INTRODUCTION:

Chronic Kidney Disease (CKD) includes the spectrum of disease ranging from mild kidney damage to End Stage Renal Disease (ESRD)¹. It is characterized by many unique features that are not experienced by the adult population. Growth failure is one of the most visible clinical manifestations of the CKD children².

According to NAPRTCS (North American Pediatric Renal Trials and Collaborative Studies) registry, more than one third of children with CKD are less than 3^rd percentile (SDS of -1. 88) for height at the time of entry to registry. Overall patients with CKD have 1.5 SDS below for age and sex specific norms for height. Infants are more severely retarded in growth with mean height SDS of -2.35 at baseline³.

The European study reported that one third of the height deficit in 3 years of age is associated with early onset of CKD and one third during the first postnatal months.

Any insult to growth during the critical period of development impacts the adult height. With renal replacement therapies 30% - 60 % of children grow up to became stunted adults⁴.The consequences of growth failure in these children includes poor body image, low self esteem, greater emotional distress and low quality of life⁵.

In UK renal registry, the incidence of children with ESRF has been reported as nine per million child population overall with the highest incidence of new patients in 10 – 15 years of age ⁶. Due to the absence of appropriate growth related data in renal registries, imposes great difficulty in estimating the prevalence of growth retardation in various stages of CKD in children and initiate with treatment. CKD children with growth retardation needs early recognition and prompt therapy.

Etiology of growth failure in CKD.

Multiple factors have been identified for impaired linear growth in these children.

A. Modifiable factors:

· GH/IGF-1 axis dysfunction.

The abnormalities in GH-IGF-1 axis which develops at any stage of renal insufficiency affects the linear growth. It also leads to decreased muscle and bone mass, impaired neuro-cognitive development, and abnormalities in plasma lipids which results in significant morbidity. Growth failure can also be due to Insensitive to the action of GH in CKD due to reduced density of GH receptors in target organs⁷.

· Hormonal abnormalities

The Gonadotropic hormone axis gets altered in adolescent patient with CKD, with decreased renal clearance of Gonodotropins leading to elevated Gonodotropin levels and reduced pituitary secretion resulting in growth failure in these children ⁷.

· Inadequate protein and calorie intake

Inadequate intake of protein and calorie is another important factor in growth failure. Children with CKD have increased catabolism, decreased sense of taste, early satiety, nausea and vomiting which in turn contribute to decreased calorie intake and further affects nutritional status.⁸

· Inadequate replacement of salt and water losses

In children with salt wasting disorder and urine concentrating defects, cellular metabolism gets altered and causes growth failure in young children.³

· Metabolic acidosis

In CKD children, the metabolic acidosis reduces GH secretion and serumIGF-1 levels. It suppresses albumin synthesis, increases calcium efflux from bones and enhances protein degradation. ³

· Mineral and bone disorder

The high turnover and low turnover bone disease affects the growth in CKD. In High turnover bone disease like secondary hyperparathyroidism, the architecture of growth plate gets altered whereas in low turnover bone disease reduced osteoblastic activity leading to decreased bone formation and impaired growth. ⁹

· Anemia

Long standing anemia in CKD children has profound systemic consequences including poor appetite, recurrent infections, cardiac complication and reduced oxygen supply and increased catabolism which leads to impaired growth.¹⁰

· Long term steroid therapy

Long term steroid therapy affects the growth by decreasing the pulsatile secretion of GH, inhibits IGF-1 production and alters cartilage and bone dynamics.³

B. Non modifiable factors:

· Age at onset of renal insufficiency

The intrauterine events linked with poor nutrition alters the prenatal development leading to reduced number of nephrons in LBW and SGA babies possess another substantial risk for CKD in later life. Untreated CKD in infants is associated with severe growth retardation during their first year.¹¹

· Degree of renal insufficiency

The degree of growth retardation is closely associated to renal dysfunction with a decrease in height SDS occurring if GFR rate falls below 25ml/min per 1.73 m2.¹²

· Type of renal disorder.

Congenital renal dysplasia or hypoplasia, obstructive uropathy with or without urinary tract infection is considered as most important cause of CKD in infancy and childhood.¹²

Even though the catch-up growth was seen with treatment of dialysis and transplantation, their extent to normal growth velocity is seems to be minimal.

Pattern of growth in CKD:

Normal growth can be divided into 3 phases:

Infancy: Nutrition is the most important factor for Growth.

Childhood: The role of the somatotrophic hormone axis becomes important, thyroid hormone and nutrition have roles of lesser importance.

Puberty: The gonadotropic hormones axis plays a major role.

In CKD the growth pattern is characterized by decreased growth velocity during infancy followed by normal growth velocity in childhood and impaired growth velocity again during adolescence. The growth velocity may also be low during childhood phase in children with CKD stage 4 or 5.¹³

Assessment of growth :

Growth parameters are particularly important in children and should be accurately measured using calibrated equipments and standardized techniques. As per the KDOQI Guidelines the growth of CKD children should be made twice/thrice in a year during early stages of CKD. In the presence of co morbidities, dialysis and transplantation frequent assessment is needed.¹⁴

1. The growth parameters like height, weight, head circumference (for children upto 2 yrs of age) and BMI should be measured and plotted on a standard growth chart to rule out the growth velocity in CKD children.

2. Combine the assessment with dietary assessment which can be done with 3 day dietary recall. Nutrient intake should be computer analyzed and reference made to national guidelines.

3. Assessment of the body composition with Bioelectric Impedance Analysis and with Dual Energy X-ray Absorptimetry (DEXA). Bioelectrical impedance estimates fluid compartment volume by measuring conduction of electrical current through body fluids and impedance by body components. The whole body DEXA provides reproducible estimates of fat mass and lean mass in children and adults by measuring the degree of dual photon attenuation produced by each tissue type. When poor measurements are applied, the errors associated with body composition estimate will be more.¹²

4. Serum albumin concentration is a reliable biochemical marker for patient’s nutritional status. But the presence of acute or chronic inflammation limits the specificity of serum albumin as a nutritional marker.¹³

Outcome of growth failure in children and adolescence:

1. Long term studies showed strong relationship between growth impairment and increased morbidity and mortality rates.

2. USRDS(United States Renal Data System) of 112 children with dialysis showed 3- fold increase in mortality rates in children with severe growth impairment.

3. Impact on neuro-cognitive and psychological development.

4. Deprivation of responsibility and respect leads to low self esteem and quality of life.

5. Frequent hospitalization.⁶

Conservative management for growth:

Optimal conservative management of children with CKD aims to minimize the complication to improve or maintain the growth in these children. It includes

· Nutrition: The most important action to prevent growth retardation in infants and young children with CKD is to achieve an adequate calorie intake. If needed supplement the feeds through nasogastric tube or gastrostomy. It is recommended that the calorie intake should be 80 -100 % of the daily recommended allowance (RDA). Intake of calorie more than the recommended results in obesity. Low protein diet is recommended for these children whereas the high protein diet causes metabolic acidosis and phosphorous overload , hence not recommended.¹⁰

· KDOQI recommended nutritional counseling based on an individualized assessment and plan of care should be considered for children with CKD stage 2 to 5 and 5D and their caregivers. Frequent reevaluation and modification of the nutritional plan of care are suggested for these children. This leads to adherence and improved outcomes in CKD children.¹⁴

· Metabolic acidosis: NKF KDOQI guidelines suggested to treat the metabolic acidosis with alkali, so that the levels of bicarbonate would be maintained at 22-24 meq/L. Timely correction of acidosis promotes growth.¹⁵ Supplement adequate water and salt for children with salt – wasting disorders) and urine concentrating defects.¹⁰

· Anemia: In CKD children the anemia can be corrected by early initiation of erythropoietin therapy.¹⁰

· Metabolic bone disease: Calcitriol deficiency produces secondary hyperparathyroidism and causes renal osteodystrophy. A low phosphorous diet with phosphate binder and vitamin D is advocated with the aim of halting the PTH secretion.¹⁵

· Dialysis in promoting growth: Dialysis corrects the uremic syndrome partially. Maintenance of residual renal function is essential for longitudinal pattern of growth. Recent studies showed that daily dialysis or longer hemodialysis induces catch –up growth in CKD children.¹⁶

· Growth in renal transplantation: In renal transplanted children the growth rate varies from normal height to short stature adult. Factors responsible to achieve adult height in transplanted children are adequate glomerular filtration rate, transplant at early age, and pubertal growth spurt in appropriate time, and post transplant immunosuppressant without steroids.¹⁷

· Growth hormone therapy: GH administration significantly increases production of IGF-1 in the liver and growth plate and slightly increases the IGFBP synthesis, thus allowing normalization of the IGF-1 bioactivity, improving longitudinal growth to achieve a normal adult height in children with CKD. It is vital to monitor the response to rGH at every 3 to 4 months. Withdrawal and reinstitution may be considered when height goal is reached or if growth velocity decreases.¹⁸

SUMMARY:

Growth Failure in CKD children results from a complex interaction between metabolic, nutritional and hormonal disturbances. Constant monitoring of these children for growth parameters and correction of co-morbid conditions helps the child to attain near normal height. This improves their quality of life not only in childhood but also in adult life.

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Received on 17.04.2014 Modified on 20.05.2014

Int. J. Adv. Nur. Management 2(2): April- June, 2014; Page 106-108