Dialysis-dependent Chronic Kidney Disease Research Articles

A Randomized Trial of the IMPACT of Ferric Citrate on Erythropoietin and Intravenous Iron Use in Patients Receiving Dialysis.

Ferric citrate (FC) is an FDA-approved iron-based phosphate binder for adults with dialysis-dependent chronic kidney disease. This study investigated the impact of FC as the primary phosphate-lowering therapy on utilization of erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron. In this randomized, open-label, active-controlled, multicenter study (NCT04922645), patients on dialysis and receiving ESAs were randomized to receive FC or remain on standard of care (SOC) phosphate-lowering therapy for up to 6 months. Primary endpoints were the difference in change from baseline to efficacy evaluation period (EEP) in mean monthly ESA and IV iron doses. Secondary endpoints included treatment differences in hemoglobin, phosphate, TSAT, and ferritin levels. 209 patients were randomized to FC and had a Day 1 Dosing Visit (n=103) or SOC (n=106). The two groups had similar baseline laboratory characteristics, however atherosclerotic CV disease, peripheral vascular disease, and congestive heart failure were more common in the SOC group. The mean treatment difference in ESA monthly dose was -30.8 µg (FC vs SOC; p=0.02). An absolute though non-statistically significant change in mean monthly IV iron dose of -37.2 mg (p=0.17) was observed with FC. Mean hemoglobin, TSAT, and ferritin all increased from baseline to the EEP with FC vs. SOC. Serious adverse events occurred in 28% of patients receiving FC vs. 37% in those receiving SOC. In patients receiving dialysis, treatment with FC as compared to remaining on SOC phosphate binders resulted in reductions in mean monthly ESA and IV iron dose.

The CONVINCE randomized trial found positive effects on quality of life for patients with chronic kidney disease treated with hemodiafiltration

In the CONVINCE trial, the primary analysis demonstrated a survival benefit for patients receiving high-dose hemodiafiltration (HDF) as compared with high-flux hemodialysis (HD). A secondary objective was to evaluate effects on health-related quality of life (HRQoL); assessed in eight domains (physical function, cognitive function, fatigue, sleep disturbance, anxiety, depression, pain interference, social participation) applying instruments from the Patient-Reported Outcome Measurement Information System (PROMIS) before randomization and every three months thereafter. In total 1360 adults with dialysis-dependent chronic kidney disease, eligible to receive high-flux HDF (23 liters or more), were randomized (1:1); 84% response rate to all questionnaires. Both groups reported a continuous deterioration in all HRQoL domains. Overall, raw score changes from baseline were more favorable in the HDF group, resulting in a significant omnibus test after a median observation period of 30 months. Most relevant single raw score differences were reported for cognitive function. Patients receiving HDF reported a decline of -0.95 units (95% confidence interval - 2.23 to +0.34) whereas HD treated patients declined by -3.90 units (-5.28 to - 2.52). A joint model, adjusted for mortality differences, utilizing all quarterly assessments, identified a significantly slower HRQoL decline in physical function, cognitive function, pain interference, and social participation for the HDF group. Their physical health summary score declined -0.46 units/year slower compared to the HD group. Thus, the CONVINCE trial showed a beneficial effect of high-dose hemodiafiltration for survival as well as a moderate positive effect on patients’ quality of life, most pronounced with respect to their cognitive function.

#2815 Single center, single arm, prospective, observational study of desidustat in chronic kidney disease-induced anemia

Abstract Background and Aims Anemia in chronic kidney disease (CKD) is multifactorial. Relative deficiency of erythropoietin is one of the key reasons for decreased RBC production. This anemia is associated with poor quality of life and increases morbidity in CKD patients. Injectable erythropoietin is the standard of care for CKD-anemia, which has safety concerns. Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), stimulates endogenous erythropoiesis and is approved for CKD anemia treatment. Hence, the present study identifies the real-world clinical efficacy and safety of the desidustat treatment for a short duration in CKD anemia. Method This is an open-label, single-center, prospective study. We analyzed the data of 130 patients who are currently in follow-up and received Desidustat as treatment for CKD-anemia. The study is for the duration of 24 weeks. We followed up on patent at 1 month, 3 months, and the end of the study (6 months). Patients were given a 100-mg Desidustat tablet orally three times in a week. The primary outcome is to assess the change in Hb from baseline, and the secondary outcome is the safety of the therapy. Results In this study, we enrolled 130 patients. Of these 130 patients, 58.4% (n = 76) were male and 41.5% (n = 54) were female. The mean age of the study population was 53.6 ± 12.3 years. The majority of the study population was in the pre-dialysis category; 80% (n = 104) and 20% (n = 26) were on dialysis. All the dialysis patients were on three times per week on Dialysis. Diabetes (68%) and hypertension (75%) are the most common co-morbid conditions in patients with CKD anemia. All the patients received desidustat at a 100 mg, three-weekly dose. During each follow-up visit, a significant rise in hemoglobin was observed (p<0.001), as shown in the figure. With desidustat therapy, adverse drug reactions were seen in 5.3% (n = 7) cases: three cases of abdominal pain, two cases of vomiting, and two cases of diarrhea. Conclusion Oral HIF-PHIs and Desidustat showed significant improvement in hemoglobin in CKD anemia patients. More studies require for safety and efficacy in Dialysis dependent CKD - Anemia patients.

#1904 Prevalence of osteoporosis in dialysis dependent CKD patients: a cross sectional study from India

Abstract Background and Aims Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. However, the data on prevalence of Osteopenia and osteoporosis in Chronic kidney disease in India is scarce This multicentric, cross sectional study was done to assess the prevalence of osteoporosis in dialysis dependent chronic kidney disease patients. Method This study was conducted in CKD patients on maintenance hemodialysis. Osteoporosis and osteopenia were confirmed on the basis of T-scores using portable- Heel Ultrasound Bone Densitometer. Results A total of 1033 Dialysis patients were screened during August 2022 to December 2022. More than half (56%) of the patients were male. The prevalence of osteoporosis and osteopenia was observed to be 17% and 66%, respectively. Mean T- Score observed in overall population was -1.71 + .0.85, while it was -1.66 + 0.86 and -1.77 + 0.83 in males and females respectively. The maximum T- score observed in males was 2.0 and in females it was 4.0. In females, the minimum T-score was -4.3 while in males it was -2.51. Overall, 16.5% of males and 18% of females were osteoporotic. Among geriatric males (>60 years), average T-score was -1.55 + 0.42 while in geriatric female it was 1.78 + 0.80 Conclusion This data of Osteopenia and osteoporosis should be alarming as osteopenia itself is considered a very serious risk factor for the development of osteoporosis. Early intervention for diagnosis and timely initiation of treatment of osteoporosis is recommended for the CKD population to prevent complications like fractures and falls.

Cataract Surgery and Chronic Kidney Disease: A Hospital-based Prospective Cohort Study.

Objective Cataract and chronic kidney disease (CKD) occur with increasing frequency with age and share common risk factors including smoking, diabetes, and hypertension. We evaluated the risk of incident cataract surgery in patients with non-dialysis-dependent CKD and dialysis-dependent CKD compared to non-CKD patients, while taking into account the competing risk of death. Methods The participants included 1,839 patients from Sado General Hospital enrolled in the Project in Sado for Total Health (PROST) between June 2008 and December 2016 (54% men; mean age, 69 years). Among these patients, 50%, 44%, and 6% had non-CKD, non-dialysis-dependent CKD, and dialysis-dependent CKD, respectively. Results During a median follow-up of 5.6 years (interquartile range, 4.7-7.1), 193 participants underwent cataract surgery [18.7 (95% confidence interval (CI), 16.2-21.5)/1,000 person-years] and 425 participants died without undergoing cataract surgery [41.0 (95% CI, 37.4-45.2)/1,000 person-years]. The cumulative incidence of cataract surgery was the highest in the dialysis-dependent CKD group, followed by the non-dialysis-dependent CKD and non-CKD groups (log-rank p=0.002). After adjusting for potential confounding factors, the dialysis-dependent CKD group [hazard ratio (HR) 2.48; 95% CI 1.43-4.31], but not the non-dialysis-dependent CKD group (HR, 1.01; 95% CI 0.74-1.38), had a higher risk of cataract surgery than the non-CKD group. However, this association was no longer significant according to a competing risk analysis (sub-hazard ratio, 1.67; 95% CI 0.93-3.03). Conclusion Dialysis-dependent CKD patients were found to have an increased risk of cataract surgery; however, the association was attenuated and no longer significant when death was considered a competing risk.

Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase3 Roxadustat Trials in Japan.

Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase3 clinical trials in Japan. Thromboembolic events with onset before and after week12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36-37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95%CI 1.52-25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95%CI 1.23-15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150mg; unadjusted OR 5.95; 95%CI 1.07-33.16; vs < 50mg) over the previous 8weeks before the event onset were associated with thromboembolic events after week12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95%CI 1.82-33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< - 2fL; adjusted OR 5.55; 95%CI 1.73-17.83; vs ≥ 0fL) were associated with increased risk of thromboembolic events. In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. NCT02780726, NCT02952092, NCT02780141, NCT02779764.

Distal AVF creation with marginal calcified radial artery: Multicentric experience of intraoperative intravascular lithotripsy.

The first-choice vascular access to starting dialysis in patients with End Stage Renal Disease (ESRD) is autogenous distal arteriovenous-fistula (AVF) to spare vascular district avoiding proximal fistula complications. One of most significant exclusion criteria to create distal AVF is still now the presence of huge calcification of the feeding artery due to large numbers of early failure (EF) and failure in maturation (FTM). In recent years the possibility to use new devices able to deliver intravascular lithotripsy (IVL) to treat high calcified stenosis could be a possibility to recruit these marginal arteries to create distal AVF. ESRD patients with totally calcified radial artery wall were enrolled to participate to this prospective, single arm, multicentric study. The selected patients were treated with intraoperative IVL at surgical time, during anastomosis creation to soften calcified radial artery. Patients were followed 1 month after surgery with eco-doppler, for flow and vessels maturation assessment. At 3 month was investigated how many patients have started dialysis treatment with two needle cannulation and good efficiency. Nineteen distal forearm radio-cephalic fistula were built in 19 patients. One-month doppler assessment showed mean AVF flow of 743 ml/min and efferent vein caliper of 6.46 mm. At 3 months 14 patient have started stable 2 needles dialysis (other three patients were not yet dialysis dependent CKD). Were observed one immediate failure, one failure in maturation, and two late failures at 4 and 16 months respectively. Sixteen months primary and secondary patency was 78.9% and 89.5% respectively. These results showed how intraoperative IVL could help to recruit huge calcified marginal artery to create autogenous distal forearm AVF, avoiding proximal AVF, risking distal ischemia syndrome, and sparing vascular district to eventually rebuilt more proximal AVF in future.

A comparative analysis of serum phosphorus levels and mineral metabolic markers in non-dialysis and dialysis chronic kidney disease patient: a cross-sectional study

Background: Chronic kidney disease is a major public health problem worldwide. As kidney function declines, it leads to several metabolic abnormalities including dysregulation of mineral metabolism. It is also reported that hyperphosphatemia in patients with advanced kidney disease is associated with an increased risk of mortality and cardiovascular events, and is higher in dialysis-dependent chronic kidney disease (CKD) patients compared to non-dialysis CKD. However, data in the Indian context is limited. Objectives were to evaluate and compare serum phosphorus levels and associated factors in non-dialysis and dialysis CKD patients. Also, the impact of dietary phosphate restriction and the use of phosphate binders on serum phosphorus is analysed. Methods: A cross-sectional study was conducted at a tertiary care hospital in Kolkata, India, with 100 CKD patients: 50 non-dialysis CKD patients and 50 dialysis-dependent CKD patients. Relevant demographic, clinical and laboratory parameters including serum phosphorus, calcium, parathyroid hormone (PTH), alkaline phosphatase, albumin and estimated glomerular filtration rate (eGFR) were collected. Data was analyzed using appropriate statistical tests. Results: Mean serum phosphorus was significantly higher in the dialysis CKD group (6.12±0.34 mg/dl) compared to the non-dialysis CKD group (4.56±0.80 mg/dl). Serum calcium and PTH were also higher while eGFR and albumin were lower in the dialysis CKD group. Serum phosphorus levels increased with advancing CKD stages in the non-dialysis group. Phosphate binder helped phosphorus control in dialysis CKD patients. Conclusions: Our study is in confluence with other reports and dietary phosphate restriction and the use of phosphate binders help optimize phosphorus levels in CKD patients.

Evaluating the Outcomes of Roxadustat Treatment for Anemia in Dialysis-Dependent CKD: A Systematic Review and Meta-Analysis

Evaluating the Outcomes of Roxadustat Treatment for Anemia in Dialysis-Dependent CKD: A Systematic Review and Meta-Analysis

Safety and Efficacy of Vadadustat Thrice Weekly in Patients with Anemia due to Dialysis-Dependent CKD

Safety and Efficacy of Vadadustat Thrice Weekly in Patients with Anemia due to Dialysis-Dependent CKD

Comparative Analysis of Tools for Assessment of Protein–Energy Wasting in Chronic Kidney Disease Patients on Maintenance Hemodialysis

Abstract Background: Patients with chronic kidney disease have muscle wasting, sarcopenia, and cachexia that contribute to frailty and morbidity. The present study assessed the prevalence of protein–energy wasting in dialysis-dependent chronic kidney disease population and evaluated the validity of various nutritional assessment tools in diagnosing protein–energy wasting. Materials and Methods: All patients above 18 years undergoing dialysis for more than 3 months without any active infection or malignancy were included in our study. Data from anthropometric measurements, dietary assessment, and blood investigations were collected. Protein–energy wasting was assessed by the International Society of Renal Nutrition and Metabolism 2008 criteria. Diagnostic validity of the nutritional assessment tools to predict protein–energy wasting was estimated by area under the curve, sensitivity, specificity, and accuracy statistics. Results: A total of 146 patients were studied. The prevalence of protein–energy wasting was 56.8%. Protein–energy wasting was significantly associated with socioeconomic status, hospitalization days, and catheter days. Normalized protein catabolism rate had the highest sensitivity (90.4%) for predicting protein–energy wasting. Malnutritional inflammatory score had the highest area under the curve (0.858), specificity (82.5%), and accuracy (82.2%). Mid-upper arm circumference, Dialysis Malnutrition Score, and albumin were also found to be significant predictors of protein–energy wasting. Conclusion: Lack of advanced equipment in suburban and rural centers to detect protein–energy wasting in India can be overcome by using the various stand-alone and combination nutrition assessment tools which have been validated in the present study.

Association between chronic kidney disease and risk of bullous pemphigoid: a nationwide population-based cohort study.

Studies have shown that bullous pemphigoid (BP) occurs in patients with chronic kidney disease (CKD). However, the risk of developing BP in patients with CKD remains inconclusive. To investigate whether CKD increases the risk of BP. Participants were recruited from the National Health Insurance Database of Taiwan between 2007 and 2018. Overall, 637,664 newly diagnosed patients with CKD and 637,664 age-, sex-, and comorbidity-matched non-CKD participants were selected. A competing risk model was used to evaluate the risk of development of BP. After adjusting for age, sex, and comorbid diseases in the multivariate model, CKD was a significant risk factor for BP (adjusted hazard ratio [aHR]: 1.29; 95% confidence interval [CI]: 1.17-1.42; p<0.001). CKD patients were classified into the dialytic or non-dialytic groups and compared to non-CKD participants, and this revealed that patients with dialysis-dependent CKD had the highest risk of BP (aHR 1.75; 95% CI 1.51-2.03), followed by patients with non-dialysis-dependent CKD (aHR 1.20; 95% CI 1.08-1.32). We lacked detailed laboratory data on the severity of CKD. Compared with individuals without CKD, those with CKD had a 1.3-fold increased risk of BP. Patients with dialysis-dependent CKD had an even higher BP risk (1.8-fold).

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.

Short-term outcomes of colorectal cancer surgery in patients with dialysis: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the effect of dialysis-dependent chronic kidney disease (CKD) on postoperative complications in colorectal cancer surgery. In April 2023, we systematically searched PubMed, the Cochrane library, and Ovid for relevant studies on short-term outcomes of colorectal cancer surgery in patients with dialysis and analyzed the findings from these studies for meta-analysis. Our systematic and meta-analysis review identified seven studies involving 50713 patients. We showed that the dialysis group had higher rates of mortality (OR = 4.12, 95%CI: 2.75-6.20, P < 0.001), cardiac complications (OR = 2.45, 95%CI: 1.88-3.21, P < 0.001), and pneumonia (OR = 2.68, 95%CI: 1.83-3.93, P < 0.001). On the other hand, there were no differences in superficial/deep surgical site infection (SSI) (odds ratio [OR] = 1.17, 95%CI: 0.90-1.53, P = 0.230) and organ/space SSI (OR = 1.35, 95%CI: 1.00-1.82, P = 0.053) between the dialysis group and non-dialysis group. Our meta-analysis showed that dialysis-dependent CKD was associated with higher rates of mortality, cardiac complications, andpneumonia after colorectal cancer surgery. However, the limitations of this meta-analysis should be taken into consideration when interpreting the results.

FREQUENCY OF HEPATITIS C SEROCONVERSION IN CHRONIC KIDNEY DISEASE PATIENTS ON HEMODIALYSIS

Background: Haemodialysis increases Hepatitis-C seroconversion risk adversely affecting Chronic Kidney Disease (CKD) prognosis. This study aimed to determine the frequency of Hepatitis C seroconversion in chronic kidney disease patients on haemodialysis. Method: This cross-sectional study was conducted at Dialysis Unit of Ayub Teaching Hospital, Abbottabad from March 2016 to January 2019. A pre-designed proforma was used for data collection. A sample of 121 patients of dialysis dependent CKD was enrolled for the study through non-probability consecutive sampling. The Glomerular Filtration Rate (GFR) was re-estimated from serum creatinine to confirm the diagnosis using Modification of Diet in Renal Disease (MDRD) study equation. Patients who were Hepatitis C virus (HCV) negative at the start of dialysis, and became positive 3 months post-dialysis were considered having undergone seroconversion. Data were analysed using SPSS-16. Results: Out of 121 participants, 80 (66.1%) were male and 41 (33.8%) were female. The mean age of the patients was 51.0±6.22 years with range from 41 to 61 years. Hepatitis C seropositivity was recorded in 40 (33.06%) of the study participants during the study period. Statistically significant (p&lt;0.05) associations were observed between HCV seropositivity and age and gender of the patients. Conclusion: Hepatitis C infection is a common complication of haemodialysis. Rigorous screening of patients for Hepatitis C and separate machines for Hepatitis C patients can lead to a decrease in the burden of this disease. Pak J Physiol 2023;19(2):32–5

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.

#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.

#6829 DIFFERENTIAL LIPIDIC PROFILE WITH THE USE OF CITRATE OR ACETATE DIALYSATES

Abstract Background and Aims Unlike other high-cardiovascular-risk populations, the efficacy obtained from lipid-lowering therapy remains uncertain in dialysis-dependent chronic kidney disease (DD-CKD) patients. This is probably given to the exclusion in clinical trials of patients with very high LDL levels, their population's heterogeneity, accompanying cardiovascular morbidities, and the higher mortality risk explained partly by chronic inflammation. The latter has been associated with the accumulation of uremic toxins, membrane biocompatibility, and acetate-based dialysates, which promote inflammation. Different dialysate weak acidifying agents such as lactic, pyruvic, hydrochloric, or citric acids have surged as less-inflammatory alternatives to acetate. This study aims to evaluate the effects of the metabolism of acetate and citrate in the lipidic profile of DD-CKD patients. Method In a unicentric, cross-over, prospective study, we compared the lipidic profile by assessing the plasma levels of total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), high-density (HDL) and very low-density (VLDL) lipoprotein cholesterol, and lipoprotein (a) [Lp(a)] comparing the use of citrate (CD) vs. acetate (AD) as dialysate buffers, after twelve sessions with each one. Prealbumin was also measured to rule out malnutrition as a potential confounding factor. Prevalent (i.e., dialysis vintage ≥3 months) adult patients on maintenance hemodialysis were included. The dialysis prescription parameters and additional medical treatments remained unchanged during their sessions with both dialysates. Quantitative variables are reported with mean and standard deviation. Normal distribution was assessed with the Shapiro-Wilk test, and the comparisons were made with the Student's paired T-test or Wilcoxon's signed-rank test, accordingly. A two-sided p-value ≤0,05 was considered statistically significant. Results After twelve dialysis sessions with CD, compared to AD, there was a statistically significant decline in TG and HDL and an increase in LDL. There was also a notable but non-significant reduction in VLDL (Table 1). Conclusion There were noteworthy differences in the lipid profile that can only be attributed to the change of dialysis fluid, as we avoided inter-individual (with a cross-over design) and intra-individual (different inflammatory or nutritional profiles would not be expected with this short-term setting) variabilities. Further studies must elucidate if the short-term changes induced in the lipidic profile of DD-CKD patients by the dialysate's weak acid translate into clinical implications.

#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).

#2962 EFFICACY AND SAFETY OF ROXADUSTAT IN NON-DIALYSIS-DEPENDENT CKD PATIENTS WITH OR WITHOUT INFLAMMATION: A POOLED ANALYSIS OF FOUR PHASE 3 STUDIES

Abstract Background and Aims Chronic kidney disease (CKD)-associated anemia is commonly treated with erythropoiesis-stimulating agents (ESAs); however, some patients respond inadequately to ESAs. Inflammation may be a cause of ESA hyporesponsiveness. Roxadustat, an oral medication, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has shown efficacy in patients with anemia of CKD. This pooled analysis examined the efficacy and safety of roxadustat in correcting hemoglobin (Hb) levels in subgroups of patients with non−dialysis-dependent (NDD) CKD with or without inflammation at baseline. Method Data from four phase 3, randomized, placebo-controlled (OLYMPUS [NCT02174627], ALPS [NCT01887600], ANDES [NCT01750190]) or erythropoiesis-stimulating agent−controlled (ESA; DOLOMITES [NCT02021318]) studies in patients with NDD CKD were pooled for this analysis. Mean Hb change from baseline to Weeks 28−52 and mean weekly total roxadustat dose (mg/kg body weight) at Week 24 in patients with or without inflammation at baseline (as determined by high-sensitivity C-reactive protein [hsCRP] levels divided into quintiles) were evaluated with an analysis of covariance model with baseline Hb and baseline estimated glomerular filtration rate as covariates. Safety data were summarized descriptively. Results In total, 3573 patients with NDD-CKD (roxadustat N = 2068; placebo = 1212; ESA N = 293) were evaluated. At baseline, the mean [SD] Hb levels (g/dL) for roxadustat (hsCRP quintiles 1−5: 9.17 [0.82], 9.26 [0.68], 9.18 [0.75], 9.15 [0.74], 9.08 [0.82]), placebo (hsCRP quintiles 1−5: 9.09 [0.74], 9.20 [0.71], 9.15 [0.69], 9.09 [0.71], 9.01 [0.76]), and ESA (hsCRP quintiles 1−5: 9.53 [0.69], 9.53 [0.64], 9.54 [0.73], 9.60 [0.66], 9.53 [0.71]) were similar across hsCRP quintiles. The mean Hb change from baseline to Weeks 28–52 was greater with roxadustat than with placebo, and comparable between roxadustat and ESA, regardless of inflammation at baseline (Fig. 1). At Week 24, roxadustat dose was not increased in patients across hsCRP quintiles (hsCRP quintiles 1−5: 3.3, 3.0, 2.7, 3.1, 3.1 mg/kg, respectively). Roxadustat dose was not significantly higher at Week 24 for patients with moderate-to-high baseline hsCRP levels (quintile 4, &amp;gt;3.48 to ≤8.67 mg/L; least squares mean [LSM], 3.05; 95% CI, 2.80−3.30; quintile 5, &amp;gt;8.67 mg/L; LSM, 3.10; 95% CI, 2.83−3.36) compared with patients with low baseline hsCRP levels (quintile 1, ≤0.71 mg/L; LSM, 3.30; 95% CI, 3.04−3.56; treatment comparison between quintile 1 and quintile 4: LSM difference, 0.25; 95% CI, −0.11 to 0.61; treatment comparison between quintile 1 and quintile 5: LSM difference, 0.20; 95% CI, −0.17 to 0.57; Fig. 2), indicating that patients with increased inflammation at baseline did not consistently require a higher roxadustat dose. The overall percentages of patients with at least one treatment-emergent adverse event were similar across hsCRP quintiles for patients treated with roxadustat (hsCRP quintiles 1−5: 88.7, 91.4, 90.3, 90.7, 90.5), placebo (hsCRP quintiles 1−5: 88.2, 84.5, 89.4, 88.5, 87.9), and ESA (hsCRP quintiles 1−5: 89.1, 90.9, 91.4, 94.1, 94.8). The most common treatment-emergent adverse events were hypertension (hsCRP quintiles 1−5 [%]; roxadustat: 16.8, 16.5, 17.4, 22.2, 18.9; placebo: 7.9, 9.5, 11.8, 9.3, 8.5; ESA: 45.7, 36.4, 39.7, 22.1, 31.2), end-stage renal disease (hsCRP quintiles 1−5 [%]; roxadustat: 21.3, 22.7, 21.1, 24.6, 23.1; placebo: 13.8, 15.9, 15.3, 18.1, 16.5; ESA: 32.6, 36.4, 34.5, 39.7, 36.4), and decreased glomerular filtration rate (hsCRP quintiles 1−5 [%]; roxadustat: 4.6, 5.0, 4.5, 5.3, 5.1; placebo: 2.0, 2.0, 2.4, 1.3, 3.1; ESA: 13.0, 22.7, 19.0, 13.2, 16.9). Conclusion Independent of baseline inflammation status, roxadustat increased Hb levels greater than placebo and comparable to ESA with a similar safety profile. Patients with high baseline hsCRP did not require increased roxadustat doses to maintain Hb levels up to Week 24. These data suggest that roxadustat is effective in patients with anemia of NDD CKD regardless of inflammation status.