Association of nephrolithiasis history with adverse outcomes in cardiovascular–kidney–metabolic syndrome

Cardiovascular-kidney-metabolic (CKM) syndrome significantly impacts a large segment of the general population. The risk factors associated with progression of CKM syndrome as well as all-cause mortality warrant further investigations. In this study, we aimed to assess whether nephrolithiasis history would help to identify the high-risk populations among CKM patients. We conducted a multi-center study involving patients with CKM syndrome at stages 2–3 from 28 urban centers across China. We employed multivariable Cox proportional hazards regression analysis to estimate hazard ratios (HRs) along with their corresponding 95% confidence intervals (CIs) for the associations with a history of nephrolithiasis. Subgroup analyses and sensitivity analyses were performed to enhance the robustness of our findings. A total of 344,220 CKM patients at stages 2–3 were included in this study. Among the participants, 28,451 had a history of nephrolithiasis. When compared to individuals without nephrolithiasis history, those with the history demonstrated an increased risk of progression to CKM stage 4 (HR 1.52, 95% CI [1.48–1.56]) and all-cause mortality (HR 1.08, 95% CI [1.03–1.14]). Similar results were obtained in the participants with asymptomatic nephrolithiasis. Consistent findings were observed through subgroup analyses and sensitivity analyses as well. The history of nephrolithiasis is associated with an elevated risk of incident cardiovascular disease and increased all-cause mortality among CKM patients. These findings highlight the significant role of nephrolithiasis in identifying high-risk populations within CKM patients. This study aimed to understand whether people with a history of kidney stones are more likely to develop cardiovascular disease or face a higher risk of death, especially if they already have Cardiovascular-Kidney-Metabolic (CKM) syndrome - a condition where heart, kidney, and metabolic health problems overlap. We collected health data from over 340,000 patients in stages 2–3 of CKM syndrome across 28 urban hospitals in China. Among them, about 28,000 had a previous history of kidney stones. After long-term follow-up, we found that CKM patients with a history of kidney stones had an approximately 52% higher risk of progressing to advanced CKM stage (where cardiovascular disease occurs) and an approximately 8% higher risk of death from any cause. Even patients with asymptomatic kidney stones showed a similarly increased risk. These findings remained consistent across different groups, regardless of age, sex, kidney function, or the presence of conditions like hypertension or diabetes. This research suggests that a history of kidney stones may serve as an important signal to identify high-risk individuals among CKM patients, helping doctors intervene and monitor them earlier. Further studies are needed to determine whether more proactive prevention or treatment strategies should be adopted for this patient group.