Dipeptidyl peptidase-4 inhibition in chronic kidney disease and potential for protection against diabetes-related renal injury.
Type 2 diabetes mellitus (T2DM) is associated with a high risk of chronic kidney disease (CKD). About 20% of patients with T2DM have CKD of stage ≥ 3; up to 40% have some degree of CKD. Beyond targeting all renal risk factors together, renin-angiotensin-aldosterone system blockers are to date the only effective mainstay for the treatment of diabetic kidney disease (DKD). Indeed, several potentially nephroprotective agents have been in use, which have been unsuccessful. Some glucose-lowering agents, including dipeptidyl peptidase-4 inhibitors (DPP-4i), have shown promising results. Here, we discuss the evidence that glucose lowering with DPP-4i may be an option for protecting against diabetes-related renal injury.



A comprehensive search was performed of the literature using the terms "alogliptin," "linagliptin," "saxagliptin," "sitagliptin," and "vildagliptin" for original articles and reviews addressing this topic. DPP-4i are an effective, well-tolerated treatment option for T2DM with any degree of renal impairment. Preclinical observations and clinical studies suggest that DPP-4i might also be a promising strategy for the treatment of DKD. The available data are in favor of saxagliptin and linagliptin, but the consistency of results points to the possible nephroprotective effect of DPP-4i. This property appears to be independent of glucose lowering and can potentially complement other therapies that preserve renal function. Larger prospective clinical trials are ongoing, which might strengthen these hypothesis-generating findings.



The improvement in albuminuria associated with DPP-4i suggests that these agents may provide renal benefits beyond their glucose-lowering effects, thus offering direct protection from DKD. These promising results must be interpreted with caution and need to be confirmed in forthcoming studies.
Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. Electronic address: pgiuse@immr.med.unipi.it.
G
G
Penno
Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
M
M
Garofolo
Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
S
S
Del Prato
D000419:Albuminuria / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D012307:Risk Factors; D016896:Treatment Outcome
D015415:Biomarkers; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
Albuminuria; Chronic kidney disease; Diabetic nephropathy; Dipeptidyl peptidase-4 inhibitor; Estimated glomerular filtration rate; Type 2 diabetes mellitus