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  • 1
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2023-03-29)
    Abstract: Chronic kidney disease (CKD) is a common comorbidity in people with diabetes mellitus, and a key risk factor for further life-threatening conditions such as cardiovascular disease. The early prediction of progression of CKD therefore is an important clinical goal, but remains difficult due to the multifaceted nature of the condition. We validated a set of established protein biomarkers for the prediction of trajectories of estimated glomerular filtration rate (eGFR) in people with moderately advanced chronic kidney disease and diabetes mellitus. Our aim was to discern which biomarkers associate with baseline eGFR or are important for the prediction of the future eGFR trajectory. Methods We used Bayesian linear mixed models with weakly informative and shrinkage priors for clinical predictors (n = 12) and protein biomarkers (n = 19) to model eGFR trajectories in a retrospective cohort study of people with diabetes mellitus (n = 838) from the nationwide German Chronic Kidney Disease study. We used baseline eGFR to update the models’ predictions, thereby assessing the importance of the predictors and improving predictive accuracy computed using repeated cross-validation. Results The model combining clinical and protein predictors had higher predictive performance than a clinical only model, with an $$R^{2}$$ R 2 of 0.44 (95% credible interval 0.37–0.50) before, and 0.59 (95% credible interval 0.51–0.65) after updating by baseline eGFR, respectively. Only few predictors were sufficient to obtain comparable performance to the main model, with markers such as Tumor Necrosis Factor Receptor 1 and Receptor for Advanced Glycation Endproducts being associated with baseline eGFR, while Kidney Injury Molecule 1 and urine albumin-creatinine-ratio were predictive for future eGFR decline. Conclusions Protein biomarkers only modestly improve predictive accuracy compared to clinical predictors alone. The different protein markers serve different roles for the prediction of longitudinal eGFR trajectories potentially reflecting their role in the disease pathway.
    Type of Medium: Online Resource
    ISSN: 1475-2840
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2093769-6
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  • 2
    In: BMC Nephrology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2020-12)
    Abstract: Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages. The iBEAt study of the BEAt-DKD project aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim) and whether they have potential as prognostic biomarkers in DKD (secondary aim). Methods iBEAt is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR ≥30 ml/min/1.73m 2 . At baseline, blood and urine will be collected, clinical examinations will be performed, and medical history will be obtained. These assessments will be repeated annually for 3 years. At baseline each participant will also undergo quantitative renal MRI and US with central processing of MRI images. Biological samples will be stored in a central laboratory for biomarker and validation studies, and data in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers improve the prediction of DKD progression. Ancillary substudies will: (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow measurements against H 2 O 15 positron-emission tomography (PET); (3) validate methods for (semi-)automated processing of renal MRI; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether glycocalyx and microvascular measures are associated with imaging biomarkers and eGFR decline; (6) explore whether the findings in T2D can be extrapolated to type 1 diabetes. Discussion iBEAt is the largest DKD imaging study to date and will provide valuable insights into the progression and heterogeneity of DKD. The results may contribute to a more personalised approach to DKD management in patients with T2D. Trial registration Clinicaltrials.gov ( NCT03716401 ).
    Type of Medium: Online Resource
    ISSN: 1471-2369
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041348-8
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  • 3
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-5-4)
    Abstract: Aim: This study aimed to identify from different stakeholders the benefits and obstacles of implementing precision medicine in diabetic kidney disease (DKD) and to build consensus about a way forward in order to treat, prevent, or even reverse this disease. Methods: As part of an ongoing effort of moving implementation of precision medicine in DKD forward, a two-day consensus-building meeting was organized with different stakeholders involved in drug development and patient care in DKD, including patients, patient representatives, pharmaceutical industry, regulatory agencies representatives, health technology assessors, healthcare professionals, basic scientists, and clinical academic researchers. The meeting consisted of plenary presentations and discussions, and small group break-out sessions. Discussion topics were based on a symposium, focus groups and literature search. Benefits, obstacles and potential solutions toward implementing precision medicine were discussed. Results from the break-out sessions were presented in plenary and formed the basis of a broad consensus discussion to reach final conclusions. Throughout the meeting, participants answered several statement and open-ended questions on their mobile device, using a real-time online survey tool. Answers to the statement questions were analyzed descriptively. Results of the open-ended survey questions, the break-out sessions and the consensus discussion were analyzed qualitatively. Results and conclusion: Seventy-one participants from 26 countries attended the consensus-building meeting in Amsterdam, April 2019. During the opening plenary on the first day, the participants agreed with the statement that precision medicine is the way forward in DKD ( n = 57, median 90, IQR [75–100]). Lack of efficient tools for implementation in practice and generating robust data were identified as significant obstacles. The identified benefits, e.g., improvement of the benefit-risk ratio of treatment, offer substantive incentives to find solutions for the identified obstacles. Earlier and increased multi-stakeholder collaboration and specific training may provide solutions to alter clinical and regulatory guidelines that lie at the basis of both obstacles and solutions. At the end of the second day, the opinion of the participants toward precision medicine in DKD was somewhat more nuanced ( n = 45, median 83, IQR [70–92]) and they concluded that precision medicine is an important way forward in improving the treatment of patients with DKD.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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