Fotis Papachristou

Increased urine interleukin-6 concentrations correlate with pyelonephritic changes on 99mTc-dimercaptosuccinic acid scans in neonates with urinary tract infections.

Interleukin (IL)-6 and -8 are important inflammatory cytokines in bacterial infections. Their serum and urine concentrations were measured in 27 neonates with urinary tract infection (UTI) at onset and the second week of therapy, as well as in 23 control neonates. Escherichia coli was isolated in 89% of cases. 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scans were performed between the 10th and 90th days after UTI and showed pyelonephritic changes in 15 neonates (56%). Increased IL-6 and IL-8 concentrations were found in urine but not in serum within the first 24 h after presumptive diagnosis of UTI (P=.036 and.010, respectively), suggesting that the neonatal urinary tract can respond to uropathogens by producing inflammatory cytokines. Urine concentrations of IL-6 correlated with findings of renal changes in 99mTc-DMSA scans (P=.012) and thus may serve as a marker of renal parenchymal outcome. All neonates exhibited undetectable urine cytokine levels during the second week of therapy.

Renal dysfunction in patients with beta-thalassemia major receiving iron chelation therapy either with deferoxamine and deferiprone or with deferasirox.

There are limited studies on renal involvement in β-thalassemia, mainly involving patients on deferoxamine, reporting both glomerular and tubular dysfunction. The aim of the present study was to investigate renal involvement in young thalassemia patients, using both conventional and early markers of renal dysfunction, and to correlate findings to iron chelation therapy. Forty-two patients aged 4–23 years were studied and, for analysis purposes, were divided into two groups based on chelation therapy (group A receiving deferasirox and group B receiving deferoxamine and deferiprone combination therapy). In addition to conventional renal biochemistries, creatinine clearance, estimated glomerular filtration rate, serum cystatin C (Cys C), fractional excretion of sodium, tubular phosphorus reabsorption and urine calcium, protein, β2-microglobulin (β2-MG) and glucose levels were measured. A considerable number of patients demonstrated impaired renal function with elevated Cys C levels (36%), glomerular dysfunction with proteinuria (24%) and tubulopathy with hypercalciuria (35.5%) and elevated excretion of β2-MG (33.5%). Renal involvement seems to be present even in young patients with β-thalassemia, therefore, routine use of early markers of renal dysfunction is recommended. Further studies are needed in order to investigate the role of new chelators in tubular function parameters.

Bilirubin levels predict renal cortical changes in jaundiced neonates with urinary tract infection

BackgroundThis study was undertaken to determine the incidence of urinary tract infection (UTI) and the frequency of anatomical abnormalities in newborns with unexplained jaundice and to find out if there is any correlation between bilirubin level and renal damage.MethodsWe studied 462 full-term neonates for UTI. They were aged 3–25 days, with either high (>10 mg/dL) or prolonged (>10 days) hyperbilirubinemia, with or without manifestations such as fever, vomiting, diarrhea, poor feeding, lethargy, and irritability. Neonates positive for UTI were further investigated with ultrasound, cystourethrography, and acute phase renal scintigraphy with technetium-99m dimercaptosuccinate acid (DMSA).ResultsThirty neonates (6.5%) were found to have UTI. Twenty-eight of them had indirect hyperbilirubinemia and two had direct hyperbilirubinemia, with total bilirubin levels of 11.8–20.1 mg/dL. None of the neonates was found to have jaundice because of other reasons such as infection. Vesicoureteral reflux was found in 5 neonates and one of them was combined with hydronephrosis. Renal scintigraphy with technetium-99m DMSA showed renal cortex changes in 14 (46.7%) of the 30 neonates with UTI. These 14 neonates also had increased levels of bilirubin in comparison to those with normal findings of DMSA.ConclusionsThe incidence of UTI in uncomplicated neonatal jaundice is relatively high. Anatomical abnormalities of the urinary tract are not rare in infected children. Increased bilirubin levels are related to pathological findings in renal scintigraphy.

Fok-I polymorphism of vitamin D receptor gene and the presence of renal dysfunction in patients with β-thalassemia major.

Recent evidence supports the presence of renal dysfunction even among young patients with β-thalassemia major. However, the possible genetic contribution has never been investigated. The aim of this study was to correlate the presence of Fok-I polymorphism of the vitamin D receptor gene with abnormal levels of early markers of renal impairment in children and young adults with thalassemia. Thirty-four patients (19 male and 15 female) with β-thalassemia major on conventional treatment, with a mean decimal age of 14.62 ± 5.47 years (range: 5–22 years), were included in the study. Markers of renal function were determined in serum and in urine and patients were genotyped for Fok-I gene polymorphism. Genotype frequencies were similar to those previously reported for other populations: 47.06% of the patients were homozygous for the F allele, 41.18% were heterozygous, and 11.76% were homozygous for the f allele. A considerable number of patients demonstrated impaired renal function with increased serum cystatin C levels (29.41%), glomerular dysfunction with proteinuria (68%), as well as significant tubulopathy with hypercalciuria (73.08%), and increased levels of urinary β2-microglobulin (29.41%). When patients were stratified according to Fok-I polymorphism, a significantly higher prevalence of abnormally increased serum levels of cystatin C was observed in patients being homozygous for the f allele (75%) compared with those being heterozygous (Ff) or homozygous for the F allele (14.29% and 31.25%, respectively, P = .02). Further studies are needed to confirm these preliminary results and elucidate the possible mechanisms involved.

NPHS2 screening with SURVEYOR in Hellenic children with steroid-resistant nephrotic syndrome

Sirs,The idiopathic nephrotic syndrome is a common clinico-pathological entity characterized by massive proteinuria,hypoalbuminaemia, hyperlipidaemia, oedema, and variousglomerular changes, occurring mainly in children in 15–20% of whom the condition is steroid-resistant. About 85%of patients with steroid-resistant nephrotic syndrome(SRNS) exhibit renal histology of focal segmental glomer-ulosclerosis (FSGS), and the rest exhibit mesangial prolif-erative glomerulonephritis (MsPGN) or other rarerhistological phenotypes [1]. Mutations in the NPHS2 gene,encoding podocin, which is one of the important proteins ofthe slit diaphragm, are a frequent cause of sporadic SRNSin children, occurring in 2.8–28% of the cases [2–4].Mutations in exons 8 and 9 of the WT1 gene have also beenreported (more frequently in girls) with isolated SRNS [5].Other genes that are responsible have been recentlyreported, accounting for rare cases of SRNS.Idiopathic nephrotic syndrome is a frequent glomerulardisease in Cyprus and Greece, where 15–20% of cases aresteroid resistant, in accordance with the literature. In thiswork we studied for the first time in Greece and Cyprus acohort of 24 children (ten boys, 14 girls) with SRNS. Renalhistology, based on 1–3 biopsies, showed changes in FSGSin 21 children and MsPGN in three children. We investi-gated these children at the molecular level by searching formutations in the NPHS2 and WT1 (exons 8 and 9) genes. Indoing so, we used, for the first time to our knowledge,SURVEYOR endonuclease (Transgenomic, UK), an en-zyme that cleaves double-stranded DNA at positions ofheteroduplex mismatches, as a method for identifyingmutations and/or polymorphic variants. For this, genomicsequences, amplified by polymerase chain reaction (PCR)and encompassing the exons, the consensus exon

Antibiotics-Induced Acute Interstitial Nephritis in 6 Children

Introduction: Antibiotics-induced acute interstitial nephritis (AIN) is a rare disorder in children, and the diagnosis is often delayed. However, many commonly prescribed antibiotics seem to be implicated. Patients and Methods: We reviewed the medical records of 6 children, age range from 10 months to 14 years, with biopsy-confirmed antibiotics-induced AIN. Clinical presentation, morphological findings, and outcomes are reported. Results: Symptoms of AIN started 2–4 weeks after antimicrobial therapy with β-lactam antibiotics in 5 children and with gentamicin in 1 child. All patients presented with acute renal failure and fever. The glomerular filtration rate was dramatically reduced in 2 cases and mildly reduced in 4 patients. Two of our patients had supportive treatment, 2 received corticosteroid therapy, and 2 children remained under peritoneal dialysis for 12 and 22 days, respectively. Five patients had a full recovery of their renal function, and 1 child, 2 years later, still presented impairment of the renal function. Conclusion: AIN should be considered in case of acute renal failure in children, mostly when other common causes have been excluded, and there is a history of drug exposure.

B lymphocyte stimulator, interferon-α and HMGB 1 interrelation in childhood onset systemic lupus erythematosus: associations with disease activity and severity

The role of B lymphocyte stimulator (Blys) in Childhood onset Systemic Lupus Erythematosus (cSLE) has not been elucidated.

PReS-FINAL-2299: Novel biomarkers for the assessment of pediatric systemic lupus erythematosus nephritis (preliminary report)

Results The pSLE nephritis patients had significantly higher serum levels of anti-NCS [median: 48.89 (IQR: 31.4880.81) U/ml versus 12.5 (11.5-27.8) U/ml, p < 0.001], anti-C1q [22.75 (12.77-56.4) U/ml versus 12.5 (12.512.5) U/ml, p < 0.001], anti-GBM [3.88 (2.25-6.94) U/ml versus 2.2 (2.2-2.4) U/ml, p = 0.002] and HMGB1 [9.9 (5.7-32.23) ng/ml versus 2.5 (2.5-2.5) ng/ml, p < 0,001], than the patients with nephritis of other causality. Serum anti-GBM levels were significantly higher in the pSLE nephritis patients compared to the pSLE patients without nephritis [3.88 (2.25-6.94) U/ml versus 2.25 (2.2-2.83) U/ml, p = 0.014], while this was not true for the rest of the biomarkers. In the pSLE nephritis patients no correlation was found between serum antiGBM levels and pSLE nephritis disease activity. Serum anti-NCS and anti-C1q levels were positively correlated with the ECLAM score in the pSLE patients as a whole (p = 0.002, rho = 0.492 and p = 0.007, rho = 0.461, respectively). Conclusion In this pure Caucasian Northern Greek pSLE population, high serum anti-GBM levels were found to be associated with the presence of nephritis, but not with the nephritis disease activity. Serum anti-GBM, anti-NCS, anti-C1q and HMGB1 may be used to differentiate patients with pSLE nephritis from patients with nephritis of other causality. Furthermore, serum anti-NCS and anti-C1q may be useful for the estimation of pSLE disease activity.

A Greek multicenter study comparing the clinical and immunologic phenotypes between adult and juvenile- onset lupus

Results At diagnosis the mean (SD) ages were 12.25(0.27) and 33.93(1.32) yrs, whereas the mean follow-up 6.63 (0.59) and 11.6 (0.7) yrs, for jSLE and aSLE respectively. General features, hepatosplenomegaly, lymphadenopathy and haematology abnormalities were more frequent in jSLE patients (p1=0.001, p2=0.025 and p3<0.0001, respectively), whereas photosensitivity was commoner in those with aSLE (p=0.047). The main difference was the higher mean number of organ/system involvement in the jSLE group (p=0.0006). At the end of 5 yrs, the cumulative number of clinical manifestations was similar in both groups. Anti-dsDNAs, anti-cardiolipin, anti-Sm, anti-URNP antibodies and low C3 and C4 were significantly commoner in jSLE (p<0.01).