Utilization of rhGH Therapy in Children with CKD and Growth Impairment Varies

Despite advances in care for children with chronic kidney disease (CKD), growth impairment remains common in the population of pediatric CKD patients. Data from the North American Pediatric Renal Trials and Collaborative Studies CKD registry show that 36.9% had height standard deviation scores (SDS) <–1.88 at time of enrollment. In a recent study in North America among children with mild to moderate CKD, median height SDS was –0.55 at study entry.

Pediatric CKD patients with short stature experience lower quality of life, which often persists into adulthood. Although there is an association between treatment with recombinant human growth hormone (rhGH) and improved physical and social functioning according to parental reports, there are no data available to support the assumption that rhGH treatment improves quality of life in children with CKD.

According to Oleh M. Akchurin, MD, PhD, and colleagues, available literature reveals a low level of utilization of rhGH in short children with CKD in North America as well as in many European countries. Requirements for diagnostic testing related to rhGH insurance approval vary; some US insurers require a bone age for short children >12 years of age whose height is below the third percentile and an estimated glomerular filtration rate <75 mL/min/1.73 m2.

Treatment with rhGH is also complicated by its high cost as well as the logistic challenges involved in its prescription. Insurance approval, evaluation and monitoring of nutritional status, management of other CKD complications, optimization of dialysis, and potential involvement of endocrinology all require system-based approaches to rhGH therapy. Those challenges coupled with the availability of resources at individual institutions may be contributing factors to the variability in prescription of rhGH therapy from practice to practice.

Dr. Akchurin et al. hypothesized that there is substantial variability in practice patterns and resources available to support rhGH treatment among pediatric nephrology centers, potentially affecting treatment decisions. The researchers conducted an analysis of the key characteristics of rhGH treatment approaches using a survey of pediatric nephrologists in the United States and Canada. They reported results of the analysis online in BMC Nephrology [doi:10.1186/s12882-017-0599-1].

The cross-sectional online survey was electronically distributed to pediatric nephrologists through the Midwest Pediatric Nephrology Consortium and the American Society of Pediatric Nephrology. The survey was offered to active members of the consortium who had provided their e-mails to the database (n=200). The response rate among individuals was 33%; the rate per institution (percentage of institutions with at least one response) was 50%. In all, 73 pediatric nephrologists responded to the survey. Respondents represented 26 states and the District of Columbia in the United States and two provinces in Canada.

The respondents who identified their institution (n=66) represented 41 pediatric nephrology practices (23 with four or less pediatric nephrologists per practice [small practice] and 18 with five or more pediatric nephrologists per practice [large practice]). On average, there were 1.6 responses per practice, with no significant differences in the number of responses per practice between the small and large practices (1.5 and 1.7 responses, respectively).

There were significant differences between the small and large practices in resources available for support of rhGH treatment program. The majority of large practices had a renal dietitian (90.9%); only half of small practices included a renal dietitian (P=.001). In one third of small centers, the pediatric nephrologist alone addressed the nutritional needs of children with CKD and growth failure. Endocrinology was utilized for most aspects of rhGH therapy in 43.6% of small centers, compared with 6.3% in large centers (P<.001).

There were significant differences in the routine workups for rhGH therapy candidates with CKD among the centers. Bone age was routinely measured by most pediatric nephrologists, but only 39.7% obtained hip and knee x-rays. Thyroid studies were obtained by approximately half of the clinicians. Endocrinology consultation was part of the initial workup almost exclusively in small centers (P<.001). In centers with endocrinology involvement, GH-insulin like growth factor-1 level was obtained more frequently: 64.7% versus 35.3% in centers with rare endocrinology involvement; P=.007. In both small and large centers, ophthalmologic evaluation was rarely utilized before initiation of rhGH therapy.

The most common reason for not treating short children with CKD with rhGH in both small and large centers was family refusal. The most common reason for family refusal was fear of injections, followed by concern about side effects. In large centers, the second most common reason for not prescribing rhGH therapy was medical contraindications, including active malignancy, uncontrolled severe hyperparathyroidism, and closed epiphyseal growth plates (P=.03, difference from small centers). The second most common reason in small centers was difficulties with insurance approval (P=.05, difference from large centers).

Ninety-five percent of the pediatric nephrologists believed that rhGH therapy improves quality of life; only 23.3% believed that it improves physical function. Approximately 40% of participating nephrologists believed that growth hormone increases lean body mass; a third said it improves nutrition and appetite. Senior nephrologists were more likely to believe that rhGH improves nutrition and appetite compared with junior nephrologists.

The researchers cited some limitations to the study, including not investigating the root causes of differences in rhGH management of children with CKD between institutions and individual nephrologists, and a possible selection bias because physicians treating more children with rhGH may have been more interested in participating in the study that those seeing fewer pediatric patients with advanced CKD and end-stage renal disease.

In conclusion the researchers said, “This study found substantial variation in practice between pediatric nephrologists caring for short children with CKD. Practice size appears to be a major determinant of the logistic approach to rhGH management. Fear of injections was perceived as a most common obstacle to rhGH therapy initiation. Pediatric nephrologists believe that rhGH improves quality of life in children with growth failure and CKD. Our data suggest that opportunities are available to standardize care to improve growth outcomes in children with CKD.”

Takeaway Points

  1. Growth impairment is common in pediatric chronic kidney disease (CKD) patients, contributing to a lower quality of life in this patient population.
  2. Treatment with recombinant human growth hormone (rhGH) is associated with improvements in physical and social functioning, according to parental reports; however, available data indicate a low level of utilization of rhGH therapy in short children with CKD.
  3. A survey conducted among 73 pediatric nephrologists revealed a wide variation in pediatric nephrology practice in addressing short stature and rhGH utilization in children with CKD. The most common obstacle to rhGH utilization was family refusal, based on fear of injections.