Berlin Initiative Study Equation Research Articles

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.

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.

Diabetes, sarcopenia and chronic kidney disease; the Screening for CKD among Older People across Europe (SCOPE) study

BackgroundSarcopenia may be more present in older adults with diabetes (DM). Accordingly, we evaluated the prevalence of sarcopenia and its associated risk factors among community-dwelling older adults with DM.MethodsA cross-sectional analysis of older people living in the community was carried out. Participants (aged 75 years and more) came from an European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test and bioelectrical impedance analysis was performed. Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate (eGFR) was calculated using Berlin Initiative Study (BIS) to define the stages of chronic kidney disease (CKD). Previous known DM was defined as physician-diagnosed DM registered in the patient's medical record or the use of DM-related medications. Hemoglobin A1c levels and specific DM therapies administered were collected. Time elapsed from the first diagnosis of DM was not collected and, therefore, was not included in the analyses.ResultsA total of 1,420 subjects were evaluated with a median age of 79.0 (6.0) years, of which 804 (56.6%) were women and 615 (43.3%) men; 315 (22.2%) participants had prior DM diagnosis, with a median age of 80.0 (6.0), 146 (46.3%) were women. Using EWGSOP2 definition, 150 (10.6%) participants in the SCOPE study met diagnostic criteria for sarcopenia. Participants without diabetes had more often normal results in the 3 sarcopenia components than participants with diabetes [887 (80.31%) vs. 227 (72.1%), p = 0.002], highlighting higher percentages of severe sarcopenia in participants with diabetes [27 (8.6%) vs. 58 (5.2%), p = 0.028]. Confirmed or severe sarcopenia was detected in 41 (13%) participants with diabetes and 109 (9.8%) participants without diabetes (p = 0.108). According to BIS equation, sarcopenia was not significantly more prevalent in the more advanced stages of CKD (p = 0.845). In multivariate analyses, older age (odds ratios [OR], 1.17; 95% confidence interval [CI], 1.08–1.27), and lower body mass index (OR, 0.79; 95% CI, 0.71–0.89 were associated with the presence of sarcopenia.ConclusionsOne tenth of all older community-dwelling subjects have sarcopenia. Older age and being thinner, but not worse renal function, were associated with higher prevalence of sarcopenia in older older adults with diabetes.

The effects of aging on the renal function of a healthy population in Beijing and an evaluation of a range of estimation equations for glomerular filtration rate.

We investigated how age affected renal function in healthy subjects in Beijing and compared different estimated glomerular filtration rate (eGFR) equations. Kidney function was evaluated by five equations: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); Modification of Diet in Renal Disease Study (MDRD); the Chinese version of the MDRD (MDRDc); Full Age Spectrum (FAS); and Berlin Initiative Study (BIS). A total of 46,708 subjects were enrolled and followed-up for 3 years. All showed an increase in sCr and a reduction in eGFR with increasing age. Over the 3 years, the eGFR and serum creatinine (sCr) remained unchanged in most subjects. Different equations showed good consistency; the intraclass correlation coefficients (ICC) was 0.849 for males, and 0.817 for females. The CKD-EPI equation yielded higher GFR values than the other equations (according to sCr levels). For subjects aged over 70 years, the BIS equation produced the lowest eGFR values. In summary, we observed that the renal function of individuals was relatively stable with increasing age, although different eGFR equations yielded data that varied across different populations of subjects and sCr levels.

Kidney Function as Risk Factor and Predictor of Cardiovascular Outcomes and Mortality Among Older Adults

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. Population-based cohort study. 1,581 participants (aged≥70 years) in the Berlin Initiative Study (BIS) without prior stroke or MI. Serum creatinine- and cystatin C-based eGFR, UACR categories, and measured GFR (n=436). Stroke, MI, and all-cause mortality. 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. 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 cystatinC-based BIS equation, eGFR of 45 to 59mL/min/1.73m2 (vs eGFR>60mL/min/1.73m2) 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/1.73m2, 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. eGFR and UACR categorization based on single assessments; lack of cause-specific death data. eGFR of 45 to 59mL/min/1.73m2 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.

Renal function and delirium in older fracture patients: different information from different formulas?

Objectivesthe association between renal function and delirium has not been investigated in older fracture patients. Creatinine is frequently low in these subjects, which may influence the association between delirium and renal function as estimated with creatinine-based formulas. Cystatin C could be a more reliable filtration marker in these patients. Aimto confirm the association between renal function and delirium in older fracture patients comparing creatinine- and cystatin-based estimated glomerular filtration rate (eGFR) Methodspatients aged 65+ requiring surgery for traumatic bone fractures were included. Six equations were used to calculate eGFR, based on serum creatinine and/or cystatin C obtained within 24 h of admission: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPIcr, CKD-EPIcys, CKD-EPIcr-cys) and Berlin Initiative Study equations (BIS-1, BIS-2). Delirium was identified with a chart-based method. Results571 patients (mean age 83) were enrolled. Delirium occurred in the 34% and was associated with a lower eGFR regardless of the equation used. In a multivariable model, the association between moderate renal impairment (eGFR 30–60 ml/min/1.73 m2) and delirium remained significant in patients aged 75–84 and only when estimated with cystatin-based or BIS-1 equations. Only dementia was significantly associated with delirium in subjects 85+. Conclusionsin older fracture patients, moderate renal impairment was independently associated with delirium only among subjects aged 75–84, when eGFR was estimated with cystatin-based or BIS 1 equations, and not with the most commonly used equations (MDRD, CKD-EPIcr).

Using a three-compartment model improves the estimation of iohexol clearance to assess glomerular filtration rate

Plasma clearance of iohexol is a key tool to precisely determine glomerular filtration rate (GFR) in clinical research and clinical practice. Despite evidence that iohexol pharmacokinetics are described best by three-compartment models, two-compartment approaches (Schwartz approach) are customary, which might result in avoidable bias and imprecision. We aimed to provide a population pharmacokinetic (popPK) model of iohexol by re-evaluating data from the Berlin Initiative Study (BIS) to compare respective clearance estimates to the Schwartz approach and to assess the impact of revised clearance estimates on the BIS equations. A popPK model was developed based on iohexol plasma samples (8–10 per subject, iohexol dose 3235 mg) from 570 elderly patients. A three-compartment model appropriately described the pharmacokinetics of iohexol (clearance 57.4 mL/min, CV 33%). Compared to the three-compartment model, clearance values were overestimated by the Schwartz approach (bias 6.5 mL/min), resulting in limited effects on regression coefficients of the BIS equations (e.g., proportionality factor of BIS2 changed from 767 to 720). Predictions based on the BIS2 equation were biased (5.4 mL/min/1.73 m²) and the sensitivity to detect a GFR < 60 mL/min/1.73 m² was low compared to the revised equation (72% versus 89%). Three-compartment models should be employed to assess iohexol pharmacokinetics.

Creatinine-Based Renal Function Estimates and Dosage of Postoperative Pain Management for Elderly Acute Hip Fracture Patients.

Many analgesics and their metabolites are renally excreted. The widely used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-estimated glomerular filtration rate (eGFR) equations are not developed for use in the elderly, while the recent Berlin Initiative Study (BIS), Full Age Spectrum (FAS), and Lund-Malmö revised (LMR) equations are. This observational study investigated differences between creatinine-based eGFR equations and how the choice of equation influences dosage of analgesics in elderly (≥70 years) patients admitted with acute hip fracture. eGFR was calculated by the CKD-EPI, BIS, Cockcroft-Gault (CG), FAS, LMR, and Modification of Diet in Renal Disease (MDRD) equations. Standard daily dose for postoperative pain medications ibuprofen, morphine and gabapentin was simulated for each equation according to dosage recommendations in Renbase®. For 118 patients, mean eGFR from the CKD-EPI, BIS, CG, FAS, LMR, and MDRD equations was 67.3 mL/min/1.73 m2, 59.1 mL/min/1.73 m2, 56.9 mL/min/1.73 m2, 60.3 mL/min/1.73 m2, 58.9 mL/min/1.73 m2, and 79.1 mL/min/1.73 m2, respectively (p < 0.0001). Mean difference to CKD-EPI was −10.4 mL/min/1.73 m2 to 11.8 mL/min/1.73 m2. Choice of eGFR equation significantly influenced the recommended dose (p < 0.0001). Shifting to BIS, FAS, or LMR equations led to a lower recommended dose in 20% to 31% of patients. Choice of eGFR equation significantly influenced dosing of ibuprofen, morphine, and gabapentin.

Renal Function and Death in Older Women: Which eGFR Formula Should We Use?

Background. The Berlin Initiative Study (BIS) eGFR equations were developed specifically for aged populations, but their predictive validity compared to standard formulae is unknown in older women. Methods. In a prospective study of 1289 community-dwelling older women (mean age 79.5 years), we compared the performance of the BIS1 SCr-based equation to the CKD-EPIcr and the BIS2 SCr- and Scysc-based equation to the CKD-EPIcr,cysc to predict cardiovascular and all-cause mortality. Results. Prevalence of specific eGFR category (i.e., ≥75, 60–74, 45–59, and <45) according to eGFR equation was 12.3%, 38.4%, 37.3%, and 12.0% for BIS1; 48.3%, 27.8%, 16.2%, and 7.8% for CKD-EPIcr; 14.1%, 38.6%, 37.6%, and 9.6% for BIS2; and 33.5%, 33.4%, 22.0%, and 11.1% for CKD-EPIcr,cysc, respectively. Over 9 ± 4 years, 667 (51.8%) women died. For each equation, women with eGFR <45 were at increased risk of mortality compared to eGFR ≥75 [adjusted HR (95% CI): BIS1, 1.5 (1.1–2.0); CKD-EPIcr, 1.7 (1.3–2.2); BIS2, 2.0 (1.4–2.8); CKD-EPIcr,cysc, 1.8 (1.4–2.3); p-trend <0.01]. Net reclassification analyses found no material difference in discriminant ability between the BIS and CKD-EPI equations. Results were similar for cardiovascular death. Conclusions. Compared to CKD-EPI, BIS equations identified a greater proportion of older women as having CKD but performed similarly to predict mortality risk. Thus, the BIS equations should not replace CKD-EPI equations to predict risk of death in older women.

Agreement between Chronic Kidney Disease Epidemiological Collaboration and Berlin Initiative Study equations for estimating glomerular filtration rate in older people: The Invecchiare in Chianti (Aging in Chianti Region) study.

The aim was to investigate to what extent chronic kidney disease (CKD) can be staged interchangeably by Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) and by Berlin Initiative Study (BIS) equations, and to verify whether cystatinC can improve concordance between formulas. Our series consisted of 828 community-dwelling individuals aged 65years or older enrolled in the Invecchiare in Chianti Study ("Aging in the Chianti Region"). Estimated glomerular filtration rate was calculated using the creatinine-based CKD-EPI, creatinine/cystatinC-based CKD-EPI, creatinine-based BIS and creatinine/cystatinC-based BIS equations. Agreement and sources of discrepancy between equations in identifying people with different degrees of kidney dysfunction was investigated by κ statistic and Bland-Altman plots. Overall, CKD-EPI values were higher than that obtained with BIS equations, especially for eGFR=30-60mL/min/1.73m2 . A total of 191 out of 828 participants were classified in stage2 by the creatinine-based CKD-EPI and in stage3a by the creatinine-based BIS equation, whereas 123 participants were classified in stage2 by creatinine/cystatinC-based CKD-EPI and in stage 3a by the creatinine/cystatinC-based BIS equation. A total of 27 participants were classified in stage3a by creatinine-based CKD-EPI and in stage3b by creatinine-based BIS equation, whereas 18 were classified as stage3a by creatinine/cystatinC-based CKD-EPI and stage3b by the creatinine/cystatinC-based BIS equation. Despite a fair overall concordance, the CKD-EPI and BIS equations cannot be considered interchangeable to assess estimated glomerular filtration rate in older people, and using creatinine/cystatinC-based rather than creatinine-based equations only marginally improves the concordance between CKD-EPI and BIS. Disagreement between equations might significantly impact the applications of stage-specific measures for managing CKD among older people. Geriatr Gerontol Int 2017; 17: 1559-1567.

Calibration and precision of serum creatinine and plasma cystatin C measurement: impact on the estimation of glomerular filtration rate

Serum creatinine (SCr) is the main variable for estimating glomerular filtration rate (GFR). Due to inter-assay differences, the prevalence of chronic kidney disease (CKD) varies according to the assay used, and calibration standardization is necessary. For SCr, isotope dilution mass spectrometry (IDMS) is the gold standard. Systematic differences are observed between Jaffe and enzymatic methods. Manufacturers subtract 0.30 mg/dl from Jaffe results to match enzymatic results ('compensated Jaffe method'). The analytical performance of enzymatic methods is superior to that of Jaffe methods. In the original Modification of Diet in Renal Disease (MDRD) equation, SCr was measured by a Jaffe Beckman assay, which was later recalibrated. A limitation of this equation was an underestimation of GFR in the high range. The Chronic Kidney Disease Epidemiology (CKD-EPI) consortium proposed an equation using calibrated and IDMS traceable SCr. The gain in performance was due to improving the bias whereas the precision was comparable. The CKD-EPI equation performs better at high GFR levels (GFR >60 ml/min/1.73 m(2)). Analytical limitations have led to the recommendation to give a grade (>60 ml/min/1.73 m(2)) rather than an absolute value with the MDRD equation. By using both enzymatic and calibrated methods, this cutoff-grade could be increased to 90 ml/min/1.73 m(2) (with MDRD) and 120 ml/min/1.73 m(2) (with CKD-EPI). The superiority of the CKD-EPI equation over MDRD is analytical, but the precision gain is limited. IDMS traceable enzymatic methods have been used in the development of the Lund-Malmö (in CKD populations) and Berlin Initiative Study equations (in the elderly). The analytical errors for cystatin C are grossly comparable to issues found with SCr. Standardization is available since 2011. A reference method for cystatin C is still lacking. Equations based on standardized cystatin C or cystatin C and creatinine have been proposed. The better performance of these equations (especially the combined CKD-EPI equation) has been demonstrated.

Two Novel Equations to Estimate Kidney Function in Persons Aged 70 Years or Older

In older adults, current equations to estimate glomerular filtration rate (GFR) are not validated and may misclassify elderly persons in terms of their stage of chronic kidney disease. To derive the Berlin Initiative Study (BIS) equation, a novel estimator of GFR in elderly participants. Cross-sectional. Data were split for analysis into 2 sets for equation development and internal validation. Random community-based population of a large insurance company. 610 participants aged 70 years or older (mean age, 78.5 years). Iohexol plasma clearance measurement as gold standard. GFR, measured as the plasma clearance of the endogenous marker iohexol, to compare performance of existing equations of estimated GFR with measured GFR of the gold standard; estimation of measured GFR from standardized creatinine and cystatin C levels, sex, and age in the learning sample; and comparison of the BIS equations (BIS1: creatinine-based; BIS2: creatinine- and cystatin C-based) with other estimating equations and determination of bias, precision, and accuracy in the validation sample. The new BIS2 equation yielded the smallest bias followed by the creatinine-based BIS1 and Cockcroft-Gault equations. All other equations considerably overestimated GFR. The BIS equations confirmed a high prevalence of persons older than 70 years with a GFR less than 60 mL/min per 1.73 m2 (BIS1, 50.4%; BIS2, 47.4%; measured GFR, 47.9%). The total misclassification rate for this criterion was smallest for the BIS2 equation (11.6%), followed by the cystatin C equation 2 (15.1%) proposed by the Chronic Kidney Disease Epidemiology Collaboration. Among the creatinine-based equations, BIS1 had the smallest misclassification rate (17.2%), followed by the Chronic Kidney Disease Epidemiology Collaboration equation (20.4%). There was no validation by an external data set. The BIS2 equation should be used to estimate GFR in persons aged 70 years or older with normal or mild to moderately reduced kidney function. If cystatin C is not available, the BIS1 equation is an acceptable alternative. Kuratorium für Dialyse und Nierentransplatation (KfH) Foundation of Preventive Medicine.