Growth and Growth Hormone Therapy in Children …annualdialysisconference.org/wordpress/wp-content/themes/adc/2016...Growth and Growth Hormone Therapy in Children with CKD ... Growth

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Growth and Growth Hormone Therapy in Children with CKD ADC 2016

John D Mahan, MD Professor of Pediatrics Nationwide Children’s/the Ohio State University

College of Medicine

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Overview Background

•Growth in Patients with CKD •Causes of Growth Failure in CKD

Growth Assessment and Evaluation for Growth Hormone Treatment in Children with CKD

Growth Hormone Therapy in Children with CKD: Benefits, Risks

Guidelines for Evaluating the Growth Response to rhGH Therapy

2

Growth: the Paramount Concern!

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1. Growth is one of the MOST important issues that children with CKD confront!

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What Concerns Children and Parents About Living with CKD*?

Percent (%)

Reynolds JM Arch Dis Child. 1995;73:36-42.

Social Outcome Following Renal Transplantation is Greatly Influenced by Adult Height

Adult height was significantly correlated with:

Characteristic P value

Year of transplantation .04

Higher educational level achieved <.001

Higher rate of paid employment .02

Greater likelihood of marriage <.0001

Greater likelihood of independent living .0003

Broyer M, Transplantation 2004: 77:1033-1037.

Height Dissatisfaction - Impacts Quality of Life

Mean adult height SDS score: –1.56 ± 1.55 Height satisfaction correlated significantly with height SDS score (r = 0.42; P = .006) Quality of life correlated significantly with height satisfaction (r = 0.41; P = .008)

0

5

10

15

20

25

30

35

40

Perc

ent o

f ind

ivid

uals

di

ssat

isfie

d w

ith a

dult

heig

ht

Adults with childhood-

onset ESRD

Healthy age-matched

controls Rosenkranz J, Pediatr Nephrol 2005;20:1288-1294.

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Growth Patterns in Patients with CKD

Child Without CKD

Child With CKD

Height

Birth Puberty

Adapted from Betts et al. Br Med J. 1974;2:189-193.

Growth in Patients with CKD

8

Patient 1 Patient 2

Furth S, Pediatrics 2002

Surv

ival

(%)

100

90

80

70

60

50

40

30 1 2 3 0

Years

Growth Failure in Children with CKD is Associated with Poorer Survival

Age >1, Z > -2.5

Age > 1, Z<-2.5

Age 0-1, Z > -2.5

Age 0-1, Z < -2.5

Height in 2,306 patients with CKD – NAPRTCS At initiation of dialysis - 1992-2001

Furth S.. Pediatr Nephrol 2002

Days

Sur

viva

l (%

)

100

95

90

85

80

75

1000 750 500 250 0 1250 1500 1750 2000

Severe growth failure

Moderate growth failure

Normal growth

Growth Failure in Children on Dialysis is Associated with Poorer Survival

1,112 patients < 18 yo ESRD – USRDS Tanner Stage I to IV, ht data Jan-Dec 1990

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2. The factors that can lead to poor growth in children with CKD include important modifiable and non-modifiable issues!

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Variables That Can Contribute to Growth Failure in CKD*

12 *Growth hormone indicated for CRI patients only, i.e., patients with GFR<75 mL/min/1.73m3.

Mahan et al. Pediatr Nephrol. 2006;21:917-930.

Age of onset of CKD Primary renal disease Calorie deficiency and abnormal protein metabolism Metabolic acidosis Renal osteodystrophy (CKD – Mineral Bone Disorder) Delayed puberty

Other comorbidities Urinary sodium loss Urine concentrating defect Glucocorticoid therapy

Abnormal GH/IGF-I axis

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Patient AC

AC - boy born at 39 weeks gestation • Birth weight: 3030 g • Birth length: 47 cm • Prune belly syndrome (renal

dysplasia) He was polyuric and required

calcitriol, NaHCO3, sodium polystyrene sulfonate, and Sim PM 60/40 formula

Patient AC: Growth Chart 0-36 months

Patient AC: Growth and Renal Status

Age (yr)

Wt (kg)

Wt SDS

Ht (cm)

Ht SDS

Wt/Ht %tile

Cr (mg)

GFR (mL/min/1.73 m2)

Birth 3.03 –0.87 47 –1.11 74 1.9 11.1

0.5 5.4 –3.57 58.5 –4.26 42 1.5 17.5

0.9 8.84 –1.27 71 –1.42 53 1.0 31.9

1.9 11.2 –0.99 82 –1.16 43 1.0 45

2.9 12.9 –0.92 87.1 –2.06 60 1.1 43.5

3.7 15 –0.36 94.6 –1.38 73 1.3 40

4.5 16.9 –0.13 100.5 –1.09 79 1.4 39.5

Patient AC: Growth Chart 2-9 yrs

Midparental height

What Do We Know About Growth Failure in CKD?

Non-Modifiable Younger age at onset of renal disease More significant uremia Tubulo-interstitial disorders Glucocorticoid therapy

Modifiable Excessive water and sodium loss Calorie deficiency and abnormal protein metabolism Metabolic acidosis Renal osteodystrophy (CKD-MBD) Gonadotropin abnormalities

Growth Failure May Occur at Any Level of CKD (GFR) Growth Does Not Typically Improve with Dialysis Growth Failure is Related to Multiple Factors:

Kaskel F. Kidney Int 2003 Tonshoff B. J Nephrol 1995

What Else Have We Learned About Growth Failure in CKD?

Breakthrough! CKD is a Growth Hormone/IGF-1 Resistance State

Growth Hormone Therapy Improves Growth in Children with CKD

Physiology of the GH/IGF-I Axis

Normal Physiology

CKD Physiology

GH – Growth Hormone ALS – Acid Labile Subunit IGFBP – Insulin-like Growth Factor 1 (IGF-1) Binding Protein

Janjua H. Adv Chronic Kid Dis 2011

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Key GH-IGF-1 Pathophysiologic Points

1. GH and IGF-I levels are not reduced in patients with CKD [increased pulses of GH release and reduced renal GH clearance]

2. CKD = reduced responsiveness to endogenous GH and IGF-I •GH resistance reflects

•Defect in post-receptor GH activated JAK2 STAT pathway [leads to blunted IGF-1 response to GH]

•Decreased density of GH receptors in tissues [bone] [as indicated by decreased levels of GHBP]

•IGF-I resistance related to increased circulating IGFBP-1,2,4,6 = up to 50% reduction in bioavailable IGF-I

3. Increased IGFBP-3 proteolysis leads to reduction in IGF-I circulating in IGF-I/ALS/IGFBP-3 complex–therefore reduced IGF-I receptor activation and reduced feedback to the hypothalamus and pituitary

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Multiple Factors Cause GH Resistance in CKD

Mehls O 2008

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GH-IGF-1 Axis in Children with CKD: CKiD

26 - short stature – no rGH Rx 206 - normal height – no rGH Rx. 34 [18 short, 16 normal Ht on rGH RX

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3. The modifiable factors that can lead to poor growth in children with CKD must be addressed in a determined manner!

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Modifiable Factors Associated with Growth Failure in CKD: Treatment Aspects

Modifiable Factor Treatment 1. Malnutrition (Cachexia) Provision of 100-120% RDA

calories - Kari 2. Salt and Water Wasting Supplemental Na/H2O 3. Acidosis Alkali – McSherry 4. Anemia Improved growth associated

with Hb>11 - Boehm 5. CKD-Mineral Bone Disorder

(Renal Osteodystrophy) Better growth with Rx – Chesney

6. Gonadotropic Hormone Abnormalities

?

7. GH/IGF-1 Resistance Distinct Benefit from rhGH Rx – Fine, Mehls

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Nutrition and Growth in CKD

• 101 infants (1986-1998); 1 and 5 year survival - 87 and 78% • Supplemental feeding as soon as growth was subnormal;

81 started enteral feeds at ages 0 to 4.5 years. • 46% gastrostomy • 22% Nissen

• Mortality highest in yr 1 • Length in normal range by 1 year of age • Weight gain better than height gain Kari JA. Kidney Inter 2000; 57:1681–1687.

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Growth in Children on Dialysis (NAPRTCS)

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Growth in Children After Transplantation NAPRTCS

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4. CKD is a state of GH and IGF-1 resistance – in some children recombinant GH will be necessary to achieve good growth.

Algorithm for Evaluation and Treatment of Growth Retardation in Children with CKD: Overview

31 Adapted from Mahan et al. Pediatr Nephrol. 2006;21:917-930.

Short stature or declining height velocity in CKD 2-5

GH therapy assessment

YES NO

Assess and treat poor growth

Continue therapy

Start GH therapy

Monitor GH therapy

IS GROWTH ADEQUATE?

Assess and correct: Dose, metabolic status,

nutrition, compliance

Continue GH therapy

Consider consult

Discontinue GH therapy if necessary*

Reinitiate GH therapy if reason for discontinuation

resolved

IS GROWTH VELOCITY IMPROVED?

YES NO

YES

NO

Is Growth Adequate?

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Evaluation of Growth in Children with CKD


A candidate for treatment of growth retardation should have •CRI (CKD) with GFR<75 mL/min/1.73m3 •Height SDS<-1.88 (3rd Percentile) or Ht Velocity SDS<-2

First, a practitioner should assess and optimally treat modifiable factors that may contribute to poor growth

•Acidosis •Insufficient nutrition/fluids •Salt-wasting •Renal osteodystrophy (CKD-MBD) •Hypothyroidism

Determine whether the growth velocity improves following these treatments

Growth Calculator: www.nutropin.com

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Assessment for GH Treatment

33 *PTH = parathyroid hormone Adapted from Mahan et al. Pediatr Nephrol. 2006;21:917-930.

Recalculate height SDS, height velocity SDS and height velocity Determine pubertal stage Analyze bone age Hip and knee X-rays Baseline fundoscopic exam

Labs •Baseline chemistries •PTH •Thyroid status

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Growth Hormone Therapy in CKD

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• Evaluation • Authorization/Insurance approval • GH Dose:

• 0.35 mg/kg/wk; • divided into daily SC injections

• Patient education

Considerations for GH Administration in CKD

Chronic ambulatory peritoneal dialysis patients should receive their injections in the evening, at the time of the overnight exchange

Chronic cyclic peritoneal dialysis patients should receive injections in the morning after dialysis

Hemodialysis patients should receive their injections at bedtime or at least 3 to 4 hours after treatment to avoid the possibility of hematoma formation from heparin use

Usually recommended to administer in the evening

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Growth Hormone Therapy in CKD: Ongoing

36

Adapted from Mahan. Ped Nephrol 2006;21:917-930.

Monitoring growth response/safety - every 3-4 months •Height, weight, height velocity OFC* (until 3 years of age) •Pubertal stage Nutritional intake •Fundoscopic exam Labs (chemistries, PTH) •Bone age, hip and knee X-rays (every year)

Adjusting GH doses as needed Encouraging compliance/measuring IGF-1 levels Consider pubertal dosing if growth response lags during puberty

• 125-200 % of standard dose • If limited time until epiphyseal closure • If IGF-1 response is not large (large = > 3-4 times normal)

Vimalachandra DV, et al. J Pediatr 2001

WMD (95% CI Random) Study

Treatment n

Control n

Weight %

WMD (95% CI Random)

Favors control Favors treatment

Maxwell 1998 Pubertal

Maxwell 1998 Prepubertal

Guest 1998

Fine 1994

Powell 1997

Total (95% CI)

4

9

41

55

30

139

3

6

44

27

14

94

–2 –1 0 1 2

3.4

6.7

19.7

24.4

45.8

100

0.60 (-0.81, 2.01)

0.90 (-0.08, 1.88)

0.30 (-0.21, 0.81)

1.10 (0.66, 1.54)

0.80 (0.56, 1.04)

0.77 (0.51, 1.04)

Effect of rhGH Rx on Height SDS in Children with CKD: A Meta-Analysis

Improved Growth After rhGH Treatment in Children with CKD

38 38 38 Fine R. J Pediatr. 1994;124:374-382.

**P<0.00005 compared to placebo.

Gro

wth

Rat

e (c

m/y

r)

Children with CKD who receive rhGH therapy have better growth rates than placebo-treated children.

**

Sample Size Growth Hormone • Boys = 32 • Girls = 6

Control • Boys = 31 • Girls = 19

Children with Poor Growth Treated with GH Experience Significant Height Prepubertal Gains

39 39

*P<0.001 rhGH vs. non-rhGH.

Haffner D. NEJM. 2004;343:923-930.

Prep

uber

tal H

eigh

t Gai

n (c

m)

Children with CKD who receive GH therapy show a significant improvement in prepubertal height gain.

GH Treatment Provides Significant Height Gains in Children with CKD During Puberty

40 40 40 Adapted from Haffner NEJM. 2004;343:923-930.

Prep

uber

tal H

eigh

t Gai

n (c

m)

Sample Size Growth Hormone • Boys = 32 • Girls = 6

Control • Boys = 31 • Girls = 19

Growth Hormone Control

Age (yr) Age (yr)

Start rhGH

Start rhGH

It is important to initiate GH therapy early in children with CKD

Children with CKD Who Receive GH Rx Have Better Final Adult Height Than Those Who Do Not

41 41 41

rhGH effectively improves Final Height in CKD RTx patients, without affecting kidney function

Gil S. Ped Nephrol 2012

Red initial height (IH) (rhGH) Black IH (control) Green final height (FH) (rhGH) Blue FH (control)

Height SDS

Duration of GH Therapy (Years)

-1

-3

-4

-5

Dialysis

CKD 2-4

Start GH

-2 -1 4

0

GH Therapy Works Better in Children with CKD 2-4 Compared to Those on Dialysis

Tönshoff B, et al. J Nephrol 1995

First Year Height Velocity in CKD: Assure Appropriate Growth Response

Height Velocity During Year 1 of Growth Hormone Treatment and Pretreatment Height Velocity:

Prepubertal Naïve Patients with Chronic Kidney Disease

Mean Height Velocity + 1*SD

Mean Height Velocity

Mean Height Velocity – 1 *SD

Mean PreTreat Height Velocity


Baseline Age (yr)

Hei

ght V

eloc

ity (c

m/y

r)

NCGS GH RX in CKD Curves

Mahan JD. Ped Nephrol. 25:1125-30, 2010.

Age at Baseline

Year

1 H

eigh

t Vel

ocity

(cm

/yr) ISS Males

CKD

Year 1 Height Mean Velocity ± 1 SD in ISS Males and CKD Males

Mean Height Velocity + 1*SD

Mean Height Velocity


ISS CKD

NCGS

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Predicting Response to GH Rx in Children with CKD

Results: Annualized height velocity (cm/year) during first year of GH Rx best predicted by:

age at start weight SDS underlying renal disorder (hereditary kidney disorder) GFR (at baseline) GH dosage Model explained 37% of variability of growth response (SE = 1.6 cm) Age = most important predictor of growth response (20.3% of

variability) followed by weight SDS at start Only 27.2% of variability of 2nd year response predicted by 1st year

response and GFR Mehls O, J Clin Endocrinol Metab. 2010;95:686-92. 2010.

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5. GH Treatment is Safe and Effective for children with CKD and children Post Renal Transplantation; careful monitoring for complications and appropriateness of growth response is necessary during GH treatment

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Guidelines for Growth Hormone Therapy Discontinuation


GH therapy should be discontinued in when: –Achieved 50th percentile for height for age based on mid-parental height –Closed epiphyses –Active neoplasia –Slipped femoral epiphyses –Intracranial hypertension –Noncompliance –Severe hyperparathyroidism (PTH>800 pg/mL – Stage V; >400 pg/mL – Stage II-IV) –At the time of renal transplantation If height velocity remains <2 cm/year over baseline and reason for discontinuation is resolved, GH therapy re-initiation should be considered

Adapted from Bell et al. J Clin Endocrinol Metab. 2010;95:167-177.

Safety: Incidence of Adverse Events in Children with CKD Treated with rhGH

48 48

Targeted Events by Indication Results NCGS CRI Number 54,996 1778 Adverse Events 6.2 10.9 Serious AE 2.4 6.5 Deaths 0.3 1.2 Malignancy* 0.1 0.0 IC Tumor Recurrence 0.3 0.1 Leukemia*† 0.0 0.0 2nd Neoplasm 0.1 0.1 Adrenal Insufficiency† 0.0 0.0 Diabetes Mellitus 0.1 0.2 Intracranial Hypertension 0.1 0.3 SCFE 0.1 0.3 Scoliosis 0.4 0.1 Pancreatitis 0.0 0.0

Data are expressed as percentage. *New onset, no risk factors. †Based on fewer than 15 reports.

3/300 post-renal Tx 1/17 post-liver Tx All 4 on concomitant immunosuppressives

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Safety: Infants with CKD Treated with rhGH

49

Santos CJASN 2010

RCT – open label – 16 infants 29 adverse events: 9 in the rhGH group 20 in the untreated group, *no adverse effects with rhGH Rx

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Safety: Post Transplant Lymphoproliferative Disorder in Patients Treated with rhGH

50

Dharnidharka V. Ped Transpl 2007

PTLD Rates According to rhGH Use During CKD (n = 1647)

No PTLD PTLD Fisher Exact p-value

All cases 1606 (97.5%) 41 (2.5%) 0.009

No rhGH pre-Tx 1217 (98.1%) 23 (1.9%) rhGH pretransplant

389 (95.6%) 18 (4.4%)

• Groups not equal for age, era or post-Tx meds. • The hazard ratio for PTLD development post-transplant, adjusted for transplant era

and age at transplant, was just borderline higher with rhGH use (ratio = 1.88, 95% CI = 1.00–3.55, p = 0.05).

• No data on length of therapy, co-morbidities or specifics of immunosuppression .

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Major Barriers to GH Therapy in Children with CKD

Lack of urgency • That rhGH treatment can be delayed • Short stature perceived as a cosmetic issue Evaluation and documentation • Uncertainty -evaluation, rhGH dosing, monitoring • Reimbursement worries – lack of appropriate

support for reimbursement Patient compliance

51 Mahan et al. Pediatr Nephrol. 2006;21:917-930.

Greenbaum L. Ped Neph 2008

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Patient RP

Boy born at 40 weeks of gestation •Birth weight: 3370 g/Birth length: 47 cm •Joubert’s syndrome with ARPKD

Polyuric and required NaHCO3, calcitriol, anti-hypertensive agents, Epogen.

Required Synthroid for hypothyroidism. Clinical course complicated by reactive airway disease, polyuria;

several admissions for dehydration with gastroenteritis. Delay in sitting and ability to walk noted during first year of life. After repeated attempts to boost caloric intake, he remained near

3rd percentile for weight and below 3rd percentile for height.

Patient RP: Growth and Renal Status

Age (yr)

Wt (kg)

Wt SDS

Ht (cm)

Ht SDS

Wt/Ht SDS

Cr (mg)

GFR (mL/min/1.73 m2)

Birth 3.37 –0.71 47 –1.11 -0.25 1.9 11.1

2.8 10.6 -2.38 85.3 -2.23 -1.45 1.0 47

GH Rx 3.5 11.7 -2.22 89.5 -2.37 -1.25 0.9 57

4.0 11.9 -2.46 89.9 -2.98 -1.15 1.2 41

4.5 13.7 -1.94 96 -2.3 -0.79 1.2 44

5.0 15 -1.73 98.5 -2.38 -0.20 1.1 49

5.5 17.6 -0.94 105.8 -1.48 0.14 1.0 58 Ht velocity

SDS = 7.90!!!

Patient RP: Growth Chart 2-20 yrs

Midparental height

RP DOB 3/9/03 3.37 kg 47 cm

3 Years/1 Month

3 Years/4 Months

4 Years/1 Month

5 Years/7 Months

On GH Rx

5 Years/11 Months

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Take Home Messages: Growth is Important!

Growth is a Vital Sign Poor growth deserves our attention Use Height SDS +/or Height Velocity to monitor growth Consider Mid Parental Height Projection

•[Mom’s ht (in) + Dad’s ht (in)]/2 •Add 2.5 in male •Subtract 2.5 in female

Use all available interventions to improve growth: Calories, fluid/Na, alkali, vitamin D, Growth Hormone The earlier GH is used, the better the final adult height

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Conclusions 1. Growth is one of the MOST important medical issues that children

with CKD confront! 2. The factors that can lead to poor growth in children with CKD

include important modifiable and non-modifiable issues! 3. CKD is a state of GH and IGF-1 resistance – in some children

recombinant GH will be necessary to achieve good growth. 4. Children with CKD who demonstrate growth failure should be

evaluated and all modifiable factors addressed – if poor growth persists, GH therapy should be utilized.

5. GH Treatment is Safe and Effective for children with CKD and children Post Renal Transplantation; careful monitoring for complications and appropriateness of growth response is necessary during GH treatment .

6. Successfully optimizing growth in children with CKD really demonstrates your value as pediatric nephrologist!

59

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References Haffner D, Schaefer F, Nessel R, et al. Effect of GH treatment on the adult height of children with

chronic renal failure. NEJM. 2000;343:923-30. Hokken-Koelga, Mulder P, De Jong R, et al. Long-term effects of GH treatment on growth and

puberty in patients with CRI. Ped Nephrol. 2000;14:701-706. Kari JA, Rees L. Growth hormone for children with chronic renal failure and on dialysis. Ped

Nephrol. 2005;20:618-621. Kaskel F. Chronic renal disease: a growing problem. Kidney Int. 2003; 64(3):1141-1151. Kuizon BD, Salusky IB. Growth retardation in children with chronic renal failure. J Bone Miner Res.

1999; 14:1680-1690. Mahan JD and Warady BA. Assessment and Treatment of Short Stature in Pediatric Patients with

Chronic Kidney Disease: A Consensus Statement. Ped Nephrol. 2006;21:917-930. Mentser MI, Breen TJ, Sullivan EK, et al. GH treatment of renal transplant recipients – A report of

NCGS and NAPRTCS. J Ped. 1997;131:S20-24. North American Pediatric Renal Transplant Cooperative Study. 2008 and 2011 Annual Reports. Renal

transplantation, dialysis, chronic renal insufficiency. Available at: http://spitfire.emmes.com/study/ped/resources/annlrept.

Mahesh S, Kaskel F. Growth hormone axis in chronic kidney disease. Ped Nephrol. 2007;23:41-48. Janjua HS, Mahan JD. Growth in Chronic Kidney Disease. Adv Chronic Kid Dis. 2011; 18:324-331.

http://spitfire.emmes.com/study/ped/resources/annlrept2006.pdf

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References Postlehwaite RJ, Eminson DM, Reynolds JM, et al. Growth in renal failure: a longitudinal study of

emotional and behavioural changes during trials of GH treatment. Arch Dis Child. 1998;78:222-229.

Roelfsema V and Clark RG. The GH and IGF Axis: Its manipulation for the benefit of growth disorders in renal failure. J Am Soc ephrol. 2001;12:1297-1306.

Schaefer F, Veldhuis JD, Robertson WR, Dunger D, Scharer K. Immunoreactive and bioactive luteinizing hormone in pubertal patients with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure. Kidney Int. 1994; 45:1465-1476.

Stefanidis CJ, Klaus G. Growth in prepubertal children on dialysis. Ped Nephrol. 2007;22:1251-1259.

Tonshoff B, Kiepe D, Ciarmatori S. Growth hormone/insulin-like growth factor system in children with chronic renal failure. Ped Nephrol. 2005; 20:279-289.

Wuhl E, Schaefer F. Puberty in chronic renal failure. Adv Ren Replace Ther. 1999; 6:335-343. Vimalachandra D, Craig JC, Cowell CT, et al. GH treatment in children with chronic renal failure: A

meta-analysis of randomized controlled trials. J Peds. 2001;139:560-7. Seikaly M, Salhab N, Warady B, Stablein D, Use of rhGH in children with chronic kidney disease:

lessons from NAPRTCS. Ped Nephrol. 2007; 22:1195–1204. Dharnidharka VR, Talley LI, Martz KL, Stablein DM, Fine RN. Recombinant growth hormone use

pretransplant and risk for post-transplant lymphoproliferative disease – a report of the NAPRTCS. Ped Transplant. 2008; 12:689-95.

Mehls O, Wuhl E, Tonshoff B, Schaefer F, Nissel N, Haffner D. Growth hormone treatment in short children with chronic kidney disease. Acta Pæd. 2008;97:1159–1164.

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References Garibotto G, Russo R, Sofia A, Ferone D, Fiorini F, Cappelli V, Tarroni A, Gandolfo MT, Vigo E, Valli

A, Arvigo M, Verzola D, Ravera G, Minuto F. Effects of uremia and inflammation on growth hormone resistance in patients with chronic kidney diseases. Kidney Int. 2008.

Mahan JD, Warady BA, Frane J, Rosenfeld RG, Swinford RD, Lippe B, Davis DA. First-year response to rhGH therapy in children with CKD: a National Cooperative Growth Study Report. Ped Nephrol. 2010; 25:1125-30.

Mehls O. Predicting the response to growth hormone treatment in short children with chronic kidney disease. J Clin Endo Metab. 2010; 95:686-92.

Moreno L, Santos F, Neto A, Ariceta G, Vara J, Alonso A, et al.Improvement in growth after one year of growth hormone therapy in well-nourished infants with growth retardation secondary to chronic renal failure: results of a multi-center, controlled, randomized, open clinical trial. Ped Nephrol. 2010;25:790.

Santos F, Moreno ML, Neto A, Ariceta G, Vara J, Alonso A, et al.Improvement in growth after 1 year of growth hormone therapy in well-nourished infants with growth retardation secondary to chronic renal failure: Results of a multicenter, controlled, randomized, open clinical trial. Clin J Am Soc Nephrol. 2010;5 (7):1190–7.

Gil S, Vaiani E, Guercio G, et al. Effectiveness of rhGH treatment on final height of renal-transplant recipients in childhood Ped Nephrol. (2012) 27:1005–1009.

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Information for Patients and Families

National Kidney Foundation http://www.kidney.org/

MAGIC Foundation http://www.magicfoundation.org/www

American Association of Kidney Patients http://www.aakp.org/

Kidney & Urology Foundation of America http://www.kidneyurology.org/

Genentech’s Growth Hormone Site (including Stepping Stones, Understanding Growth in Kidney Disease, etc)

www.nutropin.com

Algorithm for Evaluation and Treatment of Growth Retardation in Children with CKD

65

Algorithm for Evaluation and Treatment of Growth

Retardation in Children with CRI

66 66

Patient Selection GFR<75 mL/min/1.73m3

Ht SDS<-1.88 (3rd Percentile) or Ht Velocity SDS<-2

Treat Contributors to Poor Growth Acidosis, Malnutrition, Salt-wasting,

Osteodystrophy, Hypothyroidism

Continue Current Therapy

YES

Is Growth Velocity Improved?

Adapted from Mahan et al. Pediatr Nephrol. 2006;21:917-930.


Retardation in Children with CRI (Cont’d)

67 67 67 Adapted from Mahan et al. Pediatr Nephrol. 2006;21:917-930.

NO

Continue Current Therapy

YES

Baseline Assessment for GH Therapy

Recalculate Ht SDS, ht velocity SDS, and height velocity

Pubertal stage, Bone age, Hip and knee X-rays Funduscopic exam

Chemistries, PTH, Thyroid studies

Is Growth Velocity Improved?




Start Growth Hormone Therapy 0.05 mg/kg/day SC (0.35 mg/kg/wk)

Monitor Every 3-4 months

Height, weight OFC (until 3 years of age)

Pubertal stage Nutritional evaluation Funduscopic exam Chemistries, PTH

Toxicity Every year Bone age

For symptoms Hip and knee X-rays




Yes, Growth Adequate

No, Growth Inadequate

Continue GH Rx Adjust dose

every 3-4 months based on weight

Assess & Correct Dose for weight Metabolic status

Nutrition Compliance

Consider Pediatric Endocrinology consult

Adequate Growth

Is Growth Adequate? (Ht velocity 2 cm/yr>baseline)

NO

YES

70 70

Algorithm for Evaluation and Treatment of Growth Retardation in Children with CRI (Cont’d)


If height velocity<2 cm/yr, and reason for discontinuation resolved,

consider reinitiation of GH therapy

Discontinue GH Therapy for Achieved ht goal based on mid-parental ht

and/or 50th percentile for age; Closed epiphyses; Active neoplasia;

Slipped femoral epiphyses; Intracranial hypertension; Non-compliance;

Severe hyperparathyroidism (PTH>900 pg/mL – Stage V; >400 pg/mL – Stage II-IV)

Documents

Growth and Growth Hormone Therapy in Children …annualdialysisconference.org/wordpress/wp-content/themes/adc/2016...Growth and Growth Hormone Therapy in Children with CKD ... Growth