The Lack of a Standardized Definition of Chronic Dialysis Treatment in German Statutory Health Insurance Claims Data.

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.

Assessment of Cystatin C Level for Risk Stratification in Adults With Chronic Kidney Disease.

Importance: Kidney 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. Objectives: To 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 Participants: A 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 <30 mg/g), and no preexisting CVD or kidney failure. Exposures: Chronic 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 Measures: Ten-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 <65 years) age. Results: There 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 Relevance: The 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.

Assessment of kidney function: clinical indications for measured GFR.

In the vast majority of cases, glomerular filtration rate (GFR) is estimated using serum creatinine, which is highly influenced by age, sex, muscle mass, body composition, severe chronic illness and many other factors. This often leads to misclassification of patients or potentially puts patients at risk for inappropriate clinical decisions. Possible solutions are the use of cystatin C as an alternative endogenous marker or performing direct measurement of GFR using an exogenous marker such as iohexol. The purpose of this review is to highlight clinical scenarios and conditions such as extreme body composition, Black race, disagreement between creatinine- and cystatin C-based estimated GFR (eGFR), drug dosing, liver cirrhosis, advanced chronic kidney disease and the transition to kidney replacement therapy, non-kidney solid organ transplant recipients and living kidney donors where creatinine-based GFR estimation may be invalid. In contrast to the majority of literature on measured GFR (mGFR), this review does not include aspects of mGFR for research or public health settings but aims to reach practicing clinicians and raise their understanding of the substantial limitations of creatinine. While including cystatin C as a renal biomarker in GFR estimating equations has been shown to increase the accuracy of the GFR estimate, there are also limitations to eGFR based on cystatin C alone or the combination of creatinine and cystatin C in the clinical scenarios described above that can be overcome by measuring GFR with an exogenous marker. We acknowledge that mGFR is not readily available in many centres but hope that this review will highlight and promote the expansion of kidney function diagnostics using standardized mGFR procedures as an important milestone towards more accurate and personalized medicine.

Is there an association between social determinants and care dependency risk? A multi-state model analysis of a longitudinal study.

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. We used data from the Berlin Initiative Study, a prospective, population-based cohort study including 2,069 older participants living in Berlin. Care dependency was defined as requiring substantial assistance in at least two activities of daily living for 90 min daily (level 1) or 3+ hours daily (level 2). Multi-state time to event regression modeling was used to estimate the effects of social determinants (partnership status, education, income, and sex), morbidities, and health behaviors, characteristics, and conditions. During the study period, 556 participants (27.5%) changed their status of care dependency. Participants without a partner at baseline were at a higher risk to become care-dependent than participants with a partner (hazard ratio [HR], 95% confidence interval [CI]: 1.24 (1.02-1.51)). After adjustment for other social determinants, morbidities and health behaviors, characteristics, and conditions the risk decreased to a HR of 1.19 (95% CI: 0.79-1.79). Results indicate that older people without a partner may tend to be at higher risk of care dependency onset but not at higher risk of care dependency progression. Clinicians should inquire about and consider patients' partnership status as they evaluate care needs.

Risk Profiles for Care Dependency: Cross-Sectional Findings of a Population-Based Cohort Study in Germany.

Background: Rising life expectancy in Western societies is accompanied by a rising incidence of care dependency (CD) among older people. Objective: The aim of the study was to examine which health-related and social determinants were associated with CD. Method: We used cross-sectional data from the first follow-up (N = 1,699) of a prospective, population-based cohort study of older participants (≥70 years). CD was assessed if participants required substantial assistance in at least two activities of daily living for 90+ minutes daily. Multivariate logistic regressions were applied. Results: Participants' mean age was 82 years; 18.9% were care-dependent. CD was significantly associated with older age, urinary incontinence, stroke, falls, cancer, diabetes, education level, having no partner, limited mobility, and limited physical activity. Discussion: Our research highlights the importance of promoting mobility, even in care-dependent people. Further research should investigate the role of partnership in terms of the prevention and delay of CD.

Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate.

BACKGROUND: Cystatin C is increasingly used in glomerular filtration rate (GFR) estimation equations. The dependence of cystatin C results upon the analytical method has been a major source of controversy. METHODS: Cystatin C was measured with non-standardized turbidimetric Roche Generation 1 and standardized nephelometric Siemens assays in 3666 and additionally with standardized Roche Generation 2 and Siemens in 567 blood samples of the Berlin Initiative Study. Cystatin C-based GFR was assessed with CKD-EPIcys (Chronic Kidney Disease Epidemiology) and CAPA (Caucasian, Asian, Pediatric, Adult) equations and the impact of the assays on GFR estimation was determined. Equation performance compared to measured GFR was evaluated. RESULTS: Concordance of Roche Gen2 and Siemens was high with median difference of 0.003 ± 0.13 mg/L (limits of agreement: -0.12 to 0.12) and Passing Bablok correlation was essentially perfect. Roche Gen1 assay showed worse concordance with Siemens: median difference was 0.08 ± 0.13 mg/L (limits of agreement: -0.18 to 0.34) and correlation was inferior. Mean difference (± SD) of estimated GFRCKD-EPIcys was 0 ± 4 mL/min/1.73 m(2) for Gen2 and Siemens compared to -5 ± 8 with Gen1. Performance of GFR estimating equations was not influenced by the choice of Siemens or Gen2 assays. CONCLUSIONS: Standardization of Roche Gen2 assay improved accuracy of cystatin C measurement compared to Siemens. It suggests only negligible method bias and results in equal performance of both assays when estimating GFR indicating that successful calibration has led to major progress in cystatin C analysis.

An efficient approach for glomerular filtration rate assessment in older adults.

AIMS: Assessment of glomerular filtration rate (GFR) is crucial because the GFR value defines the stage of chronic kidney disease and determines the adjustment of drug dosage. The aim was to investigate a new method for the accurate determination of GFR in older adults based on the combination of an exogenous filtration marker, iohexol, and an endogenous marker, serum creatinine or cystatin C. METHODS: We combined variables for the estimation of GFR with a reduced set of measurements of the marker iohexol. In a population-based sample of 570 subjects (≥70 years old) from the Berlin Initiative Study (BIS), we investigated the following: (i) the BIS1 and BIS2 equations based on age, gender and serum creatinine with or without serum cystatin C; (ii) equations based on one or two iohexol measurements; and (iii) equations based on the combination of variables from BIS1 or BIS2 with iohexol measurements. The reference standard was based on eight iohexol measurements. The cut-off value of 60 ml min(-1) (1.73 m)(-2) was chosen to assess accuracy. Equations were constructed using a learning sample (n = 285) and an independent validation sample (n = 285). RESULTS: Misclassification rates were 17.2% (BIS1), 11.6% (BIS2), 14.7% [iohexol measurement at 240 min (iohexol240 )], 7.0% (iohexol240 combined with variables included in BIS1) and 6.7% (iohexol240 combined with variables included in BIS2). Misclassification rates did not decrease significantly after inclusion of two or three iohexol measurements. CONCLUSIONS: Combined strategies for the determination of GFR lead to a relevant increase of diagnostic validity.

Assessment of kidney function: Estimating GFR in children.

In a new study, Schwartz and colleagues have investigated the best way to estimate glomerular filtration rate (GFR) in children. Having already improved GFR estimation with the use of creatinine-based equations, the investigators now propose a more precise method for cystatin C measurement. The precision of a GFR equation will strongly depend on the analytical precision of the biological variables included.