Non-dialysis Dependent Chronic Kidney Disease Research Articles

Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease: Findings from the Salford Kidney Study.

Hypertension is commonly observed in patients living with chronic kidney disease (CKD). Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD. There remains variability in antihypertensive treatment practices. To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients. The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002. All patients are followed up annually, and their medical records including the list of medications are updated until they reach study endpoints [starting on renal replacement therapy or reaching estimated glomerular filtration rate (eGFR) expressed as mL/min/1.73 m2 ≤ 10 mL/min/1.73 m2, or the last follow-up date, or data lock on December 31, 2021, or death]. Data on antihypertensive prescription practices in correspondence to baseline eGFR, urine albumin-creatinine ratio, primary CKD aetiology, and cardiovascular disease were evaluated. Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis. Kaplan-Meier analysis demonstrated differences in survival probabilities. Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included. The median age was 65 years. A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages (53% of eGFR ≤ 15 mL/min/1.73 m2 vs 26% of eGFR ≥ 60 mL/min/1.73 m2, P < 0.001). An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased (category A3: 62% vs category A1: 40%, P < 0.001), with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers. The prescription of three or more antihypertensive agents was associated with all-cause mortality, independent of blood pressure control (hazard ratio: 1.15; 95% confidence interval: 1.04-1.27, P = 0.006). Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed (log-rank, P < 0.001). Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm. Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents. Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.

Sevelamer Use and Mortality in People with Chronic Kidney Disease Stages 4 and 5 Not on Dialysis.

Rationale and objective: Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Study design: Our research is presented in a prospective cohort study. Setting and participants: A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. Exposure: The participants were treated with sevelamer. Outcome: This study yielded all-cause and cardiovascular mortality outcomes. Analytical approach: We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. Results: After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular (n = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Limitations: Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. Conclusions: In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.

Frailty and chronic kidney disease: associations and implications.

Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

The need for standardised outcomes in pharmacist interventions in chronic kidney disease: a systematic review of randomised controlled trials

Abstract Introduction People living with chronic kidney disease (CKD) have a high prevalence of polypharmacy. Polypharmacy presents a significant burden and the risk of inappropriate prescribing in people with CKD is a cause for concern due to age-related changes associated with pharmacodynamics (e.g., increased sensitivity towards adverse drug events) and pharmacokinetics (e.g., reduced renal excretion)1. Strategies for the successful management of CKD include controlling cardiovascular risk factors, lifestyle modifications, and treating comorbidities. There is an ever-increasing role of pharmacists in managing CKD, from medication reviews to optimising risk factors2. However, currently, there is a lack of quality data on the impact of pharmacists in CKD management; this is partly due to the wide range of variable outcomes used in studies and a lack of standardised outcome reporting. Aim We aimed to explore the range of outcomes and measures used in pharmacist-led research in CKD that could be recommended for standardised use. Methods A systematic review of randomised controlled trials (RCTs) of interventions in a CKD population with significant pharmacist input was conducted. Searches were conducted in the following databases: MEDLINE, Scopus, and Web of Science. Databases were searched until January 2022; searches were re-run in February 2023. Data was extracted pertaining to clinical (e.g., mortality), economic (e.g., healthcare-associated costs), and humanistic (e.g., quality of life (QoL)) outcomes. Ethical approval was not required because this review is based exclusively on published literature. Results 38 reports of 32 RCTs were identified, with sample sizes of RCTs ranging from 24 to 32,917 participants. Most studies were conducted in the United States (16/32), whilst one was conducted in the United Kingdom. Of these, 12/32 (37.5%) were exclusively conducted in people on dialysis, six in kidney transplant recipients, 13 in those with non-dialysis dependent CKD, and one study in a mixed cohort. The interventions delivered by pharmacists were heterogenous and included medicine reconciliation, patient counselling, and dose adjustment. A wide range of outcomes were reported including blood pressure, CKD progression, and QoL. The most frequently reported outcome was blood pressure, which was used as an endpoint in 12/32 (37.5%) studies. There was significant heterogeneity in the measures and methods used for reported outcomes. For example, in 11/32 studies (34.4%) where medication adherence was assessed, five separate outcome measures were used: variations of the Morisky Medication Scale (6/11), pharmacy refill records (2/11), Basel Assessment of Adherence to Immunosuppressive Medication Scale (1/11), a comparison of the quantity of medications prescribed with those present in containers (1/11), and the endstage renal disease adherence questionnaire (1/11). Discussion/Conclusion Nephrology is well adept in the use of standardised core outcome sets (COS) (e.g., the Standardised Outcomes in Nephrology initiative)3, yet such COS may not be appropriate to more specialist interventions where different or more relevant outcomes may be needed. The plethora of outcome measures identified in our review suggests a better standardisation of reporting is needed to facilitate consolidation of pharmacy research in the area and further support for the role of the pharmacist in CKD management.

CKD-Associated Pruritus and Clinical Outcomes in Nondialysis CKD

Itching is a frequent symptom experienced by people with chronic kidney disease (CKD). We investigated the associations of CKD-associated pruritus (CKD-aP) with clinical outcomes. This was a longitudinal cohort study. Patients from Brazil, France, and the United States enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) from 2013 to 2021, an international prospective cohort study of adults with nondialysis dependent CKD, and an estimated glomerular filtration rate (eGFR) of<60 mL/min/1.73 m2 were included. CKD-aP was self-reported by response to the question: "During the past 4 weeks, to what extent were you bothered by itchy skin?" The outcomes were as follows: CKD progression, kidney replacement therapy (KRT) initiation, mortality, hospitalization, cardiovascular events, infection events. Associations with time-to-event outcomes were investigated using Cox proportional hazards models adjusted for potential confounders. There were 4,410 patients from 91 clinics with a median age of 69 years and a median eGFR at patient questionnaire completion of 29 (21-38) mL/min/1.73 m2. The proportion of patients not at all, somewhat, moderately, very much, and extremely bothered by itchy skin was 49%, 27%, 13%, 7%, and 3%, respectively. Patients with more advanced stages of CKD, older age, and greater comorbidities reported to be more likely bothered by itchy skin. Among patients at least moderately bothered, 23% were prescribed at least 1 pharmacotherapy (35% in the United States, 19% in France, 4% in Brazil), including antihistamine (10%), gabapentin (6%), topical corticosteroids (4%), pregabalin (3%), or sedating antihistamine (3%). The HR (95% CI) for patients extremely (vs not at all) bothered was 1.74 (1.11-2.73) for all-cause mortality, 1.56 (1.11-2.18) for all-cause hospitalization, and 1.84 (1.22-2.75) for cardiovascular events. As CKD-aP severity increased, patients also had higher rates of infection events (P= 0.04); CKD-aP severity was not associated with KRT initiation (P= 0.20) or CKD progression (P= 0.87). The limitations were 25% nonresponse rate, recall bias, and residual confounding factors. These results demonstrate a strong association between severe itch and clinical outcomes, providing the nephrology community new insights into the possible adverse consequences of CKD-aP in individuals with nondialysis CKD, and warrant further exploration. Chronic kidney disease-associated pruritus (CKD-aP) is a common disturbing symptom of chronic kidney disease (CKD). This article analyzes longitudinal data from the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) to describe prevalence of CKD-aP in 4,410 individuals with nondialysis CKD, and its association with clinical outcomes. We found that 51% of the surveyed population were bothered by pruritus. CKD-aP was more prevalent in those with more advanced stages of CKD, older age, and with more comorbid conditions. Compared to those not at all bothered by pruritus, those who were extremely bothered had a higher risk of all-cause mortality, hospitalizations, and cardiovascular events. Severity of CKD-aP was not associated with CKD progression or initiation of kidney replacement therapy.

Diastolic dysfunction and its association to renal outcomes in patients with chronic kidney disease

Abstract Background Left ventricular diastolic dysfunction is frequent in chronic kidney disease (CKD) and is suspected to be linked to a worse renal prognosis. Purpose To investigate the association between the ratio of early mitral inflow velocity to early diastolic tissue velocity (E/e') measured by Doppler echocardiography and development of end-stage kidney disease in patients with non-dialysis-dependent CKD. Methods This prospective cohort study included individuals with non-dialysis-dependent CKD with previous nephrology-related hospital contact. All participants underwent thorough, protocolized echocardiographic examination. Exclusion criteria were inadequate image quality for E/e'-assessment and prevalent heart failure at baseline. The primary endpoint was the composite outcome of time to dialysis treatment and/or kidney transplantation. The association between E/e' and the composite outcome was assessed with multivariable Cox proportional hazards regression models adjusted for age, sex, estimated glomerular filtration rate (eGFR), diabetes, Body Mass Index, albuminuria, systolic blood pressure, heart rate, coronary artery disease, and left ventricular ejection fraction. Results A total of 731 participants were included in the final study sample. Mean age was 57 ± 13 years and 61% were male. Median E/e' was 7.8 (IQR: 6.4; 9.5), median eGFR was 43 mL/min/1.73 m² (IQR: 28; 62), and 36% had a urine albumin/creatinine ratio &amp;gt;300. During a median follow-up of 3.8 years (IQR: 3.3; 4.5), 102 individuals met the composite outcome. In univariable Cox regression both continuous E/e' and elevated E/e' (E/e' &amp;gt;14) were significantly associated with the outcome (P&amp;lt;0.001). Following multivariable adjustments, increasing E/e' remained significantly associated with the outcome (HR = 1.09, 95% CI [1.03; 1.15], P=0.004, per 1 unit increase) (Figure 1A). Elevated E/e' also remained significantly associated with the outcome following adjustments (HR = 2.95, 95% CI [1.33; 6.53], P=0.008), and more than 40% of patients with E/e' &amp;gt;14 were estimated to have reached the primary endpoint after 4 years (Figure 1B). Conclusion In patients with non-dialysis dependent CKD increasing E/e' and E/e' &amp;gt;14 were both associated with worse renal prognosis.

A Phase 1b Double-Blind, Placebo-Controlled Study of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Non-Dialysis Dependent Chronic Kidney Disease and Anemia

Hepcidin, a central regulator of iron homeostasis, is pathologically elevated in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and anemia. Elevations in hepcidin contribute to the onset, maintenance, and severity of anemia. DISC-0974 is an investigational, first-in-class, monoclonal antibody that blocks hemojuvelin (HJV), a co-receptor in the bone morphogenetic protein-signaling pathway regulating hepcidin expression. In a healthy volunteer study, DISC-0974 demonstrated dose-dependent reductions in serum hepcidin, increases in serum iron with doses up to 56 mg administered subcutaneously (SC), and increasing trends in reticulocyte count, reticulocyte hemoglobin, mean corpuscular hemoglobin, total hemoglobin (Hgb), and red blood cell count. In a rat model of anemia in CKD, DISC-0974 decreased hepcidin, increased serum iron, and normalized hemoglobin (Wu et al., ASH 2022). DISC-0974-103 is a Phase 1b, double-blind, placebo-controlled, single-ascending dose study (NCT05745883) to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DISC-0974 in patients with NDD-CKD and anemia. Eligible participants include patients over 18 years of age with NDD-CKD, stages 2-5, hemoglobin (Hgb) &amp;lt;10.5 g/dL in women and &amp;lt;11.0 g/dL in men, serum ferritin ≥100 μg/L, and transferrin saturation (TSAT) ≤30%. Major exclusionary criteria include: concomitant treatment with therapeutic oral iron, intravenous iron, erythropoietin-stimulating agents, or blood transfusions; splenectomy; and nutritional, genetic, infectious, or autoimmune causes of anemia. Approximately 32 participants will be enrolled. On Day 1, participants will receive a single dose of DISC-0974 SC with evaluations for safety, PK, and PD through 57 days of follow-up. Dose escalation is planned across 4 cohorts consisting of 8 participants each, randomized 3:1 active treatment to placebo, treated at single doses of 28, 40, 60, and 90 mg SC DISC-0974. Safety Review Committee assessments are planned to gate escalation decisions. Primary endpoints include adverse events (AEs), clinical laboratory assessments, vital signs, physical examinations, and electrocardiograms. Secondary endpoints include changes in serum hepcidin-25, iron, TSAT, ferritin, Hgb, and other hematology biomarkers. Enrollment is currently ongoing, and available study results will be presented at the meeting.

Survey of Erythropoiesis-Stimulating Agent (ESA) Use in Non-Dialysis-Dependent CKD (NDD-CKD) in Civilian vs. Military Practice

Survey of Erythropoiesis-Stimulating Agent (ESA) Use in Non-Dialysis-Dependent CKD (NDD-CKD) in Civilian vs. Military Practice

Long-Term Efficacy of an AI-Based Health Coaching Mobile App in Slowing the Progression of Non-Dialysis Dependent CKD: A Retrospective Cohort Study.

Chronic kidney disease (CKD) is a significant public health concern, with an escalating global prevalence ranging from 11% to 13%. Therefore, practical strategies for slowing CKD progression and improving patient outcomes are imperative. There is limited evidence to substantiate the efficacy of mobile app-based nursing systems for decelerating CKD progression. This study aimed to evaluate the long-term efficacy of the KidneyOnline intelligent care system in slowing the progression of non-dialysis-dependent CKD. In this retrospective study, the KidneyOnline app was utilized for CKD patients in China who were registered between January 2017 and April 2023. Patients were divided into two groups: an intervention group using the app's nurse-led, patient-oriented management system and a conventional care group that didn't use the app. Patients' uploaded health data were processed via deep learning optical character recognition, and the AI system provided personalized healthcare plans and interventions. Conversely, the conventional care group received suggestions from nephrologists during regular visits without AI assistance. Monitoring extended for an average duration of 2.1 years post-recruitment, with the study's objective being to assess the app's effectiveness in preserving kidney function. The primary outcome was the eGFR slope over the follow-up period, and secondary outcomes included changes in albumin-to-creatinine ratio (ACR) and mean arterial pressure (MAP). A total of 12297 eligible patients who registered on the KidneyOnline app from January 2017 to April 2023 were enrolled for the analysis. Among them, 808 patients were successfully matched using 1:1 propensity score matching, resulting in 404(50%) patients in the KidneyOnline care system group and another 404(50%) patients in the conventional care group. The eGFR slope in the KidneyOnline care group was significantly lower than that in the conventional care group (-1.3, 95% CI: -2.4, -0.1 mL/min/1.73 m2 per year vs. -2.8, 95% CI: -3.8, -1.9 mL/min/1.73 m2 per year，P=.009). Subgroup analysis revealed that the effect of the KidneyOnline care group was more significant in males, patients over 45 years old, and patients with worse baseline kidney function, higher blood pressure, and heavier proteinuria. After 3 and 6 months, the MAP in the KidneyOnline care group decreased to 85.6 (SD 9.2) and 83.6 (SD 10.5) mmHg, respectively, compared to 94.9 (SD 10.6) and 95.2 (SD 11.6) mmHg in the conventional care group (P<.001). The ACR in the KidneyOnline care group showed a more significant reduction after 3 and 6 months (736 mg/g vs. 980 mg/g and 572 mg/g vs. 840 mg/g, P=.074, .027)); however, there was no significant difference in ACR between the two groups at the end of the follow-up period (618 mg/g vs. 639 mg/g, P=.904). The utilization of KidneyOnline, an AI-based, nurse-led, patient-centered care system, may be beneficial in slowing the progression of non-dialysis-dependent CKD.

Patient reported outcome measures and cardiovascular outcomes following high dose modern intravenous iron in non-dialysis dependent chronic kidney disease: secondary analysis of ExplorIRON-CKD

Intravenous iron is commonly used to treat iron deficiency anemia in non-dialysis chronic kidney disease (ND-CKD). There is a paucity of information on the potential impact of intravenous iron on patient reported outcome measures, functional status and markers of cardiovascular health. As part of the secondary analysis of this double-blind exploratory randomized controlled trial focusing on patients with iron deficiency (+ /− anemia) and ND-CKD (serum ferritin < 200 µg/L or transferrin saturation ≤ 20% and serum ferritin 200–299 µg/L; CKD stages: 3a-5), 26 patients were randomized in a 1:1 ratio to receive ferric derisomaltose or ferric carboxymaltose. Participants received 1000 mg at baseline and 500–1000 mg at one month to achieve iron repletion. Quality of life and fatigue status were assessed using the Short-Form (36) questionnaire and the fatigue severity scale. Functional status was evaluated using the Duke Activity Status Index and the 1-min-sit-to-stand test. Cardiac markers such as NT-proBNP, Troponin T and pulse wave velocity were monitored. Intravenous iron was associated with similar improvements in most domains of the Short-Form (36) questionnaire, fatigue status, and 1-min-sit-to-stand ability increased significantly by the end of the trial in both groups (p < 0.001). Markers of cardiac function remained stable, with no arterial stiffness impact. Longer term studies are required to further evaluate the impact of intravenous iron on quality of life and cardiac safety in patients with ND-CKD.

Do Alpha-Ketoanalogues Slow Down Disease Progression in Non-Dialysis Dependent Chronic Kidney Disease?

Objective: To observe the effectiveness of keto-analogues in slowing down the disease progression in non-dialysis dependent CKD patients.Study Design: Quasi-experimental study.Place and Duration of Study: The study was carried out at Nephrology Department of Combined Military Hospital (CMH), Peshawar, Pakistan from August 2022 to 28 February 2023.Methods: Data was collected on 290 kidney disease improving global outcomes (KDIGO) stage 3 and 4 CKD patients through non-probability consecutive sampling technique. The cohort was divided into group A (Low protein diet) and B (ketodiet). Group A received low protein diet in addition to standard chronic disease treatment while Group B was labelled as keto-diet group which received ketoanalogues in addition to low protein diet and standard chronic kidney disease treatment. Baseline and six months eGFR was calculated and compared for both groups. SPSS version 23.00 was used for data analysis. The P value ≤ 0.05 was considered significant.Results: 286 patients aged 51.84±18.127 were selected for our study. 188(65.73%) were males while females were 98 (34.26%). There were 142 (50.34%) and 144(50.34%) patients in group A and B respectively. Duration of CKD in group A and B was 6.45±2.55 and 6.49±1.75 years respectively. The means difference of eGFR in group A (low protein diet) at baseline and after six months was 3.64±1.09mL/ min/ 1.73m2 while that of group B was 1.48±0.41 mL/ min/ 1.73m2 (P-value&lt;0.000). Conclusion: Ketoanalogues is an emerging therapy which slows down disease progression in non-dialysis dependent CKD patients. Although its use is recommended by some clinicians in CKD stage 3 and 4 non-dialysis dependent but still controversial.&#x0D; How to cite this: Saeed B, Khayam, Afridi Z, Ullah MS. Do Alpha-Ketoanalogues Slow Down Disease Progression in Non-Dialysis Dependent Chronic Kidney Disease?. Life and Science. 2023; 4(4): 427-431. doi: http://doi.org/10.37185/LnS.1.1.407

An integrated machine learning predictive scheme for longitudinal laboratory data to evaluate the factors determining renal function changes in patients with different chronic kidney disease stages.

Chronic kidney disease (CKD) is a global health concern. This study aims to identify key factors associated with renal function changes using the proposed machine learning and important variable selection (ML&IVS) scheme on longitudinal laboratory data. The goal is to predict changes in the estimated glomerular filtration rate (eGFR) in a cohort of patients with CKD stages 3-5. A retrospective cohort study. A total of 710 outpatients who presented with stable nondialysis-dependent CKD stages 3-5 at the Shin-Kong Wu Ho-Su Memorial Hospital Medical Center from 2016 to 2021. This study analyzed trimonthly laboratory data including 47 indicators. The proposed scheme used stochastic gradient boosting, multivariate adaptive regression splines, random forest, eXtreme gradient boosting, and light gradient boosting machine algorithms to evaluate the important factors for predicting the results of the fourth eGFR examination, especially in patients with CKD stage 3 and those with CKD stages 4-5, with or without diabetes mellitus (DM). Subsequent eGFR level after three consecutive laboratory data assessments. Our ML&IVS scheme demonstrated superior predictive capabilities and identified significant factors contributing to renal function changes in various CKD groups. The latest levels of eGFR, blood urea nitrogen (BUN), proteinuria, sodium, and systolic blood pressure as well as mean levels of eGFR, BUN, proteinuria, and triglyceride were the top 10 significantly important factors for predicting the subsequent eGFR level in patients with CKD stages 3-5. In individuals with DM, the latest levels of BUN and proteinuria, mean levels of phosphate and proteinuria, and variations in diastolic blood pressure levels emerged as important factors for predicting the decline of renal function. In individuals without DM, all phosphate patterns and latest albumin levels were found to be key factors in the advanced CKD group. Moreover, proteinuria was identified as an important factor in the CKD stage 3 group without DM and CKD stages 4-5 group with DM. The proposed scheme highlighted factors associated with renal function changes in different CKD conditions, offering valuable insights to physicians for raising awareness about renal function changes.

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.

Development of a health economic model to evaluate the cost-effectiveness of roxadustat in treating anemia associated with non-dialysis-dependent chronic kidney disease

BackgroundTreatment for anemia of chronic kidney disease (CKD) largely consists of erythropoiesis-stimulating agents (ESAs) with iron supplementation. Although ESAs are well-established and efficacious, their use has been associated with considerable economic and humanistic burdens. Roxadustat, an oral medication, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that targets multiple causes of CKD and has a similar efficacy and safety profile to ESAs. The cost-effectiveness of this treatment, however, has yet to be investigated.ObjectiveThe study objective was to develop a health economic model to evaluate the cost-effectiveness of roxadustat compared with ESAs for treating anemia of non-dialysis-dependent (NDD) CKD.MethodsA cohort-based model was developed for a hypothetical cohort of 1,000 patients with anemia of NDD CKD, incorporating eight health states, representing the hemoglobin level of each patient. The model was informed by individual patient-level data from the roxadustat global phase 3 clinical trial program. Total and incremental costs as well as quality-adjusted life-years (QALYs) associated with roxadustat versus ESAs were estimated from the perspective of the UK National Health Service. Sensitivity analyses were performed to assess the robustness of the model. Analyses exploring alternative scenarios were also conducted.ResultsOn a per-person basis, over 1,000 simulations, roxadustat was found to be on average less costly (−£32) and more effective (+0.01 QALYs) than ESAs, with a dominant incremental cost-effectiveness ratio. The probability of cost-effectiveness at a £20,000 per QALY willingness-to-pay threshold from the UK perspective was 67%.ConclusionThe model developed may be a useful instrument that, alongside expert clinical opinion, can inform clinical and policy decision-making regarding treatment of anemia of NDD CKD. The model highlights the cost-effectiveness of roxadustat, as well as its potential to have a meaningful impact in reducing the burden of anemia of NDD CKD.

Loop Diuretics and Sarcopenia: A Potential Association

Background: Loop diuretics (LDs) are used to treat various health conditions including heart failure (HF), liver cirrhosis, and chronic kidney disease (CKD). Sarcopenia is a skeletal muscle health issue related to the depletion and decrease of muscle mass and strength, leading to adverse outcomes including frailty syndrome, functional decline, falls, hospitalizations, augmented length of hospital stay, and increased morbidity and mortality. Methods: This study investigated the probable association between LD use and sarcopenia via conducting a non-systematic review of the existing literature. Results: In subjects with non-dialysis-dependent chronic kidney disease (NDD-CKD), an augmented risk of sarcopenia is significantly associated with LD use. Interestingly, in patients with HF treated with LDs, thigh and arm circumferences were significantly small, which is indicative of skeletal muscle wasting. Additionally, in anorexic subjects who are more likely to be on diuretic medication, suffering also from cachexia, a higher prevalence of sarcopenia was demonstrated. In cirrhotic subjects, the treatment dosage of LDs was inversely correlated with the skeletal muscle area per year (ΔSMA). Nevertheless, in subjects with liver cirrhosis treated with LDs, who were divided into those with and those without muscle cramps, the presence of sarcopenia was similar. Conclusions: Further investigation is imperative to validate potential interplay between LDs and sarcopenia.

Effects of correcting metabolic acidosis on muscle mass and functionality in chronic kidney disease: a systematic review and meta-analysis.

Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass and functionality, but the benefits of correction are uncertain. We investigated the effects of correcting metabolic acidosis on nutritional status in patients with CKD in a systematic review and meta-analysis. A search was conducted in MEDLINE and the Cochrane Library from inception to June 2023. Study selection, bias assessment, and data extraction were independently performed by two reviewers. The Cochrane risk of bias tool was used to assess the quality of individual studies. We applied random effects meta-analysis to obtain pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). We retrieved data from 12 intervention studies including 1995 patients, with a mean age of 63.7±11.7years, a mean estimated glomerular filtration rate of 29.8±8.8mL/min per 1.73m2 , and 58% were male. Eleven studies performed an intervention with oral sodium bicarbonate compared with either placebo or with standard care and one study compared veverimer, an oral HCl-binding polymer, with placebo. The mean change in serum bicarbonate was +3.6mEq/L in the intervention group and +0.4mEq/L in the control group. Correcting metabolic acidosis significantly improved muscle mass assessed by mid-arm muscle circumference (SMD 0.35 [95% CI 0.16 to 0.54], P<0.001) and functionality assessed with the sit-to-stand test (SMD -0.31 [95% CI -0.52 to 0.11], P=0.003). We found no statistically significant effects on dietary protein intake, handgrip strength, serum albumin and prealbumin concentrations, and blood urea nitrogen. Correcting metabolic acidosis in patients with CKD improves muscle mass and physical function. Correction of metabolic acidosis should be considered as part of the nutritional care for patients with CKD.

Risk Factors for Heart Failure Readmission After Cardiac Surgery

BackgroundHeart failure (HF) is a leading cause of readmission after cardiac surgery, yet risk factors for HF readmission after cardiac surgery remain poorly characterized. ObjectivesThis study aimed to identify risk factors associated with 30-day HF-specific readmissions after cardiac surgery using a national database. MethodsWe queried the 2016 to 2018 National Readmissions Database to identify U.S. patients who underwent coronary artery bypass grafting (CABG), mitral valve repair/replacement, and/or aortic valve repair/replacement. Exclusion criteria included history of ventricular assist device or heart transplant, dialysis-dependent renal insufficiency, and death during index admission. Clinical variables were defined using International Classification of Diseases-10th Revision codes. The primary outcome was a 30-day readmission for HF following discharge. Multivariable logistic regression was used to account for relevant clinical and demographic covariates and identify independent risk factors for HF readmissions following cardiac surgery. ResultsOur study included 394,050 patients who underwent cardiac surgery (mean age 66 ± 12 years, 63% isolated CABG, 27% isolated valve, 11% CABG + valve). Of these patients, 7,318 were readmitted within 30 days of discharge for a principal diagnosis of HF. Independent risk factors of HF-specific readmission included older age, female sex, prolonged length of stay, comorbid congestive HF, nondialysis dependent chronic kidney disease, chronic obstructive pulmonary disease, chronic liver disease, obesity, atrial fibrillation, and acute kidney injury. Prior CABG was marginally protective for HF-specific readmission. ConclusionsUsing a national registry, we identified risk factors associated with HF readmission after cardiac surgery. Further analysis of these risk factors and their association with HF readmission is warranted.

Frailty and Cardiovascular Outcomes in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes in adults with kidney failure requiring dialysis. However, this relationship has not been thoroughly evaluated among those with non-dialysis-dependent CKD. Prospective cohort study. 2,539 adults in the Chronic Renal Insufficiency Cohort Study. Frailty status assessed using 5 criteria: slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss. Atherosclerotic events, incident heart failure, all-cause death, and cardiovascular death. Cause-specific hazards models. At study entry, the participants' mean age was 62 years, 46% were female, the mean estimated glomerular filtration rate was 45.4mL/min/1.73m2, and the median urine protein was 0.2mg/day. Frailty status was as follows: 12% frail, 51% prefrail, and 37% nonfrail. Over a median follow-up of 11.4 years, there were 393 atherosclerotic events, 413 heart failure events, 497 deaths, and 132 cardiovascular deaths. In multivariable regression analyses, compared with nonfrailty, both frailty and prefrailty status were each associated with higher risk of an atherosclerotic event (HR, 2.03 [95% CI, 1.41-2.91] and 1.77 [95% CI, 1.35-2.31], respectively) and incident heart failure (HR, 2.22 [95% CI, 1.59-3.10] and 1.39 [95% CI, 1.07-1.82], respectively), as well as higher risk of all-cause death (HR, 2.52 [95% CI, 1.84-3.45] and 1.76 [95% CI, 1.37-2.24], respectively) and cardiovascular death (HR, 3.01 [95% CI, 1.62-5.62] and 1.78 [95% 1.06-2.99], respectively). Self-report of aspects of the frailty assessment and comorbidities, which may have led to bias in some estimates. In adults with CKD, frailty status was associated with higher risk of cardiovascular events and mortality. Future studies are needed to evaluate the impact of interventions to reduce frailty on cardiovascular outcomes in this population. Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes. We sought to evaluate the association of frailty status with cardiovascular events and death in adults with CKD. Frailty was assessed according to the 5 phenotypic criteria detailed by Fried and colleagues. Among 2,539 participants in the CRIC Study, we found that 12% were frail, 51% were prefrail, and 37% were nonfrail. Frailty status was associated with an increased risk of atherosclerotic events, incident heart failure, and death.

Patient engagement during the transition from nondialysis-dependent chronic kidney disease to dialysis: A meta-ethnography.

Patient engagement, encompassing both patient experience and opportunities for involvement in care, has been associated with increased patient satisfaction and the overall quality of care. Despite its importance, there is limited knowledge regarding patient engagement in the transition from nondialysis-dependent chronic kidney disease (CKD) to dialysis-dependent treatment. This systematic review employs meta-ethnography to synthesize findings from qualitative studies examining patients' experiences of engagement during this transition, with the aim of developing a comprehensive theoretical understanding of patient engagement in the transition from nondialysis-dependent CKD to dialysis. A systematic search of six databases, namely the Cochrane Library, PsycINFO, Scopus, Embase, PubMedand Web of Sciencewas conducted to identify eligible articles published between 1990 and 2022. Meta-ethnography was utilized to translate and synthesize the findings and develop a novel theoretical interpretation of 'patient engagement' during the transition to dialysis. A total of 24 articles were deemed eligible for review, representing 21 studies. Patient engagement during a transition to dialysis was found to encompass three major domains: psychosocial adjustment, decision-makingand engagement in self-care. These three domains could be experienced as an iterative and mutually reinforcing process, guiding patients toward achieving control and proficiency in their lives as they adapt to dialysis. Additionally, patient engagement could be facilitated by factors including patients' basic capability to engage, the provision of appropriate education, the establishment of supportive relationshipsand the alignment with values and resources. The findings of this review underscore the necessity of involving patients in transitional dialysis care, emphasizing the need to foster their engagement across multiple domains. Recommendations for future interventions include the provision of comprehensive support to enhance patient engagement during this critical transition phase. Additional research is warranted to explore the effects of various facilitators at different levels. The studies included in our review involved 633 participants (547 patients, 14 family members, 63 healthcare providersand 9 managers). Based on their experiences, viewsand beliefs, we developed a deeper understanding of patient engagement and how to foster it in the future.

Validity of the SARC-F questionnaire in assessing sarcopenia in patients with chronic kidney disease: a cross-sectional study.

To examine the validity of the 5-component SARC-F questionnaire for screening sarcopenia among patients with chronic kidney disease (CKD). Eligible participants were enrolled from the Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2019 to November 2019. Evaluations were performed using the self-administered SARC-F questionnaire. Sarcopenia was diagnosed by grip strength, the chair stand test and appendicular skeletal muscle mass. The severity of sarcopenia was evaluated by gait speed. We calculated the sensitivity and specificity of the SARC-F to evaluate construct validity. Moreover, receiver operating characteristic (ROC) curve analysis was performed to identify the cutoff value for nondialysis-dependent (NDD) CKD patients' and maintenance hemodialysis (MHD) patients' scores. A total of 105 NDD-CKD patients and 125 MHD patients were included, and the prevalence of sarcopenia was 5.7 and 31.2%, respectively. Among them, there were 21 (16.8%) MHD patients with severe sarcopenia but no NDD-CKD patients with severe sarcopenia. The sensitivity and specificity of the SARC-F were 16.7 and 98.0% for NDD-CKD patients, and 48.7 and 89.5% for MHD patients, respectively. For NDD-CKD patients, the area under the receiver operating characteristic curve (AUROC) of the total SARC-F score was 0.978 (95% confidence interval (CI): 0.929-0.997, p < 0.001), and the cutoff value of 1 reached the highest Youden index of 0.950 and max ROC curve area of 0.974. For MHD patients, the AUROC of the total SARC-F score was 0.730 (95% CI: 0.644-0.806, p < 0.001), and the cutoff value of 4 reached the highest Youden index of 0.383 and max ROC curve area of 0.691. CKD patients, especially MHD patients, were at high risk of suffering sarcopenia. The SARC-F had low-to-moderate sensitivity but high specificity for screening sarcopenia among patients with CKD. The best cutoff values of the SARC-F score were different for screening sarcopenia among NDD-CKD and MHD patients.