Effect of two prophylactic bolus vitamin D dosing regimens (1000 IU/day vs. 400 IU/day) on bone mineral content in new-onset and infrequently-relapsing nephrotic syndrome: a randomised clinical trial.

OBJECTIVES: To examine the efficacy of two vitamin D dosages (1000 vs. 400 IU/day) for osteoprotection in children with new-onset and infrequently-relapsing nephrotic syndrome (IFRNS) receiving corticosteroids. METHODS: This parallel-group, open label, randomised clinical trial enrolled 92 children with new-onset nephrotic syndrome (NS) (n = 28) or IFRNS (n = 64) to receive 1000 IU/day (Group A, n = 46) or 400 IU/day (Group B, n = 46) vitamin D (administered as a single bolus initial supplemental dose) by block randomisation in a 1:1 allocation ratio. In Group A, vitamin D (cholecalciferol in a Calcirol® sachet) was administered in a single stat dose of 84,000 IU on Day 1 of steroid therapy (for new-onset NS), calculated for a period of 12 weeks@1000 IU/day) and 42,000 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@1000 IU/day). In Group B, vitamin D (cholecalciferol in a Calcirol® sachet) was administered as a single stat dose of 33,600 IU on Day 1 of steroid therapy (for new-onset NS, calculated for a period of 12 weeks@400 IU/day) and 16,800 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@400 IU/day). The proportionate change in bone mineral content (BMC) was analysed in both groups after vitamin D supplementation. RESULTS: Of the 92 children enrolled, 84 (n = 42 new onset, n = 42 IFRNS) completed the study and were included in the final analysis. Baseline characteristics including initial BMC, bone mineral density, cumulative prednisolone dosage and serum 25-hydroxycholecalciferol levels were comparable in the two groups. There was a greater median proportionate change in BMC in the children who received 1000 IU/day vitamin D (3.25%, IQR -1.2 to 12.4) than in those who received 400 IU/day vitamin D (1.2%, IQR -2.5 to 3.8, p = 0.048). The difference in proportionate change in BMC was only statistically significant in the combined new-onset and IFRNS, but not for IFRNS alone. There was a greater median proportionate change in serum 25-hydroxycholecalciferol, in the children who received 1000 IU/day vitamin D (20.6%, IQR 14.9-36.75) than in those who received 400 IU/day vitamin D (7.7%, IQR 3.5-18.5, p < 0.01). There was a greater median proportionate change in serum calcium in the children who received 1000 IU/day vitamin D (20%, IQR 13.1-29.0) than in those who received 400 IU/day vitamin D (11.3%, IQR 2.8-25.0, p = 0.03). Despite vitamin D therapy, BMC decreased from the baseline in 15 (32.6%) children receiving 1000 IU/day vitamin D and in 17 (36.9%) children receiving 400 IU/day vitamin D. There were no adverse effects attributable to vitamin D. CONCLUSION: The 1000 IU/day dose is marginally more effective than 400 IU/day and it is likely than an even larger dose is required. Further research is required to assess the efficacy and safety of vitamin D doses higher than 1000 IU/day.

Levamisole in Frequently-relapsing and Steroid-dependent Nephrotic Syndrome.

OBJECTIVE: To evaluate the efficacy of levamisole in children with frequently relapsing nephrotic syndrome (FRNS) and steroid dependent nephrotic syndrome (SDNS) when administered on an alternate day ('initial therapy' in all cases) or daily basis ('rescue therapy' in whom alternate day therapy failed). METHODS: The records of 95 children (age 1-18y) with FRNS (62) and SDNS (33), who were treated at the Pediatric nephrology clinic, and received levamisole therapy (maximum 2 y duration, between 2010-2013) with a follow-up period of minimum 1 y, were included. RESULTS: Alternate day levamisole therapy was efficacious in 73.7% (n=70). The overall efficacy of levamisole therapy was 88.4% (n=84). Levamisole therapy decreased the mean (SD) number of relapses from 4.22 (0.46)/y to 1.35 (0.36)/y (P<0.01); and cumulative median (IQR) prednisolone dosage from 4200 (3200-4300) mg/m2 to 1100 (IQR 500-2900) mg/m2 (P<0.001). On a one-year follow up of the cases in whom levamisole therapy was efficacious during therapy (median 24 mo) (n=84), a frequently relapsing or steroid dependent course continued to persist in 48.8% (41), necessitating oral cyclophosphamide (n= 22) or mycophenolate mofetil (n=19). CONCLUSION: Daily levamisole therapy was useful in 56% of children who demonstrated failure while on alternate day levamisole therapy, and could be a useful therapeutic option in FRNS and SDNS.