Dialysis Dependence Research Articles

Aortic arch endovascular branch and fenestrated repair: Initial Canadian experience with novel technology

ObjectiveThe objective is to describe the initial Canadian experience using novel aortic arch branched endograft technologies. MethodsWe performed a retrospective consecutive case series of all patients undergoing aortic arch branched repair with newly available endograft technology since 2020 at our site. We describe the patient characteristics, treatment characteristics, and postoperative outcomes. ResultsEleven patients received arch branched endografts, indicated for penetrating aortic ulcer in seven patients (64%), arch degeneration after prior aortic dissection repair in three (27%), and acute aortobronchial fistula in one patient (9%). Their average age was 72 ± 7 years. Complete arch repair from zone 0 to 4 was performed in six cases (55%); the remaining repairs landed proximally in zones 1 or 2. Seven repairs used a single retrograde facing inner branch (thoracic branch endoprosthesis; W.L. Gore & Associates), three used double antegrade inner branch (Bolton Relay; Terumo Interventional Systems), and one emergent case used double in situ fenestrations. Seven repairs (64%) used an adjunctive extra-anatomic bypass to complete great vessel perfusion, two of which were created during a prior aortic repair. Inferior vena cava balloon inflow occlusion during deployment was used in all cases. No mortalities, transient or permanent spinal cord paralysis, myocardial infarction, dialysis dependence, venous thromboembolism, or bleeding requiring reintervention occurred. No patient undergoing elective arch branch repair experienced a stroke. The one patient undergoing emergent repair did suffer a stroke. The median length of stay was 5 days (interquartile range, 2-8 days). Two endoleaks developed: a type Ia endoleak successfully treated with a Palmaz stent (Cordis) during the index admission, and a type II endoleak with ongoing sac regression on postoperative follow-up. Postoperatively, one patient suffered a suspected aortic graft infection that was treated with lifelong antibiotics. During a mean radiographic follow-up of 7.2 months, no cases of branch vessel instability (ie, no migration, reintervention, arterial rupture, intraluminal thrombus, occlusion, stenosis, or kinking of the branch grafts) developed. Three patients experienced sac regression of >5 mm, and no patient experienced continued postoperative dilation. ConclusionsTo the best of our knowledge, this is the largest reported Canadian volume of aortic arch repair using novel branched or fenestrated technology. The series demonstrates that a multidisciplinary program and properly selected patients can yield excellent results using endovascular repair for complex aortic arch pathology.

The efficacy and safety of roxadustat for anemia in patients with dialysis-dependent chronic kidney disease: a systematic review and meta-analysis

Background This meta-analysis aims to assess the efficacy and safety of roxadustat in treating anemia patients with dialysis-dependent (DD) chronic kidney disease (CKD). Methods We comprehensively searched 5 databases for randomized controlled trials (RCTs) investigating roxadustat for anemia in DD-CKD patients. RevMan 5.0 was used to extract and synthesize data for meta-analysis. Results Ten different RCTs (9 studies) and 5698 DD-CKD patients with anemia were included. Our findings revealed that when compared to the erythropoiesis-stimulating agents (ESAs) group, the roxadustat group showed increased hemoglobin levels [MD (Mean Difference) 0.25 g/dL (95%CI 0.14 g/dL to 0.36 g/dL), p < 0.00001] and improved iron-utilization by increasing serum iron [MD 1.85 µmol/L], total iron binding capacity [MD 35.73 µg/dL], transferrin saturation [MD 1.19%], and transferrin level [MD 0.40 g/L]. In addition, we found that roxadustat significantly decreased the low-density lipoprotein-cholesterol [MD −0.39 mmol/L] and total cholesterol [MD −0.6 mmol/L]. In patients with a C-reactive protein level that exceeds the upper limit of the normal range, hemoglobin levels were higher for roxadustat than for ESAs [MD 0.39 g/dL]. Treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events were not significantly different between the two groups. Conclusions The hemoglobin levels of DD-CKD patients were significantly increased and not affected by the inflammatory state after roxadustat treatment. Roxadustat also improved iron utilization, and it was not associated with higher treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events when compared to ESAs.

Blood transfusions post kidney transplantation are associated with inferior allograft and patient survival-it is time for rigorous patient blood management.

Patient Blood Management (PBM), endorsed by the World Health Organisation is an evidence-based, multi-disciplinary approach to minimise inappropriate blood product transfusions. Kidney transplantation presents a particular challenge to PBM, as comprehensive evidence of the risk of transfusion is lacking. The aim of this study is to investigate the prevalence of post-transplant blood transfusions across multiple centres, to analyse risk factors for transfusion and to compare transplant outcomes by transfusion status. This analysis was co-ordinated via the UK Transplant Registry within NHS Blood and Transplant (NHSBT), and was performed across 4 centres. Patients who had received a kidney transplant over a 1-year period, had their transfusion status identified and linked to data held within the national registry. Of 720 patients, 221(30.7%) were transfused, with 214(29.7%) receiving a red blood cell (RBC) transfusion. The proportion of patients transfused at each centre ranged from 20% to 35%, with a median time to transfusion of 4 (IQR:0-12) days post-transplant. On multivariate analysis, age [OR: 1.02(1.01-1.03), p=0.001], gender [OR: 2.11(1.50-2.98), p<0.0001], ethnicity [OR: 1.28(1.28-2.60), p=0.0008], and dialysis dependence pre-transplant [OR: 1.67(1.08-2.68), p=0.02], were associated with transfusion. A risk-adjusted Cox proportional hazards model showed transfusion was associated with inferior 1-year patient survival [HR 7.94(2.08-30.27), p=0.002] and allograft survival [HR: 3.33(1.65-6.71), p=0.0008], and inferior allograft function. RBC transfusions are common and are independently associated with inferior transplant outcomes. We urge that further research is needed to understand the mechanisms behind the outcomes, to support the urgent development of transplant-specific anaemia guidelines.

Depression Among Dialysis Dependent end-Stage Renal Disease Patients: A Study from Tertiary Care Hospital in Bahawalpur

Objective: To determine the frequency of depression among dialysis dependent end-stage renal disease patients, associated factors and effect on patients’ compliance and clinical performance parameters. Study Design: Cross-sectional study Place and Duration of Study: Department of Nephrology, Bahawal Victoria Hospital, Bahawalpur Pakistan, from Apr 2017 to Mar 2018. Methodology: End-stage renal disease patients above 16 years of age who were on maintenance haemodialysis for more than 6 months were requested to complete the questionnaire of Urdu version of Patient Health Questionnaire 9. The information about missed treatments, shortened sessions, fluid overload and monthly laboratory data was obtained from medical records. Patient Health Questionnaire 9 score was calculated for all the patients and categorized as mild (5), moderate (10), moderately severe (15) and severe (20) depression. Results: There were 146 dialysis dependent end-stage renal disease patients (95 males, 51 females) with mean age of 45.1±14.3 years. Duration of dialysis dependence was significantly higher among females (p=0.022). Out of 146 patients, 116 had depression and 27(18.5%) had severe depression. Patients with depression were younger (p=0.037) and lack of social support was significantly associated with depression (p=0.018). Severe depression was significantly more frequent among females (p=0.041). Serum albumin was significantly low among patients with depression (p=0.044). Conclusion: Depression is common among haemodialysis dependent end-stage renal disease patients. It is common among young patients and those who lack social support and it is associated with hypoalbuminemia.

Subgroups of Patients with Distinct Health Utility Profiles after AKI.

A large amount of inter-individual variability exists in health-related quality of life outcomes following acute kidney injury (AKI). This study aimed to determine if subgroups of early AKI survivors could be identified based on distinct health utility impairment profiles ascertained at 60 days after AKI and if these subgroups differed in clinical and biomarker characteristics at index hospitalization and outcomes at 1-year follow up. This retrospective analysis used data from the BioMaRK study, an observational subcohort of the Acute Renal Failure Trial Network study. Of 402 patients who survived to 60 days after AKI, 338 completed the Health Utility Index-3 survey which measures impairments in 8 health attributes. Latent class analysis was used to identify subgroups of patients with distinct health utility profiles. Three subgroups with distinct health utility impairment profiles were identified: Low (28% of participants), Moderate (58%) and High (14%) with a median of 1, 4, and 6 impairments across the 8 health attributes at 60 days after AKI, respectively. Patient subgroups differed in weight, history of cerebrovascular disease, intensity of dialysis, hospital length of stay, and dialysis dependence. Serum creatinine and blood urea nitrogen at index hospitalization did not differ among the 3 subgroups. The High impairment subgroup had higher levels of interleukin-6 and soluble tumor necrosis factor receptor-2 at study day 1. The 3 subgroups had different 1-year mortality rates: 5% in the Low, 21% in the Moderate, and 52% in the High impairment subgroup. Patient subgroups with distinct health utility impairment profiles can be identified 60 days after AKI. These subgroups have different characteristics at index hospitalization. A higher level of impairment at 60 days was associated with decreased survival.

Use of Mechanical Ventilation Across 3 Countries

The ability to provide invasive mechanical ventilation (IMV) is a mainstay of modern intensive care; however, whether rates of IMV vary among countries is unclear. To estimate the per capita rates of IMV in adults across 3 high-income countries with large variation in per capita intensive care unit (ICU) bed availability. This cohort study examined 2018 data of patients aged 20 years or older who received IMV in England, Canada, and the US. The country in which IMV was received. The main outcome was the age-standardized rate of IMV and ICU admissions in each country. Rates were stratified by age, specific diagnoses (acute myocardial infarction, pulmonary embolus, upper gastrointestinal bleed), and comorbidities (dementia, dialysis dependence). Data analyses were conducted between January 1, 2021, and December 1, 2022. The study included 59 873 hospital admissions with IMV in England (median [IQR] patient age, 61 [47-72] years; 59% men, 41% women), 70 250 in Canada (median [IQR] patient age, 65 [54-74] years; 64% men, 36% women), and 1 614 768 in the US (median [IQR] patient age, 65 [54-74] years; 57% men, 43% women). The age-standardized rate per 100 000 population of IMV was the lowest in England (131; 95% CI, 130-132) compared with Canada (290; 95% CI, 288-292) and the US (614; 95% CI, 614-615). Stratified by age, per capita rates of IMV were more similar across countries among younger patients and diverged markedly in older patients. Among patients aged 80 years or older, the crude rate of IMV per 100 000 population was highest in the US (1788; 95% CI, 1781-1796) compared with Canada (694; 95% CI, 679-709) and England (209; 95% CI, 203-214). Concerning measured comorbidities, 6.3% of admitted patients who received IMV in the US had a diagnosis of dementia (vs 1.4% in England and 1.3% in Canada). Similarly, 5.6% of admitted patients in the US were dependent on dialysis prior to receiving IMV (vs 1.3% in England and 0.3% in Canada). This cohort study found that patients in the US received IMV at a rate 4 times higher than in England and twice that in Canada in 2018. The greatest divergence was in the use of IMV among older adults, and patient characteristics among those who received IMV varied markedly. The differences in overall use of IMV among these countries highlight the need to better understand patient-, clinician-, and systems-level choices associated with the varied use of a limited and expensive resource.

Iron Parameters in Patients Treated with Roxadustat for Anemia of Chronic Kidney Disease.

Roxadustat is a novel agent with a distinct mechanism of action compared to erythropoiesis-stimulating agents (ESAs) and a potentially different combination of effects on iron parameters. This narrative review describes the effects of roxadustat on iron parameters and on hemoglobin levels in the context of iron supplementation in patients with anemia of non-dialysis-dependent (NDD) or dialysis-dependent (DD) chronic kidney disease (CKD). Roxadustat use was associated with a greater reduction in serum ferritin levels than seen with ESAs and an increase in serum iron levels compared to a decrease with ESAs. Decreases in transferrin saturation in patients treated with roxadustat were relatively small and, in the case of patients with NDD CKD, not observed by Week 52. These changes reflect the concomitant increases in both serum iron and total iron-binding capacity. Compared to placebo and an ESA, roxadustat improved iron availability and increased erythropoiesis while requiring less intravenous iron use. Hepcidin levels generally decreased in patients who received roxadustat compared to baseline values in all CKD populations; these decreases appear to be more robust with roxadustat than with an ESA or placebo. The mechanisms behind the effects of roxadustat and ESAs on iron availability and stores and erythropoiesis appear to differ and should be considered holistically when treating anemia of CKD.

#4424 FREQUENCY OF RED BLOOD CELL TRANSFUSION USE IN PATIENTS WITH ANEMIA OF CHRONIC KIDNEY DISEASE (CKD) IN EUROPE: A SYSTEMATIC LITERATURE REVIEW

Abstract Background and Aims Anemia of CKD is common and managed with oral or intravenous iron, erythropoiesis-stimulating agents (ESAs) and, when necessary, red blood cell transfusions (RBCT). Reducing RBCT use is a goal in the management of anemia of CKD due to known short term (e.g., hyperkalaemia, heart failure) and longer term risks (e.g., allosensitization), but there is limited collated data on their use in Europe. A systematic literature review was conducted to evaluate the frequency of RBCT use among dialysis dependent (DD) and non-dialysis (ND) patients, and associated data reported for predictors of RBCT receipt, complications, healthcare resource use (HCRU), and costs. Method A comprehensive search strategy was used to retrieve real-world (RW) studies and randomized controlled trials (RCTs) conducted in DD and ND CKD patients with anemia using Embase and Medline (1980 to June 2022). Searches of conference abstracts, bibliographies and grey literature were also conducted. Studies which included European patients’ data are described here. Results Of the 3495 citations retrieved, 182 relevant studies were identified including 54 studies with European patients. Thirteen were RW studies including 12 quantifying the frequency of RBCT use (Table). In RW studies, the overall frequency of RBCT use ranged from 4.3–35.0% across studies and for key subgroups (n=10 studies: DD only studies, 8.4–33.9%; ND only studies, 4.3–35.0%). The number of RBCT units per patient-year (PY) ranged from 1.4–2.7 among DD patients (n=2 studies; no ND studies found). RBCT use appeared to vary by patient factors (iron/ESA use, CKD stage), by study design (e.g., length of follow-up) and across countries (but with no clear patterns in geographic variation). For the 41 RCTs including European patients (single country, n=3 studies, multi-country, n=38 studies), the overall frequency of RBCT use ranged from 0–21.6% (DD only studies, 0.4–21.6%; ND only studies, 0–14.8%), which was lower than those recorded in the RW studies. The rate of RBCT use in trials ranged from 3.5–66.0 events per 100 PY overall (DD only studies, 3.5–66.0; ND only study, 8.0); the number of RBCT units per PY ranged from 0.20–1.65 among DD patients (n=2 studies; no ND studies found). No studies used statistical modelling to quantify predictors of RBCT use while adjusting for potential differences between groups. One RW study from 1986 reported detection of human T-lymphotropic virus type III (HTLV-III; subsequently known as HIV) antibodies in 4 patients who had received RBCT (in a sample of 276 screened chronic HD patients). Of three RW studies reporting data on costs, two were &amp;gt;30 years old and one provided costs relating to receipt of inpatient RBCT in ND patients stratified by oral iron, low dose, or high dose intravenous iron use from 2013–2015 (n=111). Conclusion RBCT use forms part of the management of anemia of CKD in Europe and its use is variable but not infrequent. RBCT risk in RW studies appeared elevated compared to RCTs. There were no consistent patterns in geographic variation, but risk varied by patient factors and study design. There is currently limited European data reporting on frequency of associated complications, predictors of RBCT use, associated HCRU and costs. Funding: GSK (Study 218929).

#3156 REAL WORLD CHARACTERISTICS, SYMPTOM BURDEN AND TREATMENT PATTERNS OF ANAEMIA OF CKD IN EGYPT, SAUDI ARABIA, SOUTH AFRICA, AND TURKEY

Abstract Background and aims Patients with chronic kidney disease (CKD) often have comorbid anaemia [1]. Real-world data on patient characteristics, disease burden, and treatment management for people with anaemia of CKD in the Middle East and Africa are limited. Methods SATISFY (Survey on treatment patterns in Anemia of CKD, patient Treatment satISFaction and perspectives as reported by patients with phYsicians) was a real-world survey conducted between 01 June to 01 September 2022 in Egypt, Saudi Arabia, South Africa, and Turkey. Physician and patient perceptions of treatment were captured via cross-sectional surveys; patients’ clinical characteristics were recorded by physicians in electronic case report forms via retrospective review of medical records. Eligible physicians were nephrologists with ≥1 years’ experience who managed ≥12 patients with anaemia of CKD per month and with drug management experience for anaemia of CKD. Physicians collected data on the first 7–10 patients seen in routine clinical practice during the study period. Eligible patients were ≥18 years with CKD stage 3b, 4, or 5 at the time of anaemia of CKD diagnosis and with ≥2 years’ follow-up data from diagnosis to time of survey. Patients with functioning kidney transplants or acute kidney injury were excluded. Primary outcomes were to describe clinical and demographic characteristics, monitoring test results, treatment patterns of patients with anaemia of CKD, physicians’ reasons for not treating anaemia of CKD, and physicians’ and patients’ reasons for therapy choice. Data were analysed descriptively. Results A total of 1788 patients and 217 physicians were included; 1138 patients (64%) were non-dialysis dependent (NDD) and 611 (34%) were dialysis dependent (DD) at the time of data extraction (n = 39 [2%] data missing). Mean (standard deviation [SD]) age was 46 (14) years, mean (SD) body mass index was 24.1 (3.1) kg/m2, 56% (n = 1004) were male, and median (interquartile range [IQR]) follow-up from diagnosis of anaemia of CKD was 2.6 (2.5–3.2) years. The most common comorbidities were hypertension (n = 858, 48%) and diabetes (n = 324, 18%). Symptom burden was high, with lack of energy and fatigue being among the most commonly reported symptoms by physicians and patients across both NDD and DD groups (Figure 1). Differences were seen between physician and patient symptom reporting and between NDD and DD groups. Patients’ self-reported symptom burden was greater than that reported by physicians, particularly for NDD patients. The median (IQR) times per year physicians reported testing CKD patients for anaemia was 4 (4–6) for NDD patients and 12 (10–12) for DD patients. Median test levels for haemoglobin at which patients were diagnosed were lower than those reported by physicians as being used for diagnosis; similar results were seen for thresholds used to initiate treatment (Table 1). Median (IQR) days from diagnosis to first treatment was 61 (0–419). Of those who received treatment, the most common first treatment option was erythropoietin-stimulating agents + intravenous iron for both patients with NDD and DD anaemia of CKD at diagnosis (NDD n = 291/736, 40%; DD n = 170/316, 54%). A large proportion of patients never received treatment for anaemia of CKD (n = 701, 39%). The most important reasons to not initiate treatment from a physician perspective were patient refusal (n = 172, 79%) and risk of adverse reactions (n = 168, 77%); for patients, top reasons were that their symptoms were not severe (n = 168, 22%) and their physicians’ concerns about adherence (n = 116, 15%). Similar reasons were seen for both the Middle East and Africa regions. Conclusion Symptom burden is high in patients with anaemia of CKD in the Middle East and Africa, particularly lack of energy and fatigue. Differences were seen between physician and patient perceptions of symptom burden and between NDD and DD groups. Substantial treatment inertia exists. Physicians rated patient refusal and risk of adverse reactions as main reasons for not treating patients, while patients attributed this to a belief that their symptoms were not severe.

#4811 SIZE MATTERS: EFFECT OF NUMBER OF TRANSFUSIONS ON ADVERSE RENAL AND CLINICAL EVENTS IN PATIENTS WITH AKI

Abstract Background and Aims AKI and anemia independently worsen the prognosis of hospitalized patients, but their association and adverse effects have been slightly studied. We aimed to investigate the effect of transfusions during hospitalization on hard renal and clinical outcomes of patients with AKI. In addition, we tested the influence of the number of transfusions on mortality between pure AKI (pAKI) and AKI-on-CKD (AoCKD) patients. Method Retrospective cohorts’ study, of in-patients with AKI attended by nephrology during a 12-month period. AKI severity was categorized by KDIGO-2012 criteria; we searched in a Hematology administrative data base for transfusions (and their number) during the hospitalization period. We analyzed epidemiological and clinical variables and compared the rates of the hard outcomes Length of Stay (LoS), Acute Hemodialysis (aHD), Dialysis Dependence at Discharge (DDD), and in-hospital Mortality (IHM) between individuals that didn't and received transfusions. Results We included 275 individuals, 134 (49%) were transfused; they were older and suffered more DM; with no differences in the ICU hospitalization and Charlson's Index. See Table 1A. We observed that transfused patients were classified more frequently in AKI Stage-3, had longer LoS, aHD, were more frequently dialysis dependent and their mortality rate was higher. See Table 1B. We compared patients with less or more than 5 transfusions; the latter group showed a higher rate of adverse events than the group of ≤4 transfusions. See table 1C. Figure 1 plots the K-M curve for survival between pAKI and AoCKD groups showing an excess mortality associated with the number of transfusions, especially in the AoCKD individuals. Conclusion In our study, we found that patients that received transfusions showed worst clinical and renal results including more severe AKI, longer hospital stay, higher rate of acute HD, dialysis dependence at discharge and mortality. We observed that the appearance of these adverse events was associated in a dose dependent manner with the number of transfusions; for these reasons, we consider that number of transfusions should be included in AKI risk models and calculators. Could optimizing the number of transfusions improve the rate of adverse renal and clinical events? We will need prospective and well-powered studies in order to answer this question and to deepen on the issue of AoCKD and worst clinical outcomes if transfused.

#4767 ACUTE CORTICAL NECROSIS IN PREGNANCY IS STILL AN IMPORTANT CAUSE FOR END-STAGE RENAL DISEASE IN DEVELOPING COUNTRIES

Abstract Background and Aims Renal cortical necrosis (RCN) is a serious complication of acute kidney injury (AKI) and pregnancy is a clinical state closely associated with it with poor renal outcomes. The incidence is much higher in obstetrical AKI compared to other causes of RCN. Despite better medical care facilities available, this continues to be an important cause of morbidity and mortality in developing countries. Method This is a retrospective analysis among all pregnant females presenting with AKI from January 2000 to December 2020 at a tertiary care center in the northern part of India. We looked for the incidence of obstetrical-related RCN in our renal biopsies performed in the last 20 years and to evaluate precipitating factors responsible for RCN. Results RCN constituted 8.1 % of pregnancy-related AKI cases in our institution. The overall incidence has been declining which was 9.09% from 2000 to 2008 to 8.7 % from 2009 to 2014 and 8.1% from 2014-2020. The patient's median age was 28.4 ± 4.6 years. The average time to presentation from the day of delivery was 7.8 ±3.0 days. The mortality was observed in 10.4 % of them with sepsis and multiorgan dysfunction present in all of them. The most common etiology for RCN was found to be septic abortion and puerperal sepsis accounting for - 16.2 % each. Postpartum hemorrhage was a cause in 9.67 % of patients. The most important cause of RCN was postpartum thrombotic microangiopathy which was observed in 49.5% of patients. Kidney biopsy was helpful in diagnosis in 36 patients while computed tomography scan abdomen alone helped in diagnosis in five patients. Patchy cortical necrosis in histology was seen in 36.7% of patients and morbidity in terms of prolonged hospitalization was seen in 23.4 % while dialysis dependency in 63.4% of the study population Conclusion Strategies need to be implemented in reducing the preventable causes for RCN which is not only catastrophic in terms of renal outcomes but also for social and psychological perspectives as well.

#6260 PREDICTING KIDNEY FUNCTION AND END-STAGE KIDNEY DISEASE IN ANCA-ASSOCIATED VASCULITIS USING ANCA, C-REACTIVE PROTEIN AND C3

Abstract Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are systemic autoimmune diseases that involve small- and medium-sized blood vessels. AAV compromises the overall survival of patients, and its kidney involvement can lead to end-stage kidney disease (ESKD). Our aim was to determine whether the serum C3, C-reactive protein (CRP) and ANCA levels could predict kidney survival. Method We retrospectively reviewed patients with AAV and kidney involvement (n = 62) from 2006 to 2022. Demographic, clinical and laboratory data were collected. Patients’ ANCA title were measured by ELISA, and Glomerular Filtration Rate (GFR) was estimate by CKD-EPI equation. ANCA, C3 and CRP were measure at diagnosis, remission, and last follow-up. ANCA was analyzed as continuous and categorical variable. We analyzed factors associated with dialysis dependency at diagnosis and evolution to ESKD. Multivariable adjusted Cox regression analysis was performed for assessing predictive variables associated with dialysis outcome. Results The cohort included 62 total patients, with median age of 69 (63-77) years old, 44% were female, 35.5% (n = 22) presented with alveolar haemorrhage, 82.3% (n = 51) were MPO-ANCA+ and 4 patients had concomitant anti-GBM+. At admission, the median ANCA title was 80.5 UI/mL (36.75- 112.25), C3 was 108.5 mg/dL (90-130.25) and CRP 7.5 mg/dL (2.14-14.34). The GFR was 11.17±11.16 at admission and 24% of patients required dialysis at admission (n = 15). At 3 months 30% (n = 19) required dialysis, 10% at 6 months (n = 6) and 5% at 1 year (n = 3). The median time until dialysis was 488.98 (0-5702) days. Twenty (32.3%) patients died during the study period. The title of ANCA at admission, as categorical variable, did not associate with requirement of kidney replacement therapy during follow-up (p = 0.870) nor as a continuous variable (p = 0.523). Considering C3 and CRP, only low C3 at last follow-up correlates with ESKD (p = 0.028). Median C3 at last follow-up was 91.5 mg/dl (79.5-107) in ESKD patients and 114.5 mg/dl (92-142.75) in patients that do not require dialysis. In the cox regression analysis of kidney survival, C3 levels at last follow-up were significantly associated with a shorter time until dialysis (p = 0.006). In a multivariate analysis, including age and gender, C3 levels at last follow-up lost significance to predict time until ESKD (p = 0.083, model p = 0.005). Initial GFR was not correlated with ANCA title at admission (r = 0.220, p = 0.205) nor as a categorical variable (p = 0.592). At remission, GFR was not correlated with ANCA title (r = 0.383, p = 0.349). Considering factors associated with the need for dialysis at admission, only CRP levels at admission were significantly higher (p = 0.035) in those who required dialysis. ANCA title and C3 at admission did not correlate with dialysis at admission (p = 0.875, p = 0.702). In multivariate analysis, including age and gender, CRP maintain its significancy (p = 0.036, model p = 0.044). Conclusion C3 and CRP levels have been studied as possible factors predicting kidney survival, however, results are not consistent. CRP is a marker of inflammation and C3 represents complement activity, these serologic markers could be important to identify patients at risk for ESKD. In our study CRP levels seems to be related to dialysis requirement at admission. These patients should be followed more closely and carefully to improve kidney survival.

#5121 IGM POSITIVE MINIMAL CHANGE DISEASE: CHARACTERIZING DISEASE SEVERITY AND OUTCOMES

Abstract Background and Aims Minimal change disease (MCD) is the main cause of nephrotic syndrome in pediatric age and it is responsible for 10-25% of the cases in adults. It is characterized by minimal glomerular abnormalities in light microscopy, usually without immunoglobulins or complement deposits in immunofluorescence (IF). There is a subgroup of patients that presents with IgM deposition in IF, which has been described as a more aggressive disease, with frequent relapses [1], dependence of steroids [2] and worse outcomes. Method This is a retrospective study that analyses the follow up of 50 adult MCD patients in the nephrology consult, with diagnosis in childhood or adulthood. They had renal biopsies performed between 2009 and 2022. We did not include inappropriate biopsy samples, biopsies without IF or positive for C1q. We compared the characteristics between IgM positive (IgM+) and IgM negative (IgM-) patients at diagnosis, as well as the number of relapses per year, age of presentation and association with steroid-dependence or steroid-resistance. Results There were 23 (46%) patients in the IgM+ group and 27 (54%) in the IgM- group, with a mean follow-up of 10.2± 7.8 years. The IgM- subgroup was older at biopsy time (52 (30-74) years vs IgM+ 15 (13-23) years; p = 0.001) and this is probably related with the age of disease presentation, which was younger in the IgM+ group (12 (5-16) years vs IgM- 52 (73-13) years; p = 0.001). The groups were similar in sex distribution (IgM+ male n = 15 (55.6%) vs IgM- male n = 10 (44.0%); p = 0.395). There were no differences in diabetes and dyslipidemia frequencies between the two groups (Diabetes: IgM+ n = 1 (4.3%), IgM- n = 3 (11.3%), p = 0.614; Dyslipidemia: IgM+ n = 7 (30.4%), IgM- n = 7 (25.9%), p = 0.723), but the IgM- group had more patients with hypertension (IgM+ n = 2 (8.7%), IgM- n = 9 (33%), p = 0.046). The estimated glomerular filtration rate based on creatinine (eGFRcr) at biopsy time was higher in the IgM+ group (124 (104-130) ml/min/1.73 m2 vs IgM- with 96 (84-111) ml/min/1.73 m2; p = 0.003), but this happens probably due to the age as a confounding variable. In regard to the number of relapses per year, the IgM+ group had significantly more relapses than the IgM- group (IgM+ with 0.61 (0.27-1.00) relapses per year; IgM- with 0.17 (0.01-0.65) relapses per year; p = 0.011). The steroid-dependence (IgM+ n = 15 (65%); IgM- n = 11 (47%); p = 0.084) and the steroid-resistance (IgM+ n = 6 (26%); IgM- n = 3 (11%); p = 0.270) isolated outcomes were not significantly different in the two groups, but when we analyze the composed outcome of steroid-dependence plus steroid-resistance we have worse outcomes in the IgM+ subgroup (IgM+ n = 21 (91.3%); IgM- n = 14 (51.8%); p = 0.04; ORR 9.72; IC 95% 2.37-33.33). An IgM+ patient has 9.7 times the odd of being steroid-dependent or steroid-resistant of an IgM- patient. From our 50 patients, 3 evolved to stage 5 chronic kidney disease with dialysis dependency, being all of those patients IgM+. One of those patients had a recurrency of MCD after kidney transplant. There were 3 deaths with non-related to kidney disease causes, 1 in the IgM+ and 2 in the IgM- groups. Genetic test was performed in 5 of the IgM+ patients, with 4 positive results for mutations. Only 2 IgM- patients did genetic test, all without mutation´s identification. Conclusion This study supports the evidence that MCD patients with IgM+ biopsies have younger age MCD's presentation, more relapses per year and more steroid dependence plus resistance. Dialysis was started in 3 IgM+ patients and this group seems to have higher frequency of genetic mutations. This suggests that genetic testing could be important for future prognosis prediction and treatment options in the IgM+ patients, but further studies with a bigger study population need to be done to establish this relation.

#2959 EFFICACY AND SAFETY OF ROXADUSTAT IN PATIENTS WITH ANEMIA OF DIALYSIS-DEPENDENT CKD WITH OR WITHOUT INFLAMMATION: A POOLED ANALYSIS OF 4 PHASE 3 STUDIES

Abstract Background and Aims Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia of chronic kidney disease (CKD). ESA hyporesponsiveness is prevalent in a significant portion of patients with CKD, especially those with end-stage renal disease on dialysis. Inflammation has been reported to contribute to ESA hyporesponsiveness and is associated with poor outcomes in patients with CKD. Roxadustat, an oral medication, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has previously demonstrated efficacy in patients with anemia of CKD. This pooled analysis evaluated the efficacy and safety of roxadustat in correcting hemoglobin (Hb) levels in subgroups of patients with dialysis-dependent (DD) CKD with or without inflammation at baseline. Method Data for this analysis were pooled from four phase 3, randomized, open-label, active comparator−controlled studies (HIMALAYAS [NCT02052310], ROCKIES [NCT02174731], PYRENEES [NCT02278341], SIERRAS [NCT02273726]) in patients with DD CKD. Outcomes evaluated were mean Hb change from baseline to Weeks 28−52 and mean weekly roxadustat dose (mg/kg) at Week 24 in patients with or without baseline inflammation (as determined by high-sensitivity C-reactive protein [hsCRP] level, divided into quintiles). Data were analyzed with an analysis of covariance model with baseline Hb as a covariate. Adjusted least-squares means, their difference, and corresponding confidence intervals were generated from datasets where missing data were imputed using missing at random-based multiple imputation, by treatment group, with baseline Hb, cardiovascular/cerebrovascular/thromboembolic history, geographical region (United States vs non-United States) and incident vs stable dialysis (≤4 vs &amp;gt;4 months) as predictor variables. Safety data were summarized descriptively. Results In total, 4072 patients with DD CKD (roxadustat N = 2022; ESA N = 2050) were evaluated. At baseline, mean Hb levels (g/dL [SD]) were similar in the roxadustat (9.80 [1.29]) and ESA (9.83 [1.29]) groups, regardless of baseline hsCRP levels (roxadustat hsCRP quintiles 1−5: 9.72 [1.43], 9.78 [1.27], 9.80 [1.32], 9.90 [1.18], and 9.79 [1.23], respectively; ESA hsCRP quintiles 1−5: 9.75 [1.34], 9.92 [1.23], 9.90 [1.23], 9.96 [1.23], and 9.62 [1.38], respectively). Hb change from baseline was greater in patients treated with roxadustat compared with ESA, regardless of baseline hsCRP levels (Fig. 1). At Week 24, patients with higher baseline hsCRP levels did not require higher doses of roxadustat compared to patients with lower baseline hsCRP levels (Fig. 2). The overall percentages of patients with at least one treatment-emergent adverse event were similar for patients treated with roxadustat (hsCRP quintiles 1−5: 86.7, 88.1, 86.6, 88.7, and 90.0, respectively) or ESA (hsCRP quintiles 1−5: 83.5, 84.6, 90.5, 88.2, and 87.9, respectively) across hsCRP quintiles. Conclusion In patients with anemia of DD CKD, roxadustat increased Hb levels without requiring increased doses of roxadustat in patients with or without baseline inflammation. Results from the current analysis suggest that roxadustat is effective, with a comparable safety profile to ESA, regardless of inflammation status.

#5397 FRAILTY ASSESSMENT TOOLS, SURVIVAL TIME AND TIME TO INITIATE DIALYSIS IN OLDER PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Chronic Kidney Disease (CKD) patients with frailty have been shown to have a shorter survival time compared to non-frail individuals. Additionally, frailty has been linked to earlier initiation of dialysis among CKD patients. Despite the availability of over 50 frailty assessment tools in the literature, few have been applied in studies of older adults with CKD. There is a need for a comprehensive analysis of different frailty tools to identify the most accurate tools that could predict survival time and time to start dialysis in older adults with CKD. The present study compares four commonly used assessment tools of frailty from different categories (self-reporting tools, clinical judgment tools and complex instruments) regarding their association with survival time and time to start dialysis. Method Two hundred forty patients with biochemical evidence of CKD Stages 4–5 were included in this prospective cohort study. The inclusion criteria included patients 65 years old or more with two consecutive measurements of estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73 m2 separated by more than three months, while exclusion criteria included dialysis dependence, history of kidney transplantation, recent acute kidney injury, initial visit with the provider, amputation, or cerebrovascular accident. The four frailty assessment tools used in the study were Prisma-7 and FRAIL Scale, Clinical Frailty Scale (CFS), and Frailty Phenotype (FP). Patients were followed-up for 36 months for death events or dialysis initiation. Results The study population (240 patients) comprised 46% male patients with a mean age of 73.8 ± 6.6 years. Approximately 25% of patients were considered frail using the FRAIL scale, 69% using Prisma-7, and almost 40% using CFS and FP. Except for Prisma-7, “frail” patients, as determined by the FRAIL, CFS, and FP scores (Fig. 1), had significantly shorter survival times, with a mean survival of 24.9 months (Log-rank p &amp;lt;0.001), 27.3 months (Log-rank p = 0.041), and 26.6 months (Log-rank p = 0.004) respectively. No significant differences were observed in time to dialysis initiation when comparing frail and non-frail patients using any of the frailty assessment tools (Table 1). Conclusion The findings suggest that the frailty scores derived from the FRAIL, CFS, and FP tools are better predictors of survival time in frail elderly patients with CKD, while further research is required to determine the most appropriate frailty tool to predict the time to start dialysis in this population.

#5924 LATE DIAGNOSIS OF IGA NEPHROPATHY IN LOWER SAXONY (GERMANY) – CLINICAL AND HISTOPATHOLOGICAL DATA FROM 246 PATIENTS AT TIME OF INITIAL RENAL BIOPSY

Abstract Background and Aims IgA Nephropathy (IgAN) is the most frequent glomerulonephritis and contributes significantly to the burden of dialysis dependence. If not detected in the context of screening health examinations e.g. for the military service, decline in renal function is usually unnoticed due to the lack of specific symptoms. After decades of limited pharmacological options, the advent of new therapies provides opportunities for early intervention. Age and renal function as well as proteinuria at the time of renal biopsy varies depending on healthcare systems but might influence the use of novel interventions. Publications from outside Germany report that eGFR at the time of first renal biopsy in IgAN varies between 73.8 and 94.9ml/min/1,73 m2. The age at the time of diagnosis is between 27 and 40 years. The aim of our study was to investigate renal function, degree of proteinuria as well as histological parameters at the time of first renal biopsy in patients with IgA nephropathy. Method This retrospective study evaluated data from two different tertiary care hospitals in Germany that that sent their renal biopsies to the Nephropathology Department at the Hannover Medical School from January 2012 – October 2022. Only initial biopsies from native kidneys were included. Histopathological parameters and clinical as well as laboratory parameters at the month of biopsy were obtained. eGFR was calculated according to the CKD-EPI formula. Results First time diagnosis of IgA nephropathy was made in 246 patients at a median age at of 45 (range 4–79) years, 76.8% were male. The median serum creatinine level was 1.44mg/dl, corresponding to a median eGFR of 43.0 (3.8–132) ml/min/1.73 m2. Surprisingly 49.5% of all patients were at CKD KDIGO GFR stage 3B or higher at the time of first biopsy (Figure 1). Median proteinuria was 1.84 (0.08 – 16.5) g/d in those patients where 24h urine collection was performed. 156 of 246 patients had microhematuria at the time of biopsy. Based on the Oxford classification &amp;gt;50% had hypercellularity. Endocapillary hypercellularity was present in 24%. Segmental glomerulosclerosis was almost evenly distributed (S0:116 | S1:112). Tubular atrophy and interstitial fibrosis were visible in most biopsies in 0-25% of cortical area (T0:153 | T1:59 | T2:16). In 27.2% the C-score was analyzed, showing cellular and/or fibrocellular crescent in 26.8% of those patients. Thrombosis and necrosis were rather uncommon in initial biopsies of IgA Nephropathy. Conclusion The study shows that an IgA Nephropathy shows severe renal impairment at the time of diagnosis i.e. first renal biopsy, suggesting that patients are referred rather late for this diagnostic procedure. These regional data have to be validated in larger cohorts. If confirmed, measures for earlier screening and referral should be implemented to allow timely intervention thus lowering need for renal replacement therapy.

Economic Analysis of Renal Replacement Therapy Modality in Acute Kidney Injury Patients With Fluid Overload.

Decision analytical model comparing health outcomes and healthcare costs of CRRT versus IHD initiation for AKI patients with FO. The model had an inpatient phase (over 90-d) followed by post-discharge phase (over lifetime). The 90-day phase had three health states: FO, fluid control, and death. After 90 days, surviving patients entered the lifetime phase with four health states: dialysis independent (DI), dialysis dependent (DD), renal transplantation, and death. Model parameters were informed by current literature. Sensitivity analyses were performed to evaluate results robustness to parametric uncertainty. ICU. AKI patients with FO. IHD or CRRT. The 90-day horizon revealed better outcomes for patients initiated on CRRT (survival: CRRT 59.2% vs IHD 57.5% and DD rate among survivors: CRRT 5.5% vs IHD 6.9%). Healthcare cost was 2.7% (+$2,836) higher for CRRT. Over lifetime, initial CRRT was associated with +0.313 life years (LYs) and +0.187 quality-adjusted life years (QALYs) compared with initial IHD. Even though important savings were observed for initial CRRT with a lower rate of DD among survivors (-$13,437), it did not fully offset the incremental cost of CRRT (+$1,956) and DI survival (+$12,830). The incremental cost-per-QALY gained with CRRT over IRRT was +$10,429/QALY. Results were robust to sensitivity analyses. Our analysis provides an economic rationale for CRRT as the initial modality of choice in AKI patients with FO who require renal replacement therapy. Our finding needs to be confirmed in future research.

Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK)

Continuous renal replacement therapy (CRRT) is used for the symptomatic management of acute kidney injury (AKI) and fluid overload (FO). Contemporary reports on pediatric CRRT are small and single center in design. Large international studies evaluating CRRT practice and outcomes are lacking. Herein, we describe the design of a multinational collaborative. The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) is an international collaborative of pediatric specialists whose mission is to improve short- and long-term outcomes of children treated with CRRT. The aims of this multicenter retrospective study are to describe the epidemiology, liberation patterns, association of fluid balance and timing of CRRT initiation, and CRRT prescription with outcomes. We included children (n= 996, 0-25 years) admitted to an intensive care unit (ICU) and treated with CRRT for AKI or FO at 32 centers (in 7 countries) from 2018 to 2021. Demographics and clinical characteristics before CRRT initiation, during the first 7 days of both CRRT, and liberation were collected. Outcomes include the following: (i) major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction), and (ii) functional outcomes (functional stats scale). The retrospective WE-ROCK study represents the largest international registry of children receiving CRRT for AKI or FO. It will serve as a broad and invaluable resource for the field of pediatric critical care nephrology that will improve our understanding of practice heterogeneity and the association of CRRT with clinical and patient-centered outcomes. This will generate preliminary data for future interventional trials in this area.

THE PROGNOSTIC ROLE OF CLINICAL FEATURES AND BIOMARKERS IN PATIENTS HOSPITALIZED WITH CARDIORENAL SYNDROMES

Objective: Cardiorenal syndromes (CRS), involving the heart-kidney cross-talk and the activation of neurohumoral and inflammatory pathways, is an entity characterized by high morbidity and mortality. The aim of this study was to evaluate the prognostic role of risk factors and biomarkers in patients hospitalized for CRS. Design and method: In this prospective, observational cohort study, 113 consecutive patients hospitalized for CRS were enrolled. Socio-demographic characteristics, personal medical history, and prior medication use were recorded upon admission, and echocardiography was performed. Moreover, an array of blood markers were measured. The endpoint of interest was a composite of death or dialysis dependence at discharge. Results: Patients were classified into two groups; Group 1 (N = 59): discharged being dialysis-independent, Group 2 (N = 54): death/dialysis dependence at discharge. No major differences were detected in baseline characteristics between the two groups. Group 2 patients used renin-angiotensin-aldosterone system blockers (RAASb) less often (Group 1: 69.5% vs. Group 2: 46.3%, p = 0.01) and more frequently presented with oliguria/anuria (Group 1: 28.8% vs. Group 2: 70.4%, p &lt; 0.001) and any infection (Group 1: 33.9% vs. Group 2: 55.6%, p = 0.02). No dissimilarities were noted in echocardiographic markers. Group 2 patients had significantly lower hemoglobin, serum albumin, bicarbonate, and 25-hydroxy-vitamin D (25OHD). At the same time, N-terminal prohormone brain natriuretic peptide, serum potassium, and parathyroid hormone (PTH) were significantly higher in Group 2 patients (Figure 1). In a multivariate regression analysis, lack of RAASb was independently associated with a 17.7-fold increased risk of death or dialysis dependence at discharge, while the decreasing 25OHD/PTH ratio (beta coefficient -0.01, p = 0.007) and increasing admission serum potassium levels (beta coefficient 0.82, p = 0.03) increased the possibility of facing the composite endpoint. Following a receiver operating characteristic curve analysis, 25OHD/PTH ratio emerged as the most accurate predictor of facing the composite endpoint, with an ideal cutoff of 103.7 (sensitivity 81%, specificity 74%) (Figure 2). Conclusions: Lack of prior RAASb use, high admission serum potassium, and a low 25OHD/PTH ratio are associated with poor prognosis in patients hospitalized for CRS.

Early Fluid Balance Is Associated with 90-Day Mortality in Patients Receiving Continuous Renal Replacement Therapy.

Continuous renal replacement therapy (CRRT) is widely used to control fluid balance, but the optimal fluid balance to improve the prognosis of patients remains debated. Appropriate fluid management may depend on hemodynamic status. We investigated the association between 90-day mortality and fluid balance/mean arterial pressure (MAP) in patients receiving CRRT. This single-center retrospective study was conducted between May 2018 and March 2021. Based on the cumulative fluid balance at 72 h after initiation of CRRT, the cases were divided into negative (< 0 mL) and positive (> 0 mL) fluid balance groups. Ninety-day mortality was higher in the positive fluid balance group (p=0.009). At 4 h before and after CRRT initiation, the mean MAP was lower in the positive fluid balance group (p<0.05). After multivariate cox adjustment, 72-h positive fluid balance was independently associated with 90-day mortality (p=0.004). In addition, the cumulative fluid balance was associated with 90-day mortality (p<0.05) in cases without shock, high APACHE II score, sepsis, dialysis dependence, or vasopressor use. A 72-h positive fluid balance was associated with 90-day mortality in patients receiving CRRT.