Low-dose ofatumumab for multidrug-resistant nephrotic syndrome in children: a randomized placebo-controlled trial.

BACKGROUND: Children with multidrug-resistant nephrotic syndrome (MRNS) are exposed to drug toxicity (steroids/calcineurin inhibitors (CNI)/mycophenolate mofetil (MMF)) and have an increased risk of kidney disease progression. In small case series, the fully humanized anti-CD20 antibody ofatumumab (OFA) induced remission in children with MRNS when at high dose (10,300 mg/1.73 m2) and partial remission at standard dose (1000 mg/1.73 m2). METHODS: This double-blind randomized placebo-controlled trial tested the efficacy of single infusion OFA in children with proven MRNS and initial chronic renal failure (eGFR [median/range] 119/38-155 ml/min/1.73 m2 in Placebo arm vs. 65/19-103 ml/min/1.73 m2 Intervention). Children who had been resistant to a combination of CNI and steroids, with or without MMF or rituximab, were randomized to receive single infusion OFA (1500 mg/1.73 m2) (Intervention arm) or normal saline (Placebo arm). We assessed complete or partial remission of proteinuria after 3 months (primary outcome), and after 6 and 12 months (secondary outcomes), as well as progression to end-stage kidney disease. RESULTS: After 13 of the planned 50 children (25%) were randomized, the data safety and monitoring board recommended study termination for futility. All 13 children remained nephrotic. Renal function worsened in 5 children (2 in Intervention arm, 3 in Placebo arm) who required renal replacement therapy during the study period. Circulating CD20 was reduced following OFA infusion and remained low for > 3 months. CONCLUSIONS: OFA given in one single infusion of 1500 mg/1.73 m2 doses does not induce remission in MRNS. Regimens based on higher OFA doses should be tested in clinical trials. TRIAL REGISTRATION: https://clinicaltrials.gov: NCT02394106.

Magnetic resonance urography and laparoscopy in paediatric urology: a case series.

Paediatric urology often presents challenging scenarios. Magnetic resonance urography (MRU) and laparoscopy are increasingly used. We retrospectively studied children affected by a disease of the upper urinary tract who after MRU were elected for laparoscopic treatment. This pictorial essay draws on our experience; it illustrates some specific MRU findings and highlights the usefulness of MRU for the diagnosis of upper urinary tract pathology in children. It also offers some examples of the potential additional diagnostic information provided by laparoscopy as well as its therapeutic role.

Cystosonography and voiding cystourethrography in the diagnosis of vesicoureteral reflux.

The availability of US (ultrasonography) contrast media in the last few years has prompted investigation into their use in the diagnosis of vesicoureteral reflux (VUR) in children, a common cause of urinary tract infections (UTI) or pyelonephritis. We performed voiding cystourethrography (VCUG) and cystosonography (CSG) in the same session in 158 children (M/F 97/61, mean age 3.9 years, age range 0.1-12.7 years) with clinical suspicion of VUR, studied over a year with an ATL plus 3000 real-time scanner (ATL Ultrasound, Bothell, USA), equipped with 2- to 4- and 4- to 7-MHz convex transducers. US contrast medium Levovist (Schering, Berlin, Germany) was used. VCUG and CSG diagnosed 74 (24.2%) and 77 (25.2%) cases of VUR, respectively. There was no agreement in 67 cases (22%). The percentage of false negatives was similar and high with both techniques. CSG seems to be more sensitive in detecting intermediate (second- and third-degree) VUR. In spite of the moderate relative diagnostic adequacy of both methods, we believe that CSG is an alternative to VCUG, avoiding the risk of ionizing radiation, in the following conditions: (1) first diagnosis in females (not in males, due to the poor vesical and urethral anatomical detail it provides), (2) VUR follow-up, (3) VUR diagnosis in megaureters and/or in ureteroceles, and (4) VUR diagnosis in transplanted kidneys. Further improvements of CSG, both in US contrast media and in US technique, could possibly increase its sensitivity.