Hyperuricaemia-associated all-cause mortality risk effect is increased by non-impaired kidney function – Is renal hyperuricaemia less dangerous?

Abstract

Background

Both hyperuricaemia and chronic kidney disease are known mortality risk factors. This study examined the modifying effect of renal function on hyperuricaemia-associated mortality risk, which is an issue that has not been studied before.

Methods

Data on levels of serum uric acid (SUA), creatinine, cystatin C and other variables of persons aged 52–76 years were collected. Persons with SUA >410 μmol/L (75th percentile) were classified as clearly hyperuricaemic and persons with eGFR of ≤67 ml/min (25th percentile) as having reduced kidney function.

Results

Reduced kidney function was associated with higher mortality in both SUA groups. When compared to individuals with SUA ≤410 μmol/L and eGFR >67 ml/min the hazard ratio (HR) for all-cause mortality was 1.53 (95 % CI: 1.26–1.84) in clearly hyperuricaemic persons with reduced kidney function, 1.26 (95 % CI: 1.02–1.55) in clearly hyperuricaemic persons with eGFR of >67 ml/min and 1.15 (95 % CI: 0.96–1.39) in persons with SUA ≤410 μmol/L and reduced kidney function. The HR for hyperuricaemia-related premature death was lowest in individuals with reduced eGFR, and it rose strikingly as the eGFR increased above 90 ml/min.

Conclusions

Reduced kidney function is a risk factor for mortality both in individuals with normal and elevated SUA. The hyperuricaemia-associated mortality risk is remarkably higher in individuals with normal kidney function than in individuals with reduced kidney function. Presumably overproduction of uric acid (metabolic hyperuricaemia) is a separate and more deleterious entity than hyperuricaemia resulting from reduced renal excretion of uric acid (renal hyperuricaemia).