HYPOURICEMIA, ABNORMAL RENAL TUBULAR URATE TRANSPORT, AND PLASMA NATRIURETIC FACTOR(S) IN PATIENTS WITH ALZHEIMERS-DISEASE

Objective: To study tubular urate transport in Alzheimer's disease (AD ) and measure sodium and lithium transport rates in rats exposed to AD plasma. Design: Cross-sectional study in three comparison groups. Set ting: Referral private institution involving outpatient and hospitaliz ed patients. Patients: AD, multi-infarct dementia (MID) and non-dement ed controls (C) were selected and evaluated by a geriatrician and a ps ychiatrist according to availability and willingness to participate in the study. Demented patients had brain imaging, categorized according to NINCDS-DSM III criteria, and had Mini-mental status examination (M MSE) scores determined. Interventions: Injection of 0.5 mL of plasma I .P. followed 120 minutes later by an IV plasma injection of 0.2 mL pri ming dose and infusion of 1.8 mL of plasma at 0.01 mL/min in Sprague D awley rats. Measurements: Renal clearance studies were performed in su bjects and in rats exposed to the plasma of study subjects. We measure d serum urate concentration and fractional excretion (FE) of urate in subjects and FE sodium and FE lithium in rats. Results: Serum urate wa s lower and FE urate higher in 18 AD patients compared with six patien ts with MID, P < 0.05 and P < 0.005, and 11 C, P < 0.02 and P < 0.005, respectively. Higher FE sodium and FE lithium were noted in rats give n plasma from 19 AD patients compared with 12 with MID, P < 0.005 and P < 0.0025, and 14 C, P < 0.0025 and P < 0.0005, respectively. FE sodi um and FE lithium decreased progressively after serial dilutions of th ree AD plasmas and FE lithium was negatively correlated with MMSE scor es only in AD, r = -0.71 and P < 0.0005. Conclusions: In AD there is d efective tubular urate transport and a plasma natriuretic factor(s). F E sodium and/or FE lithium in rats exposed to plasma of demented patie nts may differentiate AD from MID and estimate the severity of AD.