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Aims The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an ‘Add-on’ to incorporate CKD measures into these algorithms, using a validated approach. Methods In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets. Results In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004–0.008) and 0.016 (0.010–0.023), respectively, for SCORE2 and 0.012 (0.009–0.015) and 0.024 (0.014–0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062–0.138) for SCORE2] compared to the qualitative approach in the ESC guideline. Conclusion Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

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.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.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 mThe 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.

Zusammenfassung Hintergrund Die chronische Nierenkrankheit (CKD) ist eine häufige Erkrankung, insbesondere im höheren Alter. Um der Progression der Erkrankung und deren Komplikationen vorzubeugen, ist eine leitliniengerechte ambulante Versorgung von Patient:innen mit CKD anzustreben. Zur Messung und Bewertung der Versorgungsqualität können Qualitätsindikatoren (QI) genutzt werden. In Deutschland existieren bisher keine QI für CKD. Ziel der Arbeit war die Entwicklung von QI für die Qualitätsüberprüfung der ambulanten Versorgung von Patient:innen über 70 Jahren mit nichtdialysepflichtiger CKD. Material und Methoden Auf Grundlage der nationalen S3-Leitlinie CKD und eines Reviews internationaler QI wurde eine Liste von QI erstellt. Die ausgewählten QI wurden in 2 Sets eingeteilt: basierend auf Routinedaten (z. B. Abrechnungsdaten der Krankenkassen) und auf Datenerhebung in der Praxis (Chart-Review). Expert:innen verschiedener Fachrichtungen sowie ein Patient:innenvertreter bewerteten diese in einem Delphi-Verfahren mit 2‑stufiger Onlinebefragung im Oktober 2021 und Januar 2022 und abschließender Konsensuskonferenz im März 2022. Zusätzlich wurden Ranglisten der wichtigsten QI von jedem Set erstellt. Ergebnisse Ein Inzidenz- und ein Prävalenzindikator wurden a priori festgelegt und standen nicht zur Abstimmung. Weitere 21 QI standen zur Abstimmung durch die Expert:innen. Für jedes QI-Set wurden die 7 wichtigsten Indikatoren ausgewählt. Nur 1 QI wurde von dem Expert:innenpanel für den zusätzlichen Einsatz bei Erwachsenen unter 70 Jahren als nicht geeignet eingestuft. Diskussion Die QI sollen es ermöglichen, die Qualität der ambulanten Versorgung von Patient:innen mit CKD zu untersuchen, mit dem Ziel, die leitlinienkonforme ambulante Versorgung zu optimieren.

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 Conclusions In older adults, advanced stages of CKD and albuminuria alone were associated with 2-fold odds of frailty worsening independent of death.

Objectives Most data on glomerular filtration rate (GFR) originate from subjects Methods mGFR percentiles were calculated from a development cohort of French/Belgian living kidney donors Results Individuals in the development cohort had a higher mGFR (99.9 ± 16.4 vs. 86.4 ± 14 and 82.7 ± 15.5 mL/min/1.73 m2) compared to the individuals in the validation cohorts. In the internal validation cohort, none (0%) had mGFR below the extrapolated P5, 12 (8.2%) above P95 and 135 (91.8%) between P5–P95. In the external validation cohort, five subjects had mGFR below the extrapolated P5 (1.5%), 25 above P95 (7.6%) and 299 (90.9%) between P5–P95. Conclusions We demonstrate that extrapolation of mGFR from younger donors is possible and might aid with decision-making in elderly donors.

Background A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts. Methods Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed. Results In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of –0.6 and –3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males. Conclusion In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study.

ImportanceKidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality.ObjectivesTo evaluate whether testing concordance between estimated glomerular filtration rates based on cystatin C (eGFRcys) and creatinine (eGFRcr) levels would improve risk stratification for future outcomes and whether estimations differ by age.Design, Setting, and ParticipantsA prospective population-based cohort study (UK Biobank), with participants recruited between 2006-2010 with median follow-up of 11.5 (IQR, 10.8-12.2) years; data were collected until August 31, 2020. Participants had eGFRcr greater than or equal to 45 mL/min/1.73 m2, albuminuria (albumin ExposuresChronic kidney disease status was categorized by concordance between eGFRcr and eGFRcys across the threshold for hronic kidney disease (CKD) diagnosis (60 mL/min/1.73 m2).Main Outcomes and MeasuresTen-year probabilities of CVD, mortality, and kidney failure were assessed according to CKD status. Multivariable-adjusted Cox proportional hazards models tested associations between CVD and mortality. Area under the receiving operating curve tested discrimination of eGFRcr and eGFRcys for CVD and mortality. The Net Reclassification Index assessed the usefulness of eGFRcr and eGFRcys for CVD risk stratification. Analyses were stratified by older (age 65-73 years) and younger (age ResultsThere were 428 402 participants: median age was 57 (IQR, 50-63) years and 237 173 (55.4%) were women. Among 76 629 older participants, there were 9335 deaths and 5205 CVD events. Among 351 773 younger participants, there were 14 776 deaths and 9328 CVD events. The 10-year probability of kidney failure was less than 0.1%. Regardless of the eGFRcr, the 10-year probabilities of CVD and mortality were low when eGFRcys was greater than or equal to 60 mL/min/1.73 m2; conversely, with eGFRcys less than 60 mL/min/1.73 m2, 10-year risks were nearly doubled in older adults and more than doubled in younger adults. Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr. Across a 7.5% 10-year risk threshold for CVD, eGFRcys improved case Net Reclassification Index by 0.7% (95% CI, 0.6%-0.8%) in older people and 0.7% (95% CI, 0.7%-0.8%) in younger people; eGFRcr did not add to CVD risk estimation.Conclusions and RelevanceThe findings of this study suggest that eGFRcr 45 to 59 mL/min/1.73 m2 includes a proportion of individuals at low risk and fails to capture a substantial proportion of individuals at high-risk for CVD and mortality. The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD.

Background The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low. Objective To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations. Design Cross-sectional analysis with separate pooled data sets for development and validation. Setting Research and clinical studies (n = 13) with measured GFR available. Patients 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set). Measurements Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR. Results The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m2 [95% CI, -2.7 to 0.0 mL/min/1.73 m2] in children and -0.9 mL/min/1.73 m2 [CI, -1.2 to -0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations. Limitation No Black patients were included. Conclusion The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels. Primary funding source Swedish Research Council (Vetenskapsradet).

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.

BACKGROUND AND AIMS The gold standard for evaluation of kidney function is measured GFR [mGFR] which is challenging to perform in clinical practice. Serum creatinine and cystatin C are used to estimate GFR clinically, but neither is a perfect marker. Within any given individual, the estimated glomerular filtration rate (eGFR) can be widely different when using serum creatinine [eGFRCr] vs. cystatin C [eGFRCys]. We investigated which was closest to mGFR in elderly outpatients when results between these two eGFRs were discrepant. METHOD About 657 older ambulatory participants of the population-based Berlin Initiative Study (BIS) had GFR measured by iohexol plasma clearance (mGFR), as well as serum creatinine and cystatin C levels. eGFRCr and eGFRCys were calculated using the 2009 and 2012 CKD-EPI equations, respectively. The cohort was divided into two groups based on which of these eGFR estimates was lowest. Bias (defined as ‘eGFR-mGFR’), imprecision (standard deviation [interquartile range] of bias), as well as proportion within 30% (P30) were calculated. RESULTS Mean (±SD) age was 78 (±6) years, eGFRCys was 59 (±23), mean eGFRCr was 64 (±20) and mGFR was 55 (±20) mL/min/1.73 m2. Mean (±SD) body mass index was 28 (4) kg/m2 58% were men, and 26% had diabetes mellitus. Two-thirds of participants (448/657 = 68%) had eGFRCys CONCLUSION In a population of community-dwelling older adults, the lower value between eGFRCys and eGFRCr was closest to mGFR in 76% of participants.

BACKGROUND AND AIMS Data on the estimated glomerular filtration rate (eGFR) over time in older populations are scarce. Identifying patterns of eGFR progression is essential for a better understanding of chronic kidney disease (CKD) in older adults. METHOD We used data from the BIS, a community-dwelling cohort of 2069 people aged 70 or older. Participants were recruited between 2009 and 2011. After baseline assessment, four follow-up visits were conducted biennially over a total observation period of 8 years. During all study visits, eGFR and CKD stages based on KIDGO guidelines were assessed using the creatinine and cystatin C-based BIS2 equation (eGFRBIS2). Additionally, we used the creatinine-based EKFC equation (eGFREKFC). In a sub-analysis, we included only non-deceased participants with complete attendance at all study visits and valid eGFR values at all measurements. RESULTS At baseline, the mean age was 80.4 years (SD = 6.7), and 52.6 % were females. Prevalence was highest for CKD stage 2 (45.4%) and 3 (49.3%). After 8 years, the prevalence for CKD stages 1 and 2 decreased, whereas stages 3 and 4 showed a consistent upward trend resulting in 18.4%, 72.4% and 8.9% of participants in stages 2, 3 and 4, respectively. Mean eGFRBIS2 decreased from 58.1 (SD = 15.2) to 48.3 (SD = 13.3) mL/min/1.73 m² after 8 years. Mean eGFREKFC showed a similar trend with estimates being slightly higher (60.4 versus 54.2 mL/min/1.73 m2 after 8 years). Same trends applied to the subgroup with complete attendance (mean age: 77.4 years). However, compared with the total population they showed a higher mean eGFRBIS2 (63.3 versus 58.1 mL/min/1.73 m²) and lower prevalence of CKD stages 3 and 4 (stage 2: 59.4 versus 45.4%; stage 3: 37.1 versus 49.3% stage 4: 1.2 versus 3.6%) at baseline. CONCLUSION We found that over the observation period of 8 years, mean eGFRBIS2 decreased by 9.8 mL/min/1.73 m2 resulting in an increasing prevalence of CKD stages 3 and 4 by 23.1 and 5.3%, respectively. This was observed in the total population as well as in the subgroup with complete study attendance.

BACKGROUND AND AIMS Decreased kidney function is an established risk factor of cardiovascular morbidity including heart failure (HF) as well as cardiovascular and all-cause mortality among adults. However, the role of decreased kidney function with regard to these outcomes among old and very old adults remains poorly understood. This is an important knowledge gap given the common decline of kidney function in advanced age, which can affect both healthy individuals and patients with significant morbidity. To this end, we conducted a population-based study to assess whether decreased kidney function is associated with an increased risk of HF, cardiovascular and all-cause mortality in a prospective cohort of community-dwelling older adults. METHOD We included participants of the Berlin Initiative Study (BIS), age ≥70 years, with estimated glomerular filtration rate (eGFRBIS2) at baseline (between 2009 and 2011) and information on prior diagnosis of HF. Participants were followed from baseline until the occurrence of one of the study outcomes (see below) or December 2020, the latest date of data availability. Potential confounders included demographic characteristics, anthropometrics (body mass index), lifestyle factors (alcohol consumption, smoking, physical exercise), proxies of socioeconomic status (education, income), medications (major classes of antihypertensive drugs, oral anticoagulants, antiplatelet agents), and comorbidities measured at baseline using face-to-face interviews and administrative healthcare data. The three study outcomes were hospitalization for HF (HHF), cardiovascular death and all-cause mortality. HHF was defined based on inpatient diagnostic codes, and the mortality outcomes were defined based on a combination of administrative healthcare data, death certificates and hospital discharge notes. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of the three outcomes associated with decreased kidney function (eGFRBIS2 RESULTS Our study cohort included 1466 HF free older adults (mean age 79 years; 55% female). Compared with retained kidney function, decreased kidney function was associated with increased risks of HHF (crude incidence rates per 100/year: 2.7 versus 1.1; adjusted HR, 1.48; 95% CI, 1.06–2.07), cardiovascular death (crude incidence rates per 100/year: 2.7 versus 0.9; adjusted HR, 1.49; 95% CI, 1.06–2.09), and all-cause mortality (crude incidence rates per 100/year: 6.3 versus 2.8; adjusted HR, 1.27; 95% CI, 1.03–1.57). Kaplan-Meier curves for the three study outcomes are shown in Figure 1. Among the 590 older adults with prior HF (mean age 83 years; 54% female), the effect estimates were similar albeit less precise (HHF: HR, 1.32; 95% CI, 0.88–1.98/cardiovascular death: HR, 1.67; 95% CI, 1.06–2.63/all-cause mortality: HR, 1.22; 95% CI, 0.91–1.63). CONCLUSION Our population-based study showed that decreased kidney function is associated with increased risks of cardiovascular morbidity and cardiovascular and all-cause mortality among older adults, corroborating findings in younger populations.

BACKGROUND AND AIMS Current Glomerular filtration rate (GFR) estimating equations based on serum creatinine are facing increased criticism due to the inclusion of a race correction in black Americans with the CKD-EPI equation (CKD-EPIASR, A = Age, S = Sex, R = Race). A new equation without race (CKD-EPIAS) has been proposed. However, this equation was developed mainly from US cohorts. The performance of this new equation has been poorly compared with current European-developed creatinine-based equations, i.e. the Lund-Malmö Revised (LMR), and the new European Kidney Function Consortium (EKFC) METHOD Data from subjects over 18 years, representing 11 cohorts from Europe (previously described as the EKFC dataset, n = 13 856), and enhanced with data from Brazil (n = 100), France (n = 4429) and Africa [Democratic Republic of Congo (DRC) and Côte d'Ivoire, n = 508] were considered (n = 18 893 for the whole cohort). The EKFC cohort was considered as non-black population. All data from Africa derived from black individuals. From France, 964 subjects were self-reported as black (=Blacks from Paris). Measured GFR as a reference method and IDMS creatinine results were available. Median bias (eGFR—mGFR) with 95% confidence intervals (CI), imprecision (interquartile range: IQR), and P30 accuracy (percentage of eGFR-values within ± 30% of mGFR) with 95% CI were calculated. RESULTS Results are summarized in Table. CONCLUSION The new CKD-EPIAS has been launched in the USA for societal reasons and is now recommended by US guidelines. However, in Europe and Africa, its performance was suboptimal. The EKFC equation, using the usual Q values, or population-specific Q values (when available), displays the best performance over the whole age range for populations in Europe and Africa.

Purpose of review The goal of this update is to raise awareness of clinical scenarios where cystatin C has clear and immediate benefits as an alternative glomerular filtration rate (GFR) biomarker to supplement creatinine. An additional goal is to focus the estimated GFR (eGFR) controversy onto medication prescribing for agents with narrow therapeutic windows where better GFR estimation will lead to improved medical care. Recent findings Equations that include cystatin C predict GFR more accurately than serum creatinine in children, adults, and older adults with larger effects among persons who are acutely ill. Numerous studies have evaluated medication dosing based on either GFR estimate; vancomycin was the most frequently studied drug and its target level and elimination were better predicted by cystatin C. Overall, approaches to medication dosing and monitoring that include cystatin C concentrations have been shown to result in a better achievement of drug trough levels. Furthermore, cystatin C offers the opportunity to avoid the race coefficient that is required for any current creatinine-based eGFR equation, which has been appropriately criticized for introducing unnecessary imprecision, assumptions and values on GFR estimation. Summary Hospital laboratories must make cystatin C available for clinical care to improve the safety and efficacy of medications that have narrow therapeutic windows.

Background Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR). Methods White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age ± 3 years, BMI ± 2.5 kg/m2) and renal function (mGFR ± 3 ml/min/1.73 m2). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria. Results For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 ± 0.20 versus 0.86 ± 0.23, males 1.06 ± 0.23 versus 1.12 ± 0.37; P > .05) but significantly different from the CRIC [females 1.13 ± 0.23 (P Conclusion Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.

Polypharmacy is associated with poorer self-rated health (SRH). However, whether polypharmacy has an impact on the SRH progression is unknown. This study investigates the association of polypharmacy with SRH change in 1428 participants of the Berlin Initiative Study aged 70 years and older over four years. Polypharmacy was defined as the intake of ≥5 medications. Descriptive statistics of SRH-change categories stratified by polypharmacy status were reported. The association of polypharmacy with being in SRH change categories was assessed using multinomial regression analysis. At baseline, mean age was 79.1 (6.1) years, 54.0% were females, and prevalence of polypharmacy was 47.1%. Participants with polypharmacy were older and had more comorbidities compared to those without polypharmacy. Over four years, five SRH-change categories were identified. After covariate adjustment, individuals with polypharmacy had higher odds of being in the stable moderate category (OR 3.55; 95% CI [2.43–5.20]), stable low category (OR 3.32; 95% CI [1.65–6.70]), decline category (OR 1.87; 95% CI [1.34–2.62]), and improvement category (OR 2.01; [1.33–3.05]) compared to being in the stable high category independent of the number of comorbidities. Reducing polypharmacy could be an impactful strategy to foster favorable SRH progression in old age.

This is the peer reviewed version of the following article: Delanaye, P., Björk, J., Courbebaisse, M., Couzi, L., Ebert, N., Eriksen, B.O., .... Nyman, U. (2021). Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment. British Journal of Clinical Pharmacology, which has been published in final form at https://doi.org/10.1111/bcp.15132. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Aim: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing. Methods: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR) and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR Results: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR 2, all equations performed similarly, and for BMI 2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2). The four more recent equations also classified mGFR stages better than CG. Conclusions: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.

ispartof: KIDNEY INTERNATIONAL REPORTS vol:5 issue:7 pages:1079-1081 ispartof: location:United States status: published

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) 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.

Background Measuring glomerular filtration rate (GFR) using iohexol plasma clearance has been proposed as the preferred way for GFR determination. The extended multiple-sample protocol is based on fitting the full concentration-time decay-curve, and from the obtained fit-parameters, the area under the curve (AUC) and GFR (the injected dose divided by the AUC) were calculated. The goal of the current study is to evaluate the impact of different fitting procedures on the precision of GFR-results obtained from the full concentration-time curve, and compare these results with those obtained with simplified multiple-samples and single-sample protocols. Methods The concentration-time curves of 8 samples at times 30, 60, 90, 120, 150, 180, 240 and 300 min after bolus injection of iohexol of 570 adults, aged 70+, from the Berlin Initiative Study (BIS), were analysed. The fit-parameters for the two-compartment model (double-exponential decay curve), and from these, the AUC and GFR were obtained with 8 different fitting procedures. Results The two-compartmental non-linear least squares fitting procedure showed the best accuracy (541 out of 570 reported GFR-results were within 5% of the majority of the 8 fitting methods). The two-compartmental slope-intercept fitting procedure was not always applicable and the non-compartmental fitting procedures did not always allow to calculate the GFR. All correction formulas for the simplified late multiple-samples methods showed acceptable accuracy and precision with a preference for Ng’s correction formula (Lin’s CCC = 0.992, bias = 0.5 ± 2.5). Jacobsson’s iterative method was the best one-sample method, with Lin’s CCC = 0.983 and bias = − 0.6 ± 3.4. Conclusion The fitting procedure has an important impact on the precision of the calculated AUC and GFR. The simplified late-sample protocols and one-sample methods did not suffer from fitting problems and showed acceptable equivalence when compared to the full compartment GFR-results. Trial registration The “Berlin Initiative Study” is officially registered with the German Register for Clinical Studies (“Deutschen Register Klinischer Studien”(DRKS)) under registration number DRKS00017058, since April 12, 2019, and it is also visible on the WHO clinical trials registry platform (within the next 4 weeks after the registration date).

Background and Aims Studies of healthy individuals or candidates for living kidney donation, in various geographical areas and ethnic groups, describe a decline of glomerular filtration rate (GFR) with age. Most data on GFR are obtained from subjects in the general population or from candidates for kidney donation who are younger than 65 years. It is currently unknown whether the definition of normal GFR in subjects older than 65 years is similar to the definition in those younger than 65 years. Because the age of candidates for living kidney donation is increasing worldwide, lack of GFR references for older donors complicates the selection process. Moreover, older individuals are most likely to have a mildly decreased GFR that may be misinterpreted as chronic kidney disease. In this study, we calculated percentiles of measured GFR (mGFR) from a large cohort of effective kidney donors (EKD) younger than 65 years, and extrapolated them to subjects older than 65 years. Additionnaly, we collected mGFR data from different centers within Europe from EKD and/or healthy people (HP) from the general population older than 65 years. We tested if the distribution of mGFR of these older subjects fitted with the extrapolated percentiles. Method In this retrospective, observational, multi-center study, percentiles of mGFR in EKD were calculated from a development cohort of French and Belgian EKD younger than 65 years (n=1983). From the French kidney donor study, 147 EKD older than 65 years were considered as the internal validation cohort. In an external validation cohort, data on mGFR of subjects older than 65 years, either EKD or HP from the general population (from Germany, Sweden (2), Norway, Netherlands and France, n=2459) were included. Data were fully anonymized and this retrospective study was approved by the respective ethics committees. Percentiles were derived for the development database, using quantiles modeled as cubic splines with two linear parts joining at one age-knot of 40 years. The median quantile had a constant first part (slope of zero) and a second part with a negative slope of -0.88235 mL/min/1.73m² per year. To maintain consistency, all quantiles were adjusted to show the same shape as the medium quantile. Above 65 years, the percentile values were extrapolated using the same mathematical model. We then calculated the percentage of results from the internal and external validation cohorts that were within the 5th extrapolated percentile (P5) and 95th percentile (P95). A sensitivity analysis including the EKD only was performed. Results Individuals in the development cohort were younger than in the internal or external validation cohort (47.3±10.5 years vs. 68.8±2.9 years and 71.4±6.4 years; respectively, both p Conclusion We demonstrate that extrapolated percentiles of mGFR (calculated in individuals younger than 65) fits well with the distribution of mGFR in individuals older than 65. Extrapolation of percentiles to individuals older than 65 is useful to define age-adapted GFR thresholds for older individuals.

Background and Aims Acute kidney injury (AKI) is amongst the most common in-hospital complications especially in old age. Epidemiological data on incidence rates (IR) of nosocomial AKI in individuals aged 70+ years, stratified by age, gender and pre-existing diseases are scarce because older adults are usually underrepresented in clinical research. Method We used data from the Berlin Initiative Study (BIS), a longitudinal, population-based cohort of adults aged ≥70 with biennial follow-up visits (including blood and urine tests) in combination with claims data from the AOK Nordost insurance fund to complement information on diagnoses and in-hospital procedures (based on ICD-10 and OPS coding). Nosocomial AKI was defined as documented in-hospital diagnosis (ICD-10: N17.xx) excluding cases with AKI as admission diagnosis. Incidence rates (IR) and 95% confidence intervals (CI) of the first nosocomial AKI were calculated with the number of incident cases during observation divided by the total person-years of follow-up, for AKI cases truncated at the first incidence of nosocomial AKI. IR are reported by age strata, sex and preexisting diseases (diabetes, arterial hypertension, atrial fibrillation, heart failure, angina pectoris, peripheral artery disease and impaired kidney function). Results In 2020 individuals (mean age 80.5 years; 52.6% women), 383 developed nosocomial AKI over the median [IQR] follow up time of 8.8 [5.9-9.3] years (Fig.1). The IR of nosocomial AKI was 26.8 (95%CI 24.1-29.6) per 1000 person years among all patients, with higher IR in men compared to women, and - when stratified by age - lowest IR in age category 70-75 versus the highest IR in age category of ≥ 90 years (Fig.1). IR per 1000 person years were higher in patients with diabetes mellitus (IR: 39.3 vs 22.7), arterial hypertension (IR: 31.1 vs 12.2), chronic heart failure (IR: 41.9 vs 22.3), angina pectoris (IR: 37.6 vs 25.7), peripheral artery disease (IR: 55.0 vs 25.1) and impaired kidney function (IR: 43.3 vs 12.4), respectively (Fig.2). Conclusion Nosocomial AKI is an in-hospital complication common in older adults with IRs rising continuously with age above the age of 70 years. IR of AKI are considerably higher in patients with cardiovascular comorbidities. A better understanding of the patient population at risk is of great clinical relevance when aiming to improve prevention strategies.

Zinc-alpha 2-glycoprotein (AZGP1) is a serum protein with postulated functions in metabolism, cancer and cardiovascular disease. We developed new prediction models for mortality or cardiovascular events investigating the predictive potential of serum AZGP1 in a community-based cohort of older adults. We measured AZGP1 (μg/ml) in stored serum samples of 930 individuals of the Berlin Initiative Study, a prospective, population-based cohort of adults aged ≥ 70. We determined the prognostic potential of 20 knowledge-based predictors including AZGP1 for the outcomes of mortality or the composite endpoint of death and cardiovascular events (stroke, myocardial infarction (MI)) using Cox models; their model fit was evaluated with calibration plots, goodness-of-fit tests and c-indices. During median follow-up of 48.3 months, 70 incident strokes, 38 incident MI and 234 deaths occurred. We found no associations or correlations between AZGP1 and other candidate variables. After multivariable Cox regression with backward-selection AZGP1 remained in both models for mortality (HR = 0.44, 95%CI: 0.24–0.80) and for the composite endpoint (HR = 0.43, 95%CI: 0.23–0.82). Within newly built prediction models, we found that increased AZGP1 levels were predictive for lower risk of mortality and the composite endpoint in older adults. AZGP1 as a predictor warrants further validation in older adults.

Chronic kidney disease (CKD) causes substantial global morbidity and increases cardiovascular and all-cause mortality. Unlike other chronic diseases with established strategies for screening, there has been no consensus on whether health systems and governments should prioritize early identification and intervention for CKD. Guidelines on evaluating and managing early CKD are available but have not been universally adopted in the absence of incentives or quality measures for prioritizing CKD care. The burden of CKD falls disproportionately upon persons with lower socioeconomic status, who have a higher prevalence of CKD, limited access to treatment, and poorer outcomes. Therefore, identifying and treating CKD at the earliest stages is an equity imperative. In 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a controversies conference entitled "Early Identification and Intervention in CKD." Participants identified strategies for screening, risk stratification, and treatment for early CKD and the key health system and economic factors for implementing these processes. A consensus emerged that CKD screening coupled with risk stratification and treatment should be implemented immediately for high-risk persons and that this should ideally occur in primary or community care settings with tailoring to the local context.

Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved. Methods In a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation. Results 7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels Conclusions None of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.

Background and Aims Current guidelines on the management of heart failure (HF) recommend control of blood pressure (BP) in elderly patients. However, the exact treatment goals in this vulnerable population are unclear. Thus, our population-based prospective cohort study aimed to assess whether BP values Method The study included participants of the Berlin Initiative Study (BIS), all ≥70 years, who were treated with antihypertensive drugs and had a diagnosis of HF (ICD-10 codes: I11.0, I13.0, I13.2, I50.x) at baseline. The study period was from 2009 to 2017. Demographics, lifestyle factors, medications, and comorbidities were assessed in face-to-face interviews and from linked administrative healthcare data. Outcomes were adjudicated using death certificates and hospital discharge notes. Cox proportional hazards models yielded crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of CV death and all-cause mortality associated with normalized BP (systolic BP Results Among 1623 BIS participants treated with antihypertensive drugs at baseline, 544 (33.5%) had a diagnosis of HF. Of those, 255 (46.9%) showed normalized BP and 289 (53.1%) had non-normalized values. Mean age (standard deviation [SD]) was 82.8 (6.8) years (45.4% female). Selected patient characteristics are shown in the Table. Median (interquartile range) duration of follow-up was 6.7 (4.1-7.3) years. Compared with non-normalized BP, normalized BP was associated with a numerically increased risk of CV death (HR, 1.40; 95% CI, 0.90-2.17) and all-cause mortality (HR, 1.28; 95% CI, 0.96-1.71) in patients with HF. The associations were more pronounced or reached statistical significance when restricting to HF patients ≥80 years (CV death: HR, 1.54; 95% CI, 0.94-2.53 / all-cause mortality: HR, 1.56; 95% CI, 1.11-2.18) or HF patients with previous CV events (CV death: HR, 1.65; 95% CI, 0.83-3.29 / all-cause mortality: HR, 1.33; 95% CI, 0.85-2.07) (Figure). The effect estimates in patients without HF were comparable to those with HF (CV death: HR, 1.18; 95% CI, 0.78-1.78; p for interaction, 0.695 / all-cause mortality: HR, 1.20; 95% CI, 0.93-1.54; p for interaction, 0.604). Conclusion Our study suggests that normalized BP does not decrease the risk of CV death or all-cause mortality in elderly patients with HF and it could even increase the risk especially in high-risk subgroups. Thus, individualized benefit-risk assessment is required for the pharmacotherapy of HF in this vulnerable population.

Despite a growing body of knowledge about the morbidities and functional impairment that frequently lead to care dependency, the role of social determinants is not yet well understood. The purpose of this study was to examine the effect of social determinants on care dependency onset and progression.[for full text, please go to the a.m. URL], 65th Annual Meeting of the German Association for Medical Informatics, Biometry and Epidemiology (GMDS), Meeting of the Central European Network (CEN: German Region, Austro-Swiss Region and Polish Region) of the International Biometric Society (IBS)