Diabetic kidney disease treatment: new perspectives

Abstract

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease worldwide, as the obesity epidemic and the burden of diabetes continue to rise globally. In general, guideline management of patients with DKD recommends lifestyle modifications, blood pressure and glycemic control, and dyslipidemia treatment along with other cardiovascular disease risk reduction measures. The inhibition of the renin-angiotensin system (RAS) using an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker remains the foundational therapy for DKD. In type 2 diabetes (T2D), significant advances in therapeutics, including the sodium-glucose cotransporter-2 inhibitors (SGLT2i), the glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor agonist (MRA) finerenone, have dramatically expanded the armamentarium for treating DKD and its cardiovascular complications. Initiating, optimizing, and sustaining evidence-based pharmacological therapy using a therapeutic combination of RAS inhibitor + SGLT2i/GLP-1 RA + nonsteroidal MRA + statin is likely to significantly improve outcomes for T2D with DKD. Research into potential novel therapeutic targets for DKD remains particularly active and brings much anticipation and optimism to this field.

Keywords: Chronic kidney diseases; Diabetic kidney disease; End-stage kidney disease; Glucagon-like peptide-1 receptor; Mineralocorticoid receptor antagonists; Renin-angiotensin-system; Sodium-glucose transporter 2 inhibitors.

Figure 1.. Multidisciplinary treatment algorithm for patients with type 2 diabetes and diabetic kidney disease.

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body-mass index; BP, blood pressure; CVD, cardiovascular disease; DPP4, dipeptidyl peptidase-4; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HbA1c, glycated hemoglobin; MRA, mineralocorticoid receptor antagonist; RAAS, renin-angiotensin-aldosterone system; SGLT2i, sodium-glucose cotransporter 2 inhibitor; T2D, type 2 diabetes; UAE, urine albumin excretion. ^aSome SGLT2i can be started from an eGFR of 25 mL/min/1.73 m² (e.g., dapagliflozin) or continued if already on treatment with eGFR of <30 mL/min/1.73 m² until patients reach end-stage kidney disease (e.g., canagliflozin) for cardiovascular-related risk reduction. ^bInsulin may be used in selected patients who present with severe hyperglycemia or otherwise are not candidates for oral agents alone. ^cIndividualized consideration is recommended for setting BP and HbA1c targets, balancing potential benefits and harms from intensive BP and glycemic control.