Baseline Chronic Kidney Disease Research Articles

#2116 Socioeconomic position and incidence of chronic kidney disease in Central Italy

Abstract Background and Aims Socioeconomic position is strongly related to most chronic conditions, with higher prevalence, higher incidence, and more adverse outcomes in disadvantaged groups of the population compared to well-off counterparts. Similar to other pathologies, several studies reported inequalities in the prevalence of chronic kidney disease (CKD). Few studies investigated socioeconomic differences in disease incidence, and some analyzed socioeconomic inequalities in long-term outcomes, such as mortality or end-stage renal disease, with conflicting results. We aimed to investigate the association between educational level and CKD in the Lazio Region Longitudinal Study, i.e., the 2011 census cohort of all residents followed through administrative databases from 1 Jan 2012 to 31 Dec 2022. Method The Lazio region is one of the twenty Italian regions. With its 5.5 million inhabitants, it is located in central Italy and includes Rome, the Italian capital city. We considered the population enrolled in the Lazio Region Longitudinal Study aged 35-90 years. We used a validated algorithm to identify prevalent cases of CKD at baseline (1 Jan 2012) and incident CKD cases during the follow-up (1 Jan 2012 to 31 Dec 2022). We used the education available for each individual from the census questionnaire to indicate socioeconomic position. We used Cox proportional hazard models to investigate the association between educational level and incidence of CKD. We used age as the time scale to punctually adjust for age, and we adjusted the multivariable models for place of residence, citizenship, marital status, and occupational status. Results We selected 3 752 190 25-90-year-olds included in the Lazio Longitudinal Study. We excluded 66 376 prevalent cases, obtaining a study population of 3 685 814 CKD-free individuals. The prevalent cases were more likely males than females, increased with age, were more Italians than foreigners, were diabetics, and residents in Rome compared to the general population. The study population comprised 1 754 781 men with a mean age of 52 years and 1 997 409 women with a mean age of 54 years. During the 11 years of follow-up, we identified 88 784 new CKD cases among men and 70 217 among women, with crude incidence rates of 540 and 364 per 100, 000 person-years, respectively. The age-adjusted models showed a strong association between educational level and CKD incidence in both men and women (Table 1). In men, compared to those with a university degree, those with upper secondary education had a 30% higher risk of suffering from CKD, those with lower secondary education had a 54% higher risk, while the primary educated men had a 70% higher risk. Among women, the excess risk of low-educated compared to those with a university degree was even higher than in men, with HR = 1.33 (95% CI 1.28-1.38), HR = 1.76 (95% CI 1.69-1.82), and HR = 2.24 (95% CI 2.16-2.32) in upper secondary, lower secondary and primary school educated, respectively. The socioeconomic gap was slightly reduced when we adjusted for possible confounders. Conclusion We found strong socioeconomic inequalities in CKD incidence. Further analyses will investigate the clinical risk factors that mediate the association between educational level and CKD incidence.

Abstract PS14-01: Immune related adverse events in patients ≥65 years vs. <65 years with breast cancer treated with immunotherapy

Abstract Background: Pembrolizumab is approved for early/advanced triple negative breast cancer (TNBC), and atezolizumab was previously approved for advanced TNBC. Toxicity of immunotherapy (IO) and immune related adverse events (irAEs) in patients ≥65 years with TNBC is not described in detail in results from registration trials (KEYNOTE 522, KEYNOTE 355, and IMPassion130), where patients ≥65 years were a minority. Understanding real-world IO toxicity and irAEs in patients with breast cancer ≥65 years may inform clinical decision making. Methods: We studied IO toxicity and irAEs in patients with breast cancer ≥65 years vs. < 65 years (at IO start) who received IO at an academic institution. A retrospective review was conducted to identify IO toxicity and irAEs (classified by CTCAE v 5.0). Cohorts were compared with Pearson's chi-squared test (categorical variables) and Wilcoxon rank-sum test (continuous variables). Results: Cohorts had 25 patients ≥65 years (median age 73 years, interquartile range (IQR) 69-74 years) and 104 patients < 65 years (median age 48 years, IQR 39-56 years). Stage I-III/IV breast cancer distribution was 36%/64% for ≥65 years and 68%/32% for < 65 years. Baseline ECOG performance status was mainly 0-1 in both cohorts. IO was mainly pembrolizumab (≥65 years: 96%; < 65 years: 83% for first IO regimen) vs. atezolizumab. Table 1 depicts characteristics of IO toxicity. IO duration was longer in patients < 65 years. While rates of IO interruption for toxicity and discontinuation for toxicity were numerically higher in patients ≥65 years, these findings did not reach statisticial significance, possibly due to the sample size. Similar overall rates of irAEs were seen (≥65 years: 72%; < 65 years: 65%, p=0.47) but there were differences in the types of irAEs. Patients < 65 years had more transaminitis (≥65 years: 12%; < 65 years: 33%, p=0.04), and grade 2-3 hypothyroidism (among patients developing hypothyroidism, ≥65 years: grade 1- 75%, grade 2- 25%, grade 3- 0%; < 65 years: grade 1- 11%, grade 2- 79%, grade 3- 11%, p=0.017). Conversely, patients ≥65 years had higher rates of irAE nephritis (≥65 years: 12%; < 65 years: 1%, p=0.004); notably, none of the patients had baseline chronic kidney disease. Rates of full resolution of irAEs were similar between cohorts (≥65 years: 67%; < 65 years: 57%, p=0.47), but patients ≥65 years had more steroid use for management of first irAE while patients < 65 years required more thyroid hormone supplementation (first irAE management distribution, ≥65 years: steroids- 71%, thyroid hormone- 7%, supportive care- 21%; < 65 years: steroids- 31%, thyroid hormone- 25%, supportive care- 44%, p=0.025). Late onset irAEs and deaths from irAEs were rare in both cohorts, with 1 irAE related death in the cohort ≥65 years. Conclusions: In this real-world cohort, similar overall rates of irAEs were observed in patients ≥65 years and < 65 years. However, patients ≥65 years had higher rates of irAE nephritis and steroid use for irAEs, while patients < 65 years had more transaminitis and higher grade hypothyroidism, requiring more thyroid hormone supplementation. Given these age specific differences, validation in a larger cohort is merited. Table 1. Characteristics of IO toxicity. Citation Format: Neelima Vidula, Jennifer Hutchinson, Abigail McLaren, Lianne Ryan, Andrzej Niemierko, Aditya Bardia. Immune related adverse events in patients ≥65 years vs. <65 years with breast cancer treated with immunotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS14-01.

Extended-Release Calcifediol: A Data Journey From Phase 3 Studies to Real-world Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism.

Early secondary hyperparathyroidism (SHPT) diagnosis and treatment are crucial to delay the progression of SHPT and related complications, in particular, cardiovascular events and bone fractures. Extended-release calcifediol (ERC) has been developed for the treatment of SHPT in patients with stage 3/4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). This review compares baseline characteristics and treatment responses of SHPT patients receiving ERC in Phase 3 studies with those treated with ERC in a real-world study. Mean ± standard deviation baseline parathyroid hormone (PTH) levels were 147 ± 56 pg/mL and 148 ± 64 pg/mL in the Phase 3 ERC cohorts, and 181 ± 98 pg/mL in the real-world study. Other baseline laboratory parameters were consistent between the clinical and real-world studies. ERC treatment increased 25-hydroxyvitamin D [25(OH)D] and significantly reduced PTH levels, regardless of baseline CKD stage, in all studies. In the pooled Phase 3 per-protocol populations, 74% of the ERC cohort were up-titrated to 60 μg/day after 12 weeks at 30 μg/day, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% PTH reduction. Despite a much lower rate of uptitration in the real-world study, 70% of patients achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH. These data establish a 'continuum' of clinical and real-world evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage, baseline PTH levels, and ERC dose. This evidence supports early treatment initiation with ERC, following diagnosis of SHPT, VDI, and stage 3 CKD, to delay SHPT progression.

Association of ketone bodies with incident CKD and death: A UK Biobank study

AimsAlthough cellular and animal models have suggested a protective effect of ketone bodies (KBs), clinical data are still lacking to support these findings. This study aimed to investigate the association of KB levels with incident chronic kidney disease (CKD) and death. MethodsThis was a prospective cohort study of 87,899 UK Biobank participants without baseline CKD who had plasma levels of β-hydroxybutyrate, acetoacetate, and acetone levels measured at the time of enrollment. The main predictor was plasma total KB, which was the sum of the aforementioned three KBs. The primary outcome was a composite of incident CKD, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome. ResultsDuring a median follow-up of 11.9 years, a total of 8,145 primary outcome events occurred (incidence rate 8.0/1,000 person-years). In the multivariable Cox model, a 1-standard deviation increase in log total KB was associated with a 7 % [adjusted hazard ratio (aHR), 1.07; 95 % confidence interval (CI), 1.05–1.10] higher risk of the primary outcome. When stratified into quartiles, the aHR (95 % CI) for Q4 versus Q1 was 1.18 (1.11–1.27). This association was consistent for incident CKD (aHR, 1.04; 95 % CI, 1.01–1.07), and all-cause mortality (aHR, 1.10; 95 % CI, 1.07–1.13). Compared with Q1, Q4 was associated with a 12 % (aHR 1.12; 95 % CI 1.02–1.24) and 26 % (aHR 1.26; 95 % CI 1.15–1.37) higher risk of incident CKD and all-cause mortality, respectively. ConclusionsHigher KB levels were independently associated with higher risk of incident CKD and death.

Nephrotoxic Risk Associated With Combination Therapy of Vancomycin and Piperacillin-Tazobactam in Critically Ill Patients With Chronic Kidney Disease.

Background: The combination of vancomycin and piperacillin-tazobactam (VPT) has been associated with acute kidney injury (AKI) in hospitalized patients when compared to similar combinations. Additional studies examining this nephrotoxic risk in critically ill patients have not consistently demonstrated the aforementioned association. Furthermore, patients with baseline renal dysfunction have been excluded from almost all of these studies, creating a need to examine the risk in this patient population. Methods: This was a retrospective cohort analysis of critically ill adults with baseline chronic kidney disease (CKD) who received vancomycin plus an anti-pseudomonal beta-lactam at Emory University Hospital. The primary outcome was incidence of AKI. Secondary outcomes included stage of AKI, time to development of AKI, time to return to baseline renal function, new requirement for renal replacement therapy, intensive care unit and hospital length of stay, and in-hospital mortality. Results: A total of 109 patients were included. There was no difference observed in the primary outcome between the VPT (50%) and comparator (58%) group (P = .4), stage 2 or 3 AKI (15.9% vs 6%; P = .98), time to AKI development (1.7 vs 2 days; P = .5), time to return to baseline renal function (4 vs 3 days; P = .2), new requirement for RRT (4.5% vs 1.5%; P = .3), ICU length of stay (7.3 vs 7.4 days; P = .9), hospital length of stay (19.3 vs 20.1 days; P = .87), or in-hospital mortality (15.9% vs 10.8%; P = .4). A significant difference was observed in the duration of antibiotic exposure (3.32 vs 2.62 days; P = .045 days). Conclusion: VPT was not associated with an increased risk of AKI or adverse renal outcomes. Our findings suggest that the use of this antibiotic combination should not be avoided in this patient population. More robust prospective studies are warranted to confirm these findings.

Association between the trajectory of ideal cardiovascular health metrics and incident chronic kidney disease among 27,635 older adults in northern China–a prospective cohort study

BackgroundThere is a lack of relevant studies evaluating the long-term impact of cardiovascular health factor (CVH) metrics on chronic kidney disease (CKD).ObjectiveThis study investigates the long-term change in CVH metrics in older people and explores the relationship between CVH metrics trajectory and CKD.MethodsIn total, 27,635 older people aged over 60 from the community-based Tianjin Chronic Kidney Disease Cohort study were enrolled. The participants completed five annual physical examinations between January 01, 2014, and December 31, 2018, and a subsequent follow-up between January 01, 2019, and December 31, 2021. CVH metrics trajectories were established by the group-based trajectory model to predict CKD risk. The relationships between baseline CVH, CVH change (ΔCVH), and CKD risk were also explored by logistic regression and restricted cubic spline regression model. In addition, likelihood ratio tests were used to compare the goodness of fit of the different models.ResultsSix distinct CVH metrics trajectories were identified among the participants: low-stable (11.19%), low-medium-stable (30.58%), medium-stable (30.54%), medium-high-decreased (5.46%), medium-high-stable (18.93%), and high-stable (3.25%). After adjustment for potential confounders, higher CVH metrics trajectory was associated with decreased risk of CKD (P for trend < 0.001). Comparing the high-stable with the low-stable group, the risk of CKD decreased by 46%. All sensitivity analyses, including adjusting for baseline CVH and removing each CVH component from the total CVH, produced consistent results. Furthermore, the likelihood ratio test revealed that the model established by the CVH trajectory fit better than the baseline CVH and Δ CVH.ConclusionThe higher CVH metrics trajectory and improvement of CVH metrics were associated with decreased risk of CKD. This study emphasized the importance of improving CVH to achieve primary prevention of CKD in older people.

Low rate of severe-end-stage kidney disease after SABR for localised primary kidney cancer

BackgroundStereotactic ablative body radiotherapy (SABR) is an emerging treatment for patients with primary renal cell carcinoma (RCC). However, its impact on renal function is unclear. This study aimed to evaluate incidence and clinical factors predictive of severe to end-stage chronic kidney disease (CKD) after SABR for RCC.Methods and materialsThis was a Single institutional retrospective analysis of patients with diagnosed primary RCC receiving SABR between 2012–2020. Adult patients with no metastatic disease, baseline estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2, and at least one post-SABR eGFR at six months or later were included in this analysis. Patients with upper tract urothelial carcinoma were excluded. Primary outcome was freedom from severe to end-stage CKD, determined using the Kaplan–Meier estimator. The impact of baseline CKD, age, hypertension, diabetes, tumor size and fractionation schedule were assessed by Cox proportional hazard models.ResultsSeventy-eight consecutive patients were included, with median age of 77.8 years (IQR 70–83), tumor size of 4.5 cm (IQR 3.9–5.8) and follow-up of 42.2 months (IQR 23–60). Baseline median eGFR was 58 mls/min; 55% (n = 43) of patients had baseline CKD stage 3 and the remainder stage 1–2. By last follow-up, 1/35 (2.8%) of baseline CKD 1–2, 7/27 (25.9%) CKD 3a and 11/16 (68.8%) CKD 3b had developed CKD stage 4–5. The estimated probability of freedom from CKD stage 4–5 at 1 and 5 years was 89.6% (CI 83.0–97.6) and 65% (CI 51.4–81.7) respectively. On univariable analysis, worse baseline CKD (p < 0.0001) and multi-fraction SABR (p = 0.005) were predictive for development of stage 4–5 CKD though only the former remained significant in multivariable model.ConclusionIn this elderly cohort with pre-existing renal dysfunction, SABR achieved satisfactory nephron sparing with acceptable rates of severe to end-stage CKD. It can be an attractive option in patients who are medically inoperable.

Transcatheter aortic valve replacement in patients with chronic kidney disease: a multi-centre retrospective study

Background: Chronic kidney disease (CKD) is a common comorbid condition in patients undergoing transcatheter aortic valve replacement (TAVR). Reported outcome studies on the association of baseline CKD and mortality is currently limited. Objectives: To determine the prevalence of chronic kidney disease in patients undergoing TAVR and analyse their overall procedural outcomes. Methods: This retrospective observational study was conducted at 43 publicly funded hospitals in Hong Kong. Severe aortic stenosis patients undergoing TAVR between the years 2010 and 2019 were enroled in the study. Two groups were identified according to the presence of baseline chronic kidney disease. Results: A total of 499 patients (228, 58.6% men) were enroled in the study. Baseline hypertension was more prevalent in patients with CKD (82.8%; P=0.003). As for primary end-points, mortality rates of CKD patients were significantly higher compared to non-CKD patients (10% vs. 4.1%; P=0.04%). Gout and hypertension were found to be significantly associated with CRF. Patients with gout were nearly six times more likely to have CRF than those without gout (odds ratio = 5.96, 95% CI = 3.12–11.29, P&lt;0.001). Patients with hypertension had three times the likelihood of having CRF compared to those without hypertension (odds ratio=2.83, 95% CI=1.45–6.08, P=0.004). Conclusion: In patients with severe aortic stenosis undergoing TAVR, baseline CKD significantly contributes to mortality outcomes at long-term follow up.

Chronic kidney disease incidences in Thai outpatients diagnosed with psychiatric illnesses receiving lithium maintenance therapy: a university hospital-based study

BackgroundThere has been no previous study in Thailand regarding the incidence of lithium-induced abnormal renal function. Hence, this study aimed to assess the effect of lithium maintenance therapy on chronic kidney disease, and associated factors among outpatients diagnosed with a psychiatric illness within Southern Thailand.MethodsThis was a retrospective study, using an information review from the electronic medical records of Songklanagarind Hospital computer system in the last ten years; from 1 January 2013 until 31 September 2022. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 and persisted for three months or more. There were 461 outpatients diagnosed with a psychiatric illness who received lithium maintenance therapy. From this, 154 outpatients were excluded: 153 received lithium therapy for less than three months and 1 presented with a baseline chronic kidney disease. All data were analyzed using Rstudio 4.3.1. The incidence of lithium-induced chronic kidney disease was analyzed by survival analysis.ResultsOf the 307 outpatients diagnosed with a psychiatric illness and received lithium maintenance therapy, the most common diagnosis was bipolar disorder (59.3%). Most were female (52.8%), with the median (IQR) age of 39.0 (27.5–54.0) years. The median (IQR) age onset of lithium therapy and duration of lithium maintenance therapy were 28.0 (21.0–41.5) years, and 2.97 (0.9–9.2) years, respectively. This study identified six outpatients (1.9%) that developed chronic kidney disease stage 3 or more and one of them (0.3%) presented with chronic kidney disease stage 5 or end-stage. The incidence of lithium-induced chronic kidney disease was 0.0023 cases per exposed patient-year. When comparing outpatients who had received lithium maintenance therapy and developed chronic kidney disease with those who did not develop chronic kidney disease, this study identified that most of the group with chronic kidney disease had a lithium maintenance therapy for more than ten years, had an older age onset of lithium therapy, reported history of psychiatric hospitalization and lithium intoxication, and presented with physical illness. The associated factors between the effect of lithium maintenance therapy and chronic kidney disease could not be identified due to a limited number of outpatients having developed chronic kidney disease.ConclusionsLithium-induced chronic kidney disease was identified as a minor incidence, and it was likely safe for maintenance therapy with careful and regular monitoring. However, older patients or those receiving lithium for a longer time and present with comorbid physical illnesses should be prescribed with caution.IRB / IEC certification65-389-3-4.

Early-Stage Chronic Kidney Disease and Related Health Care Spending

The global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use. To examine the association between early-stage CKD and health care spending and its changes over time in the general population. Cohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023. The CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. The primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019). Of the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m2; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years. In this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.

Changes in Natriuretic Peptide Levels and Subsequent Kidney Function Decline in SPRINT

Rationale & ObjectiveNovel approaches to assessing kidney disease risk during hypertension treatment are needed given the uncertainty in how intensive blood pressure (BP) lowering impacts kidney outcomes. We determined whether longitudinal N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements during hypertension treatment are associated with kidney function decline. Study DesignProspective observational study. Setting& Participants: 8005 Systolic Blood Pressure Intervention Trial (SPRINT) participants with NT-proBNP measurements at baseline and 1 year. Exposure1-year change in NT-proBNP categorized as ≥25% decrease, ≥25% increase, and <25% change (stable). OutcomeAnnualized change in estimated glomerular filtration rate (eGFR) and ≥30% decline in eGFR. Analytical ApproachLinear mixed-effect and logistic regression models were used to evaluate the association of change in NT-proBNP with subsequent annualized change in eGFR and ≥30% decline in eGFR, respectively. Analyses stratified by baseline chronic kidney disease (CKD) status. ResultsCompared with stable 1-year NT-proBNP levels, a ≥25% decrease in NT-proBNP was associated with slower decline in eGFR in those with CKD (adjusted difference [% per year] =1.09 [95% CI, 0.35-1.83]) and without CKD (adjusted difference [% per year] =0.51 [95% CI, 0.21-0.81]; P for interaction =0.4). Meanwhile, ≥25% increase in NT-proBNP in those with CKD was associated with faster decline in eGFR (adjusted difference [% per year] = -1.04 [95% CI, -1.72 to -0.36]) and risk of ≥30% decline in eGFR (adjusted odds ratio: 1.44 [95% CI, 1.06-1.96]); associations were stronger in those with CKD versus without CKD (P for interactions =0.01 and <0.001, respectively). Relationships were similar irrespective of the randomized BP arm in SPRINT (P for interactions >0.2). LimitationsPersons with diabetes and proteinuria > 1 g/d were excluded. ConclusionsChanges in NT-proBNP during BP treatment are independently associated with subsequent kidney function decline, particularly in people with CKD. Studies should assess if dynamic NT-proBNP may be useful in monitoring kidney risk during hypertension treatment.

Impact of worsening renal function (WRF) and baseline chronic kidney disease (CKD) on clinical outcomes in patients with chronic coronary syndromes (CCS); insights from the REAL-CAD study

Abstract Background The impact of worsening renal function (WRF) and baseline chronic kidney disease (CKD) on clinical outcomes in patients with chronic coronary syndromes (CCS) in the era of modern PCI and optimal medical therapy is still unknown. Methods The REAL-CAD study is a prospective, multicenter, randomized trial either high-dose (pitavastatin 4 mg/day) or low-dose (pitavastatin 1 mg/day) statin therapy in 12,118 patients with CCS. The primary endpoint was composite of cardiovascular-death, nonfatal myocardial infarction and stroke, or unstable angina requiring emergency hospitalization (MACCE). CKD was defined as estimated glomerular filtration rate [eGFR]&amp;lt;60mL/min/1.73m2. WRF was defined as an annual decrease in eGFR &amp;gt;20% in the first year and Pre-WRF was defined as decrease in eGFR &amp;lt;20%. After excluding 1,247 patients who had MACCE, censored or missing eGFR within 1-year, 10,871 patients were examined. P &amp;lt; 0.05 was considered as statistically significant. Results Of the 12,118 baseline-patients, 4,340 had baseline-CKD (estimated glomerular filtration rate [eGFR]&amp;lt;60mL/min/1.73m2) and the remaining 7,778 had baseline-non-CKD (eGFR≥60mL/min/1.73m2). Five-year MACCE significantly deteriorated from 5.5% in non-CKD to 9.5% in CKD (p&amp;lt;0.0001). Of the 10,871 patients, 577 patients had WRF, 6014 patients showed Pre-WRF and the remaining 4280 patients maintained Non-WRF. In CKD patients, WRF was independent predictor for 4-year MACCE as compared to Non-WRF (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.03 to 2.73; P=0.039). In Non-CKD patients, Pre-WRF was significant predictor for 4-year MACCE as compared to Non-WRF (HR,1.40; 95%-CI,1.03-to-1.91; P=0.032). Conclusions Baseline-CKD was independent predictor for 5-year MACCE in patients with CCS. While WRF was independent predictor for 4-year MACCE in CKD patients, Pre-WRF was also predictor for 4-year MACCE in Non-CKD patients (NCT01042730).

Efficacy of implantable cardioverter-defibrillator in non-ischemic systolic heart failure in patients with and without chronic kidney disease: an extended follow-up analysis of the DANISH trial

Abstract Background Patients with heart failure (HF) and chronic kidney disease (CKD) may have an increased risk of death from causes competing with arrhythmic death, which could have implications for the efficacy of implantable cardioverter defibrillators (ICDs). Purpose In this extended follow-up study of the Danish Study to Assess the Efficacy of primary prevention of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart failure on Mortality (DANISH), adding four years of additional follow-up, we examined the long-term effects of primary-prevention ICD implantation, compared with usual medical care, according to baseline CKD status. Methods In the DANISH trial, 1,116 patients with non-ischemic systolic HF were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (eGFR ≥/&amp;lt; 60 mL/min/1.73 m2) at baseline. The primary outcome was death from any cause. Secondary outcomes were cardiovascular death and sudden cardiovascular death. Results In total, 1,113 patients had an available eGFR measurement at baseline (median eGFR 73 ml/min/1.73 m2), and 316 (28%) had CKD. During a median follow-up of 9.5 years, ICD implantation, compared with usual medical care, did not reduce the rate of death from any cause (no CKD, HR 0.81 [95% CI, 0.64-1.03]; CKD, HR 0.92 [0.68-1.26]; P for interaction=0.31) or cardiovascular death (no CKD, HR 0.76 [0.57-1.02]; CKD, HR 0.95 [0.66-1.36]; P for interaction=0.21), irrespective of baseline CKD status. Similarly, baseline CKD status did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (no CKD, HR 0.57 [0.32-1.00]; CKD, HR 0.60 [0.31-1.14]; P for interaction=0.70). Conclusions Primary-prevention ICD implantation did not provide an overall survival benefit regardless of baseline kidney function in patients with non-ischemic systolic heart failure.Figure

Abstract 16476: Association Between Atrial Fibrillation and Deep Learning Derived Retinal Features Trained on Electrocardiogram versus Coronary Artery Calcium

Introduction: This study aimed to assess the ability of a deep learning algorithm, Reti-AF, developed from retinal photos, to predict atrial fibrillation (AF) incidence. Its predictive performance was evaluated using the UK Biobank and compared to Reti-CAC, a similar algorithm trained on coronary artery calcium (CAC) scores. Hypothesis: We hypothesised that Reti-AF and Reti-CAC could potentially predict the incidence of AF. Methods: Due to the lack of atrial fibrillation (AF) patients in the UK Biobank, a Masked AutoEncoder method was used with a Vision Transformer (ViT) model. The model was first trained on 636,992 fundus images from a health screening dataset, then fine-tuned with an additional 6,068 retinal images from the UK Biobank. The survival analysis of the UK Biobank's longitudinal data was performed to assess the model's predictive performance for AF, with hazard ratios calculated. Results: In longitudinal validation among participants without baseline AF, Reti-AF was significantly associated with AF incidence (HR=5.50, 95% CI, 1.98-2.57, highest tertile of Reti-AF versus the first tertile) in a univariable model. However, this significance was not maintained in a multivariable model (HR=1.23, 95% CI, 0.93-1.30). When Reti-CAC was applied to predict AF, it showed a significant association with AF incidence in both univariable (HR=9.30, 95% CI, 6.68-12.96, highest tertile of Reti-CAC versus the first tertile) and multivariable (HR=1.84, 95% CI, 1.26-2.70) models after adjustment for age, gender, smoking, diabetes, hyperlipidemia, hypertension, and baseline chronic kidney disease. Conclusions: The study found that combining deep learning with retinal photos and coronary artery calcium (CAC) as a reference, led to more accurate prediction of atrial fibrillation (AF) incidence compared to using AF. Furthermore, Reti-CAC was shown to be capable of predicting both cardiovascular disease onset and AF incidence.

Abstract 14614: Effect of SGLT2 Inhibitors on Renal Outcomes Across Various Patient Populations

Background: The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on renal outcomes in patients with varying combinations of heart failure (HF), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) remains unclear. Methods: Online databases were queried up to May 2023 for primary and secondary analysis of trials of SGLT2i in patients with HF, CKD, or T2DM. Outcomes of interest were composite renal endpoint (defined as an eGFR &lt;15 mL/min/1.73 m2, doubling of serum creatinine, some percent change in eGFR, and/or need for kidney replacement therapy) and change in estimated glomerular filtration rate (eGFR) slope. Hazard ratios (HR) and mean difference with their 95% confidence intervals were pooled using the generic inverse variance method and a random-effects model. Results: 10 trials (n=70,117 patients) were included. Compared with placebo, SGLT2i reduced the risk of composite renal endpoint by 35% in HF (HR: 0.65; 95% CI: 0.50-0.84), 38% in CKD (HR: 0.62; 95% CI: 0.54-0.71), and 37% in DM (HR:0.63; 95% CI: 0.54, 0.73). A similar pattern of benefit was observed in different combinations of these diseases ( Figure 1 ), as well as patients without baseline HF (HR:0.57; 95% CI: 0.51, 0.63), CKD (HR:0.64; 95% CI: 0.42, 0.98) and T2DM (HR:0.62; 95% CI: 0.45, 0.86). Findings were similar for change in eGFR slope. Conclusions: SGLT2i improve renal outcomes in cohorts of HF, CKD and T2DM and these effects appear consistent across patients with different combinations of these conditions.

Abstract 16377: 68Ga-DOTATATE Measurements Predict Progression of Aortic Valve Calcification in Humans

Introduction: Aortic valve (AV) inflammation contributes to calcification (AVca). 68Ga-DOTATATE (GADT), a positron emission tomography (PET) tracer that binds to somatostatin receptors, has emerged as a reliable marker for tissue inflammation. However, the diagnostic and prognostic value of AV GADT uptake in AVca remains unexplored. Hypothesis: We aim to investigate the relationships between baseline AV GADT uptake with baseline AVca and its progression. Methods: A total of 698 individuals (median age 63, 46% male) underwent clinical GADT PET/computed tomography (CT) imaging from 2017 to 2023; 245 had follow-up scans (median 1.3 yrs interval). AV inflammation was measured as the maximum standardized uptake value of GADT uptake within the AV on baseline PET/CT. AVca was quantified in baseline and follow-up CT scans (HU&gt;130). AVca progression was assessed as the difference between baseline and follow-up AVca. Individuals with a square root difference of annualized AVca change ≥ 2.5 were characterized as “progressors” and &lt;2.5 as “non-progressors”. Demographic and clinical data were collected from medical records. Results: Baseline AV GA DT correlated with baseline AVca (standardized β=0.11; p=0.004; Fig 1A ). Further, baseline AV GA DT associated with AVca progression (odds ratio [95% confidence interval]=3.1 [1.5, 6.6]; p=0.003, Fig 1B ) and remained significant after separately adjusting for baseline AVca (3.8 [1.1, 13.8]), hypertension (2.8 [1.3, 6.2]), diabetes (3.0 [1.4, 6.3]), hyperlipidemia (2.4 [1.0, 5.3]), smoking (3.1 [1.5, 6.7]), and chronic kidney disease (2.9 [1.4, 6.3]), but became borderline with adjustment for age and sex (2.4 [0.9, 5.9]; p=0.054; Fig 1C ). Conclusions: Our study highlights the use of GADT for assessing AV inflammation and predicting AVca progression. These findings underscore the role of inflammation in driving AVca progression and have potential implications for risk assessment and evaluating therapies in AV disease.

Abstract 12444: Pulse Pressure and Cardiovascular and Renal Outcomes by Age in the Chronic Renal Insufficiency Cohort

Pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). While PP is known to widen with age, it is less clear what other clinical factors affect PP and whether the risks associated with wide PP are the same across all ages. We used Cox proportional hazards models to investigate the association of PP with development of 1) atherosclerotic cardiovascular disease (ASCVD) events (congestive heart failure hospitalization, myocardial infarction, stroke and peripheral artery disease) or death and 2) 50% reduction in estimated glomerular filtration rate (eGFR) or ESKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. In sensitivity analyses, we evaluated the association of time-updated PP with these outcomes, accounting for potential time-updated confounders using inverse probability of treatment weighting. We evaluated for effect modification by age (divided into tertiles), apparent treatment-resistant hypertension (HTN), baseline diabetes mellitus (DM) status, baseline CKD stage and baseline cardiovascular disease (CVD). Among 5,621 participants with CKD followed for ~5.4 years, mean PP was 57±19 mmHg, 1,396 (25%) had an ASCVD event, 1,186 (21%) died and 1,783 (32%) participants experienced the composite renal outcome. Every 10 mm Hg wider PP was associated with 6% higher risk of an ASCVD event or death (time-updated adjusted hazard ratio [HR]=1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite renal outcome (time-updated adjusted HR=1.17, 95% CI 1.16, 1.18). Wider PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21-61 years; Figure 1A ), but a higher risk of the composite renal outcome in the oldest age tertile (71-79 years; Figure 1B ), suggesting PP may be associated with different pathophysiology across ages.

Changes in renal blood flow after surgically induced weight loss: can bariatric surgery halt the progression of chronic kidney disease?

BackgroundWe previously demonstrated how kidney injury in patients with morbid obesity can be reversed by bariatric surgery (BaS). Objective(s)Based on previous experience, we hypothesize patients’ potentially reversible kidney injury might be secondary to reduction in renal blood flow (RBF), which improves following BaS. SettingAcademic Hospital. MethodsWe conducted a retrospective analysis of patients who underwent BaS at our institution from 2002 to 2019. We identified patients with chronic kidney disease (CKD) using the estimated glomerular filtration rate (eGFR) from the CKD Epidemiology Collaboration Study (CKD-EPI) classification system. We used the BUN/Creatinine (Cr) ratio pre- and postoperatively to determine a prerenal (decreased RBF) versus intrinsic component as the responsible cause of CKD in this patient population. Decreased RBF was defined as BUN/Cr > 20 preoperatively. ResultsOur analysis included n = 2924 patients, of which 11% (n = 325) presented decreased RBF. From our original sample, only n = 228 patients had the complete data necessary to assess both eGFR and RBF (BUN/Cr). Patients with baseline CKD stage 2 demonstrated preoperative BUN/Cr 20.85 ± 10.23 decreasing to 14.99 ± 9.10 at 12-month follow-up (P < .01). Patients with baseline CKD stage 3 presented with preoperative BUN/Cr 23.88 ± 8.75; after 12-month follow-up, BUN/Cr ratio decreased to 16.38 ± 9.27 (P < .01). Patients with CKD stage 4 and ESRD (eGFR < 30) did not demonstrate a difference for pre- and postoperative BUN/Cr 21.71 ± 9.28 and 19.21 ± 14.58, respectively. Conclusion(s)According to our findings, patients with CKD stages 1–3 present improvement of their kidney function after BaS. This amelioration could be secondary to improvement of the RBF, an unstudied reversible mechanism of kidney injury in the bariatric population.

Health-related Quality of Life in 10 years Long-term Survivors of Chronic Kidney Disease: A From-J Study

ObjectiveThe Chronic Kidney Disease (CKD) practice facilitation program in the Frontier of Renal Outcome Modifications in Japan (FROM-J) study reduced cardiovascular disease (CVD) events in patients with CKD. 10-year long-term survivors with CKD lived with serious complications, including end-stage kidney disease (ESKD) and CVD. This study aimed to measure health-related quality of life (HRQOL) in 10-year long-term CKD survivors and examine the predictors and determinants of clinical indices for measured QOL scores. MethodsThe EQ-5D-5L, a generic preference-based instrument, was administered to 1,473 CKD survivors enrolled in the FROM-J study. The 10th-year data collection was performed by either primary care physicians or participants who filled out questionnaires from October 2018 to March 31, 2019. ResultsThe response rate was 38.2% (423/1,473). The mean QOL score was 0.893 (95% confidence interval (CI), 0.880–0.906), and the median QOL score was 1.000 (interquartile range (IQR), 0.806–1.000). The mean QOL score in participants with renal replacement therapy was 0.824 (95% CI, 0.767–0.881), and the median was 0.828 (IQR, 0.755–1.000). The mean QOL score in participants with CVD was 0.877 (95% CI, 0.811–0.943), and the median was 1.000 (IQR, 0.723–1.000). The mean QOL score in participants with 50% decline in eGFR was 0.893 (95% CI, 0.860–0.926), and the median was 0.889 (IQR, 0.825–1.000). The decrease in QOL scores with baseline CKD stages was significant according to the Jonckheere–Terpstra test for trend (P = 0.002). Baseline age, systolic blood pressure, and history of hyperuricemia were significant predictors of 10th-year QOL scores. ConclusionWe suggest that CKD complications negatively affect the QOL scores in 10-year long-term survivors with CKD. CKD guideline-based practices, prevention of ESKD/CVD and management of hypertension, diabetes and hyperuricemia, might contribute to future HRQOL in patients with CKD.

Modifiable kidney disease risk factors among nondiabetic adults with obesity from the Multi-Ethnic Study of Atherosclerosis.

It is unknown whether weight change or physical fitness is associated with chronic kidney disease (CKD) risk among nondiabetic adults with obesity. This was a prospective, longitudinal cohort study of adults with obesity without baseline CKD or diabetes enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Linear mixed-effects and multistate models were adjusted for demographics, time-varying covariates including blood pressure, and comorbidities these were used to examine associations of weight change and slow walking pace (<2 miles/h) with (i) rate of annual estimated glomerular filtration rate (eGFR) decline and (ii) incident CKD, defined as eGFRCr-Cys < 60 mL/min/1.73 m2 , and tested for interaction by baseline hypertension status. Among 1208 included MESA participants (median BMI 33.0 kg/m2 [interquartile range 31.2-35.9]), 15% developed CKD. Slow walking pace was associated with eGFR decline (-0.27 mL/min/1.73 m2 /year; 95% CI: -0.42 to -0.12) and CKD risk (adjusted hazard ratio 1.48; 95% CI: 1.08 to 2.01). Weight gain was associated with CKD risk (adjusted hazard ratio 1.34; 95% CI: 1.02 to 1.78 per 5 kg weight gain from baseline). There was no significant interaction by baseline hypertension status. Slow walking pace and weight gain were associated with CKD risk among adults with obesity who did not have diabetes at baseline.