Monocyte-to-HDL ratio (MHR) is associated with overall and renal mortality in community-dwelling older individuals with chronic kidney disease (CKD).

BACKGROUND

Chronic kidney disease (CKD) in older adults is associated with high morbidity and mortality, but accurate risk stratification remains challenging. The monocyte-to-high density lipoprotein ratio (MHR), an integrative biomarker of systemic inflammation and lipid metabolism, has been associated with adverse outcomes in younger and mixed-age populations. However, its prognostic value in older adults with CKD, including its association with renal mortality, has not been explored.

METHODS

We analyzed 5,115 community-dwelling individuals aged ≥ 70 years with CKD from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 and externally validated findings in 1,684 older individuals with CKD from the 2016 Health and Retirement Study (HRS). In NHANES, CKD was defined by an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² and/or albumin-to-creatinine ratio (ACR) ≥ 30 mg/g, whereas in HRS it was defined by eGFR < 60 mL/min/1.73 m². All-cause and renal-specific mortality were ascertained through linkage to the National Death Index and analyzed using survey-weighted Cox proportional hazards models and Fine and Gray competing risk models. To enhance model robustness and reduce overfitting, final multivariable models were informed by covariate selection using least absolute shrinkage and selection operator (LASSO) regression.

RESULTS

During a mean follow-up of 82 months in NHANES, all-cause and renal-specific mortality rates were 72.7 (95% CI: 69.5-75.9) and 1.5 (95% CI: 1.1–2.1) per 1,000 person-years, respectively. Higher MHR was independently associated with an increased risk of all-cause mortality (HR 1.32, 95% CI 1.20–1.45) and renal-specific mortality (subdistribution HR 1.43, 95% CI 1.12–1.82) in fully adjusted models including ACR, eGFR, and relevant clinical and demographic covariates. Feature selection analyses identified MHR, eGFR, and ACR among the strongest predictors of renal-specific mortality. Associations were directionally consistent in the HRS validation cohort, where MHR remained independently associated with both all-cause mortality (HR 1.98, 95%CI 0.76–5.15) and renal-specific mortality (sHR 2.19, 95%CI 1.29–3.74). Stratified analyses suggested that MHR predicted all-cause mortality primarily in individuals with eGFR ≥ 45 mL/min/1.73 m², whereas its association with renal-specific mortality was strongest in those with more advanced CKD.

CONCLUSIONS

In older adults with CKD, MHR is an independent predictor of both all-cause and renal-specific mortality and provides prognostic information beyond eGFR and ACR. Given its derivation from routinely available laboratory tests, MHR may help refine risk stratification in older adults with CKD.