Characteristics and predictors of chronic kidney disease in children with myelomeningocele: a nationwide cohort study.

BACKGROUND: Myelomeningocele (MMC) is highly prevalent in developing countries, and MMC-related neurogenic bladder is an important cause of childhood chronic kidney disease (CKD). This nationwide study aimed to evaluate demographic and clinical features of pediatric patients with MMC in Turkey and risk factors associated with CKD stage 5. METHODS: Data from children aged 0-19 years old, living with MMC in 2022, were retrospectively collected from 27 pediatric nephrology centers. Patients > 1 year of age without pre-existing kidney abnormalities were divided into five groups according to eGFR; CKD stages 1-5. Patients on dialysis, kidney transplant recipients, and those with eGFR < 15 ml/min/1.73 m2 but not on kidney replacement therapy at time of study constituted the CKD stage 5 group. RESULTS: A total of 911 (57.8% female) patients were enrolled, most of whom were expectantly managed. Stages 1-4 CKD were found in 34.3%, 4.2%, 4.1%, and 2.4%, respectively. CKD stage 5 was observed in 5.3% of patients at median 13 years old (range 2-18 years). Current age, age at first abnormal DMSA scan, moderate-to-severe trabeculated bladder on US and/or VCUG, and VUR history were independent risk factors for development of CKD stage 5 (OR 0.752; 95%; CI 0.658-0.859; p < 0.001; OR 1.187; 95% CI 1.031-1.367; p = 0.017; OR 10.031; 95% CI 2.210-45.544; p = 0.003; OR 2.722; 95% CI 1.215-6.102; p = 0.015, respectively). Only eight CKD stage 5 patients underwent surgery related to a hostile bladder between 1 and 15 years old. CONCLUSION: MMC-related CKD is common in childhood in Turkey. A proactive approach to neurogenic bladder management and early protective surgery in selected cases where conservative treatment has failed should be implemented to prevent progressive kidney failure in the pediatric MMC population in our country.

Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?

BACKGROUND: C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes. METHODS: Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. RESULTS: Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group. CONCLUSIONS: This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.

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.

Plasma leucine-rich α-2-glycoprotein 1 - a novel marker of diabetic kidney disease in children and adolescents with type 1 diabetes mellitus?

BACKGROUND: Glomerular endothelial dysfunction and neoangiogenesis play a significant role in the pathogenesis of diabetic kidney disease (DKD). Leucine-rich α-2 glycoprotein 1 (LRG1) is a recently discovered protein that participates in the molecular pathway of inflammation and angiogenesis. We aimed to investigate efficacy of LRG1 to predict estimated glomerular filtration rate (eGFR) decrease in children and adolescents with type 1 diabetes mellitus (T1DM). METHODS: The study comprised 72 participants with diabetes duration for ≥ 2 years. At study initiation, LRG1, urine albumin, eGFR (cystatin C-based, and Schwartz), HbA1c, and lipid values were evaluated and diabetes-related clinical features and anthropometric measurements were collected. These results were compared with final control values after ≥ 1 year. Patients were divided into subgroups according to presence of albuminuria progression, eGFR decrease, and metabolic control parameters. RESULTS: There was positive correlation between LRG1 level and Schwartz and cystatin C-based eGFR decline (r = 0.360, p = 0.003; r = 0.447, p = 0.001, respectively), and negative correlation between final cystatin C-based eGFR and LRG1 (p = 0.01, r = -0.345). Patients with cystatin C-based eGFR decrease > 10% had significantly higher LRG1 levels (p = 0.03), however, LRG1 was not different between albuminuria progression subgroups. A 0.282 µg/ml increase in LRG1 correlated with a 1% decrease in eGFR in simple linear regression analysis (ß = 0.282, %CI 0.11-0.45, p = 0.001) and LRG1 was an independent predictor of GFR decline even in the presence of covariates. CONCLUSIONS: Our study supports the relationship between plasma LRG1 and eGFR decline and suggests LRG1 may be an early marker of DKD progression in children with T1DM. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

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.

Juvenile idiopathic arthritis in a center in the Western Anatolia region in Turkey.

AIM: To demonstrate the demographic data, subgroup distributions, responses to treatment and outcomes of long-term follow-up in patients who were followed up and treated in our clinics with a diagnosis of juvenile idiopathic arthritis, and to compare these data with national and international data. MATERIAL AND METHODS: The files of 116 patients who had been diagnosed as having juvenile idiopathic arthritis, were initiated on treatment and presented for regular follow-up visits between January 2012 and January 2018, were examined. Their demographic findings, treatments, active/inactive disease states (on-medication and off-medication) and treatment response states were evaluated. RESULTS: According to the International League of Associations for Rheumatology criteria, the subtypes were specified as enthesitis-related arthritis (n=38), oligoarticular (n=37), rheumatoid factor (-) polyarticular (n=17), systemic (n=15), rheumatoid factor (+) polyarticular (n=5), and psoriatic juvenile idiopathic arthritis (n=4). In total, the female/male ratio was found to be 1.5. The mean delay time between the first complaint and the diagnosis was found to be 5.7±5.2 months. The patients with systemic type were diagnosed at the earliest, while the patients with polyarticular and enthesitis-related subtypes were diagnosed at the latest. Thirty-two percent of the patients were treated with methotrexate alone, and 38% were given additional biologic drugs. In both treatment groups, the time to achieve inactive disease was the shortest in the oligoarticular group and the longest in the enthesitis-related arthritis group. In the study period, 38 patients were in remission off-medication (the highest rate (53.3%) was observed in the systemic group) and 71 patients were in remission on-medication (the highest rate (70.2%) was observed in the oligoarticular group). Remission was obtained in 94% of the patients. CONCLUSION: Enthesitis which is the remarkable finding of enthesitis-related arthritis, should not be overlooked in routine physical examination. Awareness of enthesitis can contribute to the prevention of diagnostic delay in children with enthesitis-related arthritis.

Rituximab experience in children with nephrotic syndrome: what have we observed differently.

AIM: We aimed to evaluate the efficacy of rituximab therapy in children with nephrotic syndromes and to share our experiences. MATERIAL AND METHODS: Twelve children with nephrotic syndrome (four with steroid-dependent, eight with steroid-resistant nephrotic syndrome) who were treated with rituximab were retrospectively evaluated in terms of clinical and laboratory data and CD19-20 levels. All patients received rituximab (375 mg/m2) once weekly for 4 weeks. A proteinuria-free period under steroid therapy was not sought prior to initiating rituximab therapy. RESULTS: The overall remission rates in patients with steroid-dependent and steroid-resistant nephrotic syndrome were 100% and 27%. Focal segmental glomerulosclerosis was diagnosed in six patients and the remission rate was 33% in this population. CD19 cell depletion was observed in 10 of the 12 children. Seven of the 10 patients with CD19 depletion achieved remission, whereas the other three had persistent nephrotic proteinuria despite CD19 depletion. Two patients without CD19 depletion never achieved remission. Relapse occurred in three of the seven patients associated with increased CD19. CONCLUSION: We observed that rituximab could be given without waiting for a proteinuria-free period under steroid therapy. Our result suggest that administering four weekly doses of rituximab increases the likelihood of remission, considering the amount of drug lost in the urine of children with nephrotic proteinuria. However, our findings must be confirmed with dose-comparison studies conducted with larger populations and an evaluation of long-term adverse effects. Some patients did not achieve remission despite B cell depletion, which suggests that B cell depletion is necessary but insufficient for remission in nephrotic syndromes.

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.

Membranous nephropathy in a child with crescentic glomerulonephritis: Coincidence or comorbidity?

Rapidly progressive glomerulonephritis (RPGN) is rare syndrome in children, characterized by clinical features of glomerulonephritis and rapid loss of renal function, and is associated with crescentic glomerulonephritis. Primary membranous nephropathy (MN) is an immune-complex-mediated cause of the adult nephrotic syndrome but occurs less frequently in children. RPGN is rarely observed in adults with primary MN. In this article, we report a case of MN, which developed during long-term follow-up of previously treated RPGN. Our case may be the first to demonstrate primary MN and crescentic glomerulonephritis in a child. We would like to underline the importance of not dropping the long-term follow-up of cases with primary RPGN (not accompanied by other glomerulonephritis and vasculitis symptoms) who had improved with treatment.

An Adolescent Girl with a Complaint of Clitoral Swelling.

BACKGROUND: We present the case of an adolescent girl with prominent clitoral swelling as the first symptom when she presented to the emergency department, and who was subsequently diagnosed with nephrotic syndrome. CASE: A 14-year-old adolescent girl was admitted with painless clitoral swelling. She denied recent masturbation, itching, or discharge. She was within the last few days of menstruation. Physical examination revealed clitoral edema without erythema or genital edema. Urine dipstick test and microscopic evaluation revealed protein 2+, blood 3+, abundant erythrocytes and 9-10 leukocytes. A few days later, additional clinical findings, such as pretibial and facial edema, were diagnosed as nephrotic syndrome. SUMMARY AND CONCLUSION: This case is a reminder that clitoral swelling is to be considered a sign in the diagnosis of nephrotic syndrome, even when it occurs alone.