RESUMEN
We investigated the effects of orally supplemented L-arginine, the substrate of nitric oxide (NO) and N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide-synthase inhibitor in gentamicin-induced renal failure. Rats were given gentamicin (100 mg/kg/day s.c.), gentamicin and L-arginine (2 g/l, drinking water), gentamicin and L-NAME (100 mg/l, drinking water) or gentamicin plus L-arginine and L-NAME. After 8 days, the gentamicin group developed marked renal failure, characterized by a significantly decreased creatinine clearance and increased blood creatinine, fractional excretion of sodium, fractional excretion of lithium, urine gamma glutamyl transferase, systolic blood pressure and daily urine volume when compared to controls. Renal histological analysis confirmed tubular necrosis. L-arginine administration caused normalization of these parameters, whereas L-NAME led to aggravation of the failure. Concomitant administration of L-NAME and L-arginine to gentamicin-treated rats caused no significant changes when compared to the rats receiving gentamicin alone. We conclude that L-arginine supplementation has beneficial effects in gentamicin-induced renal failure in rats and that these effects are reversed by the NO-synthase inhibitor, L-NAME.
Asunto(s)
Arginina/farmacología , Gentamicinas/toxicidad , Insuficiencia Renal/prevención & control , Administración Oral , Animales , Creatinina/sangre , Inhibidores Enzimáticos/farmacología , Riñón/efectos de los fármacos , Riñón/patología , Litio/farmacocinética , Litio/orina , Masculino , NG-Nitroarginina Metil Éster/farmacología , Ratas , Insuficiencia Renal/inducido químicamente , Sodio/orina , Micción/efectos de los fármacos , gamma-Glutamiltransferasa/efectos de los fármacos , gamma-Glutamiltransferasa/orinaRESUMEN
BACKGROUND: End-stage kidney disease may develop in 1% to 3% of cyclosporine-treated heart transplant recipients, and most patients show a decreased glomerular filtration rate. There are little data on kidney function in pediatric recipients, although good function is needed for their optimal development. METHODS: Kidney function was prospectively investigated in 10 children receiving triple immunosuppression (cyclosporine, azathioprine, methylprednisolone) during the first 18 months after heart transplantation. The early cyclosporine trough level target was 300 to 500 micrograms/L and 100 to 200 micrograms/L after the first year. 51Chromium-ethylenediamine tetraacetic acid, para-amino hippuric acid, lithium, and sodium clearances, measurements of serum and urinary electrolytes, and urinary concentration tests were performed. Renal biopsy specimens were obtained from four patients after 18 months. RESULTS: Heart function was good in all patients. Six patients (60%) remained rejection-free at 18 months. The mean glomerular filtration rate was 92.4 ml/min/1.73 m2 before transplantation, increased to 115 by 6 months (p < 0.05), and thereafter remained stable. The mean renal plasma flow was 487 ml/min/1.73 m2 after 18 months. Hypertension was seen in all patients at discharge but in only one at 18 months. Mild hyperuricemia was the most common sign of tubular dysfunction occurring in five patients at discharge but in only two patients at 18 months. The result of kidney histopathologic study was normal in three of four patients, and cyclosporine nephrotoxicity was not diagnosed. CONCLUSIONS: Triple immunosuppression with cyclosporine adequately protects the graft against acute rejection. It is compatible with normal glomerular function and leads to only minor tubular disturbances.
Asunto(s)
Ciclosporina/uso terapéutico , Trasplante de Corazón , Inmunosupresores/uso terapéutico , Riñón/fisiología , Adolescente , Azatioprina/uso terapéutico , Biopsia , Quelantes , Niño , Preescolar , Radioisótopos de Cromo , Ciclosporina/efectos adversos , Ciclosporina/sangre , Ácido Edético , Electrólitos/sangre , Electrólitos/orina , Tasa de Filtración Glomerular/efectos de los fármacos , Glucocorticoides/uso terapéutico , Rechazo de Injerto/prevención & control , Trasplante de Corazón/fisiología , Humanos , Hipertensión/etiología , Inmunosupresores/efectos adversos , Inmunosupresores/sangre , Riñón/efectos de los fármacos , Riñón/patología , Fallo Renal Crónico/inducido químicamente , Túbulos Renales/efectos de los fármacos , Túbulos Renales/fisiopatología , Litio/orina , Metilprednisolona/uso terapéutico , Estudios Prospectivos , Radiofármacos , Flujo Plasmático Renal/efectos de los fármacos , Flujo Plasmático Renal/fisiología , Sodio/orina , Ácido Úrico/sangre , Ácido p-Aminohipúrico/orinaRESUMEN
The effects of amlodipine and perindopril on renal hemodynamics and tubular function in cyclosporine-treated hypertensive renal allograft recipients were evaluated in a randomized, double-blind crossover fashion. Ten patients were studied after a 2-week placebo run-in and, after 8 weeks of active treatment, allowing a 2-week placebo washout between treatments. At the end of each period, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured as 51Cr-EDTA and 123I-hippuran clearance, respectively, and tubular function evaluated by the lithium clearance technique was determined. Both drugs maintained GFR and ERPF and lowered mean arterial pressure (MAP, mm Hg) to a similar extent (time x treatment, P = 0.466): amlodipine from 126.9 +/- 2.5 to 115.9 +/- 2.2; perindopril from 126.9 +/- 2.5 to 117.9 +/- 3.9 (time effect of all treatments together, P = 0.003). Accordingly, renal vascular resistance (RVR, mm Hg/mL/min/1.73 m2) was equally reduced (time x treatment, P = 0.955): amlodipine from 0.36 +/- 0.03 to 0.30 +/- 0.02; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01 (time effect all treatments together, P = 0.043). Sodium clearance and fractional excretion of sodium were not affected by either drug. Output of fluid from the proximal tubules measured as clearance of lithium (CLi, mL/min) and uric acid (CUr, mL/min) was higher after amlodipine than after perindopril (CLi 19.1 +/- 2.1 v 16.5 +/- 1.7, P =0.036 and CUr 7.0 +/- 0.6 v 5.9 +/- 0.4, P = 0.007). As a consequence, after amlodipine, distal absolute reabsorption of sodium was higher (DARNa 2.57 +/- 0.28 v 2.19 +/- 0.22 mEq/min, P = 0.027) and serum uric acid was lower (5.9 +/- 0.3 v 6.7 +/- 0.4 mg/dL, P = 0.001) in comparison with perindopril. In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent. Overall sodium excretion is not affected by either agent. Urate clearance is higher and serum uric acid lower on amlodipine as compared with perindopril.
Asunto(s)
Amlodipino/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Indoles/uso terapéutico , Glomérulos Renales/efectos de los fármacos , Trasplante de Riñón/fisiología , Túbulos Renales/efectos de los fármacos , Adulto , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Glomérulos Renales/fisiología , Túbulos Renales/fisiología , Litio/orina , Masculino , Persona de Mediana Edad , Perindopril , Placebos , Flujo Plasmático Renal Efectivo/efectos de los fármacos , Sodio/metabolismo , Sodio/orina , Trasplante Homólogo , Ácido Úrico/sangre , Ácido Úrico/orina , Resistencia Vascular/efectos de los fármacosRESUMEN
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.
Asunto(s)
Enfermedad de Alzheimer/complicaciones , Túbulos Renales/metabolismo , Natriuréticos/sangre , Ácido Úrico/sangre , Desequilibrio Hidroelectrolítico/sangre , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Animales , Bioensayo , Estudios de Casos y Controles , Creatinina/sangre , Creatinina/farmacocinética , Creatinina/orina , Estudios Transversales , Demencia por Múltiples Infartos/complicaciones , Demencia por Múltiples Infartos/diagnóstico , Femenino , Humanos , Pruebas de Función Renal , Litio/sangre , Litio/farmacocinética , Litio/orina , Masculino , Escala del Estado Mental , Tasa de Depuración Metabólica , Natriuréticos/metabolismo , Natriuréticos/farmacocinética , Fósforo/sangre , Fósforo/farmacocinética , Fósforo/orina , Potasio/sangre , Potasio/farmacocinética , Potasio/orina , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Sodio/sangre , Sodio/farmacocinética , Sodio/orina , Ácido Úrico/metabolismo , Ácido Úrico/farmacocinética , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/metabolismoAsunto(s)
Riñón/fisiología , Litio/metabolismo , Glándulas Paratiroides/fisiología , Fosfatos/metabolismo , Animales , Bicarbonatos/farmacología , Calcio/farmacología , Espacio Extracelular/metabolismo , Inulina/farmacología , Túbulos Renales/fisiología , Litio/sangre , Litio/farmacología , Litio/orina , Magnesio/farmacología , Masculino , Tasa de Depuración Metabólica , Fósforo/sangre , Fósforo/orina , Ratas , Sodio/sangre , Sodio/metabolismo , Sodio/farmacología , Sodio/orina , Cloruro de Sodio/farmacología , Espectrofotometría AtómicaRESUMEN
The use of lithium ions in the treatment of manic states is discussed. Lithium is possibly the only specific drug treatment presently available for the major psychoses and has met with enthusiasm in England, Scandinavia, Australia and, more recently, in Canada and the United States.A number of the published papers on the subject are not sufficiently comprehensive to provide guidance for even its empiric use; some lack the necessary controls and design to permit comparisons with other studies.Some clinicians with wide experience of lithium therapy do not maintain laboratory control of patients by ordering serum lithium determinations but rely entirely on clinical judgement in establishing drug schedules. This is not advised if one has little experience with lithium therapy because of the possible side effects and toxicity.