Tubuloglomerular feedback and interstitial pressure in obstructive nephropathy

Tubuloglomerular feedback and interstitial pressure in obstructive nephropathy. The possible role of the tubuloglomerular feedback (TGF) mechanism in the altered glomerular hemodynamics and tubular reabsorption which occur with prolonged (24-hr) ureteral obstruction and the changes in renal interstitial hydrostatic and oncotic pressure which may modulate TGF sensitivity were examined. The proximal tubule stop-flow pressure (PSF) response to increased distal tubular flow rates (TGF activity) was determined in rats with sham operation, 24-hr unilateral ureteral obstruction (UUO), or 24-hr bilateral ureteral obstruction (BUO), both before and for 2 hr after relief of obstruction. Subcapsular hydrostatic pressure, lymph flow and oncotic pressure, clearance and excretory data were measured in the second series of animals. During and after release of UUO, TGF sensitivity was increased, as indicated by the marked decrease in the loop perfusion rate at which 50% of the maximum decrease in PSF occurred (the turning point of TGF activation). Interstitial oncotic pressure but not hydrostatic pressure was significantly increased in UUO kidneys. In BUO rats, the turning point for TGF activation was slightly higher than the controls and the change in PSF with maximum loop perfusion rates was reduced, indicating a blunting of the TGF response before and particularly during postobstructive diuresis after release of BUO. Interstitial hydrostatic and oncotic pressures were both slightly increased resulting in no changes in net interstitial Starling forces. We conclude that enhanced TGF sensitivity after release of prolonged UUO, associated with increased interstitial oncotic pressure, may play a role in preventing postobstructive diuresis, while the blunting of TGF sensitivity after BUO may contribute to this phenomenon.Rétrocontrôle glomérulo-tubulaire et pression interstitielle au cours de la néphropathie obstructive. Le rôle possible du mécanisme de rétrocontrôle glomérulo-tubulaire (TGF) dans l'altération de l'hémadynamique glomérulaire et la réabsorption tubulaire qui se produisent lors d'une obstruction urétérale prolongée (24 heures) et les modifications des pressions hydrostatiques et oncotiques interstitielles rénales qui pourraient moduler la sensibilité TGF ont été étudiés. La réponse de pression en flux interrompu (PSF) du tubule proximal à une augmentation des débits tubulaires distaux a été déterminée chez des rats ayant subi un simulacre d'intervention, lors d'une obstruction urétérale unilatérale de 24 heures (UUO) ou lors d'une obstruction urétérale bilatérale de 24 heures (BUO), avant et 2 heures après la levée de l'obstruction. La pression hydrostatique sous-capsulaire, le flux et la pression oncotique lymphatiques, les paramètres de clearance et d'excrétion ont été mesurés chez une deuxième série d'animaux. Pendant et après levée de l'UUO, la sensibilité TGF a augmenté, comme le montrait la diminution marquée du débit de perfusion de l'anse pour lequel 50% de la chute maximale de PSF se produisait (le point d'inflexion de l'activation TGF). La pression oncotique mais non la pression hydrostatique interstitielle était significativement accrue dans les reins UUO. Chez les rats BUO, le point d'inflexion de l'activation TGF était légèrement plus élevé que chez les contrôles, et la modification de PSF aux débits de perfusion de l'anse maxima était diminuée, indiquant une altération de la réponse TGF avant et surtout pendant la diurèse post-obstructive, après levée de la BUO. Les pressions interstitielles hydrostatiques et oncotiques légèrement augmentées, d'où l'absence de modification des forces de Starling interstitielles nettes. Nous concluons que l'augmentation de la sensibilité TGF après levée d'une UUO prolongée associée à une élévation de la pression oncotique interstitielle, pourrait jouer un rôle pour prévenir la diurèse post-obstructive, alors que l'altération de la sensibilité TGF après BUO pourrait contribuer à ce phénomène

The changes in renal function after a single dose of intravenous furosemide in patients with compensated liver cirrhosis

BACKGROUND: Patients with compensated Child-A cirrhosis have sub clinical hypovolemia and diuretic treatment could result in renal impairment. AIM: To evaluate the changes in renal functional mass as reflected by DMSA uptake after single injection of intravenous furosemide in patients with compensated liver cirrhosis. METHODS: Eighteen cirrhotic patients were divided in two groups; eight patients (group 1, age 56 ± 9.6 yrs, Gender 5M/3F, 3 alcoholic and 5 non alcoholic) were given low intravenous 40 mg furosemide and ten other patients (group 2, age 54 ± 9.9, Gender 6M/4F, 4 alcoholic and 6 non alcoholic) were given high 120 mg furosemide respectively. Renoscintigraphy with 100MBq Of Tc 99 DMSA was given intravenously before and 90 minutes after furosemide administration and SPECT imaging was determined 3 hours later. All patients were kept under low sodium diet (80mEq/d) and all diuretics were withdrawn for 3 days. 8-hours UNa exertion, Calculated and measured Creatinine clearance (CCT) were performed for all patients. RESULTS: Intravenous furosemide increased the mean renal DMSA uptake in 55% of patients with compensated cirrhosis and these changes persist up to three hours after injection. This increase was at the same extent in either low or high doses of furosemide. (From 12.8% ± 3.8 to 15.2% ± 2.2, p < 0.001 in Gr I as compared to 10.6% ± 4.6 to 13.5% ± 3.6 in Gr 2, p < 0.001). In 8 patients (45%, 3 pts from Gr 1 and 5 pts from Gr 2) DMSA uptake remain unchanged. The mean 8 hrs UNa excretion after intravenous furosemide was above 80 meq/l and was higher in Gr 2 as compared to Gr 1 respectively (136 ± 37 meq/l) VS 100 ± 36.6 meq/l, P = 0.05). Finally, basal global renal DMSA uptake was decreased in 80% of patients; 22.5 ± 7.5% (NL > 40%), as compared to normal calculated creatinine clearance (CCT 101 ± 26), and measured CCT of 87 ± 30 cc/min (P < 0.001). CONCLUSION: A single furosemide injection increases renal functional mass as reflected by DMSA in 55% of patients with compensated cirrhosis and identify 45% of patients with reduced uptake and who could develop renal impairment under diuretics. Whether or not albumin infusion exerts beneficial effect in those patients with reduced DMSA uptake remains to be determined

Göttinger Bodenkundliche Berichte 29

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