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

Mulder, Skander; Hamidi, Habib; Kretzler, Matthias; Ju, Wenjun

doi:10.1111/dom.13416

Cited by 30 publications

(18 citation statements)

References 68 publications

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“…A systems biology approach, combining multiomics information, has been suggested as the way forward to better combine and understand information provided by the molecular biomarkers at different stages of disease as well as providing the platform for design of individualized treatment. Mulder et al . provide an in‐depth overview of an approach trying to integrate data from different candidate markers to be used for prediction of both risk and treatment response.…”

Section: Future Perspectivesmentioning

confidence: 99%

Urinary Proteomics and Precision Medicine for Chronic Kidney Disease: Current Status and Future Perspectives

Persson

Rossing

2019

Proteomics Clinical Apps

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Precision medicine is since long an ongoing refinement of classical medicine, integrating improved and more detailed pathophysiological understanding with rapid technological advances. In the heterogenous area of chronic kidney disease there seems to be a high potential for the improvement in treatment and prognosis for several causes, with new technologies under development, that are yet to be introduced in clinical practice. As in other medical disciplines, investigation of abundant peptide patterns (proteomics) has gained recent interest. Especially relevant for kidney disease, urinary proteomics may provide both improved diagnosis and, as reviewed here, also holds promise for personalized treatment in the future. So far, capillary electrophoresis coupled to mass spectrometry (CE-MS) is the most widely applied technique, and in addition to several cross-sectional and cohort studies, there is even an ongoing randomized controlled trial that will soon report on the concept used as a method of personalizing treatment. In addition, there is hope that urinary proteomics can turn into a "liquid biopsy," replacing the invasive diagnostic procedure. The next couple of years will provide more answers on the topic.

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Section: Future Perspectivesmentioning

confidence: 99%

Urinary Proteomics and Precision Medicine for Chronic Kidney Disease: Current Status and Future Perspectives

Persson

Rossing

2019

Proteomics Clinical Apps

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“…Likewise, not all DM patients with microalbuminuria progress to macroalbuminuria or ESRD (some patients even revert and the microalbuminuria disappears). Therefore, more broad-based approaches including systems biology and multiple omics are being applied to understanding DN pathological mechanisms today [17–19].…”

Section: Introductionmentioning

confidence: 99%

The analysis of risk factors for diabetic nephropathy progression and the construction of a prognostic database for chronic kidney diseases

et al. 2019

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Background Diabetic nephropathy (DN) affects about 40% of diabetes mellitus (DM) patients and is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) all over the world, especially in high- and middle-income countries. Most DN has been present for years before it is diagnosed. Currently, the treatment of DN is mainly to prevent or delay disease progression. Although many important molecules have been discovered in hypothesis-driven research over the past two decades, advances in DN management and new drug development have been very limited. Moreover, current animal/cell models could not replicate all the features of human DN, while the development of Epigenetics further demonstrates the complexity of the mechanism of DN progression. To capture the key pathways and molecules that actually affect DN progression from numerous published studies, we collected and analyzed human DN prognostic markers (independent risk factors for DN progression). Methods One hundred and fifty-one DN prognostic markers were collected manually by reading 2365 papers published between 01/01/2002 and 12/15/2018. One hundred and fifteen prognostic markers of other four common CKDs were also collected. GO and KEGG enrichment analysis was done using g:Profiler, and a relationship network was built based on the KEGG database. Tissue origin distribution was derived mainly from The Human Protein Atlas (HPA), and a database of these prognostic markers was constructed using PHP Version 5.5.15 and HTML5. Results Several pathways were significantly enriched corresponding to different end point events. It is shown that the TNF signaling pathway plays a role through the process of DN progression and adipocytokine signaling pathway is uniquely enriched in ESRD. Molecules, such as TNF, IL6, SOD2, etc. are very important for DN progression, among which, it seems that “AGER” plays a pivotal role in the mechanism. A database, dbPKD, was constructed containing all the collected prognostic markers. Conclusions This study developed a database for all prognostic markers of five common CKDs, offering some bioinformatics analyses of DN prognostic markers, and providing useful insights towards understanding the fundamental mechanism of human DN progression and for identifying new therapeutic targets. Electronic supplementary material The online version of this article (10.1186/s12967-019-2016-y) contains supplementary material, which is available to authorized users.

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“…Several studies in recent times have reported the discovery and validation of non-invasive biomarkers for predicting disease progression and response to treatment in DKD. [23,24] However, these studies need further validation for implementation in clinical practice. With various novel pharmacological agents such as baricitinib, a selectively Janus kinase 1 inhibitor; ruboxistaurin, a protein kinase c β inhibitor; pentoxyphylline, an anti-inflammatory and antifibrotic agent; currently under trial, [25] a miracle drug for Diabetic Kidney Disease is not far away.…”

Section: Discussionmentioning

confidence: 99%

Normoalbuminuric Diabetic Kidney Disease- Need for Renal Biopsy? An Autopsy Study on Western Indian Population

Paul

Gadgil

Padmanabhan

2020

Ann of Pathol and Lab Med

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Introduction: Persistent albuminuria and glomerular filtration rate are considered as the gold standard for the diagnosis of Diabetic Nephropathy (DN). Methods: In this autopsy study, we evaluated data from a cohort of 67 patients with Type 2 Diabetes Mellitus. We determined the histological prevalence of DN irrespective of the clinical manifestations of renal disease. Patients were stratified by proteinuria and estimated glomerular filtration rate(eGFR). The glomerular, interstitial and vascular lesions were scored as per the established histopathologic classification for DN. Results: 55 of the 67 patients had clinical as well as histological lesions consistent with DN. 12 patients had histological lesions of DN at autopsy but no clinical evidence of proteinuria, including microalbuminuria in their lifetime.4 of these patients had maintained eGFR. There was no difference in the glomerular lesions in patients with normoalbuminuria regardless of the eGFR. However,50% of the patients with low eGFR showed presence of interstitial fibrosis and tubular atrophy while no interstitial lesions were noted in patients with normoalbuminuria and maintained eGFR. Significant amount of arteriosclerosis was noted in the normoalbuminuric low eGFR patients. Haematuria was significantly associated with proteinuric low GFR patients. Conclusion: Histological evidence of DN may be seen even in the absence of clinical manifestations, suggesting that, in diabetic kidneys some amount of glomerular and tubulointerstitial damage has already occurred before the onset of proteinuria. Hence, there is a need for routine kidney biopsies in diabetic patients with normoalbuminuria. This will help in the timely diagnosis and appropriate management in the early stages of DN.

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

Cited by 30 publications

References 68 publications

Urinary Proteomics and Precision Medicine for Chronic Kidney Disease: Current Status and Future Perspectives

Urinary Proteomics and Precision Medicine for Chronic Kidney Disease: Current Status and Future Perspectives

The analysis of risk factors for diabetic nephropathy progression and the construction of a prognostic database for chronic kidney diseases

Normoalbuminuric Diabetic Kidney Disease- Need for Renal Biopsy? An Autopsy Study on Western Indian Population

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