Hereditary spherocytosis with immunoglobulin A nephropathy.

Hereditary spherocytosis is a familial hemolytic anemia. Immunoglobulin A (IgA) nephropathy associated with hereditary spherocytosis has not been reported in children. Here, we report a case of a 17-year-old boy with IgA nephropathy and hereditary spherocytosis. The patient was diagnosed with hereditary spherocytosis at the age of 12 years and splenectomy was done at the age of 15 years. Later, the patient presented with macroscopic hematuria and proteinuria. Kidney biopsy of the boy was consistent with IgA nephropathy. Treatment with angiotensin-converting enzyme inhibitor was started. The patient became free of proteinuria after the 6th month of therapy.

The co-existence of membranoproliferative glomerulonephritis type 1 and coeliac disease: a case report.

Coeliac disease is an autoimmune enteropathy characterised by chronic inflammation of the small intestinal mucosa and the presence of typical autoantibodies. Coeliac disease may be a risk factor for renal disease. Immunoglobulin A (IgA) nephropathy is reported in the majority of these cases. Only one adult patient had been reported with membranoproliferative glomerulonephritis (MPGN) and coeliac disease. Here, we report a case in a 12-year-old girl with coeliac disease who presented with severe anaemia and later developed nephrotic syndrome. Renal biopsy of the patient was consistent with MPGN type 1, which has not been previously reported in children with coeliac disease. A gluten-free diet was started. After 6 months of this diet, her nephrotic syndrome resolved completely. This case is presented to draw attention to the rare association of coeliac disease and MPGN type 1.

The protective effect of oxytocin on renal ischemia/reperfusion injury in rats.

AIM: Oxytocin was previously shown to have anti-inflammatory effects in different inflammation models. The major objective of the present study was to evaluate the protective role of oxytocin (OT) in protecting the kidney against ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Male Wistar albino rats (250-300 g) were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. OT (1 mg/kg, ip) or vehicle was administered 15 min prior to ischemia and was repeated immediately before the reperfusion period. At the end of the reperfusion period, rats were decapitated and kidney samples were taken for histological examination or determination of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Creatinine and urea concentrations in blood were measured for the evaluation of renal function, while TNF-alpha and lactate dehydrogenase (LDH) levels were determined to evaluate generalized tissue damage. Formation of reactive oxygen species in renal tissue samples was monitored by chemiluminescence technique using luminol and lucigenin probes. RESULTS: The results revealed that I/R injury increased (p<0.01-0.001) serum urea, creatinine, TNF-alpha and LDH levels, as well as MDA, MPO and reactive oxygen radical levels in the renal tissue, while decreasing renal GSH content. However, alterations in these biochemical and histopathological indices due to I/R injury were attenuated by OT treatment (p<0.05-0.001). CONCLUSIONS: Since OT administration improved renal function and microscopic damage, along with the alleviation of oxidant tissue responses, it appears that oxytocin protects renal tissue against I/R-induced oxidative damage.

Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism.

BACKGROUND: Urinary tract infection (UTI) may cause inflammation of the renal parenchyma and may lead to impairment in renal function and scar formation. Oxidant injury and reactive oxygen species (ROS) have been found responsible in the pathogenesis of UTI. The neurohypophyseal hormone oxytocin (OT) facilitates wound healing and is involved in the modulation of immune and inflammatory processes. We investigated the possible therapeutic effects of OT against Escherichia coli induced pyelonephritis in rats both in the acute and chronic setting. METHODS: Twenty-four Wistar rats were injected 0.1 ml solution containing E. coli ATCC 25922 10(10) colony forming units/ml into left renal medullae. Six rats were designed as sham group and were given 0.1 ml 0.9% NaCl. Pyelonephritic rats were treated with either saline or OT immediately after surgery and at daily intervals. Half of the pyelonephritic rats were decapitated at the 24th hour of E. coli infection, and the rest were followed for 7 days. Renal function tests (urea, creatinine), systemic inflammation markers [lactate dehydrogenase (LDH) and tumor necrosis factor alpha (TNF-alpha)] and renal tissue malondialdehyde (MDA) as an end product of lipid peroxidation, glutathione (GSH) as an antioxidant parameter and myeloperoxidase (MPO) as an indirect index of neutrophil infiltration were studied. RESULTS: Blood urea, creatinine, and TNF-alpha levels were increased, renal tissue MDA and MPO levels were elevated and GSH levels were decreased in both of the pyelonephritic (acute and chronic) rats. All of these parameters and elevation of LDH at the late phase were all reversed to normal levels by OT treatment. CONCLUSION: OT alleviates oxidant renal injury in pyelonephritic rats by its anti-oxidant actions and by preventing free radical damaging cascades that involves excessive infiltration of neutrophils.

Comparison of direct radionuclide cystography and voiding cystourethrography in detecting vesicoureteral reflux.

BACKGROUND: Fluoroscopic voiding cystourethrography (VCUG) is a widely used imaging test for the diagnosis of vesicoureteral reflux (VUR). However, high gonadal radiation and intermittent imaging are the main disadvantages of VCUG. Direct radionuclide cystography (DRC) has been advocated for the detection of VUR with increased sensitivity and low radiation doses, however, having the disadvantage of providing less anatomical details for urethral evaluation. In this study, DRC has been compared with standard fluoroscopic VCUG for detection of VUR. METHODS: A total of 41 children (82 kidney ureter units, KUU) aged 1 month-126 months (median, 15 months) were studied sequentially using DRC and VCUG. The indications of VUR studied were urinary tract infection in 29 children, VUR follow up in eight children and antenatal dilatation history in four children. RESULTS: A total of 18 refluxing ureters were detected by DRC, 22 refluxing ureters by VCUG and 14 refluxing ureters by both methods. The two methods were concordant for the detection and exclusion of VUR in 85% of KUU. VUR was missed by VCUG in four KUU (three severe, one mild) whereas VUR was missed by DRC in eight KUU (four grade I, four grade III). CONCLUSIONS: There was a good correlation between DRC and VCUG in the evaluation of VUR. DRC provides continuous monitoring and low gonadal radiation exposure. DRC can be used in the diagnosis of VUR as an alternative to VCUG in selected cases.

Paraoxonase 1 192 and 55 polymorphisms in nephrotic children.

Human paraoxonase 1 (PON1) is a serum enzyme related to high-density lipoprotein which has a major role in preventing oxidative modification of low-density lipoprotein. Due to its amino acid substitution PON1 has two genetic polymorphisms. These polymorphisms are characterized by the location of glutamine (A genotype) and arginine (B genotype) at position 192, and leucine (L genotype) and methionine (M genotype) at position 55. Hyperlipidemia and increased lipid oxidation in nephrotic syndrome may lead to glomerulosclerosis and progression of the glomerular disease. In this study we aimed to investigate PON1 192 and PON1 55 polymorphisms in children with focal segmental glomerulosclerosis (FSGS) and control subjects. The study included 25 children with biopsy-proven FSGS and 30 healthy controls. We demonstrated a statistically significant difference between FSGS patients and control subjects with respect to the distribution of the PON1 polymorphism. The AA genotype was less frequent and the AB+BB genotype was more frequent in FSGS patients than in controls (48 versus 73% for AA genotype and 52 versus 27% for AB+BB genotype, p<0.05). Distributions of PON1 55 genotypes of FSGS and control subjects were also statistically different (76 versus 43% for LL genotype and 24 versus 57% for LM+MM genotype, p<0.05) (case-control study, dominant model, Fisher's exact test). The distributions of both genotypes in subgroups of FSGS (stable renal function versus declining renal function) were not statistically different. We conclude in this preliminary study that presence of B allele and/or L allele may be risk factors for the development of FSGS in children.

Hypercalciuria and recurrent urinary tract infections: incidence and symptoms in children over 5 years of age.

Hypercalciuria is an important and common risk factor in the formation of renal stones. In this study we evaluated the incidence and the clinical presentation of hypercalciuria in 75 children over 5 years of age with the diagnosis of recurrent urinary tract infection (UTI). We measured random urinary calcium/creatinine value (three times), 24-h urinary calcium excretion, serum calcium, phosphorus, electrolytes, blood gas, blood urea nitrogen and creatinine levels. Hypercalciuria was found in 32 patients (43%). The mean urinary calcium/creatinine ratio for hypercalciuric patients was 0.50+/-0.21 mg/mg (min: 0.24, max: 2.60). The mean urinary calcium/creatinine ratio for the rest of the study population--those without hypercalciuria--was 0.10+/-0.04 mg/mg (min: 0.01, max: 0.18). Presenting symptoms of the hypercalciuric patients and normocalciuric patients were similar. History of familial urolithiasis was positive in 19 patients (59%). Predisposing urinary tract abnormalities in recurrent UTI was shown in 12 of the hypercalciuric patients (12/32, 37.5%) and 8 of the normocalciuric patients (8/43, 19%) without a statistically significant difference between. We conclude that hypercalciuria is not a rare finding among recurrent UTI cases in Turkish children. Hypercalciuria does not modify the clinical presentation of UTI, and we suggest the investigation of urinary calcium excretion in children with recurrent UTI.

Downregulation of the expression of bone morphogenetic protein 7 in experimental pyelonephritis.

Bone morphogenetic protein 7 (BMP 7) is a member of the transforming growth factor (TGF) beta superfamily and is involved in regeneration, repair, and development of specific tissues, for example kidney, gut, lens, and skeleton. BMP 7 has emerged as a renotrophic factor and experimental studies have shown its protective role against fibrotic processes. Tubulointerstitial changes are present in the pyelonephritic kidney which progresses to fibrosis. Renal fibrosis may lead to significant morbidity in the form of hypertension, proteinuria, and loss of renal function. The objective of this study was to investigate BMP 7 expression in experimental acute and chronic pyelonephritis models. Eighteen Wistar rats were injected with 0.1 mL solution containing E. coli ATCC 25922 10(10) cfu mL(-1) into left renal medullae. Six rats were used as a sham group and were given 0.1 mL 0.9% NaCl. Pyelonephritic rats were sacrificed 24 h (group I, n=6), 1 week (group II, n=6), and 6 weeks (group III, n=6) after E. coli injection. Serum creatinine levels were analyzed. Renal tissues were studied histopathologically by use of hematoxylin and eosin and scored for diagnosis of pyelonephritis. BMP 7 expression was studied semiquantitatively by immunohistochemical staining. Acute (group I) and chronic (group II and group III) pyelonephritic histopathological changes were observed in experimental pyelonephritic groups. A gradual decrease in BMP 7 expression was observed in the tubulointerstitial and tubular area of the pyelonephritic kidneys, mildest in the acute pyelonephritic group and most severe in the chronic pyelonephritic 6th week group. A statistically significant difference was observed between tubulointerstitial BMP 7 expression by groups I and III (P=0.017) and by groups III and IV (P=0.000). Tubular BMP 7 expression was statistically significantly different between groups II and IV (P=0.009) and between groups III and IV (P=0.002). The data imply that BMP 7 has a major role in chronic pyelonephritis. Tubulointerstitial and tubular BMP 7 expression also had a significant negative correlation with fibrosis, tubular, atrophy, and vascular changes. Serum creatinine levels of the study group were all normal. We conclude that the decrease in renal BMP 7 expression in experimental chronic pyelonephritis is one of the factors responsible for fibrotic changes in persistent renal damage.

Biochemical bone markers in nephrotic children.

In this study we evaluated the effects of high-dose corticosteroid (CS) therapy and the character of the nephrotic syndrome (NS) itself on bones in patients with normal glomerular filtration rate. We measured serum osteocalcin (OC), alkaline phosphatase (ALP), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, calcium (Ca), phosphorus (P), and magnesium (Mg) levels, and urinary Ca and protein excretion in nephrotic children during the active phase before (group Ia) and after CS treatment (group Ib). The results were compared with age-matched control subjects. A significant increase in urinary Ca excretion was observed after CS treatment. Serum ALP, OC, and iPTH levels were within normal limits at the time of study entry. However, both serum OC and ALP levels showed a significant decrease after the completion of CS treatment (OC from 13.6+/-9.2 ng/ml to 6.7+/-5.2 ng/ml and ALP from 151.8+/-60.2 U/l to 116+/-43.8 U/l). 25-Hydroxyvitamin D levels increased to 17.2+/-8.9 microg/l from 9.9+/-6.9 microg/l after CS treatment. The effects of recurrent use of CSs were assessed by dividing nephrotic patients into two subgroups: infrequent relapsers (IFR) and frequent relapsers (FR). The cumulative dose of CS was 28,125 mg/m(2) for IFR and 105,000 mg/m(2) for FR. The changes in OC, ALP, and 25-hydroxyvitamin D levels after CS treatment were significantly different between IFR and FR. We conclude that high-dose CS treatment causes a decrease in bone formation, as shown by the changes in OC and ALP levels. 25-Hydroxyvitamin D levels remained lower than control subjects after CS therapy. The higher the cumulative dose of CS used the more marked the changes in biochemical bone markers. The contribution of FR to baseline 25-hydroxyvitamin D levels needs further study.

The longest use of liposomal amphotericin B and 5-fluorocytosine in neonatal renal candidiasis.

Bilateral fungal obstruction of the renal collecting system is rare in infancy. Treatment options include medical or surgical procedures. Reports of successful medical treatment with liposomal amphotericin B have been published but the duration of treatment is controversial. We report a 3-week-old preterm baby with myelomeningocele who had experienced acute renal failure related to bilateral renal fungus balls, which improved with percutaneous nephrostomy and 12 weeks of liposomal amphotericin B intravenously combined with 5-fluorocytosine orally for 9 weeks.

Neonatal urinary tract infections: analysis of the patients and recurrences.

BACKGROUND: Early diagnosis and proper treatment, including long-term follow up, are very important for neonatal urinary tract infections (UTI). METHODS: The present study reports the analysis and long-term follow-up results of 71 newborns treated for UTI. RESULTS: Forty-one per cent of patients were preterm babies. Suspected sepsis and hyperbilirubinemia were the main presenting features. Community-acquired and nasocomial UTI accounted for 63% and 37% of cases, respectively. The leading causative agents were Escherichia coli for community-acquired UTI and Klebsiella pneumoniae for nasocomial UTI. The urosepsis rate was 5%. Abnormal ultrasonography findings were present in 23% and vesicoureteral reflux was present in 15% of babies. A total of 23% of patients showed renal photopenic areas on dimercaptosuccinic acid scan. The recurrence rate was 28% occurring between 1.5 and 12 months, in particular in the first 6 months. Most of the recurrences developed in patients with no predisposing abnormalities. CONCLUSION: Pediatric nephrologic follow-up of babies experiencing UTI in the neonatal period is very important to identify the predisposing congenital abnormalities and scarred kidneys, to diagnose and to treat the recurrences earlier.

Cefepime-induced non-convulsive status epilepticus in a peritoneal dialysis patient.

Non-convulsive status epilepticus related to cefepime has not been reported in childhood dialysis patients, although several adult cases have been reported. We report a state of acute confusion in a 15-year-old boy on continuous ambulatory peritoneal dialysis (CAPD) receiving cefepime that was diagnosed as status epilepticus by electroencephalography (EEG). The EEG improved after anticonvulsive therapy. All clinical symptoms disappeared dramatically within 24 h of discontinuation of cefepime. The differential diagnosis of confusional states and the mechanisms of the convulsive effects of antimicrobials in chronic renal failure are discussed. The importance that the clinician is aware of the rare side effects of antimicrobials is emphasized.