Ipek Akil

Genetic screening in adolescents with steroid-resistant nephrotic syndrome

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

An evaluation of quality of life of mothers of children with enuresis nocturna

The aim of this study was to evaluate the impact of enuresis nocturna on quality of life of the mothers. Mothers who have a child with monosymptomatic nocturnal enuresis (n = 28) and mothers who have a child without any health problems (n = 38) were enrolled in the study. Groups were in balance for background variables (child’s age, gender, and number of siblings; mother’s age, marital status, highest year of education completed, and occupation; presence of health insurance; and type of residence). Short-Form Health Survey (SF-36) Questionnaire, the Beck Depression Inventory (BDI), and Spielberg’s State-Trait Anxiety Inventory (STAI) were applied to all mothers. The mothers of children with enuresis had significantly lower quality-of-life scores in the SF-36 for the bodily pain (p = 0.015) and role emotional (p = 0.014) subscales. We observed significant difference between groups according to BDI; mean score was higher in mothers who have a child with enuresis nocturna (p = 0.017). There was no significant difference between groups according to the STAI. Significant differences according to bodily pain and role emotional subscales of SF-36, and the BDI scores, show that the mothers were negatively affected by having a child with monosymptomatic nocturnal enuresis.

Septic pulmonary emboli presenting with deep venous thrombosis secondary to acute osteomyelitis

Septic pulmonary embolism (SPE), deep vein thrombosis (DVT) and acute osteomyelitis (AOM) form a triad which is rarely seen in children. The association of DVT, SPE and AOM was first reported as a form of dissemine staphylococcal infection by Gorenstein et al . 1 This clinical syndrome is a life threatening disorder which necessitates urgent diagnosis and treatment. 2–4 SPE is manifested in a large number of patients with fever, cough and hemoptysis. The most common radiographic findings of SPE are the presence of multiple nodules of varying size located in the periphery of both lungs. 5 It is a frequent complication of right-sided bacterial endocarditis, septic thrombophlebitis, osteomyelitis, and urinary tract infections in adults, but there has been no comprehensive studies considering the etiological factors in childhood. 1,5–7 In this article, we report a 3-year-old male patient who was diagnosed with SPE which presented along with the clinical findings of DVT on admission.

Assessment of Toll-like receptor-4 gene polymorphism on pyelonephritis and renal scar

The aim of this study was to evaluate the effect of the TLR‐4 gene TLR4 c.896A

Enuresis nocturna and sleep quality

Enuresis nocturna is a common problem. Numerous etiologic factors have been investigated, and various theories have been proposed. The objectives of our study were to establish the differences in the sleep quality of nocturnal enuretic patients from that of healthy voluntary subjects, and the changes after treatment with desmopressin acetate (DDAVP), among primary school children. The study comprised 19 children with primary nocturnal enuresis and 32 healthy children in the control group. Subjective assessment of sleep was determined with the Pittsburgh Sleep Quality Index (PSQI) questionnaire. PSQI scores for each patient and control subject were determined before the study was started and after a month time interval. The sleep quality of the nocturnal enuretic children was poor. We found lower scores after a month’s treatment with DDAVP, and significant differences in two dimensions in the patient group: ‘subjective sleep quality’ and ‘sleep disturbances’. When we asked the patients’ group what caused the sleep disturbance, they replied ‘the fear or the anxiety of bedwetting during sleep’. This anxiety or fear seemed to be a factor that probably affected their sleep quality. So, active treatment (medical or behavioral) should be started as soon as the child is ready to receive it or when the enuretic child wants to be dry when asleep.

Vitamin D receptor gene polymorphism in children with urinary tract infection

It is known that small alterations leading to different vitamin D receptor (VDR) alleles affect resistance or susceptibility to infections. In this study, we examined VDR gene polymorphisms in urinary tract infections (UTI), which are common and an important cause of morbidity in children and subsequently of renal scar formation. We evaluated 92 patients diagnosed with UTI and 105 children without prior history of UTI as a control group. The VDR gene polymorphisms BsmI, FokI, ApaI, and TaqI were evaluated in patients and controls. BsmI polymorphism genotype distribution was similar between groups. There was a significant difference between groups for FokI (p = 0 < 001); for the ff genotype, the risk of UTI was significantly increased (p < 0.01) ,at 3.94 times higher (odds ratio = 3.94; 95% confidence interval 1.71-9.09). ApaI polymorphism was significantly increased in the control group (p < 0.01) and evaluated as a protective factor. Comparing the TaqI genotype between groups, there was no statistically significant difference, but in both Tt and tt genotypes, there was minimal increased risk of UTI. The results of this study suggest that VDR gene polymorphisms can be important for susceptibility to UTI and renal scar formation. Association between VDR polymorphisms and UTI is in accordance with the understanding of how vitamin D modulates the immune response against infections.

Co-existence of chronic renal failure, renal clear cell carcinoma, and Blau syndrome.

Blau syndrome is a rare, multisystem, autosomal-dominant, and granulomatous disorder caused by susceptibility variants in the NOD2 gene. We describe here a 14-year-old girl with Blau syndrome with incidentally diagnosed renal carcinoma. The index case presented with growth retardation and recurrent symmetric arthritis. Her clinical symptoms included bilateral cataract due to recurrent uveitis, camptodactyly, and persistent erythematous rash with ichthyosis. Her two sisters and her mother were affected with combinations of these conditions—symmetric polyarthritis, uveitis, and skin involvement—suggesting an autosomal dominant trait. The index case developed a chronic renal insufficiency, and an abdominal computerized tomography scan revealed a 2.5-cm mass in the left kidney. The histopathological examination showed renal clear cell carcinoma, chronic tubulointerstitial nephritis, and giant cell granulomas in both the tumor and non-neoplastic renal tissue. Granulomatous inflammation was observed in the skin biopsy specimen. The patient was diagnosed with Blau syndrome based on her family history, uveitis, granulomatous inflammation proved by skin biopsy, and polyarthritis. Sequencing of the NOD2 gene showed a heterozygous p.R334Q mutation in all affected family members. To the best of our knowledge, this is the first reported case of a patient with Blau syndrome accompanied by chronic renal failure and renal carcinoma.

Autopsy Findings of a Case with Oxalosis

Oxalosis, deposition of calcium oxalate in tissues, is the final stage of hyperoxaluric syndromes. Being a rare entity, it is often missed, or the diagnosis is delayed, since the definitive diagnosis requires special laboratory tests. Kidneys, the walls of blood vessels, and bones are the major sites for crystal deposition. We report the autopsy findings of a 4-year-old girl who presented with end-stage renal disease in which the clinical presentation was consistent with primary hyperoxaluria Type I. The case is unusual, as there was extensive crystal deposition throughout the body, including in tissues that are rarely involved, such as ovaries, fallopian tubes, uterus, thymus, salivary glands, pancreas, and bladder.

Is Helicobacter pylori related to endothelial dysfunction during childhood

Background: Helicobacter pylori infection has been proposed to have a role in the development of atherosclerosis preceded by endothelial dysfunction. The aim of the present study was to determine if a relationship exists between H. pylori infection in childhood and endothelial dysfunction and level of high‐sensitivity C‐reactive protein (hsCRP).

Hemodiafiltration for vancomycin overdose in a patient with end-stage renal failure.

Abstract. A 17-year-old anuric female patient with end-stage renal failure received a massive overdose of vancomycin and was treated with high-flux hemodiafiltration, as described in this report. The hemodiafiltration procedure with a polysulfone membrane was performed 3 times. The vancomycin concentration was decreased from 101 mg/l to 16.59 mg/l at the end of the procedure. No adverse effects were noted from either vancomycin or hemodiafiltration. Hemodiafiltration with a high-flux polysulfone membrane is a novel and safe treatment modality for vancomycin overdose in pediatric patients.