKD grades who have comorbid conditions and other health risk-factors.

Catastrophic healthcare expenditure and caregiver burden in pediatric chronic kidney disease - a mixed methods study from a low resource setting.

Caregivers of children with chronic kidney disease (CKD) in low resource settings must provide complex medical care at home while being burdened by treatment costs often paid out-of-pocket. We hypothesize that caregiver burden in our low resource setting is greater than reported from high income countries and is associated with frequent catastrophic healthcare expenditure (CHE). We conducted a mixed-methods study of primary caregivers of children with advanced CKD (stage 3b-5) in our private-sector referral hospital in a low resource setting. We assessed caregiver burden using the Pediatric Renal Caregiver Burden Scale (PRCBS) and measured financial burden by calculating the proportion of caregivers who experienced CHE (monthly out-of-pocket healthcare expenditure exceeding 10% of total household monthly expenditure). We performed a qualitative reflexive thematic analysis of caregiver interviews to explore sources of burden. Of the 45 caregivers included, 35 (78%) had children on maintenance dialysis (25 PD, 10 HD). Mean caregiver burden score was 141 (± 17), greater than previously reported. On comparative analysis, PRCBS scores were higher among caregivers of children with kidney failure (p = 0.005), recent hospitalization (p = 0.03), non-earning caregivers (p = 0.02), caring for > 2 dependents (p = 0.009), and with high medical expenditure (p = 0.006). CHE occurred in 43 (96%) caregivers of whom 37 (82%) paid out-of-pocket. The main themes derived relating to caregiver burden were severe financial burden, mental stress and isolation, and perpetual burden of concern. Parents of children with CKD experienced severe caregiver burden with frequent CHE and relentless financial stress indicating an imminent need for social support interventions.

Closing the policy gap in diabetes care for individuals with advanced CKD

AbstractAimThe co‐existence of diabetes and CKD poses significant challenges to healthcare systems, current frameworks often inadequately address the complex needs of individuals with both conditions. Recognising these gaps, we introduced a new diabetes care model for people with advanced CKD in renal satellite units.This paper aims to evaluate this new diabetes model care.MethodWe conducted a prospective audit of a new integrated diabetes kidney care model. Data were presented as mean ± SD or counts/percentages, and pre‐ and post‐intervention differences were assessed using paired samples t‐tests.ResultsA total of 291 individuals with diabetes and advanced CKD stages 4 or 5, or undergoing haemodialysis, were included. The mean age was 68.5 (±13.0) years, 58.4% were males. Nearly half of the cohort had four or more long‐term conditions, while two‐thirds experienced mild/severe frailty. Only 6% were receiving ongoing diabetes care from secondary care diabetes specialist services. For patients with CKD not receiving dialysis, comparing pre‐ and post‐intervention, there were improvements in HbA1c (−13.0 mmol/mol, p < 0.001), SBP (−13.7 mm Hg, p < 0.0001), and weight (−2.9 kg, p < 0.0001). Furthermore, there was an increase in guideline‐directed therapies, with notable usage of SGLT2i (62.9%) and GLP1‐RA (28.4%), while access to diabetes technology increased to 89%.ConclusionThis new model of care resulted in improved metabolic outcomes, increased utilisation of guideline‐directed therapies, and enhanced access to diabetes technologies. However, the model also revealed significant unmet clinical needs in areas such as access to diabetes care, diabetes eye screening and foot surveillance.

Minimisation of dialysis risk in hospital patients with chronic kidney disease (MinDial): study protocol for a multicentre, stepped-wedge, cluster-randomised controlled trial

BackgroundEarly identification of patients with chronic kidney disease (CKD) and advancing kidney insufficiency, followed by specialist care, can decelerate the progression of the disease. However, awareness of the importance and possible consequences of kidney insufficiency is low among doctors and patients. Since kidney insufficiency can be asymptomatic even in higher stages, it is often not even known to those belonging to risk groups. This study aims to clarify whether, for hospitalised patients with advanced chronic kidney disease, a risk-based appointment with a nephrology specialist reduces disease progression.MethodsThe target population of the study is hospitalised CKD patients with an increased risk of end-stage renal disease (ESRD), more specifically with an ESRD risk of at least 9% in the next 5 years. This risk is estimated by the internationally validated Kidney Failure Risk Equation (KFRE). The intervention consists of a specific appointment with a nephrology specialist after the hospital stay, while control patients are discharged from the hospital as usual. Eight medical centres include participants according to a stepped-wedge design, with randomised sequential centre-wise crossover from recruiting patients into the control group to recruitment to the intervention. The estimated glomerular filtration rate (eGFR) is measured for each patient during the hospital stay and after 12 months within the regular care by the general practitioner. The difference in the change of the eGFR over this period is compared between the intervention and control groups and considered the primary endpoint.DiscussionThis study is designed to evaluate the effect of risk-based appointments with nephrology specialists for hospitalised CKD patients with an increased risk of end-stage renal disease. If the intervention is proven to be beneficial, it may be implemented in routine care. Limitations will be examined and discussed. The evaluation will include further endpoints such as non-guideline-compliant medication, economic considerations and interviews with contributing physicians to assess the acceptance and feasibility of the intervention.Trial registrationGerman Clinical Trials Register DRKS00029691. Registered on 12 September 2022.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study

BackgroundChronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries.MethodsA retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months.ResultsOut of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing.ConclusionOur findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Contrast-induced encephalopathy in patients with advanced chronic kidney disease: What the nephrologist needs to know

Contrast-induced encephalopathy is a neurological complication related to contrast used in endovascular procedures or computed tomography (CT). The main risk factors are arterial hypertension, diabetes mellitus, chronic kidney disease (CKD), hyperosmolar contrasts, the amount of infused contrast and its direct infusion in the posterior cerebral territory, or pathologies with blood-brain barrier damage. Symptomatology is non-specific and may present as altered level of consciousness, neurological focality or seizures. Diagnosis is done by exclusion after ischemic or hemorrhagic stroke has been ruled out; CT or MRI are useful for differentiation. Generally, it appears shortly after exposure and the symptoms lasts 48−72h with complete recovery, although cases with persistence of symptoms or longer duration have been described. Treatment consists of monitoring, supportive measures and kidney replacement therapy (KRT) with hemodialysis (HD) in patients in chronic KRT program. It is important for the nephrologist to be aware of this entity given the susceptibility of the patient on HD as well as its potential therapeutic role in these patients.

Kidney transplant outcomes in children with simultaneous versus sequential heart-kidney transplants.

Heart transplant recipients frequently require kidney transplantation for concomitant advanced chronic kidney disease. Data on simultaneous (heart and kidney transplants performed simultaneously) versus sequential (heart transplant performed before kidney) heart-kidney transplants in children are limited. Herein, we compare kidney transplant outcomes between the two groups. We used the Scientific Registry of Transplant Recipients to identify all pediatric (age <21 years) heart transplant recipients who also received a kidney transplant within 10 years of the heart transplant. We divided the study cohort into simultaneous heart-kidney and sequential heart-kidney recipients. We compared patient and death-censored graft survival using the Cox regression, adjusting for age at kidney transplant, sex, race, pre-transplant dialysis, donor type, and prior kidney transplant. We evaluated delayed graft function (defined as dialysis within the first week posttransplant) using logistic regression. Our analysis cohort included 165 recipients (86 simultaneous and 79 sequential). The incidence of delayed graft function was higher in simultaneous recipients (22.4 vs. 7.7%, p=0.017), but the difference lost statistical significance on multivariable analysis. We found no difference in patient survival (aHR 0.97; 95% CI 0.39, 2.41; p=0.95) after kidney transplant but higher death-censored kidney graft survival in sequential heart-kidney recipients compared with simultaneous heart-kidney recipients (aHR 4.26; 95% CI 1.21, 14.9; p=0.02). Sequential heart-kidney transplants are associated with higher death-censored kidney allograft survival in children compared with simultaneous heart-kidney transplants.

Advanced CKD detection through optimized metaheuristic modeling in healthcare informatics

Data categorization is a top concern in medical data to predict and detect illnesses; thus, it is applied in modern healthcare informatics. In modern informatics, machine learning and deep learning models have enjoyed great attention for categorizing medical data and improving illness detection. However, the existing techniques, such as features with high dimensionality, computational complexity, and long-term execution duration, raise fundamental problems. This study presents a novel classification model employing metaheuristic methods to maximize efficient positives on Chronic Kidney Disease diagnosis. The medical data is initially massively pre-processed, where the data is purified with various mechanisms, including missing values resolution, data transformation, and the employment of normalization procedures. The focus of such processes is to leverage the handling of the missing values and prepare the data for deep analysis. We adopt the Binary Grey Wolf Optimization method, a reliable subset selection feature using metaheuristics. This operation is aimed at improving illness prediction accuracy. In the classification step, the model adopts the Extreme Learning Machine with hidden nodes through data optimization to predict the presence of CKD. The complete classifier evaluation employs established measures, including recall, specificity, kappa, F-score, and accuracy, in addition to the feature selection. Data related to the study show that the proposed approach records high levels of accuracy, which is better than the existing models.

Thyroid Hormone Profile in Advanced Chronic Kidney Disease

Thyroid Hormone Profile in Advanced Chronic Kidney Disease

Urinary cytokeratin 20 as a predictor for chronic kidney disease following acute kidney injury.

BACKGROUNDIdentifying patients with acute kidney injury (AKI) at high risk of chronic kidney disease (CKD) progression remains a challenge.METHODSKidney transcriptome sequencing was applied to identify the top upregulated genes in mice with AKI. The product of the top-ranking gene was identified in tubular cells and urine in mouse and human AKI. Two cohorts of patients with prehospitalization estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 who survived over 90 days after AKI were used to derive and validate the predictive models. AKI-CKD progression was defined as eGFR < 60 mL/min/1.73 m2 and with minimum 25% reduction from baseline 90 days after AKI in patients with prehospitalization eGFR ≥ 60 mL/min/1.73 m2. AKI-advanced CKD was defined as eGFR < 30 mL/min/1.73 m2 90 days after AKI in those with prehospitalization eGFR 45-59 mL/min/1.73 m2.RESULTSKidney cytokeratin 20 (CK20) was upregulated in injured proximal tubular cells and detectable in urine within 7 days after AKI. High concentrations of urinary CK20 (uCK20) were independently associated with the severity of histological AKI and the risk of AKI-CKD progression. In the Test set, the AUC of uCK20 for predicting AKI-CKD was 0.80, outperforming reported biomarkers for predicting AKI. Adding uCK20 to clinical variables improved the ability to predict AKI-CKD progression, with an AUC of 0.90, and improved the risk reclassification.CONCLUSIONThese findings highlight uCK20 as a useful predictor for AKI-CKD progression and may provide a tool to identify patients at high risk of CKD following AKI.FUNDINGNational Natural Science Foundation of China, National Key R&D Program of China, 111 Plan, Guangdong Key R&D Program.

The impact of the OPTN policy change on patients with a durable left ventricular assist device and chronic kidney disease: Analysis of the UNOS database.

The Organ Procurement and Transplantation Network (OPTN) implemented modifications in 2018 to the adult heart transplant allocation system to better stratify the most medically urgent transplant candidates. We evaluated the impact of these changes on patients supported by a durable left ventricular assist device (LVAD) with chronic kidney disease (CKD). To evaluate the impact of the OPTN policy change on patients supported by durable left ventricular assist devices (LVAD) with chronic kidney disease (CKD). We performed an analysis of patients from the United Network of Organ Sharing Database supported by durable LVAD listed for a heart transplant (HT) between October 17, 2016 and September 30, 2021. Patients were divided into two groups: pre- and postpolicy, depending on whether they were listed on or prior to October 17, 2018. Patients who were on dialysis prior to surgery or discharge were excluded from the analysis. Patients with simultaneous heart and kidney transplants were excluded. Patients who were listed for transplant prepolicy change but transplanted postpolicy change were excluded. This cohort was then subdivided into degrees of CKD based on estimated glomerular filtration rate (eGFR), which resulted in 678 patients (23.7%) in Stage 1 (GFR ≥89.499) (Prepolicy: 345, Postpolicy: 333), 1233 (43.1%) in Stage 2 (89.499 > GFR ≥ 59.499) (Prepolicy: 618, Postpolicy: 615), 613 (21.4%) in Stage 3a (59.499 > GFR ≥ 44.499) (Prepolicy: 291, Postpolicy: 322), 294 (10.3%) in Stage 3b (44.499 > GFR ≥ 29.499) (Prepolicy: 143, Postpolicy: 151), 36 (1.3%) in Stage 4 (29.499 > GFR ≥ 15) (Prepolicy: 21, Postpolicy: 15), and 9 (0.3%) in Stage 5 (15 > GFR) (Prepolicy: 4, Postpolicy: 5). The primary outcome was 1-year and 2-year post-HT survival. There were 2863 patients who met the study criteria (1422 prepolicy, 1441 postpolicy). Overall survival, regardless of CKD stage, was lower following the policy change (p < 0.01). There was a similar risk of primary graft failure (PGF) in the pre- and postpolicy period (1.8% vs. 1.2%, p = 0.26). 1-year overall survival was 93% (91, 94) and 89% (87, 91) in the pre- and postpolicy periods, respectively. 2-year overall survival was 89% (88, 91) and 85% (82, 87) in the pre- and postpolicy periods, respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 1 -year survival was 93% (91, 95), 92% (90,93), 89% (86, 91), 89% (86, 93), 80% (68, 94), and 100% (100, 100), respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 2-year survival was 91% (88, 93), 88% (86, 90), 84% (81, 88), 84% (80, 89), 73% (59, 90), and 100% (100, 100), respectively. Patients with CKD 1 and 2 had better survival compared to those with CKD 3 (p < 0.01) and CKD 4 and 5 (p = 0.03) in the pre- and postpolicy periods. Patients with CKD 3 did not have a survival advantage over those with CKD 4 and 5 (p = 0.25). On cox regression analysis, advancing degrees of CKD were associated with an increased risk of mortality. Patients with LVAD support had decreased overall survival after the OPTN policy change. Patients with more advanced CKD had lower survival than patients without advanced CKD, though they were not impacted by the OPTN policy change.

Derivation and Validation of a Machine Learning Model for the Prevention of Unplanned Dialysis.

Approximately half of all patients with advanced chronic kidney disease (CKD) who progress to kidney failure initiate dialysis in an unplanned fashion which is associated with high morbidity, mortality, and healthcare costs. A novel prediction model designed to identify advanced CKD patients who are at high risk for developing kidney failure over short time frames (6-12 months) may help reduce the rates of unplanned dialysis and improve the quality of transitions from CKD to kidney failure. We performed a retrospective study employing machine learning random forest algorithms incorporating routinely collected age and sex data along with time-varying trends in laboratory measurements to derive and validate six- and 12-month kidney failure risk prediction models in the advanced CKD population. The models were comprehensively characterized in three independent cohorts in Ontario, Canada - derived in a cohort of 1,849 consecutive advanced CKD patients (mean [standard deviation] age 66 [15] years, eGFR 19 [7] mL/min/1.73m2), and validated in two external advanced CKD cohorts (n=1,356; age 69 [14] years, eGFR 22 [7] mL/min/1.73m2). Across all cohorts, 55% of patients experienced kidney failure, of which 35% involved unplanned dialysis. The six- and 12-month models demonstrated excellent discrimination with area under the receiver operating characteristic curve of 0.88 (95%CI: 0.87-0.89) and 0.87 (95%CI: 0.86-0.87) along with high probabilistic accuracy with Brier scores of 0.10 (95%CI 0.09-0.10) and 0.14 (95%CI 0.13-0.14), respectively. The models were also well-calibrated and delivered timely alerts on a significant number of patients who ultimately initiated dialysis in an unplanned fashion. Similar results were found upon external validation testing. These machine-learning models using routinely collected patient data accurately predict near-future kidney failure risk among the advanced CKD population, and retrospectively deliver advanced warning on a substantial proportion of unplanned dialysis events. Optimal implementation strategies still need to be elucidated.

Advanced chronic kidney disease increases complications in anterior cervical discectomies with fusions: An analysis of 75,508 patients

BackgroundAlthough anterior cervical discectomy and fusion (ACDF) procedures for cervical spine disease have been increasing amid a growing population of patients with kidney dysfunction, there is a scarcity of literature focusing on kidney dysfunction as a risk-factor for post-operative ACDF complications. The purpose is to evaluate the differential impact of kidney dysfunction on perioperative outcomes including surgical and medical complications, extended length of hospital stay (LOS), and death within 30 days following ACDF. Patient SampleThis was a retrospective cohort study of prospectively collected data using the American College of Surgeons National Surgical Quality Improvement Program database to identify patients who had undergone an elective ACDF procedure between 2011-2021 using Current Procedural Terminology code 22551. Patients were categorized into five cohorts based on eGFR according to the “Kidney Disease: Improving Global Outcomes” Classification: values of: ≥ 90(reference cohort), 60-89 (G2), 30-59 (G3), 15-29 (G4), and <15 (G5). One-way ANOVA for continuous variables and chi-square tests for categorical variables were used to identify differences in perioperative variables between the five groups. Multivariable logistic regression analysis assessed the effect of kidney dysfunction on post-operative surgical outcomes. Significance was defined as p <0.05. Results75,508 ACDF patients were included, of who 57,480 were G1, 15,186 were G2, 2,192 were G3, 312 were G4, and 338 were G5. G4 and G5 independently increased the risk of medical complications (OR: 1.893, 95% CI [1.296-2.705]; OR: 2.241, 95% CI [1.222-3.964]) and blood transfusion. Only G5 independently increased the risk for extended LOS (OR: 2.410, 95% CI [1.281-4.371], p= 0.005). ConclusionHigh grade CKD is an independent risk factor for medical complications, extended hospital LOS, and blood transfusions following ACDF, underscoring the importance of risk stratification to optimize perioperative management and reduce the burden of complications and healthcare costs. Conversely, low grade CKD does not increase the risk of complications in ACDF.

#1230 Comparative analysis of vitamin D status between patients with advanced chronic kidney disease and those on dialysis

Abstract Background and Aims Decreased plasma concentration of 1,25-dihydroxy-vitamin D3 or calcitriol, the most active biological form of vitamin D3, in patients with advanced chronic kidney disease (ACKD) and on dialysis, is almost universal. In addition, 25-50% of these patients also have decreased levels of 25-hydroxy-vitamin D3 (calcidiol or calcifediol). The main cause of calcitriol deficiency is decreased hydroxylation in the kidney, both due to intrinsic renal damage and hyperphosphataemia. Calcifediol deficiency is directly related to decreased intake and sun exposure. We already know that this calcifediol deficiency is associated with ACKD, but we do not know if there are differences between ACKD patients and dialysis patients. The aim of this study is to analyse whether there are differences in calcifediol levels between ACKD and dialysis patients. Method An observational, analytical, ambispective, multicentre, analytical study was carried out with the participation of five Centres in Spain, under conditions of routine clinical practice. As study subjects, we included patients with ACKD and on haemodialysis from the University Hospitals of Virgen del Rocío, La Paz and Nuestra Señora de Candelaria, and the dialysis centres: Avericum, Quironsalud Tenerife. We selected demographic variables and also included serum levels of calcifediol, calcium, phosphorus and PTH; treatment with: phosphorus binders, erythropoietin synthesis analogues (ESA), ferrotherapy, calcimimetics, active vitamin D, native vitamin D. Data are organised and analysed with SPSS Statistics v22. In all analyses, the significance level is set for a P value &amp;lt; 0.05. Multivariate logistic regression analysis was also performed. Results A total of 161 patients were included. Both groups were homogeneous in the presence of diabetes, calcium levels and treatment with iron, native vitamin D, active vitamin D and calcimimetics. There were significant differences in sex, age, phosphorus levels, PTH, phosphate binders, ESA treatment. There are no significant differences in calcifediol levels or vitamin D status between the two comparison groups. Conclusion In our study, within a general context of hypovitaminosis D, patients with ACKD have a vitamin D status similar to dialysis patients.

#1313 Dicumarinics and the direct thrombin or factor Xa inhibitors (NOAs) their usefulness in advanced chronic renal disease

Abstract Background and Aims Our population with advanced chronic kidney disease (ACKD), is more prone to thrombotic and hemorrhagic processes so the indication of anticoagulation before the appearance of atrial fibrillation (AF) is complex. Since AF is the most common cardiac arrhythmia, its main complications are thromboembolism and stroke. New treatments are being developed, such as the new oral anticoagulants (NOAs), but their safety in ACKD is still uncertain. To see anticoagulation needs, safety and major adverse effects (major or minor bleeding) in population with ACKD and taking dicumarinics or NOAs. Method Retrospective study of 234 patients followed in our ACKD practice, at least two revisions, with a mean follow-up 25.5 months, in which we recorded cause of anticoagulation, type and major adverse effects. Results 26% of patients have indication for anticoagulation (66 patients), of which 55 remain anticoagulated during follow-up (45% Dicumarinics, 44% NOAs). The indication for anticoagulation was 23% AF (56 patients) and 3% mechanical prostheses (7 patients). Table 1 shows the characteristics of the overall population and the comparison between anticoagulated patients with different types of anticoagulation and non-anticoagulated patients. Non-anticoagulated patients are younger and have less ischemic heart disease, with no differences in the non-anticoagulated population. Throughout follow-up, we found a higher incidence of bleeding with NOAs (compared to the rest) and higher mortality in patients with dicumarinics (compared to the rest). There were no differences in age, sex and ischemic heart disease between the two anticoagulant treatments. Conclusion Our CKD population has a high need for anticoagulation but also a high risk of bleeding. NOAs can be used in ACKD although they are associated with a higher incidence of bleeding than dicumarinics but lower mortality. More studies are needed to conclude which is the best approach for these patients.

#2576 Effect of dialysis versus conservative care on all-cause mortality in older patients with advanced CKD: nationwide Swedish cohort study

Abstract Background and Aims Conservative care is emerging as an alternative to dialysis in older patients with advanced chronic kidney disease (CKD). However, high-quality evidence comparing the effect of dialysis versus conservative care on patient survival is lacking. Previous observational studies suffered from avoidable biases, such as immortal time bias and lead time bias, and adjusted for limited confounders. This study aimed to assess the effects of dialysis versus conservative care on mortality in older patients with advanced CKD. Method The target trial emulation framework was used to design and analyze this observational study. We conducted a nationwide observational cohort study using data from the Swedish Renal Registry between 2007-2021. We included all nephrologist-referred patients with eGFR &amp;lt; 20 ml/min/1.73 m2 who had a registered decision for dialysis or conservative care. Eligible patients were required to be ≥ 65 years with a Davies Comorbidity Score ≥ 2 or ≥ 80 years. The primary endpoint was 5-year all-cause mortality. Inverse probability of treatment weighting was used to adjust for 50 baseline confounders, including demographics, comorbidities, medication use, blood pressure, laboratory measurements, hospitalizations, and calendar year. Patients in the non-overlapping region of the propensity score distribution were excluded since they had an absolute indication for dialysis or conservative care. Cox proportional hazards regression was used to estimate intention-to-treat hazard ratios (HRs) with 95% confidence intervals (CIs), and the Kaplan-Meier estimator was used to estimate absolute risks. Additionally, we calculated the 5-year restricted mean survival times (RMST) and the 5-year RMST difference between dialysis and conservative care arms. To test the robustness and consistency of our main results, we performed a subgroup analysis in patients aged ≥80. Results Of 2834 eligible patients, 1903 had a registered choice for dialysis and 931 for conservative care. The median age was 81 years, 36.1% were female and median eGFR was 13.1 ml/min/1.73 m2. During the 5-year follow-up period, 29 conservative care patients started dialysis and 430 patients died before starting dialysis. After weighting, all confounders were balanced (standardized mean difference &amp;lt; 0.10). Compared to dialysis, conservative care was associated with a higher absolute 5-year risk of death (91.8% vs. 74.1%), corresponding with an absolute risk difference of 17.6% (95% CI 13.3%-21.9%) (Fig. 1). The adjusted hazard ratio for conservative care vs. dialysis was 2.3 (95% CI 2.0-2.6). The 5-year restricted mean survival times were 34.8 (95% CI 33.2-37.3) months for dialysis and 21.5 (95% CI 19.4-23.6) months for conservative care groups. The 5-year RMST difference was 13.3 months (95% CI 10.8-16.6), meaning that dialysis patients would live on average 13.3 months longer over a 5-year follow-up period than conservative care patients (Table 1). The results were consistent among people ≥ 80 years (adjusted HR 2.2, 95% CI 1.9-2.5; 5-year RMST difference 9.4 months, 95% CI 7.2-13.9). Conclusion In older patients with advanced CKD under nephrologist care, conservative care was associated with a higher risk of mortality than dialysis. These findings could improve the shared decision-making process with patients on the choice of kidney failure treatment.

#430 Risk factors for major bleeding in patients with non-valvular atrial fibrillation and CKD G3-G5D on oral anticoagulants

Abstract Background and Aims We previously published a register-based cohort study comparing direct oral anticoagulants (DOAC) and warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) GFR category 3-5 (G3-G5) including patients on dialysis (G5D) (1). This study showed that DOAC was associated with lower risk of major bleeding but similar risk of ischemic stroke compared to warfarin. Bleedings were however more common than strokes, especially in advanced CKD (G5-G5D) where the risk of major bleeding was up to 10 times higher than the risk of stroke. Subsequently, the stroke- and bleeding risk in patients with AF and advanced CKD must be carefully evaluated when deciding on whether to prescribe oral anticoagulants (OAC) or not. Available stroke- and bleeding scoring systems do not perform well in CKD (2, 3). This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-G5D. Method Data was collected from high quality Swedish healthcare registers including Swedish Renal Registry and Auricula, a register for atrial fibrillation and oral anticoagulants and the National Patient Register. Patients with eGFR&amp;lt;60 ml/min/1.73m2 and non-valvular atrial fibrillation and either DOAC (apixaban, rivaroxaban, edoxaban and dabigatran) or warfarin treatment between 2009-2018 where included. DOAC treatment periods were collected from the Swedish Prescribed Drug Register (PDR), starting from dispense date covering assumed standard pill use and an additional 30 days grace period. Warfarin treatment periods were collected directly from Auricula. An undefined treatment was a period of no OAC or a period of warfarin from PDR not matching a treatment period in Auricula. All periods of OAC treatment with either DOAC or warfarin were evaluated in a multivariate Cox regression model regarding the risk of major bleeding requiring inpatient care. Time-dependent covariates adjusted for in the model were age, sex, years from study start, GFR category, congestive heart failure, diabetes mellitus, hypertension, excessive alcohol use, liver disease, vascular disease, previous gastrointestinal bleeding, intracranial bleeding, other bleeding, ischemic stroke/ transient ischemic attack (TIA), myocardial infarction, PCI and exposures (DOAC, warfarin and periods of undefined treatment). Results Of 2453 included patients, 59% had warfarin (time in therapeutic range, TTR, 67%) and 41% DOAC at inclusion, predominantly apixaban (81% of DOAC users). The mean age was 77 years, 28.3% had G3, 45.4% G4, 9.1% G5 and 17.3% G5D (Table 1). Mean follow up was 2.2 years. During follow up 424 major bleedings occurred yielding 8.9 (95% confidence interval 8.1-9.8) bleedings per 100 patient-years. Table 2 shows effect estimates of each covariate on the outcome major bleeding. Covariates, besides warfarin, associated with increased risk of major bleeding were GFR category, G5/5D versus G3, hazard ratio 1.92 (95% CI 1.43-2.56), previous GI bleeding, 1.77 (1.39-2.25) and previous other bleeding 1.33 (1.09-1.62). Other factors associated with major bleeding were congestive heart failure 1.36 (1.11-1.68), male sex 1.28 (1.03-1.60) and vascular disease, 1.35 (1.01-1.79). Conclusion Patients with non-valvular atrial fibrillation and CKD G3-G5D on OAC are at high risk of major bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding, this reiterates the results of many previous studies. The present study also shows an association between OAC-associated major bleeding in CKD and male sex, congestive heart failure and vascular disease. Similar associations have been showed in non-CKD cohorts previously but is inadequately studied in CKD. Knowledge about risk factors for major bleeding on OAC in advanced CKD is essential when deciding on when to anticoagulate or not.

#356 Low-dose thiazide/fludrocortisone use in advanced CKD can rapidly improve potassium-elevated metabolic acidosis with renal and cardiovascular safety

Abstract Background and Aims Advanced chronic kidney disease (CKD) is often complicated by metabolic acidosis(MA) with elevated serum potassium(K). MA is a risk factor for CKD progression, and elevated serum K forces dietary K restriction, which is also undesirable in CKD, stalling the use and escalation of renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium bicarbonate(SB) and K binders, which are not well tolerated due to gastrointestinal symptoms, are often used to correct MA and hyperkalemia. On the other hand, the concurrent use of thiazide and fludrocortisone to promote urinary excretion of K and hydrogen ions has been reported in the type IV renal tubular acidosis, but its efficacy and safety in advanced CKD is unclear. Method This single-center, retrospective, observational study included CKDG3b-G5 outpatients with MA([HCO3−]&amp;lt;22 mM) and elevated K (serum [K]≥ 5.0 mEq/L) at our center. A total of 59 patients were selected, excluding those who had already been prepared for renal replacement therapy at the start of treatment. Patients who continued to receive trichlormethiazide (1 mg, at 1-3 day intervals) plus fludrocortisone (0.1 mg, at 1-3 day intervals) (low-T/F group, N = 10) or SB(0.5 g-5 g/day) alone (SB group, N = 49) were followed up until 2 years after the start of treatment and the two groups were compared. Background factors including age, sex, cause of CKD, estimated glomerular filtration rate (eGFR), CKD stage, urinary protein(g/gCr),serum [K]/ [HCO3−]/[Na]/[CL]/albumin/phosphate, hemoglobin levels, and the use of RAASi/K binders/diuretics were investigated. Efficacy and safety comparisons between the two groups were evaluated based on changes in serum [HCO3−]and [K] levels before and after starting of treatment (at 2, 6, 12, 18, and 24 months), percentage of patients achieving [HCO3−] ≥22 mM, change in eGFR, incidence of renal events (&amp;gt;30% reduction in eGFR or renal replacement therapy), the incidence of cardiovascular events, and the incidence of treatment-modified events such as initiation or increase of antihypertensive, K-binding, and uric acid-lowering agents. Results In all 59 subjects, the mean age was 72.0±11.7 years, 81% were male, mean eGFR was 19.6 ± 7.2 mL/min/1.73 m2, CKDG4/5 account for 92% (G4 60%/G5 32%), primary disease was diabetic nephropathy 30%, nephrosclerosis 43%, RAASi use 68%, mean [K] was 5.5 ± 0.4 mEq/L and mean [HCO3−] was 18.1 ± 2.2 mM. The low-T/F group consisted of patients who switched due to prior SB intolerance or in whom SB was ineffective, and included 5 patients who received concomitant SB. Comparison of background factors showed no significant difference between the two groups. The changes in the serum [HCO3−] and [K] levels 2 months after starting the treatment were significantly larger in the low-T/F group compared with the SB group ([K]after - [K]before (mEq/L):median −1.2, IQR-1.6 to −0.48 vs −0.57, −0.80 to −0.10, p = 0.036; {[K]after -[K]before}×100/[K]before(%): median −20.3, IQR −26.4 to −9.2 vs −9.3, −14.8 to −1.85, p = 0.032; [HCO3−]after-[HCO3−]before (mM):median +5.2, IQR +3.75 to +8.23 vs +3.2, +1.7 to +5.1, p = 0.022) . The percentage of patients achieving [HCO3−] ≥22 mM at 2 months after treatment was significantly higher in the low-T/F group at 88.9% (SB group 38.8%, p = 0.007). There were no renal events in the low-T/F group, and cumulative renal survival (no renal events) tended to be higher in the low-T/F group than in the SB group in the all conditions such as unadjusted condition, presence of RAASi, CKDG4/5 and matched for age, sex, primary cause of CKD and eGFR (p = 0.06, p = 0.265, p = 0.16, p = 0.14, respectively) (Figure). In patients with no renal events, the low-T/F group had a significantly better mean eGFR change of +4.2% at 6 months (SB group: −11.0%, p = 0.019). There were also no cardiovascular events in the low-T/F group, and there were no significant differences between the two groups in either cardiovascular events or treatment-modified events (Table). Conclusion Even in advanced CKD, the low-dose combination of thiazide and fludrocortisone can rapidly improve K-elevating MA and continue without adverse renal or cardiovascular outcomes.

#2477 Longitudinal serum bicarbonate and mortality risk in older patients with advanced chronic kidney disease: analyses from the EQUAL cohort

Abstract Background and Aims Serum bicarbonate (SBC) disorders have been consistently linked to mortality in chronic kidney disease (CKD) patients. Low SBC levels have been extensively associated with increased mortality in CKD patients, possibly due to the detrimental effects of acidosis on various organs and systems. Likewise, several studies have identified high levels of SBC as a risk factor for mortality in the CKD population. To date, most studies have focused on the association between SBC levels and patient survival during the pre-kidney replacement therapy (KRT) period or the period after KRT initiation, considered separately. None have explored this association across the continuum of CKD (e.g., from pre-KRT to post-KRT start), which is relevant since metabolic acidosis is expected to be managed through dialysis in the KRT population, and thus its clinical outcomes might change after KRT initiation. To provide new insights on this topic, we aimed to explore the relationship between SBC and mortality in advanced CKD during three distinct treatment periods: during the pre-KRT period, during the transition phase surrounding the start of KRT (transition-CKD), and during KRT. Method Using the European QUALity Study on treatment in advanced CKD (EQUAL) cohort, which includes patients aged ≥65 years and eGFR ≤20 ml/min per 1.73 m2 from six European countries, we explored the association between longitudinal SBC and all-cause mortality in three separate CKD populations: pre-KRT, transition-CKD and in the KRT populations, using multivariable time-dependent Cox regression models. The cumulative time-averaged, the cumulative exposure of SBC, and the slope of the SBC trajectory during the pre-KRT phase were calculated and evaluated for association with all-cause mortality in the transition-CKD population. Subgroup analysis were used to evaluate the effect modification by pre-specified variables on the relationship between SBC and mortality. Results We included 1485 patients with a median follow-up of 2.9 (IQR 2.7) years, during which 529 (35.6%) patients died. A U-shaped relationship between SBC levels and all-cause mortality was observed in the pre-KRT population (p = 0.03; Fig.). Low cumulative exposure, defined as the area under the SBC trajectory before KRT initiation, was associated with increased mortality risk after transitioning to KRT (p = 0.01). Similarly, in the KRT population, low SBC levels showed a trend towards increased mortality risk (p = 0.13). We observed effect modification on the relationship between SBC and mortality by subjective global assessment category (p-value for interaction = 0.02) and KRT initiation (p-value for interaction = 0.02). Conclusion Our study has provided important insights into the relationship between SBC and mortality in advanced CKD patients. A U-shaped relationship describes the association between SBC and mortality in the advanced CKD pre-KRT population, whereas in patients that initiate KRT only low SBC levels are associated with an increased mortality risk. Our findings suggest that the relationship between SBC and mortality varies across different stages of CKD and that this relationship is modified by KRT initiation. From this point of view, it would be appropriate to consider a personalized management of acid-base balance disorders based on a comprehensive evaluation of the clinical status of the patient.