Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome

Abstract

The use of corticosteroids in the treatment of steroid-sensitive nephrotic (SSNS) syndrome in children has evolved surprisingly slowly since the ISKDC consensus over 50 years ago. From a move towards longer courses of corticosteroid to treat the first episode in the 1990s and 2000s, more recent large, well-designed randomized controlled trials (RCTs) have unequivocally shown no benefit from an extended course, although doubt remains whether this applies across all age groups. With regard to prevention of relapses, daily ultra-low-dose prednisolone has recently been shown to be more effective than low-dose alternate-day prednisolone. Daily low-dose prednisolone for a week at the time of acute viral infection seems to be effective in the prevention of relapses but the results of a larger RCT are awaited. Recently, corticosteroid dosing to treat relapses has been questioned, with data suggesting lower doses may be as effective. The need for large RCTs to address the question of whether corticosteroid doses can be reduced was the conclusion of the authors of the recent corticosteroid therapy for nephrotic syndrome in children Cochrane update. This review summarizes development in thinking on corticosteroid use in SSNS and makes suggestions for areas that merit further scrutiny.

Clinical practice guidelines for nephrotic syndrome: consensus is emerging

“…Comparison between recent clinical practice guidelines of the Kidney Disease Improving Global Outcomes (KDIGO) [6], German Society for Pediatric Nephrology (GSPN) [7], and the Indian Society of Pediatric Nephrology (ISPN) [3] (adapted with permission from [3]) Prednisone is dosed either by body surface area or by weight. While dosing using body weight is convenient, it might result in considerable underdosing, especially in younger children [15]. However, the evidence that short-and medium-term outcomes are better following dosing of initial therapy based on body surface area versus body weight is equivocal [12,15].…”

“…While dosing using body weight is convenient, it might result in considerable underdosing, especially in younger children [15]. However, the evidence that short-and medium-term outcomes are better following dosing of initial therapy based on body surface area versus body weight is equivocal [12,15]. While the ISKDC and GSPN recommend that prednisone be dosed on body surface area, guidelines from ISPN and KDIGO recommend either approach, with preference to surface area-based dosing in young children [3,6,7].…”

Therapeutic trials in difficult to treat steroid sensitive nephrotic syndrome: challenges and future directions

“…There was a move toward longer regimens of 12 weeks from the original ISKDC 8-week course after the 2007 Cochrane review found longer steroid courses resulted in higher rates of sustained remission at 12-24 months, without an increase in adverse effects [51]. Recent randomized control trials (RCTs) have called this into question, and some centers have returned to an 8-week prednisone course for the initial presentation of NS (see an in-depth review of the use of corticosteroids in NS [52]). The PREDNOS trial, with 237 children at first episode of SSNS, found no advantage of 16 weeks over 8 weeks of prednisolone.…”

“…The dose and duration of corticosteroids for NS relapses to optimize remission rates and minimize corticosteroid toxicities were recently reviewed [52]. While the optimal steroid regimen for relapse is yet to be identified, in the quest to achieve long-term remission for children with nephrotic syndrome, it is unlikely the dose or duration will substantially alter the course of NS [1].…”

Commentary on “Pediatric Idiopathic Steroid-sensitive Nephrotic Syndrome Diagnosis and Therapy - Short version of the updated German Best Practice Guideline (S2e)”

“…Of note, younger children below the age of 4 to 6 years may have an advantage of an extended course of steroids in the first flare [24,25,30]. There are currently two ongoing clinical trials of 3 versus 6 months: a Chinese trial in children under 6 years (NCT04536181) and an Indian trial in children under 4 years (CTRI/2015/06/005939) to challenge the conclusion of the recent Cochrane update [31] against extended initial steroid duration [32]. Results of these trials may open the door for a more individual age-dependent treatment approach.…”