Prognosis of non-albuminuric patients with the cardiovascular–kidney–metabolic syndrome

Background: Cardiovascular-kidney-metabolic (CKM) syndrome affects a significant portion of the general population. Urinary albumin-to-creatinine ratio (UACR) is an important indicator of kidney injury. While some studies have indicated associations between UACR within the normal range and mortality outcomes, it remains uncertain whether traditionally normal UACR could help to distinguish the prognosis of CKM patients. Methods: This cohort study included patients with CKM syndrome at stages 2 and 3 and traditionally normal UACR from the China Renal Data System (CRDS) and UK Biobank (UKB) databases. UACR was treated as a continuous variable and categorized into low-normal and high-normal. The associations were initially assessed in the CRDS database and subsequently validated in the UKB database. Multivariable Cox proportional hazards regression was employed to estimate the associations with UACR. Additionally, subgroup analyses and sensitivity analyses were conducted to enhance the robustness of the results. Results: The study encompassed a total of 14 602 patients from the CRDS database and 82 694 patients from the UKB database. Near-linear associations were identified between continuous UACR levels and progression to CKM stage 4, as well as all-cause mortality. When compared with the low-normal UACR group, individuals with high-normal UACR exhibited an elevated risk of progression to CKM stage 4 (HR 1.133, 95% CI 1.026-1.250) and increased all-cause mortality (HR 2.321, 95% CI 1.679-3.208) within the CRDS database. These associations were further corroborated in the UKB database. Consistent findings were also observed through subgroup analyses and sensitivity analyses. Conclusions: The findings indicate that elevated UACR levels within the normal range are significantly associated with poor prognosis among CKM patients at stages 2 and 3. These results underscore the critical role of UACR in identifying high-risk populations, particularly among individuals with metabolic disorders. This information may prove valuable for monitoring and implementing risk intervention strategies for CKM patients.