Sylva Skalova

Bone mineral density and urinary N-acetyl-beta-D-glucosaminidase activity in paediatric patients with idiopathic hypercalciuria.

Background:  Idiopathic hypercalciuria (IH) is defined as hypercalciuria that persists after correction of dietary inbalances and has no detectable causes. Patients with IH have a higher prevalence of osteoporosis. Defective reabsorption of calcium by the renal tubule is considered a likely mechanism of IH. N‐acetyl‐beta‐ d‐glucosaminidase (NAG) is a lysosomal enzyme that is a very sensitive marker of renal tubular impairment.

Urinary N-acetyl-beta-D-glucosaminidase activity in healthy children.

Aim:  The principal aim was to establish paediatric reference data for the urinary N‐acetyl‐β‐D‐glucosaminidase  (U‐NAG)  activity.

Rituximab resistant evans syndrome and autoimmunity in Schimke immuno-osseous dysplasia

Autoimmunity is often observed among individuals with primary immune deficiencies; however, the frequency and role of autoimmunity in Schimke immuno-osseous dysplasia (SIOD) has not been fully assessed. SIOD, which is caused by mutations of SMARCAL1, is a rare autosomal recessive disease with its prominent features being skeletal dysplasia, T cell deficiency, and renal failure. We present a child with severe SIOD who developed rituximab resistant Evans syndrome (ES). Consistent with observations in several other immunodeficiency disorders, a review of SIOD patients showed that approximately a fifth of SIOD patients have some features of autoimmune disease. To our best knowledge this case represents the first patient with SIOD and rituximab resistant ES and the first study of autoimmune disease in SIOD.

Mesalazine-Induced Interstitial Nephritis

5-aminosalicylate compounds (mesalazine, sulfasalazine) are widely used in therapy of inflammatory bowel diseases. Mesalazine-induced interstitial nephritis is a rare complication; however, the morbidity in an affected individual is high. Regular renal screening in patients treated with 5-aminosalicylate compounds is important. A 15-year-old boy with treated idiopathic proctocolitis, consequent mesalazine-induced nephritis, and a favorable response to corticotherapy is presented.

Increased urinary n-acetyl-beta-d-glucosaminidase activity in children with hydronephrosis

OBJECTIVE Hydronephrosis leads to deterioration of renal function. As urinary N-acetyl-beta-D-glucosaminidase (U-NAG) activity is considered a sensitive marker of renal tubular impairment, our aim was to measure U-NAG in children with hydronephrosis and to look for a relationship among selected clinical parameters. MATERIALS AND METHODS We studied 31 children (22 boys and 9 girls, mean age 2.3 +/- 2.5 years) with hydronephrosis grade 1-4 that had U-NAG/creatinine ratio (U-NAG/Cr) measured. RESULTS The U-NAG/Cr was significantly higher in patients with hydronephrosis compared to reference data (p = 0.002). There was no difference in U-NAG/Cr between children with unilateral and bilateral hydronephrosis (p = 0.51). There was no significant difference in U-NAG/Cr between children with grades 1-3 (pooled data) and grade 4, respectively (p = 0.89). There was no correlation between U-NAG/Cr and the grade of hydronephrosis (r = 0.01). CONCLUSIONS U-NAG/Cr is increased in children with hydronephrosis grade 1-4, and there is no relationship with the grade of hydronephrosis. U-NAG is a useful marker of renal tubular dysfunction, however its relationship with the degree of kidney damage in patients with hydronephrosis should be considered as doubtful.

Plasmapheresis-induced clinical improvement in a patient with steroid-resistant nephrotic syndrome due to podocin (NPHS2) gene mutation.

Podocin mutations (NPHS2 gene) are mostly responsible for steroid-resistant nephrotic syndrome (SRNS) of childhood onset. Patients with NPHS2 gene mutations do not respond to corticoids and other immunosuppressive agents; partial remission can be rarely induced by cyclosporin A. We present a boy, where SRNS was diagnosed within first year of life. By the age of 15 years, proteinuria reached 9000 mg/24 h, cholesterolemia 15 mmol/L, albuminemia 19.6 g/L, in spite of combined therapy with cyclosporine A, methylprednisolone, enalapril and losartan. At that time a combined heterozygous form of two NPHS2 gene mutations (p.R138Q and p.V290M) was diagnosed, methylprednisolone was discontinued and patient underwent ten plasmapheresis procedures. This resulted in clinical improvement (proteinuria 3000 mg/24 h, S-cholesterol 6 mmol/L, albumin 30g/L) lasting for three years. In conclusion, plasmapheresis can result in clinical improvement and stabilization of SRNS caused by podocine mutation, before renal replacement therapy is initiated.

Transient hyperphosphatasemia in pediatric renal transplant patients – Is there a need for concern and when?

Kutílek Š, Skálová S, Vethamuthu J, Geier P, Feber J. Transient hyperphosphatasemia in pediatric renal transplant patients – Is there a need for concern and when? 
Pediatr Transplantation 2012: 16: E5–E9.

Níveis séricos de homocisteína em crianças e adolescentes com comprometimento da saúde óssea

INTRODUCTION Association between high serum homocysteine (S-Hcy) levels and low bone mineral density (BMD) and increased fracture risk in postmenopausal women has been documented. Data concerning S-Hcy and bone health in children are scarce. OBJECTIVE Our aim was to evaluate S-Hcy in children and adolescents with impaired bone health and look for correlations with clinical and laboratory data. PATIENTS AND METHODS We assessed S-Hcy levels in 37 children and adolescents (22 boys and 15 girls; mean age 13.9 ± 3.5 years) with prevalent low-energy trauma fractures (mean 3.3 ± 2.3 per patient) and/or low spinal L1-L4 BMD (below -2SD Z-score; DXA Lunar GE). We also evaluated S-ALP, serum CrossLaps, osteocalcin (S-OC), body height, weight, body mass index (BMI) and serum levels of folate and vitamin B12. At the time of assessment, the children were not taking any drugs known to influence bone metabolism. The age-dependent parameters were expressed as Z-scores ± SD. RESULTS S-Hcy Z-score was significantly higher (1.3 ± 1.5; P < 0.0001) and L1-L4 BMD Z-score was significantly lower (-1.7 ± 1.3; P < 0.0001), respectively, in comparison with reference values. S-ALP did not differ from reference values (P = 0.88), while S-CrossLaps and S-osteocalcin were higher (1.2 ± 1.8 and 0.4 ± 0.5; P = 0.0001 and P = 0.001, respectively). S-Hcy was inversely correlated to L1-L4 BMD (r = -0.33; P = 0.05) and S-ALP (r = -0.36; P = 0.04) and not related to number of prevalent fractures (r = 0.01), S-osteocalcin (r = -0.22) or S-CrossLaps (r = 0.003). CONCLUSION These results suggest increased bone turnover and negative influence of elevated S-Hcy on bone formation and BMD in children and adolescents with recurrent fractures.

RENAL VEIN THROMBOSIS WITH PULMONARY EMBOLISM: FIRST MANIFESTATION OF LUPUS NEPHRITIS

1 Shearer MJ. Vitamin K metabolism and nutriture. Blood Rev. 1992; 6: 92–104. 2 Kumar R, Marwaha N, Marwaha RK, Garewal G. Vitamin K deficiency in diarrhoea. Indian J. Pediatr. 2001; 68: 235–8. 3 Motohara K, Matsukura M, Matsuda I et al. Severe vitamin K deficiency in breast-fed infants. J. Pediatr. 1984; 105: 943–5. 4 Kayaalp SO. Tıbbi Farmakoloji. Ankara, Turkey: Hacettepe-Taş Kitabevi, 2000; 232–3. 5 Norrby SR. Side effects of cephalosporins. Drugs 1987; 2: 105.

Parathyroid hormone – reference values and association with other bone metabolism markers in very low birth weight infants – pilot study

Abstract Purpose: The aim of this pilot study was to estimate physiological parathyroid hormone (PTH) levels and their relationship with bone metabolism parameters in otherwise healthy preterm newborns with birth weight 1000–1500 g. Methods: PTH, 25(OH)D, S-Ca, S-P, and ALP were analysed from blood samples obtained from 20 preterm infants once a week up to the 36th gestational week. Results: Of the total 134 examined serum samples for PTH levels, the estimated range was 1.6–9.3 pmol/l (15.1–87.7 pg/ml). No statistically significant correlation of PTH level with that of S-Ca, S-P, or ALP was observed, except for the 56th day of life (p = .03; Rho = 0.76; n = 8). From the second month of life, there was a statistically significant relationship only between PTH and 25(OH)D (Rho = −0.71, p ≤ .0001). In our cohort, vitamin D deficiency (20 ng/ml) occurred in 75% at birth and at 30% in the 36th gestational week. Conclusions: The physiological range indicated by the measurements was close to the reference limits for adults (1–7 pmol/l; 9.4–66 pg/ml). PTH level above this range can be considered as hyperparathyroidism in preterm neonates.