Defining a therapeutic range for adalimumab serum concentrations in the management of pediatric noninfectious uveitis, a step towards personalized treatment.

BACKGROUND: Adalimumab is currently considered the most efficacious anti-TNFα agent for childhood noninfectious uveitis (NIU). The objective of this study was to define a therapeutic range for adalimumab trough levels in the treatment of childhood NIU. METHODS: A retrospective, observational, pilot study of 36 children with NIU aged < 18 years, treated with adalimumab. Serum adalimumab through levels and adalimumab anti-drug antibodies (ADA) were analysed at least 24 weeks after start adalimumab. RESULTS: Adalimumab trough levels were significantly higher in complete responders 11.8 µg/mL (range 6.9-33.0) compared to partial or non-responders 9,2 µg/mL (range 0-13.6) (p = 0,004). Receiver-operator characteristics analyses with an area under the curve of 0,749 (95% CI, 0,561-0,937) defined 9.6 µg/mL as the lower margin for the therapeutic range. This cut-off corresponds with a sensitivity of 88% and a specificity of 56% (positive predictive value, 85%; negative predictive value, 62.5%). A concentration effect curve defined 13 µg/mL as the upper margin. Approximately one-third (30.5%) of patients had an adalimumab trough concentration exceeding 13 µg/mL. Free ADA were observed in 2 patients (5.5%). CONCLUSIONS: A therapeutic range of adalimumab trough levels of 9.6 to 13 µg/mL, which corresponds with an optimal clinical effect, was identified. Therapeutic drug monitoring may guide the optimisation of treatment efficacy in children with NIU in the treat-to-target era.

Pediatric lupus nephritis presenting with terminal renal failure.

A 12-year-old Congolese girl presented with acute renal failure, edema, hypertension, hemoptysis, hematuria, and proteinuria after a history of throat infection. Renal ultrasound showed kidneys of normal size, with increased echogenicity of the cortical parenchyma and decreased corticomedullary differentiation. Other additional investigations showed pancytopenia with decreased complement (low C3 and C4). Antinuclear antibodies were strongly positive, including anti-double stranded DNA. Renal biopsy confirmed severe grade IV lupus nephritis. She was treated with high-dose steroids, mycophenolate mofetil and hydroxychloroquine, in addition to hemodialysis. After one week of intensive treatment, diuresis recovered and dialysis could be stopped after six sessions. We describe an uncommon case of severe lupus nephritis, presenting with terminal renal failure. Since the rarity of this disease presentation, other more common diagnoses have to be considered. Once the diagnosis of lupus nephritis is established, a choice has to be made between the different induction treatment protocols. The patient's ethnic background and other supportive therapies, such as the need for dialysis, can help to make this choice.

Desmopressin resistant nocturnal polyuria secondary to increased nocturnal osmotic excretion.

PURPOSE: We investigated the role of increased solute excretion in children with desmopressin resistant nocturnal enuresis and nocturnal polyuria. MATERIALS AND METHODS: A total of 42 children with monosymptomatic nocturnal enuresis and significant nocturnal polyuria with high nocturnal urinary osmolality (more than 850 mmol/l) were not responding to desmopressin. A 24-hour urinary concentration profile was obtained with measurement of urine volume, osmolality, osmotic excretion and creatinine. The control group consisted of 100 children without enuresis. RESULTS: Based on osmotic excretion patients were classified into 3 groups. Group 1 had 24-hour increased osmotic excretion, most likely secondary to a high renal osmotic load. This was probably diet related since 11 of these 12 patients were obese. Group 2 had increased osmotic excretion in the evening and night, probably due to a high renal osmotic load caused by the diet characteristics of the evening meal. Group 3 had deficient osmotic excretion during the day, secondary to extremely low fluid intake to compensate for small bladder capacity. CONCLUSIONS: Nocturnal polyuria with high urinary osmolality in our patients with desmopressin resistant monosymptomatic nocturnal enuresis is related to abnormal increased osmotic excretion. This may be explained by their fluid and diet habits, eg daytime fluid restriction, and high protein and salt intake.

Desmopressin toxicity due to prolonged half-life in 18 patients with nocturnal enuresis.

PURPOSE: Desmopressin has been used extensively for primary nocturnal enuresis and it is associated with a low incidence of adverse effects. The only reported serious side effect is seizure or altered levels of consciousness resulting from water intoxication, which has been reported for the nasal spray. We describe 18 children with clinical symptoms of water intoxication due to the prolonged bioactivity of desmopressin nasal spray. MATERIALS AND METHODS: We evaluated 18 patients with clinical suspicion of prolonged desmopressin bioactivity during treatment with intranasal desmopressin for primary nocturnal enuresis. The control group consisted of 50 children with primary nocturnal enuresis and proven nocturnal polyuria who were treated with the same desmopressin regimen. RESULTS: All patients had prolonged maximal urinary concentration capacity and delayed restoration of daytime diluting capacity (p <0.01). Of the patients 15 had the characteristic clinical symptoms of water intoxication with vomiting, headache, decreased consciousness and hyponatremia. We suspect that these symptoms are secondary to prolonged desmopressin bioactivity. CONCLUSIONS: Prolonged desmopressin bioactivity may increase the risk of water intoxication.