Weight or body surface area dosing of steroids in nephrotic syndrome: is there an outcome difference?

Abstract

Although prednisone is the treatment of choice for nephrotic syndrome (NS) in childhood, the dosing regimen varies between 60 mg/m(2)/day, as recommended in early studies, to the often prescribed 2 mg/kg/day dose, which is used in common practice. Mathematical models have demonstrated that weight-based dosing can be less than body surface area (BSA)-based dosing in smaller children. To test our hypothesis that weight-based dosing would result in altered treatment outcomes in children with NS, we analyzed a cohort of 56 children (mean age 5.4 ± 3.8 years) treated with a weight-based dosing regimen. Theoretical underdosing of corticosteroids was tested by calculating a relative underdosing percentage (RUP), which was defined as the dose difference between the theoretical BSA-based dose and the actual weight-based doses divided by the BSA-based dose × 100. We found that the mean "actual" prednisone dose in our patients was 43.6 ± 19.3 mg/day; in contrast, the mean theoretical BSA-based dose was calculated to be 48.8 ± 16.7 mg/day. Among the 56 patients, 43 (76.7%) were initial responders, of whom 58% followed a frequently relapsing (FR) course. RUP was significantly higher in FR (16.6 ± 7.9%) than in infrequent relapsers (8.7 ± 9.8%) (P = 0.03). RUP was not significantly different among initial responders and nonresponders. Based on these results, we conclude that prednisone underdosing, when dosing is prescribed according to weight, does not affect the initial response to treatment, but it does increase the likelihood of a FR course in responders.

Dosing of glucocorticosteroids in nephrotic syndrome

“…Without precise knowledge of the pathogenesis, optimal dosing cannot be established. The finding of Saadeh et al [1] that dosing of glucocorticoids per body surface area is superior to dosing per kilogram body weight (BW) in terms of reducing the recurrence rate of NS is interesting; however, an overriding effect of age cannot be ruled out.…”

“…As a consequence of all these uncertainties, the interesting results of Saadeh et al [1] need confirmation by larger randomized prospective studies over longer periods of time before it can be certain that relative small dose differences are responsible for the frequency of relapses.…”

“…Dosing based on body weight results in an absolute smaller dose than that calculated on the basis of body surface area. In this issue of Pediatric Nephrology, Saadeh et al describe for the first time the effect of weightbased relative 'underdosing' of prednisone [1]: while the initial response was not influenced by such 'underdosing', the frequency of relapses during the first 6 months appeared to be higher in this relatively 'underdosed' group. This result is an argument for a prednisone dosing regimen based on body surface area, at least for the initial and relapse treatment of NS in children.…”

“…The study by Saadeh et al [1] is rather limited by the small number of patients, its retrospective approach, and its association design. An example of the pitfalls of too few patients is the painful experience of the APN: due to an insufficient number of patients, the absolute number of relapses in the standard treatment groups varied from one study to the next [5,6].…”

“…Without precise knowledge of the pathogenesis, optimal dosing cannot be established. The finding of Saadeh et al [1] that dosing of glucocorticoids per body surface area is superior to dosing per kilogram body weight (BW) in terms of reducing the recurrence rate of NS is interesting; however, an overriding effect of age cannot be ruled out.It is unlikely that all patients with an initial presentation of NS require the same amount of glucocorticoid treatment as patients with recurrent disease. In the future, it may be more important to establish individual treatment strategies than to adapt high doses of glucocorticoids according to anthropometric measurements.…”