Non-dialysis Dependent Chronic Kidney Disease Research Articles

#2320 The impact of interventions for people with chronic kidney disease on health-related quality of life: a systematic review

Abstract Background and Aims Health-related quality of life (HRQoL) is poorer for those with chronic kidney disease (CKD) than the general population and worsens as CKD progresses. Evidence is mixed as to which interventions improve HRQoL for those with CKD, and HRQoL is often under-reported in randomised controlled trials where it is most commonly a secondary outcome. Reviews including HRQoL as an outcome have thus far focused on the impact per intervention, therefore we aimed to ascertain which interventions, of any type, have an impact on HRQoL outcomes for those with non-dialysis dependent CKD (NDD-CKD). Method The protocol was prospectively registered on PROSPERO (CRD42022364474) and PRISMA guidelines were followed. Inclusion criteria were randomised controlled trials in an NDD-CKD population (excluding transplant recipients), any intervention type, usual care/placebo comparators, using validated and reported HRQoL outcomes measures. Databases searched were Embase, Medline, PsychINFO, CINAHL plus, Web of Science, PubMed, and Google Scholar, with reference searching of included studies. Reports were independently screened by two researchers who also performed data extraction and quality assessment (using the Cochrane Risk of Bias 2.0 tool). Synthesis was undertaken using Synthesis without Meta-analysis (SWiM) methods. Conversion to one-sided p-values, synthesising outcomes in albatross plots and combining p-values via Fisher's method was performed using the metap package in R. HRQoL measures were broken down into physical, mental, kidney disease symptoms, adverse effects of kidney disease, burden of kidney disease, overall kidney disease, and overall HRQoL domains for analysis. Results Searches yielded 8983 records, and 39 studies met inclusion criteria, with a total of 11,940 participants. Nine groups were formed based on type of intervention, with data synthesis possible in the eight groups with more than one study (Fig. 1). 26 (66%) studies were rated as having high risk of bias, largely due to frequent lack of blinding and HRQoL being a patient reported outcome. 37 studies had sufficient data for presentation in albatross plots (Fig. 2). Using combined p-values for all HRQoL outcomes in each group of studies, benefit to HRQoL in at least one study was shown for education interventions (p < 0.001, seven studies, none with low risk of bias), exercise interventions (p < 0.001, eight studies, all with high risk of bias), medications to treat CKD-related anaemia (p < 0.001, eight studies, four with low risk of bias), nutritional interventions (p < 0.001, four studies, all with high risk of bias) and weight loss interventions (p < 0.001, two studies, one with low risk of bias). No benefit to HRQoL was shown for medications aimed at slowing CKD progression (p = 0.492, five studies), medications for depression (p = 0.266, two studies) and medications to treat acidosis (p = 0.99, two studies). Conclusion This review identified several interventions with evidence of benefit to HRQoL for people with NDD-CKD, including medications to treat anaemia and weight loss interventions. Studies of education, exercise and nutritional interventions showed potential benefit, but with high risk of bias. Further high-quality randomised controlled trials of interventions for people with NDD-CKD should include and report HRQoL outcomes, in addition to targeting potentially modifiable determinants of HRQoL in these groups.

#2264 Efficacy and safety of oral iron supplementation with liposomal iron in non-dialysis chronic kidney disease patients with iron deficiency

Abstract Background and Aims Iron deficiency (ID) is very common in patients with non-dialysis dependent chronic kidney disease (NDD-CKD). In these patients, oral iron supplementation is recommended as first-line treatment for ID. However, the efficacy of oral iron supplementation is frequently impaired by a higher incidence of adverse gastrointestinal side effects. Liposomal iron is a compound with ferric pyrophosphate enclosed in a phospholipid nucleus, providing high gastrointestinal absorption and bioavailability and a lower incidence of side effects. However, few data are available on its efficacy in patients with NDD-CKD. Method This single-arm pilot study was carried out in in patients with NDD-CKD stages 1-5 and ID, defined as serum ferritin (SF)<100 ng/mL and/or transferrin saturation (TSAT)< 20%, consecutively seen in two Nephrology units (Naples and Bari) from 01/12/2022 to 01/04/2023. We assessed the efficacy of six months of liposomal iron therapy in correcting ID across three visits after baseline (month 1, 3 and 6). All patients received liposomal iron (30 mg/day twice daily for the first month followed by 30 mg daily for the remaining five months). The primary endpoints were the achievement of SF ≥100 ng/mL and TSAT ≥20%. Secondary outcomes were hemoglobin (Hb) changes and safety of liposomal iron; adherence to the iron supplementation was assessed by monthly pill counting. Changes of continuous variables during the study were analyzed by linear mixed models assuming an unstructured covariance matrix; this was done to take into account the correlation between repeated measures and missing points for patients not completing the study. Change of prevalence of corrected SF and TSAT values from baseline to month 1, 3 and 6 was analyzed by McNemar test. Results 38 patients (65.3 ± 15.2 years, 52.6% males, 35.1% diabetes, eGFR 38.5 ± 28.8 mL/min/1.73 m2) received at least one dose of liposomal iron (safety population). Efficacy population included 34 patients with at least one control visit after baseline. Clinical characteristics of patients enrolled in the two clinics did not differ. In efficacy population, baseline SF was 44 (IQR 19-82) ng/mL and TSAT 14.3 ± 5.9%, corresponding to a percentage of SF<100 ng/mL of 78.9%, and TSAT<20% in 89.5%; 64.7% had both parameters below the cut-offs. Anemia (defined as Hb<12 g/dL in women and <13 g/dL in men) was detected in 22/34 patients. Liposomal iron induced a progressive increase of TSAT from 14.3 ± 5.9%, at baseline to 20.0 ± 7.6% at month-6 (P = 0.009) whereas no difference was detected for SF (Fig. 1A and 1C). Accordingly, at the end of study, the prevalence of TSAT>20% significantly increased from 11.8% to 50.0% (P = 0.002) while correction of SF, mildly improved (from 23.5% to 30.0%, P = 0.214, Fig. 1B and 1D). When patients were stratified by anemia, a significant improvement of TSAT was observed in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, P = 0.012), whereas no significant improvement was found in patients without anemia (P = 0.093). Adherence to iron supplementation was 100% in patients completing the study. Hb values did not significantly increase at month-6 in either anemic (+0.60 ± 1.39 g/dL, P = 0.258) or non-anemic (+0.08 ± 0.78 g/dL, P = 1.0) patients. In safety population (n = 38), 7 patients dropped out (18.4%). In particular, treatment was discontinued in 4 patients in the first month (2 for diarrhea, 1 for dyspepsia and constipation, and 1 for death), 1 patient after 3 months (switch to intravenous iron for symptomatic anemia), and 2 after five months (1 for dyspepsia and 1 for death). Conclusion The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of functional ID (TSAT<20%), with no significant effect on iron storage. The small sample size prevents any causative conclusion, though it may provide some insights into using these compounds in patients with CKD.

#2856 Sleep disturbances in non-dialysis dependent chronic kidney disease—The CKD-REIN cohort study

Abstract Background and Aims Sleep disturbances are common in patients on dialysis, but little is known about their prevalence and determinants in earlier chronic kidney disease (CKD) stages. We assessed the prevalence of insomnia, excessive daytime sleepiness (EDS), and sleep apnea, and studied their relation with kidney function, before and after accounting for various other potential determinants in patients with moderate or severe CKD. Method This study included 2657 nephrology outpatients with non-dialysis dependent CKD (mean age, 67 ± 12 years; 66% men; mean eGFR, 33 ± 12 mL/min/1.73 m2) from the French CKD-REIN (CKD-Renal Epidemiology and Information Network) cohort study who completed the Basic Nordic Sleep Questionnaire at baseline. Insomnia was defined as having badly or rather badly been sleeping, or having had difficulties falling asleep or awakened too early without being able to fall asleep again at least 3 times per week, over the past 3 months. And EDS, as feeling excessively sleepy during daytime at least 3 times per week over the past 3 months. Sleep apnea with or without continuous positive airway pressure use were identified from medical records. For each sleep disturbance, we assessed the crude prevalence by sex and by estimated glomerular filtration rate (eGFR) categories. We estimated adjusted odds ratios (OR) with 95% confidence interval (95% CI) associated with eGFR decrease (per 10 mL/min/1.73 m2) and urinary albumin-to-creatinine ratio (ACR) categories (A1-A3), as well as with age, sex, education (years), smoking, alcohol consumption, physical activity (estimated by the Global Physical Activity Questionnaire), performance score in Instrumental Activities of Daily Living [IADL], obesity, diabetes, cardiovascular disease, depression, patient-reported cramps, itching and stress or worry about CKD, and relevant drug use. Results Overall prevalence of insomnia, EDS, and sleep apnea were 23%, 15%, and 14%, respectively, with differences between women and men for insomnia, 30% vs 19%, EDS, 17% vs 13%, and sleep apnea, 10% vs 17%, respectively (all P-values <.001). Crude prevalence of EDS significantly increased with decreasing eGFR category (without interaction with sex), but not those for insomnia and sleep apnea (Figure). ACR categories were not associated with either sleep disturbances. In multivariable analyses, factors significantly associated with higher prevalence of insomnia included female sex, smoking, low physical activity, depression, and thyroid hormone use. There were also strong dose-response relations between insomnia prevalence and to what extend patients reported being bothered by cramps or itching, or stressed/worried about CKD. The crude relation of eGFR with EDS tended to weaken (ORs [95% CI], 1.10 [0.99-1.22] per 10 mL/min decrease, p-value 0.09) in multivariable analysis, which showed higher ORs associated with past smoking, depression, lower IADL score, insomnia, and betablocker use, as well as dose-response relations with itching, and stress/worry about CKD. Factors significantly associated with increased prevalence of sleep apnea included male sex, alcohol consumption, lower IADL score, obesity, depression, and cardiovascular disease. Conclusion This analysis of baseline data from the CKD-REIN cohort shows that, in patients with non-dialysis dependent CKD, EDS alone appeared to be related to kidney function level. The study, however, suggests the potential role of modifiable CKD-related symptoms, cramps and itching, and of being stressed or worried about CKD, in addition to that well-documented for behavioral and clinical risk factors, and drugs in the risk of insomnia and EDS.

#2285 Potentially modifiable factors influencing longitudinal health-related quality of life for those with chronic kidney disease in the NURTuRE-CKD cohort

Abstract Background and Aims Factors affecting poor health-related quality of life (HRQoL) for people with chronic kidney disease (CKD) have been previously described in literature, and worse HRQoL is associated with CKD progression and death. Little emphasis has been placed on which factors may be potentially modifiable, and longitudinal HRQoL outcome analyses in non-dialysis dependent CKD cohorts are few in number. Baseline analysis of the NURTuRE-CKD cohort identified several associations between these factors and HRQoL and these associations can now be examined with longitudinal data. Method The NURTuRE-CKD cohort study recruited 2996 participants with non-dialysis dependent CKD between 2017-2019, collecting biochemical, anthropometric, sociodemographic, medical history and patient reported outcome measure (PROM) data. Face-to-face follow-up repeated these measures. Longitudinal worsening overall HRQoL was the main outcome of interest, represented by mapped EQ-5D-3L index value and visual analogue score (VAS). Multivariable linear mixed effects models were fitted in R using the lmer and lmerTest packages. Models for index value were fit separately for each independent variable of interest and collated, as well as fitting models with all variables of interest. Models were adjusted for available confounders, repeated measures and follow-up time. P-values were adjusted for multiple testing using false discovery rate correction. Results 2054/2996 (68.6%) had complete HRQoL data at follow-up, of whom most had CKD stage G3a-G4 (n = 1597, 77.8%). 1817 (88.5%) were white and 1196 (58.2%) were male. Mean age was 63.7 (SD ±14.5) years and the mean number of comorbidities was 3.7 (SD ±2.2). Median (IQR) time between baseline and follow-up was 518 (410) days. At follow-up, mean mapped EQ-5D-3L index value was 0.72 (SD ±0.3) and mean VAS score was 70.4/100 (SD ±20.6). 1595 (77.7%) reported problems in at least one EQ-5D-5L dimension, with 255 (12.4%) developing issues since baseline. 1203 (58.6%) reported worse HRQoL index values at follow up and 910 (44.3%) reported worse VAS. The dimension with the highest number of newly reported issues at follow-up was ‘usual activities’ with 301 (14.7%). Multivariable linear mixed methods models showed independent associations with worse HRQoL (Figs 1 and 2) for those on ten or more medications (β −0.118, CI −0.137 to −0.100, p < 0.001), current smokers (β −0.036, CI −0.067 to −0.006, p = 0.0.012), obesity (β-0.059, CI −0.080 to-0.039, p < 0.001), haemoglobin of <100g/L (β-0.044, CI −0.073 to-0.016, p = 0.014), hospital anxiety and depression scale scores of 8 or above for anxiety (β-0.146, CI −0.161 to-0.130, p < 0.001) and depression (β-0.202, CI-0.219 to −0.186, p < 0.001), worse health literacy (β −0.099, CI −0.136 to −0.063, p < 0.001), and pain (β −0.148, CI −0.161 to −0.135, p ≤ 0.001), weakness (β −0.106, CI −0.120 to −0.092, p < 0.001) and shortness of breath symptoms (β −0.074, CI −0.087 to −0.060, p < 0.001). Conclusion Potentially modifiable factors influencing longitudinal worsening of HRQoL for people with CKD include polypharmacy, smoking, obesity, anaemia, depression and anxiety, limited health literacy, pain, weakness and shortness of breath symptoms. This highlights the need for high quality randomised controlled trials to test interventions addressing these factors with reported HRQoL outcomes. Further work in this cohort is required, examining a third timepoint for HRQoL and linked clinical outcome data.

#1218 Investigating the association of chronic obstructive pulmonary disease with outcomes in patients with non-dialysis dependent chronic kidney disease

Abstract Background and Aims Kidneys and lungs have a strong pathophysiological link. However, studies on the association between chronic conditions involving these two organs, chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), are limited. Nephrologists better understand the pathophysiology and management of acute manifestations of these two organs' dysfunction, i.e., pulmonary-renal syndrome accompanying vasculitis, compared to their chronic alterations. Our study aims to investigate the prevalence and association of COPD with adverse outcomes in patients with CKD (stages 3-5). Method This retrospective observational cohort study was conducted on CKD patients (stages 3-5) enrolled in the Global Collaborative Network (GCN) of the TriNetX research platform between the years 2003 and 2023. TriNetX provides access to anonymized electronic medical records across large healthcare organizations (HCOs). This report includes patients from 112 HCOs with different demographic backgrounds. The study compared outcomes of patients aged 18-80, with and without COPD, in a propensity score matched (PSM) cohort of CKD patients. The characteristics included in the PSM were age, sex, ethnicity, comorbidities (neurological, hematological, cardiovascular, gastroenterological, and endocrine conditions) and baseline serum creatinine. 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. The Kaplan- Meier (KM) method was used for the survival probability. Statistical significance was defined as p-value < 0.05. Outcome events were included 180 days after the index event (COPD diagnosis) and ended 3650 days after. Results Of the total of 1 045 536 CKD patients, 181 207 had a co-existent diagnosis of COPD (prevalence rate—17.3%). A PSM generated a matched cohort of 174 308 patients each. The mean age of the cohort was 66.7 ± 7.9 years, with a predominance of white ethnicity (65.8%) and an equal male-to-female ratio. 73.1%, 51.5%, 69.6%, 54.1%, and 37.2% had a history of cardiovascular, nervous system, endocrine, gastroenterological, and hematological disease, respectively. The mean serum creatine at baseline was 1.3 ± 1.2 mg/dL. The comparison of differences in the outcomes on follow-up between the matched cohorts is illustrated in Table 1. CKD patients with concomitant COPD had a higher all-cause mortality (17.3% vs 8.7%, p < 0.0001), higher all-cause hospitalizations (14.7% vs 12.7%, p < 0.0001), and higher cardiovascular events. Proportional hazard models showed that COPD is a strong risk factor associated with all-cause mortality (HR: 2.189; 95% CI (2.13-2.22, p < 0.0001)), hospitalizations (HR:1.39; 95% CI (1.36–1.44); p < 0.0001), and other cardiovascular and mental health illness (Table 1). KM chart illustrates the differences in survival probability between the two groups (Log-Rank p < 0.001) (Fig. 1). Conclusion Our ‘real-world data’ findings emphasize that patients with CKD and COPD are a cluster that requires special attention due to poorer outcomes. Given the high frequency of these associations between these two chronic conditions, an improved awareness is warranted among the nephrological community.

#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.

#596 The Borg Scale—efficient and safe for exercise prescription in self-administered balance and strength exercise in patients with CKD

Abstract Background and Aims With the continued rise in chronic kidney disease (CKD), there is a critical need for sustainable, home-based exercise interventions. While supervised, centre-based exercise improves physical performance in CKD patients, unsupervised, self-administered exercise poses challenges in ensuring adherence, safety, and efficacy. This study investigates the Borg Rating of Perceived Exertion (RPE) scale, a subjective measure of exertion, as a method for prescribing and monitoring the intensity of balance and strength exercise in non-dialysis dependent CKD patients. The aims of this study were: Method This sub study of the RENEXC-trial included 148 patients with CKD stages 3-5, with a mean age of 66 ± 14 years and mean measured GFR of 22 ± 8 ml/min/1.73 m2. Patients were prescribed 90 minutes/week of balance or strength exercise at a Borg RPE of 13-17 (corresponding to an exercise intensity of somewhat hard to very hard), along with 60 minutes/week of endurance exercise. Exercise programs were individually prescribed by a physiotherapist according to randomization and each patient's baseline performance and were performed at home or in a gym according to the patient's preference. Duration and RPE of the performed exercise were reported in an exercise diary. Progress was monitored by the physiotherapist through phone contact, every week for the first three months of the study and every other week for the rest of the study year. The continuous follow up provided motivation and enabled adjustments of the exercise program to maintain the goal RPE, adapt intensity and the weekly duration of exercise. Outcome measures included the Berg Balance Scale (BBS) and Functional Reach Test (FRT), the 30-second sit-to-stand test (30STS) and isometric quadriceps strength (IQS). Balance and strength measures were evaluated at baseline and after 12 months of exercise. Previous publications of the RENEXC-trial showed no difference between patients who performed balance exercise and patients who performed strength exercise; therefore, this sub-study analysed all included patients as one group. Results Of 148 participants, 112 completed the study. At 12 months, 79% reported performed exercise, with 86% of these patients adhering to the prescribed intensity. The median (25th-75th percentile) exercise intensity was a RPE of 14 (13-15) on the Borg scale, and the median (min-max) exercise duration was 48 (0-241) minutes/week. Only 18% of the patients reached the 90-minute/week target. No exercise-related incidents were reported. Significant improvements were noted in BBS (p = 0.0464), FRT (p = 0.009), 30STS (p = 0.047), and IQS (right/left p = 0.022 / p = 0.049). Conclusion The Borg RPE scale is an effective and safe method for prescribing and monitoring self-administered balance and strength exercise in patients with CKD. Using the Borg scale for prescribing and monitoring exercise intensity during balance and strength exercise resulted in a good level of adherence to the 12-months exercise program and the prescribed exercise intensity. As no exercise related incidents were reported, we conclude that the self-administered exercise was safe to perform. Significant improvements in balance and strength were observed with a moderate to high exercise intensity prescription within a wide range of performed weekly duration of exercise, suggesting the Borg scale's value in exercise prescription in both well- and deconditioned patients with CKD. These findings show that the integration of the Borg scale into routine exercise prescription in people with CKD can promote patient autonomy and efficient resource utilization in healthcare.

Personalized nutritional management in the transition from non-dialysis dependent chronic kidney disease to dialysis.

Dialysis has been the dominant treatment regimen in end-stage kidney disease as a means to remove uremic waste products and to maintain electrolyte, acid base, and fluid balance. However, given that dialysis may not always provide a survival benefit nor improved quality of life in certain subpopulations, there is growing recognition of the need for conservative and preservative management as an alternative treatment strategy for advanced chronic kidney disease (CKD). Personalized nutritional management tailored to patient's sociodemographics, social needs, psychological status, health literacy level, and preferences is a key component of conservative and preservative care, as well as in the management of patients transitioning from non-dialysis dependent CKD to dialysis. In this review, we discuss the nutritional and metabolic alterations that ensue in CKD; the rationale for low-protein diets in the conservative and preservative management of advanced CKD; the role of plant-based diets in kidney health; emerging data on dietary potassium and sodium intake on CKD outcomes; and the practical implementation of dietary interventions in advanced kidney disease.

Changes in Bone Mineral Density in Patients With Non-dialysis-Dependent Chronic Kidney Disease Are Associated With Body Composition

Chronic kidney disease (CKD) and low bone mineral density (BMD) are highly prevalent and can co-exist. Parameters of mineral metabolism are associated with BMD in CKD, but other contributing factors may contribute. The aim of this study was to assess changes in BMD and its determinants in patients with non-dialysis-dependent CKD (NDD-CKD). Body composition and biochemical profiles were assessed in a retrospective hospital-based cohort study of patients with NDD-CKD. BMD, lean soft tissue (LST), appendicular LST (ALST), and percentage fat mass were assessed by dual-energy X-ray absorptiometry (DXA). ALST index (ALSTI, ALST/height2) and load-capacity index (LCI, fat mass/LST) were calculated. Low BMD was defined as t-score ≤-1.0. Mean time between assessments was 2.8±1.3 years, 46 patients were included. A reduction in renal function was observed. Changes in body composition included reductions in ALST (p=0.031), ALSTI (p=0.021) and a trend for BMD (p=0.053); and an increase in percentage fat mass (p=0.044) and LCI (p=0.032). Females had a reduction in BMD (p=0.034), ALST (p=0.026), and ALSTI (p=0.037). Patients with low BMD at baseline had lower LST (p=0.013), ALST (p=0.023), and percentage fat mass (p=0.037) than those with normal BMD. Additionally, reductions in LST (p=0.041), ALST (p=0.006), and ALSTI (p=0.008) were observed in patients who had low BMD at baseline, while no significant changes in body composition were observed in those with normal BMD at baseline. The following body composition parameters at baseline were determinants of BMD status at follow-up: LST (OR:0.899, 95%CI:0.829-0.976, p=0.010), ALST (OR:0.825, 95%CI:0.704-0.967, p=0.017), and ALSTI (OR:0.586, 95%CI:0.354-0.968, p=0.037), independent of fat mass, and LCI. Detrimental body composition changes were observed without changes in body weight; these were more significant in females. Moreover, this is the first longitudinal study showing a protective effect of LST against BMD loss in patients with NDD-CKD.

Efficacy and Safety of Oral Supplementation with Liposomal Iron in Non-Dialysis Chronic Kidney Disease Patients with Iron Deficiency.

Iron deficiency is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Oral iron supplementation is recommended in these patients, but it is associated with a higher incidence of gastrointestinal adverse reactions. Liposomal iron therapy has been proposed as a new iron formulation, improving iron bioavailability with less side effects; however, few data are available in patients with NDD-CKD. We designed a single-arm pilot study to evaluate the efficacy of liposomal iron administered for six months in correcting iron deficiency (defined as serum ferritin < 100 ng/mL and/or transferrin saturation < 20%) in patients with NDD-CKD stages 1-5. The primary endpoints were the achievement of serum ferritin ≥ 100 ng/mL and transferrin saturation ≥ 20%. Secondary outcomes were hemoglobin (Hb) changes and the safety of liposomal iron. The efficacy population included 34/38 patients, who completed at least one visit after baseline. Liposomal iron increased the achievement of transferrin saturation targets from 11.8% at baseline to 50.0% at month 6 (p = 0.002), while no significant correction of serum ferritin (p = 0.214) and Hb was found (p = 0.465). When patients were stratified by anemia (Hb < 12 g/dL in women and Hb < 13 g/dL in men), a significant improvement of transferrin saturation was observed only in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, p = 0.012). Hb values slightly increased at month 6 only in anemic patients (+0.60 g/dL, 95%CI -0.27 to +1.48), but not in those without anemia (+0.08 g/dL, 95%CI -0.73 to +0.88). In patients taking at least one dose of liposomal iron (safety population, n = 38), the study drug was discontinued in eight patients due to death (n = 2), a switch to intravenous iron (n = 2), and the occurrence of side effects (n = 4). The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of transferrin saturation, with no significant effect on iron storage and Hb levels.

Prognostic effect of masked morning hypertension in Chinese inpatients with non-dialysis chronic kidney disease: A multi-center retrospective study.

This study aimed to elucidate the prognostic role of Masked Morning Hypertension (MMH) in non-dialysis-dependent chronic kidney disease (NDD-CKD). 2,130 NDD-CKD patients of inpatient department were categorized into four blood pressure groups: clinical normotension (CH-), clinical hypertension (CH+) with morning hypertension (MH+), and without MH+ (MH-) respectively. The correlation between these four blood pressure types and the primary (all-cause mortality) and secondary endpoints (cardio-cerebrovascular disease [CVD] and end-stage kidney disease [ESKD]) was analyzed. The prevalences of morning hypertension and masked morning hypertension were 47.4% and 14.98%, respectively. Morning hypertension independently increased the risk of all-cause mortality (P=0.004) and CVD (P<0.001) but not ESKD (P=0.092). Masked morning hypertension was associated with heightened all-cause mortality (HR = 4.22, 95% CI = 1.31-13.59; P=0.02) and CVD events (HR = 5.14, 95% CI = 1.37-19.23; P=0.02), with no significant association with ESKD (HR = 1.18, 95% CI = 0.65-2.15; P=0.60). When considering non-CVD deaths as a competing risk factor, a high cumulative incidence of CVD events was observed in the masked morning hypertension group (HR = 5.16, 95% CI = 1.39-19.08). MMH is an independent risk factor for all-cause mortality and combined cardiovascular and cerebrovascular events in NDD-CKD patients, underscoring its prognostic significance. This highlights the need for comprehensive management of morning hypertension in this population.

Outcomes of Early Versus Delayed Anemia Treatment in Nondialysis-Dependent CKD

IntroductionThe association of hemoglobin level at treatment initiation with renal and cardiovascular outcomes in patients with anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) is unclear. MethodsThis retrospective cohort study utilized two Japanese databases (Medical Data Vision [MDV] and Real World Data [RWD]). Patients initiated long-acting erythropoiesis-stimulating agent treatment were divided into early (hemoglobin levels ≥9.0 g/dL) and delayed (<9.0 g/dL) treatment groups. The primary outcome was a renal composite (renal replacement therapy, ≥50% estimated glomerular filtration rate [eGFR] reduction, eGFR <6.0 mL/min/1.73 m2, and all-cause mortality), and secondary outcomes were a cardiovascular composite (hospitalization by ischemic heart disease including myocardial infarction, hospitalization by stroke and heart failure, and cardiovascular death) and components of the composite outcomes. ResultsAfter propensity score matching, 1472 (MDV) and 1264 (RWD) patients were evaluated. Delayed treatment was not associated with a risk of the renal composite outcome (MDV: hazard ratio [HR] 1.15, 95% confidence intervals [CI] 0.99–1.33; RWD: 1.08, 0.92–1.28). However, delay was associated with higher risks of the cardiovascular composite outcome (MDV: HR 1.47, 95% CI 1.16–1.84; RWD: 1.34, 1.09–1.64), heart failure (MDV: HR 1.50, 95% CI 1.13–2.00; RWD: 1.53, 1.20–1.96) and all-cause mortality (MDV: HR 1.83, 95% CI 1.32–2.54; RWD: 1.64, 1.21–2.22). ConclusionAlthough the risk of renal events was not increased following delayed treatment of anemia in patients with NDD-CKD, the risks of cardiovascular events and all-cause mortality were increased, suggesting the importance of early intervention before hemoglobin fall below 9.0 g/dL.

217 A Phase 1B/2A Double-blind, Placebo-Controlled Study of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Non-Dialysis Dependent Chronic Kidney Disease and Anemia

217 A Phase 1B/2A Double-blind, Placebo-Controlled Study of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Non-Dialysis Dependent Chronic Kidney Disease and Anemia

Factors affecting responsiveness of vadadustat in patients with anemia associated with chronic kidney disease: a post-hoc subgroup analysis of Japanese phase 3 randomized studies

BackgroundVadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease (CKD). The purpose of this post-hoc analysis was to investigate the factors affecting the responsiveness to vadadustat in anemia patients with nondialysis-dependent (NDD) or hemodialysis-dependent (HDD) CKD in two Japanese phase 3 studies.MethodsOf 151 and 162 patients enrolled in NDD-CKD and HDD-CKD studies, 136 and 140 patients, respectively, were included and divided into subgroups for the analysis. To assess vadadustat responsiveness, the resistance index was defined as the mean body weight-adjusted dose of vadadustat (mg/kg) at weeks 20–24 divided by the mean hemoglobin (g/dL) at weeks 20–24. Multivariate analysis was performed to identify the variables affecting the resistance index.ResultsIndependent factors identified as determinants for better response to vadadustat were as follows: high baseline hemoglobin, low baseline eGFR, high week-20–24 ferritin, and CKD not caused by autoimmune disease/glomerulonephritis/vasculitis in NDD-CKD; and male sex, high baseline C-reactive protein, and low baseline erythropoiesis-stimulating agent resistance index (ERI) in HDD-CKD.ConclusionsIn this post-hoc analysis, several factors were identified as affecting the response to vadadustat. These results may provide useful information leading to an appropriate dose modification for vadadustat.Clinical trial registrationNCT03329196 (MT-6548-J01) and NCT03439137 (MT-6548-J03).

Glycated Albumin and Adverse Clinical Outcomes in Patients With CKD: A Prospective Cohort Study

Rationale & ObjectiveHbA1c is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis dependent CKD population remains unknown. Study DesignProspective cohort study. Setting& Participants: 3110 participants with CKD from the Chronic Renal Insufficiency Cohort study. ExposureBaseline GA levels. OutcomesIncident end-stage kidney disease (ESKD), cardiovascular disease (CVD) events, and all-cause mortality. Analytical ApproachCox proportional hazards regression. ResultsParticipant characteristics included mean age 59.0 (SD 10.8) years; 1357 (43.6%) female; 1550 (49.8%) with diabetes. The median GA was 18.7 (interquartile range, 15.8-23.3)%. During an average 7.9-year follow-up, there were 980 ESKD events, 968 CVD events, and 1084 deaths. Higher GA levels were associated with greater risks of all outcomes, regardless of diabetes status: hazard ratios for ESKD, CVD, and death among participants with the highest quartile compared with quartile 2 (reference) were 1.42 (95%CI, 1.19-1.69), 1.67 (CI, 1.39-2.01), and 1.63 (CI, 1.37-1.94), respectively. The associations with CVD and death appeared J-shaped, with increased risk also seen at the lowest GA levels. Among patients with coexisting CKD and diabetes, the associations of GA with outcomes remained significant even after adjusting for HbA1c. For each outcome, we observed a significant increase in the fraction of new prognostic information when both GA and HbA1c were added to models. LimitationsLack of longitudinal GA measurements; HbA1c measurements were largely unavailable in participants without diabetes. ConclusionsAmong patients with CKD, GA levels were independently associated with risks of ESKD, CVD, and mortality, regardless of diabetes status. GA added prognostic value to HbA1c among patients with coexisting CKD and diabetes.

The differential effect of modern intravenous iron on fibroblast growth factor 23 and phosphate in non-dialysis dependent CKD – the exploratory randomized controlled double-blind ExplorIRON-CKD study

BackgroundIntravenous iron is commonly used in patients with non-dialysis-dependent chronic kidney disease (CKD). Modern intravenous iron compounds (e.g. ferric derisomaltose (FDI), ferric carboxymaltose (FCM)) are increasingly utilized with similar efficacy. A differential effect in terms of hypophosphatemia has been noted following administration of FCM, which may be related to fibroblast growth factor 23 (FGF23). This study was designed to examine the comparative effects of FDI and FCM on FGF23, phosphate and other markers of bone turnover.MethodsThe single-center double-blind randomized controlled trial “Iron and Phosphaturia – ExplorIRON-CKD” primarily assessed the effects of FCM and FDI on intact FGF23 and phosphate, whilst also studying the impact on vitamin D, parathyroid hormone and phosphaturia. Bone markers including alkaline phosphatase, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide and carboxy-terminal collagen cross-linked telopeptide were monitored. Non-dialysis-dependent CKD patients (stage 3a-5) with iron deficiency with/without anemia (serum ferritin < 200 µg/L or transferrin saturation = 20% and serum ferritin 200-299 µg/L) were randomized to receive FDI or FCM in a 1:1 ratio. At baseline 1000 mg of intravenous iron was administered followed by 500-1000 mg at 1 month to achieve replenishment. Measurements were performed at baseline, 1–2 days following iron administration, 2 weeks, 1 month (second iron administration), 1–2 days following second administration, 2 months and 3 months following initial infusion.ResultsTwenty-six patients participated in the trial; 14 randomized to FDI and 12 to FCM. Intact FGF23 increased following administration of iron, and the increase was significantly higher with FCM compared to FDI (Baseline to 1–2 days following 1st administration: FDI: 3.0 (IQR: - 15.1 - 13.8) % vs. FCM: 146.1 (IQR: 108.1–203.1) %; p < 0.001 and Baseline to 1–2 days following 2nd administration: FDI: 3.2 (IQR: - 3.5 – 25.4) % vs. FCM: 235.1 (138.5–434.6) %; p = 0.001). Phosphate levels decreased in the FCM group, causing a significant difference versus FDI 2 weeks following administration of the first dose. A significantly greater decrease in 1,25 (OH)2 Vitamin D was noted with FCM. Several markers of bone turnover significantly changed following administration of FCM but not FDI.ConclusionsThe study suggests a differential effect on FGF23 following administration of FCM compared to FDI in non-dialysis-dependent CKD patients, similar to other patient groups. This may lead to changes consistent with hypovitaminosis D and alterations in bone turnover with potential clinical consequences. Further definitive studies are required to understand these differences of intravenous iron compounds.Trial registrationEuropean Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2019–004370-26 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004370-26/GB) (First date of trial registration: 03/12/2019).

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.

Potentially modifiable factors associated with health-related quality of life among people with chronic kidney disease: baseline findings from the National Unified Renal Translational Research Enterprise CKD (NURTuRE-CKD) cohort.

Many non-modifiable factors are associated with poorer health-related quality of life (HRQoL) experienced by people with chronic kidney disease (CKD). We hypothesize that potentially modifiable factors for poor HRQoL can be identified among CKD patients, providing potential targets for intervention. The National Unified Renal Translational Research Enterprise Chronic Kidney Disease (NURTuRE-CKD) cohort study recruited 2996 participants from nephrology centres with all stages of non-dialysis-dependent CKD. Baseline data collection for sociodemographic, anthropometric, biochemical and clinical information, including Integrated Palliative care Outcome Scale renal, Hospital Anxiety and Depression score (HADS) and the 5-level EuroQol-5D (EQ-5D-5L) as HRQoL measure, took place between 2017 and 2019. EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were mapped to an EQ-5D-3L value set to derive index value. Multivariable mixed effects regression models, adjusted for known factors affecting HRQoL with recruitment region as a random effect, were fit to assess potentially modifiable factors associated with index value (linear) and within each dimension (logistic). Among the 2958/2996 (98.7%) participants with complete EQ-5D data, 2201 (74.4%) reported problems in at least one EQ-5D-5L dimension. Multivariable linear regression identified independent associations between poorer HRQoL (EQ-5D-3L index value) and obesity (body mass index ≥30.0kg/m2, β -0.037, 95% CI -0.058 to -0.016, P=.001), HADS depression score ≥8 (β -0.159, -0.182 to -0.137, P<.001), anxiety score ≥8 (β -0.090, -0.110 to -0.069, P<.001), taking ≥10 medications (β -0.065, -0.085 to -0.046, P<.001), sarcopenia (β -0.062, -0.080 to -0.043, P<.001) haemoglobin <100g/L (β -0.047, -0.085 to -0.010, P=.012) and pain (β -0.134, -0.152 to -0.117, P<.001). Smoking and prescription of prednisolone independently associated with problems in self-care and usual activities respectively. Renin-angiotensin system inhibitor (RASi) prescription associated with fewer problems with mobility and usual activities. Potentially modifiable factors including obesity, pain, depression, anxiety, anaemia, polypharmacy, smoking, steroid use and sarcopenia associated with poorer HRQoL in this cohort, whilst RASi use was associated with better HRQoL in two dimensions.

Evaluation of Restless Leg Syndrome in Patients with Non-Dialysis Dependent Chronic Kidney Disease at Fatima Memorial Hospital Lahore: A Cross-sectional Study

Objective: To determine the occurrence of restless leg syndrome in individuals with non-dialysis-dependent chronic kidney disease.Study Design: A descriptive cross-sectional study.Place and Duration of Study: The study was carried out at the Outpatient Department (OPD) of Fatima Memorial Hospital, Lahore, Pakistan, from March 2020 to August 2020.Methods: A total of 280 CKD patients not dependent on dialysis were included in the study. The data were collected through interviews containing questions from international restless leg syndrome study group (IRLSSG). Patients were stratified into different stages according to the estimated glomerular filtration rate (eGFR). Restless leg syndrome was diagnosed by analyzing the responses of the interview marked by the examiner. Results: Among 280 patients, 15.7% (n=44) of chronic kidney disease patients were noted to have restless leg syndrome. The syndrome was significantly more frequent in females and was associated with higher CKD stages (Stage V &gt; Stage III and IV). There was no association with either age or BMI.Conclusion: Restless leg syndrome is more common in chronic kidney disease stage V as compared to lower chronic kidney disease stages (III &amp; IV). If untreated, it can affect patients' quality of life and increase the risk of cardiovascular activities.&#x0D; How to cite this: Basit MB, Sabir O, Shahid AH, Kanwal A, Qadri GA, Rizvi N. Evaluation of Restless Leg Syndrome in Patients with NonDialysis Dependent Chronic Kidney Disease at Fatima Memorial Hospital Lahore: A Cross-sectional study. Life and Science. 2024; 5(1): 95-100.doi: http://doi.org/10.37185/LnS.1.1.516

Humoral Response Following 3 Doses of mRNA COVID-19 Vaccines in Patients With Non-Dialysis-Dependent CKD: An Observational Study.

Chronic kidney disease (CKD) is associated with a lower serologic response to vaccination compared to the general population. There is limited information regarding the serologic response to coronavirus disease 2019 (COVID-19) vaccination in the non-dialysis-dependent CKD (NDD-CKD) population, particularly after the third dose and whether this response varies by estimated glomerular filtration rate (eGFR). The NDD-CKD (G1-G5) patients who received 3 doses of mRNA COVID-19 vaccines were recruited from renal clinics within British Columbia and Ontario, Canada. Between August 27, 2021, and November 30, 2022, blood samples were collected serially for serological testing every 3 months within a 9-month follow-up period. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike, anti-receptor binding domain (RBD), and anti-nucleocapsid protein (NP) levels were determined by enzyme-linked immunosorbent assay (ELISA). Among 285 NDD-CKD patients, the median age was 67 (interquartile range [IQR], 52-77) years, 58% were men, 48% received BNT162b2 as their third dose, 22% were on immunosuppressive treatment, and COVID-19 infection by anti-NP seropositivity was observed in 37 of 285 (13%) patients. Following the third dose, anti-spike and anti-RBD levels peaked at 2 months, with geometric mean levels at 1131 and 1672 binding antibody units per milliliter (BAU/mL), respectively, and seropositivity rates above 93% and 85%, respectively, over the 9-month follow-up period. There was no association between eGFR or urine albumin-creatinine ratio (ACR) with mounting a robust antibody response or in antibody levels over time. The NDD-CKD patients on immunosuppressive treatment were less likely to mount a robust anti-spike response in univariable (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.20, 0.93) and multivariable (OR 0.52, 95% CI: 0.25, 1.10) analyses. An interaction between age, immunoglobulin G (IgG) antibody levels, and time was observed in both unadjusted (anti-spike: P = .005; anti-RBD: P = .03) and adjusted (anti-spike: P = .004; anti-RBD: P = .03) models, with older individuals having a more pronounced decline in antibody levels over time. Most NDD-CKD patients were seropositive for anti-spike and anti-RBD after 3 doses of mRNA COVID-19 vaccines and we did not observe any differences in the antibody response by eGFR.