What has changed in pediatric kidney transplantation in Turkey? Experience of an evolving center.

INTRODUCTION: Reluctance to perform kidney transplantations on children is an ongoing problem in Turkey. Moreover, urological pathologies still constitute the largest portion of the underlying etiologies in chronic renal failure patients. Herein, we retrospective analyzed the data acquired from our pediatric renal transplantation patients and reviewed the registry of dialysis and transplantation data prepared by the Turkish Society of Nephrology. MATERIAL AND METHODS: Forty-six living donor kidney transplantations were performed in children between 2008 and 2012. Seventeen of 46 (37%) transplantations were preemptive. The mean age at operation time was 10.8 ± 5 years. The mean patient weight was 31.3 ± 15.8 kg (range, 9.4 to 66.4 kg). A detailed urologic evaluation was performed for every child with an underlying lower urinary tract disease. One enterocystoplasty and 2 ureterocystoplasties were performed for augmentation of the bladder, simultaneously. RESULTS: One-year death-censored graft survival and patient survival rates were 100% and 97.8%, respectively. The mean serum creatinine level was 0.86 ± 0.32 mg/dL (range, 0.3 to 1.8 mg/dL). None of the patients had vascular complications or acute tubular necrosis. One patient suffered graft-versus-host disease during the second month after renal transplantation and died with a functioning graft. In one patient with massive proteinuria detected after transplantation, recurrence of primary disease (focal segmental glomerulosclerosis) was considered and the patient was treated successfully with plasmapheresis. One child had an acute cellular rejection and was administered pulse steroid treatment. CONCLUSION: Although challenging, all patients in all pediatric age groups can successfully be operated and managed. With careful surgical technique, close postoperative follow-up, and efforts by the experienced and respectful surgical teams in this country, we could change the negative trends toward perform kidney transplantation in the Turkish pediatric population.

Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11).

BACKGROUND: Nephronophthisis (NPHP), a rare recessive cystic kidney disease, is the most frequent genetic cause of chronic renal failure in children and young adults. Mutations in nine genes (NPHP1-9) have been identified. NPHP can be associated with retinal degeneration (Senior-Løken syndrome), brainstem and cerebellar anomalies (Joubert syndrome), or liver fibrosis. METHODS: To identify a causative gene for the subset of patients with associated liver fibrosis, the authors performed a genome wide linkage search in a consanguineous family with three affected patients using 50K SNP microarrays and homozygosity mapping. RESULTS: The authors obtained a significant maximum parametric LOD (logarithm of odds) score of Z(max) = 3.72 on chromosome 8q22 and identified a homozygous missense mutation in the gene MKS3/TMEM67. When examining a worldwide cohort of 62 independent patients with NPHP and associated liver fibrosis we identified altogether four novel mutations (p.W290L, p.C615R, p.G821S, and p.G821R) in five of them. Mutations of MKS3/TMEM67, found recently in Meckel-Gruber syndrome (MKS) type 3 and Joubert syndrome (JBTS) type 6, are predominantly truncating mutations. In contrast, the mutations detected here in patients with NPHP and associated liver fibrosis are exclusively missense mutations. This suggests that they may represent hypomorphic alleles, leading to a milder phenotype compared with the more severe MKS or JBTS phenotype. Additionally, mutation analysis for MKS3/TMEM67 in 120 patients with JBTS yielded seven different (four novel) mutations in five patients, four of whom also presented with congenital liver fibrosis. CONCLUSIONS: Hypomorphic MKS3/TMEM67 mutations cause NPHP with liver fibrosis (NPHP11). This is the first report of MKS3 mutations in patients with no vermian agenesis and without neurological signs. Thus NPHP, JBTS, and MKS represent allelic disorders.

Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss.

Autosomal recessive distal renal tubular acidosis (rdRTA) is characterised by severe hyperchloraemic metabolic acidosis in childhood, hypokalaemia, decreased urinary calcium solubility, and impaired bone physiology and growth. Two types of rdRTA have been differentiated by the presence or absence of sensorineural hearing loss, but appear otherwise clinically similar. Recently, we identified mutations in genes encoding two different subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA. Defects in the B1 subunit gene ATP6V1B1, and the a4 subunit gene ATP6V0A4, cause rdRTA with deafness and with preserved hearing, respectively. We have investigated 26 new rdRTA kindreds, of which 23 are consanguineous. Linkage analysis of seven novel SNPs and five polymorphic markers in, and tightly linked to, ATP6V1B1 and ATP6V0A4 suggested that four families do not link to either locus, providing strong evidence for additional genetic heterogeneity. In ATP6V1B1, one novel and five previously reported mutations were found in 10 kindreds. In 12 ATP6V0A4 kindreds, seven of 10 mutations were novel. A further nine novel ATP6V0A4 mutations were found in "sporadic" cases. The previously reported association between ATP6V1B1 defects and severe hearing loss in childhood was maintained. However, several patients with ATP6V0A4 mutations have developed hearing loss, usually in young adulthood. We show here that ATP6V0A4 is expressed within the human inner ear. These findings provide further evidence for genetic heterogeneity in rdRTA, extend the spectrum of disease causing mutations in ATP6V1B1 and ATP6V0A4, and show ATP6V0A4 expression within the cochlea for the first time.

Arterial changes in paediatric haemodialysis patients undergoing renal transplantation.

BACKGROUND: The relationship between primary renal disease and arterial wall changes in paediatric haemodialysis patients has been little studied. The aim of the present work was to determine the influence of primary renal disease on arterial wall pathology in uraemic paediatric patients. METHODS: Twelve paediatric haemodialysis patients (seven girls, five boys) aged 11-17 years were included in the study. The primary renal diseases were urinary malformations in six patients (uropathy group) and acquired glomerular diseases (glomerulopathy group) in six patients. Age, sex distribution, duration of chronic renal failure, duration of haemodialysis, blood pressure, serum glucose, triglycerides, cholesterol, fibrinogen, calcium, phosphorus and parathyroid hormone levels were compared. Internal iliac artery samples were obtained at the time of related-donor renal transplantation. Artery samples were fixed in formaldehyde and sections were stained separately with haematoxylin and eosin, Orcein, Verhoef-van Gieson, and Masson trichrome. RESULTS: Five arteries had fibrous or fibroelastic intimal thickening, medial mucoid ground substance and disruption of the internal elastic lamella. Two of these had microcalcification in the intimal layer; another two demonstrated atheromatous plaques; the remaining five were normal. These pathological changes were found in the arteries of all six patients with uropathy, whereas of the six patients with glomerulopathy only one had arterial changes (P<0.001). The duration of chronic renal failure was 4.8+/-1.9 years in the uropathy group and 2.2+/-1.2 in the glomerulopathy group (P<0.05). The two groups were comparable in terms of serum glucose, triglycerides, cholesterol, fibrinogen, calcium, and parathyroid hormone levels, presence of hypertension, sex distribution, and duration of haemodialysis. Plasma phosphorus and the calcium x phosphate product were higher in the uropathy group than in the glomerulopathy group (P<0.05). CONCLUSIONS: This study demonstrated that pathological changes are common in the arteries of uraemic paediatric patients, and that calcification and atherosclerosis are integral to this disease process. In our study, these alterations were more common in the patients with uropathy. We speculate that the patients with uropathy are more prone to these alterations due to slower progression and a longer duration of renal insufficiency.

Lupus nephritis in children: prognostic significance of clinicopathological findings.

BACKGROUND: We aimed to review our experience with childhood lupus nephritis (LN) in respect to the analysis of the clinical and histopathological presentation of LN and prognostic factors affecting the kidney and patient outcomes. METHOD: Forty-three children (39 girls, 4 boys) with biopsy-proven LN were included in the study. The mean age of the children was 12.0 +/- 2.8 years. Based on the renal histopathology and clinical presentation, patients were treated with oral prednisone, intravenous pulses of methylprednisolone or intravenous cyclophosphamide. The final clinical status was classified as follows: (1) renal and extrarenal remission; (2) clinically active renal disease, or (3) adverse outcome, i.e., end-stage renal failure (ESRF) or death. RESULTS: The mean duration of follow-up was 7.2 +/- 2.8 years (1 month to 14.2 years). All 43 children had hematuria and 53.5% had proteinuria at admission. Fourteen children were in nephrotic status at the onset of disease. Class IV (diffuse proliferative) nephritis was observed in 29 patients as the most frequent histopathology (67.4%). The patients with class IV nephritis had a tendency to develop nephrotic syndrome, heavy proteinuria, increased Cr levels and persistent hypertension at initial evaluation. Thirty-two of 43 children (74.4%) were in renal remission at the last visit. Five-year kidney and patient survival rates from the time of diagnosis to the endpoints of ESRF or death were 83.7 and 90.7% respectively in the whole group while it was 75.9 and 86.2% respectively in the class IV group. Adverse outcome was significantly associated with the persistent hypertension, anemia, high serum Cr level, heavy proteinuria, nephrotic syndrome and class IV nephritis at presentation. CONCLUSION: We can conclude that the prognosis of LN in children is primarily dependent on the histopathological lesions. Severity of the clinical renal disease at admission and presence of persistent hypertension are the main poor prognostic factors rather than age, gender, low C3 and C4 levels, ANA positivity and the treatment modalities in Turkish children.

Circumcision for the prevention of significant bacteriuria in boys.

The aim of this study was to determine whether circumcision affects significant bacteriuria in boys. During a 60-month prospective study, 100 boys with microbiologically confirmed symptomatic urinary tract infection (UTI) were evaluated. Twelve patients with abnormal ultrasonography findings were excluded from the study. Eighteen of the boys had not been circumcised due to parental choice. The remaining 70 boys with normal renal ultrasonography were randomly allocated into two groups. In the first group 35 boys ranging in age from 6 months to 10 years (mean 33.2+/-30.9 months) were observed for 6 months and urinary cultures were taken monthly. When they had a positive urine culture (with or without any symptoms), they received antibiotic treatment. After 6 months they were circumcised and then observed for another 6-month period. Group 2 comprised 35 boys aged from 3 months to 9 years (mean 29.1+/-36.7 months). They were circumcised immediately after the first UTI and were followed for 6 months. Urine samples were obtained by the bag technique in infants and by the mid-stream technique in older patients. In the uncircumcised group, the rate of significant bacteriuria per patient did not change in two 6-month follow-up periods (3.46+/-0.91 and 3.33+/-0.97 episodes). In group 1, the rate of positive urine cultures dropped from 3.57+/-1.11 to 0.14+/-0.35 episodes after circumcision (P<0.001). In the second group, the rate of significant bacteriuria was 0.17+/-0.38 episodes after circumcision. Among the uncircumcised patients, symptomatic UTI was observed in 6 cases (3 cases in the first period of group 1, 1 case in the first and 2 cases in the second period of the uncircumcised group), whereas after circumcision no patient had symptomatic UTI. The mean age at circumcision was 42.7+/-28.4 months. No complication due to circumcision occurred in any patient. UTI may also occur in boys after the 1st year of life. The present study indicated that circumcision in boys decreases the rate of positive urine cultures. Therefore circumcision could be considered as a part of UTI therapy.

Frequency of renal malformations in Turner syndrome: analysis of 82 Turkish children.

We evaluated the frequency of renal malformations in relation to nonmosaic 45,X (group A, 45 patients, 54.9%) and mosaic/structural abnormalities of X (group B, 37 patients, 45.1%) in 82 Turkish patients with Turner syndrome (TS). Ultrasonography of the kidneys and collecting system was performed in all patients. Of the 82 patients, 31 had different renal malformations (37.8%). Horse-shoe kidney was observed in 9 (29.0%) of the 31 patients, and 17 patients (54.8%) had various collecting system malformations, while 5 (16.2%) had malrotation and other positional abnormalities. The prevalence of renal malformations was significantly higher in group A (51.1%) than group B (21.6%) (2:7.94, P<0.05). Although 8 of the 9 patients with horse-shoe kidney had the 45,X karyotype, collecting system malformations were observed more frequently in group B. Recurrent urinary tract infections (UTIs) were detected during follow-up in 7 patients, and hypertension developed in 3 patients. In patients who had a normal baseline nephrological evaluation, no problem suggesting renal disease developed during follow-up. We conclude that all forms of TS should have routine nephrological screening on diagnosis, since structural malformations of the kidney occur more frequently in nonmosaic 45,X TS, while collecting system malformations are mostly seen in mosaic/structural X forms. Those included in the group for nephrological follow-up had an increased risk for hypertension and/or UTI.

Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing.

The multi-subunit H+-ATPase pump is present at particularly high density on the apical (luminal) surface of -intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification. The complete subunit composition of the apical ATPase, however, has not been fully agreed upon. Functional failure of -intercalated cells results in a group of disorders, the distal renal tubular acidoses (dRTA), whose features include metabolic acidosis accompanied by disturbances of potassium balance, urinary calcium solubility, bone physiology and growth. Mutations in the gene encoding the B-subunit of the apical pump (ATP6B1) cause dRTA accompanied by deafness. We previously localized a gene for dRTA with preserved hearing to 7q33-34 (ref. 4). We report here the identification of this gene, ATP6N1B, which encodes an 840 amino acid novel kidney-specific isoform of ATP6N1A, the 116-kD non-catalytic accessory subunit of the proton pump. Northern-blot analysis demonstrated ATP6N1B expression in kidney but not other main organs. Immunofluorescence studies in human kidney cortex revealed that ATP6N1B localizes almost exclusively to the apical surface of -intercalated cells. We screened nine dRTA kindreds with normal audiometry that linked to the ATP6N1B locus, and identified different homozygous mutations in ATP6N1B in eight. These include nonsense, deletion and splice-site changes, all of which will truncate the protein. Our findings identify a new kidney-specific proton pump 116-kD accessory subunit that is highly expressed in proton-secreting cells in the distal nephron, and illustrate its essential role in normal vectorial acid transport into the urine by the kidney.

Hemostatic problems and thromboembolic complications in nephrotic children.

A hypercoagulable state and the risk of thromboembolism in both arterial and venous circulation is a relatively frequent and serious feature of nephrotic syndrome (NS) in children and adults. The aim of this study was to evaluate the coagulation states of children with NS before and after corticosteroid (CS) therapy and to compare the results with a healthy control group. The first group consisted of 49 nephrotic children (30 boys and 19 girls) with a mean age of 6. 5+/-4.9 years (range 1-16 years). The control group included 17 healthy children (9 boys and 8 girls). At the time of admission, all patients were evaluated for the presence of clinical thromboembolism, hematological and biochemical indicators of a hypercoagulative state, and renal disease. This was repeated after CS treatment. Deep vein thrombosis was observed in 2 nephrotic patients who had very low plasma antithrombin III (AT III) levels and fibrinogen levels above 750 mg/dl. Thus, the prevalence of thromboembolism was 4% in our pediatric nephrotic population. The mean AT III level of the study group was 68.2+/-23.4% at the onset of the disease, which was significantly lower than the level of the control group (84.0+/-7. 6%). Plasma AT III levels increased to 74.4+/-15.3% after CS treatment, which correlated with the serum albumin levels. However, there was no correlation with urinary protein excretion. Protein C levels were higher than controls during all stages of the disease in both steroid-responsive and -unresponsive patients. The mean protein S level was similar in both groups. Plasma fibrinogen and cholesterol levels were significantly higher in the study group but decreased to within normal limits with remission. Our study suggests that thromboembolic complications are not infrequent in children with NS, and may be related to low plasma AT III and albumin and high fibrinogen and cholesterol levels.

Localization of a gene for autosomal recessive distal renal tubular acidosis with normal hearing (rdRTA2) to 7q33-34.

Failure of distal nephrons to excrete excess acid results in the "distal renal tubular acidoses" (dRTA). Early childhood features of autosomal recessive dRTA include severe metabolic acidosis with inappropriately alkaline urine, poor growth, rickets, and renal calcification. Progressive bilateral sensorineural hearing loss (SNHL) is evident in approximately one-third of patients. We have recently identified mutations in ATP6B1, encoding the B-subunit of the collecting-duct apical proton pump, as a cause of recessive dRTA with SNHL. We now report the results of genetic analysis of 13 kindreds with recessive dRTA and normal hearing. Analysis of linkage and molecular examination of ATP6B1 indicated that mutation in ATP6B1 rarely, if ever, accounts for this phenotype, prompting a genomewide linkage search for loci underlying this trait. The results strongly supported linkage with locus heterogeneity to a segment of 7q33-34, yielding a maximum multipoint LOD score of 8.84 with 68% of kindreds linked. The LOD-3 support interval defines a 14-cM region flanked by D7S500 and D7S688. That 4 of these 13 kindreds do not support linkage to rdRTA2 and ATP6B1 implies the existence of at least one additional dRTA locus. These findings establish that genes causing recessive dRTA with normal and impaired hearing are different, and they identify, at 7q33-34, a new locus, rdRTA2, for recessive dRTA with normal hearing.

Endovascular treatment of arteriovenous fistulas complicating percutaneous renal biopsy in three paediatric cases.

DESIGN: We evaluated the incidence and history of arteriovenous fistula (AVF) after kidney biopsy and assessed the use of superselective embolization for treatment. OBSERVATIONS: During the last 10 years, 896 kidney biopsies (age range of the patients: 1 month-18.6 years) have been performed in our institution under real-time ultrasonographic guidance with a 14 gauge cutting biopsy needle, and 32 of the patients had renal allografts (3.4%). We observed three cases of AVF (two in allograft kidneys, one in a native kidney) among all biopsies (0.34%), and the incidence of developing AVF after renal allograft biopsy was 6.3%. All three patients with AVF were symptomatic, and intravascular therapy was indicated. INTERVENTIONS: An angiographic study combined with endovascular treatment of the intrarenal AVF and pseudoaneurysm was performed in all three patients. Embolization was performed with bucrylate and lipiodol in two patients and with micro-coils in one. After successful embolization, all three patients became asymptomatic (in two renal bleeding stopped, in one patient with severe uncontrollable hypertension blood pressure returned to normal limits). No complications were observed secondary to the embolization procedure. CONCLUSION: The technique of superselective embolization using a coaxial catheter is an effective and safe method in the treatment of post-biopsy AVFs and pseudoaneurysm.

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness.

H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease.

Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis.

Primary distal renal tubular acidosis (dRTA) is characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Kindreds showing either autosomal dominant or recessive transmission are described. Mutations in the chloride-bicarbonate exchanger AE1 have recently been reported in four autosomal dominant dRTA kindreds, three of these altering codon Arg589. We have screened 26 kindreds with primary dRTA for mutations in AE1. Inheritance was autosomal recessive in seventeen kindreds, autosomal dominant in one, and uncertain due to unknown parental phenotype or sporadic disease in eight kindreds. No mutations in AE1 were detected in any of the autosomal recessive kindreds, and analysis of linkage showed no evidence of linkage of recessive dRTA to AE1. In contrast, heterozygous mutations in AE1 were identified in the one known dominant dRTA kindred, in one sporadic case, and one kindred with two affected brothers. In the dominant kindred, the mutation Arg-589/Ser cosegregated with dRTA in the extended pedigree. An Arg-589/His mutation in the sporadic case proved to be a de novo mutation. In the third kindred, affected brothers both have an intragenic 13-bp duplication resulting in deletion of the last 11 amino acids of AE1. These mutations were not detected in 80 alleles from unrelated normal individuals. These findings underscore the key role of Arg-589 and the C terminus in normal AE1 function, and indicate that while mutations in AE1 cause autosomal dominant dRTA, defects in this gene are not responsible for recessive disease.

Coexistence of VATER association and recurrent urolithiasis: a case report.

VATER association is diagnosed by the combined presence of at least three of the following features: vertebral anomalies, anal atresia, tracheo-esophageal fistula and/or esophageal atresia, radial ray anomalies, and renal anomalies (53%). Urolithiasis has not been reported in this syndrome. A 4-month old girl presented because of irritability, and the presence of stones in the diapers. Physical examination revealed anal atresia for which colostomy was performed in the newborn period. The diagnosis of VATER association was established by the additional findings of hemivertebrae, sacral dysgenesis, and horseshoe kidney which was partly non-functional. Urinary pH was repeatedly below 6. An excreted stone consisted of pure uric acid. Metabolic investigations detected no specific pathology in purine metabolism. Urolithiasis did not recur after reconstructive anal and anorecto-vaginoplasty, implying that it was a consequence of colostomy and/or of the underlying renal anomaly. We suggest that after colostomy patients with VATER association should be followed for possible urate stones, e.g. by regular screening of urinary pH.

Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III.

Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination of this gene reveals loss-of-function mutations that impair renal chloride reabsorption in the thick ascending limb of Henle's loop. Mutations in seventeen kindreds have been identified, and they include large deletions and nonsense and missense mutations. Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA. Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper- or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent. These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents.

T-lymphocyte populations, cytokines and other growth factors in serum and urine of children with idiopathic nephrotic syndrome.

The T-cell defect present in the idiopathic nephrotic syndrome (INS) was investigated in 29 steroid-sensitive and 14 steroid-resistant children aged 2-19 years. Nine different lymphocyte subpopulations and 15 cytokines, receptors and other growth factors were measured in blood, and some also in urine. In steroid-sensitive patients we found a decreased ratio of helper/inducer cells (CD4+) versus suppressor/cytotoxic cells (CD8+) in relapse and remission, and an increased proportion of natural killer cells (CD16+) during relapse vs long-term remission, as a sign of an elevated cytotoxic potential. Among the serum cytokines mainly produced by monocytes/macrophages interleukin (IL)-8 levels were decreased in steroid-sensitive patients vs controls, with normal levels observed for IL-1 alpha, IL-1 beta, IL-1RA and tumor necrosis factor (TNF-alpha). IL-2 was the only cytokine produced by TH1 cells which was significantly increased during relapse vs long-term remission. We also observed a trend for elevated levels of sIL-2R and IFN-gamma. Serum levels of cytokines derived from TH2 cells were variable. IL-4 was decreased during relapse but increased in patients with long-term remission. SIL-6 receptors were increased during relapse. Finally we observed decreased serum levels of IL-3 and of the adhesion molecule ICAM-1 in active INS. Patients with steroid-resistant INS exhibited similar changes of T-cell populations and cytokines as steroid-sensitive patients; their CD4+/CD8+ ratio was reduced to the same degree and sIL-2R levels were even higher than in steroid-sensitive patients. In conclusion this study indicates that active INS is associated with an increased number of cytotoxic cells in the blood and an elevated TH1 cytokine production. Long-term remission appears to be related to increased TH2 cytokine production downregulating TH1 cytokines and cytotoxic cells. Our data give evidence that different immune mechanisms are involved in the pathogenesis of INS.

Haemoperfusion in Amanita phalloides poisoning.

Amanita phalloides is responsible for about 90 per cent of all fatal cases of mushroom intoxication. The amatoxins, the main toxic component of these fungi, are responsible for gastro-intestinal symptoms as well as hepatic and renal failure. Three brothers with Amanita phalloides poisoning were admitted with gastro-intestinal symptoms beginning 12 h after ingestion. Jaundice, hepatomegaly and neurological symptoms were not present, but liver enzymes were moderately increased. Alfa-amanitin was detected in sera of all patients. All patients underwent charcoal hemoperfusion and two of them had additional hemodialysis along with conservative therapy. Liver enzymes that showed a marked increase on the second day of therapy decreased to normal levels on the 28th day. All of our patients survived. This life saving role of early haemoperfusion in Amanita phalloides poisoning is emphasized.

Causes of increased renal medullary echogenicity in Turkish children.

The primary disorders of 50 children with increased renal medullary echogenicity on renal ultrasound were studied; 28 girls and 22 boys aged from 1 month to 16 years were classified into four groups based on underlying disease and ultrasound findings. Group 1 was composed of 17 patients with distal renal tubular acidosis (34%); intense echoes throughout the pyramid were predominant. Group 2 consisted of 14 patients with vitamin D toxicity (28%) and an intense echogenic rim around the pyramids. Group 3 included 10 patients with different types of tubulopathies. A slight hyperechogenic rim around the sides and tip of the medullary pyramids was detected. Group 4 was made up of 9 patients with rare underlying conditions. Abdominal X-rays detected medullary calcinosis in only 12 (24%) of the total 50 patients. Ultrasonography appears to be an important tool in the early diagnosis of increased renal medullary echogenicity and medullary nephrocalcinosis.

Etiology of chronic renal failure in Turkish children.

The etiology of chronic renal failure (CRF) was studied in 459 Turkish children (205 girls, 254 boys) for the period January 1979-December 1993. Their mean age at onset of CRF was 9.5 +/- 4.2 years (range 1-16 years); CRF was defined as a glomerular filtration rate (GFR) below 50 ml/min per 1.73 m2 for at least 6 months. When a GFR determination was not available, the serum creatinine concentration was used: greater than 1 mg/dl for children aged 1-3 years, greater than 1.5 mg/dl for those 3-10 years and greater than 2 mg/dl for those 10-16 years. Primary renal disorders were as follows: reflux nephropathy 32.4% glomerular diseases 22.2%, hereditary renal disorders 11.4%, amyloidosis 10.6%, urinary stones 8% and other renal disorders 15.4%. Twenty-three cases of reflux nephropathy (15.4%) were associated with neural tube defects (NTD) and 20 (13.4%) were caused by infravesical obstruction. CRF caused vesicoureteral reflux associated with NTD and amyloidosis are more frequent in our series compared with west European and Nordic countries.