RESUMO
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. SETTING: Referral private institution involving outpatient and hospitalized patients. PATIENTS: 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. INTERVENTIONS: 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. MEASUREMENTS: 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.
Assuntos
Doença de Alzheimer/complicações , Túbulos Renais/metabolismo , Natriuréticos/sangue , Ácido Úrico/sangue , Desequilíbrio Hidroeletrolítico/sangue , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Animais , Bioensaio , Estudos de Casos e Controles , Creatinina/sangue , Creatinina/farmacocinética , Creatinina/urina , Estudos Transversais , Demência por Múltiplos Infartos/complicações , Demência por Múltiplos Infartos/diagnóstico , Feminino , Humanos , Testes de Função Renal , Lítio/sangue , Lítio/farmacocinética , Lítio/urina , Masculino , Entrevista Psiquiátrica Padronizada , Taxa de Depuração Metabólica , Natriuréticos/metabolismo , Natriuréticos/farmacocinética , Fósforo/sangue , Fósforo/farmacocinética , Fósforo/urina , Potássio/sangue , Potássio/farmacocinética , Potássio/urina , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Sódio/sangue , Sódio/farmacocinética , Sódio/urina , Ácido Úrico/metabolismo , Ácido Úrico/farmacocinética , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/metabolismoRESUMO
To test our hypothesis that a circulating factor(s) may be causing the renal salt and urate wasting in patients (pts) with intracranial diseases, we exposed rats to the plasma of these patients and studied sodium and lithium transport. We selected 21 neurosurgical pts, 13 of whom had increased fractional excretion (FE) of urate, and 14 age and sex-matched controls. Plasma from pts and controls were injected IP (0.5 mL) and infused, 0.2 ml prime and 1.8 mL at 0.01 mL/min, to Sprague Dawley rats anesthetized with Inactin. Renal transport of sodium (Na), lithium (Li) and potassium (K) was determined. There were higher mean +/- SEM for FENa, 0.59 +/- 0.07% vs 0.29 +/- 0.05%, P < 0.01, FELi, 36.6 +/- 1.9% vs 24.0 +/- 1.6%, P < 0.001 and K excretion rates, 1.69 +/- 0.13 vs 1.31 +/- 0.09 mumol/min, p < 0.02, in rats infused with plasma of pts as compared to controls, respectively. FENa decreased with increasing dilution of plasma of 2 pts with ICD. There was no difference in mean weight of rats, blood pressure, urine flow rate or insulin clearance between pts and controls. These data suggest that pts with ICD have a plasma factor(s) which decreases net Na, Li and K reabsorption.
Assuntos
Encefalopatias/metabolismo , Nefropatias/metabolismo , Natriuréticos/sangue , Sódio/metabolismo , Ácido Úrico/metabolismo , Adulto , Animais , Transporte Biológico , Encefalopatias/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Nefropatias/urina , Lítio/metabolismo , Masculino , Pessoa de Meia-Idade , Natriuréticos/metabolismo , Ratos , Sódio/urina , Ácido Úrico/urinaRESUMO
Based on our demonstration of a high incidence of hypouricemia, tubular urate transport abnormality, and cerebral atrophy in patients with acquired immunodeficiency syndrome (AIDS), we performed prospective renal clearance studies in 29 consecutive neurosurgical patients with intracranial diseases of multiple etiologies to test our hypothesis that patients with intracranial disorders had defective tubular urate transport. Similar studies were performed in 21 age-matched controls. None of the subjects had serum creatinine greater than 123.8 mumol/L (1.4 mg/dL), sickle cell or liver diseases, or received intravenous fluid or uricosuric drugs at the time of study. Seven patients had no surgical procedures, 12 were studied after a neurosurgical procedure, and 10 had preoperative and postoperative studies. Ten had more than one postoperative study. Twelve had 24-hour urine collections. We found that 18 of 29 patients had elevated fractional excretion (FE) of urate greater than 10%. There was no difference in preoperative and postoperative FE urate by nonpaired t test for all patients and by paired t test in the 10 patients who had preoperative and postoperative studies performed. Seven patients had hypouricemia, defined as serum urate less than or equal to 0.18 mmol/L (3 mg/dL). Only one had hyponatremia (serum sodium less than 130 mmol/L). Urate excretion averaged 3.6 +/- 0.32 mmol (603 +/- 52.7 mg)/24 h, suggesting that the hypouricemia was not due to decreased urate production. None of the medications or surgical procedures could be considered to have caused the urate transport abnormality, nor was it associated with any specific intracranial location or type of disease.(ABSTRACT TRUNCATED AT 250 WORDS)