PREDICTORS OF CARDIOVASCULAR-KIDNEY-METABOLIC SYNDROME PROGRESSION AND GAPS IN CARE AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE

Cardiovascular-kidney-metabolic syndrome (CKM) is the bidirectional relationship between cardiovascular disease (CVD), chronic kidney disease (CKD), diabetes, and obesity. CKM stage 2 includes metabolic risk factors of CVD, CKM stage 3 includes subclinical CVD, and CKM stage 4 includes clinical CVD.  These CKM stages encompass heterogeneous patient phenotypes with varying presence and severity of CKD who may have different risks of cardiovascular and kidney adverse events. Our goal is to describe the distribution of CKM stages among patients with CKD, identify predictors of progression to CKM stage 4, and evaluate gaps in evidence-based care before and after transitioning to CKM stage 4. 

We conducted a retrospective study using CKD registry data from electronic health records of a large US health care system. The CKD registry includes patients with an eGFR <60 mL/min/1.73m2 or ICD-10 diagnosis code for CKD. We included adults aged 18 to 75 years with at least 2 outpatient eGFR <60 mL/min/1.73m2 between 1/1/ 2013 and 12/31/2024. We excluded patients with kidney failure at baseline. CKM stages were identified in 1-year intervals starting from the first date of eGFR <60 mL/min/1.73m2; death or kidney failure was considered as competing risk. Demographic, clinical and social factors were evaluated as predictors of CKM stage 4 transition. Among those with CKM stage 4, evidence-based care metrics 1 year before and 1 year after CKM stage 4 transition were compared. Metrics evaluated were processes of care (BP <130/80 and < 140/90 mmHg, HbA1c <7%, and UACR <30 mg/g) and medication use (ACEi/ARB, moderate-high intensity statin, SGLT2i, and GLP1Ra). SGLT2i and GLP1Ra evaluation was limited to those who transitioned to CKM stage 4 in 2021 or after to align with emergence of evidence on these medications. 

Of 145,261 CKD registry patients, 83,323 met eligibility criteria. The cohort had a baseline mean age of 62 years, 61% were female, 88% were White race, and mean eGFR was 55 mL/min/1.73m2.  At baseline, 56%, 10%, and 34% had CKM stage 2, 3, and 4, respectively (Fig 1). Among those with CKM stage 2 or 3 at baseline, 11,753 (21%) transitioned to CKM stage 4 with a median time to transition of 3 years. Older age, male sex, higher systolic BP, diabetes, and albuminuria were significantly associated with transition to CKM stage 4. Among those who transitioned to CKM stage 4, there were significant gaps in evidence-based care (Fig 2). Achievement of BP <130/80 mmHg (adjusted OR 1.15 [95% CI 1.07-1.24]) and HbA1c <7% (adjusted OR 1.15 [95% CI 1.05-1.26]) were significantly more likely post-transition compared to pre-transition. Although the prescription of moderate or high intensity statin, SGLT2i, and GLP1Ra were more likely in the post-transition year, the overall rates remained suboptimal. Transition to CKM stage 4 was not associated with increased ACEi/ARB prescription or UACR <30 mg/g.

We identified heterogeneity in CKM stage distribution among adults with eGFR <60 mL/min/1.73m2. One in 5 patients with CKM stage 2 or 3 at baseline transitioned to CKM stage 4. Gaps in processes of care and evidence-based medication use were prevalent in those with CKM stage 2 and 3, and persisted even after transition to CKM stage 4. Efforts to close gaps in care are needed to delay and prevent CKM progression.