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Association between Monocyte Count and Risk of Incident CKD and Progression to ESRD
Benjamin Bowe1, Yan Xie1, Hong Xian1,2
1Clinical Epidemiology Center, Research and Education Service and.
Insights
Higher monocyte counts are linked to increased risk of chronic kidney disease (CKD) and its progression to end-stage renal disease (ESRD). This large study confirms a graded association between monocyte levels and adverse kidney outcomes.
Area of Science:
- Nephrology
- Immunology
- Epidemiology
Background:
- Monocytes are implicated in kidney disease progression.
- Large-scale epidemiological data on monocyte count and chronic kidney disease (CKD) risk are lacking.
Purpose of the Study:
- To investigate the association between monocyte count and the risk of incident CKD, CKD progression, and end-stage renal disease (ESRD).
Main Methods:
- A longitudinal observational cohort of 1,594,700 US veterans was analyzed.
- Monocyte counts were categorized into quartiles.
- Survival models examined associations with incident eGFR<60, incident CKD, and CKD progression (doubling of serum creatinine, eGFR decline ≥30%, or composite renal endpoint).
Main Results:
- A graded association was observed between higher monocyte counts and increased risk of renal outcomes.
- The highest monocyte quartile (quartile 4) showed significantly higher risks for incident eGFR<60 (HR, 1.13) and incident CKD (HR, 1.15) compared to the lowest quartile (quartile 1).
- Higher monocyte counts were linearly associated with increased risk of CKD progression, including doubling of serum creatinine (HR, 1.22) and the composite renal endpoint (HR, 1.19).
Conclusions:
- Elevated monocyte counts are significantly associated with increased risks of developing CKD.
- Higher monocyte counts predict progression of CKD towards end-stage renal disease (ESRD).
Background And Objectives:
Experimental evidence suggests a role for monocytes in the biology of kidney disease progression; however, whether monocyte count is associated with risk of incident CKD, CKD progression, and ESRD has not been examined in large epidemiologic studies.
Design, Settings, Participants, & Measurements:
We built a longitudinal observational cohort of 1,594,700 United States veterans with at least one eGFR during fiscal year 2004 (date of last eGFR during this period designated time zero) and no prior history of ESRD, dialysis, or kidney transplant. Cohort participants were followed until September 30, 2013 or death. Monocyte count closest to and before time zero was categorized in quartiles: quartile 1, >0.00 to ≤0.40 thousand cells per cubic millimeter (k/cmm); quartile 2, >0.40 to ≤0.55 k/cmm; quartile 3, >0.55 to ≤0.70 k/cmm; and quartile 4, >0.70 k/cmm. Survival models were built to examine the association between monocyte count and risk of incident eGFR<60 ml/min per 1.73 m2, risk of incident CKD, and risk of CKD progression defined as doubling of serum creatinine, eGFR decline ≥30%, or the composite outcome of ESRD, dialysis, or renal transplantation.
Results:
Over a median follow-up of 9.2 years (interquartile range, 8.3-9.4); in adjusted survival models, there was a graded association between monocyte counts and risk of renal outcomes. Compared with quartile 1, quartile 4 was associated with higher risk of incident eGFR<60 ml/min per 1.73 m2 (hazard ratio, 1.13; 95% confidence interval, 1.12 to 1.14) and risk of incident CKD (hazard ratio, 1.15; 95% confidence interval, 1.13 to 1.16). Quartile 4 was associated with higher risk of doubling of serum creatinine (hazard ratio, 1.22; 95% confidence interval, 1.20 to 1.24), ≥30% eGFR decline (hazard ratio, 1.18; 95% confidence interval, 1.17 to 1.19), and the composite renal end point (hazard ratio, 1.19; 95% confidence interval, 1.16 to 1.22). Cubic spline analyses of the relationship between monocyte count levels and renal outcomes showed a linear relationship, in which risk was higher with higher monocyte count. Results were robust to changes in sensitivity analyses.
Conclusions:
Our results show a significant association between higher monocyte count and risks of incident CKD and CKD progression to ESRD.
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