Treatment strategies to reduce cardiovascular risk in persons with chronic kidney disease and Type 2 diabetes

Abstract

Chronic kidney disease (CKD) is a prevalent and progressive condition associated with significant mortality and morbidity. Diabetes is a common cause of CKD, and both diabetes and CKD increase the risk of cardiovascular disease (CVD), the leading cause of death in individuals with CKD. This review will discuss the importance of early detection of CKD and prompt pharmacological intervention to slow CKD progression and delay the development of CVD for improving outcomes. Early CKD is often asymptomatic, and diagnosis usually requires laboratory testing. The combination of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) measurements is used to diagnose and determine CKD severity. Guidelines recommend at least annual screening for CKD in at-risk individuals. While eGFR testing rates are consistently high, rates of UACR testing remain low. This results in underdiagnosis and undertreatment of CKD, leaving many individuals at risk of CKD progression and CVD. UACR testing is an actionable component of the CKD definition. A four-pillar treatment approach for slowing the progression of diabetic kidney disease is suggested, comprising a renin-angiotensin-system (RAS) inhibitor, a sodium-glucose cotransporter 2 inhibitor, a glucagon-like peptide 1 receptor agonist, and the nonsteroidal mineralocorticoid receptor antagonist finerenone. The combination of these agents provides a greater cardiorenal risk reduction compared with RAS inhibitors alone. Early detection of CKD and prompt intervention with guideline-directed medical therapy are crucial for reducing CVD risk in individuals with CKD and diabetes. Evidence from ongoing studies will advance our understanding of optimal therapy in this population.

Keywords: Type 2 diabetes; cardiovascular risk factors; kidney disease.

Fig. 1

(a) Prognosis and (b) severity of CKD by GFR and albuminuria categories ^†No CKD if there is no other evidence of kidney damage. A, albuminuria category; CKD, chronic kidney disease; CVD, cardiovascular disease; GFR, glomerular filtration rate; UACR, urine albumin‐to‐creatinine ratio. Source: Panel A adapted from KDIGO 2024 [4] under the terms of the CC BY‐NC‐ND license.

Fig. 2

All‐cause mortality rates according to UACR by age category. UACR, urine albumin‐to‐creatinine ratio. Source: Conceptual image derived from Hallan et al. [30].

Fig. 3

Screening algorithm for diagnosis and staging of CKD in adults. ^†Markers of kidney damage other than albuminuria may also be used to diagnose CKD, but UACR and eGFR are still required to determine stage and estimate risk of progression. The orange boxes indicate actions in people at risk for CKD and in whom testing should be performed. The blue boxes indicate testing steps. The green boxes indicate the identification of CKD and its stages and the initiation of treatment. The pink box indicates the identification of AKD/AKI. AKD, acute kidney disease; AKI, acute kidney injury; CKD, chronic kidney disease; eGFRcr‐cys, creatinine and cystatin C–based estimated glomerular filtration rate; eGFR, estimated glomerular filtration rate; T2D, Type 2 diabetes; UACR, urine albumin‐to‐creatinine ratio. Source: Adapted from KDIGO 2024 [4] under the terms of the CC BY‐NC‐ND license.

Fig. 4

Pillars of therapy for slowing CKD progression in T2D. CKD, chronic kidney disease; GLP‐1 RA, glucagon‐like peptide 1 receptor agonist; MRA, mineralocorticoid receptor antagonist; RAS, renin–angiotensin–system; SLGT2, sodium–glucose cotransporter 2; T2D, Type 2 diabetes.