Trachtman H, Futterweit S, Schwob N, Maesaka J, Valderrama E
Department of Pediatrics (Division of Nephrology), Schneider Children's Hospital of Long Island Jewish Medical Center, Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York.
Kidney Int. 1993 Dec;44(6):1281-8. doi: 10.1038/ki.1993.380.
Growth failure is a cardinal feature of chronic renal failure in children. Administration of recombinant human growth hormone (rhGH) ameliorates this problem but may adversely affect the kidney and hasten the progression to end-stage renal disease. We conducted experiments to examine the impact of rhGH on the severity of chronic puromycin aminonucleoside (PAMN) nephropathy in rats. The glomerulopathy was induced by serial injections of PAMN over a 12 week period. Experimental animals (N = 6) received rhGH, 0.5 mg per dose, three times weekly, while control rats (N = 6) received hormone vehicle. rhGH had no effect on weight gain, hematocrit, or blood pressure in rats with the experimental renal disease. Urinary protein excretion increased approximately 50% in rhGH-treated rats with chronic PAMN nephropathy compared to untreated animals between four to eight weeks of the observation period. After 12 weeks, the inulin clearance was significantly lower in rhGH-treated rats, 0.26 +/- 0.05 versus 0.50 +/- 0.06 ml/min/100 g body wt in control PAMN animals, P < 0.05. Compared to untreated rats with PAMN nephropathy, administration of rhGH increased the extent of segmental glomerulosclerosis from 11 +/- 3 to 46 +/- 9% (P < 0.005) and elevated the tubulointerstitial injury score from 0.5 +/- 0.1 to 1.4 +/- 0.4 (P < 0.05). Furthermore, glomerular hypertrophy was enhanced in animals with chronic PAMN nephropathy given rhGH, as evidenced by a larger glomerular planar area, 9.2 +/- 0.3 x 10(-3) versus 11.9 +/- 0.5 x 10(-3) mm2, P < 0.005.(ABSTRACT TRUNCATED AT 250 WORDS)
生长发育迟缓是儿童慢性肾衰竭的主要特征。给予重组人生长激素（rhGH）可改善这一问题，但可能对肾脏产生不利影响，并加速疾病进展至终末期肾病。我们进行了实验，以研究rhGH对大鼠慢性嘌呤霉素氨基核苷（PAMN）肾病严重程度的影响。通过在12周内连续注射PAMN诱导肾小球病变。实验动物（N = 6）每周接受3次rhGH注射，每次剂量为0.5 mg，而对照大鼠（N = 6）接受激素载体。rhGH对患有实验性肾病的大鼠的体重增加、血细胞比容或血压没有影响。在观察期的4至8周内，与未治疗的动物相比，接受rhGH治疗的患有慢性PAMN肾病的大鼠尿蛋白排泄增加了约50%。12周后，接受rhGH治疗的大鼠菊粉清除率显著降低，为0.26 +/- 0.05 ml/min/100 g体重，而对照PAMN动物为0.50 +/- 0.06 ml/min/100 g体重，P < 0.05。与未治疗的PAMN肾病大鼠相比，给予rhGH使节段性肾小球硬化的程度从11 +/- 3%增加到46 +/- 9%（P < 0.005），并使肾小管间质损伤评分从0.5 +/- 0.1提高到1.4 +/- 0.4（P < 0.05）。此外，给予rhGH的慢性PAMN肾病动物肾小球肥大增强，表现为更大的肾小球平面面积，分别为9.2 +/- 0.3 x 10(-3)与11.9 +/- 0.5 x 10(-3) mm2，P < 0.005。（摘要截断于250字）
