ABSTRACT:The pathogenesis of idiopathic nephrotic syndrome (INS) remains unknown. Several findings suggest a role for the immune system. This study aimed to evaluate immune mediators in INS by measuring plasma and urinary levels of transforming growth factor ␤ 1 (TGF-␤ 1 ), monocyte chemoattractant protein-1 (MCP-1/ CCL2), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and IL-8 (IL-8/CXCL8) in pediatric patients with INS and in age-matched healthy controls. Patients were divided according to their response to corticosteroids: steroid-sensitive (SS, n ϭ 8), or steroid-resistant (SR, n ϭ 24). Immune mediators were also compared in regard with disease activity (relapse and remission). Immune mediators were measured by ELISA. Plasma TGF-␤ 1 levels in SR patients were approximately 2.8-fold higher than control values (p Ͻ 0.05). Urinary IL-8/CXCL8 was 2.9-fold higher in INS patients in relapse (proteinuria Ͼ100 mg/m 2 /24 h) when compared with patients in remission (p Ͻ 0.05), and levels had a positive correlation with individual proteinuria values (p Ͻ 0.05). Urinary IL-8/CXCL8 was significantly higher in relapsed SR than in SS patients in remission. No changes in MCP-1/CCL2 and RANTES/CCL5 levels were detected. Our findings suggest that IL-8/CXCL8 and TGF-␤ 1 are involved in the pathogenesis of INS: IL-8/CXCL8 associated with local changes in glomerular permeability and TGF-␤ 1 could be related to worse response to corticosteroids. (Pediatr Res 64: 637-642, 2008)

Some children with idiopathic hypercalciuria (IH) develop bone alterations at some stage of the disease. The aims of this study were to evaluate bone mass in 88 children with IH (G1) at the time of diagnosis and to compare the findings with data for a control group of 29 normal children (G2). Kidney and bone metabolism markers were measured in both groups, and bone densitometry was performed. Serum alkaline phosphatase, intact parathyroid hormone, urinary calcium and uric acid were significantly higher in G1, whereas urinary volume and urinary citrate excretion were lower. The following densitometric parameters were significantly lower in G1: (1) lumbar spine (L 2 -L 4 ) bone mineral density (BMD), bone mineral content (BMC), BMC corrected for height and for width of the vertebra, volumetric BMD (BMDvol), and Z score; (2) wholebody BMD; (3) femoral neck BMD. Lumbar spine BMDvol was reduced (osteopenia) in 35% of the patients compared with G2. N telopeptide, a urinary marker of bone resorption, was significantly higher in G1 than in G2, and was negatively correlated with lumbar spine BMD and BMDvol. Children with urinary lithiasis or idiopathic hyperuricosuria associated with IH showed no significant differences in bone metabolism compared with children without these associations. We conclude that (1) there is an altered bone metabolism in IH, with osteopenia already present at diagnosis in 35% of the patients; (2) N telopeptide is one of the most useful markers of bone alterations in IH, especially at an early stage of the disease; (3) investigation of bone metabolism is necessary in IH to prevent future serious consequences such as osteoporosis and bone fractures.Keywords Idiopathic hypercalciuria · Osteopenia N telopeptide · Bone densitometry · Urinary calculi Subjects and methods SubjectsTwo groups were studied: group 1 (G1) consisted of 88 children with IH (50 males, 38 females) aged 2.2-17.8 years (median 9.4 years) who were studied at the time of diagnosis (calciuria

Children with IH and associated HC may have a higher risk of bone mass loss and consequent osteopenia. Further studies are needed to assess the role that hypocitraturia may have in this form of bone disease.