Matrix metalloproteinases in ureteropelvic junction obstruction.

BACKGROUND: Management of ureteropelvic junction obstruction (UPJO) remains controversial. The aim of the present study was to measure the levels of matrix metalloproteinases (MMPs) in UPJO patients who were planned to undergo surgery and thus clarify if MMPs levels could serve as potential biomarkers of surgical obstruction in UPJO. METHODS: Serum samples of infants with UPJO diagnosis were compared to serum samples of healthy age-matched controls. MMP2 and MMP9 were quantified using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 17 infants with UPJO diagnosis, and median age 1.5 months, were prospectively recruited. MMP9 levels were significantly decreased in the serum samples of UPJO infants compared to controls (p =0.037). Also MMP2 values were higher in UPJO infants compared to controls, but the difference was not statistically significant (p =0.206). CONCLUSIONS: This study found decreased concentrations of MMP9 in infants with obstructive hydronephrosis. However, the results should be tested in larger population samples and even be evaluated simultaneously with urine samples in order to delineate the ability of MMPs to serve as obstruction biomarkers. HIPPOKRATIA 2017, 21(3): 136-139.

Novel biomarkers for the assessment of paediatric systemic lupus erythematosus nephritis.

The discovery of serum biomarkers specific for paediatric lupus nephritis (pLN) will facilitate the non-invasive diagnosis, follow-up and more appropriate use of treatment. The aim of this study was to explore the role of serum high-mobility group box 1 (HMGB1) protein, antibodies against nucleosomes (anti-NCS), complement factor C1q (anti-C1q) and glomerular basement membrane (anti-GBM) in pLN. Serum samples of 42 patients with paediatric systemic lupus erythematosus (pSLE) (22 with pLN and 20 without renal involvement), 15 patients with other autoimmune nephritis (AN) and 26 healthy controls (HCs) were examined using enzyme-linked immunosorbent assay (ELISA). The activity of both pSLE and pLN was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) tool. The levels of all four biomarkers were significantly higher in pLN compared to AN and to HCs. The anti-NCS, anti-GBM and HMGB1 serum levels were significantly higher in pLN than in pSLE without renal involvement. The anti-C1q and the HMGB1 serum levels were correlated positively with pSLE activity. The HMGB1 serum levels were also correlated positively with pLN activity. These findings suggest that serum anti-NCS, anti-GBM and HMGB1 may serve as biomarkers specific for the presence of nephritis in pSLE. HMGB1 emerged as a useful biomarker for the assessment of pLN and pSLE activity, whereas anti-C1q only of pSLE activity.

Perilobar nephroblastomatosis: natural history and management.

Nephroblastomatosis (NB) has been considered as a precursor of Wilms tumor (WT). The natural history of NB seems to present significant variation as some lesions may regress spontaneously, while others may grow and expand or relapse and develop into WT later in childhood. Although, most investigators suggest adjutant chemotherapy, the effect and duration of treatment are not well established. Children with diffuse perilobar NB, Beckwith-Wiedemann syndrome, and hemihypertrophy seem to particularly benefit from treatment. We discuss our experience on two cases of NB and we review the literature for the management of this rare condition.

Laboratory investigation of platelet function in patients with thalassaemia.

The aim of this study was to investigate platelet function in patients with thalassaemia and to detect any relation to chelation treatment (deferasirox or deferiprone/deferiprone plus desferioxamine). Thirty-three transfusion-dependent patients with thalassaemia were included. The investigation consisted of aggregation testing of platelet-rich plasma by light transmission aggregometry (LTA) with the use of 5 agonists as well as the global test of haemostasis by means of the PFA-100 platelet function analyser. In 66.67% of the patients, there was reduced LTA to at least one agonist and in 18.18% there was reduced LTA to two or more agonists. The PFA-100 test was prolonged in 60.6% of the cases. An abnormal LTA and a prolonged PFA-100 time were recorded in 33.3% of the patients and 27.4% had a normal aggregation and PFA-100 test. No correlation between chelation regimen and either LTA or PFA-100 test was found. The abnormal LTA can be explained either by the release of ADP from the haemolysed red blood cells, which leads to defective platelet aggregation, or by the presence of two platelet populations. An in vitro effect without an in vivo impact could be an alternative explanation. In patients with thalassaemia, the reduced LTA and the prolonged PFA-100 closure time could be an in vitro effect and has a close correlation to the bleeding phenotype of each patient.

Simultaneous changes in serum HMGB1 and IFN-α levels and in LAIR-1 expression on plasmatoid dendritic cells of patients with juvenile SLE. New therapeutic options?

We investigated the simultaneous changes in serum levels of HMGB1 and IFN-α as well as in LAIR-1 expression on plasmatoid dendritic cells (pDCs) of juvenile systemic lupus erythematosus (jSLE) patients in order to explore their involvement in the disease pathogenesis and their correlation with disease activity and other characteristics. In total, 62 blood samples were studied from 26 jSLE patients (18 girls), aged 8-16 years. Twenty healthy subjects (16 girls) of comparable age were included as healthy controls (HCs). Concentrations of serum HMGB1 and IFN-α were assessed by ELISA and LAIR-1 expression on pDCs by five-color flow cytometry. The disease activity index was assessed by SLEDAI and ECLAM scores. It was found that mean serum levels both of HMGB1 and IFN-α were significantly increased in jSLE patients compared to HCs and in jSLE patients with active disease with or without active nephritis compared to those with inactive disease. Mean serum levels of HMGB1 were positively correlated with levels of IFN-α and both were positively correlated with the SLEDAI and ECLAM scores. The expression of LAIR -1 on pDCs of jSLE patients was significantly lower than that of HCs. In conclusion, our findings indicate that serum HMGB1 not only represents a potential marker of disease activity but together with the lack of LAIR-1 inhibitory function may contribute to the sustained inflammatory action of IFN-α in jSLE. In this regard, blocking the action of HMGB1 and its receptors or enhancing the expression/inhibitory function of LAIR-1 on pDCs should be included in future immune interventions for controlling jSLE.

Nutrition assessment of children with advanced stages of chronic kidney disease-A single center study.

BACKGROUND: Malnutrition is a major problem among children with Chronic Kidney Disease (CKD) and it is essential to be recognized as early as possible. Aim of our study was to assess the nutrition status of children with CKD. METHODS: Nutrition status of 30 children (1-16 years) with CKD stages IIIV and on peritoneal dialysis was evaluated. Malnutrition risk was assessed by Pediatric Digital Scaled MAlnutrition Risk screening Tool (PeDiSMART) score software.Anthropometry was expressed as Z-scores for age and sex. Phase angle (PhA) and body cell mass were assessed by bioelectrical impedance analysis (BIA). Three-day food intake was recorded and analyzed. Biochemical indexes were assessed. RESULTS: Depending on the marker used for assessment 20-40% of our patients were malnourished. Intake/requirements ratio (median) was 86.5% for actual energy intake and 127% for actual protein intake. Multiple regression analysis has shown that the most determinant factor for Mid Upper Arm Circumference (MUAMC) was actual protein intake, Glomerular Filtration Rate (GFR) and age at diagnosis. PhA was mainly affected by GFR and energy intake. Statistically significant inverse correlation was found between PeDiSMART score and PhA (p=0.001), MUAMC (p=0.008) as well as protein intake (p=0.016). CONCLUSIONS: A considerable proportion of children with advanced CKD are undernourished. Regular dietitian evaluation based on novel tools as PeDiSMART score and PhA may identify earlier patients at risk for malnutrition. Hippokratia 2014; 18 (3): 212-216.

Peritonitis due to uncommon gram-positive pathogens in children undergoing peritoneal dialysis.

Peritonitis is still the main complication of peritoneal dialysis (PD) in children. Staphylococcus, especially Staphylococcus epidermidis and Staphylococcus aureus, are the predominant species isolated, followed by Streptococcus spp. and by far by gram-negative bacteria and fungi. We describe three cases of PD-related peritonitis in pediatric patients due to uncommon gram-positive pathogens, which were treated with intraperitoneal antibiotic agents.

Percutaneous ultrasound-guided renal biopsy in children: a single centre experience.

BACKGROUND AND AIM: The contribution of renal biopsy is of major importance in many renal diseases in children. In our study we aimed to evaluate retrospectively the indications, safety, efficacy and the spectrum of histopathological findings of percutaneous ultrasound-guided renal (PRB) biopsy during a 7 year period as well as to analyze specific groups of renal patients. PATIENTS AND METHODS: A total of 84 renal biopsies were performed in 81 children. Demographic data, clinical symptoms at presentation, indications for renal biopsy, laboratory findings, complications of the procedure and histological diagnosis were obtained from all patients who underwent PRB. RESULTS: The commonest indication for biopsy accounted was steroid resistant, steroid dependent or frequent relapsing idiopathic nephrotic syndrome (INS). Subcapsular hematoma presented 11% of the patients, but none of them needed blood transfusion. Adequate renal tissue sample was obtained in 97.7% of the renal biopsies. In 80% the histopathology revealed glomerular diseases. The most frequent types of biopsy-proven renal diseases were: focal segmental glomerulosclerosis (FSGS) (15%), IgA nephropathy (13.5%), minimal change disease (10%), various stages of lupus nephritis (8.5%), Henoch-Schonlein nephritis (7.5%), membranous glomerulonephritis (7.5%), mesangioproliferative glomerulonephritis (6%), post-infectious glomerulonephritis (6%), hemolytic uremic syndrome (5%), tubulointerstitial nephropathies (3.5%), acute tubular necrosis 2.5%. Among the 28 cases of INS, FSGS accounted for 43%. The leading histopathological pattern found in patients with recurrent episodes of gross haematuria was IgAN (84.5%). Among 7 cases of lupus nephritis, the observed histological types were: IV+V in 3/7, IIIA in 3/7 (43%) and IIB in 1/7. CONCLUSIONS: Our study shows that percutaneous ultrasound-guided renal biopsy is a safe, reliable and effective technique in children. It also provides updated information for childhood renal disease pattern.

A "sweet" hydrothorax in a child on peritoneal dialysis.

Peritoneal dialysis (PD) is an established, effective long term renal replacement treatment modality for children with end stage renal disease (ESRD). A rarely reported complication of PD in children is the development of hydrothorax1. We report the case of an 8-year-old boy that developed a right-sided pleural effusion during automated PD (APD), in order to raise awareness amongst paediatricians; we also review the diversity of clinical presentation and the available diagnostic tools, discuss theories regarding aetiology and highlight the available treatment options.

Leiomyomas of spermatic cord and testis presenting as hernia--chromosomal analysis.

We report a rare case of three leiomyomas of the permatic cord and testis in a 73-year-old man. Indirect, large, painful, non-reducible inguinal hernia was diagnosed at admission. During surgery, the hernia was revealed. Furthermore, two tumors were found, both attached on the spermatic cord, and a third tumor close to the testis. All the tumors were carefully removed and no orchidectomy was performed. Hernia repair was performed and the removed tumors were sent to the Pathology Department. All tumors were benign. At the first follow up, chromosomal analysis was also performed. Chromosomal lymphocyte analysis revealed increased fragility at site 4q31. Two years after surgery, the patient was admitted again with a new similar tumor, and underwent a new surgical treatment. In the case of large non-reducible inguinal hernias, surgeons have to consider tumors in the inguinal area in their differential diagnosis.

Cytoprotective activity of amifostine on cultured human lymphocytes exposed to irinotecan.

Irinotecan (camptothecin, CAM) is a topoisomerase-I inhibitor with a well established action in the chemotherapy of colorectal and ovarian cancer. Hematological and intestinal toxicity are commonly noted in patients treated with CAM. In this study, we examined the cytoprotective efficacy of amifostine (ethyol, ETH) against chromosomal damage induced by this drug on cultured peripheral human lymphocytes. Cultured lymphocytes were exposed to CAM (50 and 100 ng/ml of final concentrations) without or with ETH (in concentrations varying between 40 and 800 microg/ml of final culture volume). CAM's genotoxicity was quantified by counting the Sister Chromatid Exchange (SCEs) rate. The mitotic index (MI) and proliferation rate index (PRI) were also assessed. The SCE rate was increased following incubation with CAM, but the combined treatment of CAM with ETH significantly reduced the SCE formation, especially when ETH added at high concentrations. The MIs and PRIs remained also unaltered in cultures with CAM, but MIs were reduced with the combined treatment at high ETH concentrations. Clinical studies are required to assess the predicted benefits from ETH in patients receiving CAM.

Mesangioproliferative glomerulonephritis in an infant with Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a neurobehavioral disorder characterized mainly by neonatal hypotonia, dysmorphic features, hypogonadism, mental retardation and behavioral problems. The PWS has not been associated with renal complications. We report the case of an infant with Prader-Willi syndrome due to loss of the paternal copy of chromosome 15q11.2-13, who presented with severe proteinuria and microscopic hematuria. Renal biopsy revealed mesangioproliferative glomerulonephritis (MPGN). The early onset of the primary MPGN in this infant make us consider a possible association between the deficiency of the paternally expressed genes from the 15q11-q13 region and the renal disease.

Shockwave lithotripsy and endourological management of urinary calculi in children: a single-center 10-year experience.

PURPOSE: Shock wave lithotripsy (SWL) and endourological techniques revolutionized the management of pediatric urolithiasis. We sought to assess the impact of new technology and local practice in the treatment of pediatric urolithiasis during a 10-year period. MATERIALS AND METHODS: Between 1997 and 2006, 125 children (90 boys and 35 girls), aged 18 months to 15 years, were managed in our department for urolithiasis. Stone localization, stone composition, presence of anatomic abnormalities, and treatment modality were evaluated retrospectively. RESULTS: In 102 children, the stone was located in renal pelvis (0.5-45-mm diameter), in eight in the renal pelvis and one in the calyx; three had staghorn calculi; and 12 had ureteral stone (4-12-mm diameter). Ninety-three of 125 children underwent a total of 108 SWL sessions. Stone size ranged from 0.5 to 35 mm. The stone-free rates were 86%, 92%, and 96% after first, second, and third SWL session, respectively. Ureteroscopy was performed in 12/125 children, and 10/12 (83.5%) were rendered stone free. Nine of 125 children underwent percutaneous nephrolithotomy, and four of nine were stone free (44.5%), although five of the nine children (55.5%) required SWL for residual stone fragments. Open surgery was performed as initial procedure in 11 (9%) children. In 9 of 11 children, ureteropelvic junction obstruction was corrected simultaneously. Open surgery was followed by SWL in 3 of 11 patients. Two of three patients with staghorn calculi underwent nephrolithotomy and SWL and one of three with cysteinuria was managed with SWL. CONCLUSIONS: SWL and endourological techniques are safe and effective in managing urolithiasis in pediatric patients. These minimally invasive methods reduced dramatically the cases of open surgery, which should be undertaken mainly in coexisting anatomic abnormalities.

Efficacy of captopril therapy in cystinuria lithiasis. A case report.

We present a 7-year old girl with severe urolithiasis due to cystinouria. Medical treatment after the surgical procedures was initiated with intensive hydration, urine alkalinisation and captopril. We discuss the therapeutic efficacy of captopril in resolving lithiasis as well as in preventing new stone formation.

The characteristics and outcome of primary vesicoureteric reflux diagnosed in the first year of life.

A retrospective trial was performed to study presentation, evaluation, management, complications and outcome of 186 infants with vesicoureteral reflux (VUR). Medical records of 103 male and 83 female infants with mean age at entry 5.97 months were reviewed. Diagnosis was established using radiographic voiding cystourethrogram. At diagnosis, a renal ultrasound and dimercaptosuccinic acid renal scintigraphy were performed in all children. The follow-up included blood pressure measurements, serial urine cultures, haematological and biochemical tests, radionuclide cystography, renal ultrasounds and renal scintigraphy. The majority of infants with reflux, 176/186, presented with one or more episodes of urinary tract infections. In 113 children, reflux resolved spontaneously, 27 underwent surgical or endoscopic correction and 46 are being followed-up to date. Spontaneous resolution after prophylaxis was more frequent in boys (p < 0.0001), in children with grade I or II (p < 0.0001) and unilateral reflux at diagnosis (p = 0.0215). No significant difference could be established with respect to the presence of scars (p = 0.1680) and the number of breakthrough urinary tract infections (p = 0.1078). The data of the present study indicate that spontaneous resolution rate is high in infants, and therefore, early antireflux

Urine biochemical markers of early renal dysfunction are associated with iron overload in beta-thalassaemia.

Renal dysfunction in thalassemia patients can be attributed to chronic anemia, and iron overload as well as to desferioxamine (DFO) toxicity. We analyzed the urine of 91 well-maintained homozygous beta-thalassemia patients, with no evidence of renal disease, for early evidence of kidney dysfunction by means of electrophoresis and quantitative biochemical tests. Measurement of liver magnetic resonance imaging (MRI) T2 values and serum ferritin concentration was used to estimate iron overload. In 55 of the 91 patients, urine analysis indicated signs of tubular dysfunction. The urine concentration of albumin and beta 2-microglobulin, as well as the activity of N-acetyl-beta-D-glucosaminidase (NAG), correlated positively with serum ferritin concentration and liver iron deposition, as detected by MRI T2 values. This suggested that the cause of renal dysfunction in homozygous beta-thalassemia is iron overload. On the other hand, the same urine markers did not correlate with age, indicating that chronic anemia or desferrioxamine (DFO) treatment are not related to renal dysfunction in thalassemia.