This study was performed to evaluate the effects of cyclosporine-A (CsA) on linear growth in pediatric patients with steroid-dependent (SDNS) or resistant nephrotic syndrome (SRNS).
Thirty-five pediatric patients with SDNS or SRNS undergoing glucocorticoid (GC) and/or CsA treatment were retrospectively reviewed. Seventeen patients were treated with GC alone and 18 were treated with GC and CsA. The cumulative doses of GC and CsA were quantified (mg/kg/day). Linear growth during the follow-up period was defined as the difference in Z-score between the initial and final height according to the follow-up period (Δ height Z score/year). The associations between linear growth and clinical parameters were analyzed.
The linear growth of patients in the two groups was not significantly different (
In children with SDNS or SRNS undergoing GC therapy, added CsA treatment may not have harmful effects on linear growth.
Idiopathic nephrotic syndrome, one of the most common nephropathies occurring in childhood, is characterized by edema, nephrotic-range proteinuria, hypoalbuminemia, and hyperlipidemia. Glucocorticoid (GC) therapy is the mainstay of treatment for childhood nephrotic syndrome. Although it has much improved the prognosis of these patients, the long-term use of GC may have several adverse effects, including growth retardation and bone loss, especially in growing children [
Data from 35 pediatric patients with SDNS or SRNS who received GC treatment with or without CsA at Kyung Hee University Hospital and Bucheon St. Mary’s Hospital of the Catholic University of Korea between March 2003 and December 2014 were reviewed retrospectively. SDNS was defined when patients had two consecutive relapses during corticosteroid therapy, or within 14 days of ceasing therapy, and SRNS was defined when children with nephrotic syndrome did not achieve remission after 8 weeks treatment of daily corticosteroid [
The initial height, assessed at the time of diagnosis, the height at starting CsA treatment, and final height, assessed at the end of the follow-up period, were expressed as Z scores according to the standards of the 2007 Korea National Growth Charts8). Linear growth during the follow-up period was defined as the difference between the Z scores of the initial and final heights (Δheight Z score/year).
Data were presented as means±standard deviations (SD) for normally distributed variables and as medians and interquartile ranges for nonparametric variables. Differences between groups were analyzed using unpaired Student’s t-tests (for variables with parametric distributions) and the Mann–Whitney U-test (for variables with nonparametric distributions). Associations between linear growth and clinical parameters were analyzed using Spearman’s correlation coefficient (r). Linear regression was used to evaluate the associations of the cumulative doses of GC and CsA with linear growth in two separate univariate models. Multivariate analyses were used to adjust for potential confounders, such as sex, age, duration of follow up, and initial height Z score. Statistical analyses were performed using SPSS software (version 20.0; IBM Corporation, Armonk, NY, USA). Significance was defined as
All subjects in the GC group had SDNS. In the CsA group, 7 patients had SDNS and 11 had SRNS. The subjects in the CsA group were well matched with those in the GC group with regard to sex distribution, age at the time of diagnosis, age at the end of follow up, duration of follow up, height at the time of diagnosis, and cumulative dose of GC received during the observational period (
The linear growth of patients (Δheight Z score/year) did not differ significantly between GC group and CsA group (
In the present study, the effect of GC combined with CsA treatment on the linear growth of nephrotic patients did not differ from that of treatment with GC alone. Results of two previous studies suggested that CsA therapy had no harmful effect, and indeed had a positive effect, on linear growth [
The observed effects of GC on growth were in accordance with those reported previously [
In conclusion, in children with SDNS or SRNS undergoing steroid therapy, the addition of CsA to the treatment regimen may not have a harmful effect on linear growth. However, the steroid dose was associated negatively with linear growth.
No potential conflict of interest relevant to this article was reported.
Clinical Characteristics and Growth Data of Children with Steroid-dependent and Steroid-resistant Nephrotic Syndrome
GC group (n=17) | CsA group (n=18) | ||
---|---|---|---|
SDNS:SRNS | 17:0 | 7:11 | |
Sex (M:F) | 10:7 | 16:2 | 0.096 |
Age at diagnosis (years) | 5.87±2.15 | 5.01±2.03 | 0.229 |
Age at the end of follow up (years) | 8.40±1.90 | 8.69±2.33 | 0.690 |
Duration of follow-up period (months) | 36.2 (22.2-45.23) | 41.7 (24.25-62.08) | 0.373 |
Duration of administering GC (months) | 22.5 (6.81-43.3) | 15.4 (11.80-25.33) | 0.817 |
1)Cumulative dose of GC (mg/kg/day) | 0.57 (0.36-0.69) | 0.42 (0.27-0.53) | 0.121 |
Before administering CsA | 2.34 (0.64-3.64) | 0.006 | |
Since administering CsA | 0.21 (0.07-0.45) | ||
Duration of administering CsA (months) | 13.9 (7.6-40.7) | ||
Cumulative dose of CsA (mg/kg/day) | 0.85 (0.54-1.43) | ||
2)Height at diagnosis (Z score) | 0.36±1.56 | -0.18±0.93 | 0.223 |
3)Height at the end of follow up (Z score) | -0.26±1.31 | -0.19±0.91 | 0.853 |
4)Δheight Z score/year | -0.06 (-0.42-0.11) | -0.01 (-0.08-0.06) | 0.262 |
5)Height at starting CsA (Z score) | -0.28 ±0.93 | ||
6)Δheight Z score/year before administering CsA | 0 (-0.01-0) | 0.001 | |
7)Δheight Z score/year since administering CsA | 0.21 (0.07-0.45) |
Abbreviations: GC group: patients treated with glucocorticoid only; CsA group: patients treated with glucocorticoid and cyclosporine A; SDNS: steroiddependent nephrotic syndrome; SRNS: steroid-resistant nephrotic syndrome; 4) Δheight Z score: difference between Z scores 2) and 3); 6) Δheight Z score: difference between Z scores 2) and 5); 7) Δheight Z score: difference between Z scores 3) and 5).
Regression Analyses of Linear Growth in Children with Nephrotic Syndrome
Univariate |
Multivariate |
|||||||
---|---|---|---|---|---|---|---|---|
Standard β | R | CI (95%) | Standard β | R | CI (95%) | |||
Cumulative dose of steroids | -0.540 | 0.001 | 0.348 | -0.351~0.008 | -0.543 | <0.001 | 0.746 | -0.709~0.790 |
Cumulative dose of cyclosporine | -0.004 | 0.983 | 0.475 | -0.181~-0.002 | -0.068 | 0.615 | -0.317~0.062 | |
Sex | -0.255 | 0.074 | -0.096~0.625 | |||||
Age at diagnosis | -0.045 | 0.749 | -0.266~0.132 | |||||
Age at the end of follow up | -0.026 | 0.846 | -0.150~0.259 | |||||
Duration of follow-up period | -0.006 | 0.964 | -0.019~0.018 | |||||
Z score of height at the time of diagnosis | -0.410 | 0.003 | -0.186~0.035 |
Abbreviation: CI, confidence interval.