Hypouricemia, abnormal renal tubular urate transport, and plasma natriuretic factor(s) in patients with Alzheimer's 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.


METHODS
Cross-sectional study in three comparison groups.


METHODS
Referral private institution involving outpatient and hospitalized patients.


METHODS
AD, multi-infarct dementia (MID) and non-demented controls (C) were selected and evaluated by a geriatrician and a psychiatrist 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 (MMSE) scores determined.


METHODS
Injection of 0.5 mL of plasma I.P. followed 120 minutes later by an IV plasma injection of 0.2 mL priming dose and infusion of 1.8 mL of plasma at 0.01 mL/min in Sprague Dawley rats.


METHODS
Renal clearance studies were performed in subjects and in rats exposed to the plasma of study subjects. We measured serum urate concentration and fractional excretion (FE) of urate in subjects and FE sodium and FE lithium in rats.


RESULTS
Serum urate was lower and FE urate higher in 18 AD patients compared with six patients 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 given 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 sodium and FE lithium decreased progressively after serial dilutions of three AD plasmas and FE lithium was negatively correlated with MMSE scores only in AD, r = -0.71 and P < 0.0005.


CONCLUSIONS
In AD there is defective tubular urate transport and a plasma natriuretic factor(s). FE sodium and/or FE lithium in rats exposed to plasma of demented patients may differentiate AD from MID and estimate the severity of AD.
Maesaka
J K
JK
Division of Nephrology, Long Island Jewish Medical Center, New Hyde Park, NY 11042.
Wolf-Klein
G
G
Piccione
J M
JM
Ma
C M
CM
D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D000818:Animals; D001681:Biological Assay; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D003430:Cross-Sectional Studies; D015161:Dementia, Multi-Infarct / Q000150:complications / Q000175:diagnosis; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000378:metabolism*; D008094:Lithium / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D008297:Male; D008609:Mental Status Schedule; D008657:Metabolic Clearance Rate; D045283:Natriuretic Agents / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D010758:Phosphorus / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D011188:Potassium / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D012964:Sodium / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D014527:Uric Acid / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D014883:Water-Electrolyte Imbalance / Q000097:blood* / Q000209:etiology / Q000378:metabolism
D045283:Natriuretic Agents; D014527:Uric Acid; D010758:Phosphorus; D008094:Lithium; D012964:Sodium; D003404:Creatinine; D011188:Potassium