2. Why Might Kidney Disease Cause Short Stature?
a) Electrolyte Disturbance.
Imbalances in sodium, potassium and the acid base status can cause failure to grow. Excessive accumulation of acid occurs in some kinds of kidney disease. The child may have no symptoms except for a poor appetite and poor growth. When excessive acid builds up in the blood stream it reduces the appetite and also makes the bones softer, preventing calcium from being deposited in the bones to make them strong. Treatment of this kind of disturbance may simply be with supplements of proper electrolytes such as sodium bicarbonate pills or the medication “Polycitra”. Correcting the imbalance of the acid-base system can often cause a tremendous increase of the appetite and catch up growth as the bones are finally able to properly minimize.
b) Lack of Appetite.
Children with many kinds of kidney disease may simply not be hungry or they may not have the energy to eat. When children with kidney disease become malnourished a vicious cycle may be set up in which they actually lose their appetite further or lose their energy to eat further and become more and more malnourished in a vicious circle. Infants and young children may require tube feeding through a “gastrostomy” tube which is surgically placed into the stomach. Each evening, this tube is attached to a special pump for nightly tube feeds which allows them to live like a normal child during the day but get their extra calories by tube at night at home. Most families who do tube feeding find that it is quickly accepted by the family members and the child and does not interfere tremendously with their life. Specialty clinics which look after children with chronic kidney disease usually have a dietician on staff to provide the necessary dietary manipulations and access to special formulas that may be needed by these children. Improvement in calorie intake can also lead to a marked increase in growth rate.
c ) Bone Disease due to Chronic Kidney Disease
The kidney is critically important in regulating a number of signals for bone growth. First of all the kidney converts vitamin D from the diet into an active form which the bones and intestine respond to. In addition, four tiny little glands at the base of the neck called the parathyroids are affected by the vitamin D that the kidneys produce. Dietary and standard vitamin D supplements must be converted to active vitamin D, and in the presence of kidney failure, this vitamin D conversion may be inadequate, in turn leading to hyperactivity of the parathyroid glands and stimulation of hormones which cause the bones to waste away and be demineralized. Proper treatment of kidney disease often includes use of special varieties of vitamin D which are preactivated and do not require healthy kidneys (Calcitriol, Hectoral, Zemplar).
An imbalance in the calcium and phosphorous in the blood may also slow down bone growth. Some children with kidney disease lose too much phosphate (Fanconi syndrome or proximal tubular dysfunction in diseases like cystinosis). Supplements with phosphate may improve bone growth. Conversely, children with chronic kidney disease (chronic kidney failure) may retain excessive amounts of phosphate. This can be treated by reducing dietary phosphate with special diets, taking medicines that bind phosphorous from meals in the digestive system, preventing it from being absorbed into the body and finally, by dialysis. Improving the balance of calcium, phosphorous and vitamin D can often markedly improve bone growth.
d.) Excess Urine Output (Polyuria)
Some children have kidney disease which causes them to make large quantities of dilute urine. They actually make too much urine, and have to drink constantly to keep up to their urine losses of water. These conditions can include Chronic kidney disease, cystinosis, nephrogenic diabetes insipidus amongst others. These children live in a chronically borderline dehydrated state. If they stop drinking for even a short period of time, for example, if they develop the stomach flu, they can rapidly become dehydrated leading to shock and severe illness. These children may often be so thirsty that they reject solid fluid or even formula and only want water. In this situation, occasionally medications can be used to correct the polyuria, but more frequently tube feeds must be performed to ensure that the child gets adequate calories.
e.) Chronic Kidney Disease (Kidney Failure)
When children have reduced kidney function, in spite of optimization of the acid base balance, electrolyte balance, calcium phosphorous, vitamin D and nutrition their growth still may be suboptimal. Often children who require dialysis will have delayed growth which will not improve on dialysis. We no longer test for growth hormone production in children with this kind of kidney disease because these children do not respond to normal levels of growth hormone in their blood. Growth hormone dosage for children with kidney disease is higher than what is required by children who are simply growth hormone deficient. Many studies have shown marked improvement in the growth rate of children with kidney failure taking growth hormone supplements. Very small children have a higher risk of complications from the surgical procedure of a kidney transplant. Occasionally growth hormone treatment is used to hasten growth of a small child so as to make the child bigger, with more room for the surgeon to ‘insert’ the kidney.
f.) Medications Used to Treat Kidney Disease
Kidney diseases that are newly acquired are often treated with medications that may stunt growth. Diseases such as systemic lupus erythematosis (lupus), membranoproliferative glomerulonephritis (MPGN), nephrotic syndrome, focal and segmental glomerulonephritis (FSGS), etc. all require treatment with corticosteroids such as prednisone or methylprednisolone given by mouth or intravenously. When given for short periods of time (measured in days to weeks) with a holiday in between, growth usually does not suffer. While the children are taking the prednisone, growth slows, but it catches up during the drug holiday. Some kidney diseases, however, require continuous prednisone treatment, with the potential for permanent loss of growth.
g.) Following a Kidney Transplant
Patients who require prednisone following a kidney transplant also may not have normal growth. It has been known for many years that children who have received a kidney transplant have an inadequate growth spurt during their adolescence so in spite of having normal kidney function, the growth spurt is below what would be expected from a normal child. Therefore, pediatric nephrologists will always try to optimize growth while on dialysis or post transplant to ensure that they are starting from the highest possible size at the onset of the final adolescent growth spurt.
Unfortunately, not all kidney transplants have perfect long term function. Episodes of acute
rejection are treated with high doses of prednisone, sometimes for extended periods of time. The high dose prednisone often reduces growth. Some kidney transplants develop chronic damage that leads to the gradual development of kidney failure in the transplant. These children may have many years of life with a failing graft prior to restarting dialysis or retransplantation. The combination of prednisone therapy AND reduced kidney function can conspire to limit growth.
3. Complications of Growth Hormone Therapy in Kidney Disease
Whether children with kidney disease who receive growth hormone therapy have increased risk for selected complications is controversial. General complications of growth hormone therapy (in patients other than with kidney disease) are not discussed here.
In patients with kidney failure and pre existing bone disease the addition of growth hormone and resultant increased growth may aggravate their bone disease. Close surveillance of bone disease and parathyroid hormone levels are necessary and medication such as phosphate binders and activated vitamin D may need to be frequently adjusted. It is recommended that uncontrolled bone disease should be treated and brought under control prior to starting growth hormone therapy. A rare complication that may be seen in patients with renal disease is ‘slipped capital epiphyses’. This is a problem that can lead to long term hip complaints. The child may have hip or knee pain and or a limp. This can be detected with x-rays, and if caught early can be treated.
Growth hormone therapy may bring out a pre existing tendency toward diabetes mellitus. In children who have a predisposition to diabetes mellitus, many drugs may aggravate this condition. Often more than one of these drugs may be needed to treat kidney disease or prevent transplant rejection. These medications include prednisone and tacrolimus immunosuppressive medications. Close monitoring of blood sugar is important in these patients. Patients with kidney disease may develop increased pressure in the fluid around the brain when treated with growth hormone. This can lead to changes in vision and headaches. Your physician will check the eyes with an ophthalmoscope during regular clinic visits and if symptoms arise.
4. How to Determine if Your Child Who is Growing poorly has Kidney Disease
As you have read earlier in this pamphlet, many kidney related problems can lead to growth failure. If you are reading this because your child is not growing well it is important for you to know that kidney disease is quite rare in childhood. Of all the children who grow poorly only a few will be found to have kidney disease. Most will have some other reason for their growth failure.
Most of the time the possibility of kidney disease can be assessed by your primary physician. A detailed history, family history and physical exam can point to problems suggestive of kidney disease. This includes measuring the blood pressure. The history and physical exam are the most important part of the investigation. Laboratory testing may help support or refute the possibility of kidney disease. Testing of the blood includes measuring the level of acid, base, sodium, chloride, potassium, calcium and phosphate. These are called ‘electrolytes’. Kidney function is crudely measured using blood levels of urea and creatinine. These waste products are excreted by the kidney. If the blood levels are elevated this suggests reduced kidney function (kidney failure). The standard urinalysis will often identify diseases such as glomerulonephritis, chronic damage and other kidney problems.
If the history, physical examination and these tests do not point to kidney disease, the odds are that kidney disease is not the cause of your child’s failure to grow.
If the results of the history, physical exam and lab testing are abnormal, more specific testing may be performed. These might include a 24 hour urine collection to more accurately measure kidney function, renal ultrasound to determine the structure of the kidneys, xrays and hormone testing to look for bone disease caused by chronic kidney disease.
If you have further questions about kidney disease consider talking to your primary care doctor or endocrinologist. You may also contact the local branch of the National Kidney Foundation.
Contributed By:
Paul Grimm, M.D.
Professor of Clinical Pediatrics
Division of Pediatric Nephrology
UCSD Medical Center
San Diego, CA
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