This study explores the association between the systemic inflammation response index (SIRI) and chronic kidney disease (CKD) using data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2020. The study found a positive correlation between SIRI and CKD, with SIRI levels increasing the risk of CKD by 24%. SIRI also showed a nonlinear relationship with CKD, with a breakpoint at 2.04. Additionally, SIRI was positively correlated with albuminuria and low estimated glomerular filtration rate (eGFR), with breakpoints at 2.18 and 1.85, respectively. SIRI was also found to be a better predictor of CKD, albuminuria, and low-eGFR compared to other inflammatory biomarkers such as SII, NHR, LHR, MHR, and PHR, as demonstrated by the area under the curve (AUC) values. The study also found that SIRI was positively correlated with CKD across different subgroups, including age, BMI, diabetes, and hypertension. However, the study had limitations, including a cross-sectional design that precluded causal inference and potential confounding factors. Despite these limitations, the study suggests that SIRI may be a useful inflammatory biomarker for predicting CKD and related conditions in adult Americans. The study highlights the importance of monitoring SIRI levels in individuals with elevated levels of other inflammatory biomarkers to assess their risk of kidney disease.This study explores the association between the systemic inflammation response index (SIRI) and chronic kidney disease (CKD) using data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2020. The study found a positive correlation between SIRI and CKD, with SIRI levels increasing the risk of CKD by 24%. SIRI also showed a nonlinear relationship with CKD, with a breakpoint at 2.04. Additionally, SIRI was positively correlated with albuminuria and low estimated glomerular filtration rate (eGFR), with breakpoints at 2.18 and 1.85, respectively. SIRI was also found to be a better predictor of CKD, albuminuria, and low-eGFR compared to other inflammatory biomarkers such as SII, NHR, LHR, MHR, and PHR, as demonstrated by the area under the curve (AUC) values. The study also found that SIRI was positively correlated with CKD across different subgroups, including age, BMI, diabetes, and hypertension. However, the study had limitations, including a cross-sectional design that precluded causal inference and potential confounding factors. Despite these limitations, the study suggests that SIRI may be a useful inflammatory biomarker for predicting CKD and related conditions in adult Americans. The study highlights the importance of monitoring SIRI levels in individuals with elevated levels of other inflammatory biomarkers to assess their risk of kidney disease.