High measured GFR as a predictor of all-cause mortality and cardiovascular disease in a prospective non-diabetic population cohort

Background

High glomerular filtration rate (GFR) is generally regarded as beneficial but has been associated with cardiovascular disease (CVD) and all-cause mortality in epidemiological studies. However, these investigations may have been biased by the non-GFR determinants of estimated GFR (eGFR). We compared the risk of high baseline iohexol clearance [measured GFR (mGFR)] and eGFR based on creatinine or cystatin C in a prospective longitudinal population-based study of the Renal Iohexol Clearance Survey (RENIS) cohort.

Methods

The cohort consists of a representative sample of the general population of persons 50–64 years of age without baseline CVD, diabetes or kidney disease in the municipality of Tromsø, Norway. We investigated non-linear associations in general additive Cox regression models adjusted for CVD risk factors.

Results

During a median follow-up of 14.1 years, 232 CVD outcomes and 117 deaths occurred in a study population of 1552 persons. For all-cause mortality, no association was found for mGFR, but the previously reported association between high eGFR with creatinine (eGFRcrea) and increased risk was confirmed. For the CVD outcome, the best fitting model included interactions between mGFR or eGFR and the urine albumin:creatinine ratio (ACR). An mGFR or eGFR with cystatin C (eGFRcys) >85 ml/min/1.73 m2 was associated with an elevated hazard ratio for CVD in participants with high-normal urine ACR (>10 mg/g) only.

Conclusions

A high mGFR or eGFRcys is not associated with an increased risk of CVD or all-cause mortality in the general non-diabetic population with normal urine ACR. Previous findings of an association with high eGFRcrea were most likely caused by non-GFR confounders. In persons with high-normal ACR, high mGFR or eGFRcys is associated with an increased risk of CVD.