Berlin Initiative Study Research Articles

Medical Suitability and Willingness for Living Kidney Donation Among Older Adults

Rationale & ObjectiveThe benefits of kidney transplantation compared to treatment with dialysis, including in older adult, are primarily limited by the number of donated kidneys. We studied the potential to expand the use of older living kidney donors. Study DesignSecondary analysis of the Berlin Initiative Study, a population-based cohort. Setting& Participants: 2069 adults aged ≥70 years in Germany. ExposuresAge and sex. OutcomesSuitability for living donation assessed by the absence of kidney-related exclusions for donation including albuminuria and low estimated glomerular filtration rate (eGFR) as well as absence of other medical exclusions. Willingness for living and deceased kidney donation assessed by participant survey. Analytical ApproachDescriptive analysis. ResultsAmong the 2069 participants (median age 80 years, 53% women, median eGFR 63 ml/min/1.73m2), 93% had ≥1 medical contraindication for living donation at study entry unrelated to eGFR or albuminuria. Using two published eGFR and albuminuria thresholds for donor acceptance, 38% to 54% of participants had kidney-related exclusions for donation. Among the 5% to 6% of participants with neither medical nor kidney-related exclusions for living donation at baseline, 11% to 12% remained suitable for donation during 8 years of follow-up. Willingness for living or deceased donation was high (73% and 60%, respectively). LimitationsGFR was not measured and medical exclusions unrelated to eGFR and albuminuria were assessed using a cohort database complemented by claims data. ConclusionsOne in twenty older adults were potentially suitable for living kidney donation and willingness for living donation was high. Further studies are warranted to define the feasibility of expanding living kidney donation among older adults.

Social support and frailty progression in community-dwelling older adults.

Despite the growing evidence regarding the influence of social factors on frailty in older adults, the effect of social support remains unclear. This study aims to assess the association between social support and frailty progression (transition and incidence) in a sample of community-dwelling older adults. Using a cohort study design, 1,059 older adults from the Berlin Initiative Study were followed up for 2.1 years. Multinomial and logistic regression analyses were performed to assess the association of social support using Oslo Social Support Scale-3 with frailty transition and incidence, respectively. Gender differences were explored using stratified analyses. At baseline, frailty prevalence in the study population [mean (SD) age 84.3 (5.6) years; 55.8% women] reached 33.1% with 47.0, 29.4 and 23.6% of the participants reporting moderate, strong and poor social support, respectively. Over the follow-up period, social support was not significantly associated with the frailty transition categories in the adjusted model. Conversely, the adjusted logistic regression analysis showed that participants with poor social support had twice the odds of becoming frail compared to those with strong social support (OR 2.07; 95% CI 1.08-3.95). Gender-stratified analyses showed comparable estimates to the main analysis but were statistically non-significant. Our study results underpin the role of social factors in frailty incidence and highlight social support as a potential target for frailty-preventing interventions in older adults. Therefore, it is important to adopt a biopsychosocial model rather than a purely biomedical model to understand and holistically improve the health of community-dwelling older adults.

Evidence for a relationship between genetic polymorphisms of the L-DOPA transporter LAT2/4F2hc and risk of hypertension in the context of chronic kidney disease

BackgroundChronic kidney disease (CKD) and hypertension are chronic diseases affecting a large portion of the population frequently coexistent and interdependent. The inability to produce/use adequate renal dopamine may contribute to the development of hypertension and renal dysfunction. The heterodimeric amino acid transporter LAT2/4F2hc (SLC7A8/SLC3A2 genes) promotes the uptake of L-DOPA, the natural precursor of dopamine. We examined the plausibility that SLC7A8/SLC3A2 gene polymorphisms may contribute to hypertensive CKD by affecting the L-DOPA uptake.Methods421 subjects (203 men and 218 women, mean age of 78.9 ± 9.6 years) were recruited and divided in four groups according to presence/absence of CKD, defined as reduced estimated glomerular filtration rate (eGFR < 60 ml/min/m2) calculated using the creatinine-based Berlin Initiative Study–1 (BIS1) equation, and to presence/absence of hypertension (systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg). Subjects were analysed for selected SNPs spanning the SLC7A8 and SLC3A2 loci by Sequenom MassARRAY iPLEX platform.ResultsThe most significant SNP at the SLC3A2 (4F2hc) locus was rs2282477-T/C, with carriers of the C-allele having a lower chance to develop hypertension among CKD affected individuals [OR = 0.33 (CI 0.14–0.82); p = 0.016]. A similar association with hypertensive CKD was found for the SLC7A8 (LAT2) rs3783436-T/C, whose C-allele resulted associated with decreased risk of hypertension among subjects affected by CKD [OR = 0.56 (95% CI 0.35–0.90; p = 0.017]. The two variants were predicted to be potentially functional.ConclusionsThe association between SLC3A2 and SLC7A8 variants to hypertension development in patients with renal failure could be linked to changes in L-DOPA uptake and consequently dopamine synthesis. Although the associations do not survive correction for Bonferroni multiple testing, and additional research is needed, our study opens new avenues for future basic and translational research in the field of hypertensive CKD.

Effect modification of polypharmacy on incident frailty by chronic kidney disease in older adults

BackgroundFrailty and polypharmacy are common conditions in older adults, especially in those with chronic kidney disease (CKD). Therefore, we analyzed the association of polypharmacy and incident frailty and the effect modification by CKD in very old adults.MethodsIn non-frail individuals within the Berlin Initiative (cohort) Study, polypharmacy (≥ 5 medications) was assessed according to multiple definitions based on the number of regular and on demand prescription and over the counter drugs, as well as vitamins and supplements. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2 and/or an albumin-creatinine ratio ≥ 30 mg/g. Incident frailty was assessed at follow-up using Fried criteria. Logistic regression was applied to assess (1) the association of different polypharmacy definitions with incident frailty and (2) effect modification by CKD.ResultsIn this cohort study, out of 757 non-frail participants (mean age 82.9 years, 52% female, 74% CKD), 298 (39%) participants reported polypharmacy. Over the observation period of 2.1 years, 105 became frail. Individuals with polypharmacy had 1.96 adjusted odds (95% confidence interval (CI): 1.20–3.19) of becoming frail compared to participants without polypharmacy. The effect of polypharmacy on incident frailty was modified by CKD on the additive scale (relative excess risk due to interaction: 1.56; 95% CI 0.01–3.12).ConclusionsThis study demonstrates an association of polypharmacy and incident frailty and suggests strong evidence for an effect modification of CKD on polypharmacy and incident frailty. Revision of prescriptions could be a target strategy to prevent frailty occurrence, especially in older adults with CKD.

Prevalence of Sarcopenia in Chronic Heart Failure and Modulating Role of Chronic Kidney Disease

Introduction: Sarcopenia, heart failure (HF), and chronic kidney disease (CKD) are common among the older people. Our objective was to evaluate the frequency of sarcopenia, among community-dwelling older adults with HF, possible causative factors, and the additive factor of CKD. Methods: A cross-sectional analysis of 1,420 older people living in the community was carried out. Participants (aged 75 years and more) came from a European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test, and bioelectrical impedance analysis was performed. Previous known HF was defined as physician-diagnosed HF registered in the patient’s medical record or the use of HF-related medications, regardless of left ventricular ejection fraction (LVEF). Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate was calculated using Berlin Initiative Study (BIS) to define the stages of CKD. Two-year mortality was also collected. Results: A total of 226 (15.9%) participants had a prior chronic HF diagnosis, with a median age of 80.0 (5.0), and 123 (54.4%) were women. Using EWGSOP2 definition, 11.5% HF and 10.7% in non-HF participants met diagnostic criteria for sarcopenia. In multivariate analyses, only a lower body mass index (BMI) (odds ratios [OR], 0.82; 95% confidence interval [CI], 0.73–0.93) and lower short physical performance battery score (OR, 0.81; 95% CI, 0.69–0.96) were associated with sarcopenia. Patients with HF and sarcopenia have a similar all-cause mortality risk but higher 2-year cardiovascular mortality risk (p = 0.047). Discussion/Conclusion: One out of ten community-dwelling older adults with concurrent clinical stable chronic HF, without considering LVEF, have sarcopenia. Lower BMI and poor physical performance are associated with sarcopenia in this population, but not CKD.

Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population.

The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFCCys) and one creatinine-cystatin C combined equation (EKFCCr-Cys). This study compared their performance with the previous creatinine-based EKFC equation (EKFCCr) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults. A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROCAUC). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30 % of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed. Average rGFR was 73.37 mL/min/1.73 m2. EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFCCr-Cys demonstrating the greatest improvement (R=0.771, ROCAUC=0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFCCr-Cys and EKFCCr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFCCys, showed similar P30 accuracy across sexes. EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFCCys did not outperform EKFCCr, EKFCCr-Cys improved the accuracy of single-marker equations.

Diagnostic Validity of Chronic Kidney Disease in Health Claims Data Over Time: Results from a Cohort of Community-Dwelling Older Adults in Germany.

The validity of ICD-10 diagnostic codes for chronic kidney disease (CKD) in health claims data has not been sufficiently studied in the general population and over time. We used data from the Berlin Initiative Study (BIS), a prospective longitudinal cohort of community-dwelling individuals aged ≥70 years in Berlin, Germany. With estimated glomerular filtration rate (eGFR) as reference, we assessed the diagnostic validity (sensitivity, specificity, positive [PPV], and negative predictive values [NPV]) of different claims-based ICD-10 codes for CKD stages G3-5 (eGFR <60mL/min/1.73m²: ICD-10 N18.x-N19), G3 (eGFR 30-<60mL/min/1.73m²: N18.3), and G4-5 (eGFR <30mL/min/1.73m²: N18.4-5). We analysed trends over five study visits (2009-2019). We included data of 2068 participants at baseline (2009-2011) and 870 at follow-up 4 (2018-2019), of whom 784 (38.9%) and 440 (50.6%) had CKD G3-5, respectively. At baseline, sensitivity for CKD in claims data ranged from 0.25 (95%-confidence interval [CI] 0.22-0.28) to 0.51 (95%-CI 0.48-0.55) for G3-5, depending on the included ICD-10 codes, 0.20 (95%-CI 0.18-0.24) for G3, and 0.36 (95%-CI 0.25-0.49) for G4-5. Over the course of 10 years, sensitivity increased by 0.17 to 0.29 in all groups. Specificity, PPVs, and NPVs remained mostly stable over time and ranged from 0.82-0.99, 0.47-0.89, and 0.66-0.98 across all study visits, respectively. German claims data showed overall agreeable performance in identifying older adults with CKD, while differentiation between stages was limited. Our results suggest increasing sensitivity over time possibly attributable to improved CKD diagnosis and awareness.

Utility of cystatin C and serum creatinine-based glomerular filtration rate equations in predicting vancomycin clearance: A population pharmacokinetics analysis in elderly Chinese patients.

Renal function is an important factor affecting the pharmacokinetics of vancomycin. The renal function in elderly patients gradually decreases with age. An accurate estimated glomerular filtration rate (GFR) is essential in drug dosing. The study aimed to determine the most appropriate renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients using population pharmacokinetic analysis. Data were obtained retrospectively from elderly patients aged ≥65years who received vancomycin for infection from September 2016 to January 2022. Renal function was estimated using the Cockcroft-Gault equation (CG), Modification of Diet in Renal Disease equation (MDRD), three Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPIcys-scr , CKD-EPIscr , and CKD-EPIcys ) and two Berlin Initiative Study equations (BIS-1 and BIS-2). The CKD-EPIcys-scr and BIS-2 equations were based on cystatin C (Cys C) and serum creatinine (Scr). The others were based on Cys C or Scr. A nonlinear mixed effects model (NONMEM) was used to develop the population pharmacokinetic model. A total of 471 serum concentrations from 313 elderly patients were used to develop the population pharmacokinetic model. Weight and GFR were identified as significant covariates affecting the pharmacokinetics of vancomycin. Cys C and Scr-based GFR (CKD-EPIcys-scr and BIS-2) yielded significant improvement performance compared with the other equations in model building. The interindividual variability of CL was reduced from 49.4% to 23.6% and 49.4% to 23.7% in CKD-EPIcys-scr and BIS-2 based models, respectively. However, greater interindividual variabilities of CL (from 26.6% to 29.0%) were represented in the other five models which were based on either Cys C or Scr. The GFR estimated by EPIcys-scr and BIS-2 equations and vancomycin CL exhibited a good correlation (r=0.834 and 0.833). In the external validation with 124 serum concentrations, the predictive performances of the CKD-EPIcys-scr and BIS-2 based models (the mean relative prediction errors were less than 1%, the mean relative absolute prediction errors were about 23%) were also superior to the other five models (the mean relative prediction errors were about 2%, the mean relative absolute prediction errors were greater than 25%) which are based on either Cys C or Scr. In this study, we determined that the equation used to estimate GFR can affect the population pharmacokinetic model fitting result. Population pharmacokinetics model with CKD-EPIcys-scr or BIS-2 can be used to optimize vancomycin dosage in elderly Chinese patients.

Optimal assessment of the glomerular filtration rate in older chinese patients using the equations of the Berlin Initiative Study

AimTo evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese.MethodsThis study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation.ResultsWe enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77–2.18)], highest precision [interquartile range 11.82 (10.32–13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best.ConclusionsAlthough no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency.

Discrepancies among equations to estimate the glomerular filtration rate for drug dosing decision making in aged patients: a cross sectional study

BackgroundPatients often require adjustments to drug doses due to impaired renal function. Glomerular filtration rate (GFR) estimation using various equations can result in discrepancies, potentially leading to different dose adjustment recommendations.AimTo determine the clinical significance of discrepancies observed between different equations used to estimate GFR for drug dose adjustments in a real-world group of patients over 65 years in primary care.MethodThe Cockcroft–Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Berlin Initiative Study 1 equations were applied to estimate GFR in a group of patients over 65 years old attending a primary care center. Results were compared using Bland–Altman plots, and limits of agreement (LoA) and overall bias were calculated. Regression analyses were conducted to identify the null difference GFR and the slope of differences for each pairwise comparison.ResultsA total of 1886 patients were analyzed. Differences between patient-adjusted and body surface area (BSA)-normalized versions of the equations were not clinically relevant for dose adjustments, with LoAs below 20 mL/min. However, discrepancies among the original versions of several equations presented LoAs over 30 mL/min. Greater differences were found between CG and MDRD or CKD-EPI equations.ConclusionClinically relevant differences in GFR estimation were observed among different equations, potentially impacting drug dose adjustments. However, discrepancies were not considered significant when comparing patient-adjusted and BSA-normalized versions of the equations, particularly for patients with BSA close to the average.

Kidney function estimators for drug dose adjustment of direct oral anticoagulants in older adults with atrial fibrillation.

The Cockcroft-Gault equation (CrClC-G) is recommended for dose adjustment of direct oral anticoagulant drugs (DOACs) to kidney function. We aimed to assess whether defining DOAC dose appropriateness according to various kidney function estimators changed the associations between dose appropriateness and adverse events in older adults with atrial fibrillation (AF). Participants of the Berlin Initiative Study with AF and treated with DOACs were included. We investigated CrClC-G and estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration and European Kidney Function Consortium equations based on creatinine and/or cystatin C. Marginal structural Cox models yielded confounder-adjusted hazard ratios for the risk of mortality, thromboembolism and bleeding associated with dose status. A total of 224 patients were included in the analysis (median age 87years). Using CrClC-G, 154 (69%) had an appropriate dose of DOACs, 52 (23%) were underdosed and 18 (8%) were overdosed. During a 39-month median follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced thromboembolism and 60 (9.8/100 person-years) experienced bleeding. Dose status was not associated with mortality and thromboembolism, independent of the equation. Underdose status was associated with a lower risk of bleeding with all the equations compared with the appropriate dose group. In participants with discrepancies in dose status using CrClC-G and eGFR equations, the occurrence of endpoints did not differ between participants having an appropriate dose using CrClC-G or eGFR. In older adults with AF, the association of DOAC dose status with adverse events did not differ when using CrClC-G or eGFR. Our results suggest that eGFR equations are not inferior to CrClC-G within this context.

Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk.

Hypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk. Older adults (age>65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH> 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests. Finally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p<0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 vs. 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p<0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p<0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R2 = 0.25) was found an independent predictor of GFR. In older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies.

Incidence of hospital-acquired acute kidney injury and trajectories of glomerular filtration rate in older adults

BackgroundIn older adults, epidemiological data on incidence rates (IR) of hospital-acquired acute kidney injury (AKI) are scarce. Also, little is known about trajectories of kidney function before hospitalization with AKI.MethodsWe used data from biennial face-to-face study visits from the prospective Berlin Initiative Study (BIS) including community-dwelling participants aged 70+ with repeat estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. Primary outcome was first incident of hospital-acquired AKI assessed through linked insurance claims data. In a nested case-control study, kidney function decline prior to hospitalization with and without AKI was investigated using eGFR trajectories estimated with mixed-effects models adjusted for traditional cardiovascular comorbidities.ResultsOut of 2020 study participants (52.9% women; mean age 80.4 years) without prior AKI, 383 developed a first incident AKI, 1518 were hospitalized without AKI, and 119 were never hospitalized during a median follow-up of 8.8 years. IR per 1000 person years for hospital-acquired AKI was 26.8 (95% confidence interval (CI): 24.1–29.6); higher for men than women (33.9 (29.5–38.7) vs. 21.2 (18.1–24.6)). IR (CI) were lowest for persons aged 70–75 (13.1; 10.0-16.8) and highest for ≥ 90 years (54.6; 40.0-72.9). eGFR trajectories declined more steeply in men and women with AKI compared to men and women without AKI years before hospitalization. These differences in eGFR trajectories remained after adjustment for traditional comorbidities.ConclusionAKI is a frequent in-hospital complication in individuals aged 70 + showing a striking increase of IR with age. eGFR decline was steeper in elderly patients with AKI compared to elderly patients without AKI years prior to hospitalization emphasising the need for long-term kidney function monitoring pre-admission to improve risk stratification.

#3207 KIDNEY FUNCTION ESTIMATORS FOR DRUG DOSE ADJUSTMENT OF DIRECT ORAL ANTICOAGULANTS IN OLDER ADULTS WITH ATRIAL FIBRILLATION

Abstract Background and Aims The Food and Drug Administration and the European Medicines Agency (EMA) recommend using the Cockcroft-Gault equation (CG) for drug dose adjustment of direct oral anticoagulant drugs (DOACs) in non-valvular atrial fibrillation (NVAF), whereas Cardiology guidelines recommend using estimated glomerular filtration rate (eGFR). This issue is of great importance in older adults, which are more prone to adverse drug reactions and have higher prevalence of atrial fibrillation as compared to younger adults, and in whom CG has worse diagnostic performance than most eGFR equations. We aimed to assess if prognosis was similar according to drug dose status using different kidney function estimators based on creatinine and/or cystatin C in older adults with NVAF. Method We used data from the Berlin Initiative Study (BIS): a population-based prospective cohort study initiated in 2009, with five biennial study visits. Participants with a history of NVAF (based on ICD-10 codes) and a dispensed prescription of DOAC four months prior to baseline or a follow-up visit according to claims data were included. Drug dose status was defined according to the EMA guidelines. CG, deindexed (in ml/min) creatinine and/or cystatin C-based CKD-EPI, and deindexed BIS 1 (creatinine-based) and BIS 2 (creatinine and cystatin C-based) equations were included. Associations between dosing status and mortality, stroke or systemic embolism, and bleeding events were assessed using marginal structural Cox models with time-varying variables and taking account of various confounders. Subgroup analyses were performed in rivaroxaban and apixaban users, but not in dabigatran and edoxaban users because of too small sample sizes. Results Two hundred twenty four patients treated with DOACs were included in this analysis (median age 87 years, median eGFRCKD-EPIcr 56 ml/min/1.73m², median follow-up length 40 months for the mortality analysis). Of those, 99 (44%) were taking rivaroxaban, 86 (38%) apixaban, 21 (9%) edoxaban, and 18 (8%) dabigatran. Using CG, 154 (69%) had appropriate DOAC dose at baseline, 52 (23%) were underdosed, and 18 (8%) were overdosed. Discrepancies were found by comparing dosing status according to CG and eGFR equations (Figure 1). During the follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced a stroke or systemic embolism, and 60 (9.9/100 person-years) experienced a bleeding event. Drug dose status was not significantly associated with mortality and the occurrence of stroke or systemic embolism, whatever equation was used. Underdose status was associated with a significantly lower risk of bleeding events with all the equations but overdose status was not associated with a higher risk of bleeding events (Figure 2). In subgroup analyses, drug dose status was not associated with mortality and bleeding event in apixaban users, whatever equation was used. In rivaroxaban users, underdose status was associated with a significant higher risk of death by using CG, eGFRCKD-EPIcys, and BIS 2, and a lower risk of bleeding event by using eGFRCKD-EPIcr. Conclusion In this population of very old adults with NVAF, drug dose status of DOAC was not associated with mortality or the occurrence of stroke or systemic embolism for any of the studied equations. However, underdose status was associated with bleeding events occurrence regardless of the equation used. These associations differed according to the used drug, but this should be interpreted with cautious due to small sample sizes. Our results do not allow us to provide any guidance which equation to use in this context. A study including a larger group of patients with discrepancy in dose status according to the used equations would be of great interest.

#5673 ESTIMATING AND VALIDATING MEASURES OF CKD PREVALENCE AND INCIDENCE USING OBSERVATIONAL AND CLAIMS DATA IN PERSONS AGED 70+

Abstract Background and Aims Estimating prevalence and incidence of chronic kidney disease (CKD) based on claims data often underlies bias and limitations due to uncertainty of diagnostic validity. We investigated CKD prevalence and incidence over time using data from a community-dwelling cohort of individuals aged 70+ linked to individual claims data. We assessed the diagnostic validity of the claims-based compared with the eGFR-based CKD definition. Method We assessed CKD prevalence and incidence in two data sources: 1) eGFR values of participants aged 70+ (n = 2,069) of the Berlin Initiative Study (BIS), including five biennial study visits from 2009-2019, and 2) claims data of BIS participants matched on person-level. Using eGFR, we defined CKD prevalence as eGFR &amp;lt;60 ml/min/1.73m² calculated with the creatinine-based CKD-EPI (2009) equation. For each study visit, prevalent CKD cases were considered as incident if eGFR was ≥60 ml/min/1.73m² in the respective previous study visit. In claims data, in- and outpatient ICD-10 diagnoses (N18.3, N18.4, N18.5, N18.8, N18.9, N19) in the year preceding and/or following the study visit date were used to determine CKD prevalence. Incidence was defined as prevalent cases without a diagnosis in the year preceding the first CKD diagnosis. The denominator for incidence was defined as all persons at risk, i.e., who were not prevalent in a respective previous study visit and still under observation. We assessed the diagnostic validity of claims-based CKD prevalence and incidence using eGFR data as a reference. Analyses were stratified by sex. Results Between 2009 and 2019, CKD prevalence increased from 0.42 to 0.51 based on eGFR and from 0.30 to 0.43 based on claims data. Incidence varied between 0.16–0.22 using eGFR and 0.07–0.13 using BIS claims data. There was no clear time trend for incidence in any data source. Diagnostic validity of claims-based CKD prevalence and incidence detection is displayed in Table 1. Sensitivity for prevalence increased while other indicators remained stable over time. Detection of incident cases showed lower sensitivity (0.18–0.30 vs. 0.58–0.70) and PPVs (0.40–0.60 vs. 0.79–0.83) compared to prevalence, respectively. Prevalence and incidence based on claims data were slightly higher in males compared to females (Figure 1). Conclusion Using the eGFR-based or claims-based definition of CKD we found an increase in prevalence between 2009 and 2019. This might be due to the introduction of the KDIGO guidelines in 2012. During the same time, CKD incidence rates were stable. Comparing the claims-based with eGFR-based CKD definition, we found a sensitivity of 0.58-0.70 for prevalence and 0.18-0.30 for incidence, indicating that there is a risk of underdetection of CKD when using solely claims data, in particular for incident cases.

Prediction of worsening postoperative renal function in older candidates to elective cardiac surgery: Choosing the best eGFR formula may not be enough

BackgroundThough renal impairment is highly prevalent in older patients and influence post-operative outcomes in cardiac surgery; its prognostic relevance is debated and not fully assessed by surgical risk scores. ObjectiveWe investigated the predictive role of estimated glomerular filtration rate formulas for in-hospital worsening renal function (WRF) after cardiac surgery. MethodsWe prospectively enrolled in single-center cohort study, patients aged ≥ 75 years candidate to elective cardiac surgery. Four creatinine-based equations were used to calculate estimated glomerular filtration rate (eGFR) formulas: Cockroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology, and Berlin Initiative Study 1 formulas. Each patient underwent geriatric and clinical evaluation before surgery with calculation of the Society of Thoracic Surgeons scores. In-hospital WRF was defined as a composite of an increase in SCr ≥0.5 mg/dl or the occurrence of grade III KDIGO acute kidney injury. The association between each eGFR equation, alone and in models including clinical variables, and WRF was analyzed using logistic regressions and ROC analysis. ResultsWRF occurred in 69 patients (19.8%), and the predictors of WRF were previous acute myocardial infarction, hypertension, 4-mt gait speed performance, and preoperative eGFR, irrespective of the equation used. With all equations, inclusion of these additional variables in the logistic regression models improved the prediction of WRF (AUCs 0.798–0.810). ConclusionsAn accurate assessment of renal function and of physical performance should be incorporated into cardiac surgery risk scores to improve prediction of in-hospital WRF and, hence, risk stratification in older adults undergoing elective cardiac surgery.

A back propagation neural network approach to estimate the glomerular filtration rate in an older population

BackgroundThe use of creatinine-based glomerular filtration rate (GFR)-estimating equations to evaluate kidney function in elderly individuals does not appear to offer any performance advantages. We therefore aimed to develop an accurate GFR-estimating tool for this age group.MethodsAdults aged ≥ 65 years who underwent GFR measurement by technetium-99 m-diethylene triamine pentaacetic acid (99mTc-DTPA) renal dynamic imaging were included. Data were randomly split into a training set containing 80% of the participants and a test set containing the remaining 20% of the subjects. The Back propagation neural network (BPNN) approach was used to derive a novel GFR estimation tool; then we compared the performance of the BPNN tool with six creatinine-based equations (Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI], European Kidney Function Consortium [EKFC], Berlin Initiative Study-1 [BIS1], Lund-Malmö Revised [LMR], Asian modified CKD-EPI, and Modification of Diet in Renal Disease [MDRD]) in the test cohort. Three equation performance criteria were considered: bias (difference between measured GFR and estimated GFR), precision (interquartile range [IQR] of the median difference), and accuracy P30 (percentage of GFR estimates that are within 30% of measured GFR).ResultsThe study included 1,222 older adults. The mean age of both the training cohort (n = 978) and the test cohort (n = 244) was 72 ± 6 years, with 544 (55.6%) and 129 (52.9%) males, respectively. The median bias of BPNN was 2.06 ml/min/1.73 m2, which was smaller than that of LMR (4.59 ml/min/1.73 m2; p = 0.03), and higher than that of the Asian modified CKD-EPI (-1.43 ml/min/1.73 m2; p = 0.02). The median bias between BPNN and each of CKD-EPI (2.19 ml/min/1.73 m2; p = 0.31), EKFC (-1.41 ml/min/1.73 m2; p = 0.26), BIS1 (0.64 ml/min/1.73 m2; p = 0.99), and MDRD (1.11 ml/min/1.73 m2; p = 0.45) was not significant. However, the BPNN had the highest precision IQR (14.31 ml/min/1.73 m2) and the greatest accuracy P30 among all equations (78.28%). At measured GFR < 45 ml/min/1.73 m2, the BPNN has highest accuracy P30 (70.69%), and highest precision IQR (12.46 ml/min/1.73 m2). The biases of BPNN and BIS1 equations were similar (0.74 [-1.55−2.78] and 0.24 [-2.58−1.61], respectively), smaller than any other equation.ConclusionsThe novel BPNN tool is more accurate than the currently available creatinine-based GFR estimation equations in an older population and could be recommended for routine clinical use.

Association of kidney function and albuminuria with frailty worsening and death in very old adults.

Studies analysing the association of albuminuria and prevalent frailty in community-dwelling very old adults are scarce and lack information on incident frailty. We investigated the association of kidney function decline and increase of albuminuria with frailty worsening or death in very old adults. Longitudinal analyses with biennial visits of the Berlin Initiative (cohort) Study and a frailty follow-up of 2.1years. 1,076 participants with a mean age of 84.3 (5.6) years of whom 54% were female. Partial proportional odds models were used to assess the association of estimated glomerular filtration rate (eGFR) decline and/or albuminuria (albumin creatinine ratio, ACR) with frailty worsening or death. At frailty baseline, 1,076 participants with an eGFR of 50 (13) ml/min/1.73m2, 48% being prefrail and 31% frail were included. After median 2.1years, 960 (90%) participants had valid information on frailty transition: 187 (17.5%) worsened and 111 (10.3%) died. In the multivariable model, the odds of frailty worsening for participants with albuminuria in combination with eGFR <60ml/min/1.73m2 were elevated [OR (95% CI): 2.47 (1.41-4.31)] compared to participants without albuminuria and eGFR ≥60ml/min/1.73m2 as there was a rapid eGFR decline of ≥3ml/min/1.73m2 per year [1.55 (1.04-2.33)] and albuminuria trajectories six years prior [1.53 (1.11-2.10)] to frailty baseline. The odds of death for each exposure were even higher. In older adults, advanced stages of CKD and albuminuria alone were associated with 2-fold odds of frailty worsening independent of death.

Concordance and Discrepancies Among 5 Creatinine-Based Equations for Assessing Estimated Glomerular Filtration Rate in Older Adults

There is uncertainty as to which estimated glomerular filtration rate (eGFR) equation should be used among older adults. To compare the 5 most commonly used creatinine-based eGFR equations in older adults, quantifying the concordance among the equations, comparing their discriminative capacity in regards to 15-year mortality, and identifying sources of potential discrepancies. This cohort study used data from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal study of adults aged 60 years or older in Sweden. Participants were recruited between 2001 and 2004 and followed up for mortality until December 2016. Participants missing creatinine values were excluded. Data were originally analyzed March through July 2022, and were rerun in January 2023. Five creatinine-based equations were considered: Modification of Diet in Renal Disease (MDRD), 2009 Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI), Revised Lund-Malmö (RLM), Berlin Initiative Study (BIS), and European Kidney Function Consortium (EKFC). Concordance between equations was quantified using Cohen κ. Discriminative capacity for mortality was quantified using area under the receiver operating characteristic curve (AUC) and the Harrel C statistic. Calf circumference, body mass index (BMI), and age were explored as correlates of discrepancies. The study sample consisted of 3094 older adults (1972 [63.7%] female; median [IQR] age, 72 [66-81] years). Cohen κ between dyads of equations ranged from 0.42 to 0.91, with poorest concordance between MDRD and BIS, and best between RLM and EKFC. MDRD and CKD-EPI provided higher estimates of GFR compared with the other equations. The best mix of AUC and Harrel C statistic was observed for BIS (0.80 and 0.73, respectively); however, the prognostic accuracy for death decreased among those aged over 78 years and those with low calf circumference. Differences between equations were inconsistent across levels of calf circumference, BMI, and age. In this cohort study, we found that eGFR equations were not interchangeable when assessing kidney function. BIS outperformed other equations in predicting mortality; however, its discriminative capacity was reduced in subgroup analyses. Clinicians should consider these discrepancies when monitoring kidney function in old age.

Estimated GFR Accuracy When Cystatin C– and Creatinine-Based Estimates Are Discrepant in Older Adults

Serum creatinine and cystatin C are used to estimate glomerular filtration rate, but creatinine-based estimated glomerular filtration rate (eGFRcr), cystatin C-based estimated glomerular filtration rate (eGFRcys), and combined creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) are often divergent, particularly in older adults. We investigated which estimated glomerular filtration rate (eGFR) was more accurate and less biased compared with measured glomerular filtration rate (mGFR). A diagnostic test study from the Berlin Initiative Study. The study population included 657 individuals aged 70 years or older with iohexol plasma clearance (mGFR) and serum creatinine and cystatin C measurements: 567 community-dwelling participants and 90 with a serum creatinine of≥1.5 mg/dL. We defined 3 groups on the basis of the difference eGFRcys-eGFRcr: whether< -5 mL/min/1.73 m2 (lower eGFRcys), within 5 mL/min/1.73 m2 (reference), or≥ 5 mL/min/1.73 m2 (lower eGFRcr). eGFRcr, eGFRcys, and eGFRcr-cys were compared to mGFR to assess bias and accuracy. Median bias (eGFR minus mGFR) with 95% CIs and accuracy (percentage of eGFR values within±30% of mGFR). The mean±standard deviation age was 78±6 years; the mean eGFRcys, eGFRcr, and eGFRcr-cys were 59±23, 64±20, and 61±22 mL/min/1.73 m2, respectively, and the mean mGFR was 56±19 mL/min. Half of the participants were in the lower eGFRcys group (n=337, 51%). Among them, the median bias for eGFRcys was the lowest (median bias,-2.7; 95% CI,-3.8 to-1.9) compared with the other eGFR equations. Conversely, in the lower eGFRcr group (n=121, 18%), the median bias for eGFRcr was the lowest compared with those for eGFRcys and eGFRcr-cys (2.9; [95% CI, 0.9-4.8] vs 13.8 [95% CI, 11.4-15.6] and 9.5 [95% CI, 7.7-11.0], respectively). Accuracy (percentage of eGFR values within±30% of mGFR) was 93% for eGFRcr in the lower eGFRcr group and 92% for eGFRcys and 94% for eGFRcr-cys in the lower eGFRcys group. Untested generalizability in younger populations. Among older adults, the lower eGFR between eGFRcys and eGFRcr was a more accurate and less biased estimate of mGFR when comparing the groups.