Predicting albuminuria response to spironolactone treatment with urinary proteomics in patients with type 2 diabetes and hypertension

Lindhardt, Morten; Persson, Frederik; Oxlund, Christina Stolzenburg; Jacobsen, I.A.; Zürbig, Petra; Mischak, Harald; Rossing, Peter; Heerspink, Hiddo J L

doi:10.1093/ndt/gfw406

Cited by 34 publications

(38 citation statements)

References 39 publications

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“…It has been applied multiple times for the diagnosis of CKD and even other diseases since its initial publication. CKD273 was recently used to predict mortality in individuals with type 2 diabetes and their response to albuminuria treatment . Other examples for the application of multi‐dimensional marker were published , and the application of CE‐MS in urinary peptidomics for the diagnosis of CKD was reviewed recently .…”

Section: Analytical Applicationsmentioning

confidence: 99%

Recent advances in capillary electrophoresis‐mass spectrometry: Instrumentation, methodology and applications

et al. 2018

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Capillary electrophoresis (CE) offers fast and high‐resolution separation of charged analytes from small injection volumes. Coupled to mass spectrometry (MS), it represents a powerful analytical technique providing (exact) mass information and enables molecular characterization based on fragmentation. Although hyphenation of CE and MS is not straightforward, much emphasis has been placed on enabling efficient ionization and user‐friendly coupling. Though several interfaces are now commercially available, research on more efficient and robust interfacing with nano‐electrospray ionization (ESI), matrix‐assisted laser desorption/ionization (MALDI) and inductively coupled plasma mass spectrometry (ICP) continues with considerable results. At the same time, CE‐MS has been used in many fields, predominantly for the analysis of proteins, peptides and metabolites. This review belongs to a series of regularly published articles, summarizing 248 articles covering the time between June 2016 and May 2018. Latest developments on hyphenation of CE with MS as well as instrumental developments such as two‐dimensional separation systems with MS detection are mentioned. Furthermore, applications of various CE‐modes including capillary zone electrophoresis (CZE), nonaqueous capillary electrophoresis (NACE), capillary gel electrophoresis (CGE) and capillary isoelectric focusing (CIEF) coupled to MS in biological, pharmaceutical and environmental research are summarized.

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Section: Analytical Applicationsmentioning

confidence: 99%

Recent advances in capillary electrophoresis‐mass spectrometry: Instrumentation, methodology and applications

et al. 2018

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“…In addition, one collagen alpha‐1 (I) chain (Figure , peptide with #) peptide was also identified in another study dealing with the prediction of albuminuria response to spironolactone treatment with urinary proteomics in patients with type 2 diabetes and hypertension . In this study, the patients were also stratified in responders and nonresponders.…”

Section: Discussionmentioning

confidence: 78%

“…Using proteomic analysis, previous studies were able to show the effects of different treatments on CKD . Also in this study, we analyzed urine samples from patients, who suffer from resistant HTN with potential complications based on CKD.…”

Section: Discussionmentioning

confidence: 99%

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Kidney protective effects of baroreflex activation therapy in patients with resistant hypertension

Wallbach

Zürbig

Dihazi

et al. 2018

J of Clinical Hypertension

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Baroreflex activation therapy (BAT) is approved for the treatment of resistant hypertension. In addition to blood pressure (BP) reduction, pilot studies suggested several organoprotective effects of BAT. Thirty-two patients with resistant hypertension were prospectively treated with BAT. Besides office BP and 24-hour ambulatory BP (ABP) measurements, detection of a urinary proteome-based classifier (CKD273), which has been shown to predict chronic kidney disease (CKD) progression, was carried out at baseline and after 6 months of BAT. Office BP significantly decreased from 170 ± 25/90 ± 18 to 149 ± 29/82 ± 18 mm Hg. Analysis of CKD273 score and eGFR with CKD-EPI equation at baseline revealed strong correlation (r = 0.568, P < 0.001). After 6 months of BAT, there was no significant change in CKD273 score (-0.061 [95% CI: -0.262 to 0.140], P = 0.601). However, by stratification of the data regarding ABP response, there was a statistically significant (P = 0.0113) reduction in the CKD273 score from a mean of 0.161 [95% CI: -0.093 to 0.414] to -0.346 [95% CI: -0.632 to -0.060] after BAT in patients with systolic ABP decrease of ≥5 mm Hg. These data emphasized potential nephroprotective effects of BAT in patients with sufficient BP response.

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“…To improve DKD patient care, an individualized molecular‐based treatment algorithm is needed to ensure that treatment recommendations are based on an individual's molecular disease process. Systems biology approaches can comprehensively evaluate the molecular mechanisms driving the diverse responses to therapies as well as identify biomarkers that are able to predict the response to a therapy before treatment is initiated (predictive marker) or select individuals more likely to benefit from subsequent clinical outcomes after a few weeks' of therapy (dynamic marker) . An exemplary study in developing a predictive response to therapy was carried out by Lindhardt et al in patients with type 2 diabetes and therapy‐resistant hypertension .…”

Section: The Use Of Systems Biology Approach To Predict Patients' Resmentioning

confidence: 99%

An integrative systems biology approach for precision medicine in diabetic kidney disease

Mulder

Hamidi

Kretzler

et al. 2018

Diabetes Obesity Metabolism

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Current therapeutic approaches are ineffective in many patients with established Diabetic Kidney Disease (DKD) disease, an epidemic affecting one in three patients with diabetes. Early identification of patients at high risk for progression and individualizing therapies have the potential to mitigate kidney complications due to diabetes. To achieve this, a better understanding of the complex pathophysiology of DKD is needed. A system biology approach integrating large scale omic data is well suited to unravel the molecular mechanisms driving DKD and may offer new perspectives how to personalize therapy. Recent studies indeed demonstrate that integrating genome scale data sets generated from prospectively designed clinical cohort studies with model systems using innovative bioinformatics analysis revealed critical molecular pathways in DKD and led to the development of candidate prognostic molecular biomarkers. This review seeks to provide an overview of the recent progress in the application of the integrative systems biology approaches specifically in the field of molecular biomarkers for DKD. We will mainly focus the discussion on how to use integrative system biology approach to firstly identify patients at high risk of progression, and secondly to identify patients who may or may not respond to treatment. Challenges and opportunities in applying precision medicine in DKD will also be discussed.

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Predicting albuminuria response to spironolactone treatment with urinary proteomics in patients with type 2 diabetes and hypertension

Cited by 34 publications

References 39 publications

Recent advances in capillary electrophoresis‐mass spectrometry: Instrumentation, methodology and applications

Recent advances in capillary electrophoresis‐mass spectrometry: Instrumentation, methodology and applications

Kidney protective effects of baroreflex activation therapy in patients with resistant hypertension

An integrative systems biology approach for precision medicine in diabetic kidney disease

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