Surabhi, Choudhary (2009) Open randomised controlled interventional prospective study to evaluate the role of prophylactic calcium and vitamin D in preventing short term steroid induced bone loss in new onset nephrotic syndrome. Masters thesis, Christian Medical College, Vellore.
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Abstract
INTRODUCTION: Nephrotic Syndrome is a common glomerular disorder affecting children. It is characterized by heavy proteinuria, hypoalbuminemia, edema and hypercholesterolemia. The incidence is 2-3 per 1, 00,000 children per year. Approximately 90% of children with Nephrotic Syndrome have some form Idiopathic Nephrotic Syndrome. This includes 3 histological types: 1. Minimal Change Disease. 2. Mesangial Proliferative Glomerulonephritis (MesPGN). 3. Focal Segmental Glomerulosclerosis. Corticosteroids like Prednisolone are the recommended first line treatment for nephrotic syndrome. Majority of children have Steroid Sensitive Minimal Change Disease. Most children with Steroid Sensitive Nephrotic Syndrome (SSNS) have repeated relapses, which generally decrease in frequency as the child grows older. Glucocorticoids are used in myriad other pediatric diseases. It is estimated that 10% of children may require some form of glucocorticoids at some point in their childhood. Prolonged steroid use is known to cause osteoporosis. Decreased bone mineral density (BMD) has been described in various pediatric disorders that require glucocorticoids, including asthma, juvenile rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and organ transplantation . Impairment of childhood growth with an approximate cortisone dose of 1.5 mg/kg/day was first described over 40 years ago; osteopenia in children receiving a Prednisolone dose of less than 0.16 mg/kg/day has also been reported. 37,000 children were studied in UK by Van Staa et al, to evaluate the incidence of fractures among pediatric glucocorticoid users .Results showed that the risk of fracture was increased in children who received four or more courses of oral corticosteroids for a mean duration of 6.4 days. Fracture risk was also increased among children using 30 mg Prednisolone or more each day. Childhood Steroid sensitive nephrotic syndrome provides a clinical model of chronic glucocorticoid therapy in the absence of significant underlying disease activity. The course of SSNS is characterized by relapses which result in protracted, repeated courses of glucocorticoids. The standard Prednisolone dose for new onset disease and relapses is 2 mg/kg per day which far exceeds the 5 mg/day that is considered a risk factor for Glucocorticoid induced osteoporosis in adults. While osteoporosis has long been considered a disease of the aging, there is increasing awareness that children are not exempt from developing the disease. Threats to bone health that are operative during the pediatric years may be particularly costly long-term, since growth and development of the skeletal system play a critical role in determining bone strength and stability in later years. Although the deteriorative effect of steroid treatment on children’s bones has been well known for years, no recommendations have been suggested for the prevention of diminished BMD and BMC in children with nephrotic syndrome. There are no clear cut guidelines as to when bone protective strategies must be instituted. This study was thus undertaken to determine the protective efficacy of Calcium and Vitamin D supplementation in children with Nephrotic Syndrome on short term steroids. Using Bone Mineral Density (BMD) and Bone Mineral Content (BMC) as tools, those receiving supplementation were compared with those not receiving it. The results will enable us to draw protocols / guidelines for institution of bone protective therapy for children on short term steroids. AIM OF THE STUDY: To study the effect of short term corticosteroid therapy and the prophylactic role of Calcium and Vitamin D on bone health in children with nephrotic syndrome. OBJECTIVES: PRIMARY OBJECTIVES: 1. To study the effect of short term steroids on bone in children with nephrotic syndrome using serial measurements of Bone Mineral Density (BMD) & Bone Mineral Content (BMC)at the Lumbar spine. 2. To evaluate the role of prophylactic Calcium and Vitamin D in preventing short term steroid induced bone loss in children with new onset Nephrotic Syndrome. SECONDARY OBJECTIVE: 1. To study the adverse effects of steroid therapy. METHODOLOGY: Study Design and Duration: This open randomised controlled interventional prospective study was conducted in the Paediatric Nephrology and Endocrine Departments of Christian Medical College Hospital, Vellore. The study was conducted for a duration of 3 months from May 2007 to July 2008. Selection of Subjects: Children with new onset nephrotic syndrome were recruited into the study. Inclusion Criteria: 1. Patients in the age group of 1 to 13 years. 2. Children with first presentation of Nephrotic syndrome. 3.(Proteinuria more than 40 mg / m2 /hr or Urine spot protein/creatinine ratio of >2). 4.No history of prior steroid use. 5. No clinical or biochemical evidence of metabolic bone disease. Exclusion Criteria: 1. Patients with a history of previously known kidney or bone disease. 2. Patients with a history, clinical or biochemical evidence of metabolic bone disease (e.g. chronic renal failure, liver disease). 3. Children not fulfilling the criteria for Nephrotic syndrome (with gross hematuria, persistent hypertension or evidence of renal disease other than nephrotic syndrome). 4. Patients with a serum creatinine > 1.5 mg/dl. 5. Patients who were on or had received glucocorticoid therapy. 6. Children with onset of puberty - Tanner stage >1. 7. Patients on steroid sparing immunosuppression (Azathioprine, Mycophenolate. Mofetil, Cyclophosphamide, Cyclosporine). 8. Patients with known or suspected history of hypersensitivity to Prednisolone. SUMMARY: 46 children were recruited into the study and followed up over 12 weeks. 34 children had completed the study at the time of analysis, 4 were dropouts and 8 are still undergoing treatment. The children were randomized into 2 groups: Group 1: 18 children received steroids and Calcium and Vitamin D, Group 2: 16 children received steroids only. • Children in the age group of 1 year to 12.42 years were recruited into the study over a period of 15 months. The mean age was 4.13 years. Group 1 and Group 2 had similar age distribution. • There were 24 boys and 10 girls. The male: female ratio was 2.4: 1. • Majority of the children belonged to Tamil Nadu (24), followed by West Bengal (5), Jharkhand (2) , Tripura (2) and Andhra Pradesh (1). • In 35% (12/34) children, infections triggered onset, majority being LRI (6/12), followed by URI (4/12). 1 each had Acute Gastroenteritis, Hepatitis A and Urinary Tract Infection. • 20.6% (7/34) children had hypertension at onset. • By 2 weeks, 82.4% (28/34) children were in remission, 88.2% (30/34) by 4 weeks and 97% (33/34) by 6 weeks. • By 12weeks, 91.2% (31/34) remained in remission. • 38.6% (13/34) patients relapsed, 85% after stopping steroids and 15% while tapering steroids. In 46% (6/13), relapse was triggered by an infection. Viral fever and URI were the most common infections precipitating relapse. • Cushingoid features (100%), gastritis (79.4%), hypertrichosis (67.8%) and infections (20.6%) were the most commonly observed side effects of steroids. 8.8% had behavior changes and 5.9% had striae. • Higher incidence of gastritis and infections at 6 weeks compared to 12 weeks may reflect dose dependent nature of these side effects. • 76.4% (26/34) received additional medications in the form of diuretics – spironolactone (64.7%) and frusemide (50%), antibiotics (41.2%), antihypertensives – nifedipine (14.7%), atenolol (2.9%) and ATT (2.9%). • Change in Weight, Height and BMI and Serum Calcium over 12 weeks calculated over baseline showed no statistically significant difference between the 2 groups. • A net weight gain of 1.24 % in Group I and 7.7% in Group II was observed. • Group I & II showed 1.88 % and 2.11 % increase in height respectively. • BMI decreased by 1.78 % in Group I; in Group II it increased by 3.826% • Serum Calcium (corrected for the corresponding Serum albumin) was maintained in the normal physiological range in all children. • Serum Calcium dropped by 1.16% in Group I and 0.69 % in Group II. Despite the drop, Serum calcium values remained within the normal range at 12 weeks. • There was a small gain in BMD in both groups 2.77% in Group I and 1.63% in Group II. The difference between the 2 Groups was not significant. • Children receiving Calcium and Vitamin D supplements showed a marked increase in BMC (11.3%) in contrast to controls who showed a 10.4 % fall in the same. The difference in the 2 groups was highly significant ( z = - 4.175 , p < 0.001). • The net intervention (Ca & Vitamin D administration) attributable difference in Bone. • Mineral Content in the 2 groups was 21.6%. CONCLUSIONS: 1. Bone Mineral Content of growing children decreased by 10% after 12 weeks of steroid therapy in the control group confirming the detrimental effects of high dose short term steroids on the bone. 2. BMD increased only marginally both in absolute value as well as a percentage change over baseline in both treatment and control groups. BMD measurements failed to detect steroid induced bone changes in our study. This confirms the superiority of BMC rather than BMD in determining changes in bone health in growing children. 3. Children receiving Calcium and Vitamin D supplements showed a significant improvement (11.3%) in the BMC in contrast to controls who showed a 10% decrease in the same. 4. Prophylactic Calcium and Vitamin D supplementation is useful in preventing steroid induced bone changes as demonstrated by a net treatment attributable change in BMC of 21.6%. 5. Short term steroid therapy had minor adverse effects - Cushingoid features, Gastritis and Hypertrichosis being the most common. Infections were the only serious adverse effect noted.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | prophylactic calcium ; vitamin D ; short term steroid ; induced bone loss ; new onset nephrotic syndrome ; Open randomised controlled interventional prospective study. |
| Subjects: | MEDICAL > Paediatrics |
| Depositing User: | Subramani R |
| Date Deposited: | 11 Jun 2018 01:02 |
| Last Modified: | 11 Jun 2018 01:02 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/8369 |
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