The Importance of Sphingomyelin Phosphodiesterase Acid-Like 3b (SMPDL-3b) Levels in Kidney Biopsy Specimens of Children With Nephrotic Syndrome.

OBJECTIVE: It remains unclear whether the low amount of SMPDL-3b required for rituximab binding is the cause of treatment resistance in patients with treatment-resistant nephrotic syndrome with advanced podocyte injury. Given the limited number of studies on the relationship between rituximab and SMPDL-3b, this study was conducted to assess whether SMPDL-3b levels in pretreatment renal biopsy specimens can be used to predict the clinical effectiveness of immunosuppressive drugs, especially rituximab, in children with nephrotic syndrome. METHODS: Kidney biopsy specimens from 44 patients diagnosed with idiopatic nephrotic syndrome were analyzed using immunohistochemical staining with an anti-SMPDL-3b antibody and real-time polymerase chain reaction (PCR) for SMPDL-3b mRNA expression. RESULTS: We showed that SMPDL-3b mRNA expression and anti-SMPDL-3b antibody staining did not differ significantly between the patient groups with different responses to immunosuppressive therapies. CONCLUSION: Our results suggest that SMPDL-3b may actually be an indicator of disease progression rather than a marker for predicting response to a particular immunosuppressive agent.

Severe acute kidney injury induced by crescentic glomerulonephritis in a child with infective endocarditis.

BACKGROUND: Kidney involvement related to infective endocarditis (IE) may present with different clinical findings. The most common histopathological finding of renal involvement is a combination of proliferative and exudative glomerulonephritis. However, severe acute kidney injury (AKI) induced by crescentic glomerulonephritis (CGN) is extremely rare in children with IE. To date, only 4 pediatric cases with IE-induced CGN had been reported. We present a 14-year old girl with IE-induced CGN. CASE: A 14-year old girl with fever, macroscopic hematuria, oliguria, and acute kidney injury (AKI) was admitted to our clinic. The medical history revealed that the patient had undergone several cardiac interventions due to truncus arteriosus type 1, and she recovered from IE-induced glomerulonephritis following antibiotherapy six months ago. During admission, the patient was diagnosed with IE according to one major (positive imaging finding) and three minor (fever, predisposing cardiac disease, and immunological criterion) criteria. Immediate antibiotic treatment was initiated. A kidney biopsy was performed, which showed crescentic glomerulonephritis (CGN with crescents, > 50%). Daily pulse steroid (3 days), monthly pulse cyclophosphamide (6 doses), and oral steroid (2 mg/kg/day) therapy were initiated with gradual dose tapering. The patient underwent 12 hemodialysis sessions until the 38 < sup > th < /sup > day of the treatment. She was discharged on the 45th day of treatment with normal kidney function tests and negative acute phase reactants. Treatment was maintained with mycophenolate mofetil (MMF) after a 6-month course of cyclophosphamide. MMF was discontinued in the 12th month. At the 18thmonth follow-up visit the patient had mild proteinuria, and was on ramipril therapy. CONCLUSIONS: The occurrence of CGN should be considered in children with predisposing cardiac disease, who develop hematuria, proteinuria, and severe AKI. Although antibiotic therapy alone is often sufficient in this immune complex GN induced by infection, early initiation of additional immunosuppressive therapy in the presence of CGN may be beneficial for long term preservation of kidney functions.

Therapeutic Effect of Teneligliptin in Drug-Induced Nephrotoxicity: An In-Vitro Study.

Background Drug-induced nephrotoxicity is an important side effect of many commonly used drugs. In this study, we planned to evaluate the effects of teneligliptin (TG), which is a dipeptidyl peptidase-4 (DPP-4) inhibitor, on cell healing by creating nephrotoxicity models in human renal proximal tubule cell and human embryonic kidney epithelial cells cell lines in-vitro with cisplatin, vancomycin, and gentamicin. Methodology First, we determined the 50% inhibitory concentration doses of nephrotoxic drugs and the nephroprotective dose of TG. Then, we analyzed the difference in cell viability, apoptosis, and oxidative stress (reactive oxygen and nitrogen species (ROS/RNS) production) between TG-treated and untreated cells after nephrotoxicity occurred. Moreover, we evaluated the expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in cells. Results We found that when cell lines were treated after toxicity was induced with TG, cell viability increased, apoptosis and ROS/RNS production were significantly decreased, and expressions of KIM-1 and NGAL were significantly reduced. Conclusions This study showed that TG has positive effects on the recovery of drug-induced nephrotoxicity in an in-vitro setting.

Acute focal bacterial nephritis and prolonged fever.

Acute focal bacterial nephritis (AFBN) is characterised by a complicated upper urinary tract infection ranging from acute pyelonephritis to renal abscess. Timely diagnosis of AFBN is important because antibiotic therapy of longer duration is required. A 10-year-old boy presented with fever for 5 days and bilateral flank pain. He was oriented and cooperative but appeared ill. Physical examination did not reveal any oedema or costovertebral angle tenderness. Acute phase reactants such as erythrocyte sedimentation rate and C-reactive protein were raised, serum creatinine was 1.25 mg/dL (0.31-0.88) and leucocyte esterase was positive in the urine. Ultrasonographic examination demonstrated bilaterally enlarged kidneys with increased echogenicity. Because of the high creatinine level, abdominal magnetic resonance imaging (MRI) was performed instead of computed tomography (CT) for further evaluation. The MRI showed an increase in the size of both kidneys, renal cortical heterogeneity and multiple cortical nodular lesions with diffusion restriction (constrained Brownian movement of water molecules) on diffusion-weighted MRI. A negative urine culture result in children presenting with fever and abdominal pain may mislead the clinicians, causing them to miss a nephro-urological diagnosis. It is therefore recommended that patients in whom the cause of fever cannot be determined be scanned by ultrasound and examined by CT or MRI so that undiagnosed and/or suspected cases of AFBN might be detected.

Severe hypercalcaemia and acute renal failure in an infant with subcutaneous fat necrosis.

Subcutaneous fat necrosis (SFN) in the newborn is a form of panniculitis which presents with erythematous nodules and indurated plaques. Severe life-threatening hypercalcaemia can occur as a late complication. A 2-month-old girl presented with severe hypercalcaemia and acute renal injury as a complication of SFN. She was admitted to hospital with the chief complaint of failure to thrive. She had a history of therapeutic hypothermia. After successful treatment of the hypercalcaemia with bisphosphonates, the acute renal injury recovered spontaneously. In neonates with SFN, acute renal injury is a rare complication of hypercalcaemia. Timely prevention of the complications of hypercalcaemia in SFN is essential.

Myocarditis and intracardiac thrombus due to Henoch-Schönlein purpura: case report and literature review.

Cardiac involvement is very rare in patients with Henoch-Schönlein purpura (HSP). In this case study, we present an 8-year-old girl presenting with HSP-induced myocarditis and thrombus in the right atrium and HSP nephritis. To date, 15 cases of HSP-related cardiac involvement have been reported in the PubMed/MEDLINE, Scopus, and Google Scholar databases. These cases, together with our case, are included in this review. We excluded those patients with other rheumatologic diseases (acute rheumatic fever, acute post-streptococcal glomerulonephritis, Kawasaki disease) accompanied by HSP. Three were children and 13 were adults and all were male except our case. This review revealed tachyarrhythmia, chest pain, dyspnea, murmur, and heart failure as the major signs. Cardiac tests, electrocardiogram (ECG), and imaging methods (echocardiography in all patients, cardiac magnetic resonance imaging (MRI) in three, cardiac biopsy in one, and post-mortem necropsy in three) showed that the cardiac involvements were pericardial effusion, intra-atrial thrombus, myocarditis, coronary artery changes, myocardial ischemia, infarction and necrosis, subendocardial hemorrhage, and left ventricular dilatation. Kidney involvement was not observed in three patients. As the treatment, high-dose prednisolone and cyclophosphamide, oral corticosteroid, azathioprine, nadroparin calcium, ACE inhibitors, calcium antagonists, beta-blockers, and diuretics were used. Eleven patients (all three children and eight of the adults) had a complete cardiac recovery. Cardiac involvement in adults was more likely to be fatal. Death (three patients), ischemia, and infarct have been reported only in adults. We suggested that early and aggressive treatment can be life-saving. MRI examination is effective at identifying cardiac involvement.

Evaluation of the composition of urinary tract stones in children from the Inner Western Anatolian Region in Turkey.

OBJECTIVE: Pediatric urolithiasis is a globally growing problem. The composition and frequency of urinary tract stones vary not only among different countries, but across various regions in a country. Hence, we aimed to identify the types and frequencies of urinary tract stones in children from our region (Inner Western Anatolian part of Turkey), and to compare our findings with the results from other regions in our country. MATERIAL AND METHODS: In this retrospective analysis of 53 pediatric urolithiasis cases that were treated in our hospital between 2009 and 2019, the demographic data, clinical course, radiological and metabolic findings, the recurrence rate, and the composition of the stones were evaluated. RESULTS: The mean age of the patients was 5.9±4.6 (0.5-18) years, and there were 30 (56.6%) girls and 23 (43.4%) boys. An analysis of the composition of the stones revealed that the majority (85%) consisted of calcium oxalate. The highest risk of recurrence and the need for multiple shockwave lithotripsy (SWL) sessions or surgical intervention appeared to be related with the presence of whewellite stones, which are the most challenging stones in childhood. CONCLUSION: According the study results, the urinary stone types vary across different regions in our country, and the frequency of uric acid stones decreased going westward, while the frequency of oxalate stones increased. We conclude that this difference in the frequency of the type of urinary stones might reflect the regional dietary habits. Regional frequency and etiology studies for the types of urolithiasis may facilitate the approach to the treatment of urolithiasis.

Urinary excretion of pentraxin-3 correlates with the presence of renal scar following acute pyelonephritis in children.

PURPOSE: Acute pyelonephritis is associated with considerable morbidity and potential for renal scarring. Pentraxin3 (PTX3) is a recently discovered mediator of inflammation. The objective of this study was to investigate the changes in serum and urine PTX3 levels in children who had a history of pyelonephritis and were diagnosed with renal parenchymal scar (RPS) and/or vesicoureteral reflux (VUR). METHODS: The study included 88 children (31 males, 57 females) aged between 3 months and 18 years. The children included in the study were divided into four groups: VUR with RPS (Group 1), RPS without VUR (Group 2), VUR without RPS (Group 3), and healthy children without a history of hydronephrosis or UTI history (Group 4). After the initial evaluation, the participants were further divided into two more groups and re-evaluated: Children with RPS (Group 1 + 2), children without RPS (Group 3 + 4), children with VUR (Group 1 + 3), and children without VUR (Group 2 + 4). RESULTS: We found that urine pentraxin 3 (uPTX3) and uPTX3/Creatinine levels were significantly higher in the groups with renal scar with or without VUR than the ones without RPS [mean uPTX3, 3.5 pg/ml (min-max 0.0022-12.3668) vs. 2.2 pg/ml (min-max 0.0022-18.5868) and uPTX3/creatinine, 10.5 pg/mg (min-max 0.0035-51.1) vs. 5.8 pg/mg (min-max 0.0004-78.7), p < 0.01]. uPTX3 levels were not different among the groups with and without VUR. In addition, serum PTX3 levels were not different among the groups. CONCLUSIONS: We showed that urinary PTX3 increased only in patients with scarred kidneys. These results might be helpful to predict RPS due to past pyelonephritis.

First-Line, Early and Long-Term Eculizumab Therapy in Atypical Hemolytic Uremic Syndrome: A Case Series in Pediatric Patients.

INTRODUCTION: Studies relating to first-line, early, and long-term eculizumab treatment and outcomes in children with atypical hemolytic uremic syndrome (aHUS) are scarce and unclear. The aim of this case-series study was to evaluate the outcomes of first-line, early, and long-term eculizumab treatment in our aHUS patients. MATERIALS AND METHODS: We reviewed the data from four pediatric patients with aHUS who were treated with eculizumab. In three of them, eculizumab was used as a first-line therapy, and the follow-up period was ≥2 years in three patients. RESULTS: Plasma exchange could not be performed in any patient. Plasma infusions were used only in Patient 1 (a 14-month-old boy) for 8 days without any response. Therefore, eculizumab was started on day 11 after admission. Patient 2 (a 16-month-old boy), Patient 3 (an 11-year-old girl), and Patient 4 (a 32-month-old girl) were treated with eculizumab as a first-line therapy, which was started 2-4 days after admission. The dosage of eculizumab was adjusted according to body weight. The hematologic parameters (the time frames were 3-17 days) and C 3 (the time frames were 10-17 days) returned to normal in all patients after receipt of eculizumab. Although Patient 1 developed stage III chronic kidney disease, complete renal recovery occurred in Patients 2 and 4. Patient 3 also had reflux nephropathy with bilateral grade III vesicoureteral reflux and renal scars. Her creatinine clearance returned to the baseline value after receiving eculizumab. No complications related to eculizumab were observed in any patient during the follow-up period. CONCLUSION: Eculizumab can be successfully used as a first-line therapy in pediatric aHUS patients. We observed that the early initiation of eculizumab was associated with the complete recovery of renal function.

Could serum pentraxin 3 levels and IgM deposition in skin biopsies predict subsequent renal involvement in children with Henoch-Schönlein purpura?

BACKGROUND: The aim of this study was to evaluate the potential of serum pentraxin 3 (PTX3) values as an early predictor of subsequent renal involvement in patients with Henoch-Schönlein purpura (HSP) with no abnormalities on urinary examination and in renal function tests at disease onset. METHODS: This was a prospective cohort study which included 60 pediatric patients with HSP (age range 3-15 years) who were diagnosed between February 2011 and October 2012 and 60 age- and sex-matched healthy controls. The patients were followed up for at least 18 months. Clinical findings were recorded for all patients at first examination, and blood samples for routine laboratory parameters and PTX3 value as well as skin biopsy specimens were obtained from each subject. RESULTS: Of the 60 patients with HSP, 29 (48.3 %) developed subsequent renal involvement, of whom four underwent kidney biopsy. The mean serum PTX3 level of patients with subsequent renal involvement was significantly higher than those of patients without renal involvement and of the controls (2.20 ± 1.30 vs. 1.36 ± 0.85 and 1.03 ± 0.7 ng/ml, respectively; p = 0.004). Immunofluorescence evaluation of skin biopsy revealed that in addition to immunoglobulin A (IgA) deposition, the IgM deposition was significantly associated with subsequent renal involvement (p = 0.008). CONCLUSIONS: A high PTX3 level and IgM staining in skin biopsies from HSP patients may be harbingers of subsequent renal involvement.

The prevalence of asthma diagnosis and symptoms is still increasing in early adolescents in Turkey.

BACKGROUND: This study was performed to evaluate the time trends in prevalence of asthma and related factors in Denizli, Turkey. METHODS: Two cross-sectional surveys were performed, 6 years apart (2002 and 2008) using the ISAAC protocol, in the 13-14 age groups and comparisons were made between the results. RESULTS: Lifetime prevalence of wheeze, 12 month prevalence of wheeze, and the prevalence of wheeze after exercise in the previous 12 months were significantly increased respectively from 10.2% to 13.4% (POR = 1.37, 95%CI = 1.18-1.58, p < 0.001), from 5.0% to 6.2% (POR = 1.26, 95%CI = 1.02-1.55, p = 0.016) and from 9% to 10.2% (POR = 1.15, 95%CI = 0.98-1.35, p = 0.046) in 2008 study. Doctor diagnosed asthma prevalence also increased significantly from 2.1% to 12.9 (POR = 6.80, 95%CI = 5.22-8.85, p < 0.001). Prevalence of sleep disturbed by wheeze in the last 12 months; but, never woken with wheezing (POR = 1.62, 95%CI = 1.26-2.09, p = < 0.001) and less than one night per week (POR = 1.58, 95%CI = 1.06-2.36, p = 0.013) were significantly increased in 2008 study. Severe attacks of wheeze limiting speech in the last year was increased from 1.3% to 2.2% (POR = 1.67, 95%CI = 1.14-2.43, p = 0.004). The number of wheeze attacks in the previous 12 months was increased significantly for 4-to-12 attacks (POR = 1.54, 95%CI = 1.03-2.32, p = 0.02) in 2008 study. However, prevalence of waking with cough in the last 12 months did not change. While history of family atopy and domestic animal at home were found as significant risk factors for asthma in 2002 study, male gender, history of family atopy and stuffed toys were found significant in 2008. CONCLUSIONS: The prevalence of asthma symptoms were increased in Denizli. History of family atopy, male gender and stuffed toys were important risk factors for asthma in 2008.

Rising trend of allergic rhinitis prevalence among Turkish schoolchildren.

OBJECTIVES: To assess the time trends and possible risk factors associated with allergic rhinitis symptoms in schoolchildren from Denizli, Turkey. METHOD: Two identical cross-sectional surveys were performed in the 13- to 14-yr age group at intervals of six years using ISAAC questionnaire. Possible risk factors were also asked and the children completed questionnaires by self. RESULTS: A total of 4078 children (response rate 75%) in the 2008 and 3004 children (response rate, 93.8%) in 2002 were included. The lifetime prevalence of rhinitis, 12-month prevalence of rhinitis, prevalence of associated itchy eye in the previous 12 months and doctor diagnosed allergic rhinitis prevalence were increased from 34.2% to 49.4% (POR=1.87, 95% CI=47.8-50.9 and p ≤ 0.001), from 23.5.0% to 32.9% (POR=1.59, 95% CI=31.4-34.3 and p ≤ 0.001), from 9.6% to 14.9% (POR=1.64, 95% CI=13.8-16.0 and p ≤ 0.001), and from 4.3% to 7% (POR=1.67, 95% CI=6.2-7.8 and p ≤ 0.001) respectively. Severe interference with daily activity in the previous 12 months did not change. In multivariate analysis, history of family atopy, stuffed toys, high annual family income, presence of allergy in mother, father and accompaniment of children to their parents after school hours in textile industry were found as risk factors in 2008 study. CONCLUSION: The prevalence of allergic rhinitis increased significantly in 2008. Family history of atopy, stuffed toys, high annual family income and accompaniment of children to their parents in textile industry were found as risk factors for doctor diagnosed allergic rhinitis.