System Inhibitor Use Research Articles

Economic burden of recurrent hyperkalemia in patients with chronic kidney disease.

Hyperkalemia is a common complication of chronic kidney disease (CKD) and can become recurrent in half of cases. However, the incremental economic burden associated with recurrent hyperkalemia is unknown. To evaluate all-cause health care resource utilization (HRU) and medical costs in patients with stage 3/4 CKD with recurrent hyperkalemia vs normokalaemia and vs nonrecurrent hyperkalemia. Data were from Optum's de-identified Market Clarity Data (January 1, 2016, to August 1, 2022). This retrospective observational cohort study compared patients with stage 3/4 CKD with recurrent hyperkalemia (≥2 hyperkalemia events within 1 year [hyperkalemia event: hyperkalemia diagnosis or potassium [K+]>5 mmol/l]; index was the first hyperkalemia event) with an exact- and propensity score-matched cohort of patients with normokalemia (K+ ≥3.5 to ≤5 mmol/l; random K+ as index) and separately with a matched cohort of patients with nonrecurrent hyperkalemia (1 hyperkalemia event within 1 year; index was hyperkalemia event). Patient characteristics, medication use, HRU, and medical costs were compared between cohorts using standardized mean differences during the 12-month baseline period. All-cause HRU and medical costs during the 12-month follow-up were compared using Wilcoxon rank sum tests for continuous variables and McNemar tests for categorical variables. Substudies of recurrent hyperkalemia vs normokalemia were conducted for patients with Medicare coverage and renin-angiotensin-aldosterone system inhibitor (RAASi) use. The recurrent hyperkalemia vs normokalemia sample comprised 4,549 matched pairs (Medicare substudy: 3,151; RAASi substudy: 3,535) and the recurrent hyperkalemia vs nonrecurrent hyperkalemia sample comprised 1,599 matched pairs. Baseline characteristics, HRU, and medical costs of the cohorts were similar after matching. During follow-up, patients with recurrent hyperkalemia had a mean of 11.2 more health care encounters (0.5 more inpatient admissions, 0.3 more emergency department visits, and 7.2 more outpatient visits) than patients with normokalemia. Patients with recurrent hyperkalemia also had double the total annual medical costs vs normokalemia ($34,163 vs $15,175; P < 0.001), mainly driven by inpatient costs ($21,250 vs $7,392), which accounted for 62.2% and 48.7% of total costs, respectively. Results were similar in the RAASi and Medicare substudies. Recurrent hyperkalemia was associated with a mean 4.3 more all-cause health care encounters and $14,057 higher medical costs (both P < 0.001) than nonrecurrent hyperkalemia. Recurrent hyperkalemia in patients with stage 3/4 CKD was associated with higher all-cause HRU and medical costs compared with normokalemia (including in patients with Medicare coverage and RAASi use) and nonrecurrent hyperkalemia. Research is needed to understand if long-term treatment strategies aimed at preventing hyperkalemia recurrence may alleviate this economic burden.

The Impact of Renin–Angiotensin System Inhibitor Use on Clinical Outcomes by GRACE Score in ST-elevation MI Patients Undergoing Successful Percutaneous Coronary Intervention with Drug-eluting Stents

The Impact of Renin–Angiotensin System Inhibitor Use on Clinical Outcomes by GRACE Score in ST-elevation MI Patients Undergoing Successful Percutaneous Coronary Intervention with Drug-eluting Stents

Identification of risk factors associated with oral 5-aminolevulinic acid induced adverse events in photodynamic diagnosis−transurethral resection of bladder tumor

BackgroundOral 5-aminolevulinic acid for transurethral resection of bladder tumor reduces bladder cancer recurrence compared with standard white-light transurethral resection of bladder tumor. However, data regarding risks of adverse events with this drug are unclear. The aim of the present study was to identify risk factors associated with oral 5-aminolevulinic acid induced adverse events in photodynamic diagnosis-transurethral resection of bladder tumor. MethodsWe studied 104 cases of 5-aminolevulinic acid-photodynamic diagnosis-transurethral resection of bladder tumor from October 2021 to April 2023, administering 20 mg/kg 5-aminolevulinic acid orally at least 2 h pre-surgery. Four major adverse events associated with 5-aminolevulinic acid were selected to identify risk factors for their occurrence, including perioperative hypotension, nausea and/or vomiting, photosensitivity, and liver dysfunction. Univariate and multivariate analyses were conducted to identify the risk factors of those adverse events. ResultsPerioperative hypotension (11.5 %), nausea and/or vomiting (37.5 %) photosensitivity (31.7 %), and liver dysfunction (51.9 %) were observed. Multivariate analyses revealed that spinal anesthesia was associated with hypotension (p = 0.02), whereas advanced age (p < 0.01) and higher body mass index (p < 0.01) were associated with nausea and/or vomiting. Also, male sex (p < 0.01) and longer operative time (p = 0.01) were associated with photosensitivity, and renin-angiotensin system inhibitors use was associated with postoperative liver dysfunction (p < 0.01). ConclusionsFor elderly male obese patients taking renin-angiotensin system inhibitors, particular attention is needed during the perioperative period of photodynamic diagnosis-transurethral resection of bladder tumor under spinal anesthesia due to the higher risk of onset of the adverse events involved in oral administration of 5-aminolevulinic acid.

Kidney outcomes with SGLT2 inhibitor vs. DPP4 inhibitor use in older adults with diabetes.

While the kidney protective effects of sodium glucose co-transporter-2 (SGLT2) inhibitors have attracted much attention, there are limited real-world clinical data examining the effects of SGLT2 inhibitors on kidney function in older individuals. We aimed to compare the kidney outcomes between SGLT2 inhibitor and dipeptidyl peptidase 4 (DPP4) inhibitor use in older adults with diabetes. Using a nationwide claims database, we studied 6354 older adults (≥ 60 years of age) who had diabetes and newly initiated on SGLT2 inhibitors or DPP4 inhibitors. A 1:4 propensity score matching algorithm was used to compare changes in eGFR between SGLT2 inhibitor and DPP4 inhibitor users. The primary outcome was a decline in the rate of estimated glomerular filtration rate (eGFR), which was obtained using a linear mixed-effects model with an unstructured covariance. Following propensity score matching, 6354 individuals including 1271 SGLT2 inhibitor users and 5083 DPP4 inhibitor users (median age: 68 [65-70] years); men, 60.4%; median eGFR:69.0 [59.1-79.0] ml/min/1.73 m2, median hemoglobin A1c [HbA1c]:6.9 [6.5-7.4]%) were analyzed. SGLT2 inhibitor users had a slower eGFR decline than did DPP4 inhibitor users (-0.97 [95% CI, -1.24 to -0.70] ml/min/1.73m2 vs. -1.83 [95% CI, -1.97 to -1.69] ml/min/1.73m2 per year; p for interaction<0.001). This finding remained consistent across subgroups based on age, sex, body mass index, HbA1c level, renin-angiotensin system inhibitor use, and baseline eGFR. Additionally, the risk of a≥20%, ≥ 30%, and≥40% decrease in eGFR from baseline was significantly lower in SGLT2 inhibitor users than that in DPP4 inhibitor users. Our analysis, utilizing a nationwide epidemiological dataset, demonstrated that the decline in eGFR was slower in individuals aged≥60 years with diabetes who were prescribed SGLT2 inhibitors compared to those prescribed DPP4 inhibitors, suggesting a potential advantage of SGLT2 inhibitors for kidney outcomes even in older individuals with diabetes.

Associations of renin-angiotensin system inhibitor use with brain insulin signaling and neuropathology.

To examine the associations of renin-angiotensin system (RAS) inhibitor use with postmortem brain insulin signaling and neuropathology. Among Religious Orders Study participants, 150 deceased and autopsied older individuals (75 with diabetes matched to 75 without by age at death, sex, and education) had measurements of insulin receptor substrate-1 (IRS-1) and RAC-alpha serine/threonine protein kinase (AKT1) collected in the prefrontal cortex using ELISA and immunohistochemistry. Alzheimer's disease (AD), brain infarcts, and cerebral vessel pathology data were assessed by systematic neuropathologic evaluations. RAS inhibitor use was determined based on visual inspection of medication containers during study visits. The associations of RAS inhibitor use with brain insulin signaling measures and neuropathology were examined using adjusted regression analyses. Of the 90 RAS inhibitor users (54 with diabetes), 65 had used only angiotensin-converting enzyme inhibitors, 11 only angiotensin II receptor blockers, and 14 used both. RAS inhibitor use was associated with lower pT308AKT1/total AKT1, but not with pS307IRS-1/total IRS-1 or the density of cells stained positive for pS616 IRS-1. RAS inhibitor use was not associated with the level of global AD pathology or amyloid beta burden, but it was associated with a lower tau-neurofibrillary tangle density. Additionally, we found a significant interaction between diabetes and RAS inhibitors on tangle density. Furthermore, AKT1 phosphorylation partially mediated the association of RAS inhibitor use with tau tangle density. Lastly, RAS inhibitor use was associated with more atherosclerosis, but not with other cerebral blood vessel pathologies or cerebral infarcts. Late-life RAS inhibitor use may be associated with lower brain AKT1 phosphorylation and fewer neurofibrillary tangles.

Renin-angiotensin system inhibitor use and risk of Parkinson's disease: a meta-analysis.

Hypertension is a recognized risk factor for Parkinson's disease (PD). The renin-angiotensin system (RAS) inhibitors are widely used to treat hypertension. However, the association of RAS inhibitor use with PD has still been an area of controversy. Thus, we conducted a meta-analysis to investigate the relationship between RAS inhibitor use and PD. PUBMEDand EMBASE databases were searched for articles published up to Oct 2023. All studies that examined the relationship between RAS inhibitor use and the incidence of PD were included. Seven studies with total 3,495,218 individuals met our inclusion criteria for this meta-analysis. Overall, RAS inhibitor use was associated with a reduction in PD risk (OR = 0.88, 95%CI = 0.79-0.98) compared with the controls. When restricted the analysis to individuals with RAS inhibitor use indication, RAS inhibitor exposure was also associated with a decreased risk of PD (OR = 0.76, 95%CI = 0.62-0.92). Pooled results of cohort studies also did support a protective role of angiotensin converting enzyme inhibitors (ACEIs) (OR = 0.97, 95%CI = 0.89-1.07) users and angiotensin II receptor blockers (ARBs) (OR = 0.8, 95%CI = 0.63-1.02) in PD. Overall, RAS inhibitor use as a class is associated with a reduction in PD risk. However, the findings of ACEIs and ARBs may be limited by small sample size. Future well-designed studies considering the classification by inhibitor type, duration, dose, or property of BBB penetration of RAS inhibitors are needed to clarify the contribution of these exposure parameters on the risk of PD.

Effects of renin-angiotensin system inhibitor and beta-blocker use on mortality in older patients with heart failure with reduced ejection fraction in Japan.

Guideline-directed medical therapy with renin-angiotensin system (RAS) inhibitors and beta-blockers has improved the survival of patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, it is unclear whether RAS inhibitors and beta-blockers can be administered to older patients with HF. Therefore, this study aimed to investigate the effects of beta-blockers and RAS inhibitors on the prognosis of older patients with HFrEF. Demographic, clinical, and pharmacological data from 1,061 patients with acute decompensated HF, enrolled in the Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI study), were analyzed to assess their impact on mortality. Additionally, a machine learning approach was applied to complement the conventional statistical model for analysis. Patients with HFrEF (n = 314) were divided into the all-cause mortality within 2 years group (n = 80) and the survivor group (n = 234). Overall, 41.1% (129/314) of the patients were aged ≥80, and 25.5% (80/314) experienced all-cause mortality within 2 years. Furthermore, 57.6% (181/314) and 79.0% (248/314) were prescribed RAS inhibitors and beta-blockers, respectively. Our analysis showed that RAS inhibitor use was associated with reduced all-cause mortality and cardiac death in patients with HFrEF of all ages (P < 0.001), and beta-blocker use had an interaction with age. Machine learning revealed that the use of beta-blockers altered the risk of mortality, with a threshold of approximately 80 years of age. Beta-blocker use was associated with lower all-cause mortality and cardiac death in patients with HFrEF aged <80 years (P < 0.001) but not in those aged ≥80 years (P = 0.319 and P = 0.246, respectively). These results suggest that beta blockers may differ in their all-cause mortality benefits according to age. RAS inhibitors prevented all-cause mortality and cardiac death at all ages, whereas beta-blockers had different effects depending on the patient's age. This study suggested that the choice of beta-blockers and RAS inhibitors is more important in older patients with HFrEF than in younger patients with the same condition.

Understanding Prescribing Practices and Patient Experiences with Renin Angiotensin System Inhibitors Use in Chronic Kidney Disease: A Qualitative Study

Introduction: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) improve outcomes but are underutilized in patients with chronic kidney disease (CKD). Little is known about reasons for discontinuation and lack of reinitiating these medications. We aimed to explore clinicians’ and patients’ experiences and perceptions of ACEI/ARB use in CKD. Methods: A multi-profession sample of health care clinicians and patients with documented ACEI/ARB-associated side effects in the past 6 months. Participants were recruited from 2 Veterans Affairs healthcare systems in Texas and Tennessee. A total of 15 clinicians and 10 patients completed interviews. We used inductive and deductive qualitative data analysis approaches to identify themes related to clinician and patient experiences with ACEI/ARB. Thematic analysis focused on prescribing decisions and practices, clinical guidelines, and perception of side effects. Data were analyzed as they amassed, and recruitment was stopped at the point of thematic saturation. Results: Clinicians prescribe ACEI/ARB for blood pressure control and kidney protection and underscored the importance of these medications in patients with diabetes. While clinicians described providing comprehensive patient education about ACEI/ARB in CKD, patient interviews revealed significant knowledge gaps about CKD and ACEI/ARB use. Many patients were unaware of their CKD status, and some did not know why they were prescribed ACEI/ARB. Clinicians’ drug management strategies varied widely, as did their understanding of prescribing guidelines. They identified structural and patient-level barriers to prescribing and many endorsed the development of a decision support tool to facilitate ACEI/ARB prescribing and management. Discussion/Conclusion: Our qualitative study of clinicians and providers identified key target areas for improvement to increase ACEI/ARB utilization in patients with CKD with the goal to improve long-term outcomes in high-risk patients. These findings will also inform the development of a decision support tool to assist with prescribing ACEI/ARBs for patients with CKD.

PCR44 Work and Activity Impairment in Individuals With Chronic Kidney Disease According to Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Use

PCR44 Work and Activity Impairment in Individuals With Chronic Kidney Disease According to Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Use

Abstract 12768: Recurrent Hyperkalemia is Associated With Higher Rates of Cardiovascular Outcomes and All-Cause Mortality in Patients With Chronic Kidney Disease: The Revolutionize III Study

Introduction: The impact of recurrent hyperkalemia (rHK) on the time to cardiovascular (CV) outcomes and mortality in patients with chronic kidney disease (CKD) has not been well studied. This real-world study described and compared rates of CV outcomes and all-cause mortality between patients with rHK and matched patients without HK (nonHK). Methods: Patients with rHK were matched 1:1 to nonHK controls via exact and propensity score matching with the date of rHK or nonHK as index. Patients were adults with stage 3 or 4 CKD identified from Optum’s de-identified Market Clarity Data spanning 1/2016 to 8/2022. For each outcome sample, the corresponding CV events in baseline were excluded. CV outcomes included major adverse cardiovascular events plus (MACE+; all-cause mortality or inpatient [IP] heart failure, myocardial infarction, or stroke) and IP cardiac arrhythmia. Rates of CV outcomes and mortality were compared between matched cohorts using cause-specific Cox proportional hazard models and reported as hazard ratios (HR) with 95% confidence intervals (CI). Subgroups analyses were conducted by renin-angiotensin-aldosterone system inhibitor (RAASi) use at index. Results: Of 6,337 matched pairs, mean age was 73.3 years and 47.7% of patients were female. Patients with rHK compared to nonHK had higher rates of CV outcomes, including MACE+ (N = 5,258, HR=1.53 95% CI=[1.43, 1.65]) and IP arrhythmia (N = 5,485, 1.94 [1.74, 2.16]) (all p&lt;0.001, Figure 1 ). Results were consistent in the RAASi subgroup (MACE+: 1.46 [1.31, 1.63]; IP arrhythmia: 1.84 [1.57, 2.16], both p&lt;0.001). Patients with rHK also had higher rates of mortality (Overall: N = 6,337; 1.29 [1.20, 1.38]; RAASi subgroup: 1.25 [1.11, 1.41], both p&lt;0.001) compared to nonHK controls. Conclusions: This study demonstrates that patients with CKD and rHK had significantly higher rates of mortality, MACE+, and IP cardiac arrhythmia compared to matched patients with CKD and nonHK.

Incremental Value of Right Ventricular Outflow Tract Diameter in Risk Assessment of Chronic Heart Failure Patients with Implantable Cardioverter Defibrillators: Development of RVOTD-ICD Benefit Score in Real-World Setting.

Left ventricular ejection fraction (LVEF) remains the basic reference for the prevention of sudden cardiac death (SCD) patients, while right ventricular (RV) abnormalities have now been associated with SCD risk. A modified benefit assessment tool incorporating RV function parameters in consideration of implantable cardioverter defibrillators (ICD) insertion should be taken into account. We enrolled 954 chronic heart failure (CHF) patients (age 58.8 13.1 years; 79.0% male) with quantitative measurements of right ventricular outflow tract diameter (RVOTD) before ICD implantation and then divided them according to the median level of RVOTD. The predictive value of RVOTD in life-threatening ventricular tachycardia (VT)/ventricular fibrillation (VF) vs. non-arrhythmic mortality (defined as death without prior sustained VT/VF), was evaluated respectively. Based on RVOTD and other identified risk factors, a simple risk assessment tool, RVOTD-ICD benefit score, was developed. A higher RVOTD level was significantly associated with an increased risk of VT/VF (per 1 standard deviation (SD) increase, hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.11-1.33; p = 0.002) but not non-arrhythmic mortality (per 1 SD increase, hazard ratio, 0.93; 95% CI, 0.66-1.33; p = 0.709) after multivariable adjustment. Three benefit groups were created based on RVOTD-ICD benefit score, which was calculated from VT/VF score (younger age, higher RVOTD, diuretic use, prior non-sustainable VT, prior sustainable VT/VF) and non-arrhythmic mortality scores (older age, renin-angiotensin-aldosterone system inhibitors use, diabetes, higher left ventricular end-diastolic diameter, New York Heart Association III/IV, higher N-terminal pro-B-type natriuretic peptide levels). In the highest RVOTD-ICD benefit group, the 3-year risk of VT/VF was nearly 8-fold higher than the corresponding risk of non-arrhythmic mortality (39.2% vs. 4.8%, p 0.001). On the contrary, the 3-year risk of VT/VF was similar to the risk of non-arrhythmic mortality (21.9% vs. 21.3%, p = 0.405) in the lowest benefit group. RVOTD-ICD benefit score system yielded improvement in discrimination for VT/VF, non-arrhythmic mortality, and all-cause mortality than Multicenter Automatic Defibrillator Implantation Trial (MADIT)-ICD benefit score in this cohort. Higher RVOTD was associated with significantly increased risk of sustained VT/VF in CHF patients. A simple risk assessment tool incorporating RVOTD (RVOTD-ICD benefit score) could be generalized to ICD populations, and optimize the decision-making process of ICD implantation.

Does Heterogeneity Exist in Treatment Associations With Renin–Angiotensin–System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?

BackgroundWe explored the association between use of renin–angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF). Methods and ResultsWe analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young–low comorbidity burden (12%), atrial fibrillation–hypertensive (32%), older–atrial fibrillation (24%), obese–diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin–angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P = .03) and non-CV hospitalisation (P = .001). In the young–low comorbidity burden and atrial fibrillation–hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese–diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar. ConclusionsIn patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.

Liver Disease Is a Risk Factor for Recurrent Hyperkalemia: A Retrospective Cohort Study.

Liver disease is often associated with dysfunctional potassium homeostasis but is not a well-established risk factor for hyperkalemia. This retrospective cohort study examined the potential relationship between liver disease and recurrent hyperkalemia. Patients with ≥1 serum potassium measurement between January 2004 and December 2018 who experienced hyperkalemia (serum potassium >5.0 mmol/L) were identified from the United States Veterans Affairs database. A competing risk regression model was used to analyze the relationship between patient characteristics and recurrent hyperkalemia. Of 1,493,539 patients with incident hyperkalemia, 71,790 (4.8%) had liver disease (one inpatient or two outpatient records) within 1 year before the index hyperkalemia event. Recurrent hyperkalemia within 1 year after the index event occurred in 234,807 patients (15.7%) overall, 19,518 (27.2%) with liver disease, and 215,289 (15.1%) without liver disease. The risk of recurrent hyperkalemia was significantly increased in patients with liver disease versus those without (subhazard ratio, 1.34; 95% confidence interval, 1.32-1.37; p < 0.0001). Aside from vasodilator therapy, the risk of recurrent hyperkalemia was not increased with concomitant medication. In this cohort study, liver disease was an independent risk factor strongly associated with recurrent hyperkalemia within 1 year, independent of concomitant renin-angiotensin-aldosterone system inhibitor or potassium-sparing diuretic use.

Electronic health record based population health management to optimize care in CKD: Design of the Kidney Coordinated HeAlth Management Partnership (K-CHAMP) trial

Primary care physicians (PCPs) provide the majority of medical care to patients with non-dialysis dependent CKD. However, PCPs report numerous limitations to providing expert CKD care, including poor patient education, inadequate diagnostic evaluation, suboptimal use of medications, and time limitations. The Kidney Coordinated HeAlth Management Partnership (Kidney CHAMP) trial is a cluster randomized controlled trial to evaluate the effectiveness of a novel centralized electronic health records (EHR)-delivered population health management (PHM) strategy for high-risk CKD patients on patient care, safety, and other outcomes of interest to patients, providers, and payors. Over a 42-month period, the trial will compare the effectiveness of a multifaceted intervention that combines early identification of high-risk patients, timely nephrology guidance, pharmacist-led medication management services, and CKD patient education to usual care and enroll 1650 high-risk CKD patients from 100 primary care practices. The primary outcome will be ≥40% decline in estimated glomerular filtration rate (eGFR) or end stage kidney disease. Key secondary outcomes will include blood pressure, renin-angiotensin aldosterone system inhibitors use, and exposure to potentially unsafe medications. If successful, our treatment approach could improve CKD care delivery and safety, resource allocation, and adoption of evidence-based CKD guideline-concordant care.

#3393 PATIENT-REPORTED OUTCOMES IN EARLY VERSUS ADVANCED CHRONIC KIDNEY DISEASE: EVIDENCE FROM BASELINE DATA IN THE DISCOVER CKD PROSPECTIVE STUDY

Abstract Background and Aims Chronic kidney disease (CKD) negatively impacts patients' psychological and social wellbeing. Prior studies have suggested that CKD progression is associated with worsening of health-related quality of life (HRQoL), but these studies were limited in terms of racial and geographic composition. We compared patient-reported outcomes, including symptom burden, work productivity and HRQoL of patients with early versus advanced CKD, based on contemporary data from DISCOVER CKD, a multinational non-interventional cohort study of patients with CKD. Methods DISCOVER CKD (clinicaltrials.gov identifier: NCT04034992) is an ongoing study that aims to generate real-world evidence on the clinical management and experiences of patients with CKD. The study adopted a hybrid design comprising both retrospective and prospective cohorts. For the prospective phase, patients were recruited from the USA, Japan, Sweden, Italy, Spain, and the UK. Clinical data were extracted manually from existing patients’ health records into a standardised case report form. HRQoL was measured via the Short Form (SF)-36 questionnaire, work productivity was assessed with the Work Productivity and Activity Impairment (WPAI)-CKD questionnaire. Symptoms were recorded using a mobile phone application. In this analysis, early CKD was defined as stages 2-3 CKD and advanced CKD as stages 4-5 CKD (inclusive of dialysis patients). For each outcome, baseline scores were compared between patients with early and advanced CKD using an ANCOVA model with adjustment for age, sex, diabetes, hypertension and renin-angiotensin-aldosterone system inhibitor use. P&amp;lt;0.05 was considered statistically significant. DISCOVER CKD received research ethics board approval and informed consent was obtained from all patients. Results A total of 1051 patients with CKD (early CKD, 69.2% [N = 727]: advanced CKD, 30.8% [N = 324]) were enrolled in the prospective phase of DISCOVER CKD. The population was racially diverse with approximately one-third being non-White. The mean age was 62.5 years (early CKD, 63.4 years: advanced CKD, 60.6 years) and 37% (early CKD, 37.7%: advanced CKD, 35.2%) were female. The mean WPAI-CKD scores for percentage work time missed, activity impairment, impairment at work and overall work productivity loss were significantly higher in patients with advanced CKD compared to those with early CKD, suggesting greater work and activity impairment (Figure 1). The mean symptom scores for fatigue, pruritis, problems with sleep, nausea, muscle cramping and overall feel about health were all significantly higher in the advanced CKD population (Table 1). The results of the SF-36 questionnaire reported significantly lower mean scores across more domains for patients with advanced CKD, and in particular for general health perception, vitality, physical functioning, social functioning, physical role functioning and emotional role functioning, suggestive of a less favourable overall HRQoL (Table 1). Of note, anxious and depressed feelings were similar for early and advanced CKD. Conclusion In this multinational cohort of patients with CKD, those with advanced disease appeared to experience greater symptom burden, lower HRQoL, and higher work and activity impairment. These findings highlight the need for early detection and treatment of CKD and its reported symptoms to reduce the likelihood of disease progression, which could adversely impact patients’ QoL.

#5507 ANTIHYPERTENSIVE PRESCRIBING PATTERNS IN CKD: FINDINGS FROM THE SALFORD KIDNEY STUDY

Abstract Background and Aims Hypertension is the second leading cause of chronic kidney disease (CKD) following diabetes and occurs in most patients with CKD. Finding an optimal treatment regime for hypertension remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD, and hypertensive CKD patients may require treatment with multiple antihypertensive drugs. Database studies and practice guidelines have continued to demonstrate international variability in antihypertensive treatment practices. We analysed data from the Salford Kidney Study (SKS) database in relation to antihypertensive prescribing patterns amongst study patients. Method The SKS is an ongoing prospective study recruiting patients with CKD since the year 2002. Data including patient demographics, comorbidities, physical parameters, concurrent medications, and biochemical results are collected at baseline (study enrolment). All patients are followed up annually until they reach their endpoints [reaching end-stage kidney disease (ESKD), death, or discharge from follow-up] individually, with updates in their medical records including a list of medications. We have used Cox regression analysis and Kaplan Meier charts to investigate the associations between Renin-Angiotensin-Aldosterone System inhibitor (RAASi) use and the number of antihypertensive agents (binary groups of ≤3 or &amp;gt;3), and clinical outcomes (ESKD and all-cause mortality). Results A total of 3230 patients recruited between October 2002 and December 2019 were included in this analysis. At baseline, the median age of the cohort was 67 years with a predominance of males (62%) and those of white ethnicity (96%). 90% had a history of hypertension and 32% were diabetic. The median blood pressure was 138/75 mmHg. Previous myocardial infarction was recorded in 15%, congestive cardiac failure in 17% and cerebrovascular disease in 7.7% of the patients. The median estimated glomerular filtration rate (eGFR) was 30 ml/min/1.73 m2 and the median urine protein creatinine ratio (uPCR) was 33 mg/mmol. RAASi agents (ACEi &amp; ARB) (56%) were the most common antihypertensive medications to be prescribed, followed by diuretics (50%), calcium channel blockers (45%), and beta blockers (34%). The proportion of patients prescribed RAASi was associated with greater proteinuria (43 vs 33%, p&amp;lt;0.001). CKD patients with preexisting cardiovascular comorbidities were more likely to be prescribed beta blockers (44 vs 27%, p&amp;lt;0.001), diuretics (58 vs 39%, p&amp;lt;0.001) and mineralocorticoid antagonists (6.4 vs 1.85%, p&amp;lt;0.001). An increasing number of CKD patients were being prescribed ARBs over 24-month follow-up (34 vs 28%, p = 0.02). In a multivariable Cox-regression analysis, RAASi intake was not associated with reaching ESKD (HR 0.91; p = 0.49) but was associated with a significant survival benefit (HR 0.84; p = 0.001) (Figure 1). Use of a higher number of antihypertensive agents (i.e. &amp;gt;3) was associated with both greater mortality (HR 1.28; p = 0.02) and worse dialysis-free survival (HR 1.46; p = 0.007) (Figure 2). Conclusion Antihypertensive prescribing patterns in the SKS were consistent with current guidelines in the U.K. (e.g. NICE guidance 2022), with RAASi being predominantly prescribed as the first-line antihypertensive agent. An overall survival benefit was noted with RAASi use, although there was no signal for reducing progression towards ESRD. Outcomes were poor in patients with resistant hypertension needing multiple antihypertensive agents. Considering existing variations between the U.K. and other international guidelines regarding antihypertensive treatment in CKD, continued research is indicated to bridge the gaps between these recommendations and optimise patient outcomes.

"Renalism" with Renin Angiotensin Aldosterone System Inhibitor use in Patients Enrolled in Trials for Heart Failure with Reduced Ejection Fraction and Advanced Chronic Kidney Disease: A Systematic Review.

Angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRA) reduce mortality and hospitalizations in heart failure with reduced ejection fraction (HFrEF) but their use is limited in advanced chronic kidney disease (CKD). We carried out a systematic review of studies on HFrEF and CKD patients. The mean overall percentage of reported ACEI, ARB, MRA, and ARNI use, and the proportion of trials that included patients with advanced CKD grades 4-5 (estimated glomerular filtration rate (eGFR) <15-30 ml/min/1.73m2) were recorded per year. The proportion of trials with advanced CKD was log-transformed, and then fitted into a time regression model. The interactions between the proportion of trials that included CKD grades 4-5 and the proportion of reported use of ACEI, ARB, and MRAs per year were explored using Pearson's correlation and univariate linear regression. A total of 706 articles were included; 76% reported background ACEI/ARB use, while 51% reported MRA use. ACEI/ARB use averaged 83% and MRA 50%. Of the trials, 57% included CKD grades 4-5. Over 10 years, the proportion of trials with CKD grades 4-5 increased while ACEI/ARB use decreased. MRA use rates remained about the same. There was an inverse association found between the proportion of trials with CKD grades 4-5 and ACEI/ARB use per year. In the past 10 years, CKD grades 4-5 patients have been increasingly included in HFrEF clinical trials. Concurrently, ACEI/ARB use has reportedly decreased.

The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors.

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.

IgA vasculitis presenting as nephrotic syndrome following COVID-19 vaccination: a case report

BackgroundFollowing the strong recommendation for coronavirus disease 2019 (COVID‑19) vaccination, many patients with medical comorbidities are being immunized. However, the safety of vaccination in patients with autoimmune diseases has not been well established. We report a new case of biopsy-proven IgA vasculitis with nephritis presenting as a nephrotic syndrome after mRNA COVID-19 vaccination in a patient with a history of leukocytoclastic vasculitis.Case presentationA 76-year-old man with a history of cutaneous leukocytoclastic vasculitis presented with purpura in both lower limbs, followed by nephrotic syndrome after the second dose of BNT162b2 mRNA COVID-19 vaccination. Skin and renal biopsy revealed IgA vasculitis with nephritis. The patient’s past medical history of leukocytoclastic vasculitis and features of chronicity in renal pathology suggest an acute exacerbation of preexisting IgA vasculitis after COVID-19 vaccination. After the steroid and renin-angiotensin system inhibitor use, purpura and acute kidney injury recovered within a month. Subnephrotic proteinuria with microscopic hematuria remained upon follow-up.ConclusionPhysicians should keep in mind the potential (re)activation of IgA vasculitis following mRNA COVID-19 vaccines. It is important to closely monitor COVID-19 vaccinated patients, particularly those with autoimmune diseases.

The Association Between Beta-blocker and Renin–Angiotensin System Inhibitor Use After Heart Failure With Reduced Ejection Fraction Hospitalization and Outcomes in Older Patients

IntroductionBeta-blockers (BB) and renin–angiotensin system inhibitors (RASi) are foundational for the treatment of heart failure with reduced ejection fraction (HFrEF). However, given the increased risk of side effects in older patients, uncertainty remains as to whether, on net, older patients benefit as much as the younger patients studied in trials. Methods and ResultsUsing the Get With The Guidelines–Heart Failure registry linked with Medicare data, overlap propensity weighted Cox proportional hazard models were used to examine the association between BB and RASi use at hospital discharge and 30-day and 1-year outcomes among patients with HFrEF. Among the 48,711 patients (aged ≥65 years) hospitalized with HFrEF, there were significant associations between BB and/or RASi use at discharge and lower rates of 30-day and 1-year mortality, including those over age 85 (30-day hazard ratio 0.56, 95% confidence interval 0.45–0.70; 1-year hazard ratio 0.69, 95% confidence interval 0.61–0.78). In addition, the magnitude of benefit associated with BB and/or RASi use after discharge did not decrease with advancing age. Even among the oldest patients, those over age 85, with hypotension, renal insufficiency or frailty, BB and/or RASi use at discharge was still associated with lower 1-year mortality or readmission. ConclusionsAmong older patients hospitalized with HFrEF, BB and/or RASi use at discharge is associated with lower rates of 30-day and 1-year mortality across all age groups and the magnitude of this benefit does not seem to decrease with advancing age. These data suggest that, absent a clinical contraindication, BB and RASi should be considered in all patients hospitalized with HFrEF before or at hospital discharge, regardless of age.