Marcelo Ferraz de Oliveira Souto

Bone alterations in children with idiopathic hypercalciuria at the time of diagnosis

Abstract.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 (L2-L4) 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) whole-body 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.

Immune Mediators in Idiopathic Nephrotic Syndrome: Evidence for a Relation Between Interleukin 8 and Proteinuria

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 β1 (TGF-β1), 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 = 8), or steroid-resistant (SR, n = 24). Immune mediators were also compared in regard with disease activity (relapse and remission). Immune mediators were measured by ELISA. Plasma TGF-β1 levels in SR patients were approximately 2.8-fold higher than control values (p < 0.05). Urinary IL-8/CXCL8 was 2.9-fold higher in INS patients in relapse (proteinuria >100 mg/m2/24 h) when compared with patients in remission (p < 0.05), and levels had a positive correlation with individual proteinuria values (p < 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-β1 are involved in the pathogenesis of INS: IL-8/CXCL8 associated with local changes in glomerular permeability and TGF-β1 could be related to worse response to corticosteroids.

Idiopathic hypercalciuria: presentation of 471 cases

OBJETIVO: analisar a historia clinica e evolucao de criancas e adolescentes com HI, ressaltando peculiaridades proprias destes pacientes. METODOS: 471 pacientes portadores de HI tem sido acompanhados em regime ambulatorial, sendo submetidos ao protocolo: Rx de abdome, ultra-sonografia de rins e vias urinarias; ionograma, gasometria e bioquimica de sangue; urina de 24 horas para dosagem de calcio e outros eletrolitos e creatinina; urinalise, urocultura e microscopia de contraste de fase; urina de segunda miccao matinal em jejum para dosagem de calcio e creatinina. RESULTADOS: 56% masculinos e 44% femininos; 56% brancos, 37% nao-brancos e 7% sem relato da cor da pele. Ao diagnostico 6% eram lactentes, 15% pre-escolares, 55% escolares e 24% adolescentes. 47% tinha hematuria associada a dor abdominal, 31% hematuria isolada, 14% dor abdominal isolada, e 8% tinham infeccao urinaria, enurese noturna, dor suprapubica ou uretral ou a sindrome miccional com frequencia/urgencia e incontinencia urinaria. A associacao de hipercalciuria com litiase do trato urinario foi positiva em 56% dos pacientes. Em 18,5% houve associacao com hiperuricosuria e em 8,5% com hipocitraturia. 33% dos pacientes tiveram ma evolucao com recorrencia de nefrolitiase, persistencia de hematuria e dor abdominal. CONCLUSOES: a HI deve ser diagnosticada e tratada criteriosamente com o objetivo de reduzir suas consequencias como hematuria, dor abdominal, formacao de calculos urinarios e as possiveis alteracoes osseas. Sinais e sintomas como urgencia e incontinencia urinarias, dor suprapubica e enurese noturna podem ter como causa a hiperexcrecao renal de calcio.

[Urinary excretion of calcium, uric acid and citrate in healthy children and adolescents].

OBJECTIVE To obtain regional reference values for calcium, uric acid and citrate urinary excretion and establish a correlation between those excretions in 24-hour urine sample and single urine sample for their use in clinical practice. METHODS A hundred and twenty-five healthy children and adolescents were randomly chosen and submitted to the following protocol: clinical examination, biochemical analysis of blood, blood cell count, parathormone, 24-hour urine, fasting urine sample and stool test. RESULTS The maximum value of calcium excretion in 24-hour urine was 3.75 mg/kg; in mg/dl of the glomerular filtration rate, it was 0.10; and for the calcium/creatinine (mg/dl) ratio in the fasting urine sample was 0.25. Positive correlation was observed between calcium excretion in the 24-hour urine and the fasting sample (mg/dl and mg/dl of glomerular filtration rate). The maximum values of uric acid excretion in 24-hour urine were 600, 450, and 320 mg and 13, 15 and 18 mg/kg for adolescents, school and preschool children, respectively; in mg/dl of glomerular filtration rate, in the fasting urine sample, it was 0.47. Positive correlation was observed for the uric acid excretion in 24-hour urine and fasting urine samples. The mean values for the citrate excretion in 24-hour urine were 1.6, 1.1 and 0.5 mmol for adolescents, school and preschool children, respectively; for citrate/creatinine ratio, in the fasting urine sample the mean value was 0.3. CONCLUSIONS The calcium and uric acid excretion in 24-hour urine showed correlation with those in the fasting urine sample, which allows their use for metabolic diagnosis, population studies and follow-up of patients with hypercalciuria and hyperuricosuria without voiding control; the citrate/creatinine ratio in the fasting urine sample can be used for controlling patients with hypocitraturia.