Diabetic nephropathy: early detection and therapeutic strategies

Currie, Gemma Elizabeth (2017) Diabetic nephropathy: early detection and therapeutic strategies. PhD thesis, University of Glasgow.

Abstract

The increasing global prevalence of diabetes poses a huge challenge to health services. The diagnosis is accompanied by a reduction in life expectancy, primarily due to cardiovascular disease which is inextricably linked to microvascular complications such as diabetic nephropathy (DN). Microalbuminuria (MA) is generally accepted as the primary clinical hallmark of DN, but despite widespread prescribing of agents blocking the renin angiotensin aldosterone system (RAAS) in these patients many continue to progress towards end-stage renal disease (ESRD). Clinical trials evaluating early initiation of RAAS blocking agents in untargeted, nonalbuminuric diabetic patients have shown potential for delaying disease progression but these effects are generally counterbalanced by side effects and adverse events associated with these therapies. Discovery of novel biomarkers to identify individuals at highest risk of DN who would stand to benefit most from targeted preclinical intervention would be a significant step towards implementation of personalised medicine in this population.

One technique which shows promise is proteomics, based on the concept of separation and quantification of peptides in a biological sample to produce a disease-specific pattern. A panel of 273 urinary peptides (CKD273) has been shown to have potential for identification of nonalbuminuric diabetic patients who are at risk of progression to overt DN. However, many such novel biomarkers are described in the literature and to date none have successfully made the transition from research studies to routine clinical practice. In order to be considered for clinical implementation novel biomarkers are required to be subject to a rigorous evaluation process. In brief there are several key steps beginning with proof-of-concept studies; progressing through validation in independent populations to demonstration of incremental value beyond the current guideline-endorsed tests; thereafter proof of clinical applicability in determining treatment strategies and cost-effectiveness are required. The work contained within this thesis is designed to address each of these aspects with regard to use of the CKD273 proteomic panel as a biomarker for early detection of DN.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: R Medicine > R Medicine (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Supervisor's Name: Delles, Professor Christian, Petrie, Professor John and Freel, Dr. Marie
• Date of Award: 2017
• Depositing User: Dr Gemma Currie
• Unique ID: glathesis:2017-8008
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 13 Mar 2017 12:11
• Last Modified: 11 Mar 2020 13:32
• URI: https://theses.gla.ac.uk/id/eprint/8008