Hyperphosphatemia in Children With Chronic Kidney Disease
Status:
Unknown status
Trial end date:
2018-12-01
Target enrollment:
Participant gender:
Summary
"Chronic Kidney Disease-Mineral and Bone Disorder " is a systemic disorder of mineral and
bone metabolism, due to chronic kidney disease that is manifested by either one or a
combination of the following :
1. Abnormalities of calcium, phosphate, parathyroid hormone or vitamin D metabolism
2. Vascular and/or soft tissue calcification.
3. Abnormalities in bone turnover, metabolism, volume, linear growth or strength. According
to glomerular filtration rate , Kidney Disease Improving Global Outcomesclassify chronic
kidney disease into 5 stages,stage 5 also known as End Stage Renal disease is defined as
glomerular filtration rate less than 15 ml/Min/1.73 m2, or the need for renal
replacement therapy for survival The kidney plays a major role in phosphate
homoeostasis. The kidneys excrete the total net amount of absorbed phosphate.Under
normal physiological condition phosphate is freely filtered through the glomerulus. The
majority (85-90%) of filtered phosphate undergoes tubular reabsorption primarily in
proximal tubules.
Progressive renal insufficiency leads to hyperphosphatemia, hypocalcemia, and secondary
hyperparathyroidism .
Hyperphosphatemia known as hidden killer in chronic kidney disease defined as an abnormally
high serum phosphate concentration of >1.46 mmol/L (4.5 mg/dL). Its long term complications
are renal osteodystrophy, hyperparathyroidism, and increased cardiovascular calcification
leading to increased mortality and morbidity .
High serum phosphate can interact with calcium to precipitate calcium phosphate salts in
non-skeletal tissues Calcification generally occurs in the blood vessels, heart valves,
myocardium, and other soft tissues .
Cardiovascular calcification is probably the main reason for the high prevalence of
cardiovascular diseases in chronic kidney disease patients Studies have shown that
hyperphosphatemia is associated with increased vascular stiffening and arterial and valvular
calcification This is postulated to be caused by elevated serum phosphorus promoting the
transformation of vascular smooth muscle cells into an osteoblast phenotype that can
mineralize These vascular calcification also lead to left ventricular hypertrophy by
decreasing vascular compliance . Poor control of mineral metabolism also has been associated
with functional and structural cardiac abnormalities Efforts to reduce morbidity and
mortality associated with Chronic Kidney Disease-Mineral and Bone Disorder are therefore
primarily directed at controlling hyperphosphatemia via diet, phosphorus binders, and
dialysis
Dialysis alone is inadequate in assisting hemodialysis patients to obtain and maintain normal
serum phosphate levels . So, other methods of achieving prescribed levels of serum phosphate
in hemodialysis patients include the use of phosphate binders and phosphorus dietary
restrictions.:
Phosphate binders have been approved by the Federal Drug Administration (FDA) for patients
treated with maintenance dialysis, and calcium-containing salts are used worldwide not only
for the control of hyperphosphatemia but also as a source of supplemental calcium. Several
calcium salts are commercially available, including calcium carbonate, calcium acetate, and
calcium citrate Sevelamer hydrochloride is a recently developed phosphate binder, which is a
quaternary amine anion exchanger without calcium or aluminum. Sevelamer is effective in
controlling hyperphosphatemia without increasing the calcium load in chronic hemodialysis
patients In addition to its effects on serum phosphorous levels, sevelamer has been shown to
decrease total serum cholesterol and low-density lipoprotein cholesterol and to increase
high-density lipoprotein levels . These effects may offer additional benefits in reducing
cardiovascular complications in patients with end-stage renal disease.
Controlling abnormal laboratory parameters such as calcium ,phosphate and parathyroid hormone
as well as preventing the progression of extraskeletal calcification is considered a major
component for prevention of the bone disease and other related morbidities and hopefully
mortality in chronic kidney disease patients