甲状腺機能亢進症 (Graves病) 患者における腎からの尿素, クレアチニン, 水, 電解質排泄の変化

抄録

To delineate the pathophysiological basis for increased blood urea nitrogen (BUN), decreased serum creatinine (SCr) and increased BUN/SCr ratio in patients with hyperthyroidism due to Graves' disease, systematic evaluation on renal handling of solutes and water was carried out before and during treatment of the disease.
First, BUN, SCr, serum sodium (Na), serum potassium (K), serum chloride (Cl), creatine kinase (CK), serum triiodothyronine (T₃) and serum thyroxine (T₄) were consecutively measured in 16 patients (aged 18-62 yrs, 4 males and 12 females) with Graves' disease before and during antithyroid drug therapy, and 16 healthy subjects (aged 22-64 yrs, 4 males and 12 females) served as controls.
BUN (14.8±2.9mg/100ml) was significantly higher (p<0.01), and SCr (0.62±0.16mg/100ml) and CK (41.7±23.6U/l) were significantly lower (p<0.01) in untreated patients compared to respective values in the control group (BUN, 13.2±2.9mg/100ml; SCr, 0.87±0.16mg/100ml; CK, 99.3±49.5U/l). Consequently, BUN/SCr ratio was significantly elevated (p<0.01) in the patients. As T₄ and T₃ returned to normal, BUN, SCr, BUN/SCr ratio and CK of the patients also normalized. Serum electrolytes were not significantly different in the patients compared to the controls.
Second, renal clearance of para-aminohippurate (C_PAH), inulin (C_IN), creatinine (C_Cr), free water (C_H2O) and chloride (C_Cl) was evaluated in 7 untreated patients (aged 17-44 yrs, 4 males and 3 females) and in 7 controls (aged 24-39 yrs, 5 males and 2 females).
In patients with untreated Graves' disease, C_PAH/C_Cr and C_urea. were significantly greater than in the controls (847±367 vs 442±124ml/min, p<0.05, 132.7±14.7 vs 76.6±14.4ml/min, p<0.01, and 86.9±16.0ml/min vs 52.1±12.6ml/min, p<0.05, respectively). C_In. was slightly but insignificantly increased in the patients (95.3±20.8ml/min) compared to the controls (76.7±13.3ml/min). As a result, C_Cr/C_In and C_urea/C_In were significantly greater in the patients than in the controls (142.7±32.0 vs 100.7±7.1%, p<0.01, 92.4±18.7 vs 68.4±14.4%, p<0.05, respectively). The difference between C_Cr and C_In indicates that 40% of urinary creatinine is of tubular origin. Renal excretion of urea and creatinine was increased by 117% and decreased by 77%, respectively in the patients, but the differences were not statistically significant. Distal tubule delivery{DTD, (C_H2O+C_Cl)/C_In×100}in the patients was significantly less than in the controls (6.76±4.60 vs 13.1±2.7%, p<0.05), but distal fractional chloride reabsorption{DFCR, C_H2O/(C_H2O+C_Cl)×100}was not significantly different.
We conclude that in patients with Graves' disease, 1) BUN/SCr ratio is increased due to elevation of BUN and decrease of SCr, 2) elevation of BUN is due to increased urea production but not due to decreased urinary excretion, 3) decreased serum creatinine is due to increased renal clearance resulting from excessive tubular secretion, and decreased creatinine production may also contribute to low SCr, 4) distal tubule delivery is decreased, suggesting an increase in reabsorption of water and sodium from the proximal tubule and/or the loop of Henle.