Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study.

BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Evaluation of liver elasticity with shear-wave elastography in juvenile idiopathic arthritis patients receiving methotrexate.

BACKGROUND: Methotrexate (MTX) is the first-choice disease-modifying drug in juvenile idiopathic arthritis (JIA) treatment. Methotrexate is metabolized in the liver and can cause liver toxicity and fibrosis with long-term use. Ultrasound shear wave elastography (SWE) is a non-invasive method and can detect liver fibrosis by evaluating the liver elasticity. The aim of this study was to assess liver stiffness and detect if there is an increase in liver stiffness or fibrosis findings with the non-invasive SWE method in JIA patients under MTX treatment. METHOD: The study included 49 JIA patients under MTX treatment and 48 healthy controls, matched for age and sex with a body mass index below the 95th percentile. The demographic data and clinical characteristics of patients were obtained from medical records. Liver function tests were evaluated, and liver tissue stiffness measurements were performed with SWE. RESULTS: Of the 49 patients, 67.35% were girls and the mean age was 10.69 (±4.33) years. The duration of MTX treatment was 23.00 (1-80) months, and the cumulative dose of MTX was 1,280.867 mg (±934.2) in the patient group. There was no statistically significant difference in liver stiffness between patients receiving MTX and healthy controls (P = 0.313). There was no relationship between MTX duration, cumulative dose, route of administration, and liver stiffness. Only gamma glutamyl transferase values were weakly correlated with liver stiffness (P = 0.029). CONCLUSIONS: We did not detect an increase in liver tissue stiffness in JIA patients using methotrexate in comparison with controls.

Unexpected condition in a rare disease: encephalopathy in early-onset sarcoidosis.

BACKGROUND: Granulomatous autoinflammatory diseases are monogenic syndromes caused by mutations in the region encoding the nucleotide-binding domain of the nucleotide-binding oligomerization domain-containing 2 gene. Blau syndrome and early-onset sarcoidosis are familial and sporadic forms of the same disease and are very rare. Many organ systems may be involved; however, neurologic involvement is infrequent. We reported a case of encephalitis in a 12-year-old girl followed with a diagnosis of early-onset sarcoidosis. CASE: The patient was diagnosed with juvenile idiopathic arthritis at 3 years of age. We considered druginduced sarcoidosis at 6 years of age with granulomatous inflammation of liver and kidney. Small joint involvement and camptodactyly developed during follow-up. M315T mutation was detected in the NOD2 gene supporting the diagnosis of early-onset sarcoidosis. The patient suffered from encephalopathy when she was under methotrexate, infliximab, and systemic steroid treatment at 12 years of age. Cerebrospinal fluid limbic encephalitis antibody panel was negative. CONCLUSION: Encephalopathy is not common in Blau syndrome and early-onset sarcoidosis. The cause of encephalopathy in our patient was interpreted as autoimmune encephalitis.

Erythropoietin Resistance Index and the Affecting Factors in Children with Peritoneal Dialysis.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are used to treat anemia in CKD. Erythropoietin resistance index (ERI) is a useful tool used to evaluate the response to ESAs. In this study, we aimed to evaluate the causes of high ERI in children undergoing peritoneal dialysis (PD). METHOD: Patients who had been on PD for at least 1 year were included in this retrospective study. Demographic characteristics, residual kidney function (RKF), adequacy of dialysis, peritoneal glucose exposure, the number and reason for hospitalization, and medications were recorded. Anemia and laboratory parameters that may affect anemia were noted by taking the average of laboratory values in the last follow-up year (time-averaged). The weekly ESA dose was proportioned to the annual average hemoglobin value and body weight to calculate the ERI in terms of U/kg/week/g/dL. RESULTS: A total of 100 patients were included in the study. The mean ESA dose and ERI value were 119.8 ± 66.22 U/kg/week and 13.01 ± 7.52 U/kg/week/g/dL, respectively. It was determined that the patients <5 years of age have very high ERI value, and these patients need 2 times more ESA than those >10 years of age. Absence of RKF, large number of hospitalization, and ACEI use were also found to affect the ERI value negatively. CONCLUSION: We demonstrate that the most important factor affecting ERI value is young age. We also reveal that absence of RKF, large number of hospitalization, and ACEI use are also important variables affecting the ERI value.

Magnesium levels in children with chronic kidney disease stages 1-3 / Niveles de magnesio en niños con enfermedad renal crónica estadios 1-3

ABSTRACT Objective: The objective of this study was to assess serum and urinary magnesium levels in children who have chronic kidney disease stages 1-3. Methods: Eighty-seven patients who were followed at pediatric nephrology department for chronic kidney disease were included in the study. Age, gender, magnesium, dietary magnesium, and creatinine levels, and fractionated magnesium excretion for all cases were recorded. Patients with chronic kidney disease and control groups were compared in terms of these data. Results: Thirty-nine cases with chronic kidney disease were stage 1, 26 were stage 2, and 22 were stage 3. Average age was 9.9 ± 2.8 years in the control group and 10.2 ± 2.6 years in the chronic kidney disease group. The serum magnesium levels were significantly higher in the stage 3 group than in the control group (P<0.001). Also, in stage 3, fractionated magnesium excretion levels were higher compared to the control group (P<0.001). Conclusion: In chronic kidney disease with advancing renal failure, hypermagnesemia is frequently seen. Serum magnesium levels should be measured periodically in all the children with chronic kidney disease stage 3 to investigate magnesium abnormalities and assess clinical results.

RESUMEN Objetivo: El objetivo de este estudio fue evaluar los niveles de magnesio sérico y urinario en niños con enfermedad renal crónica en estadios 1-3. Material y métodos: Se incluyeron en el estudio 87 pacientes que tuvieron seguimiento en el servicio de nefrología pediátrica por enfermedad renal crónica. Se registraron los siguientes datos: edad, sexo, niveles de magnesio, ingesta de alimentos con magnesio, y creatinina, así como también la excreción fraccionada de magnesio para todos estos casos. Sobre la base de dichos datos, se compararon los pacientes con enfermedad renal crónica y los grupos de control. Resultados: De los 87 casos de enfermedad renal crónica, 39 se hallaban en estadio 1; 26, en estadio 2, y 22, en estadio 3. La edad promedio fue de 9,9 ± 2,8 años en el grupo control y de 10,2 ± 2,6 años en el grupo de enfermedad renal crónica. Los niveles de magnesio en suero fueron significativamente más altos en el grupo del estadio 3 que en el grupo control (p <0,001). Además, en el estadio 3, los niveles de excreción fraccionada de magnesio fueron más altos en comparación con el grupo control (p <0,001). Conclusión: En la enfermedad renal crónica con insuficiencia renal avanzada, se observa con frecuencia una hipermagnesemia. Los niveles séricos de magnesio deben medirse periódicamente en todos los niños con enfermedad renal crónica en estadio 3 para investigar las anomalías del magnesio y evaluar los resultados clínicos.

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.

Blau Syndrome and Early-Onset Sarcoidosis: A Six Case Series and Review of the Literature.

OBJECTIVES: This study aims to discuss the clinical, laboratory and genetic findings, and treatment options for six patients who were diagnosed with Blau syndrome (BS)/early-onset sarcoidosis (EOS). PATIENTS AND METHODS: The study included four patients (2 males,2 females; mean age 7 years; range 4 to 10 years) with EOS and two siblings (1 male, 1 female; mean age 10 years; range, 9 to 11 years) with BS. Age, age of initial symptoms, age of diagnosis; articular involvement, presence of uveitis, dermatitis, or fever, other organ involvement, laboratory findings, results of metabolic tests for mucopolysaccharidosis and mucolipidosis, results of genetic, pathologic, and immunologic tests, radiologic findings to evaluate skeletal dysplasia, and treatment options were collected. RESULTS: The median age at diagnosis of all patients was 6 years (range, 1 to 10 years). Five patients had camptodactyly and bilateral boggy synovitis in the wrists and ankles, one had granulomatous inflammatory changes in the liver and kidney biopsy, and one had attacks of fever and granulomatous dermatitis. None had uveitis. The detected mutations in nucleotide-binding oligomerization domain containing 2 (NOD2) were P268S (rs2066842), M513T (rs104895473), R702W (rs2066844), V955I (rs5743291), H343Y (rs199858111), and M491L (16:50745293). The treatments of patients included corticosteroids, non-steroid anti-inflammatory drugs, methotrexate, infliximab, adalimumab, anakinra, and canacinumab. CONCLUSION: Camptodactyly and boggy synovitis are important signs of BS/EOS. Methotrexate and tumor necrosis factor blockers are more effective in patients with predominantly articular symptoms. In patients 5 and 6 and their mother, we determined a novel M491L mutation in the NOD2 gene. Currently, this work is in progress towards identifying the pathogenesis and treatment options for this disease.

Evaluation of the children with C3 glomerulopathy.

C3 glomerulopathy (C3G) is a clinical spectrum that presents with a variety of symptoms, ranging from a mild disease with asymptomatic microhematuria and/or proteinuria to severe disease with nephritic or nephrotic syndrome and renal impairment. Herein, we aim to document the clinical and laboratory findings, response to immunosuppressive and supportive treatment and prognosis of the children with C3G. We retrospectively reviewed the medical records of patients diagnosed with membranoproliferative glomerulonephritis (MPGN). Kidney biopsy materials were reexamined for the diagnosis of C3G. The inclusion criteria for C3G are the dominant C3 staining with or without scanty immunoglobulins (Ig) deposition on immuno- fluorescence (IF) and MPGN patterns on light microscope. Twelve of 69 patients with MPGN were included in the study based on the definition criteria of C3G. Ten of them had only C3 staining and the rest of the patients had both C3 staining and a small amount of IgG/M staining on IF microscopy. One patient was on remission with only ACEI. The rest of the patients used immunosuppressive treatment and two of them needed eculizumab therapy. One of them did not respond to the treatment of eculizumab and progressed to end-stage renal failure. C3G is a disease characterized by a heterogeneous clinical presentation and outcome. Because of this broad spectrum of disease, treatment may vary widely. We think that complement-targeting therapy with eculizumab should be an alternative option for refractory cases, especially in the early stage of disease, if they did not respond to immunosuppressive treatment.

Patient Outcomes of Henoch-Schönlein Purpura Nephritis According to the New Semiquantitative Classification.

Background: A new semiquantitative classification (SQC) for pediatric Henoch-Schönlein nephritis (HSN) was defined recently. The outcomes of pediatric HSN patients are reevaluated according to the new classification. Methods: Primary kidney biopsies from 80 HSN patients were scored using the new SQC. The International Study of Kidney Disease in Children (ISKDC) and SQC classifications were compared in terms of the patient outcomes. Outcomes were defined as: Outcome A (n = 44) patients with no sign of renal disease, Outcome B (n = 32) patients with minor urinary abnormalities, and Outcome C (n = 4) patients with active renal disease. Results: The patients with outcome C had significantly higher biopsy scores and chronicity indices than patients in group A. There was no significant difference in areas under the curve between total biopsy SQC scores and ISKDC findings. Conclusions: Our results suggest that the modified SQC is not more sensitive than ISKDC classification for predicting the outcome in HSN cases.

Evaluation of factors affecting the duration of disease-modifying anti-rheumatic drugs application in patients with enthesitis-related arthritis.

OBJECTIVE: Treatments for enthesitis-related arthritis (ERA) consist of a mono- or combination therapy with non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs (DMARDs), and biological agents, and they are primarily based on adult studies and studies on other forms of juvenile idiopathic arthritis, depending on whether there is axial or peripheral involvement. We use DMARDs frequently in our daily practice, even in patients with axial involvement. The main reason for this is that the health insurance system in Turkey does not allow the use of Tumor Negrosis Factor (TNF) blockers as the first line of treatment. The aim of this study is to evaluate the factors affecting the duration of DMARDs application in patients with ERA. METHODS: Fifty-two patients with ERA were accepted in this retrospective cohort study. These patients did not have an inflammatory bowel disease, reactive arthritis or undifferentiated arthritis, psoriasis, and familial Mediterranean fever. Demographic characteristics, medical history, the initial and follow-up physical examination, initial Juvenile Spondyloarthritis Disease Activity Index (JSpADA), initial laboratory tests, radiographic tests, Juvenile Arthritis Damage Index-articulary (JADI-A) and extra-articulary (JADI-E) on the last admission, and data on medical treatments were recorded from the registered data. The univariate Cox proportional hazards regression analyses was used to determine factors affecting the non-response time of ERA patients to DMARDs before the biological treatment was started. RESULTS: Twenty-seven patients (52%) achieved remission with DMARDs, while 25 (48%) patients did not. The age at diagnosis (HR=1.12; p=0.247); gender (HR=2.53; p=0.210); family history of ankylosing spondylitis (HR=1.17; p=0.730); inflammatory back pain (HR=0.57; p=0.175); the shoulder (HR=0.75 p=0.706), hip (HR=0.45; p=0.129), and small-joint involvement (HR=1.53; p=0.439); sacroiliitis with physical examination (HR=0.90; p=0.814) and magnetic resonance imaging (MRI) (HR=2.84; p=0.110); enthesitis (HR=0.83; p=0.670); presence of uveitis (HR=2.04; p=0.342); presence of HLA-B27 (HR=1.39; p=0.524); initial high acute phase reactants levels(HR=1.89; p=0.183); initial JSpADA score (HR=0.98; p=0.944); and last JADI-A (HR=1.41; p=0.060) score did not affect the duration of DMARDs treatment before switching to biological treatments. CONCLUSION: In our study, the absence of factors affecting the duration of DMARDs application in patients with ERA showed that DMARDs may still be applied as the first line of treatment.

Clinical and histopathological prognostic factors affecting the renal outcomes in childhood ANCA-associated vasculitis.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are very rare in childhood with an increased risk of morbidity and mortality. We aimed to evaluate renal prognostic factors in childhood AAV from the perspective of ANCA serotype, histopathological classification, and five-factor score (FFS). METHODS: Pediatric AAV patients from 11 referral centers in Turkey had been included to the study. The demographics, clinical findings, AAV subtypes, outcomes, and FFS were evaluated retrospectively. Kidney biopsies were classified histopathologically. RESULTS: Totally, 39 patients were enrolled in the study. Among all patients, 74.4% had renal involvement, 56.4% ear-throat-nose involvement, and 51.3% had musculoskeletal involvement. Proteinase 3 (PR3)-ANCA was positive in 48.7%, and myeloperoxidase (MPO)-ANCA was positive in 30.8%. 69.2% of patients had impaired renal function, and 28.2% had progressed to end-stage renal disease (ESRD) during the follow-up. At the time of diagnosis, FFS was ≥ 2 in 53.8%. The most common histopathologic classifications were as follows: crescentic type in 40.7% and sclerotic type in 25.9%. Gastrointestinal and renal involvement, MPO-ANCA positivity, serum creatinine levels, and impaired renal function during the follow-up were significantly higher in patients with FFS ≥ 2, compared to patients with FFS < 2. Patients with FFS ≥ 2 had more common crescentic, mixed and sclerotic histopathologic findings in biopsies. By logistic regression analysis forward method, the strongest single-risk factor among all the parameters was the initial level of creatinine in patients with ESRD, compared to the other patients (p = 0,007). CONCLUSIONS: Evaluation of the FFS, ANCA serology, and the creatinine levels may help to predict renal prognosis.

Epidermolysis bullosa complicated with nephrotic syndrome due to AA amyloidosis: A case report and brief review of literature.

Epidermolysis bullosa (EB) encompasses a clinically and genetically heterogeneous group of rare inherited diseases characterized by marked mechanical fragility of epithelial tissues with blistering and erosions following minor trauma. Amyloidosis is one of the most important complications of EB mostly seen in recessive dystrophic EB (RDEB) patients and can involve the kidney, bowel, liver, and also respiratory system. Herein, we present a child, who is probably the youngest case of genetically diagnosed RDEB, complicated with amyloidosis reported in literature. A 6-year-old boy who was diagnosed with EB was referred to our center with nephrotic-range proteinuria and hypoalbuminemia. He had homozygous mutation in COL7A1 gene. Kidney biopsy was remarkable for amyloidosis with positive Congo red staining, and amyloid fibrils were seen on electron microscopy. Although he did not have any symptoms of autoimmune diseases and mutation in the MEFV gene, he was given colchicine because of positive family history for familial Mediterranean fever and amyloidosis.

Increased circulating endothelial microparticles in children with FMF.

OBJECTIVE: Endothelial microparticles (EMPs) are considered as markers of endothelial dysfunction. In this study, we aimed to examine whether there is endothelial dysfunction in children with familial Mediterranean fever (FMF), hypothesizing that endothelial dysfunction would be present especially with acute-phase response in the active period of the disease. METHODS: This cross-sectional study included 65 FMF patients (41 attack free, 24 attack period) and 35 healthy controls. Circulating EMPs, serum amyloid A (SAA), and other inflammation markers were measured in all groups. Circulating EMPs were measured using flow cytometry. Study groups were compared for circulating EMP and inflammatory markers. The relationship between EMPs and the activation of the disease was evaluated. RESULTS: The levels of CD144+ and CD146+ EMPs in the FMF attack period group were significantly higher than those of the control group (p < 0.05). The levels of inflammation markers in the attack period group were significantly higher than those of the control and attack-free groups (p < 0.05). In the FMF attack group, the CD144+ and CD146+ EMP were significantly correlated with CRP. CONCLUSIONS: Our results suggest that endothelial damage is present especially in the active period of the disease in children with FMF. The endothelial dysfunction becomes an overt parallel with inflammation.

Voiding cystourethrogram: How much should we be selective?

OBJECTIVE: In this study, we examined the patients' characteristics, who underwent voiding cystourethrography (VCUG), in order to determine any selectivity for indication of this invasive method. MATERIAL AND METHODS: After exclusion of indications of neurogenic bladder or antenatal hydronephrosis and control VCUGs, 159 VCUGs performed in our clinic within one year were evaluated. Patients are divided into three groups accoding to age. Clinical characteristic and findings of renal ultrasonography (US) and renal scintigraphy were examined. RESULTS: Vesicoureteral reflux (VUR) was detected in 61 (38.3%) of 159 patients who underwent cystourethrographic examinations, in 45.8% of the patients with a history of recurrent urinary tract infection (UTI), in 22.0% of the patients with pathological urinary system US without history of recurrent UTI. High-grade reflux rate was significantly more frequent in renal units with pathological US findings. Severe scar was significantly more frequent in renal units with high-grade reflux when compared to renal units without reflux and those with low-grade reflux. Predictive values of recurrent UTI, scarring status and pathological US for VUR were separately analyzed and seen that likelihood of indicating VUR was increased when all 3 risk factors were assessed together. CONCLUSION: Vesicoureteral reflux is a problem in which diagnostic process and management strategy should have to be considered in individualized manner for each patient. Before prescribing invasive VCUG, imaging urinary system by US and scintigraphy and determining whether there is recurrent UTI will improve selectivity and success of VCUG.

Neurological Manifestations in Familial Mediterranean Fever: Results of 22 Children from a Reference Center in Kayseri, an Urban Area in Central Anatolia, Turkey.

Background Familial Mediterranean fever (FMF) is an inherited inflammatory disorder characterized by attacks of fever with polyserositis. Objective The purpose of this study was to evaluate pediatric patients with FMF who had central nervous system (CNS) findings. Materials and Methods Our medical records database for 2003 to 2014 was screened retrospectively. In total, 104 patients with FMF were identified, 22 of whom had undergone neurological examination for CNS symptoms. Results Neurological findings included headache in 16 patients (72.7%), epilepsy in 6 patients (27.3%), pseudotumor cerebri in 2 patients (9.1%), tremor in 2 patients (9.1%), and multiple sclerosis in 1 patient (4.5%). The most common MEFV gene mutation was homozygous M694V (40.9%). Conclusions Patients with FMF can present with various CNS manifestations. Further studies that include large populations are needed to elucidate the neurological manifestations of FMF.

Compare the effects of intravenous and intraperitoneal mesenchymal stem cell transplantation on ultrafiltration failure in a rat model of chronic peritoneal dialysis.

AIM: The purpose of this study was to compare the possible healing effects of intraperitoneal (IP) and intravenous (IV) mesenchymal stem cell (MSC) transplantation on ultrafiltration failure (UFF) in a chronic rat model of peritoneal dialysis (PD). METHODS: Rats were initially divided into two groups. The UFF-group received once-daily IP injections of 20 mL of 3.86% glucose PD solution for six weeks to stimulate the development of UFF, and a control group received no injections. The UFF group was sub-divided into four groups: an UFF-C group, a MSC-IP group, a MSC-IV group and a placebo (P) group. Peritoneal equilibration tests (PETs) and peritoneal biopsies were performed in the control and UFF-C groups. MSCs were administered by IP injection in the MSC-IP group and by IV injection in the MSC-IV group. The P group received IP injection of placebo. PETs and peritoneal biopsies were performed in the MSC-IP, MSC-IV and P groups at the three weeks after receiving MSCs or placebo. RESULTS: When compared with the control group, ultrafiltration capacity significantly decreased, and the submesothelial thickness increased in the UFF-C and P group, but there were no differences between the control and MSC-IP and MSC-IV groups. The rate of glucose transport was high in the UFF-C and P group compared with the control group, and D/PCr rates in the UFF-C and P group were lower than in the control group. However, D/D0glucose was higher and D/PCr was lower in the MSC-IP group than in the UFF-C and P groups, but D/D0glucose rate of MSC-IV group similar to UFF-C and P groups and there was no difference between MSC-IV group and the other groups in terms of D/PCr rates. The MSC-IP, MSC-IV and P groups had significantly decreased tumor necrosis factor α concentrations compared with the UFF-C group. MSC-IP group had lower levels of TGF-ß1 compared with the P group; MSC-IP group had also lower levels of interleukin-6 compared with UFF-C group. CONCLUSION: The UFF group had a high permeability UFF. These results showed that IV and IP MSC transplantation exerted positive effects on UFF in a chronic rat model of PD. However, healing effect of small solute transport in MSC-IP group was better than MSC-IV group. IP MSC transplantation may be more effective than IV MSC transplantation for the renewal of the peritoneum in chronic PD patients with UFF.

Neurofibromas of the bladder in a child with neurofibromatosis type 1 causing chronic renal disease.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant inherited disorder and its prominent feature is the neurofibroma and renal involvement includes renal artery stenosis and renal artery aneurysms causing renovascular hypertension. The genitourinary tract may be rarely involved, leading to urinary symptoms of obstruction and hydronephrosis. Herein, we report a 12-year-old boy with chronic renal failure associated with neurofibromas of the bladder, which leads to urinary obstruction.

Mesenchymal stem cell transplantation may provide a new therapy for ultrafiltration failure in chronic peritoneal dialysis.

BACKGROUND: The purpose of this study was to investigate possible healing effects of intraperitoneal (IP) mesenchymal stem cell (MSC) transplantation on ultrafiltration failure (UFF) in a chronic rat model of peritoneal dialysis (PD). METHODS: Rats were initially divided into two groups. The APUF group received once-daily IP injections of 20 mL of 3.86% glucose PD solution for 6 weeks to stimulate the development of UFF and a control group received noinjections. The PUF group was sub-divided into three groups: a PUF-C group, an MSC group and a Placebo (P) group. Peritoneal equilibration tests (PETs) and peritoneal biopsies were performed in the control and PUF-C groups. MSCs were administered by IP injection in the MSC group and the PUF-C and P groups received IP injection of placebo. PETs and peritoneal biopsies were performed in the MSC and P groups at the first [P-1 (and MSC-1 groups] and second [P-2 and MSC-2 groups] week after receiving MSCs or placebo. RESULTS: When compared with the control group, ultrafiltration capacity significantly decreased and the submesothelial thickness increased in the PUF-C and P groups (P-1, P-2) (P < 0.05), but there were no differences between the control and MSC groups (MSC-1, MSC-2). The rate of glucose transport was high in the PUF-C and P-2 groups compared with the control group, and D/PCr rates in the PUF-C and P-2 groups were lower than in the control group (P < 0.05). However, D/D0(glucose) was higher and D/P(Cr)was lower in the MSC-2 group than in the PUF-C and P-2 groups (P < 0.05). Transforming growth factor-ß (TGF-ß) levels were lower in the MSC groups than in the P and PUF-C groups (P < 0.05). CONCLUSION: The PUF-C group had a high permeability UFF. These results showed that MSC transplantation exerted positive effects on UFF in a chronic rat model of PD. MSC transplantation may provide new options for the renewal of the peritoneum in chronic PD patients with UFF.

Amyloidosis in a child with hyperimmunoglobulinemia D syndrome.

Hereditary periodic fever syndromes are a group of genetic diseases clinically characterized by recurrent febrile attacks. Patients are at variable risks for the development of systemic reactive (AA) amyloidosis, leading to the nephrotic syndrome and kidney failure. We present the first report of the occurrence of renal AA amyloidosis causing severe nephrotic syndrome in a Turkish child affected with hyperimmunoglobulinemia D syndrome.

Modulation of inflammation by mesenchymal stem cell transplantation in peritoneal dialysis in rats.

AIM: The purpose of this study was to determine the effect of mesenchymal stem cell (MSC) transplantation on the peritoneal morphology and inflammation markers in rat models of peritoneal dialysis (PD). MATERIALS AND METHODS: Wistar albino rats were divided into two groups: control (C) (n = 8) and experimental groups (n = 50). PD solution was given to the experimental group during 6 weeks. Then, experimental group was divided into three groups as PD, MSC, and placebo (P) groups. MSC group was treated with MSC (1.5 × 10(6) cells/kg) and P group was treated with phosphate buffer solution via intraperitoneal injection. Evaluation was performed to C and PD groups at the end of 6 weeks and to MSC and P groups at second and third week of the treatment (MSC-2, P-2, MSC-3, and P-3 groups). RESULTS: The submesothelial area was significantly thickened in PD and P groups compared to C and MSC groups. Peritoneal fibrosis was seen in P-3 group but not in MSC group. There were no significant differences between the MSC-3 and C groups according to morphological findings. Levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly increased in MSC-2 group compared to the other groups (p-values ranged from 0.0001 to 0.04). TNF-α and IL-6 levels in MSC-3 and P-3 groups were lower than PD and C groups (p < 0.0001 for TNF-α and p = 0.0001-0.002 for IL-6). CONCLUSION: Giving MSC may protect the peritoneal membrane from the deleterious effect of PD and extend the life of the peritoneal membrane. Our study is the first on this issue and more detailed studies are needed.