Patterns of recombinant growth hormone therapy use and growth responses among children with chronic kidney disease

Abstract

Background: Recombinant growth hormone (rGH) is an efficacious therapy for growth failure in children with chronic kidney disease (CKD). We described rGH use and estimated its relationship with growth and kidney function in the Chronic Kidney Disease in Children (CKiD) cohort.

Methods: Participants included those with growth failure, prevalent rGH users, and rGH initiators who did not meet growth failure criteria. Among those with growth failure, height z scores and GFR were compared between rGH initiators and non-initiators across 42 months. Inverse probability weights accounted for differences in baseline variables in weighted linear regressions.

Results: Among 148 children with growth failure and no previous rGH therapy, 42 (28%) initiated rGH therapy. Of the initiators, average age was 8.9 years, height z score was 2.50 standard deviations (SDs) (0.6th percentile), and GFR was 44 ml/min/1.73m2. They were compared to 106 children with growth failure who never initiated therapy (8.8 years, -2.33 SDs, and 51 ml/min/1.73m2). At 30 and 42 months after rGH, height increased +0.26 (95%CI: -0.11, +0.62) and +0.35 (95%CI: -0.17, +0.87) SDs, respectively, relative to those who did not initiate rGH. rGH was not associated with GFR.

Conclusions: Participants with growth failure receiving rGH experienced significant growth, although this was attenuated relative to RCTs, and were more likely to have higher household income and lower GFR. A substantial number of participants, predominantly boys, without diagnosed growth failure received rGH and had the highest achieved height relative to mid-parental height. Since rGH was not associated with accelerated GFR decline, increasing rGH use in this population is warranted.

Keywords: Children; Chronic kidney disease; Growth; Growth hormone; Pediatric nephrology.

Conflict of interest statement

Conflicts of interest: All co-authors declare no conflict of interest.

© 2021. IPNA.

Figures

Figure 1.

Longitudinal height z-scores after treatment initiation, by treatment group, displaying individual data (○) and mean levels at each time point (●). Values atop the left and right panels display differences in height z-score (95% CI) at each time point with the treatment group as the reference (center).

Figure 2.

Weighted mean change in height z-scores from baseline comparing children with growth failure who received recombinant growth hormone and those who did not. Time of initiating was assumed to be the midpoint of two visits. p-value indicates difference in change in height z-score between treated and untreated groups at each time point from linear regression models using generalized estimating equations.

Figure 3.

Weighted mean GFR over time comparing children with growth failure who received recombinant growth hormone and those who did not. p-value indicates difference in percentage change in eGFR between treated and untreated groups at each time point from linear regression models using generalized estimating equations.

Figure 4.

Oldest observed participant height relative to mid-parental height by age, stratified by four rGH therapy groups: prevalent users who initiated rGH therapy prior to study enrollment (n= 95), incident rGH users without evidence of growth failure (n= 36), incident rGH users with growth failure (n= 42) and participants with growth failure who did not receive therapy (n= 106). Nonparametric Lowess splines summarize average levels across ages by rGH therapy groups.