RESUMO
BACKGROUND: Urea transport depends on the diffusion through cell membrane and the facilitated urea transport. Two groups of urea transporters (UT-A and UT-B) have been identified in mammals, and both are involved in intrarenal recycling of urea. The aim of our study was to examine the renal urea handling in rats with chronic renal failure (CRF). METHODS: CRF rats were induced by 5/6 nephrectomy followed by a high-protein (HP) diet to increase the progressive loss of renal function for 5 months. Functional studies on water and urea handling were performed. RT-PCR, immunoblotting and immunohistochemistry were used to identify UT-A proteins in remnant kidney. RESULTS: A significant decrease in creatinine clearance consistent with development of CRF was observed. The remnant kidneys were hypertrophied, and total renal mass was increased. Urine production increased markedly, whereas urine osmolality and solute-free water reabsorption decreased significantly. Fractional urea excretion was increased reaching values of 105% -/+ 8%. UT-A protein was localized in pars recta by immunohistochemical studies, and it was identified as UT-A2 in outer medulla from remnant kidneys by RT-PCR and immunoblotting. CONCLUSION: In uremic rats, an urea transporter type UT-A2 was expressed in the pars recta, suggesting a possible relation with the fractional urea excretion increase. This expression may be a consequence of an adaptive mechanism in the handling of urea during development of CRF. Further studies will be necessary to elucidate the contribution of this mechanism to renal damage observed in the progression of CRF.
Assuntos
Expressão Gênica , Falência Renal Crônica/genética , Medula Renal/metabolismo , Proteínas de Membrana Transportadoras/genética , RNA Mensageiro/genética , Animais , Modelos Animais de Doenças , Seguimentos , Humanos , Immunoblotting , Imuno-Histoquímica , Sistema do Grupo Sanguíneo Kidd , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Medula Renal/patologia , Proteínas de Membrana Transportadoras/biossíntese , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transportadores de UreiaRESUMO
BACKGROUND: Salt delivery to the distal nephron and sodium reabsorption in this segment are considered critical factors that modulate kaliuresis in chronic kidney disease (CKD). Amiloride, a drug that blocks Na(+) reabsorption in the distal nephron, can help to assess the role of Na+ transport in this segment on the kaliuresis of CKD patients. METHODS: A bolus of amiloride (1 mg/kg body weight) followed by an intravenous infusion (1 mg/kg body weight per hour) was administered to 6 normal subjects and 10 patients with CKD undergoing water diuresis. Serum and urine electrolytes were measured. Glomerular filtration rate (GFR) was measured with clearance of (125)I-iodothalamate. RESULTS: Normal subjects and CKD patients had a control fractional excretion of potassium (FE(K)(+)) of 26% +/- 11% and 126% +/- 28%, respectively; the corresponding FE(Na)(+) was 2.3% +/- 0.8% and 15% +/- 3%. In response to amiloride, FE(Na)(+)increased significantly to 3.5% +/- 0.6% and 20% +/- 3% in normal and CKD subjects, respectively, and FE(K)(+) decreased significantly to 6.5% +/- 0.6% and 39% +/- 8%, respectively. Amiloride-sensitive and amiloride-insensitive kaliuresis in normal subjects were 71.4% and 28.6%, respectively; the corresponding values for CKD patients were 73% and 27%, respectively. Urine output correlated positively with kaliuresis in CKD. CONCLUSIONS: The very high FEK+ observed in CKD occurs in the absence of hyperkalemia and is largely amiloride-sensitive; therefore maintenance of potassium balance by the kidney in CKD is mostly dependent on sodium reabsorption through channels along the distal nephron. The high urinary flow of CKD further promotes potassium excretion.
