Effect of perinatal risk factors on neutrophil gelatinase-associated lipocalin (NGAL) level in umbilical and peripheral blood in neonates.

INTRODUCTION: Acute kidney injury biomarkers are opening a new era in diagnosing kidney failure. The requirement for a specific and sensitive marker of kidney function is highly desirable in neonates because the diagnostic possibilities in this age group are not sufficient. Recent research show that neutrophil gelatinase-associated lipocalin (NGAL) can have a great potential but there is a wide range of medical conditions, that may influence their expression. THE AIM OF THE STUDY: was to evaluate the impact of perinatal risk factors on NGAL level in neonates. MATERIAL AND METHODS: NGAL was measured in umbilical cord blood and peripheral blood in full term neonates with perinatal risk factors during the first days of life. RESULTS: We found significantly higher umbilical cord blood NGAL levels in neonates with perinatal risk factors (117.69 ng/ml) compared to the control group (64.37 ng/ml). No significant difference in peripheral blood NGAL level was shown between the two groups. Umbilical cord blood NGAL level correlated positively with peripheral blood NGAL level (r = 0.36, p < 0.01). Umbilical cord blood NGAL level was significantly higher in neonates with fetal distress and infection compared to neonates with other perinatal risk factors. Peripheral blood NGAL level was significantly higher in neonates with infection compared to neonates with other perinatal risk factors. Significantly higher umbilical cord blood NGAL levels were seen in neonates born by operative delivery compared to born by natural delivery.

[Abdominal symptoms necessitating surgical intervention as the initial presentation of Henoch-Schönlein purpura in children - case reports]. / Objawy brzuszne wymagajace interwencji chirurgicznej inicjujace zespól Schönleina-Henocha u dzieci - opis przypadków.

Henoch-Schönlein purpura (HSP) is the most common pediatric autoimmune vasculitis. Gastrointestinal symptoms of HSP including abdominal pain, diarrhea, and vomiting may precede skin changes by several days. We present diagnostic challenges in two adolescents with HSP and severe abdominal symptoms necessitating surgical intervention before the development of skin changes. CASE REPORT 1: A 15-year old boy with 7 day history of abdominal pain, and bloody vomiting (1-2 x per day) without diarrhea. A suspicion of acute appendicitis was raised and the boy was operated on the 7th day since the initial symptoms. The appendix showed some reactive inflammation and was removed during laparotomy which also revealed enlarged mesenteric lymph nodes and a modest amount of fluid in the pelvic cavity. During the first day after the surgery, skin changes typical for HSP developed on lower limbs and buttocks. CASE REPORT 2: A 12-year old girl with 7 day history of abdominal pain, without diarrhea or vomiting. On the day of admission hemorrhagic rash appeared on lower limbs. Laparotomy was performed on 14th day after onset of abdominal pain - large amounts of serous, blood-stained fluid, massive dilation of small intestine with ecchymoses in mucous membrane, segmental infiltration and stiffening of intestinal wall were found. Normal appendix was removed. CONCLUSIONS: Severe abdominal symptoms may precede skin changes in children with HSP, resulting in diagnostic and therapeutic challenges. When considering laparotomy in children with an atypical "acute abdomen" presentation, other manifestations of HSP should be sought.

Markers of bone metabolism in children with nephrotic syndrome treated with corticosteroids.

The aim of the study was to assess bone mineral density, bone metabolism markers, and vitamin D level in children with idiopathic nephrotic syndrome in the course of 1-year observation. Twenty five children with nephrotic syndrome aged 5-17 years were enrolled into the study. The median number of relapses was 6 (range 1-22). All patients were treated with prednisone and vitamin D (800 IU/day). Bone mineral density of total body (TB-BMD) and lumbar spine (L-BMD), evaluated by dual energy X-ray absorptiometry (DXA) expressed as Z-score, and serum calcium, phosphorus, parathormone (iPTH), alkaline phosphatase (ALP), bone alkaline phosphatase (BAP), osteocalcin (OC), albumin, creatinine, 25(OH)D3, 1,25(OH)2D3 and urine calcium/creatinine ratio (uCa/Cr) were evaluated at the enrollment visit and after 1 year of therapy. After 1 year significant decreases of TB-BMD Z-score (from -0.24±1.34 to -0.74±1.31, p<0.05) and 25(OH)D3 serum level (from 31.7±16.3 to 23.7±9.3; p<0.05) were observed. No other appreciable differences were found. At the study onset, negative correlations were found between L-BMD Z-score and serum ALP, BAP, and phosphorus and between TB-BMD Z-score and urine uCa/Cr. After 1 year, L-BMD Z-score correlated negatively with serum BAP and OC, and positively with serum 25(OH)D3. Multivariate analysis showed that BAP was the strongest predictor of L-BMD Z-score (beta=-0.49; p<0.05). We conclude that children with nephrotic syndrome treated with corticosteroids are at risk of bone mass loss. Serum BAP concentration seems to be a good indicator of spongy bone metabolism in these children, who should be supplemented with vitamin D in an adjustable dose, possibly higher than 800 IU/24 h to prevent osteopenia.

[Vitamin D status in children with renal diseases]. / Zasoby witaminy D u dzieci chorobami nerek.

AIM: Assessment of vitamin D status in children with selected renal diseases based on serum 25OHD3 level taking into consideration type of kidney disease, vitamin D supplementation and season of the year. MATERIAL AND METHODS: Retrospective analysis of 127 children aged from 0.6 to 17.7 years, median 9.5 [24 with risk status of urolithiasis (RSU), 29 with urolithiasis, 15 with glomerulonephritis, 59 with idiopathic nephrotic syndrome (INS)] was performed. Serum concentrations of 25OHD3, 1,25(OH)2 D3, calcium, and phosphorus were measured. The correlation of 25OHD3 with the type of kidney disease, supplementation of vitamin D, seasons, gender, age, and the dose of glucocorticosteroids (in children with glomerulopathies) were analyzed. RESULTS: In all children serum concentration of 25OHD3 from 4.3 to 72.6 ng/mL (median 21.1 ng/mL). The deficiency or insufficiency of vitamin D were observed in 55 (43.3%) analyzed children with kidney diseases. The deficiency or insufficiency of vitamin D were observed in 49.1% children with RSU and urolithiasis, and in 39.2% with glomerulonephritis and INS: in 36% children supplemented with vitamin D and 54% not supplemented (NS). In winter, 25OHD3 serum concentration was significantly higher in children supplemented with vitamin D compared to not supplemented [median 21.5 ng/mL vs 16.5 ng/mL (p<0.05)]. There were no significant differences in serum concentrations of 25OHD3 , 1,25(OH)2 D3 , calcium, phosphorus and calcium x phophorus product depending on type of kidney disease and gender. The significant negative correlation was found between 25OHD3 and patients' age (r=-0.26 p<0.01) and between calcium (r=0.31, p<0.05) and calcium x phosphorus in children supplemented with vitamin D (r=0.28, p<0.05). CONCLUSIONS: Our results suggest the necessity to develop new strategies in vitamin D supplementation in children with kidney diseases. Futher studies shoud also be performed to evaluate their efficiency.

Continuous veno-venous hemodiafiltration in methotrexate intoxication.

UNLABELLED: Methotrexate is a highly nephro- and hepatotoxic drug used in osteosarcoma treatment protocols, in children and adults. High dose methotrexate therapy may lead to kidney injury and decrease of methotrexate clearance, followed by an increase of its serum concentration. As a result, systemic intoxication may develop. Prophylaxis based on intensive fluid therapy and urine alkalization may not be sufficient to prevent the formation of methotrexate crystals in kidney tubules. THE AIM of the study was to present three cases of methotrexate intoxication treated with continuous veno-venous hemodiafiltration. PATIENTS AND METHODS: Three children aged 9-16 years old with tibial or fibular osteosarcoma were admitted to the Nephrology Department due to severe methotrexate intoxication. All children presented with multiorgan injury, including liver, kidney, gastrointestinal tract and bone marrow impairment. Methotrexate concentration, 24 hours after drug administration, was 660-1238 µmol/L. Although intensive fluid therapy, urine alkalisation and administration of high doses of folinic acid (leucovorin), methotrexate serum concentration remained toxic. Effective reduction of methotrexate concentration (<1.5 µmol/L) was achieved 24-156 hours after CVVHDF initiation. Kidney and liver function recovered completely in all of the patients. CONCLUSION: Continuous veno-venous hemodiafiltration is an effective supportive method in methotrexate elimination in patients with severe intoxication.

Expression, purification and catalytic activity of Lupinus luteus asparagine beta-amidohydrolase and its Escherichia coli homolog.

We describe the expression, purification, and biochemical characterization of two homologous enzymes, with amidohydrolase activities, of plant (Lupinus luteus potassium-independent asparaginase, LlA) and bacterial (Escherichia coli, ybiK/spt/iaaA gene product, EcAIII) origin. Both enzymes were expressed in E. coli cells, with (LlA) or without (EcAIII) a His-tag sequence. The proteins were purified, yielding 6 or 30 mg.L(-1) of culture, respectively. The enzymes are heat-stable up to 60 degrees C and show both isoaspartyl dipeptidase and l-asparaginase activities. Kinetic parameters for both enzymatic reactions have been determined, showing that the isoaspartyl peptidase activity is the dominating one. Despite sequence similarity to aspartylglucosaminidases, no aspartylglucosaminidase activity could be detected. Phylogenetic analysis demonstrated the relationship of these proteins to other asparaginases and aspartylglucosaminidases and suggested their classification as N-terminal nucleophile hydrolases. This is consistent with the observed autocatalytic breakdown of the immature proteins into two subunits, with liberation of an N-terminal threonine as a potential catalytic residue.