Randomized, Controlled Trial of Tacrolimus and Prednisolone Monotherapy for Adults with De Novo Minimal Change Disease

• DOI: 10.2215/cjn.06180519
• Publication Date: 2020-01-17T20:05:12Z
• Authors: Nicholas Rhys Med...; Christopher Lawrence; Marie Condon; Bhrigu Sood; Paul Warwicker; Heather Brown; James Pattison; Sunil Bhandari; Jonathan Barratt; Neil Turner; H. Terence Cook; Jeremy B. Levy; Liz Lightstone; Charles Pusey; Jack Galliford; Thomas D. Cairns; Megan Griffith
• Keywords: remission induction; Adult; Male; recurrence; METHYLPREDNISOLONE; Time Factors; Adolescent; LONG-TERM; Prednisolone; Calcineurin Inhibitors; nephrology; STEROID-AVOIDANCE; 610; CHILDREN; Tacrolimus; DOUBLE-BLIND; Young Adult; Glomerulonephritis; Adrenal Cortex Hormones; Recurrence; Humans; Prospective Studies; tacrolimus; humans; IDIOPATHIC NEPHROTIC SYNDROME; Aged; CHANGE NEPHROPATHY; Science & Technology; nephrotic syndrome; adult; Nephrosis, Lipoid; Remission Induction; prednisolone; 1103 Clinical Sciences; Urology & Nephrology; Middle Aged; PREVENTION; prospective studies; United Kingdom; 3. Good health; Treatment Outcome; lipoid nephrosis; treatment outcome; CYCLOSPORINE; Female; Life Sciences & Biomedicine; CYCLOPHOSPHAMIDE THERAPY; Immunosuppressive Agents

Background and objectives Minimal change disease is an important cause of nephrotic syndrome in adults. Corticosteroids are first-line therapy for minimal change disease, but a prolonged course of treatment is often required and relapse rates are high. Patients with minimal change disease are therefore often exposed to high cumulative corticosteroid doses and are at risk of associated adverse effects. This study investigated whether tacrolimus monotherapy without corticosteroids would be effective for the treatment of de novo minimal change disease.

Design, setting, participants, & measurements This was a multicenter, prospective, open-label, randomized, controlled trial involving six nephrology units across the United Kingdom. Adult patients with first presentation of minimal change disease and nephrotic syndrome were randomized to treatment with either oral tacrolimus at 0.05 mg/kg twice daily, or prednisolone at 1 mg/kg daily up to 60 mg daily. The primary outcome was complete remission of nephrotic syndrome after 8 weeks of therapy. Secondary outcomes included remission of nephrotic syndrome at 16 and 26 weeks, rates of relapse of nephrotic syndrome, and changes from baseline kidney function.

Results There were no significant differences between the tacrolimus and prednisolone treatment cohorts in the proportion of patients in complete remission at 8 weeks (21 out of 25 [84%] for prednisolone and 17 out of 25 [68%] for tacrolimus cohorts; P=0.32; difference in remission rates was 16%; 95% confidence interval [95% CI], −11% to 40%), 16 weeks (23 out of 25 [92%] for prednisolone and 19 out of 25 [76%] for tacrolimus cohorts; P=0.25; difference in remission rates was 16%; 95% CI, −8% to 38%), or 26 weeks (23 out of 25 [92%] for prednisolone and 22 out of 25 [88%] for tacrolimus cohorts; P=0.99; difference in remission rates was 4%; 95% CI, −17% to 25%). There was no significant difference in relapse rates (17 out of 23 [74%] for prednisolone and 16 out of 22 [73%] for tacrolimus cohorts) for patients in each group who achieved complete remission (P=0.99) or in the time from complete remission to relapse.

Conclusions Tacrolimus monotherapy can be effective alternative treatment for patients wishing to avoid steroid therapy for minimal change disease.

Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_01_16_CJN06180519.mp3