On the Role of the Kidneys in the Pathogenesis of Edema Formation during Permanent Morphine Application

Abstract

In order to assess possible renal mechanisms causing the as yet unexplained side-effects of peripheral edema, weight gain and swollen limbs seen during the chronic administration of opioids in patients, a rat study was designed, mimicking a constant infusion (24 h) of morphine (CAS 57-27-2) using subcutaneous drug delivery device systems. Subcutaneous (s.c.) morphine infusions (0, 10, 30 mg/kg body weight/24 h) have been administered using implantable mini-osmotic pumps with a delivery rate of 10 microl/h. In addition, s.c. implantable inulin/PAH clearance depot systems were used in order to measure renal functions such as glomerular filtration rate (GFR = inulin clearance), renal plasma flow (RPF = PAH clearance), creatinine clearance and urea clearance in the conscious rat. Compared to controls, morphine caused an increase in PAH clearance, creatinine clearance (both dose dependent), urea clearance (higher dose), body weight, and urine potassium concentration (both groups). Urine minute volume was reduced in the 10 mg morphine group, a dose dependent highly significant decrease of urine sodium in the 30 mg morphine group compared to controls and a significant decrease compared to the 10 mg group could be found. Serum sodium was highly significant and food uptake was significantly increased in the 30 mg group compared to controls. The histological examination of kidneys revealed no differences among the various groups. These data indicate a role of the kidney in the induction of peripheral edema during permanent morphine administration.