Advanced Chronic Kidney Disease Patients Research Articles

#5815 INTERNATIONAL VARIATIONS IN TRANSITION OF CARE PRACTICES AND TWO-YEAR OUTCOMES IN ADVANCED CHRONIC KIDNEY DISEASE

Abstract Background and Aims The transition to kidney failure is the period of the highest risk for adverse outcomes in chronic kidney disease (CKD). A smooth and timely transition of care, assuring informed and patient-centric decision-making, is paramount to fostering better kidney care. We described the two-year incidence of clinical outcomes and nephrology practices among advanced CKD patients in CKDopps. Method CKDopps is a prospective cohort study designed to describe and evaluate variations in CKD practices and outcomes in nephrologist-led CKD clinics. For this analysis, we included CKDopps participants who reached a three-month average estimated glomerular filtration rate (eGFR) of less than 20 mL/min/1.73 m2 in the US, France, and Brazil. Time at risk for outcomes started at the end of the first three-month window in which the average eGFR was lower than 20 mL/min/1.73 m2 during study follow-up. Education was defined as participation in at least one educational session about KRT modalities. They were considered to have been referred to vascular access (VA) creation if reported in medical records. Education or VA referral happening before the start of follow-up were classified as occurring at baseline. Patients were considered waitlisted if they had been registered on a pre-emptive kidney transplant waiting list. Cumulative incidence functions adjusting for the competing risk of mortality or KRT were used to estimate the 2-year probability of clinical outcomes and planning events. Results 2,645 patients were included – 51% from France, 36% from the US, and 14% from Brazil. Overall, 56% of patients were male, the mean age was 66 ± 14 years, approximately 50% had diabetes, 27% had coronary artery disease, and 16% had heart failure. Patients in Brazil tended to be younger (63 years) than those in France (67) and the US (67); patients in the US had the greatest burden of cardiovascular comorbidities. The mean eGFR at the study baseline was 16.6 mL/min/1.73m² (15.4 in Brazil, 15.9 in the US, and 17.3 in France). Over a median follow-up of 15.7 [7.2–24] months, 1140 patients (43.1%) started KRT, whereas 377 (14.3%) died before KRT. The 2-year cumulative incidence of KRT was 32% in Brazil, 33% in France, and 44% in the US (Figure 1). The median eGFR at KRT initiation was 11.7 in Brazil, 9.0 in France, and 10.3 in the US. Pre-KRT death risk in two years was 7.3% in Brazil, 10.9% in France, and 16.4% in the US. In two years, approximately one-third of patients had a VA created across countries (Table 1). The probability of transplant waitlisting was higher in France and the US, while patient-reported KRT education was more common in Brazil (Table 1). Conclusion In this international analysis of advanced CKD patients, we found important variations in nephrology practice and outcomes across countries. Patients in the US have a higher risk of both pre-KRT death and KRT. Patient-reported education was far more common in Brazil than in the US and France. Although patients in Brazil are referred for VA creation earlier in the course of advanced CKD, 2-year cumulative incidences for such are similar across countries. The 2-year probability of pre-emptive kidney transplant listing was higher in France and the US. Further international studies evaluating risk factors for adverse outcomes and barriers to KRT planning among advanced CKD patients are warranted.

#3841 ASSOCIATION BETWEEN BODY MASS INDEX, WAIST CIRCUMFERENCE AND CLINICAL OUTCOMES IN KOREAN ADVANCED CHRONIC KIDNEY DISEASE PATIENTS

Abstract Background and Aims This study analysed the association between body mass index (BMI) and waist circumference (WC) with all-cause death, 3-point major cardiovascular event (MACE), end-stage kidney disease (ESKD) and total composite events in nation-wide cohort of Korean advanced chronic kidney disease (CKD) patients. Method This nationwide cohort study, using the National Health Insurance Database, included adult health examinees who received two or more check-ups from 2009 to 2012. Among them, CKD patients (N = 325,657, stage G3a, G3b and 4) were identified. Patients were classified into three groups for BMI (<18.5, 18.5-25 [reference] and ≥25) and four groups for WC (female; <75 cm or male; <85 cm [WC1], female; 75 cm≤WC<85 cm or male; 85 cm≤WC<95 cm [reference], female; 85 cm≤WC<95 cm, male; 95 cm≤WC<105 cm [WC2] and female; ≥95 cm, male; ≥105 cm [WC3]). Risks were evaluated using Cox proportional hazard analysis. Results Patients (58.6±7.7 years) had mean eGFR of 54.32±5.83ml/min/1.73 m2. The underweight (BMI<18.5) group had increased risks of death [HR 1.757, 95% CI (1.573-1.964)] and total events [HR 1.244, (1.144-1.353)]. Overweight (BMI≥25) group showed lower risks of death [HR 0.888, (0.86-0.917)], ESKD [HR 0.855, (0.788-0.927)] and total events [HR 0.975, (0.956-0.995)]. However, the risk was increased for 3-point MACE [HR 1.056, (1.031-1.081)]. For the association between WC and clinical outcomes, the low WC group (WC1) had increased risk of death [HR 1.129, (1.089-1.17)] and reduced risk for 3-point MACE [HR 0.92, (0.894-0.947)]. In higher WC groups, increased risks were observed for death [WC2: HR 1.052, (1.008-1.098), WC3: HR 1.32, (1.213-1.437)], 3-point MACE [WC2: HR 1.071, (1.038-1.104), WC3: HR 1.104, (1.036-1.176)] and total events [WC2: HR 1.049, (1.022-1.077), WC3: HR 1.12, (1.062-1.181)]. Conclusion In CKD patients, both lower BMI and WC were risk factors for mortality and ESKD. However, compared to the reference group, higher BMI group exhibited better outcomes while higher WC groups exhibited poorer outcomes. As increased WC is more specifically related to central obesity, we need different approaches to interpreting clinical risks associated with different BMI and WC criteria.

Predicting hyperkalemia in patients with advanced chronic kidney disease using the XGBoost model

BackgroundHyperkalemia is a common complication of chronic kidney disease (CKD). Hyperkalemia is associated with mortality, CKD progression, hospitalization, and high healthcare costs in patients with CKD. We developed a machine learning model to predict hyperkalemia in patients with advanced CKD at an outpatient clinic.MethodsThis retrospective study included 1,965 advanced CKD patients between January 1, 2010, and December 31, 2020 in Taiwan. We randomly divided all patients into the training (75%) and testing (25%) datasets. The primary outcome was to predict hyperkalemia (K+ > 5.5 mEq/L) in the next clinic vist. Two nephrologists were enrolled in a human-machine competition. The area under the receiver operating characteristic curves (AUCs), sensitivity, specificity, and accuracy were used to evaluate the performance of XGBoost and conventional logistic regression models with that of these physicians.ResultsIn a human-machine competition of hyperkalemia prediction, the AUC, PPV, and accuracy of the XGBoost model were 0.867 (95% confidence interval: 0.840–0.894), 0.700, and 0.933, which was significantly better than that of our clinicians. There were four variables that were chosen as high-ranking variables in XGBoost and logistic regression models, including hemoglobin, the serum potassium level in the previous visit, angiotensin receptor blocker use, and calcium polystyrene sulfonate use.ConclusionsThe XGBoost model provided better predictive performance for hyperkalemia than physicians at the outpatient clinic.

CARD26: Renal replacement therapy after Left Ventricular Assist Device (LVAD) placement: a single center post hospitalization outcome analysis

Background: Historically, advanced chronic kidney disease (CKD) stage 4 or greater and dialysis are often considered to be a relative contraindication for left ventricular assist device (LVAD) implantation. We aim to describe our experience with advanced CKD patients receiving LVADs. Methods: Data was collected by retrospective chart review at our institution. We reviewed all CKD patients who underwent durable LVAD placement requiring perioperative renal replacement therapy (RRT) at our institution between November 2014 and July 2021. Fifty-nine patients were identified, inclusive of patients acutely requiring perioperative RRT and those going on to require chronic RRT. Clinical events of interest included need for dialysis, mortality, infection, thrombotic events, bleeding, and readmission rates at 1, 3, 6 and 12 months. Data was analyzed using multivariate logistic regression. Results: Of the 59 patients, 88.7% were male with an average age of 56 years. Twenty eight had HeartMate III (HM3) LVAD, 24 had HVAD and 7 had HMII. Patients with CKD at baseline were stratified by their pre-VAD CKD stages and majority fell in CKD stage 3a/b. Table 1 depicts further analysis for patients with CKD and non-CKD pre-VAD. CKD stage prior to LVAD did not show a correlation with the need for dialysis post implant (p=0.34, table 2). Conclusion: In this small, single center, retrospective analysis, pre-VAD CKD stage is not necessarily predictive of dialysis. Furthermore, no significant difference was identified between CKD and non-CKD patients. Further studies to determine risk factors for dialysis and subsequent morbidity and mortality in this population to appropriately characterize risk for CKD patients will be of utmost importance.

Comprehensive Conservative Care: what doctors say, what patients hear.

The demographic evolution of patients with advanced chronic kidney disease (CKD) has led to the advent of an alternative treatment option to kidney replacement therapy in the past couple of decades. The KDIGO controversies on Kidney Supportive Care called this approach 'comprehensive conservative care' (CCC) and defined it as planned holistic patient-centered care for patients with CKD stage 5, which does not include dialysis. Although the benefit of this treatment option is now well-recognized, especially for the elderly, comorbid and frail patients, its development remains limited in practice. While shared decision-making process and advance care planning represent the cornerstones of the CCC approach, one of the main barriers in its development is the perfectible communication between nephrologists and patients, but also between all healthcare professionals involved in the care of advanced CKD patients. As a result, a significant gap has opened up between what doctors say and what patients hear. Indeed, although CCC is reported by nephrologists to be widely available in their facilities, few of patients say they have actually heard of it. The objectives of this review are to explore discrepancies between what doctors say and what patients hear, to identify the factors underlying this gap, and to formulate practical proposals for narrowing this gap in practice.

Risks of Topical Carbonic Anhydrase Inhibitors in Glaucoma Patients With Chronic Kidney Disease: A Nationwide Population-Based Study

To investigate the risks of metabolic acidosis and renal outcomes after topical carbonic anhydrase inhibitor (CAI) use in patients with both primary open-angle glaucoma (POAG) and advanced chronic kidney disease (CKD). Nationwide, population-based cohort study. This study was conducted with population data from Taiwan's National Health Insurance (NHI) Research Database between January 2000 and June 2009. Patients with advanced CKD who were diagnosed with glaucoma (International Classification of Diseases, Ninth Revision [ICD-9] code 365) and had been receiving eye drops for glaucoma (including carbonic anhydrase inhibitors selected by NHI drug code) were enrolled. Using Kaplan-Meier methods, we compared the cumulative incidence of mortality, long-term dialysis, and cumulative incidence of metabolic acidosis over time between CAI users and CAI non-users. Primary outcomes comprised mortality, renal outcome (progression to hemodialysis), and metabolic acidosis. In this cohort, topical CAI users had a higher incidence of long-term dialysis than non-users (incidence=1,216.85 vs 764.17 events per 100 patient-years; adjusted hazard ratio=1.17, 95% CI=1.01-1.37). Hospital admissions due to metabolic acidosis were higher in CAI users compared with non-users (incidence=21.54 vs 11.87 events per 100 patient-years; adjusted hazard ratio=1.89, 95% CI=1.07-3.36). Topical CAIs may be associated with higher risks of long-term dialysis and metabolic acidosis in patients with POAG and pre-dialysis advanced CKD. Therefore, topical CAIs should be used with caution in advanced CKD patients.

Connection between Cardiac Fibrosis Biomarkers and Echocardiography Parameters in Advanced Chronic Kidney Disease Patients.

Myocardial fibrosis represents a mainstay pathway in the pathophysiology of uremic cardiomyopathy. This process leads to structural and functional changes in the heart, which can be detected by echocardiography. The purpose of our study was to determine the association between four echocardiographic parameters (ejection fraction (EF), global longitudinal strain (GLS), mean E/e' ratio, and left atrial volume indexed) and biomarkers associated with cardiac fibrosis, such as procollagen type I carboxy-terminal propeptide (PICP), procollagen type III N-terminal peptide (P3NP), and galectin-3 (Gal-3) in patients with end-stage renal disease (ESRD). 140 patients with ESRD were enrolled and investigated by echocardiography and the serum levels of the aforementioned biomarkers were determined at baseline. The mean EF was 53.63 ± 8%, the mean GLS was -10.2 ± 5.3%, the mean E/e' ratio was 9.8 ± 4.3, and the mean left atrial volume indexed (LAVI) was 45.8 ± 14.2 mL/m2. The average levels for PICP, P3NP, and Gal-3 were 457.2 ± 240 µg/L, 242 ± 199.9 µg/L, and 10.7 ± 3.7 ng/mL, respectively. In regression analysis, PICP was strongly associated with all four echocardiographic parameters (EF: p = 0.0002, R2 = 0.69; GLS: p = 0.00001, R2 = 0.81; mean E/e': p = 0.00002; R2 = 0.89; LAVI: p = 0.003; R2 = 0.73). P3NP and Gal-3 were only associated with the EF (p = 0.01, R2 = 0.31 and p = 0.02; R2 = 0.35, respectively). Our study evidenced that PICP, a collagen-derived biomarker, is associated with important echocardiography parameters, suggesting that it can serve as an indicator of the presence of subclinical systolic and diastolic dysfunction in patients with advanced CKD.

Nephron index rather than serum FGF 23 predicts endothelial dysfunction in early but not advanced chronic kidney disease patients

BackgroundEndothelial dysfunction is the primary step for the development of CKD-related cardiovascular disease. Early prediction and management can influence patient survival. Serum testing of FGF 23 hormone and urinary phosphate excretion were studied as predictors of all-cause cardiovascular morbidity in CKD patients; however, their relation to endothelial dysfunction is controversial. A combination of both in one index is hypothesized to increase their sensitivity in detecting endothelial dysfunction, especially in the early stages of CKD before the dominance of hyperphosphatemia, the original risk.MethodsA cross-sectional comparative analysis between thirty CKD stage 3 patients and sixty stage 4–5 CKD patients was conducted. All patients were tested for markers of mineral bone disorders including serum FGF 23 and 24-h urinary phosphate excretion. A combination of both in one index (nephron index) is calculated and hypothesized to correlate with nephron number. Endothelial dysfunction was assessed by measuring the post-occlusion brachial flow-mediated dilatation (FMD).ResultsIn univariate and multivariate regression analyses, the nephron index was the only predictor of endothelial dysfunction in individuals with stage 3 CKD (r = 0.74, P 0.01). This was not applied to stage 4–5 CKD patients where serum phosphorus (r = − 0.53, P 0.001), intact PTH (r = − 0.53, P 0.001), uric acid (r = − 0.5, P 0.001), and measured GFR (r = 0.59, P 0.001) were the highest correlates to FMD; the Nephron index had the weakest correlation (r = 0.28, P = 0.02) and is not predictive of endothelial dysfunction.ConclusionNephron index calculation showed better correlation with endothelial dysfunction than using any of its determinants alone in early stages of CKD when FGF 23 levels are just beginning to rise. In advanced CKD patients, hyperphosphatemia, hyperparathyroidism, hyperuricemia, and measured GFR are more reliable than nephron index.

Preparing for kidney replacement therapy in pediatric advanced CKD: a review of literature and defining a multi-disciplinary clinical approach to patient-caregiver education.

Pediatric patients with progressive chronic kidney disease (CKD) approaching kidney replacement therapy (KRT) make up a small population but carry significant morbidity and mortality. Patients and caregivers require comprehensive kidney failure education to ensure a smooth start to KRT. Choice of KRT modality can be influenced by medical comorbidities, patient/caregiver comprehension, and comfort with a particular modality, social and economic factors, and/or implicit bias of the health care team. As KRT modality can influence morbidity, mortality, and quality of life, we created a pediatric advanced CKD clinic to provide comprehensive KRT education and to promote informed decision-making for our advanced CKD patients and their caregivers.

Impact of hyperkalemia on hospitalization days in advanced chronic kidney disease patients with Type-2 diabetes mellitus: A prospective study.

This study aimed to explore the impact of hyperkalemia at admission on hospitalization days (HDs) among advanced chronic kidney disease patients (CKD) with type two diabetes mellitus (T2DM) in China. A total of 270 CKD patients with T2DM were prospectively selected from January 1, 2020 to December 31, 2021. These patients were divided into Group-A (n = 150, serum potassium ≤ 5.5 mmol/L) and B (n = 120, serum potassium > 5.5 mmol/L). The comparison method between the two groups was taken. Linear correlation analysis was performed using the Spearman correlation method, and multivariate analysis was tested using linear regression. The study found statistically significant result between the two groups (Group-A vs Group-B): HDs (7.4 (5.3-11.2) vs 12.1 (8.2-16.5), p < 0.001), renin-angiotensin-aldosterone system inhibitors (RAASIs) (36.2% vs 55.8%, p = 0.014), systolic blood pressure (148.35 ± 19.51 vs 162.26 ± 21.31, p < 0.05), estimated glomerular filtration (eGFR) (20.35) (18.31-25.26) vs13.4 (12.50-18.50), p < 0.001, N-terminal pro-B type natriuretic peptide (NT-proBNP) (2245.42 ± 61.09 vs 3163.39 ± 85.15,p < 0.001), and Hb (88.45 ± 12.35 vs 72.26 ± 14.2, p = 0.023). Correlation analysis showed that HDs were positively correlated with age, serum potassium, systolic blood pressure, and NT-proBNP, while negatively with eGFR and Hb. After adjusting for relevant confounding variables, the multivariable linear regression analysis showed that hyperkalemia was an independent risk factor for HDs. Hyperkalemia could be an independent risk factor increasing HDs of advanced CKD patients with T2DM.

All-Cause and Cardiovascular-Related Mortality in CKD Patients With and Without Heart Failure: A Population-Based Cohort Study in Kaiser Permanente Southern California

Heart failure and chronic kidney disease (CKD) frequently coexist reflective of the strong interplay between these organ systems. A better understanding of the prevalence of different types of heart failure (preserved and reduced ejection fraction) and their subsequent mortality risks among advanced CKD patients would provide important epidemiologic insights and may pave the way for more focused and proactive management strategies. Retrospective cohort study. Patients aged≥18 years with incident CKD (estimated glomerular filtration rate≤45mL/min/1.73m2) with and without heart failure in a large integrated health care system in Southern California. Heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF). All-cause and cardiovascular-related mortality within one year of CKD identification. HRs were estimated using Cox proportional-hazards model for risk of all-cause mortality and Fine-Gray subdistribution hazard model for risk of cardiovascular-related mortality within 1 year. The study cohort included 76,688 patients with incident CKD between 2007 and 2017, of which 14,249 (18.6%) had prevalent heart failure. Among these patients, 8,436 (59.2%) had HFpEF and 3,328 (23.3%) had HFrEF. Compared with patients without heart failure, the HR for 1-year all-cause mortality was 1.70 (95% CI, 1.60-1.80) among patients with heart failure. The HRs were 1.59 (95% CI, 1.48-1.70) for patients with HFpEF and 2.43 (95% CI, 2.23-2.65) for patients with HFrEF. Compared with patients without heart failure, the 1-year cardiovascular-related mortality HR for patients with heart failure was 6.69 (95% CI, 5.93-7.54). Cardiovascular-related mortality HR was even higher among those with HFrEF (HR, 11.47; 95% CI, 9.90-13.28). Retrospective design with a short 1-year follow-up period. Additional variables including medication adherence, medication changes, and time-varying variables were not accounted for in this intention-to-treat analysis. Among patients with incident CKD, heart failure was highly prevalent with HFpEF accounting for over 70% among patients with known ejection fraction. Although the presence of heart failure was associated with higher 1-year all-cause and cardiovascular-related mortality, patients with HFrEF were the most vulnerable.

WCN23-0325 Preliminary Efficacy and Safety results of Accelerated Versus Standard Hepatitis B vaccination schedules among Advanced Chronic Kidney Disease patients: A Randomized Controlled Trial

WCN23-0325 Preliminary Efficacy and Safety results of Accelerated Versus Standard Hepatitis B vaccination schedules among Advanced Chronic Kidney Disease patients: A Randomized Controlled Trial

Abstract P539A: Advanced Chronic Kidney Disease Does Not Significantly Affect All-Cause Mortality and Rate of Hemodynamic Complications in Acute Pericarditis

Background: Advanced chronic kidney disease (advanced CKD) patients have several metabolic, immunologic, and hemodynamic derangements that can negatively impact the natural history of cardiac disease. Some efficacious treatments for acute pericarditis such as colchicine and NSAIDS may not be well tolerated by advanced CKD patients. Hypothesis: Advanced CKD may portend worse outcomes based on clinical severity and likely higher side effect of treatments among patients hospitalized with acute pericarditis. Method: A retrospective cohort study with data from the 2016 to 2018 combined National Inpatient Sample (NIS) database was employed. ICD-10 codes were used to sample all adult admissions for acute pericarditis who were dichotomized based on the presence of a secondary diagnosis of advanced CKD including CKD stage 4, stage 5 and dialysis dependent patients. Primary outcomes of study were Mortality rate, length of stay and total hospital charge. Secondary outcomes were cardiac tamponade, cardiogenic shock, pericardial window rate, supraventricular tachycardia (SVT), ventricular tachycardia (VT) and gastrointestinal (GI) bleeding rate. Multivariate linear and logistic regressions were used to adjust for confounders. Results: We identified a total of 36570 admissions for acute pericarditis and among these, 4139.99 representing 5.96% had associated advanced CKD diagnosis. These patients were averagely 5 years older (57.14 vs 52.35, adjusted difference of 4.80 years, 95%CI: 3.11 - 6.48, p-value &lt;0.001) and predominantly female (44.5% vs 39.12%, AOR 1.25, 95%CI: 1.02 - 1.52, p value: 0.029) compared to the counterpart cohort group. Details of study outcomes are summarized in table 1 below. Conclusion: Among patients hospitalized with acute pericarditis, the presence of advanced CKD as a secondary diagnosis was associated with increase length of stay and total charge but without statistical significance effect on odds of mortality and odds of relevant hemodynamic complications.

Assessment of uremic toxins in advanced chronic kidney disease patients on maintenance hemodialysis by LC-ESI-MS/MS.

In the advanced stage of chronic kidney disease (CKD), electrolytes, fluids, and metabolic wastes including various uremic toxins, accumulate at high concentrations in the patients' blood. Hemodialysis (HD) is the conventional procedure used worldwide to remove metabolic wastes. The creatinine and urea levels have been routinely monitored to estimate kidney function and effectiveness of the HD process. This study, first from in Indian perspective, aimed at the identification and quantification of major uremic toxins in CKD patients on maintenance HD (PRE-HD), and compared with the healthy controls (HC) as well as after HD (POST-HD). The study mainly focused on the identification of major uremic toxins in Indian perspective and the quantitative analysis of indoxyl sulfate and p-cresol sulfate (routinely targeted uremic toxins), and phenyl sulfate, catechol sulfate, and guaiacol sulfate (targeted for the first time), apart from creatinine and urea in PRE-HD, POST-HD, and HC groups. Blood samples were collected from 90 HD patients (both PRE-HD and POST-HD), and 74 HCs. The plasma samples were subjected to direct ESI-HRMS and LC/HRMS for untargeted metabolomics and LC-MS/MS for quantitative analysis. Various known uremic toxins, and a few new and unknown peaks were detected in PRE-HD patients. The p-cresol sulfate and indoxyl sulfate were dominant in PRE-HD, the concentrations of phenyl sulfate, catechol sulfate, and guaiacol sulfate were about 50% of that of indoxyl sulfate. Statistical evaluation on the levels of targeted uremic toxins in PRE-HD, POST-HD, and HC groups showed a significant difference among the three groups. The dialytic clearance of indoxyl sulfate and p-cresol sulfate was found to be < 35%, while that of the other three sulfates was 50-58%. LC-MS/MS method was developed and validated to evaluate five major uremic toxins in CKD patients on HD. The levels of the targeted uremic toxins could be used to assess kidney function and the effectiveness of HD.

Predictive Value of Collagen Biomarkers in Advanced Chronic Kidney Disease Patients.

Patients with chronic kidney disease have an increased risk of all-cause death. The value of collagen biomarkers such as procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III N-terminal peptide (P3NP), in end-stage renal disease (ESRD), has not yet been defined (in the literature and in clinics). The purpose of this study was to determine the potential value of these new biomarkers in the prediction of mortality in this population. Plasma PICP and P3NP levels were determined in 140 patients with ESRD, not yet on dialysis, who were followed up for 36 ± 5.3 months. During follow-up, 58 deaths were recorded (41.4%), with the majority of them being cardiovascular deaths (43, 74.13%). Using the ROC curve, the cut-off value for the prediction of mortality for PICP was 297.31 µg/L, while for P3NP, the cut-off value was 126.67 µg/L. In univariate analysis, a value of PICP above the cut-off point was associated with a fivefold increased risk of mortality (hazard ratio (HR) 5.071, 95% confidence interval 1.935-13.29, p = 0.001) and a value of P3NP above the cut-off point was associated with a twofold increased risk of mortality (HR 2.089, 95% CI 1.044-4.178, p = 0.002). In a multivariable Cox proportional hazards model, PICP values remained independent predictors of mortality (HR 1.22, 95% CI 1.1-1.31, p < 0.0001). Our data suggest that the collagen biomarker PICP is an independent predictor of mortality in ESRD patients who are not yet on dialysis.

Systematic review and meta-analysis of preoperative interventions to support the maturation of arteriovenous fistulae in patients with advanced kidney disease.

There is great potential to improve outcomes of arteriovenous fistulas (AVFs) by focusing more on the preoperative period of AVF creation. We aim to systematically review the evidence on safety and efficacy of various preoperative interventions that have been tried to improve AVF maturation and success rate. We searched five databases: PubMed, Embase, CINAHL, Cochrane Library and King's Fund Library. Experimental studies that investigated the effect of various preoperative interventions to improve AVF outcomes among advanced chronic kidney disease (CKD) patients were searched. The effect size for primary outcome was calculated as the weighted mean difference in the final vessel calibre, rate of AVF maturation or primary failure between the intervention and control arm. We also assessed adverse effects and dropout rates. This review was preregistered in the International Prospective Register of Systematic Reviews (CRD42020193257). Eight eligible studies were identified involving three types of intervention: hand exercise (n=6), cholecalciferol supplementation (n=1) and pneumatic compression of the arm using a Fist Assist device (n=1). The overall effect size of hand exercise on distal cephalic vein calibre was 0.24mm [95% confidence interval (CI) 0.03-0.45] on meta-analysis of hand exercise studies. On restricting analysis to two randomized controlled trials (RCTs) that had independent control groups, the effect size was higher, at 0.29mm (95% CI 0.11-0.47). Hand exercise was a well-tolerated intervention, especially when confined to the first 4weeks. Hand exercise is the predominant intervention tried in the preoperative period of AVF creation, although there is methodological heterogeneity. Intermittent pneumatic compression using a Fist Assist device is a novel intervention that has shown some promise. Well-designed prospective RCTs are needed on preoperative interventions among advanced CKD patients, aimed at improving AVF outcomes.

Impact of urine cyclic AMP relative to plasma arginine vasopressin on response to tolvaptan in patients with chronic kidney disease and heart failure.

The clinical utility of tolvaptan in chronic kidney disease (CKD) patients with heart failure remains uncertain. The level of urine cyclic adenosine monophosphate (AMP) relative to plasma arginine vasopressin (AVP) indicates the residual function of the collecting ducts in response to AVP stimulation and might be a key to predicting response of tolvaptan. CKD patients who were hospitalized to treat their congestive heart failure refractory to conventional loop diuretics were considered to receive tolvaptan and included in this prospective study. The impact of urine cyclic AMP/plasma AVP ratio for prediction of response to tolvaptan, which was defined as any increase in urine volume at day 7 from day 0, was investigated. A total of 30 patients (median 75years old, 24 men, and median estimated glomerular filtration rate 14.4mL/min/1.73 m2) were included. As compared to baseline, urine volume increased at day 7 in 17 responders, whereas urine volume decreased at day 7 in 13 non-responders. Baseline urine cyclic AMP/plasma AVP ratio distributed between 0.25 and 4.01 with median 1.90. The urine cyclic AMP/plasma AVP ratio was a significant predictor of response to tolvaptan, which was adjusted for 6 potential confounders with a cutoff of 1.24. Baseline urine cyclic AMP/plasma AVP ratio is an independent predictor of response to tolvaptan in advanced CKD patients with heart failure. UMIN000022422.

Integrated Osteoporosis Care to Reduce Denosumab-Associated Hypocalcemia for Patients with Advanced Chronic Kidney Disease and End-Stage Renal Disease.

The incidence of hypocalcemia is high in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) undergoing denosumab treatment. Since 2018, we have carried out a "multidisciplinary integrated care program for osteoporosis among patients with CKD and ESRD" in our hospital. The aim of this study was to compare the incidence of denosumab-associated hypocalcemia among patients with advanced CKD and ESRD before and after the integrated care program. We retrospectively reviewed the records of patients on their first dose of denosumab treatment from January 2012 to December 2021. A total of 3208 patients were included in our study. Among the 3208 patients, there were 101 dialysis patients, 150 patients with advanced CKD (stage 4 and 5), and 2957 patients with an estimated glomerular filtration rate (eGFR) higher than or equal to 30. The incidence of post-treatment severe hypocalcemia (corrected calcium level less than 7.0 mg/dl) within 30 days was significantly higher in the dialysis and advanced CKD group than in patients with an eGFR higher than or equal to 30 (6.9% vs. 2.0% vs. 0.1%, respectively, p < 0.001). Based on the results of the multivariate regression model, poor renal function (p < 0.05) and lower baseline corrected calcium level (p < 0.05) were associated with severe hypocalcemia within 30 days following the first dose of denosumab treatment. The incidence of post-treatment severe hypocalcemia within 30 days in advanced CKD and dialysis patients was significantly lower after the integrated care program (6.8% vs. 0.8%, p < 0.05). Our study shows that multidisciplinary integrated care may reduce the incidence rate of denosumab-associated severe hypocalcemia among patients with advanced CKD and ESRD.

PS-C27-10: SHORT-TERM EFFICACY OF DAPAGLIFLOZIN FOR CHRONIC KIDNEY DISEASE PATIENTS

Background: Dapagliflozin, a SGLT-2 inhibitor, has been reported to prevent renal and cardiovascular events. Dapagliflozin has been approved for use in chronic kidney disease (CKD) without diabetes, so that it has been widely used in CKD patients. Methods: This study was a single-center, retrospective, and longitudinal study consisting of 102 patients (75% male, mean age 61.5 ± 15.7 years, 30.3% diabetes), who were started dapagliflozin prescription at our department between April 2021 and March 2022. The efficacy of treatment on proteinuria, blood pressure and blood sample findings (hemoglobin, uric acid, phosphorus and creatinine) in the short term (64.1 ± 46.7 days) between initiation of treatment and the first return visit were compared in two groups: advanced CKD (eGFR under 30 mL/min/1.73 m2) and moderate CKD (GFR more than 30 mL/min/1.73 m2). Results: Advanced CKD patients were older (mean age 65.1 ± 14.7 years vs. 58.2 ± 15.9 years) and had more diabetes (45.8% vs. 16.7%) compared with Moderate CKD patients, but the sex ratio was similar between the two groups. Proteinuria did not change in Advanced CKD, but decreased significantly from 2.1 ± 2.1 g/gCr to 1.8 ± 2.0 g/gCr in Moderate CKD. Systolic blood pressure significantly decreased from 144.1 ± 15.0 mmHg to 136.6 ± 26.1 mmHg in Advanced CKD and tended to decrease from 140.0 ± 17.4 mmHg to 135.4 ± 18.2 mmHg in Moderate CKD. Hemoglobin increased significantly in Moderate CKD (from 14.2 ± 1.8 g/dL to 14.7 ± 1.8 g/dL) and uric acid decreased significantly (from 6.4 ± 1.4 mg/dL to 5.4 ± 1.3 mg/dL), but no significant change was observed in Advanced CKD. On the other hand, Advanced CKD patients showed a significant increase in serum phosphorus (from 4.0 ± 1.3 mg/dL to 4.3 ± 1.5 mg/dL) and serum creatinine (from 3.2 ± 1.6 mg/dL to 3.3 ± 1.8 mg/dL). Serum creatinine elevation above 0.3 mg/dL was found in 29% of Advanced CKD patients, but not in any Moderate CKD patients. Conclusions: Dapagliflozin may reduce blood pressure and improve anemia, proteinuria, and hyperuricemia in short-term treatment of moderate CKD patients, while acute exacerbation of kidney function should be considered in short-term treatment of advanced CKD patients.

The echocardiographic changes following arterio-venous fistula creation in advanced chronic kidney disease patients: A preliminary report

Echocardiographic changes following the creation of arterio-venous fistula (AVF) in end-stage renal disease (ESRD) patients undergoing regular haemodialysis have been reported. Pre-emptive AVF creation in advanced chronic kidney disease (CKD) patients and its effects on echocardiographic parameters remained unclear.