Table 2.

Summary of experimental and clinical studies about the renal safety of growth hormone (n = 9)

Dose & Duration	Subjects	Type of study	Main results	Reference
2.5, 5, 10, and 20 lU/kg/day subcutaneously for 4–60 days	Female rats	Experimental	- Dose-dependent increase in renal weight - No change in kidney dry weight/body weight ratio - Increase in renal glomerular and tubular cell proliferation and renal DNA/protein ratio	Mehls et al. 1993 [86]
0.025, 0.1, and 1 IU/kg/day subcutaneously for 14 weeks	Male and female dogs	Experimental	- Increase in body weight gain and kidney weights - Glomerular deposits, mesangial thickening, and very slight cellular infiltration in glomeruli - Increase in the renal glomerular area - Glomerular basal lamina thickening - Increase in mesangial matrix	Molon-Noblot et al. 2000 [87]
5–10 mg/day for 3–9 days	2 patients with hypopituitarism, 1 with cirrhosis of the liver and 2 with chronic nephritis and uremia	Case report	- Decrease in plasma urea level and urea excretion - Prompt increase in creatinine clearance and phosphorus reabsorption	Gershberg 1960 [80]
More than 400 mg/week testosterone proprionate and/or nandrolone deconate intramuscularly	4 body builders aged between 20 and 26 years	Case report	- Increase in serum creatinine and decreased in eGFR - Development of acute tubular necrosis	Almukhtar et al. 2015 [22]
50 ng/kg/min as an infusion for 2 h	Healthy men	Pilot clinical trial	- Decrease in renal plasma flow - No change in GFR	Parving et al. 1978 [81]
2 IU in the morning and 4 IU in the evening subcutaneously for 1 week	Healthy men	Pilot clinical trial	- Increase in GFR and renal plasma flow - No significant change in kidney size and urinary excretion rates of albumin and β2-microglobulin	Christiansen et al. 1981 [93]
0.125 IU/kg per week subcutaneously for the first 4 weeks and 0.25 IU/kg per week for the subsequent 5 months	Growth hormone deficient adults	Double-blind, placebo-controlled, cross-over clinical trial	- No change in GFR and renal plasma flow - No effect on kidney size	Riedl et al. 1995 [82]
0·02 IU/kg/day (or 7 μg/kg/day) subcutaneously for 10 months	Adults with childhood onset GH deficiency	Pilot clinical trial	- Increase in left ventricular-mass index and kidney length - No abnormalities or change in the urine analysis	Link et al. 2001 [94]
6 IU/m2 per day subcutaneously for 6 days	Healthy volunteer males	Randomized, cross-over clinical trial	- Increase in the plasma renin - Increase in distal tubule sodium and water reabsorption - Decrease in mean 24-h urinary output and mean 24-h urinary sodium excretion	Hansen et al. 2001 [99]