Nephrotic syndrome (NS) is a non-specific kidney disease characterized by the body excreting too much protein into the urine. It is non-specific because it can be caused by various disorders that damage the kidney. The excess protein in urine comes from the protein that is normally kept in the bloodstream. Protein in the bloodstream helps to control fluids in the bloodstream. Without enough protein in the blood, the fluids can leak out of the bloodstream and cause swellings in different areas of the body, commonly in the legs and the eyes. Additionally, NS can lead to weight gain as the uncontrolled fluids are retained in the body.
The most common cause of NS in children is minimal change disease. Minimal change disease is when the glomeruli, the filtering units that make urine and remove waste, are damaged. While the cause is relatively unknown, it is suggested that immune related conditions such as allergic reactions, vaccinations, and viral infections can cause the disease.
Because immune related conditions can cause minimal change disease and subsequent NS, a common treatment is the use of glucocorticoids, a form of corticosteroids. Corticosteroids are commonly used to control the immune system and have been shown to help in the treatment of NS.
One drawback in using glucocorticoids, however, is that it is known to reduce bone density and increase the risk of fractures. Any reduction to bone health in children can be detrimental as it can have long-term effects on growth and development.
Therefore, researchers in the present study wondered, can vitamin D and calcium help protect bone health in children with newly-onset NS who have just started taking glucocorticoids?
To answer this question, the research team sought out pre-pubertal children with newly diagnosed NS. To be included in the study, the children had to be between the ages of 1 and 13 years old and had never used glucocorticoids in the past.
They eventually had a group of 41 children that met the criteria. All of the children received oral glucocorticoids for the 12 weeks of the study. For the first 6 weeks, they received 60 mg/m2/day. For the last 6 weeks, they received 40 mg/m2 every other day.
The children were then randomized into two groups. Twenty-one were randomized to receive one large dose of 90,000 IU of vitamin D (roughly 1,000 IU/day over 12 weeks) and 500 mg of calcium every day for the 12 weeks of the trial. The other 20 children received nothing beyond the glucocorticoids.
At the end of the trial, the researchers conducted a dual-energy X-ray absorptiometry scan to determine bone mineral content (BMC) and bone mineral density (BMD) at the lumbar spine. They were mainly focusing on the BMC because it has been shown to be more sensitive in measuring bone health and bone growth in children. This is because it accounts for the size of the bone as well as the amount of minerals in the bone in unit area.
Here is what the researchers found:
- The BMC increased by 11.2% in the children who received vitamin D and calcium compared with an 8.9 decrease in the children in the control group (p<0.0001).
- The BMD increased by 2.8% in the children who received vitamin D and calcium compared with a 0.74% increase in the children in the control group, although this was not significant (p=0.27).
- The children in the vitamin D and calcium group and in the control group saw an average height gain of 1.80% and 1.84%, respectively. The researchers attributed this to the normal growth of children (p=0.82).
The researchers concluded,
“A 12-week course of glucocorticoids for new-onset NS decreases lumbar spine BMC by 8.9% in growing pre-pubertal children. Vitamin D and calcium co-administration not only prevents this decrease, but actually increases BMC by 11.2%, such that there is a treatment-attributable 20.1% increment in lumbar spine BMC at the end of 12 weeks.”
There are some limitations in this study. The first is that this study only looked at children in India, and the results cannot be generalized to all populations. They didn’t measure total vitamin D levels, so we don’t know what baseline and final vitamin D levels are. And the biggest limitation of the study is that the control group didn’t take a placebo pill, so there is room for some bias in the results, in that the vitamin D and calcium group may have benefited from a placebo effect. The researchers were not clear if the researchers who examined BMC and BMD were blinded from who was taking vitamin D and calcium.
Considering that glucocorticoids are both a valuable treatment for children with NS and a detriment to bone health and bone growth, these results are promising. However, there needs to be longer studies on larger populations with long-term follow-up to determine the greater effects of this intervention.
Choudhary, S. et al. Calcium and vitamin D for osteoprotection in children with new-onset nephrotic syndrome treated with steroids: a prospective, randomized, controlled, interventional study. Pediatric Nephrology, 2014.