Introduction Nephrotic syndrome (NS) relapses are common in children and are diagnosed and treated before the development of oedema, when urine testing shows proteinuria 3+ on >3 consecutive days. However, febrile episodes can also induce proteinuria, 30% of which are transient and require no therapy. Differentiating between them is essential to avoid unnecessary therapy. In a mouse model proven suitable to study human minimal change NS as well as fever, we compare urinary cytokines after experimentally induced NS versus controls with experimentally induced fever.
Material and methods A group (NS) of 10 adult mice had experimentally induced NS with intraperitoneal injection of 5 mg/kg of Doxorubicin. Another group (F) of 10 mice had experimentally induced fever with subcutaneous injection of 10 ml/kg of 20% brewer's yeast suspension. They were kept in a metabolic cage and their temperature measured with a rodent monitoring thermometer with a rectal probe. Fever was defined when rectal temperature exceeded 380°C. 24-h urine was collected from the metabolic cage and analysed for interleukins (IL 2 and IL6) and tumour necrosis factor (TNF) by the colorimetric sandwich enzyme-linked immunosorbent assay technique, at baseline and after induction of fever (after 18 h) or NS (after 5 days).
Results Urinary IL2 levels remained unchanged in group F and increased by an average of 2.16 pg/ml (SE 1.21) in NS. IL 6 levels increased by 7.9 pg/ml (SE 1.9) or twofold (95% CI 1.8, 2.3) in group F and by 0.4 pg/ml (SE 1.4) or 1.09-fold (95% CI 0.9, 1.3) in NS (p<0.001).
TNF levels increased by 183 pg/ml (SE 45) or 3.7-fold (95% CI 0.5 to 7.0) in group F and by 371 pg/ml (SE 85) or 12-fold (95% CI 8.0 to 16.0) in NS (p=0.02).
Conclusion(s) Urinary IL2 increased only in the NS group, with TNF increase significantly higher with NS than the group with fever. IL6 increased significantly more in those with fever. Extending this study to children with NS might enable adequate differentiation between genuine NS relapses and proteinuria associated with a febrile illness.