Chronic kidney disease incidence and cardiorespiratory fitness association in hypertensive patients

Objective: Chronic hypertension (HTN) is considered a strong risk factor for developing chronic kidney disease (CKD). Increased cardiorespiratory fitness (CRF) is associated with lower CKD risk. However, the CRF-CKD association in patients with HTN has not been assessed. Thus, we examined the the association between CRF and the risk of developing CKD in hypertensive patients. Design and method: Hypertensive individuals (n=471,579; age 63.0+8.8 years) with normal kidney function prior to HTN and no evidence of ischemia indicated by a maximal standardized exercise treadmill test (ETT). The cohort was part of the ETHOS study (n=750,302). We established five CRF categories based on age-and-gender-adjusted peak metabolic equivalents (METs) achieved: Least-Fit (4.5±1.2 METs; n=106,955); Low-Fit Fit (6.9±1.1 METs; n=122,612); Moderate-Fit (8.3±1.2 METs; n=91,995); Fit (10.3±1.2 METs; n=111,472); and High-Fit (13.2±1.6 METs; n=38,545). CKD risk across CRF categories was assessed by multivariable Cox Regression analysis, adjusted for age, blood pressure, body mass index (BMI), alcohol abuse, traditional risk factors, and medications. Results: During 6,146,773.0 person-years of follow-up (median 12.9 years), 58,701 individuals developed CKD (9.6 events/1,000 person-years of observation). The CRF-CKD association was inverse, independent of comorbidities and graded. The risk of developing CKD was 9% lower for each 1-MET increase (Hazard Ratio [HR] 0.91; 95% confidence interval [CI] 0.90-0.93). When CKD risk was assessed across CRF categories using the Least-fit category as the referent, the risk was 20% lower (HR 0.80; CI 0.78-0.81, p<0.001) for those in the Low-fit category (6.9±1.1 METs). The risk declined progressively with increased CRF and was 49% lower for those in the highest CRF category (HR 0.49; CI 0.47-0.51, p<0.001). Similar findings were observed in the subgroup of hypertensive patients with diabetes mellitus (n=192,966). Conclusions: We noted an inverse and dose-response association between CRF and CKD incidence. The risk was attenuated significantly beyond a MET level of 6.9±1.1 METs, suggesting that moderate increases in exercise capacity lowers the risk of developing CKD in hypertensive patients.