Mechanisms of hyperkalemia associated with hyporeninemic hypoaldosteronism in streptozotocin-induced diabetic rats.
This study was aimed at investigating the mechanisms of clinically important overt hyperkalemia in diabetes mellitus with underlying hyporeninemic hypoaldosteronism known as a classic model of the syndrome of hyporeninemic hypoaldosteronism (SHH). Rats (Sprague-Dawley, male) were streptozotocin-treated (60 mg/kg, ip) and used after 60 days. Rats with plasma glucose levels higher than 300 mg/dL (mean +/- SEM, 423 +/- 20 mg/dL, n = 8) were selected as the diabetic group. Age-matched normal rats served as control (mean plasma glucose, 88 +/- 2, mg/dL, n = 8). Serum potassium concentrations and osmolalities as well as serum creatinine levels were significantly higher in the diabetic than in the control group (5.07 +/- 0.09 vs. 4.68 +/- 0.11 mEq/L; 330 +/- 14 vs 290 +/- 3 mOsm/L; 0.40 +/- 0.03 vs 0.31 +/- 0.02 mg/dL, p < 0.05). Plasma renin activity (PRA) in the diabetic group was significantly lower than that in the control group (6.0 +/- 1.0 vs 12.1 +/- 1.1 ng Al/ml/h, p < 0.001). Plasma aldosterone concentration (PAC) was also significantly lower in the former than in the latter (368 +/- 30 vs 761 +/- 57 pg/ml, p < 0.001). Renomegaly, abnormal distal tubular cells with few organelles, and increased lipid droplets with pyknotic nucleus in zona glomerulosa of the adrenal glands were noted in the diabetic group. In conclusion, multifactorial causes including insulinopenia, hyperosmolality, elevated serum creatinine level and hypoaldosteronism with possible contribution of altered distal tubular response to aldosterone may have interacted to develop hyperkalemia in these diabetic rats.
Kim
H J
HJ
Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D006947:Hyperkalemia / Q000150:complications*; D006994:Hypoaldosteronism / Q000150:complications*; D007686:Kidney Tubules, Distal / Q000648:ultrastructure; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015384:Zona Glomerulosa / Q000648:ultrastructure