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Insulin Resistance Associated with Clinical Manifestations of Diabetic Kidney Disease (Glomerular Hyperfiltration, Albuminuria, and Kidney Function Decline)

Author(s):

María M. Adeva-Andany*, Carlos Fernández-Fernández, Raquel Funcasta-Calderón, Eva Ameneiros-Rodríguez, Lucía Adeva-Contreras and Elvira Castro-Quintela  

Abstract:


Clinical features of diabetic kidney disease include glomerular hyperfiltration, albuminuria, and kidney function decline towards End-Stage Kidney Disease (ESKD). There are presently neither specific markers of kidney involvement in patients with diabetes nor strong predictors of rapid progression to ESKD. Serum-creatinine-based equations used to estimate glomerular filtration rate are notoriously unreliable in patients with diabetes. Early kidney function decline, reduced glomerular filtration rate, and proteinuria contribute to identifying diabetic patients at higher risk for rapid kidney function decline. Unlike proteinuria, the elevation of urinary albumin excretion in the range of microalbuminuria is frequently transient in patients with diabetes and does not always predict progression towards ESKD. Although the rate of progression of kidney function decline is usually accelerated in the presence of proteinuria, histological lesions of diabetes and ESKD may occur with normal urinary albumin excretion. No substantial reduction in the rate of ESKD associated with diabetes has been observed during the last decades despite intensified glycemic control and reno-protective strategies, indicating that existing therapies do not target underlying pathogenic mechanisms of kidney function decline. Very long-term effects of sodium-glucose transporters-2 inhibitors and glucagon-like peptide-1 analogs remain to be defined. In patients with diabetes, glucagon secretion is typically elevated and induces insulin resistance. Insulin resistance is consistently and strongly associated with clinical manifestations of diabetic kidney disease, suggesting that reduced insulin sensitivity participates in the pathogenesis of the disease and may represent a therapeutic objective. Amelioration of insulin sensitivity in patients with diabetes is associated with cardioprotective and kidney-protective effects.

Keywords:

Glomerular hyperfiltration, albuminuria, chronic kidney disease, glucagon, glomerular filtration rate, metabolic syndrome, hypertension, serum triglycerides

Affiliation:

Nephrology Division Internal Medicine Department Hospital General Juan Cardona c/ Pardo Bazán s/n 15406 Ferrol, Nephrology Division Internal Medicine Department Hospital General Juan Cardona c/ Pardo Bazán s/n 15406 Ferrol, Nephrology Division Internal Medicine Department Hospital General Juan Cardona c/ Pardo Bazán s/n 15406 Ferrol, Nephrology Division Internal Medicine Department Hospital General Juan Cardona c/ Pardo Bazán s/n 15406 Ferrol, University of Santiago de Compostela Santiago de Compostela La Coruña, Nephrology Division Internal Medicine Department Hospital General Juan Cardona c/ Pardo Bazán s/n 15406 Ferrol



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