Clinical Implications of Missed CKD Diagnosis in Adults with and without Diabetes Mellitus

KEY POINTS: CKD was undiagnosed in 56% of patients and linked to early mortality, kidney failure, and cardiovascular events despite milder disease. First-year mortality was two-fold higher among undiagnosed patients, emphasizing the short-term risks of missed diagnosis. Sodium-glucose cotransporter 2 inhibitors were associated with better cardiovascular and kidney outcomes, yet their uptake remained low. BACKGROUND: CKD is a global public health challenge, yet underdiagnosis in routine care remains pervasive, leading to missed opportunities for early intervention. Evidence directly linking missed diagnosis to adverse outcomes in large, nationwide populations is limited. METHODS: We conducted a nationwide, population-based cohort study including 640,217 adults meeting Kidney Disease Improving Global Outcomes (KDIGO) laboratory criteria for CKD (eGFR<60 ml/min per 1.73 m 2 and/or urinary albumin-creatinine ratio >30 mg/g on at least two occasions ≥3 months apart) between 2000 and 2023. CKD underdiagnosis was defined as absence of a documented diagnosis in electronic medical records. The primary end point was a composite of all-cause mortality or KRT. Secondary end points included first-year mortality and time to all-cause mortality, KRT, and major cardiovascular events. Associations were assessed using multivariable Cox proportional hazards models, stratified by diabetes status, with additional propensity score-matched sensitivity analyses. RESULTS: Of 640,217 patients who met laboratory criteria for CKD, 359,805 (56%) lacked a documented diagnosis. Undiagnosed patients were younger, more often female, and disproportionately from minoritized populations. Absence of a CKD diagnosis was associated with a markedly shorter time to death or KRT (hazard ratio, 1.10; 95% confidence intervals [CI], 1.09 to 1.11). First-year mortality was higher in undiagnosed versus diagnosed CKD (8.0% [95% CI, 7.9 to 8.1] versus 4.1% [95% CI, 4.0 to 4.2]), despite less advanced disease at baseline. Use of renoprotective and cardioprotective medications was significantly lower in undiagnosed patients. Sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy was independently associated with lower risks of death, kidney failure, and cardiovascular events, showing a consistent protective effect in both diabetic and nondiabetic subgroups. Findings were consistent across sensitivity analyses. CONCLUSIONS: In this real-world nationwide CKD cohort, underdiagnosis was common and associated with premature death, kidney failure, and cardiovascular morbidity. There was consistent association of SGLT2 inhibitors with better cardiovascular and kidney health outcomes.