Growth hormone replacement does not elevate albuminuria in GH-deficient adults

Abstract

Minor elevations in urinary albumin excretion rate (Ualb.V) are likely to be associated with renal function loss and increased cardiovascular risk. Since urinary albumin excretion is affected by the growth hormone (GH)--insulin-like growth factor-1 (IGF-1) axis, we evaluated the effect of 6 months GH replacement (1 U/day, n = 8 and 2 U/day, n = 16) on urinary protein handling in 24 non-diabetic, normotensive GH-deficient adults (12 men and 12 women), of whom 8 patients received placebo during 6 months, followed by active GH treatment. Plasma IGF-1 increased from 11.4 (8.1-15.8) nmol/L (median, interquartile range) to 35.4 (22.3-44.1) nmol/L (p < 0.001 versus change after placebo; median Z-score reached +0.2) after 6 months GH, and remained unaltered after placebo. Overnight Ualb.V was 4.0 (3.1-4.9) w g/min before and 4.6 (2.4-8.2) w g/min after GH (p > 0.10). Likewise, urinary IgG excretion rate did not significantly change after GH (0.71 (0.52-1.20) w g/min before GH versus 0.80 (0.51-1.56) w g/min after GH; p > 0.10). No significant changes were observed in creatinine clearance (p > 0.10) and mean arterial pressure (p > 0.10). No changes in any of these parameters were observed after placebo. Individual changes in Ualb.V were positively correlated with changes in plasma IGF-1 (r 2 = 0.41, p = 0.05) and with changes in mean arterial pressure (r 2 = 0.49, p < 0.02). The present study shows that 6 months GH replacement, increasing plasma IGF-1 within the physiological range, does not result in a clinically relevant increase in urinary protein excretion in GH-deficient adults. The correlation between changes in plasma IGF-1 and in albuminuria supports the rationale to avoid supraphysiological IGF-1 levels.