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Saudi Journal of Kidney Diseases and Transplantation
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REVIEW ARTICLE Table of Contents   
Year : 1997  |  Volume : 8  |  Issue : 3  |  Page : 274-278
Growth in Children with Chronic Renal Disease


Consultant Pediatrician, Sudbury, Ontario, Canada

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How to cite this article:
Abdurrahman M B. Growth in Children with Chronic Renal Disease. Saudi J Kidney Dis Transpl 1997;8:274-8

How to cite this URL:
Abdurrahman M B. Growth in Children with Chronic Renal Disease. Saudi J Kidney Dis Transpl [serial online] 1997 [cited 2014 Dec 25];8:274-8. Available from: http://www.sjkdt.org/text.asp?1997/8/3/274/39354

   Introduction Top


Varying degrees of growth impairment has long been recognized as a consistent and pervasive feature of chronic renal disease in children [1],[2],[3],[4] . The hope that maintenance dialysis would considerably improve growth in these children has not been realized [5],[6],[7],[8] , although growth is better with peritoneal dialysis than with hemodialysis [6],[7],[8] , Although renal transplantation results in Improved growth velocity [3],[9] , it does not normalize growth, and catch-up growth occurs only in those patients transplanted before the age of five years [10] . Thus, children with chronic renal insufficiency who have had renal replacement therapy often have markedly short adult stature [11],[12],[13] .

This review of growth in children with chronic renal disease begins with a few comments on normal growth. The clinico-pathological features of chronic renal disease which are relevant in the pathogenesis of growth impairment are described. Finally, ways of optimizing growth in children with chronic renal disease are discussed.

A review of the literature was carried out by a systematic search of the MED LINE database for English language articles published from 1992 to 1995. The key words used were: chronic renal disease, chronic renal failure, end-stage renal disease, renal failure, dialysis, hemodialysis, peritoneal dialysis, growth and children­


   Normal Growth Top


The hallmark of normal childhood is continual growth and development; growth and development in healthy children are so interwoven that they are inseparable. However, since physical growth is accurately measurable it has become the epitome of growth, and growth percentile velocity curves for length/height, weight and head circumference are commonly available. It must be emphasized that growth encompasses physical as well as emotional, sexual and psycho-social changes during a lifetime. The endocrinology of growth centers around the pituitary gland. The pituitary gland is under the control of the hypothalamus (through hypothalamic releasing factors), which in turn is influenced by other higher centers in the brain. The most widely recognized growth axes are the growth hormone axis, the thyroid axis, and the sex hormone axis.

Physical growth is commonly expressed as percentiles or standard deviation. A practical definition of growth retardation is, therefore, an anthropometric measurement (usually the height or length) below the third percentile or below two standard deviation from the mean for age and sex. With this approach, if the growth is below the third percentile, further quantification of the growth deficiency is not possible. The concept of standard deviation score (SDS), or Z score, was introduced to overcome this problem. Z scores interpret data in terms of the number of SDS above ( + ) or below (-) the median or 50th percentile value for the normal controls. SDS = value for an individual patient minus the 50th percentile for age and sex divided by standard deviation for normal children.

This SDS is used to compare the same individual at different ages, or between individuals of the same age and sex. In a normal population, the mean SDS will have a value of 0 (zero), standard deviation of 1, and 95% confidence limits of - 2 to + 2 SDS.


   Characteristics of Chronic Renal Disease with Cause or Contribute to Growth Impairment Top


For practical purposes chronic renal insufficiency (CRI) is defined as a glomerular filtration rate (GFR) of less than 60 ml/ min/1.73 m2 or a GFR less than 50% of normal for age. Functionally, chronic renal failure (CRF) can be defined as CRI of such severity that metabolic adaptation is insufficient to avoid manifestation of those clinical signs related to metabolic abnormalities. This usually corresponds to a GFR less than 25% of normal or an absolute GFR of less than 30 ml/min/1.73 m2. End-stage renal disease or failure (ESRD or ESRF) is a stage of CRI where renal replacement therapy becomes inevitable, commonly at a GFR < 5% of normal.

For the purpose of this review, the term chronic renal disease (CRD) is used as a generic term to cover all stages of CRI. A detailed description of the clinicopathological features of CRD in children in the Arabian Peninsula is outside the scope of the review. This has been covered elsewhere [14],[15],[16] .

The etiology and pathogenesis of growth impairment in CRD are multifactorial and inter-related, often in vicious circles. Some of the relevant factors are listed in [Table - 1]. It should be emphasized that several of these factors are often present in the same patient, and additional ones are added as the disease progresses.

Age at Onset

Growth impairment is most severe in children with congenital renal disorders and impaired renal function from early in life. This is partly due to the fact that the rate of growth in this period is greater, and also because renal tubular dysfunction is more prevalent. Moreover, these children often have anorexia, nausea and vomiting.

Natural History of the Disease

The underlying primary renal disorder causing CRD may be associated with rapidly progressive deteriorating course and with other features, which by themselves can cause further growth impairment. Examples include cystinosis. Fanconi syndrome, and other congenital renal disorders characterized by salt-wasting or bicarbonate wasting.

Calorie and Protein Malnutrition

Children with CRD have anorexia, nausea and, at times, vomiting. Their intake of calories and protein is poor [17],[18] . Moreover, there is evidence that their energy and protein metabolism is less efficient. Calorie intake is regulated by a combination of several factors: basal metabolic rate, level of physical activity, and the energy stored as part of the growth process. Growth impairment may be viewed as an adaptive and protective mechanism in CRD. If growth were to proceed normally in children with CRD, there will be increased metabolic activity resulting in increased accumulation of metabolic end-products which cannot be eliminated as a result of the CRD.

Anemia

A child with CRD sometimes presents initially as refractory anemia. The anemia of CRD may be profound, especially in children with certain congenital renal diseases such as medullary cystic kidney and in those on hemodialysis. However, there is considerable variation in the hemoglobin level at any given level of renal dysfunction, suggesting that the etiology of the anemia is multifactorial. The nature of the underlying renal disease and the duration of CRD as well as inability of the kidney to produce adequate amount of erythropoietin are among the most important factors. Pathogenesis of anemia of CRD includes bone marrow hypoplasia, increased hemolysis, shortened erythrocyte life span, and blood loss mainly through the gastro-intestinal tract. The consequent reduced tissue oxygenation along with the presence of metabolic acidosis and uremic toxins, contribute to structural and functional changes in other organ systems.

Biochemical Derangement

The child with CRD has limited reserve capacity in coping with fluid, electrolyte and acid-base changes in the body. Metabolic acidosis, salt-wasting, retention of potassium and phosphate, and accumulation of nitrogenous waste products in one combination or another are all features of CRD. These contribute to the growth impairment that is the hallmark of CRD. Uremic toxins have several adverse effects, including bone marrow depression, apathy and encephalopathy.

Renal Osteodystrophy (ROD)

ROD is a peculiar clinicopathologic feature of CRD that is associated with growth impairment [19] . ROD is characterized by simultaneous presence of vitamin D deficiency rickets and of parathyroid hormone hyperactivity. The pathogenesis of ROD is complex and incompletely understood; a simplified approach is depicted in [Table - 2]. ROD in combination with delay in skeletal maturation contributes significantly to growth impairment in CRD.

Hormonal Disturbances

Several endocrine changes have been described in children with CRD. In addition to impaired synthesis of 1,25-dihydroxy vitamin D and erythropoietin mentioned earlier, there are also normal or increased levels of growth hormone but increased growth hormone resistance, and decreased insulin-like growth factors. Growth hormone resistance and decreased insulin-like growth factors are thought to play a crucial role in the growth impairment of CRD. There are also abnormalities in insulin and glucose metabolism [20] , biochemical hypothyroidism [21] , and variable levels of catecholamines and corticosteroids.

Psychosocial Problems

Like any other chronic disease, CRD as well as its various treatment modalities often generate a lot of psychosocial problems in children and their families. Some of these problems are incapacitation, disrupted schooling, disrupted family life, and unvoiced rejection of the child by his/her parents. Probably the most visible problems are the short stature [3],[5],[6],[7],[8],[11],[12],[13] and delayed sexual maturation [22] .


   Management Top


Management of a complex problem such as growth impairment in CRD can never be simple. Management of any child with CRD should be multi-disciplinary, involving physicians, nurses, dieticians, social workers, and psychologist. With regard to growth of the child with CRD, the dietician is the most important member of the team. A meticulous attention to detail is required to document accurately the intake of the patient. The dietician must be someone conversant with the local food habits in order to translate a prescribed diet into a menu that is familiar to, and acceptable by, the family. The physician must document the growth parameters at the appropriate times; length/ height, head circumference, skinfold thickness using a calibrated caliper, midarm circumference and weight, and calculate the growth velocities. Radiographic bone age is done as required. Also, the height of both parents should be measured in order to calculate the normal expected height of the child.

Nutrition

The aims of nutritional management are to achieve proper balance between the limits of need and tolerance, and to minimize the production of nitrogenous waste products by limiting protein intake to that of high biological value. The latter may involve supplementation with essential amino acids or a mixture of the ketoacid analogues of the essential aminoacids. Because of anorexia and nausea, institution of nasogastric or gastrostomy tube feeding is almost a necessity in infants. Feeds are given four times during the day, and any deficit in caloric intake is made up by continuous drip feeding during the night. In the occasional patient, intravenous hyperalimentation (total parenteral nutrition) may be necessary. Such an aggressive approach is necessary in order to optimize growth in young infants.

Drug Therapy

CRD is one of the conditions where polypharmacy is inevitable. Thus, administration of vitamin D, calcium, phosphate binders, alkali, and erythropoietin are only some of the medications a child with CRD has to take. The chances of error in drug administration rise with increasing number of medications; attempts must be made to minimize them.

Growth Hormone

Aggressive treatment of the factors that cause growth impairment in CRD has not resulted in consistent improved growth and catch-up growth. This led to an interest in exploring other ways of boosting growth in these children. The use of recombinant human growth hormone at supraphysiological doses to produce accelerated growth in children with CRD has been shown to be efficacious and relatively safe [23],[24] . The growth promoting effect of growth hormone is less in children already on dialysis than in children who have not started dialysis [23] . Recombinant human growth hormone has now been labeled for use in children with chronic renal failure before transplantation [25] . Concern has been expressed regarding the possible association between the use of growth hormone and the development of pseudotumor cerebri, renal graft rejection, and also increased risk of malignancy. Moreover, the optimal dose and the duration of the therapy have not been established [26] .

Renal Replacement Therapy

Renal replacement therapy should be started earlier rather than later. Instead of using a predetermined level of GFR or serum creatinine the persistence of poor growth velocities and fluid and electrolyte derangement should be used to define the need to begin dialysis. Continuous ambulatory peritoneal dialysis and cyclic peritoneal dialysis are better tolerated, more convenient and readily available for infants and young children than hemodialysis. As mentioned earlier, neither conservative management nor dialysis normalizes growth and sexual maturation [5],[6],[7],[8] . Early renal transplantation is therefore the ultimate goal and the treatment of choice for the child with end-stage renal disease. Pre-emptive renal transplantation has been introduced to shorten the period of uremia with its attendant complications [27] . Living-related donor transplantation offers the best prognosis in young children, whereas both recipient and donor age younger than seven years have been identified as significant risk factors for poor cadaver donor graft survival [28] .

Growth after renal transplantation appears to be related to: a) the presence of functioning graft; b) the patient's age at the time of transplantation; c) the degree of growth retardation before the transplant; and d) the dosage of prednisone used for immunosuppression. Growth is most likely to occur in those under seven years of age in whom true catch-up growth may occur, whereas growth is least likely to occur in children with bone age above 12 years.

 
   References Top

1.Betts PR, Magrath G. Growth pattern and dietary intake of children with chronic renal insufficiency. Br Med J 1974;2:189-93.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Potter DE, Greifer I. Statural growth of children with renal disease. Kidney Int 1978;14:334-9.  Back to cited text no. 2  [PUBMED]  
3.Broyer M. Growth in children with renal insufficiency. Pediatr Clin North Am 1982;29:991-1003.  Back to cited text no. 3  [PUBMED]  
4.Rizzoni G, Broyer M, Guest G, Fine R, Holliday MA. Growth retardation in children with chronic renal disease: scope of the problem. Am J Kidney Dis 1986;7:256-61.  Back to cited text no. 4  [PUBMED]  
5.Kleinknecht C, Broyer M, Gagnadoux MF, et al. Growth in children treated with long-term dialysis. A study of 76 patients. Adv Nephrol Necker Hosp 1980;9:133-64.  Back to cited text no. 5    
6.Fennell RS 3d, Orak JK, Hudson T, et al. Growth in children with various therapies for end-stage renal disease. Am J Dis Child 1984;138:28-31.  Back to cited text no. 6    
7.Stefanidis CJ, Hewitt IK, Balfe JW. Growth in children receiving continuous ambulatory peritoneal dialysis. J Pediatr 1983; 102:681-5.  Back to cited text no. 7  [PUBMED]  
8.Kaiser BA. Polinsky MS, Stover J, Morgenstern BZ, Baluarte HG. Growth of children following the initiation of dialysis: a comparison of three dialysis modalities. Pediatr Nephrol 1994;8:733-8.  Back to cited text no. 8    
9.McEnery PT, Alexander SR, Sullivan K, Tejani A. Renal transplantation in children and adolescents: the 1992 annual report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 1993;7:711-20.  Back to cited text no. 9  [PUBMED]  
10.Ingelfinger JR, Grupe WE, Harmon WE, Fernbach SK, Levey RH. Growth acceleration following renal transplantation in children less than 7 years of age. Pediatrics 1981;68:255-9.  Back to cited text no. 10  [PUBMED]  
11.Potter D, Feduska N, Melzer J, et al. Twenty years of renal transplantation in children. Pediatrics 1986;77:465-70.  Back to cited text no. 11  [PUBMED]  
12.van Diemen-Steenvoorde R, Donckerwolcke RA, Brackel H, Wolff ED, de Jong MC. Growth and sexual maturation in children after kidney transplantation. J Pediatr 1987;110:351-6.  Back to cited text no. 12  [PUBMED]  
13.Gilli G, Scharer K, Mehls O. Adult height in pediatric patients with chronic renal failure. Proc Eur Dial Transplant Assoc Eur Ren Assoc 1985;21:830-6.  Back to cited text no. 13    
14.Aldrees A, Kurpad R, Al-Sabban EA, Ikram M, Abu-Aisha H. Chronic renal failure in children in 36 Saudi Arabian Hospitals. Saudi Kidney Dis Transplant Bull 1991;2:134-8.  Back to cited text no. 14    
15.Mattoo TK, Al-Mohalhal S, Al-Sowailem AM, Al-Harbi M, Mahmood MA. Chronic renal failure in children in Saudi Arabia. Ann Saudi Med 1990;10:496-9.  Back to cited text no. 15    
16.Abdurrahman MB, Al-Mugeiren M, Al Rasheed SA. Chronic renal failure in children in Saudi Arabia. J Nephrol 1990;2:93-6.  Back to cited text no. 16    
17.Chantler C, El-Bishti M, Counahan R. Nutritional therapy in children with chronic renal failure. Am J Clin Nutr 1980;33:1682-9.  Back to cited text no. 17    
18.Kleinknecht C, Broyer M, Huot D, Marti-Henne- berg C, Dartois AM. Growth and development of non dialyzed children with chronic renal failure. Kidney Int Suppl l983;15:S40-7.  Back to cited text no. 18    
19.Hodson EM, Shaw PF, Evans RA, et al. Growth retardation and renal osteodystrophy in children with chronic renal failure. J Pediatr 1983;l03:735-40.  Back to cited text no. 19    
20.Mak RH, Haycock GB, Chantler C. Insulin and growth in chronic renal failure. Pediatr Nephrol 1994;8:309-12.  Back to cited text no. 20  [PUBMED]  
21.El-Hana NA, El Shaikh S, Shaheen FAM. Thyroid function in children with chronic renal failure. Saudi J Kidney Dis Transplant 1996;7:297-300.  Back to cited text no. 21    
22.Broyer M, Donckerwolcke RA, Brunner FP, et al. Combined report on regular dialysis and transplantation of children in Europe, 1980. Proc Eur Dial Transplant "Assoc 1981;18:60-87.  Back to cited text no. 22    
23.Mehls O, Broyer M. Growth response to recombinant human growth hormone in short prepubertal children with chronic renal failure with or without dialysis. The European/Australian Study Group. Acta Pediatr Suppl 1994;399:81-7.  Back to cited text no. 23    
24.Lippe B, Yadin O, Fine RN, Moulton L, Nelson PA. Use of recombinant human growth hormone in children with chronic renal insufficiency: an update. Horm Res 1993;40:102-8.  Back to cited text no. 24  [PUBMED]  
25.Committee on Drugs and Committee on Bioethics of the American Academy of Pediatrics. Considerations related to the use of recombinant human growth hormone in children. Pediatrics 1997;99:122-9.  Back to cited text no. 25    
26.Fine RN, Brown DF, Kuntze J, Wooster P, Kohaut EE. Growth after discontinuation of recombinant human growth hormone therapy in children with chronic renal insufficiency. The Genentech Cooperative Study Group. J Pediatr 1996;129:883-91.  Back to cited text no. 26    
27.Offner G, Hoyer PF, Meyer B, Pichlmayr R, Brodehl J. Pre-emptive renal transplantation in children and adolescents. Transpl Int 1993;6:125-8.  Back to cited text no. 27  [PUBMED]  
28.Schurman SJ, McEnery PT. Factors influencing short-term and long-term pediatric renal transplant survival. J Pediatr 1997;130:455-62.  Back to cited text no. 28  [PUBMED]  [FULLTEXT]

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M B Abdurrahman
362 Brandy Street, Sudbury, Ontario, P3B 2P7
Canada
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    Introduction
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    References
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