Three Times Weekly (TIW) Growth Hormone Therapy in Children on Hemodialysis

Objectives/Aims:

1. To demonstrate the beneficial effects of thrice weekly SQ rGH Rx on growth in children
on HD

2. To demonstrate the beneficial effects of thrice weekly SQ rGH Rx in terms of improved
lean body mass, nutritional status and quality of life in children on HD

Study Design:

1. Study group - Provision of standard weekly dose of SQ rGH (0.35 mg/kg/week divided into
3 doses, each dose being given at the conclusion of dialysis therapy) for up to 2 years
to growth retarded (Height SDS < -1.88 or Height velocity < -1.88 SD) children
receiving HD who are naïve to rGH or who have not been on rGH for at least 12 months.
Inclusion criteria are: medically cleared for SQ rGH Rx (14); growth potential based on
Tanner stage 1 with open epiphyses on Bone Age radiographs (Bone age < 12 years);
expected to require HD for at least 6 more months; at least 6 months of standardized
historical pre-study anthropometric data (including stadiometer height). Exclusion
criteria include all medical factors that indicate that rGH therapy should not be used
(14), e.g., poor nutritional status, poorly controlled acidosis, poor dialysis adequacy
(defined by Kt/V < 1.2), poorly controlled renal osteodystrophy (PTH > 800). Once the
complicating factor is addressed and corrected, the child may be considered for the
study.

2. SQ rGH to be provided in-center at the conclusion of dialysis session three times
weekly for up to 24 months. SQ rGH dose to be adjusted based on dry (euvolemic)
weight every month during the intervention.

3. Baseline and monitoring data obtained on each patient on SQ rGH Rx. This will include
stadiometer measured height for at least 6 months prior to initiation of SQ rGH Rx to
provide important baseline height and growth velocity to be used to determine magnitude
of the response.

4. For children with suboptimal response after 6 months of standard SQ rGH Rx dose
(annualized growth rate < 2 cm more than the preceding year), the rGH dose will be
increased to 0.70 mg/kg/week divided into 3 doses (similar to the reported "pubertal"
dosing regimen used in some GH deficient children).

Baseline data: Height (stadiometer), Weight, BMI, Height SDS, Height velocity SDS
(historical past 6 months), Weight SDS, BMI SDS, Hb, BUN, nPCR, serum albumin, serum
calcium, serum phosphorus, iPTH, electrolytes, high sensitivity CRP (as a marker of
inflammation), dialysis adequacy (defined by single and double pool Kt/V - Kt/V is a
unitless number used to quantify hemodialysis and peritoneal dialysis treatment adequacy: K
- dialyzer clearance of urea, t - dialysis time, V - patient's total body water; in HD the
target is 1.2), IGF-1, IGFBP-3, hip films and bone age (4,5,6,9). In addition, lean body
mass/and fat mass will be assessed by DEXA (to standardize the determination of LBM, DEXA to
be done mid week, after the dialysis treatment, to avoid the excess fluid commonly present
after 2 days off dialysis each weekend) and quality of life will be assessed by the PedsQL
4.0 Generic Core Scales (10). The nutritional parameters that will be determined (wt/ht, ht
SDS, BMI, nPCR and serum albumin) represent the currently used assessments of nutrition for
these patients and have been validated as best measures of nutrition in children on dialysis
(12).

Assessments to be repeated at the following intervals:

1. Height (stadiometer), Weight, Hgb, BUN, nPCR, serum albumin, serum calcium, phosphorus,
and electrolytes, Kt/V - monthly

2. CRP, iPTH, IGF-1, IGFBP-3 - every 3 months

3. PedsQL - every 6 months

4. DEXA and Bone Age - yearly (and within 1 week of renal transplant if this occurs
anytime 6 months after start of study) - DEXA and Bone Age results will be sent to
Nationwide Children's and analyzed by our collaborating pediatric radiologist (Larry
Binkovitz, MD).

Inclusion Criteria:

- Chronic Renal Failure on Hemodialysis

- Tanner 1

- Bone Age <12

- Below the 3rd %tile for height or have growth velocity < 3rd %tile and are not
on SQ rGH Rx

- At baseline, study population will also have to have documentation of normal thyroid
status, secondary hyperparathyroidism will be controlled in acceptable range (iPTH <
800), adequate dialysis (Kt/V >1.2) and normal acid-base status.

- expected to be on hemodialysis at least 6 months

Exclusion Criteria:

- Anyone not meeting the inclusion criteria.