Predictors of poor kidney outcome in children with C3 glomerulopathy.

BACKGROUND: C3 glomerulopathy (C3G) is characterized by heterogeneous clinical presentation, outcome, and predominant C3 accumulation in glomeruli without significant IgG. There is scarce outcome data regarding childhood C3G. We describe clinical and pathological features, treatment and outcomes, and risk factors for progression to chronic kidney disease stage 5 (CKD5) in the largest pediatric series with biopsy-proven C3G. METHODS: Sixty pediatric patients with C3G from 21 referral centers in Turkey were included in this retrospective study. Patients were categorized according to CKD stage at last visit as CKD5 or non-CKD5. Demographic data, clinicopathologic findings, treatment, and outcome data were compared and possible risk factors for CKD5 progression determined using Cox proportional hazards model. RESULTS: Mean age at diagnosis was 10.6 ± 3.0 years and follow-up time 48.3 ± 36.3 months. Almost half the patients had gross hematuria and hypertension at diagnosis. Nephritic-nephrotic syndrome was the commonest presenting feature (41.6%) and 1/5 of patients presented with nephrotic syndrome. Membranoproliferative glomerulonephritis was the leading injury pattern, while 40 patients had only C3 staining. Patients with DDD had significantly lower baseline serum albumin compared with C3GN. Eighteen patients received eculizumab. Clinical remission was achieved in 68.3%. At last follow-up, 10 patients (16.6%) developed CKD5: they had lower baseline eGFR and albumin and higher frequency of nephrotic syndrome and dialysis requirement than non-CKD5 patients. Lower serum albumin and eGFR at diagnosis were independent predictors for CKD5 development. CONCLUSIONS: Children with C3G who have impaired kidney function and hypoalbuminemia at diagnosis should be carefully monitored for risk of progression to CKD5. Graphical abstract.

Amitriptyline Intoxication in Children: Twenty Years' Experience in a Tertiary Care Center in Turkey.

BACKGROUND: Amitriptyline ingestion is an important cause of poisoning morbidity and mortality in Turkey and other countries. In contrast to adults, data concerning amitriptyline intoxication in children are limited. The purpose of this study was to investigate amitriptyline intoxication findings in the pediatric population, based on age groups and reported dosages. METHODS: The medical records of 192 patients admitted to the Karadeniz Technical University Medical Faculty Farabi Hospital Pediatric Emergency Department, Turkey, due to amitriptyline intoxication in 1997-2017 were examined retrospectively. Patients were divided into 6 groups based on amitriptyline doses and 4 groups based on age. Complete blood count, blood glucose, serum electrolytes, renal and liver function tests, coagulation tests (prothrombin time and partial thromboplastin time), and blood gas analysis were studied in all patients. Electrocardiography was performed on all children, and chest radiography and electroencephalography on those with respiratory or central nervous system symptoms. RESULTS: Amitriptyline intoxication was most frequently observed between the ages of 1 and 4 years. The most common signs and symptoms observed at time of hospital admission were lethargy and drowsiness (45.3%), sinus tachycardia (19.2%), and nausea and vomiting (13%). The most common laboratory finding was hyperglycemia (17.7). Six patients were intubated because of respiratory failure, and mechanical ventilation was initiated in these cases. One patient with amitriptyline overdose had persistent supraventricular tachycardia. Four children died due to amitriptyline intoxication. CONCLUSIONS: Tricyclic antidepressant intoxication is a leading cause of mortality and morbidity in children. It is therefore particularly important to identify the clinical and laboratory findings that develop with high-dose consumption.

Atypical Hemolytic Uremic Syndrome in Children Aged <2 Years.

BACKGROUND: There are limited data on infants with atypical hemolytic uremic syndrome (aHUS). The aim of this study was to determine the clinical and laboratory features, and to evaluate treatment modalities and outcomes in infants with aHUS. MATERIALS AND METHODS: Relevant data on patients with onset of aHUS at age <2 years were obtained from the Turkish Pediatric aHUS Registry. RESULTS: Among the 146 patients included in the Registry, 53 (36%) (23 male and 30 female) were enrolled for the study. Age at disease onset was ≤1 year in 29 of the patients. In all, 21 (40%) of the patients developed neurological symptoms. Disease-causing mutations were noted in 14 (36%) of the 39 patients in which genetic analysis was performed. Plasma therapy was performed in 42 (79%) patients; eculizumab therapy was administered to treat the first episode of aHUS in 33 (62%) patients and in 5 patients as the first- line therapy. In total, 38 (72%) patients received renal replacement therapy (RRT), 3 (6%) died due to acute illness, and 4 (8%) were discharged from hospital with RRT. Follow-up visit data were available for 46 patients and the median duration was 23 months (range 3-129 months). End-stage renal disease developed only in 1 patient. Proteinuria and hypertension persisted in 17 (37%) and 20 patients (44%) respectively. Eculizumab treatment was continued in 25 of the 39 patients during the follow-up period. CONCLUSION: One-third of the aHUS patients had disease onset during infancy. The prognosis of this life-threatening disease seems to get better with improved treatment modalities.

Hereditary renal tubular disorders in Turkey: demographic, clinical, and laboratory features.

BACKGROUND: The Turkish Renal Tubular Disorders Working Group aimed to form a patient registry database and gathered demographic, clinical, and laboratory data in various hereditary renal tubular disorders (HRTDs). METHODS: A questionnaire comprising HRTDs was sent to the centers. The cohort was composed of 226 patients (109 girls, 117 boys). RESULTS: The distribution of patients according to HRTD was as follows: 45.6% distal renal tubular acidosis (dRTA), 26.6% proximal RTA (pRTA), 3.5% type IV RTA, 21.7% Bartter's syndrome, and 2.6% Gitelman's syndrome. Cystinosis was the most common cause for renal Fanconi syndrome. Age at diagnosis was between 1 month and 16 years. Overall consanguinity rate was as high as 72%. Rate of affected siblings was 28.5%. pRTA and type IV RTA were more common in males. Most common presenting symptoms were failure to thrive, lack of appetite, and vomiting. Nephropathic cystinosis was the most common HRTD leading to renal failure, followed by dRTA. Hearing loss was present in 23% of patients with dRTA and 6.3% of patients with Bartter's syndrome. No other patient had hearing loss. Convulsions were noted in Bartter's syndrome patients with failure to thrive, especially in those with height below 3%. Polyuria and nephrocalcinosis were more common in dRTA patients with deafness compared with patients without deafness. CONCLUSIONS: This data reflected a high number of HRTDs as a result of high consanguinity rate in Turkey. Our data serve as a database of demographic, clinical, and laboratory features of this rare disease group.

Charcoal hemoperfusion in an infant with supraventricular tachycardia and seizures secondary to amitriptyline intoxication.

Tricyclic antidepressant (TCA) overdose is one of the common causes of drug poisoning and it has cardiovascular, respiratory and neurological side effects. An 18-month male infant was admitted to our pediatric emergency service due to poisoning with amitriptyline. The infant was unconscious. Tachycardia, irregular and shallow breathing, and tonic-clonic seizures were observed on physical examination. An electrocardiogram displayed a narrow complex tachycardia that was consistent with re-entrant supraventricular tachycardia (SVT). Although antiarrhythmic and anticonvulsive agents were administrated, SVT and seizures persisted. Charcoal hemoperfusion (HP) was performed for 4 hours. The infant's clinical condition has improved after the charcoal HP, seizures and SVT were not observed. It is concluded that charcoal HP can be used efficiently in patients with severe amitriptyline intoxication.

High-dose methylprednisolone in children with Crimean-Congo haemorrhagic fever.

Treatment options for Crimean-Congo haemorrhagic fever (CCHF) are limited and based on general supportive managements. Thrombocytopenia is the major risk factor of CCHF. We report our experience with high-dose methylprednisolone (HDMP). This study included five patients with CCHF. Patients were given HDMP if there were findings compatible with virus-associated haemophagocytic syndrome and the effects of HDMP were evaluated. Following this, HDMP fever subsided and platelet counts increased within 24 hours. Leukocyte counts began to increase and visceral bleedings were improved. HDMP treatment was discontinued within approximately five days. After HDMP, only one patient required blood products. HDMP is effective in CCHF, especially on fever and platelet counts. Dependency on blood products was decreased. Further controlled randomized studies with large series are needed in order to analyse the timing and duration of HDMP treatment and its effect on outcome.

An unusual case of an aldosterone-producing adrenocortical adenoma presenting with rhabdomyolysis.

Rhabdomyolysis is a rare presentation of hypokalemia, although muscle weakness is a well known manifestation of marked hypokalemia. Here, we report a case of primary hyperaldosteronism due to unilateral aldosterone-producing adenoma in a 14 year-old girl who developed rhabdomyolysis following hypokalemia. To our knowledge, this is the first case of adrenocortical adenoma presenting with rhabdomyolysis in a child.

Mutations of ESRRB encoding estrogen-related receptor beta cause autosomal-recessive nonsyndromic hearing impairment DFNB35.

In a large consanguineous family of Turkish origin, genome-wide homozygosity mapping revealed a locus for recessive nonsyndromic hearing impairment on chromosome 14q24.3-q34.12. Fine mapping with microsatellite markers defined the critical linkage interval to a 18.7 cM region flanked by markers D14S53 and D14S1015. This region partially overlapped with the DFNB35 locus. Mutation analysis of ESRRB, a candidate gene in the overlapping region, revealed a homozygous 7 bp duplication in exon 8 in all affected individuals. This duplication results in a frame shift and premature stop codon. Sequence analysis of the ESRRB gene in the affected individuals of the original DFNB35 family and in three other DFNB35-linked consanguineous families from Pakistan revealed four missense mutations. ESRRB encodes the estrogen-related receptor beta protein, and one of the substitutions (p.A110V) is located in the DNA-binding domain of ESRRB, whereas the other three are substitutions (p.L320P, p.V342L, and p.L347P) located within the ligand-binding domain. Molecular modeling of this nuclear receptor showed that the missense mutations are likely to affect the structure and stability of these domains. RNA in situ hybridization in mice revealed that Esrrb is expressed during inner-ear development, whereas immunohistochemical analysis showed that ESRRB is present postnatally in the cochlea. Our data indicate that ESRRB is essential for inner-ear development and function. To our knowledge, this is the first report of pathogenic mutations of an estrogen-related receptor gene.

Parental-reported drug allergy in 6- to 9-yr-old urban schoolchildren.

Epidemiologic studies about the prevalence of adverse drug reactions in children are scarce compared to reports in adults. To assess the prevalence of parental-reported drug allergy in 6- to 9-yr-old urban school children, we performed a cross-sectional study of 6- to 9-yr-old urban children from the eastern Black Sea region of Turkey during the year 2004, using a self-administered questionnaire by parents. Response rate was 81.6% (2855/3500). The prevalence of parental-reported drug allergy was 2.8% (81/2855). The most common parental-reported drugs were penicillins and other beta-lactams (59.3%), trimethoprim-sulfamethoxazole (11.1%), and acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) (9.9%). The most commonly reported clinical manifestations were cutaneous (n = 76, 93.8%) followed by gastrointestinal (n = 17, 21%) symptoms. In 19 (23.5%) children, the reaction involved more than one organ system. Of these 19 children, 14 used beta-lactams. Systemic reactions were not reported with NSAIDs. Medications were taken by mouth in 88.9% of the reactions. Most of the reported allergic reactions occurred in the first day of treatment (61.7%). The reported time to reaction after the last intake of the drug was <2 h in 35 (43.2%) children and 2-24 h in 45 (55.6%). Oral reactions occurred later than reactions to parentally administered drugs. Parents of 58 children (71.6%) reported that they completely avoided the suspected culprit drug following the reaction. Relapse occurred after re-administration of the drug in 21 (25.9%) children. A diagnostic approach for drug allergy was not undertaken in any of the children. This study may provide some information about the prevalence of drug allergy, although it is based on parental perception and results are unlikely to conform well to true prevalence.

Adjuvant effect of vitamin A on recurrent lower urinary tract infections.

BACKGROUND: The purpose of the present paper was to investigate the effects of vitamin A supplementation on recurrent lower urinary tract infections (RUTI). METHODS: Twenty-four patients with non-complicated RUTI were included in a placebo-controlled, double-blinded study. Twelve patients received a single dose of 200,000 IU vitamin A in addition to antimicrobial therapy. Patient and control groups (each containing 12 patients) were followed for up to 1 year and were evaluated for eradication and frequency of lower urinary tract infections (UTI). Serum levels of vitamin A and beta-carotene were determined periodically. RESULTS: During the first 6 months follow-up period the infection rate of the vitamin A-supplemented group reduced from 3.58 to 0.75 per 6 months, and in the subsequent 6 months the infection rate was 1.75 per 6 months. These values were calculated as 2.75, 2.83 and 2.66, respectively, in the placebo group. CONCLUSION: Vitamin A supplementation may have an adjuvant effect on the treatment of RUTI.

Comparison of pulse and oral steroid in childhood membranoproliferative glomerulonephritis.

BACKGROUND: There has been no controlled study comparing efficacy of pulse versus oral steroid therapy in childhood membranoproliferative glomerulonephritis (MPGN). This study aimed to compare these therapies and renal outcome over a long-term period for MPGN. METHODS: Outcome measures in 11 patients with MPGN treated with pulse methylprednisolone (MP) were compared with 8 patients with MPGN treated with oral prednisolone (P). RESULTS: Nineteen children with idiopathic MPGN (mean age 9.75 years, range 3.7-14 years) were followed for a mean period of 68.21 months (range 4-124 months). Both treatment groups were similar in demographic, clinical, laboratory and histopathological characteristics on presentation. In the pulse MP group, only 1 patient out of 11 progressed to end-stage renal failure (ESRF), compared with 4 patients out of 8 in the oral P group (p=0.041). For long-term renal survival, those patients with more than 8 years of follow-up were further evaluated. Twelve patients had completed 8 years of follow-up; in the pulse MP group, 1 of 7 patients, compared with 4 of 5 patients in the oral P group progressed to ESRF (p=0.039). Chronic damage in the presentation biopsy and lack of remission in patients with nephrotic syndrome (NS) were positively associated with adverse renal outcome (p=0.02, p=0.006, respectively). CONCLUSIONS: Pulse MP therapy may be superior to oral P therapy in children with MPGN in preserving renal function without any increase in steroid-related side effects. Chronic damage in the presentation biopsy and lack of remission of NS are adverse features.

Diagnostic difficulties in children with coexisting pelvi-ureteric and vesico-ureteric junction obstruction.

OBJECTIVE: To assess the diagnosis of children with coexisting pelvi-ureteric junction (PUJ) and vesico-ureteric junction (VUJ) obstruction, and the management of such patients, as having these two anomalies in the same ureter creates serious diagnostic difficulties, but any delay in diagnosis might cause a deterioration of renal function and affect the success of surgery to correct either anomaly. PATIENTS AND METHODS: We assessed the diagnostic difficulties and approach to 14 patients with coexistent PUJ and VUJ obstruction, who were treated surgically in our clinic between 1994 and 2005; we also review related published reports in English. RESULTS: Surgery was used in all 14 patients over the 11-year period; only five patients had an accurate diagnosis before surgery. Six patients were diagnosed with uroradiological techniques immediately after pyeloplasty; three were diagnosed on investigating an associated anomaly later. CONCLUSION: In children with coexisting PUJ and VUJ obstruction there are serious diagnostic problems; to prevent any deterioration in renal function due to obstruction, these anomalies require early diagnosis and treatment. For an early and accurate diagnosis, the coexistence of these two anomalies in the same ureter should be considered.

Effects of melatonin on suppression of renal scarring in experimental model of pyelonephritis.

OBJECTIVES: To determine the effects of melatonin combined with antibiotic administration on the suppression of renal scarring in an experimental pyelonephritis model. METHODS: The control group underwent a sham operation without infection. In the other groups, treatment began 72 hours after direct bacterial inoculation. In the no-treatment group, rats received daily intraperitoneal injections of saline. In the antibiotic-only group, the rats were treated only with ceftriaxone intramuscularly at a dose of 50 mg/kg once daily for 5 days. In the melatonin-only group, only 20 mg/kg of melatonin once daily was given by intraperitoneal injection for 5 days. In the antibiotic plus melatonin group, melatonin and ceftriaxone were administered at the same dosages and duration as for the single-modality treatment groups. After 6 weeks, the kidneys were removed for malondialdehyde measurements and histopathologic examination (inflammatory response and cicatrization). RESULTS: Melatonin only (134.25 +/- 13.42) and antibiotic plus melatonin treatment (122.62 +/- 8.91) caused a marked reduction in the mean malondialdehyde values compared with no treatment (214.12 +/- 17.77) and antibiotic-only treatment (161.37 +/- 16.03), with no significant difference compared with that of the control group (120.75 +/- 9.83). Histopathologically, in the no-treatment group, the severity of scarring correlated directly with the severity of inflammation (r = 0.93). No significant differences were found in the renal scarring scores in rats receiving no treatment and those treated only with antibiotic or melatonin. In the antibiotic plus melatonin treatment group, the cicatrization score was not statistically different from that of the control group. CONCLUSIONS: When combined with antibiotics, melatonin causes a significant inhibition of malondialdehyde production and neutrophil infiltration caused by acute pyelonephritis in an experimental rat model, and these are responsible for the protective effect of melatonin against renal damage, preventing renal scarring formation.

Rapid decline of anti-pneumococcal antibody levels in nephrotic children.

Nephrotic children are at increased risk for pneumococcal infections. Antibody responses to the currently recommended pneumococcal polysaccharide vaccine have been variable and maintenance of adequate antibody levels over time has not been well documented. In this study, we determined total IgG antibody levels against pneumococcal polysaccharides before and 1, 6, 12 and 36 months after 23-valent pneumococcal polysaccharide vaccine (PPV) administration in nine children with steroid-responsive nephrotic syndrome during remission while off corticosteroids. The baseline antibody levels were between 4 and 86 mg/l. Four weeks after vaccination, the titer increased at least twofold in all patients with a mean arithmetic value of 165.4 mg/l. At the 6th month, the levels decreased in six out of nine subjects to a mean of 94.6 mg/l. At the 36th month, the control antibody levels were below the baseline or below the early postvaccination values in four out of nine subjects. Only two patients had stable high concentrations through the study period. Our data show that nephrotic patients may not retain their antibody levels despite reasonably good initial responses to the pneumococcal vaccine and that susceptibility to infections may continue in vaccinated children.

Visceral Kaposi's sarcoma with intracranial metastasis: a rare complication of renal transplantation.

The incidence of Kaposi's sarcoma (KS) has increased in solid organ transplantation recipients. This type of KS tends to be aggressive, involving lymph nodes, mucosa and visceral organs in about half of patients, sometimes in the absence of skin lesions. Brain involvement of KS has rarely been reported. A 16-yr-old Turkish boy underwent renal transplantation from his mother. The immunosuppressive regimen included prednisolone, cyclosporin A and azathioprine. Fourteen months later the azathioprine was changed to cyclophosphamide (3 mg/kg/day) because of the development of a nephrotic syndrome. After 12 weeks, the cyclophosphamide was changed to mycophenolate mofetil (MMF) to control the nephrotic syndrome. At this time his serum creatinine level rose to 2.1 mg/dL. Polyclonal or monoclonal antibodies were never given. Multiple intra-abdominal lymphadenopathy was detected on abdominal tomography at the 32nd month after renal transplantation. Kaposi's sarcoma was diagnosed via laparotomy and biopsy. He had a generalized tonic and clonic seizure and contrast enhanced cranial tomography showed two intracranial masses which had an abundant vascular component which caused a mild shift. One of the masses was removed via a burr-hole with the aim of diagnosis and treatment of the shift. A pathologic examination of the intracranial lesion was also reported as Kaposi's sarcoma. Herpes virus-8 DNA was detected by PCR in the intracranial lesion.

Late diagnosis of severe colchicine intoxication.

A 4-year-old Turkish girl was referred to our hospital with the findings of encephalopathy and pancytopenia. She had a history of severe abdominal cramps and gastrointestinal bleeding. A confused state, muscle pain and weakness, erythema-bullous and erythema-nodosum-like skin lesions, and alopecia were observed at her hospitalization. All of these symptoms resolved on follow-up. On laboratory investigation severe thrombocytopenia and leukopenia, mild anemia, a moderate increase in aspartate aminotransferase and alanine aminotransferase levels were detected. After reevaluating her medical history, it was learned that she had accidentally taken 1.3 to 1.5 mg/kg of colchicine 3 to 4 days before her first hospitalization. The possibility of misdiagnosis of colchicine intoxication should be borne in mind, and pediatricians must be aware of its toxic effects, especially in areas where patients with familial Mediterranean fever are present.