The response to 40 mg furosemide p.o. in 6 healthy kidney donors and 6 renal transplant recipients with and without naproxen pretreatment has been studied. No volume replacement was given in order to study the development of tolerance. The subjects showed an average dehydration of 1.5 kg · 6 h
–1.
While mean creatinine clearance was equal in patients and donors (76 vs 80 ml/min), renal furosemide clearance was significantly lower in the patients (47 vs 81 ml/min; P<0.05). the="" patients="" also="" excreted="" a="" smaller="" fraction="" of="" the="" dose="" in="" the="" urine="" (5.7="" vs="" 7.8="" mg/6="" h;="">P<0.05). as="" the="" overall="" renal="" sensitivity="" was="" similar="" in="" the="" two="" groups,="" the="" natriuretic="" response="" was="" correspondingly="" smaller="" in="" transplant="" recipients="" as="" compared="" to="">
Within the observation period of 6 h after dosing, acute tolerance developed in the donors and in 4 of the 6 patients, as shown by clockwise hysteresis in the dose (urine furosemide excretion rate)-response (natriuresis) curves. Pretreatment with naproxen reduced renal sensitivity to furosemide (right shift of the dose response curve) in all the donors but in only 2 of the patients.
In both groups acute tolerance was less pronounced after naproxen, which may indicate involvement of the prostaglandin system in the development of acute tolerance. The results may also indicate regeneration of sympathetic nerves with functional capacity in at least some renal transplants, or that other mechanisms of salt regulation compensate for loss of sympathetic nerve activity.
Key words Furosemide - renal transplant recipients - kidney donors - naproxen - dehydration - pharmacokinetics - salt-regulation