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Pharmacokinetics of rituximab in a pediatric patient with therapy-resistant nephrotic syndrome
Authors:Clare?E.?Counsilman,Cornelia?M.?Jol–van der Zijde,Jasper?Stevens,Karlien?Cransberg,Robbert?G.?M.?Bredius,Ram?N.?Sukhai  author-information"  >  author-information__contact u-icon-before"  >  mailto:r.n.sukhai@lumc.nl"   title="  r.n.sukhai@lumc.nl"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author
Affiliation:1.Department of Pediatrics,Leiden University Medical Center (LUMC),Leiden,The Netherlands;2.Department of Pediatric Nephrology,Erasmus MC Sophia,Rotterdam,The Netherlands;3.Center for Human Drug Research,Leiden,The Netherlands
Abstract:

Background

Rituximab (RTX) has recently been introduced as a second-line therapy for nephrotic syndrome in children. Studies show that RTX given during the nephrotic state may be less effective than treatment during a non-nephrotic state, possibly due to loss of RTX in the urine.

Case-Diagnosis/Treatment

We describe a 10-year-old boy with steroid-resistant nephrotic syndrome (SRNS) treated with RTX during a phase of active non-selective proteinuria. The serum half-life of RTX in this patient was less than 1 day compared to 20 days in patients without protein losses. Urinary clearance was at least 25 %, compared to approximately 0 % in control patients. However, RTX loss in the urine, as well as in pleural effusion and ascites, only partly explains the rapid drop in the serum RTX concentration of this patient.

Conclusions

Serum half-life of RTX can be extremely short, partly due to excessive urinary losses in therapy-resistant nephrotic syndrome with non-selective proteinuria, as seen in our patient. These findings may help to explain the poor results of RTX treatment in patients with active proteinuria.
Keywords:
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