Non-dialysis Dependent Patients Research Articles

#1168 Responsiveness to roxadustat in chronic kidney disease associated anemia patients by baseline hemoglobin: a secondary analysis of ROXSTAR Registry

Abstract Background and Aims Anemia is a common complication of chronic kidney disease (CKD), and associated with increased morbidity and mortality, as well as a reduced quality of life (QoL). Various studies have shown anemia treatment in CKD patients improved the QoL. However, in ROXSTAR Registry (ChiCTR2100046322), although roxadustat corrected anemia and maintained hemoglobin (Hb) effectively, no improvement in QoL was observed. Hence, we conduct this secondary analysis of ROXSTAR to evaluate the Hb response to roxadustat treatment and the change of QoL in dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients stratified by baseline Hb. Method This was a secondary analysis using existing data collected in the ROXSTAR Registry. DD & NDD Patients who received at least one dose of roxadustat and had at least one post baseline Hb were included. We described the Hb response to roxadustat in patients with lower baseline (Hb <80) g/L & higher baseline Hb (≥80 g/L). The changes from baseline to week 12 & week 24 in Quality of Life (QoL) assessed by SF-36 Vitality (V) & Physical Function (PF) subscales, and Rapid Assessment of Physical Activity (RAPA) Strength & Flexibility scores were also analyzed respectively. Results Overall, 1998 patients (1508 DD patients and 490 NDD patients) were included, there were 238 patients (131 male [55.0%]) with a mean (standard deviation [SD]) age of 49.1 (13.6) years in the lower baseline Hb group, and 1760 patients (947 male [53.8%]) with a mean age of 50.3 (13.5) in the higher baseline Hb group. The overall mean baseline Hb was 97.3 (13.9) g/L, with 71.4 (7.2) g/L and 100.8 (10.5) g/L in the two groups respectively. The median (min, max) ferritin and mean transferrin saturation were 149.6 (3.3, 2304.0) ng/mL & 22.8% (15.5) % in the lower baseline Hb group and 169.8 (3.8, 3966.0) ng/mL & 30.6% (15.7%) in the higher baseline Hb group. More patients with CRP above normal limit were in the lower baseline Hb group (30.7%) compared to patients in the other group (19.7%) (Table 1). Mean weekly roxadustat dose started at 320 mg and was maintained during the first 12 weeks (correction phase) then slightly decreased to 300 mg from week 12 until week 52 (maintenance phase) in patients with baseline Hb <80 g/L, while it was from 286 mg to 260 mg during the correction phase then decreased and maintained at around 230 mg from week 12 to week 52 in patients with baseline Hb ≥80 g/L. The mean Hb change from baseline averaged over weeks 24-36 and 36-52 was 31.9 [95% CI: 29.9, 33.9] g/L & 33.7 [95% CI: 31.8, 35.6] g/L in the lower baseline Hb group, and 11.3 [95% CI: 10.6, 12.0] g/L & 11.1 [95% CI: 10.5, 11.8] g/L in the higher baseline Hb group. The proportion (%) of patients with mean Hb ≥100 g/L averaged over the same period were 58.8% [95% CI: 51.8%, 65.7%] & 68.6% [95% CI: 61.8%, 75.3%] in the lower baseline Hb group, and 86.5% [95% CI: 84.7%, 88.3%] & 88.2% [95% CI: 86.5%, 90.0%] in the higher baseline Hb group. Patients with baseline Hb <80 g/L had numerically higher mean increases from baseline to week 12 and 24 in SF-36 V and PF sub-scores (Table 2), though no clinical meaningful change was observed in either group. Conclusion Roxadustat effectively corrected anemia in DD and NDD patients regardless of baseline Hb level. There was no clinical meaningful improvement in QoL for either group. The weekly dose of roxadustat to correct and maintain Hb was higher in patient with baseline Hb <80 g/L than in patients with baseline Hb ≥80 g/L.

#254 PaCE CKD: examining health status and financial burden in patients with chronic kidney disease: assessing the non-clinical burden of disease

Abstract Background and Aims There is a detrimental effect of chronic kidney disease (CKD) on health states, with many patients worldwide experiencing considerable symptom burden and development of comorbidities, leading to frequent medical appointments and hospitalisations. Patients experience disease-associated financial strain as their ability to work is impaired. The aim of this multinational study was to characterise the non-clinical burden of CKD by quantifying the effect of CKD on health states and productivity in patients versus general population in several regions. Method Patients with early (stages 1-3) to advanced (stages 4-5) of CKD, including those receiving dialysis treatment, in Germany, Mexico, Taiwan, the UK, and the US were enrolled to a cross-sectional non-interventional survey measuring: Scores were compared with a general population cohort, matched 1:1 in sample size against patient cohorts and for demographic characteristics (e.g. age and area of residence). Results Across five countries, an average of 201 (range: 190–212) patients were enrolled, of whom 42% were receiving dialysis in Germany, 57% in Mexico, and 55% in the UK with smaller proportions of patients on dialysis cohorts in the US (32%) and Taiwan (15%). Haemodialysis was the most prevalent mode of dialysis in all countries, with most patients receiving dialysis in a clinic or hospital. Enrolled patients who had received a kidney transplant accounted for 11.5% on average across all countries. Compared with general population, people with CKD experienced a 24% reduction in mean [SD] EQ-5D utility scores, with patients in the US experiencing the greatest disparity in health states (0.64 [0.27] versus 0.95 [0.08]). Patients with CKD reported significantly more problems across all EQ-5D domains in Germany, Mexico, the US, and UK than general population cohorts. The highest percentage of patients reporting problems was in Mexico, with 81.4% reporting problems in usual activities compared with 4.4% in the general population. Patients receiving dialysis reported a mean EQ-VAS value of 70.3 compared with 91.8 in non-dialysis dependent patients, indicating that treatment burden negatively contributes towards patients perception of their health. In addition to impaired health states, patients reported elevated impairment across work and non-work activities in all countries. Patients reported increased rates of absenteeism, presenteeism, work impairment and non-work activity impairment, with the greatest impairment observed in the UK of 46.4% in non-work activity impairment compared with the general population. Conclusion These results indicate that people with CKD experience substantial burden of disease that extends beyond its clinical aspects. Decision makers should consider broader disease effects when addressing the burden of CKD.

#1490 Long-term health outcomes in non-dialysis dependent chronic kidney disease patients with cognitive impairment or dementia

Abstract Background and Aims A decline in cognitive function, with a spectrum ranging from mild cognitive impairment to dementia (CI-D), is common in patients with chronic kidney diseases (CKD), rendering them frailer. Whether the coexistence of CKD and CI-D increases the health risk profile remains unclear. Our work aims to clarify how this association increases adverse outcomes for CKD patients (stages 3-5). Method This retrospective observational cohort study was conducted on CKD patients (stages 3-5) from the Global Collaborative Network (GCN) of the TriNetX research platform between 2004 and 2024. TriNetX provides access to anonymized electronic medical records from over half a million CKD patients in large healthcare organizations (HCOs) across the world. Our report includes patients from 110 HCOs with different demographic backgrounds. The study compared outcomes of patients with CKD stages 3-5, aged 18-70 years, with and without pre-existent CI-D (diagnosed within 5 years). The two cohorts were propensity score-matched (PSM) for age, sex, ethnicity, comorbidities (neurological, haematological, musculoskeletal, respiratory including smoking history, oncological, cardiovascular, gastroenterological and endocrine conditions) and CKD stage. The proportional hazard assumption was tested using the generalized Schoenfeld approach built in the TriNetX platform. A 95% confidence interval (95% CI) was considered evidence of statistical significance throughout the analyses. Kaplan- Meier (KM) was used for survival probability. Statistical significance was defined as p-value < 0.05. Outcome events were included from 1 day after the index event (CKD diagnosis) until 3650 days after. Results Of the total of 503,298 CKD patients, 7,891 had a co-existent diagnosis of CI-D made within 5 years (prevalence rate 1.56%). A PSM generated a matched cohort of 7,890 patients each. The mean age of the cohort was 60.7 ± 7.0 years, with a predominance of white ethnicity (53.7%) and an equal male-to-female ratio. Standardized difference (Std diff) was used to evaluate the balance of baseline characteristics in the PSM populations. Generally, Std diff < 0.1 is considered a small difference and all comorbidities fell below this threshold after PSM (Table 1). The comparison of the outcomes at follow-up between the matched cohorts is illustrated in Table 2. CKD patients with concomitant CI-D had higher all-cause mortality (18.4% vs 12.1%, p < 0.0001), a higher risk of cerebrovascular disease (10.8% vs 7.8%), malnutrition (6.7% vs 4.3%), mood disorders (13.7% vs 8.9%), anxiety (13.2% vs 10.9%), encephalopathy (9.6% vs 4.5%), epilepsy (4.3% vs 1.3%). All findings were statistically significant with a p < 0.0001. Proportional hazard models showed that CI-D was a strong risk factor associated with all-cause mortality (HR: 1.761; 95% CI (1.621-1.913, p < 0.0001)) and other cerebrovascular and mental health illnesses. Conclusion Our “real-world data” demonstrate that a concomitant CI-D diagnosis is a strong risk factor for negative health outcomes and mortality in patients with CKD stages 3-5. These results highlight the need for routine cognitive assessments in patients with advanced CKD to deliver personalised care.

#255 PaCE CKD: the impact of caregiving on health states and work productivity in chronic kidney disease: results from an international survey

Abstract Background and Aims Patients with chronic kidney disease (CKD) often rely on informal caregivers for support with their condition, but the effect of these responsibilities on caregivers’ lives is poorly understood. The aim of this study was to quantify the effect of CKD on caregivers’ health states and work productivity across five countries compared with the general population. Method Unpaid informal caregivers of patients with CKD, hereafter referred to as caregivers, in Germany, Mexico, Taiwan, the US, and the UK were enrolled to a non-interventional survey. Caregivers of patients with early (stages 1-3) to advanced (stages 4-5) CKD, including those receiving dialysis were enrolled in the study. A general population cohort was included, matched in sample size and demographic characteristics. The surveys assessed health states and work productivity with the following instruments: Results Across five countries, an average of 112 (range: 94–138) caregivers were enrolled to the study. Most respondents cared for a patient receiving dialysis—in Germany (65%), Mexico (65%), UK (67%), US (81%), though less than half (48%) of respondents in Taiwan cared for a dialysis dependent patient. Frequently reported caregiving duties were help with household duties and driving to medical appointments. Caregivers in Germany, Mexico, the US, and UK experienced significantly impaired health states compared with the general population, as demonstrated by lower EQ-5D-5L utility scores. The greatest difference was observed from respondents in Mexico, with 16% lower mean [SD] index scores compared with the general population (0.79 [0.18] versus 0.94 [0.07]). Caregivers of dialysis dependent patients had similar CarerQol utility scores as those caregiving for non-dialysis dependent patients. Caregivers for dialysis dependent patients reported more problems across all CarerQol domains than caregivers for non-dialysis dependent patients. Caregivers in the UK reported significantly more financial problems (33%) as a result of caregiving; caregivers in the US reported significantly more problems (30%) in combining daily activities with care tasks. Caregiving also had a negative effect on work productivity. Rates of absenteeism, presenteeism, work impairment and non-work activity impairment were worse in caregivers compared with the general population. The largest effects were observed in Mexico where a 40% increase in non-work activity impairment was reported. Conclusion This study highlights the global burden for caregivers of patients with CKD. The broader impact of disease on caregivers should be accounted for when considering interventions relating to CKD.

The efficacy and safety of molidustat for anemia in dialysis-dependent and non-dialysis-dependent chronic kidney disease patients: A systematic review and meta-analysis

ObjectiveMolidustat is a novel agent investigated for the treatment of anemia in both dialysisdependent (DD) and non-dialysis-dependent (NDD) patients. Its efficacy and safety are still unclear. MethodsWe searched five databases to identify randomized controlled trials comparing molidustat to erythropoiesis-stimulating agents (ESAs) or placebo in patients with anemia. ResultsSix studies containing 2025 eligible participants were identified. For NDD patients, the change in Hb levels from baseline (ΔHb) was significantly higher for molidustat than for placebo [mean difference (MD) = 1.47 (95 % CI: 1.18 to 1.75), P < 0.00001] and ΔHb was also significantly higher for molidustat than for ESAs [MD = 0.25 (95 % CI 0.09 to 0.40), P = 0.002]. For NDD patients, Δhepcidin was significantly lower for molidustat than for placebo [MD = −20.66 (95 % CI: −31.67 to −9.66), P = 0.0002] and Δhepcidin was also significantly lower for molidustat than for ESAs [MD = −24.51 (95 % CI: −29.12 to −19.90), P < 0.00001]. For NDD patients, Δiron was significantly lower for molidustat than for ESAs [MD = −11.85 (95 % CI: −15.52 to −8.18), P < 0.00001], and ΔTSAT was also significantly lower for molidustat than for ESAs [MD = −5.29 (95 % CI: −6.81 to −3.78), P < 0.00001]. For NDD patients, Δferritin was significantly lower for molidustat than for placebo [MD = −90.01 (95 % CI: −134.77 to −45.25), P < 0.00001]. However, for DD-CKD patients, molidustat showed an effect similar to that of ESAs on increasing the Hb level [MD = −0.18 (95 % CI: −0.47 to 0.11), P = 0.23], Δiron level [MD = 3.78 (95 % CI: −7.21 to 14.76), P = 0.5], Δferritin level [MD = 25.03 (95 % CI: −34.69 to 84.75), P = 0.41], and Δhepcidin level [MD = 1.20 (95 % CI: −4.36 to 6.76), P = 0.67]. For DD-CKD patients, compared with the placebo or ESA group, molidustat showed a significantly higher level on ΔTSAT[MD = 3.88 (95 % CI: 2.10 to 5.65), P < 0.0001] and a slightly increased level on ΔTIBC level [MD = 1.08 (95 % CI: −0.07 to 2.23), P = 0.07]. There was no significant difference in the incidence of severe adverse events (SAEs), death, and cardio-related adverse events between molidustat and the ESAs groups. ConclusionsMoricizine can effectively improves Hb levels in NDD patients and corrects anemia in DD patients without increasing adverse event incidence.

FRAIL scale as a screening tool and a predictor of mortality in non-dialysis dependent patients.

This study aimed to compare the diagnostic yield of the FRAIL scale with respect tothe physical frailty phenotype measure and their association with mortality in non-dialysis-dependent patients. In this prospective cohort study, non-dialysis dependent patients with chronic kidney disease (CKD) stages 3b-5 seen in the nephrology outpatient clinics of two university hospitals were included. The presence of frailty was evaluated by physical frailty phenotype measure and the FRAIL scale. Patients were evaluated for six months, and mortality was recorded. The Kappa test was used to evaluate the diagnostic properties between the methods, and logistic regression to test the association between frailty and mortality. One hundred fifty-three patients were evaluated; average age was 65 (56-70) years, 50.9% were women, and the all-cause mortality rate was 2.6%. Forty-six patients were classified as living with frailty according to the physical frailty phenotype while 36patients were rated frail by the FRAIL scale. In adults < 60years of age, the FRAIL scale showed good accuracy (84.9%) and specificity (93.2%) but had low sensitivity (41.3%) and moderate agreement (Kappa = 0.41; p < 0.001) compared to the definition of thephysical frailtyphenotype.The adjusted logistic regression model showedthat the patients with frailty assessed by the FRAIL scale had a greater chance of mortality than the non-frail patients (OR: 6.8; CI95%:1.477-31.513; p = 0.014). Physical frailty phenotype identifies more patients as having pre-frailty and frailty in non-dialysis dependent patientsas compared to the FRAIL scale. However, the FRAIL scale is a simple bedside tool that can be useful for screening forfrailty and whose results were associated with mortality.

Predicting CKD progression using time-series clustering and light gradient boosting machines

Predicting the transition of kidney function in chronic kidney disease is difficult as specific symptoms are lacking and often overlooked, and progress occurs due to complicating factors. In this study, we applied time-series cluster analysis and a light gradient boosting machine to predict the trajectories of kidney function in non-dialysis dependent chronic kidney disease patients with baseline estimated glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2. Based on 5-year changes in estimated GFR, participants were stratified into groups with similar trajectories by cluster analysis. Next, we applied the light gradient boosting machine algorithm and Shapley addictive explanation to develop a prediction model for clusters and identify important parameters for prediction. Data from 780 participants were available for analysis. Participants were classified into five classes (Class 1: n = 78, mean [± standard deviation] estimated GFR 100 ± 19.3 mL/min/1.73 m2; Class 2: n = 176, 76.0 ± 9.3 mL/min/1.73 m2; Class 3: n = 191, 59.8 ± 5.9 mL/min/1.73 m2; Class 4: n = 261, 52.7 ± 4.6 mL/min/1.73 m2; and Class 5: n = 74, 53.5 ± 12.0 mL/min/1.73 m2). Declines in estimated GFR were 8.9% in Class 1, 12.2% in Class 2, 4.9% in Class 3, 12.0% in Class 4, and 45.1% in Class 5 during the 5-year period. The accuracy of prediction was 0.675, and the top three most important Shapley addictive explanation values were 1.61 for baseline estimated GFR, 0.12 for hemoglobin, and 0.11 for body mass index. The estimated GFR transition of patients with preserved chronic kidney disease mostly depended on baseline estimated GFR, and the borderline for estimated GFR trajectory was nearly 50 mL/min/1.73 m2.

B-171 Comparison of Intact PTH and PTH Assays using LC-MS/MS Among Non-Dialysis Dependent Chronic Kidney Disease Patients

Abstract Background Parathyroid hormone (PTH) is an important regulator of calcium and phosphate homeostasis and bone remodeling. It is metabolized into PTH fragments, which are measured to a different extent by PTH assays of different generations because of differences in fragments recognized and lack of assay standardization. Therefore, we developed an LC-MS/MS method for 1-84 PTH and aimed to compare with immunoassay among patients with chronic kidney disease (CKD) stages 3 to 5 not yet on dialysis. Methods Blood samples were collected from 252 patients with CKD stages 3 to 5. PTH concentrations were measured simultaneously by using the second-generation—PTH intact and immunocapture in situ digestion LC-MS/MS spectrometry assays. The severity of the kidney disease was based on the eGFR calculated by using the Modification of Diet in Renal Disease (MDRD) formula. Results Serum 1-84 PTH concentrations were strongly correlated but significantly lower than the intact PTH concentrations (r = 0.956, P &amp;lt; 0.0001). This finding was consistent among CKD stages 3 to 5. PTH concentrations by both assays (intact and 1-84 PTH) positively correlated with BUN (r = 0.613, r = 0.61; P &amp;lt; 0.0001, respectively), phosphorus (r = 0.423, r = 0.427; P &amp;lt; 0.0001, respectively) and negatively correlated with blood calcium (r = −0.355, r = −0.421; P &amp;lt; 0.0001, respectively), protein (r = −0.289, r = −0.305; respectively, P &amp;lt; 0.0001) and the estimated glomerular filtration rate (r = −0.468, r = −0.485; P &amp;lt; 0.0001, respectively). Conclusion Among patients with CKD stages 3 to 5 not on dialysis, the 1-84 PTH assay detected significantly lower PTH concentrations compared with intact PTH assay. This LC-MS/MS method can provide accurate and precise PTH results in patients with severe chronic renal failure. Additional studies that correlate the diagnosis and management of CKD mineral and bone disorders are needed to determine whether 1-84 PTH assay results are better surrogate markers in these early stages of CKD.

#4529 PACE-CKD: FINANCIAL BURDEN AND WORK PRODUCTIVITY OF PATIENTS WITH CKD AND CAREGIVERS: RESULTS FROM A US SURVEY

Abstract Background and Aims Chronic kidney disease (CKD) is a progressive condition, conferring serious mortality and morbidity in patients with advanced disease. Upon reaching end-stage kidney disease (ESKD), dialysis or kidney transplantation is typically required, leading to considerable burden to health care systems worldwide. There is a paucity of data assessing the financial wellbeing and work productivity of patients with CKD and their caregivers, compared to the general population. Therefore, the objective of this study was to conduct a quantitative online survey to estimate the financial burden and work productivity of patients with CKD and their caregivers relative to the general population. Method This non-interventional survey included adult patients with a diagnosis of CKD for at least 3 months and unpaid caregivers of CKD patients for a minimum of 1 hour per week in the previous 4 weeks. ESKD was defined by patients with CKD stage 5 or patients undergoing kidney transplantation or dialysis. Patients and caregivers were matched by key demographic characteristics (e.g. age, gender and area of residence) to respective general population cohorts. Patients and caregivers were assessed using the Consumer Financial Protection Bureau (CFPB) general financial well-being scale (scores from 0 to 100) and financial burden was assessed using the FACIT-COST score (5 point Likert type scale). Work productivity was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire (WPAI:GH for patients, adjusted WPAI-CG ADAPTED for caregivers). Results The study enrolled 199 patients (median age: 58 years) with CKD and 113 caregivers (median age: 38 years) in the United States. Candidates were enrolled between June and July 2022. In the patient cohort, 32.2% of participants were dialysis-dependent, who predominately received treatment in a clinic or hospital (79.7%) rather than at home. Caregivers most commonly cared for their parent (45.1%) or partner (25.7%); the most frequent role for caregivers was providing transport to/from medical appointments (89.4%). Patients were considered to have 17.8% worse financial wellbeing compared to the general population according to the CFPB scale (52.0 vs 63.2, respectively). Caregivers reported slightly lower financial wellbeing than the general population (55.8 vs 56.4, respectively). Patients receiving dialysis experienced a similar financial burden to non-dialysis dependent patients, with slightly worse FACIT-COST scores (22.9 vs 23.4, respectively). Further, patients and caregivers reported losses to work productivity with dialysis patients (21.6%) reporting higher absenteeism from work than non-dialysis patients (9.6%) when compared to the general population (3.6%). Similarly, carers of dialysis-dependent patients reported a higher rate of absenteeism (14.8%) compared to carers of non-dialysis dependent patients (10.6%) and the general population (5.2%). Total activity impairment was higher for dialysis dependent patients (55.5%) than for non-dialysis dependent patients (43.7%) and considerably higher versus the general population (5.7%). Caregivers for dialysis dependent patients had greater total activity impairment (44.3%) than caregivers for non-dialysis dependent patients (34.3%) and the general population (17.3%). Results for patients and caregivers in other countries (United Kingdom, Germany, and Mexico) will also be presented at the congress. Conclusion The results of this survey suggest that work productivity is impaired in both CKD patients and their caregivers and is also exacerbated further in patients who progress to dialysis and their caregivers. The survey also provides indications that the financial wellbeing in patients with CKD may be affected in comparison to the general population. Evidence based policy interventions ought to consider the progressive nature of CKD and should aim to reduce the societal burden of disease for patients and carers. Funding This study was supported by AstraZeneca.

#4018 CHARACTERISATION OF THE CLINICAL, HUMANISTIC AND ECONOMIC BURDEN OF ANAEMIA IN CHRONIC KIDNEY DISEASE: A SYSTEMATIC LITERATURE REVIEW

Abstract Background and Aims Chronic kidney disease (CKD) is defined as structural kidney damage and/or decreased kidney function (glomerular filtration rate &amp;lt;60mL/min/1.73 m2) persisting for ≥3 months [1]. Anaemia is a frequent CKD comorbidity associated with increased cardiovascular (CV) morbidity, mortality, reduced health-related quality of life (HRQoL) and greater healthcare resource utilisation (HRU) [2]. Our systematic literature review provided an overview of the clinical, humanistic and economic burden of anaemia of CKD. Method A search was performed in MEDLINE, EMBASE, MEDLINE IN-PROCESS, Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews from database inception to 10 April 2022, using predefined criteria to identify cohort, cross-sectional, observational and cost studies, economic evaluations, conceptual model studies, systematic and literature reviews (complemented by grey literature and congress abstract searches and back-referencing relevant review papers [2016–2021]). Full-text selected citations were examined by two independent reviewers. Clinical burden parameters included CKD progression, differences in progression between patients with/without CKD anaemia, time to blood transfusion and association of CKD stage/progression with CV outcomes or mortality. Humanistic burden included HRQoL and caregiver burden. Economic burden was determined by HRU and direct/indirect costs. Results Data were extracted from 115 studies (12,109 database records, 79 supplementary items; Figure 1), including patients: pre- or non-dialysis (n = 61), on dialysis (n = 21), mixed non-/on dialysis (n = 19) and unknown dialysis status (n = 14). Incidence of advanced CKD was significantly higher in adult non-dialysis dependent (NDD) patients with anaemia of CKD vs those without (incidence per 1000 person-years: 15 to ∼85 vs 3 to ∼25). Patients with CKD anaemia had a higher risk of disease progression than those without anaemia (n = 21), e.g. non-dialysis stage 1–5 adults with CKD anaemia had ∼double the risk of developing end-stage CKD (hazard ratio [95% confidence interval [CI]] = 2.08 [1.50–2.89]). Median time to dialysis initiation was significantly lower in adult NDD stage 1–5 patients with anaemia of CKD vs those without anaemia (45.1 vs 68.3 months p&amp;lt;0.01). A higher proportion of stage 3 adult NDD patients with anaemia of CKD progressed to stage 4 or 5 over follow-up periods of 1, 2 and 3 years vs those without anaemia (40% vs 20%; 60% vs 25%; 75% vs 30%, respectively). Available data from the 43 studies reporting humanistic burden suggested significantly worse HRQoL in patients with vs without CKD anaemia; e.g. non-dialysis adults with CKD anaemia had worse 36-item kidney disease and QoL scores for symptoms/problems, effect- and burden-of CKD. Comparative caregiver burden data in patients with/without CKD anaemia were limited. Limited available evidence from an economic perspective suggested higher HRU in patients with anaemia of CKD vs those without. Patients with anaemia of CKD has ∼2 times greater risk of hospitalisation due to heart failure vs those without (crude incidence rate ratio [95% CI] = 1.9 [1.6–2.1]). Similarly, patients with anaemia of CKD has significantly higher risk of hospitalisations (adjusted relative risk [ARR] [95% CI] = 1.33 [1.31–1.34]) and emergency department visits (ARR [95% CI] = 1.14 [1.12–1.15]) in a multivariate logistic regressions model. No data were available on change in economic parameters over time or on inter-relationships between humanistic/economic burden parameters. There were no published disease models in CKD anaemia; Figure 2 illustrates identified relationships between clinical, humanistic and economic burden parameters. Conclusion Based on limited moderate-to-good quality data, we found that patients with CKD anaemia face greater clinical, humanistic and economic burdens than those without anaemia, with significantly worse HRQoL and greater HRU. CKD anaemia was also associated with a higher risk of CKD progression.

#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.

Effectiveness of iron-based phosphate binders in reduction of hyperphosphataemia in chronic kidney disease patients

Background: Ferric citrate is novel iron-based phosphate-binding drug for management of hyperphosphataemia and iron-deficiency anaemia in chronic kidney disease (CKD) patients. Objectives: To evaluate impact of ferric citrate therapy on reduction of phosphate levels and improvement in haematological parameters in CKD stages 3-5. Methods: This analytical, observational study was conducted at Kathmandu Medical College Teaching Hospital from 2020 July-December after ethical clearance using convenience sampling method. Non-dialysis dependent patients at CKD stages 3-5, having hyperphosphataemia (serum phosphate &gt;=4.6mg/dL) and anaemia (serum haemoglobin &lt;12 gm%, transferrin saturation &lt;=30%, ferritin &lt;=300ng/mL) were administered with 2gm twice daily dose of ferric citrate for 12 weeks and evaluated on outcomes in terms of reduction in serum phosphate levels and improvement in haematological parameters as study endpoints. Data were entered in Microsoft Excel and analysed in SPSS v.25. Significance level was set at p &lt;0.05. Results: Of 84 study participants, majority had CKD stage 4 (46, 54.76%). A significant reduction (p &lt;0.001) in mean serum phosphate levels of 6.21 ± 1.062 mg/dL from baseline to 4.89 ± 1.100 mg/dL in 12-weeks was observed. Patients with CKD stages 3, 4, and 5 had mean reduction of 1.67 (p = 0.005), 1.40 (p &lt;0.001), and 1.04 mg/dL (p = 0.002) of serum Phosphate level respectively. Significant (p &lt;0.001) improvements in hemoglobin level, serum iron, ferritin, total iron binding capacity, and transferrin saturation were reported. Conclusion: Ferric citrate is effective and well-tolerated phosphate-binder to improve hyperphosphataemia and iron deficiency anaemia in non-dialysis CKD stage 3, 4, and 5.

Prioritizing the Sickest Among the Sickest: A Matter of Tact and Moderation, but the Game Is Worth the Candle.

Prioritizing the Sickest Among the Sickest: A Matter of Tact and Moderation, but the Game Is Worth the Candle.

Retrospective Assessment of Total Cost of Care in Non-Dialysis Dependent Chronic Kidney Disease Patients Receiving Parenteral Iron Therapy for Iron Deficiency Anemia

Introduction Iron deficiency anemia (IDA) is a common comorbidity among patients with chronic kidney disease. Iron deficiency occurs in 15% to 48% of non-dialysis dependent chronic kidney disease (ND-CKD) patients with anemia. Parenteral iron therapy is often required in ND-CKD patients with IDA who cannot tolerate or are nonresponsive to oral iron. Available IV iron treatments vary in the amount of iron dose per administration, the number of infusions required to achieve complete iron repletion and drug acquisition cost. The objective of this study was to compare healthcare costs between ferric carboxymaltose (FCM) and low dose IV iron (LDI) for the treatment of IDA in ND-CKD patients. Methods Medical and pharmacy claims from IQVIA PharMetrics® Plus data were analyzed. Adult patients who received first (index) dose of FCM or LDI (i.e., iron sucrose, iron dextran, sodium ferric gluconate complex in sucrose) from 2017 to 2019 were included. Eligible patients were required to be continuously eligible 6 months before (baseline) and 12 months after index IV iron infusion and had medical claims associated with diagnosis of chronic kidney disease (ICD-10: N18.1 to N18.5) and IDA (ICD-10: D50.x) anytime during the 18-month study observation period. In addition, eligible FCM patients were required to receive a second dose of FCM within 21 days of index date. Patients who had claims associated with end stage renal disease (ICD-10: N18.5 and N18.6) or dialysis (HCPCS CPT code: 90935-90999) and patients who had received other IV iron products in the 6-month baseline period were excluded. Unadjusted mean number of IV iron infusions, outpatient visits and hospital admissions in the 6 months before and 12 months following index IV iron dose were summarized on a per-patient-per-month basis. Post-index monthly inpatient, outpatient, and total healthcare costs for FCM and LDI were compared using generalized linear model with gamma log-link adjusting for pre-index monthly cost, age, gender, year of index treatment and the Charlson Comorbidity Index (CCI). Sensitivity analyses comparing FCM versus iron sucrose were performed. Results Data from 3,727 FCM patients [mean (SD) age= 67.9 (13.8) years, 61% females, CCI (SD)=1.9 (2.5)] and 5,068 LDI patients [mean (SD) age=64.8 (15.0) years, 60% females, CCI (SD)=1.6 (2.4)] were analyzed. Within the LDI cohort, 3,489 patients received index iron sucrose treatment [mean (SD) age=64.6 (15.1) years, 60% females, CCI (SD)=1.5(2.4)]. Mean (SD) number of IV iron infusions was 0.24 (0.26) for FCM, 0.43 (0.52) for LDI and 0.46 (0.52) for iron sucrose during the post-index period. During the post-index period, FCM has a smaller increase in the number of outpatient visits (mean change from baseline=0.13) than LDI (mean change from baseline=0.64) and iron sucrose (mean change from baseline=0.70). The number of hospital admissions in the post-index period were numerically lower for FCM (mean change from baseline=-0.05) but numerically higher for LDI (mean change from baseline=0.04) and iron sucrose (mean change from baseline=0.05). Mean total health care cost increased during the 12-month period after IV iron treatment compared to baseline in all treatment groups. After adjusting for pre-index cost and other covariates, FCM treatment was associated with significantly lower post-index inpatient costs [adjusted cost ratio (ACR)= 0.73, p<0.0001], ER costs (ACR=0.76, p<0.0001), outpatient costs (ACR=0.73, p<0.0001) and total costs (including IV iron) (ACR = 0.81, p<0.0001) than LDI. Similar results were observed in the comparisons between FCM and iron sucrose. Conclusion Higher drug acquisition cost of FCM compared to LDI was primarily offset by lower inpatient and outpatient costs during the 12 months after FCM treatment for IDA in ND-CKD patients than LDI, resulting in significantly lower overall total health care cost for FCM compared to LDI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Post-COVID-19 outcomes of non-dialysis dependent chronic kidney disease patients: a national, multicenter, controlled study.

PurposeCoronavirus disease 2019 (COVID-19) has a higher mortality in the presence of chronic kidney disease (CKD). However, there has not been much research in the literature concerning the outcomes of CKD patients in the post-COVID-19 period. We aimed to investigate the outcomes of CKD patients not receiving renal replacement therapy.MethodsIn this multicenter observational study, we included CKD patients with a GFR < 60 ml/min/1.73 m2 who survived after confirmed COVID-19. Patients with CKD whose kidney disease was due to diabetic nephropathy, polycystic kidney disease and glomerulonephritis were not included in this study. CKD patients with similar characteristics, who did not have COVID-19 were included as the control group.ResultsThere were 173 patients in the COVID-19 group and 207 patients in the control group. Most patients (72.8%) were treated as inpatient in the COVID-19 group (intensive care unit hospitalization: 16.7%, acute kidney injury: 54.8%, needing dialysis: 7.9%). While there was no significant difference between the baseline creatinine values of the COVID-19 group and the control group (1.86 and 1.9, p = 0.978, respectively), on the 1st month, creatinine values were significantly higher in the COVID-19 group (2.09 and 1.8, respectively, p = 0.028). Respiratory system symptoms were more common in COVID-19 patients compared to the control group in the 1st month and 3rd month follow-ups (p < 0.001). Mortality at 3 months after the diagnosis of COVID-19 was significantly higher in the COVID-19 group than in the control group (respectively; 5.2% and 1.4%, p:0.037). Similarly, the rate of patients requiring dialysis for COVID-19 was significantly higher than the control group (respectively; 8.1% and 3.4%, p: 0.045).ConclusionsIn CKD patients, COVID-19 was associated with increased mortality, as well as more deterioration in kidney function and higher need for dialysis in the post-COVID-19 period. These patients also had higher rate of ongoing respiratory symptoms after COVID-19.

Subclinical Hypothyroidism in Advanced Chronic Kidney Disease Patients: Prevalence and Associated Factors.

Introduction Renal function and thyroid metabolism are tightly related. However, evidence about subclinical hypothyroidism prevalence in patients with chronic kidney disease and its related factors is scarce. Objectives Our aim is to analyze subclinical hypothyroidism prevalence and its related factors in patients with advanced chronic kidney disease. Materials and methods. Nondialysis-dependent patients with chronic kidney disease at stages 3 to 5 were included. Other inclusion criteria were age above 18 years and clinical stability. Patients with diagnosed thyroid illnesses were excluded. Subclinical hypothyroidism was defined as thyroid stimulating hormone (TSH) > 5.3 mU/L, with free thyroxine 4 (FT4) between 0.54 and 1.24 ng/dl. Filiation data, comorbidities, and routine blood and urine test results were registered. Results A total of 299 patients were included. Of them, 184 (61.5%) were men. The mean age was 71 ± 13 years old. The mean glomerular filtration rate (CKD-EPI) was 22 ± 9 ml/min/1.73 m2. According to chronic kidney disease stages, global distribution of patients was as follows: Stage 3, 67 patients (22.4%); Stage 4, 155 patients (51.8%); and Stage 5, 77 patients (25.8%). We found subclinical hypothyroidism in 54 (18.1%) patients. According to chronic kidney disease stages, distribution of affected patients was as follows: Stage 3, 9 patients (13%); Stage 4, 25 patients (16.1%); and Stage 5, 20 patients (26%). Differences among stages were statistically significant. By univariate analysis, factors related with subclinical hypothyroidism were as follows: age RR 1.048 (95% CI 1.019–1.078; p=0.001), hypertension RR 2.705 (95% CI 1.026–7.130; p=0.04), glomerular filtration rate RR 0.962 (95% CI 0.929–0.996; p=0.03), and proteinuria higher than 1 gram/day RR 2.387 (95% CI 1.303–4.374; p=0.005). By multivariate analysis adjusted by age, hypertension, glomerular filtration rate, proteinuria, diabetes, and cardiovascular disease history, only age RR 1.016 (95% CI 1.009–1.028; p=0.04) and glomerular filtration rate RR 0.963 (95% CI 0.930–0.997; p=0.03) preserved their independent association with subclinical hypothyroidism. Conclusions Subclinical hypothyroidism prevalence in patients with chronic kidney disease is high and increases with renal disease severity. Factors independently related to subclinical hypothyroidism are age and glomerular filtration rate.

MO601: Using the Borg Scale for Exercise Prescription and for Monitoring Self-Administered Aerobic Endurance Exercise is Safe and Effective for Patients with CKD

Abstract BACKGROUND AND AIMS Decline in physical function starts relatively early in the course of CKD and has an impact on activities in daily life, such as walking capacity. Several studies with supervised centre-based exercise training as well as studies with self-administered home-based exercise have shown improvement in walking capacity. However, monitoring intensity and safety is important when exercise is self-administrated. There are to our knowledge no studies evaluating the Borg RPE scale as a tool to prescribe exercise intensity and as an instrument for self-monitoring exercise training in patients with CKD. The aims of this study were to examine the adherence, performance, and safety of self-administered aerobic endurance exercise when exercise intensity was prescribed and self-monitored with the Borg rating of perceived exertion (RPE) scale in non-dialysis dependent patients with CKD stages 3–5, and the relationship between performed exercise and change in walking distance. METHOD In this sub-study of the RENEXC trial 147 patients (97 men, 50 women), irrespective of age and comorbidities, were included. Mean age was 66 ± 14 years and the mean measured GFR 22 ± 8 mL/min/1.73 m2. Twelve months of aerobic endurance exercise (60 min/week) was combined with either balance or strength exercises (90 min/week). All exercise was individually prescribed by a research physiotherapist, based on each patient's baseline tests. The aerobic endurance exercise was prescribed to have a level of intensity between 13 (somewhat strenuous) to 15 (strenuous) using the Borg RPE scale. Exercise was self-monitored and recorded in a training diary. Follow up was performed by the physiotherapist through phone contact. The 6-min walk test was measured at baseline and after 4, 8 and 12 months of exercise. RESULTS Hundred patients completed the study. Our training program had an excellent level of adherence, at 12 months 80% of the patients reported performed exercise and 74% performed exercise within the prescribed intensity. The mean intensity of the aerobic endurance exercise was rated at 13 ± 1 on the Borg RPE scale. Median duration of aerobic endurance exercise was 56 (33–109) minutes/week. However, there was a wide range of weekly duration where patients with a low walking distance at baseline performed less minutes of exercise/week (P = 0.039). Irrespective of weekly duration the patients were able to perform exercise within the prescribed interval of RPE 13–15. No exercise related incidents were reported. Walking distance improved significantly by mean 30 ± 56 meters (P &amp;lt; 0.001). There was no correlation between weekly duration of exercise and change in walking distance, indicating that deconditioned patients with a short baseline walking distance can increase walking capacity when performing a shorter weekly duration of somewhat strenuous to strenuous exercise, whereas patients with a higher baseline walking distance must perform a longer duration of exercise to increase walking capacity. CONCLUSION The Borg RPE scale is a useful, acceptable, simple and safe method for prescribing and monitoring intensity of self-administered aerobic endurance exercise in patients with CKD. A RPE of somewhat strenuous to strenuous improved walking capacity in deconditioned patients with CKD, within a wide range of weekly duration of exercise.

The efficacy and safety of roxadustat for the treatment of anemia in non-dialysis dependent chronic kidney disease patients: An updated systematic review and meta-analysis of randomized clinical trials.

Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX, especially on the cardiovascular risks, for anemia in NDD-CKD patients. Electronic databases were searched systematically from inception to July 2021 to look for randomized control trials (RCTs) that evaluated ROX NDD-CKD patients. Hemoglobin level and iron utilization parameters, including ferritin, serum iron, transferrin saturation (TSAT), total iron-binding capacity (TIBC), transferrin, and hepcidin were analyzed for efficacy. Pooled risk ratios (RRs) and standardized mean differences (SMDs) were calculated and presented with their 95% confidential intervals (CIs). Nine RCTs included a total of 3,175 patients in the ROX group and 2,446 patients in the control group. When compared the control group, ROX increased Hb level significantly (SMD: 1.65; 95% CI: 1.08, 2.22; P< 0.00001) and improved iron utilization parameters by decreasing ferritin (SMD: -0.32; 95% CI: -0.51, -0.14; P = 0.0006), TSAT (SMD: -0.19; 95% CI: -0.32, -0.07; P = 0.003), and hepcidin (SMD: -0.74; 95% CI: -1.09, -0.39; P< 0.0001) and increasing TIBC (SMD: 0.99; 95% CI: 0.76, 1.22; P< 0.00001) and transferrin (SMD: 1.20; 95% CI: 0.70, 1.71; P< 0.00001). As for safety, ROX was associated with higher serious adverse effects (RR: 1.07; 95% CI: 1.01, 1.13; P = 0.01), deep venous thrombosis (DVT) (RR: 3.80; 95% CI: 1.5, 9.64; P = 0.08), and hypertension (HTN) (RR: 1.37; 95% CI: 1.13, 1.65; P = 0.001). We concluded that ROX increased Hb level and improved iron utilization parameters in NDD-CKD patients, but ROX was associated with higher serious adverse effects, especially DVT and HTN. Our results support the use of ROX for NDD-CKD patients with anemia. However, higher-quality RCTs are still needed to ensure its safety and risk of thrombosis.

Two Phase 3 Studies on Ophthalmologic Effects of Roxadustat Versus Darbepoetin

IntroductionRoxadustat is an orally administered hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that represents a novel therapeutic option for patients with anemia of chronic kidney disease (CKD).MethodsConducted in Japan, CL-0307 (NCT02952092) and CL-310 (NCT02988973) were phase 3, darbepoetin alfa (DA)-controlled studies conducted in dialysis-dependent (DD) and non–DD (NDD) patients with CKD, respectively, where patients were randomized to receive roxadustat or DA. Ophthalmic imaging and assessments of visual acuity were performed up to week 24 or at study discontinuation. Ophthalmic imaging was centrally evaluated by independent readers masked to the study treatment.ResultsIn CL-0307, 302 patients (roxadustat, n = 150; DA, n = 152) received ≥1 dose of the study drug and were included in this analysis. In CL-0310, 262 patients (roxadustat, n = 131; DA, n = 131) received ≥1 dose of the study drug and were included in this analysis. Proportions of DD patients with new or worsening retinal hemorrhages (RHs) in the roxadustat group and DA group were 32.4% (46 of 142) and 36.6% (53 of 145), respectively. Proportions of NDD patients with CKD with new or worsening RH in the roxadustat and DA groups were 31.4% (38 of 121) and 39.8% (51 of 128), respectively. Similar trends were apparent in subgroup analyses: patients with/without RH at baseline and with/without diabetes mellitus at baseline. In both studies, there were no differences in retinal thickness, visual acuity, presence of hard exudates or cotton wool spots, or presence of intra- and subretinal fluid between groups, at any given time point.ConclusionIn these studies, roxadustat, compared with DA, was not associated with an increased risk of adverse ophthalmologic events in these cohorts.

Frequency and risk factors of frailty in nondialyzable chronic kidney disease geriatric patients

Background Frailty is an additional clinical and economic burden in the setting of chronic kidney disease (CKD). In this study, we aimed to determine the frequency and the risk factors for the occurrence of frailty in nondialyzable CKD geriatric patients' (stages 3–4). Patients and methods We conducted a cross-sectional, analytical study, which included consecutive patients with CKD, who attended the Nephrology Unit of Assiut University Hospital from April 2017 to April 2020. The total number of cases is 77 (21 of the control group and 56 of the patient group). Geriatric patients with aged more than or equal to 60 years and CKD stages 3–4 nondialysis dependent patients were included. The patients will be followed-up for 1 year. Results In terms of the frequency of frailty in geriatric CKD patients, the present study showed that 14.3% of the nondialyzable geriatric CKD patients had frailty. Regarding the predictors of frailty, the present study showed that nondialysis patients with frailty had significantly lower hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, lymphocyte count, monocyte count, higher blood urea, higher serum creatinine, and higher basophil count. Notably, a lower serum magnesium level was noticed in the frail group. Conclusion In conclusion, frailty is not common in geriatric nondialysis dependent CKD patients. Independent risk factors for frailty in CKD include low serum magnesium and high serum creatinine.