Elke Schaeffner

Background: Conservative kidney management (CKM) offers a treatment option for older adults with chronic kidney failure (CKF) and limited life expectancy. International evidence suggests that nephrologists face challenges in providing CKM. However, in Germany, in-depth research on this topic remains limited. Therefore, this study aims to explore barriers and facilitators experienced by nephrologists in CKM delivery to derive measures for improving its implementation. Methods: Semi-structured interviews were conducted with nephrologists working in inpatient or outpatient settings in Berlin and the Federal State of Brandenburg, Germany in 2024. The Theoretical Domains Framework (TDF) guided data collection. The data were analyzed using qualitative content analysis. Results: Eleven interviews were conducted. Nephrologists reported barriers and facilitators across ten TDF domains, overall. Barriers in delivering CKM were identified across nine TDF domains, such as knowledge (lack of CKM education), skills (insufficient shared-decision-making, SDM), social/professional role and identity (lack of clarification of nephrologists’ role in palliative care, divergence from professional role perception), beliefs about consequences (caregiver burden), reinforcement (unattractive reimbursement), environmental context and resources (insufficient intersectoral and interdisciplinary collaboration), and social influences ( relatives, societal expectations). Facilitators were also reported in nine TDF domains, for example knowledge (CKM training), reinforcement (adequate reimbursement), intentions (adjustment of treatment goals for older patients), environmental context and resources (improved interdisciplinary and intersectoral collaboration, patient decision aids), and social influences (treatment discussions with and without relatives). Conclusions: CKM delivery is challenging at multiple levels. Our findings align with international barriers and complement previous national evidence by providing deeper insight into nephrologists’ attitudes, barriers within SDM, and the role of relatives. Improving CKM implementation requires multifaceted strategies, particularly system-level measures such as adequate reimbursement and CKM-related training to strengthen awareness and acceptance. In addition, structured SDM approaches and guidance on involving and considering relatives may be crucial to support CKM as a valid treatment option.

Frailty increases the risk of adverse outcomes in older adults and is an important target for preventive care. Clinical frailty measures are established but rarely available at scale due to limited functional data in routine healthcare records. Claims-based frailty prediction models offer a pragmatic approach for population-level risk stratification but are often developed in specific healthcare systems and lack external validation. We aimed to externally validate and recalibrate the Claims-Based-Frailty-Indicator (CFI) and develop a claims-based frailty model for the German healthcare context. We used data from the Berlin Initiative Study, a cohort of older adults with assessment of the frailty phenotype, linked to individual health insurance claims and cause-of-death data. External validation of CFI was assessed by discrimination and calibration. Additionally, a new claims-based frailty model was developed. Model performance and application were evaluated through associations with mortality and hospital admission. Reporting followed TRIPOD statement. Among 1,151 participants (mean age 84.4 years; 55% women), the CFI demonstrated good discrimination (AUC 0.78) but poor calibration; recalibration of intercept improved calibration. Maximizing the Youden Index identified an optimal frailty threshold corresponding to a predicted probability of 0.39. The new model showed improved discrimination (AUC 0.82). Predicted frailty was similarly associated with mortality and hospital admissions as the frailty phenotype. Claims-based frailty models can be validated, recalibrated, and adapted to the German healthcare system. They provide a feasible approach for population-level frailty assessment and may support health services research, risk stratification, and care planning for older adults.

Joint models offer an unbiased statistical approach for analyzing the effects of longitudinal biomarkers on time-to-event outcomes, providing an alternative to time-varying Cox proportional-hazards regression and the two-stage approach. However, whether available implementations of these methods perform reliably across different practically relevant scenarios remains insufficiently studied. We conducted a simulation study based on the Berlin Initiative Study examining kidney function and survival in older adults. In a manner comparable to phase IV studies in clinical research, our evaluation aims to provide insights into the practical performance of commonly used R package implementations of these methods, mostly under their default settings. By varying data generating scenarios, we assessed how different numbers of events and longitudinal measurements affect performance of Bayesian (JMbayes2) and frequentist joint model implementations (JM and joineRML), time-varying Cox PH regression (survival), and the two-stage approach (nlme and survival), focusing on bias in parameter estimates. Results revealed substantial variability across implementations. The JM package exhibited considerable bias and frequent convergence issues. In contrast, joineRML performed robustly with approximately unbiased estimates for association parameters and high convergence frequencies comparable to the implementations of the simpler methods across diverse scenarios. However, both frequentist packages systematically underestimated the effects of baseline covariates in the survival model. The Bayesian JMbayes2 was largely unbiased, but performance deteriorated under two conditions: with few events (< 70), convergence was low and bias persisted even in converged models; and with observation-to-event ratios below 2, convergence declined, although estimates from converged models remained approximately unbiased. Time-varying Cox PH regression and the two-stage approach showed more bias than JMbayes2 in certain settings but tended to achieve more robust performance and convergence across most scenarios.

Knowledge of kidney function is a key component for diagnosing CKD and initiating treatment. The eGFR, which is most commonly used in clinical practice as an approximation of kidney function, is the most practical for everyday use. It has, however, disadvantages because the two most common biomarkers used in eGFR calculations, creatinine and cystatin C, are influenced by patient characteristics such as body composition, inflammation, and many others, leading to significantly inaccurate GFR estimation at times. In patients who are prone to distorted eGFR values, measured GFR (mGFR) should be considered to ensure accurate assessment of kidney function. mGFR is not as influenced by patient characteristics as it uses exogenous biomarkers instead of endogenous ones. It is, however, more complex to perform and has also its limitations. Several different mGFR measurement methods exist. The one that has become most widely accepted and is the only method for which there is an internationally standardized protocol is plasma iohexol clearance. Other mGFR markers include iothalamate, mostly applied as urinary clearance and radioactive markers. Newer techniques that measure GFR transdermally have been developed, although they have yet to be sufficiently externally validated.

The extent to which eGFR varies across populations, in the absence of risk factors and comorbidities associated with kidney disease, remains uncertain. We aimed to develop eGFR reference values in healthy American adults and to compare them with previously described European eGFR reference values. This cross-sectional study compared newly described age-specific and sex-specific creatinine-based eGFR reference values from over 9000 healthy Americans from National Health and Nutrition Examination Survey with previously described eGFR reference values from over 1.5 million healthy individuals in the European CKD Burden Consortium. Health status was based on 14 criteria related to comorbidities, lifestyle factors, and medication use. eGFR was calculated using the European Kidney Function Consortium equation and modeled over the age span and by sex using a generalized additive model. The median eGFR in both 20-year-old American and European men was 98 ml/min per 1.73 m ² . In both 20-year-old American and European women, the median eGFR was 101 ml/min per 1.73 m ² . eGFR started to decrease at age 40 years, a result of the structure of the European Kidney Function Consortium equation. By age 79 years, the median eGFR in American and European men was 68 and 67 ml/min per 1.73 m ² , respectively. The median eGFR in 79-year-old American and European women was 63 and 64 ml/min per 1.73 m ² , respectively. When removing the effect of comorbidities, lifestyle factors and medication use associated with kidney function, achieved by restricting the analyses to individuals who did not have a presence or history of certain criteria, the distribution of eGFR was similar between healthy Americans and Europeans. This supports the notion that eGFR reference values may be generalizable to populations they were not derived from.

Background: Data on the healthcare service quality for patients with chronic kidney disease (CKD) are vital for guiding practitioners, patients and healthcare policy makers. We examined new quality indicators for outpatient diagnostics and treatments in older patients with CKD, focusing on trends between 2012 and 2018. Methods: The study included cross-sectional German statutory health insurance claims data from four independent random samples (2012, 2014, 2016, 2018), each with 62 200 individuals aged ≥70 years. We analyzed coded CKD prevalence and incidence, non-recommended drug prescriptions (dual prescriptions of angiotensin-converting enzyme inhibitors with angiotensin II receptor blockers; non-steroidal anti-inflammatory drugs in CKD stage 4–5), as well as albumin/creatinine ratio (ACR) and dipstick testing in incident CKD cases. Results: After standardization, the samples included 58.4%–59.3% females, and mean ages ranging from 77.4 to 78.9 years. CKD prevalence increased from 17.8% [95% confidence interval (CI) 17.5; 18.1] in 2012 to 25.7% (95% CI 25.4; 26.1) in 2018. CKD incidence rose slightly from 6.4% (95% CI 6.2; 6.6) to 7.6% (95% CI 7.4; 7.9). Non-recommended drug prescriptions, which were below 5% in 2012, decreased by more than half by 2018. ACR and dipstick testing varied inconsistently over time, ranging from 11.4% to 13.5% and 55.4% to 57.2%, respectively. Conclusions: CKD prevalence in older adults in Germany rose by eight percentage points from 2012 to 2018 while prescriptions of non-recommended drugs decreased in patients with CKD, indicating better diagnosis and guideline adherence. However, ACR and dipstick diagnostic was alarmingly low, and remained below recommended levels outside kidney specialist care, showing areas for improvement.

Rationale & Objective: Accurate risk prediction of adverse kidney-related outcomes in individuals with chronic kidney disease (CKD) is essential to guide personalized clinical interventions. Metabolites measured in plasma and urine may offer additional prognostic information beyond established clinical predictors. Study Design: Prospective German CKD cohort study. Setting & Participants: 5,217 individuals with predominantly CKD stage G3 at baseline, followed for a median of 6.5 years (IQR 6.5-6.5). Exposure(s) or • Predictor(s): Baseline metabolite levels measured via untargeted mass spectrometry (Metabolon Inc.) in plasma (N=5,144; 1,096 metabolites) and urine (N=5,088; 1,129 metabolites). Outcome(s): (i) Kidney failure (KF), defined as initiation of maintenance dialysis, kidney transplantation, or death due to untreated KF; (ii) composite kidney endpoint (CKE), defined as KF, a ≥40% decline in estimated glomerular filtration rate (eGFR), or an eGFR <15 mL/min/1.73 m². Analytical Approach: Time-to-event data were analyzed using subdistribution hazard models to predict outcomes. A component-wise boosting algorithm was employed to select metabolites in various scenarios, including models based on plasma, urine, or combined data. Predictive performance was assessed at multiple time points using time-dependent area under the curve (AUC) and Brier scores, and compared to benchmark models. Results: Several individual metabolites were predictive of KF or CKE and provided marginal improvements beyond established prognostic factors (age, sex, eGFR, and urinary albumin-to-creatinine ratio [UACR]). For example, plasma pseudouridine increased the AUC at year 6 by 0.012 (95% CI: 0.005–0.018) when added to the clinical model. Multi-metabolite models developed under different scenarios included a median of 53 metabolites (range: 14-86). Some metabolites, such as plasma N2,N5-diacetylornithine and urine 1-palmitoyl-2-oleoyl-GPC (16:0/18:1), were selected more often than others. Predictive performance of all models declined over time. For KF, models achieved AUCs ≥0.89 at year 2 and ≥0.85 at year 6; for CKE, AUCs were ≥0.85 and ≥0.77, respectively. Compared to benchmark models with only clinical variables, metabolite-based models performed better but not to a clinically meaningful extent. AUC values were comparable to those reported for other published KF prediction models. Limitations: Use of single baseline measurements and semi-quantitative nature of the metabolite measurements. Conclusions: While certain metabolites improved prediction of adverse kidney-related outcomes, the observed gains were not clinically meaningful. Nonetheless, these findings may provide insights into metabolic pathways and processes related to the progression of CKD, thereby complementing current knowledge. Further research is warranted to refine predictive models and explore the biological relevance of identified metabolites.

The Kidney Disease: Improving Global Outcomes (KDIGO) organization updated its existing clinical practice guideline in 2024 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving kidney replacement therapy. The KDIGO CKD Guideline Work Group defined the scope of the guideline and determined topics for systematic review. An independent Evidence Review Team systematically reviewed the evidence and graded the certainty of evidence for each of the review topics. Latest searches of the English-language literature were done in July 2023. Final modification of the guideline was informed by a public review process during summer of 2023 involving registered stakeholders. The full guideline included 28 recommendations and 141 practice points. This synopsis focuses on the recommendations that have the greatest evidence. Practice points reflect the expert opinion of the group where evidence is not that strong. Recommendations include greater emphasis on cystatin C for assessment of glomerular filtration rate, point-of-care testing in remote areas, a shift to an individualized risk-based approach to predict kidney failure, sodium-glucose cotransporter-2 inhibitors for some patients with CKD with and without diabetes, and statin use for adults older than 50 years and CKD. Together the recommendations and practice points provide guidance for how to evaluate and manage persons with CKD.

The aim of the present study was to extend the creatinine-based Lund-Malmö GFR equation for use with rescaled cystatin C (r-LMR_Cys) and validate it against measured GFR (mGFR) in the EKFC cystatin C cohort of children (n = 2,293) and adults (n = 7,727). Rescaling was obtained by dividing each biomarker by a Q-value, representing the population-specific median biomarker level among healthy individuals. Validation included median bias/precision/accuracy (percent estimates within ±30% of mGFR, P₃₀). Performance was compared with the EKFC-equation (EKFC_Cys), the CAPA cystatin C equation, the corresponding equations based on rescaled creatinine (r-LMR_Cr and EKFC_Cr) and the arithmetic mean of r-LMR_Cr and CAPA (r-LMR_Cr+CAPA), r-LMR_Cr and r-LMR_Cys (r-LMR_Mean), and EKFC_Cr and EKFC_Cys (EKFC_Mean). The overall P₃₀ of r-LMR_Cys in adults was 86.2% (95% CI 85.4%-86.9%), which was 6.6 percentage points (pp; 95% CI 5.8-7.4 pp) higher than for CAPA and similar to r-LMR_Cr (P₃₀ 87.4%, 95% CI 86.6%-88.1%). r-LMR_Cys and EKFC_Cys exhibited similar performance both overall and across subgroups of age, sex, GFR and BMI and in children. All three arithmetic mean equations had similar P₃₀-accuracy and generally performed better than the corresponding single-marker equations. Our results show that the Lund-Malmö GFR equation can be adapted for use with rescaled cystatin C with performance that is similar to the best-performing equations based on rescaled creatinine. The generality of the applied biomarker rescaling principle implies that the future demand for population- and biomarker-specific GFR estimating equations can be expected to decrease substantially.

Background: The development of clinical guidelines aimed at GPs is a key strategy to improving the management of chronic kidney disease (CKD). In 2019, the first CKD guideline aimed specifically at GPs practicing in Germany was published by the German College of General Practitioners and Family Physicians (DEGAM.) Aims: The aim of this study is to identify the barriers and enablers for the implementation of this guideline. The results of this project, together with quantitative evaluation against quality indicators for CKD in primary care will inform an update to the guideline. Methods: We performed 17 semi-structured interviews with GPs practicing in Berlin and Brandenburg. Transcripts were analysed using qualitative content analysis as described by Mayring. Results: We found that the perception of low clinical priority of CKD compared to other chronic diseases, opportunity cost of using guidelines, as well as poor patient understanding were significant barriers. GPs expressed that improved graphic design or integration of guideline recommendations in clinical decision support systems were enabling factors. Clinical problems concerning CKD were mostly solved by recourse to informal communication with specialists. GPs reported that they rarely consulted CKD guidelines as an aide to clinical decision making. Conclusion: The most significant barrier to use was that guidelines were not used as step-by-step decision aide in consultations with patients. Our analysis suggests that informal contact between primary and secondary care is significant conduit for evidence-based information on CKD in German primary care. Implementation projects should support the development of these relationships.