Background: Growth suppression is a known complication of prolonged steroid therapy in children with nephrotic syndrome (NS). Those with frequent relapses (FR) and those steroid-dependent (SD) have a significant growth delay compared to children with infrequent relapses (IR). There is substantial variability in the way childhood NS is treated and the majority of these children will exhibit improved growth rate after cessation of therapy, though some will not undergo catch-up growth, experiencing issues related to short stature later in life. The aims of our study were to assess growth deficits in children with FR/SD NS and evaluate the impact and the appropriate time to introduce a steroid-sparing agent (SSA).
Methods and findings: We are presenting the growth data in pre-pubertal children (<10 years of age) followed in two geographically distinct pediatric centers, and discuss approaches to reduce the negative impact of steroids on growth. The main data collected were growth rate (GR) and height standard deviation score (HtSDS). Statistical analysis was performed using ANOVA, regression analysis and student t-test.
The GR (in cm/yr) was 6.94 ± 4.99 and 10.2 ± 5.4 in IR, and 5.86 ± 5.06 and 4.36 ± 2.45 in FR/SD, at 6 and 12 months after diagnosis, respectively. The GR was slower in the second 6 months period in FR/SD (n=9) compared to IR (n=16): 4.4 ± 2.5 vs. 10.2 ± 5.4 cm/yr (p<0.001). The HtSDS change, independent of location, was more pronounced in FR/SD:-0.53 ± 0.47 compared to 0.16 ± 0.53 in patients with IR, p=0.003. Previous reports of early detrimental impact of steroids on growth have suggested the possibility of a positive effect of therapy with a SSA. We have retrospectively looked at 10 patients with FR/SD disease course whose therapy was switched from steroids to SSA, and HtSDS improved from -1.12 ± 1.23 to -0.73 ± 1.21, p<0.001. We discuss additional facts about steroid therapy in NS and strategies to limit the patients’ exposure to them.
Conclusion: We conclude that strategies to minimize steroid exposure, such as reducing the duration of therapy based on response time and the use of SSA can prevent the growth deficit seen in children with FR/SD NS.
Alex R Constantinescu, Simona Maruntelu, Evelio Velis, Teofana O Bizerea-Moga, Manuela C Almaguer, Tamara M Marcovici, Alexandru B Constantinescu and Otilia Marginean