Hyperuricaemia is associated with renal damage independently of hypertension and intrarenal renin-angiotensin system activation, as well as their circadian rhythms

AimBoth hyperuricaemia and activation of the intrarenal renin-angiotensin system (RAS) play an important role in the development of hypertension and renal damage. However, it has not been clear whether hyperuricaemia is associated with renal damage due to hypertension or intrarenal RAS activation, as well as their circadian rhythms. MethodsWe recruited 43 chronic kidney disease (CKD) patients who did not receive RAS blockers and antihyperuricaemic drugs, and investigated the relationship among serum uric acid (sUA) levels, the circadian rhythm of urinary angiotensinogen (U-AGT) excretion levels, and the levels of albuminuria (U-ACR) and proteinuria (U-P/Cr). ResultssUA levels were significantly associated with estimated glomerular filtration rate (eGFR) (P=0.002), systolic blood pressure (SBP) (daytime, P=0.031), and U-ACR (daytime, P=0.006 and nighttime, P=0.008) and U-P/Cr (daytime, P=0.017 and nighttime, P=0.013). However, there were no significant differences between sUA levels and SBP in nighttime and U-AGT excretion levels in both time periods. Multiple regression analyses for sUA levels were performed using age, sex, eGFR and each parameter (SBP, U-AGT/Cr, U-ACR or U-P/Cr). sUA levels were not associated with SBP or U-AGT/Cr in both time periods. sUA levels tended to correlate with U-P/Cr levels in nighttime, and were significantly associated with U-P/Cr in daytime (P=0.026) and U-ACR in daytime (P=0.017) and nighttime (P=0.046). Moreover, no significant differences were found between sUA levels and night-to-day ratios of some parameters. ConclusionThese data suggest that hyperuricaemia is associated with renal damage, independently of hypertension and intrarenal RAS activation, as well as their circadian rhythms. Summary at a Glance Confirmatory study on 43 patients with CKD showing the association between elevated uric acid with albuminuria. The independence of the association from hypertension and RAS blockade highlighted in the study has not been widely reported before.