ESPN 51th Annual Meeting

ESPN 2018


 
Rituximab treatment for difficult-to-treat nephrotic syndrome in children: a multicenter study
Mehmet Taşdemir 1 Nur Canpolat 2 Nurdan Yıldız 3 Gül Özçelik 4 Meryem Benzer 5 Seha Kamil Saygılı 2 Neşe Özkayın 6 Özde Nisa Türkkan 7 Ayşe Balat 8 Cengiz Candan 9 Mehtap Ezel Çelakıl 10 Sevgi Yavuz 11 Nurver Akıncı 4 Nilüfer Göknar 12 Cihangir Akgün 13 Sebahat Tülpar 5 Harika Alpay 3 Lale Sever 2 Ilmay Bilge 1

1- Division of Pediatric Nephrology, Department of Pediatrics, Koç University School of Medicine, Istanbul, Turkey
2- Division of Pediatric Nephrology, Department of Pediatrics, Istanbul University Cerrahpaşa School of Medicine, Istanbul, Turkey
3- Division of Pediatric Nephrology, Department of Pediatrics, Marmara University School of Medicine, Istanbul, Turkey
4- Division of Pediatric Nephrology, Department of Pediatrics, Şişli Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey
5- Division of Pediatric Nephrology, Department of Pediatrics, Bakırköy Dr. Sadi Konuk Education and Research Hospital, Istanbul, Turkey
6- Division of Pediatric Nephrology, Department of Pediatrics, Trakya University School of Medicine, Edirne, Turkey
7- Division of Pediatric Nephrology, Department of Pediatrics, Istanbul University Istanbul School of Medicine, Istanbul, Turkey
8- Division of Pediatric Nephrology, Department of Pediatrics, Istanbul Aydın University School of Medicine, Istanbul, Turkey
9- Division of Pediatric Nephrology, Department of Pediatrics, Istanbul Medeniyet University Göztepe Education and Research Hospital, Istanbul, Turkey
10- Division of Pediatric Nephrology, Department of Pediatrics, Kocaeli University School of Medicine, Kocaeli, Turkey
11- Division of Pediatric Nephrology, Department of Pediatrics, Kanuni Sultan Süleyman Education and Research Hospital, Istanbul, Turkey
12- Division of Pediatric Nephrology, Department of Pediatrics, Bağcılar Education and Research Hospital, Istanbul, Turkey
13- Division of Pediatric Nephrology, Department of Pediatrics, Istanbul Medipol University School of Medicine, Istanbul, Turkey
 
Introduction:

 

Children with difficult-to-treat steroid-dependent/resistant (idiopathic) nephrotic syndrome (SDNS or SRNS) need long-term and cumulative high-dose immunosuppressive therapy. Rituximab (RTX) may be a good alternative agent for patients with NS uncontrolled by conventional treatment. This study aimed to evaluate the efficacy and safety of rituximab at varying doses and intervals in children with difficult-to-treat NS.

Material and methods:

 

This retrospective study enrolled 49 children (20 male) (aged 1.9 to 18.1 years) with difficult-to-treat idiopathic NS from 13 tertiary centers in Istanbul. In addition to steroids, all patients received another immunosuppressant. Upon the failure of the conventional treatment, RTX was added. The patients were classified based on the following: steroid response (SDNS, n=26 or SRNS, n=23) and renal histology [minimal-change disease (MCD, n=19), focal segmental glomerulosclerosis (FSGS, n=23)]. 

Results:

 

The median age was 10.3 years [interquartile range (IQR), 8.4] during the first RTX administration. The median disease duration was 7.7 years (range 1.10-19.2). At the beginning, RTX was administered at a dose of 375 mg/m2/week once (n=26), two times (n=6), three times (n=6) or four times (n=11). The median follow-up periods pre- and post-RTX therapy were 4.24 (IQR, 7.01) and 1.60 (IQR, 2.70) years, respectively. The rates of complete/partial remission were higher in patients with SDNS (80%) than with SRNS (52%), and in those with a histology of MCD (78%) compared with FSGS (60%).  Of different dose groups, the highest rate of complete/partial remission was obtained with the 4-dose regimen (n=13, 72%). Compared with the pre-RTX period, overall per-patient-per-year median number of relapses significantly decreased from 1.94 (IQR, 1.89, range 0.23-13.7) to 0.00 (IQR, 0.49, range 0.00-2.58) (p<0.001) during a median follow-up of 1.5 years (range 0.1-8.2). In 21 patients, no additional immunosuppressants apart from steroid were required in post-RTX period. The most common adverse effects were rashes (n=6) and cough (n=6) on the administration day, and hypogammaglobinemia (n=4) and infections (n=3) in the long-term period.

Conclusions:

 

Rituximab therapy seems to be an effective and safe option for difficult-to-treat nephrotic syndrome cases in childhood, requiring new recommendations about its dosage and intervals.