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Purpose: 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. Patients and Methods: 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). Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background 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). Methods 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. Results A total of 224 patients were included in the analysis (median age 87 years). 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Background and objectives 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. Design Longitudinal analyses with biennial visits of the Berlin Initiative (cohort) Study and a frailty follow-up of 2.1 years. Setting/subjects 1,076 participants with a mean age of 84.3 (5.6) years of whom 54% were female. Methods 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. Results At frailty baseline, 1,076 participants with an eGFR of 50 (13) ml/min/1.73 m2, 48% being prefrail and 31% frail were included. After median 2.1 years, 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 <60 ml/min/1.73 m2 were elevated [OR (95% CI): 2.47 (1.41–4.31)] compared to participants without albuminuria and eGFR ≥60 ml/min/1.73 m2 as there was a rapid eGFR decline of ≥3 ml/min/1.73 m2 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. Conclusions In older adults, advanced stages of CKD and albuminuria alone were associated with 2-fold odds of frailty worsening independent of death. [ABSTRACT FROM AUTHOR]

Background treatment goals for blood pressure (BP) lowering in older patients with heart failure (HF) are unclear. Objective to assess whether BP control < 140/90 mmHg is associated with a decreased risk of mortality in older HF patients. Design population-based prospective cohort study. Setting/subjects participants of the Berlin Initiative Study, a prospective cohort of community-dwelling older adults launched in 2009. Clinical information was obtained in face-to-face interviews and linked to administrative healthcare data. Methods Cox proportional hazards models estimated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular death and all-cause mortality associated with normalised BP (systolic BP < 140 mmHg and diastolic BP < 90 mmHg) compared with non-normalised BP (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) in HF patients. The primary analysis considered only baseline BP ('time-fixed'); an additional analysis updated BP during follow-up ('time-dependent'). Results at baseline, 544 patients were diagnosed with HF and treated with antihypertensive drugs (mean age 82.8 years; 45.4% female). During a median follow-up of 7.5 years and compared with non-normalised BP, normalised BP was associated with similar risks of cardiovascular death (HR, 1.24; 95% CI, 0.84–1.85) and all-cause mortality (HR, 1.16; 95% CI, 0.89–1.51) in the time-fixed analysis but with increased risks of cardiovascular death (HR, 1.79; 95% CI, 1.23–2.61) and all-cause mortality (HR, 1.48; 95% CI, 1.15–1.90) in the time-dependent analysis. Conclusions BP control < 140/90 mmHg was not associated with a decreased risk of mortality in older HF patients. The increased risk in the time-dependent analysis requires further corroboration. [ABSTRACT FROM AUTHOR]

Background: European guidelines recommend the use of the Systematic COronary Risk Evaluation (SCORE) to assess 10-year risk of fatal cardiovascular events in people aged 40 to 65. The SCORE Older Persons (SCORE OP, 5-year and 10-year versions) was recently developed for people aged 65 or older. We assessed the performance of these risk scores in predicting fatal cardiovascular events in older persons in Berlin. Methods and findings: Data from the Berlin Initiative Study (BIS), a prospective, population-based study of older persons recruited from a German public health insurance company database were used. 1,657 participants aged 70 or older without reported previous myocardial infarction were included. We assessed calibration by comparing predicted risks to observed (for 5-year versions, 5y) or projected (for 10-year versions) probabilities. During follow-up (median: 4.8 years), 118 cardiovascular deaths occurred. The calibration assessment of the SCORE OP-H 5y and SCORE OP-L 5y equations revealed 2.1- and 1.5-fold overestimation. Comparing 10-year versions, the SCORE OP showed better discrimination ability compared to the SCORE (C-indices of around 0.80 compared to 0.72) and the SCORE for high-risk regions showed the best calibration (chi-square = 29.68). The SCORE OP overestimated the true risk; 519 and 677 events were predicted using the low-risk and high-risk region SCORE OP equations compared to 397 to 399 events projected based on BIS follow-up data (predicted/actual ratios of 1.3 and 1.7). Conclusions: Given the low transportability of the SCORE OP observed in our population, we caution against its use in routine clinical practice until further information is available to avoid possible overtreatment among older persons in Berlin. [ABSTRACT FROM AUTHOR]

Aims To assess whether blood pressure (BP) values below 140/90 mmHg during antihypertensive treatment are associated with a decreased risk of all-cause mortality in community-dwelling older adults. Methods and results Within the Berlin Initiative Study, we assembled a cohort of patients ≥70 years treated with antihypertensive drugs at baseline (November 2009–June 2011). End of prospective follow-up was December 2016. Cox proportional hazards models yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality associated with normalized BP [systolic BP (SBP) <140 mmHg and diastolic BP (DBP) <90 mmHg] compared with non-normalized BP (SBP ≥140 mmHg or DBP ≥90 mmHg) overall and after stratification by age or previous cardiovascular events. Among 1628 patients (mean age 81 years) on antihypertensive drugs, 636 exhibited normalized BP. During 8853 person-years of follow-up, 469 patients died. Compared with non-normalized BP, normalized BP was associated with an increased risk of all-cause mortality (incidence rates: 60.3 vs. 48.5 per 1000/year; HR 1.26; 95% CI 1.04–1.54). Increased risks were observed in patients ≥80 years (102.2 vs. 77.5 per 1000/year; HR 1.40; 95% CI 1.12–1.74) and with previous cardiovascular events (98.3 vs. 63.6 per 1000/year; HR 1.61; 95% CI 1.14–2.27) but not in patients aged 70–79 years (22.6 vs. 22.7 per 1000/year; HR 0.83; 95% CI 0.54–1.27) or without previous cardiovascular events (45.2 vs. 44.4 per 1000/year; HR 1.16, 95% CI 0.90–1.48). Conclusion Blood pressure values below 140/90 mmHg during antihypertensive treatment may be associated with an increased risk of mortality in octogenarians or elderly patients with previous cardiovascular events. View large Download slide View large Download slide [ABSTRACT FROM AUTHOR]

Background: Although CKD is said to increase among older adults, epidemiologic data on kidney function in people ≥70 years of age are scarce. The Berlin Initiative Study (BIS) aims to fill this gap by evaluating the CKD burden in older adults.Methods: The BIS is a prospective population-based cohort study whose participants are members of Germany's biggest insurance company. This cross-sectional analysis (i) gives a detailed baseline characterization of the participants, (ii) analyses the representativeness of the cohort's disease profile, (iii) assesses GFR and albuminuria levels across age categories, (iv) associates cardiovascular risk factors with GFR as well as albuminuria and (v) compares means of GFR values according to different estimating equations with measured GFR.Results: A total of 2069 participants (52.6% female, mean age 80.4 years) were enrolled: 26.1% were diabetic, 78.8% were on antihypertensive medication, 8.7% had experienced a stroke, 14% a myocardial infarction, 22.6% had cancer, 17.8% were anaemic and 26.5% were obese. The distribution of comorbidities in the BIS cohort was very similar to that in the insurance ‘source population’. Creatinine and cystatin C as well as the albumin:creatinine ratio (ACR) increased with increasing age. After multivariate adjustments, reduced GFR and elevated ACR were associated with most cardiovascular risk factors. The prevalence of a GFR <60 mL/min/1.73 m2 ranged from 38 to 62% depending on the estimation equation used.Conclusions: The BIS is a very well-characterized, representative cohort of older adults. Participants with an ACR ≥30 had significantly higher odds for most cardiovascular risk factors compared with an ACR <30 mg/g. Kidney function declined and ACR rose with increasing age. [ABSTRACT FROM AUTHOR]

Rationale & Objective: The 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 Design: Secondary analysis of the Berlin Initiative Study, a population-based cohort., Setting: & Participants: 2069 adults aged ≥70 years in Germany., Exposures: Age and sex., Outcomes: Suitability 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 Approach: Descriptive analysis., Results: Among the 2069 participants (median age 80 years, 53% women, median eGFR 63 ml/min/1.73m 2 ), 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)., Limitations: GFR was not measured and medical exclusions unrelated to eGFR and albuminuria were assessed using a cohort database complemented by claims data., Conclusions: One 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., (Copyright © 2024. Published by Elsevier Inc.)

Background: Chronic kidney failure (CKF) is often treated with dialysis, which is invasive and costly and carries major medical risks. The existing studies of patients with CKF requiring dialysis that are based on claims data from German statutory health insurance (SHI) carriers employ varying definitions of this entity, with unclear consequences for the resulting statistical estimates., Methods: We carried out a cohort study on four random samples, each consisting of 62 200 persons aged 70 or above, from among the insurees of the SHI AOK Nordost, with one sample for each of the years 2012, 2014, 2016, and 2018. The prevalence, incidence, mortality, and direct health care costs of CKF requiring dialysis were estimated and compared on the basis of four different definitions from literature and a new definition developed by the authors in reference to billing data., Results: The different definitions led to variation in 12-month prevalences (range: 0.33-0.61%) and 6-month incidences (0.058-0.100%). The percentage of patients with prior acute kidney injury (AKI) ranged from 27.6% to 61.8%. Among incident patients, three-month survival ranged from 70.2% to 88.1%, and six-month survival from 60.5% to 81.3%. In CKF patients without prior AKI, the survival curves differed less across definitions (80.2-91.8% at three months, 70.7-84.4% at six months). The monthly health care costs ranged from €6010 to €9606, with marked variability across definitions in the costs of inpatient and outpatient care., Conclusion: The lack of a standardized definition of CKF requiring dialysis in German SHI claims data leads to variability in the estimated case numbers, mortality, and health care costs. These differences are most probably in part due to the variable inclusion of inpatients who received short-term dialysis after AKI.

Background and Objectives: In older adults, data on the age-related course of GFR are scarce, which might lead to misjudgment of the clinical relevance of reduced GFR in old age., Design, Setting, Participants, & Measurements: To describe the course of eGFR in older adults and derive reference values in population-based individuals, we used the longitudinal design of the Berlin Initiative Study (BIS) with a repeated estimation of GFR over a median of 6.1 years of follow-up. In 2069 community-dwelling older individuals (mean inclusion age 80 years, range 70-99), GFR was estimated biennially with the BIS-2 equation, including standardized creatinine and cystatin C levels, sex, and age. We described the crude and adjusted course using a mixed-effects model and analyzed the influence of death on the GFR course applying joint models. GFR slopes were compared using GFR equations on the basis of creatinine and/or cystatin C., Results: We observed a decreasing, thus nonlinear, eGFR decline with increasing age in a population of old adults. The estimated 1-year slope for ages 75 and 90 diminished for men from -1.67 to -0.99 and for women from -1.52 to -0.97. The modeled mean eGFR for men aged ≥79 and women ≥78 was below 60 ml/min per 1.73 m 2 . Multivariable adjustment attenuated slopes only minimally. Taking death into account by applying joint models did not alter the nonlinear eGFR decline. Using eGFR equations on the basis of creatinine only showed linear slope patterns in contrast to nonlinear patterns for equations including cystatin C., Conclusions: The eGFR decline depended on sex and age and changed only marginally after multivariable adjustment but decelerated with increasing age. Equations including cystatin C demonstrated a nonlinear slope challenging the previously assumed linearity of the decline of eGFR in old age., (Copyright © 2022 by the American Society of Nephrology.)

Rationale & Objective: Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) are associated with cardiovascular events in the general population but their utility among older adults is unclear. We investigated the associations of eGFR and UACR with stroke, myocardial infarction (MI), and death among older adults., Study Design: Population-based cohort study., Setting & Participants: 1,581 participants (aged≥70 years) in the Berlin Initiative Study (BIS) without prior stroke or MI., Exposures & Predictors: Serum creatinine- and cystatin C-based eGFR, UACR categories, and measured GFR (n=436)., Outcomes: Stroke, MI, and all-cause mortality., Analytical Approach: HRs and 95% CIs derived from multivariable-adjusted Cox proportional hazards models for association analyses. Net reclassification improvement (NRI) and C statistic differences comparing the predictive benefit of kidney measures with a traditional cardiovascular risk model., Results: During a median follow-up of 8.2 years, 193 strokes, 125 MIs, and 531 deaths occurred. Independent of UACR, when GFR was estimated using the creatinine- and cystatin C-based BIS equation, eGFR of 45 to 59mL/min/1.73m 2 (vs eGFR>60mL/min/1.73m 2 ) was associated with stroke (HR, 2.23; 95% CI, 1.55-3.21) but not MI or all-cause mortality. For those with eGFR<45mL/min/1.73m 2 , the HRs were 1.99 (95% CI, 1.23-3.20) for stroke, 1.38 (95% CI, 0.81-2.36) for MI, and 1.57 (95% CI, 1.20-2.06) for mortality. Compared with UACR<30mg/g, UACR of 30 to 300mg/g was not associated with stroke (HR, 0.91; 95% CI, 0.63-1.33) but was associated with MI (HR, 1.65; 95% CI, 1.09-2.51) and all-cause mortality (HR, 1.63; 95% CI, 1.34-1.98). Prediction analysis for stroke showed significant positive NRI for eGFR calculated using the cystatin C-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the creatinine- and cystatin C-based BIS and Full Age Spectrum equations. UACR demonstrated significant positive NRIs for MI and mortality., Limitations: eGFR and UACR categorization based on single assessments; lack of cause-specific death data., Conclusions: eGFR of 45 to 59mL/min/1.73m 2 without albuminuria was associated with stroke but not MI or all-cause mortality in older adults. In contrast, UACR of 30 to 300mg/g was associated with MI and all-cause mortality but not with stroke. Furthermore, cystatin C-based eGFR improved risk prediction for stroke in this cohort of older adults., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The control of translation initiation is a crucial component in the regulation of gene expression. The eukaryotic initiation factor 2α (eIF2α) mediates binding of the initiator transfer-messenger-RNA to the AUG initiation codon, and thus controls a rate-limiting step in translation initiation. Phosphorylation of eIF2α at serine 51 is linked to cellular stress response and attenuates translation initiation. The biochemistry of translation inhibition mediated by eIF2α phosphorylation is well characterized, yet the physiological importance in hematopoiesis remains only partially known., Design and Methods: Using hematopoietic stem cells carrying a non-phosphorylatable mutant form of eIF2α (eIF2αAA), we examined the efficiency of reconstitution in wild-type and B-cell-deficient microMT C57BL/6 recipients in two independent models., Results: We provide evidence that phosphorylation-deficient eIF2α mutant hematopoietic stem cells may repopulate lethally irradiated mice but have a defect in the development and maintenance of newly formed B cells in the bone marrow and of naïve follicular B cells in the periphery. The mature B-cell compartment is markedly reduced in bone marrow, spleen and peripheral blood, and B-cell receptor-mediated proliferation in vitro and serum immunoglobulin secretion in vivo are impaired., Conclusions: The data suggest that regulation of translation through eIF2α phosphorylation is dispensable in hematopoietic reconstitution but essential during late B-cell development.