Cardiovascular (CV), renal, and metabolic (CRM) conditions are interconnected. Worsening of one condition predicts an increased risk of progression of the others, underscoring the importance of early, multifactorial intervention. In an interview with MIMS Doctor, Professor Melanie Davies from the University of Leicester, UK, called for an integrated approach to CKM care, highlighting current evidence and international guideline updates relevant to clinical practice.
Interconnectedness of CRM conditions: See one, look for others
Diabetes mellitus, kidney diseases, ischaemic heart disease, and stroke are among the top 10 causes of death worldwide. [www.who.int/news-room/ fact-sheets/detail/the-top-10-causes-of-death]
CRM conditions, such as CV disease (CVD), heart failure (HF), type 2 diabetes (T2D), and chronic kidney disease (CKD), frequently coexist due to shared risk factors. [Cardiovasc Diabetol 2023;22:195]
“In the clinical setting, however, specialists tend to focus on their area of expertise, and primary care clinicians may not have access to a comprehensive treatment plan that spans the CRM spectrum,” remarked Davies. “Therefore, patients may not receive the optimal care they require as a whole person. A comprehensive patient-centred approach is needed to improve outcomes.”
“If you see one [CRM condition], look for the others — prevent or treat accordingly. Any one of these interrelated CRM conditions can amplify the risk of and accelerate progression of others,” emphasized Davies. “Early multifactorial intervention is the best way to protect patients by reducing the amplifying risks associated with interrelated CRM conditions.”
Low awareness of CKD in T2D
As exemplified by the case of Mrs X below, patients with an earlier diagnosis of T2D may develop CKD, as evidenced by either increased albuminuria or decreased estimated glomerular filtration rate (eGFR).
However, according to a multicentre, observational study conducted in the primary care setting in the US, 52.9 percent of patients with T2D were not tested for urine albumin-to-creatinine ratio (UACR), and 15.2 percent were not tested for eGFR. Only 6.5 percent of patients with CKD received a diagnosis, while 47.6 percent remained undiagnosed. [PLoS One 2014;9:e110535]
Notably, albuminuria often precedes eGFR decline. UACR testing is thus critical for early diagnosis of CKD. “UACR testing is now easier to perform using a spot urine sample, preferably an early morning sample. Additionally, eGFR can be measured from blood tests,” said Davies. “Yearly CKD screening with these two relatively simple, widely available tests is recommended for patients with T2D.” [Pediatr Nephrol 2015;30:65-74; Clin J Am Soc Nephrol 2017;12:2032-2045]
Early cardiorenal protection with SGLT2i
Along with lifestyle modifications to address potential risk factors, international guidelines recommended sodium-glucose cotransporter 2 inhibitors (SGLT2i; eg, empagliflozin) as first-line treatment across a spectrum of CRM conditions, including T2D with high CV risk, HF regardless of left ventricular ejection fraction, and CKD. [Circulation 2022;145:e895-e1032; Kidney Int 2024;105:S117-S314; Diabetes Care 2022;45:2753-2786]
“CV death is the leading cause of death in CKD and T2D. In CKD, the risk of CV death is higher than that of progressing to end-stage kidney disease,” said Davies.
“Unlike other CKD trials of SGLT2i, the EMPA-KIDNEY trial of empagliflozin included patients with or without diabetes, and those with normal to mildly increased albuminuria [A1; UACR <3 mg/mmol or <30 mg/g],” she pointed out. Despite the broad inclusion criteria, empagliflozin significantly reduced the risk of kidney disease progression or CV death by 28 percent vs placebo (hazard ratio [HR], 0.72; 95 percent confidence interval [CI], 0.64–0.82; p<0.001), with a number needed to treat of 28. [N Engl J Med 2023;388:117-127; Davies M. EMW 2025]
After an initial dip of eGFR in the first 2 months, empagliflozin halved mean eGFR decline vs placebo. (Figure 1A) Of note, the reduction in eGFR decline with empagliflozin was observed across the UACR spectrum. (Figure 1B) [N Engl J Med 2023;388:117-127]
Empagliflozin also significantly reduced the risk of all-cause hospitalization — both first and recurrent — by 14 percent vs placebo (HR, 0.86; 95 percent CI, 0.78–0.95; p=0.003). “This benefit was not limited to hospitalizations due to CKD or CVD,” Davies highlighted. [N Engl J Med 2023;388:117-127]
Early initiation of empagliflozin at an eGFR of 65 mL/min/1.73 m2 could potentially delay kidney failure by 19.5 years vs placebo and avoid >3,000 haemodialysis sessions per patient. When initiated at an eGFR of 20 mL/min/1.73 m2, empagliflozin is estimated to delay kidney failure by 1.9 years vs placebo and avoid about 300 haemodialysis sessions per patient. “Starting empagliflozin at an eGFR of 20 mL/min/1.73 m2 is still not too late, but we get more benefits when it is initiated early,” Davies emphasized. [Clin Kidney J 2023;16:1187-1198]
Call to action
CRM care requires an early, holistic approach, which not only improves risk factors in the short term, but also reduces the long-term risk of cardiorenal complications by integrating care across specialties and promoting comprehensive, multifactorial interventions. Owing to the cardiorenal benefits, SGLT2 inhibitors is the first-line treatment across a spectrum of CRM conditions. [Front Cardiovasc Med 2025;12:1583702; Front Endocrinol (Lausanne) 2023;14:1111984]
