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Recombinant human growth hormone exacerbates chronic puromycin aminonucleoside nephropathy in rats
H Trachtman1, S Futterweit, N Schwob
1Department 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.
Insights
Recombinant human growth hormone (rhGH) treatment worsened chronic kidney disease in rats. rhGH increased protein in urine, reduced kidney function, and worsened kidney damage, indicating potential risks for patients with renal failure.
Area of Science:
- Nephrology
- Endocrinology
- Pediatric Nephrology
Background:
- Chronic renal failure in children often presents with growth failure.
- Recombinant human growth hormone (rhGH) can improve growth but may harm kidneys.
- Potential adverse effects of rhGH on kidney function and disease progression are a concern.
Purpose of the Study:
- To investigate the impact of rhGH on the severity of chronic puromycin aminonucleoside (PAMN) nephropathy in a rat model.
- To assess whether rhGH exacerbates or ameliorates established chronic kidney disease.
Main Methods:
- Chronic glomerulopathy was induced in rats using serial puromycin aminonucleoside injections over 12 weeks.
- Experimental rats received rhGH (0.5 mg thrice weekly); control rats received vehicle.
- Evaluated parameters included weight, hematocrit, blood pressure, urinary protein, inulin clearance, glomerulosclerosis, tubulointerstitial injury, and glomerular hypertrophy.
Main Results:
- rhGH did not affect weight gain, hematocrit, or blood pressure in rats with nephropathy.
- Urinary protein excretion increased by approximately 50% in rhGH-treated rats.
- rhGH significantly reduced inulin clearance, increased glomerulosclerosis and tubulointerstitial injury, and enhanced glomerular hypertrophy compared to controls.
Conclusions:
- rhGH administration worsened experimental chronic kidney disease in rats.
- rhGH treatment led to increased proteinuria, reduced glomerular filtration, and exacerbated kidney damage.
- Findings suggest rhGH may adversely affect kidney function and disease progression in chronic renal failure.
Abstract:
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)