Effects of glycaemic management on diabetic kidney disease

Abstract

Hyperglycaemia contributes to the onset and progression of diabetic kidney disease (DKD). Observational studies have not consistently demonstrated a glucose threshold, in terms of HbA1c levels, for the onset of DKD. Tight glucose control has clearly been shown to reduce the incidence of micro- or macroalbuminuria. However, evidence is now also emerging to suggest that intensive glucose control can slow glomerular filtration rate loss and possibly progression to end stage kidney disease. Achieving tight glucose control needs to be balanced against the increasing appreciation that glucose targets for the prevention of diabetes related complications need be individualised for each patient. Recently, empagliflozin which is an oral glucose lowering agent of the sodium glucose cotransporter-2 inhibitor class has been shown to have renal protective effects. However, the magnitude of empagliflozin's reno-protective properties are over and above that expected from its glucose lowering effects and most likely largely result from mechanisms involving alterations in intra-renal haemodynamics. Liraglutide and semaglutide, both injectable glucose lowering agents which are analogues of human glucagon like peptide-1 have also been shown to reduce progression to macroalbuminuria through mechanisms that remain to be fully elucidated. Here we review the evidence from observational and interventional studies that link good glucose control with improved renal outcomes. We also briefly review the potential reno-protective effects of newer glucose lowering agents.

Keywords: Albuminuria; Chronic kidney disease; Diabetes; Diabetic nephropathy; Empagliflozin; Glomerular filtration rate; Glucose control; Liraglutide; Semaglutide.

Figure 1

Renal outcomes in the trial Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome. ¹Four-point renal outcome = progression to macroalbuminuria, doubling of serum creatinine, initiation of RRT or death from renal disease; ²Macroalbuminuria = albumin to creatinine ratio > 30 mg/mmol; ³Plus eGFR < 45 mL/min per 1.73 m². eGFR: Estimated glomerular filtration rate; HR: Hazard ratio; NS: Non statistically significant; RRT: Renal replacement therapy.

Figure 2

Cardiovascular outcomes in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome (A) and cardiovascular safety trial of empagliflozin (B) studies according to estimated glomerular filtration rate. MACE: Major adverse cardiovascular event; eGFR: Estimated glomerular filtration rate; HR: Hazard ratio.

Figure 3

Renal outcomes in the cardiovascular safety trial of empagliflozin study. ¹Four-point renal outcome = progression to macroalbuminuria plus three-point renal outcome; ²Three-point renal outcome = doubling of serum creatinine, initiation of RRT or death from renal disease; ³Macroalbuminuria = albumin to creatinine ratio > 30 mg/mmol; ⁴Plus eGFR < 45 mL/min per 1.73 m². HR: Hazard ratio; eGFR: Estimated glomerular filtration rate; CV: Cardiovascular; RRT: Renal replacement therapy.