title: C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis.
abstract: C-peptide has intrinsic biological activity and may be renoprotective. We conducted a systematic review to determine whether C-peptide had a beneficial effect on renal outcomes. MEDLINE, EMBASE, and the Cochrane Central Databases were searched for human and animal studies in which C-peptide was administered and renal endpoints were subsequently measured. We identified 4 human trials involving 74 patients as well as 18 animal studies involving 35 separate experiments with a total of 641 animals. In humans, the renal effects of exogenously delivered C-peptide were only studied in type 1 diabetics with either normal renal function or incipient nephropathy. Pooled analysis showed no difference in GFR (mean difference, -1.36 mL/min/1.73 m2, p = 0.72) in patients receiving C-peptide compared to a control group, but two studies reported a reduction in glomerular hyperfiltration (p<0.05). Reduction in albuminuria was also reported in the C-peptide group (p<0.05). In diabetic rodent models, C-peptide led to a reduction in GFR (mean difference, -0.62 mL/min, p<0.00001) reflecting a partial reduction in glomerular hyperfiltration. C-peptide also reduced proteinuria (mean difference, -186.25 mg/day, p = 0.05), glomerular volume (p<0.00001), and mesangial matrix area (p<0.00001) in diabetic animals without affecting blood pressure or plasma glucose. Most studies were relatively short-term in duration, ranging from 1 hour to 3 months. Human studies of sufficient sample size and duration are needed to determine if the beneficial effects of C-peptide seen in animal models translate into improved long-term clinical outcomes for patients with chronic kidney disease. (PROSPERO CRD42014007472).
authors.affiliation: Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: Shaw
authors.affiliation: Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Division of Nephrology, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Partha
authors.initials: P
authors.lastname: Shetty
authors.affiliation: Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Division of Nephrology, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Burns
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Dean
authors.initials: D
authors.lastname: Fergusson
authors.affiliation: Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Division of Nephrology, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Greg A
authors.initials: GA
authors.lastname: Knoll
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D002096:C-Peptide / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D002096:C-Peptide