INTRODUCTION
Nephrotic Syndrome is a clinical manifestation of glomerular disease associated with heavy (nephrotic range) proteinuria. Nephrotic range proteinuria is defined as proteinuria >3.5g/24 hour or a urine protein creatinine ratio of > 2. Triad of clinical findings associated with Nephrotic Syndrome arising from the large urinary losses of protein are hypoalbuminemia (<2.5g/dl), edema, hyperlipidemia (cholesterol > 200mg/dl) 1. Nephrotic Syndrome affects 1-3 per lac children less than 16 years of age per year 1.
Nephrotic Syndrome was first documented in 1484 by Cornelius Roleans of Mecheln, Belgium (1450–1525).
In his work “Liber de aegritudinibusinfantiumum,” which was published in 1484, he listed 52 children, in which he described Swelling of the whole body in child due to Nephrotic Syndrome 2.
Glomerular filtration barrier plays the key role in pathogenesis of proteinuria in Nephrotic Syndrome. Glomerular filtration barrier is consisting of fenestrated capillary endothelium, glomerular basement membrane, podocytes (with foot process and intercalated slit diaphragm). GFB selectively permits ultrafiltration of solutes and water. Large molecular weight molecules (>40000 Dalton), such as albumin and clotting factors are prevented from passing through the ultrafiltration process. In Nephrotic Syndrome increase permeability of GFB due to damage of podocytes (effacement of foot process). As a result, increase the passes of albumin across GFR into urinary space 3.
Glucocorticoid therapy is the standard therapy for Nephrotic Syndrome4. Corticosteroid have been used to treat childhood Nephrotic Syndrome since 1950. It causes diuresis, loss of edema and proteinuria. Corticosteroid usage has reduced the mortality rate in childhood Nephrotic Syndrome to around 3%. In new cases of Nephrotic Syndrome, approximately 80% will achieve remission with 12 weeks corticosteroid therapy. In relapse cases of Nephrotic Syndrome corticosteroid is used 9-18 months 5.
Use of steroid on long term basis can cause growth impairment, cataracts, excessive weight gain or obesity, osteoporosis and affect bone mineral density 6. Corticosteroid can be direct inhibition of the bone forming osteoblast. Its prolonged uses increase 24-hydroxylase activity. The 24-hydroxylase enzyme break down the active form of vitamin D, called 1,25-dihydroxy vitamin D3 or calcitriol to an inactive form when the vitamin is longer needed7.
Vitamin D is not really a vitamin. It behaves like a hormone and carries out essential biological functions through endocrine, paracrine and intracrine mechanisms. Maintenances of adequate level of vitamin D recommended, not only to maintain good bone health, but also to provide for its non-osseous function 8. Many physiological processes depend on vitamin D and it’s lack is linked to a variety of acute and chronic diseases, such as problems with calcium metabolism, autoimmune disorders, some malignancies, type 2 diabetes mellitus, infections, and cardiovascular diseases 8.
In order to promote bone health, the Endocrine Society Clinical Practice Guideline recommends that children and infants aged 0 to 1 year require at least 400 IU/d (IU = 25 ng) of vitamin D and older child require at least 600 IU/d. However, it may take at least 1000 IU/d of vitamin D to consistently increase the blood level of 25(OH)D above 30 ng/ml. In order to meet their body's vitamin D needs, there is additional recommendation that patients using glucocorticoids obtain two to three times the recommended amount of vitamin D for their age group 9.
Vitamin D (25 hydroxyvitamin D) is bounded to vitamin D binding protein (DBP). Vitamin D and its metabolites are transported from the site of production to target tissue by binding with Vitamin D binding protein (DBP). DBP maintain adequate Vitamin D level in blood. It has anti-inflammatory, anti-oxidant properties that play a role in disease prevention and treatment. It is involved in the regulation of calcium metabolism which is critical for maintaining healthy bones and it regulates immune function, helps in removal of toxin and pathogen from blood and have anti-cancer properties in the form of Vitamin D binding protein macrophage activating factor (DBP-MAF) 10.
The patient with Nephrotic Syndrome loses 25 hydroxy D along with the binding protein in urine 11.
Deficiency of 25(OH) vitamin D may lead to hypocalcemia, hyperparathyroidism, diminished bone mineral density. According to several research, taking calcium and vitamin D supplements can help to stop bone resorption. High doses of vitamin D3 may be utilized to treat the abnormalities, suggesting that vitamin D3 can be administered in children with Nephrotic Syndrome 12.