The therapeutic potential of C-peptide in kidney disease: a protocol for a systematic review and meta-analysis

BACKGROUND: Kidney disease remains a major cause of morbidity and mortality in Canada and worldwide. New medical treatments are needed to reduce the progression of kidney disease to improve patient outcomes. C-peptide is normally released by pancreatic beta-cells along with insulin in healthy individuals, and has been shown to have intrinsic biological activity and to potentially be renoprotective. The effect of exogenous C-peptide on kidney structure and function, and the role of C-peptide in the treatment of kidney disease have not yet been fully elucidated. METHODS/DESIGN: We will conduct a systematic review of the literature in human clinical trials and mammalian experimental models to ascertain the current evidence for the role of C-peptide as a potential therapeutic agent for the treatment of kidney disease. We aim to identify whether exogenously delivered C-peptide has an effect on clinically relevant outcomes such as glomerular filtration rate, proteinuria, kidney histology, requirement of renal replacement therapy, and mortality. We will search MEDLINE, EMBASE, and the Cochrane Central Databases for human or animal studies in which C-peptide was administered and renal endpoints were subsequently measured. Study quality will be assessed using the Cochrane Collaboration’s tool for assessing risk of bias. If appropriate, a meta-analysis will be performed as per standard techniques. DISCUSSION: The results of this study will determine the potential role of C-peptide as a therapeutic intervention for patients with kidney disease and will help guide subsequent clinical trials. The study may also provide insight into which patients or disease states are likely to benefit the most from C-peptide. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014007472