Publications by authors named "Sevgi Mir"

97 Publications

Interleukin-8 is increased in chronic kidney disease in children, but not related to cardiovascular disease.

J Bras Nefrol 2021 Mar 12. Epub 2021 Mar 12.

Ege University Faculty of Medicine, Department of Pediatric Nephrology, İzmir, Turkey.

Introduction: In this study, we aimed to detect the cytokine that is involved in the early stage of chronic kidney disease and associated with cardiovascular disease.

Methods: We included 50 patients who were diagnosed with predialytic chronic kidney disease and 30 healthy pediatric patients in Ege University Medical Faculty Pediatric Clinic, İzmir/Turkey. Interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-13 (IL-13), and transforming grow factor-β1 (TGF-β1) levels (pg/mL) were measured by ELISA. Carotid-femoral pulse wave velocity (PWV), augmentation index (Aix), carotid intima media thickness (cIMT), and left ventricular mass index (LVMI) were evaluated as markers of cardiovascular disease. The presence of a cardiovascular disease marker was defined as an abnormality in any of the parameters (cIMT, PWV, Aix, and left ventricular mass index (SVKI)). The patient group was divided into two groups as with and without cardiovascular disease.

Results: Mean Aix and PWV values were higher in CKD patients than controls (Aix: CKD 32.8±11.11%, healthy subjects: 6.74±6.58%, PWV CKD: 7.31±4.34m/s, healthy subjects: 3.42±3.01m/s, respectively; p=0.02, p=0.03). The serum IL-8 levels of CKD were significantly higher than of healthy subjects 568.48±487.35pg/mL, 33.67±47.47pg/mL, respectively (p<0.001). There was no statistically significant difference between IL-8, IL-10, IL-13, TGF-1, in CKD patients with and without cardiovascular disease (p> 0.05).

Discussion: IL-8 is the sole cytokine that increases in pediatric patients with chronic kidney disease among other cytokines (IL-10, IL-13 and TGF-β1). However, we did not show that IL-8 is related to the presence of cardiovascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/2175-8239-JBN-2020-0225DOI Listing
March 2021

Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3-5.

Nephrol Dial Transplant 2021 Feb;36(3):442-451

Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School Children's Hospital, Hannover, Germany.

Background: Uraemic cardiac remodelling is associated with vitamin D and Klotho deficiency, elevated fibroblast growth factor 23 (FGF23) and activation of the renin-angiotensin system (RAS). The cardioprotective properties of active vitamin D analogues in this setting are unclear.

Methods: In rats with 5/6 nephrectomy (5/6Nx) treated with calcitriol, the cardiac phenotype and local RAS activation were investigated compared with controls. A nested case-control study was performed within the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, including children with chronic kidney disease (CKD) Stages 3-5 [estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2] treated with and without active vitamin D. Echocardiograms, plasma FGF23 and soluble Klotho (sKlotho) were assessed at baseline and after 9 months.

Results: In rats with 5/6Nx, left ventricular (LV) hypertrophy, LV fibrosis and upregulated cardiac RAS were dose-dependently attenuated by calcitriol. Calcitriol further stimulated FGF23 synthesis in bone but not in the heart, and normalized suppressed renal Klotho expression. In the 4C study cohort, treatment over a mean period of 9 months with active vitamin D was associated with increased FGF23 and phosphate and decreased sKlotho and eGFR compared with vitamin D naïve controls, whereas LV mass index did not differ between groups.

Conclusions: Active vitamin D ameliorates cardiac remodelling and normalizes renal Klotho expression in 5/6Nx rats but does not improve the cardiac phenotype in children with CKD Stages 3-5. This discrepancy may be due to further enhancement of circulating FGF23 and faster progression of CKD associated with reduced sKlotho and higher serum phosphate in vitamin D-treated patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfaa227DOI Listing
February 2021

Genetics and outcome of atypical hemolytic-uremic syndrome in Turkish children: a retrospective study between 2010 and 2017, a single-center experience.

Iran J Kidney Dis 2019 09;13(5):316-321

.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is associated with mutations or antibodies that affect the regulation of the alternative complement pathway. In the recent years several studies have been published describing these mutations. In this study, the initial clinical findings, treatments and long-term follow-up results of 19 patients who were hospitalized with the diagnosis of aHUS were presented.

Materials And Methods: Nineteen patients who were diagnosed as aHUS were enrolled from January 2010 to March 2017. Initial clinical signs and clinical follow-up of patients with aHUS were evaluated. Disease causing complement factor H (CFH) mutations were determined.  Results. CFH mutations were detected in 5 of 19 aHUS cases. Of these, one was novel and 4 were previously reported. We reported here the clinical course of aHUS patients with CFH mutations (p.Glu936Asp, Val 1197Ala) and a novel mutation (Glu927Lys) which caused  previously defined aHUS. Two of the CFH mutation cases developed end stage kidney disease that required hemodialysis, 1 case developed chronic kidney disease. Two cases were in remission, one of them with supportive therapy and the other case was in remission with eculizumab treatment.

Conclusions: Morbidity rate is higher in children with aHUS. The renal prognosis and morbidity rate is higher in children with CFH mutations than other children with aHUS. Poor prognosis in aHUS children with CFH mutation depends on the genetic background.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2019

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

Saudi J Kidney Dis Transpl 2019 Sep-Oct;30(5):1156-1160

Department of Pediatrics, Pediatric Nephrology Units, Faculty of Medicine, Ege University, Izmir, Turkey.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1319-2442.270273DOI Listing
April 2020

Determinants of Statural Growth in European Children With Chronic Kidney Disease: Findings From the Cardiovascular Comorbidity in Children With Chronic Kidney Disease (4C) Study.

Front Pediatr 2019 5;7:278. Epub 2019 Jul 5.

Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.

Failure of statural growth is one of the major long-term sequelae of chronic kidney disease (CKD) in children. In recent years effective therapeutic strategies have become available that lead to evidence based practice recommendations. To assess the current growth performance of European children and adolescents with CKD, we analyzed a cohort of 594 patients from 12 European countries who were followed prospectively for up to 6 years in the 4C Study. While all patients were on conservative treatment with a mean estimated glomerular filtration rate of 28 ml/min/1.73 m at study entry, 130 children commenced dialysis during the observation period. At time of enrolment the mean height standard deviation score (SDS) was -1.57; 36% of patients had a height below the third percentile. The prevalence of growth failure varied between countries from 7 to 44% Whereas patients on conservative treatment showed stable growth, height SDS gradually declined on those on dialysis. Parental height, pubertal status and treatment with recombinant growth hormone (GH) were positively, and the diagnosis of syndromic disease and CKD stage were negatively associated with height SDS during the observation period. Unexpectedly, higher body mass index (BMI) SDS was associated with lower height SDS both at enrolment and during follow up. Renal anemia, metabolic acidosis, and hyperparathyroidism were mostly mild and not predictive of growth rates by multivariable analysis. GH therapy was applied in only 15% of growth retarded patients with large variation between countries. When adjusting for all significant covariates listed above, the country of residence remained a highly significant predictor of overall growth performance. In conclusion, growth failure remains common in European children with CKD, despite improved general management of CKD complications. The widespread underutilization of GH, an approved efficacious therapy for CKD-associated growth failure, deserves further exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2019.00278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625460PMC
July 2019

Acute dialysis in children: results of a European survey.

J Nephrol 2019 Jun 4;32(3):445-451. Epub 2019 Apr 4.

Nephrology and Dialysis Unit, Pediatric Subspecialties Department, Institute for Scientific Research, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.

The number of children with acute kidney injury (AKI) requiring dialysis is increasing. To date, systematic analysis has been largely limited to critically ill children treated with continuous renal replacement therapy (CRRT). We conducted a survey among 35 European Pediatric Nephrology Centers to investigate dialysis practices in European children with AKI. Altogether, the centers perform dialysis in more than 900 pediatric patients with AKI per year. PD and CRRT are the most frequently used dialysis modalities, accounting for 39.4% and 38.2% of treatments, followed by intermittent HD (22.4%). In units treating more than 25 cases per year and in those with cardiothoracic surgery programs, PD is the most commonly chosen dialysis modality. Also, nearly one quarter of centers, in countries with a gross domestic product below $35,000/year, do not utilize CRRT at all. Dialysis nurses are exclusively in charge of CRRT management in 45% of the cases and pediatric intensive care nurses in 25%, while shared management is practiced in 30%. In conclusion, this survey indicates that the choice of treatment modalities for dialysis in children with AKI in Europe is affected by the underlying ethiology of the disease, organization/set-up of centers and socioeconomic conditions. PD is utilized as often as CRRT, and also intermittent HD is a commonly applied treatment option. A prospective European AKI registry is planned to provide further insights on the epidemiology, management and outcomes of dialysis in pediatric AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-019-00606-1DOI Listing
June 2019

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study.

J Am Soc Nephrol 2019 04 7;30(4):678-691. Epub 2019 Mar 7.

Nephrology Unit, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.

Background: Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce.

Methods: The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score.

Results: We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher 2-microglobulin. The HDF cohort had lower 2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time.

Conclusions: HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2018100990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442347PMC
April 2019

Association of Vitamin D Deficiency with Increased Pulse Wave Velocity and Augmentation Index in Children With Chronic Kidney Disease.

Iran J Kidney Dis 2018 Oct;12(5):275-280

Ege University Faculty of Medicine, Department of Pediatric Nephrology, ?zmir, Turkey.

Introduction: It is known that in children with chronic kidney disease (CKD), cardiovascular damage starts in the form of arterial stiffness. There are risk factors other than the traditional ones such as arterial stiffness hypertension, obesity, hypercholesterolemia, and insulin resistance. Vitamin D deficiency is rather common in CKD, and it was introduced as a risk factor for atherosclerosis; however, its relationship with arterial stiffness is not known completely. The purpose of this study was to research the relationship between 25-hydroxyvitamin D levels and arterial stiffness.

Materials And Methods: Arterial stiffness was evaluated by measuring augmentation index (AI) and pulse wave velocity (PWV) from the radial and carotid arteries with a Vicorder. The 25-hydroxyvitamin D levels were measured by an immunoassay method.

Results: In the 81 CKD patients (mean age, 13.21 ± 6.02 years; mean body mass index, 19.42 ± 5.12 kg/m2; and 56.8% male), the mean vitamin D level was 60.71 ± 39.52 ng/mL, the mean AI was 7.93 ± 7.77%, and the mean PWV was 9.79 ± 4.36 m/s. Serum levels of 25-hydroxyvitamin D was correlated with AI (r = -0.482, P = 0.001) and PWV (r = -0.57, P = .001).

Conclusions: In this study, it was proven that vitamin D deficiency in children was related to nondiabetic and nondialysis CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2018

Effect of haemodiafiltration vs conventional haemodialysis on growth and cardiovascular outcomes in children - the HDF, heart and height (3H) study.

BMC Nephrol 2018 08 10;19(1):199. Epub 2018 Aug 10.

Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.

Background: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population.

Methods: 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38).

Discussion: This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD.

Trial Registration: ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the 14 Feb 2014.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-018-0998-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086045PMC
August 2018

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

J Pediatr 2018 08 9;199:22-28.e6. Epub 2018 May 9.

Department of Pediatrics, University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine, University Hospital of Cologne, Cologne, Germany.

Objective: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis.

Study Design: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life.

Results: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys.

Conclusions: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2018.03.052DOI Listing
August 2018

Urine Flow Cytometry in the Diagnosis of Urinary Tract Infection.

Indian J Pediatr 2018 Nov 26;85(11):995-999. Epub 2018 Apr 26.

Department of Pediatric Nephrology, Ege University Faculty of Medicine, 3500, İzmir, Turkey.

Objectives: To determine the cut-off value of bacteria with urine flow cytometer in diagnosing urinary tract infection.

Methods: From a total of 546 patients admitted to the hospital with urinary tract infection (UTI), two urine samples were obtained for each patient. Urine samples in sterile containers were divided into two; first for urine culture and second for simultaneous measurement with UF-1000i flow cytometry device. The presence of a single type of bacteria over 10 CFU/mL in urine culture was accepted as UTI.

Results: Of 546 patients, 210 (38.5%) were boys and 336 (61.5%) were girls. There was no growth in 489 (89.5%) of the urine specimens and 57 (10.4%) samples showed growth (>10 CFU/ml). A threshold of 10 bacteria/μL in flow cytometry (sensitivity = 100%) showed the best compatibility with culture. Diagnostic values in terms of sensitivity (100%), specificity (43.5%), negative predictive value (100%) and positive predictive value (17.7%) were satisfactory.

Conclusions: The UF-1000i flow cytometer can give results quickly and exclude UTI using the determined number of cut-off bacteria at low cost. Thus, if Sysmex UF-1000i is used, quick and accurate results can be obtained and unnecessary laboratory tests can be prevented. Also, patient convenience can be increased.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12098-018-2689-xDOI Listing
November 2018

Comparing different estimated glomerular filtration rate equations in assessing glomerular function in children based on creatinine and cystatin C.

J Clin Lab Anal 2018 Jul 27;32(6):e22413. Epub 2018 Feb 27.

Faculty of Medicine, Department of Biostatistics and Medical Informatics, Gülden Hakverdi Ege University, Izmir, Turkey.

Background: Glomerular filtration rate (GFR) is the best marker used to assess renal function. Estimated GFR (eGFR) equations have been developed, and the ideal formula is still under discussion. We wanted to find the most practical and reliable GFR in eGFR formulas. We compared serum creatinine (Scr)- and cystatin C (cysC)-based eGFR formulas in the literature. We also aimed to determine the suitability and the reliability of cysC for practical use in determining GFR in children.

Methods: We have enrolled 238 children in the study. Measurement of 24-hour creatinine clearance was compared with eGFR equations which are based on Scr, cysC, and creatinine plus cysC.

Results: Of the patients (n = 238), 117 were males (49.2%), and 121 (50.8%) were females with a median age of 9.0 years. The areas under the ROC curves of Counahan-Barratt and Bedside Schwartz were equal and 0.89 (with a 95% CI 0.80-0.97). The areas under the ROC curves were not significantly different in all cystatin C-based eGFR equations. The highest AUC values for differentiating normal vs abnormal renal functions according to CrCl were for the CKiD-cysC and CKiD-Scr-cysC equations.

Conclusions: In our study, compared with creatinine-based ones, the cystatin C-based formulas did not show much superiority in predicting eGFR. Still, we think Bedside Schwartz is a good formula to provide ease of use because, in this equation, the constant k is same for all age groups. However, the most valuable equations in determining chronic kidney disease are the CKiD-cysC and CKiD-Scr-cysC equations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.22413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817194PMC
July 2018

A novel mutation of interleukin-1 receptor antagonist (IL1RN) in a DIRA patient from Turkey: Diagnosis and treatment.

Turk J Pediatr 2018 ;60(5):588-592

Departments of Pediatric Rheumatology, Ege University Faculty of Medicine, Izmir, Turkey.

Sözeri B, Gerçeker-Türk B, Yıldız-Atıkan B, Mir S, Berdeli A. A novel mutation of interleukin-1 receptor antagonist (IL1RN) in a DIRA patient from Turkey: Diagnosis and treatment. Turk J Pediatr 2018; 60: 588-592. Autoinflammatory diseases can cause severe inflammation in bone and skin such as neonatal-onset multisystem inflammatory disease (NOMID), Majeed syndrome, interleukin-36 receptor antagonist deficiency (DITRA) and deficiency of interleukin-1 (IL-1) receptor antagonist (DIRA) syndrome. Here we report a five-year old boy who was admitted to the hospital with pustular skin lesions and fever in the first month of his life. Molecular analysis of IL1RN gene revealed a single homozygous C nucleotide deletion at nucleotide position 396 (p.Thr133Profs*118). The novel p.Thr133Profs*118 mutation found in our study caused frameshift mutation and as a result, the respective protein is most likely non-functional. The patient, who received a variety of treatments for various preliminary diagnoses until the final diagnosis (DIRA), was treated with recombinant IL-1Ra, anakinra, and experienced significant clinical improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.24953/turkjped.2018.05.020DOI Listing
June 2019

Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome.

J Clin Invest 2017 12 23;127(12):4257-4269. Epub 2017 Oct 23.

Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted colocalization with F-actin, thereby leading to impaired actin binding and severing. Additionally, AVIL colocalized and interacted with the phospholipase enzyme PLCE1 and with the ARP2/3 actin-modulating complex. Knockdown of AVIL in human podocytes reduced actin stress fibers at the cell periphery, prevented recruitment of PLCE1 to the ARP3-rich lamellipodia, blocked EGF-induced generation of diacylglycerol (DAG) by PLCE1, and attenuated the podocyte migration rate (PMR). These effects were reversed by overexpression of WT AVIL but not by overexpression of any of the 3 patient-derived AVIL mutants. The PMR was increased by overexpression of WT Avil or PLCE1, or by EGF stimulation; however, this increased PMR was ameliorated by inhibition of the ARP2/3 complex, indicating that ARP-dependent lamellipodia formation occurs downstream of AVIL and PLCE1 function. Together, these results delineate a comprehensive pathogenic axis of SRNS that integrates loss of AVIL function with alterations in the action of PLCE1, an established SRNS protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI94138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707164PMC
December 2017

Relationship of insulin resistance to vitamin d status in children with nondiabetic chronic kidney disease.

Saudi J Kidney Dis Transpl 2017 Sep-Oct;28(5):1078-1084

Department of Pediatric Nephrology, Ege University Medical Faculty, Izmir, Turkey.

Insulin Resistance is common in patients with mild-to-moderate stage chronic kidney disease (CKD), even when the glomerular filtration rate is within the normal range. This study aimed to investigate the association of IR and 25-hydroxyvitamin D levels. In this study, we evaluated the frequency of IR in predialysis patients and the association with 25-hydroxyvitamin (OH)D levels. A total of 32 non-diabetic patients with predialysis were included in the study. Homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated to show presence of IR. Data were analyzed with the Statistical Package for the Social Sciences (SPSS) program version 13.0 (SPSS Inc, Chicago, Ill, USA) using the Chi-square, Student t-test, and logistic regression analysis. Nineteen of 32 subjects (59.4%) were detected to have IR. There was no consistent relationship was detected between IR and glomerular filtration rate, body mass index, and blood pressure in chronic kidney disease (CKD). However; significant difference was detected in 25(OH)D levels with IR in CKD (P = 0.49). The regression analysis showed that 25(OH)D was an independent predictor of IR with an odds ratio of 1.2. In our study, we demonstrated that IR was high in different stages of CKD. Insulin-resistance in non-diabetic CKD was correlated with 25(OH)D levels. 25(OH) vitamin D levels can play a significant role in the development of IR in pediatric patients with CKD. This is important for the early detection and intervention of vitamin D deficiency thereby preventing potentially future complications related to IR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1319-2442.215144DOI Listing
August 2019

Early Effects of Renal Replacement Therapy on Cardiovascular Comorbidity in Children With End-Stage Kidney Disease: Findings From the 4C-T Study.

Transplantation 2018 03;102(3):484-492

Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany.

Background: The early impact of renal transplantation on subclinical cardiovascular measures in pediatric patients has not been widely investigated. This analysis is performed for pediatric patients participating in the prospective cardiovascular comorbidity in children with chronic kidney disease study and focuses on the early effects of renal replacement therapy (RRT) modality on cardiovascular comorbidity in patients receiving a preemptive transplant or started on dialysis.

Methods: We compared measures indicating subclinical cardiovascular organ damage (aortal pulse wave velocity, carotid intima media thickness, left ventricular mass index) and evaluated cardiovascular risk factors in 166 pediatric patients before and 6 to 18 months after start of RRT (n = 76 transplantation, n = 90 dialysis).

Results: RRT modality had a significant impact on the change in arterial structure and function: compared to dialysis treatment, transplantation was independently associated with decreases in pulse wave velocity (ß = -0.67; P < 0.001) and intima media thickness (ß = -0.40; P = 0.008). Independent of RRT modality, an increase in pulse wave velocity was associated with an increase in diastolic blood pressure (ß = 0.31; P < 0.001). Increasing intima media thickness was associated with a larger increase in body mass index (ß = 0.26; P = 0.003) and the use of antihypertensive agents after RRT (ß = 0.41; P = 0.007). Changes in left ventricular mass index were associated with changes in systolic blood pressure (ß = 1.47; P = 0.01).

Conclusions: In comparison with initiating dialysis, preemptive transplantation prevented further deterioration of the subclinical vascular organ damage early after transplantation. Classic cardiovascular risk factors, such as hypertension and obesity are of major importance for the development of cardiovascular organ damage after renal transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000001948DOI Listing
March 2018

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children.

JAMA Pediatr 2017 11 6;171(11):e172914. Epub 2017 Nov 6.

Department of Medicine, Rush University Medical Center, Chicago, Illinois.

Importance: Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C-derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults.

Objective: To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD.

Design, Setting, And Participants: Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016.

Exposures: Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy.

Main Outcomes And Measures: The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2.

Results: Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34 (16) mL/min/1.73 m2. The 5-year end point-free renal survival was 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9% (95% CI, 28.7-43.0) in those in the highest quartile (P < .001). By multivariable analysis, the risk of attaining the end point was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria, and lower eGFR at baseline. In patients with baseline eGFR greater than 40 mL/min/1.73 m2, higher log-transformed suPAR levels were associated with a higher risk of CKD progression after adjustment for traditional risk factors (hazard ratio, 5.12; 95% CI, 1.56-16.7; P = .007).

Conclusions And Relevance: Patients with high suPAR levels were more likely to have progression of their kidney disease. Further studies should determine whether suPAR levels can identify children at risk for future CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2017.2914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121753PMC
November 2017

Evaluation of development of subclinical atherosclerosis in children with uveitis.

Clin Rheumatol 2018 May 10;37(5):1305-1308. Epub 2017 Jul 10.

Department of Pediatric Nephrology, Ege University Faculty of Medicine, İzmir, Turkey.

Uveitis is a chronic inflammatory disease. Chronic inflammation has been shown to have a role in pathogenesis of atherosclerosis. Atherosclerosis is the most important risk factor of cardiovascular diseases and is shown to start as early as childhood. In this study, we investigated the presence of subclinical atherosclerosis in children with uveitis. Seventy five patients who were diagnosed as having uveitis in ophthalmology and pediatric rheumatology clinics were included in the study. Patients with hypertension, obesity, dyslipidemia, diabetes, and with history of early cardiovascular disease were excluded. Arterial stiffness, carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), and carotid artery intima-media thickness (cIMT) were measured for each patient. These measurements were compared with 50 healthy children with similar age and sex as controls. The mean age of patients in this study was 12.24 ± 2.69 years, and the mean age of controls was 11.32 ± 4.52 years. PWV and AIx values were higher in the patient group (p = 0.04, p = 0.03). cIMT levels were not different in patient and control groups. When patients were grouped as having uveitis for more than 5 years or not, patients with longer duration of uveitis had higher PWV, AIx, and cIMT levels (p values were 0.01, 0.02, and 0.04 respectively). Vascular functions deteriorate first with endothelial damage in children with uveitis and as disease continues, increase in cIMT is added. We think that for follow-up of the disease and evaluation of the treatment, non-invasive subclinical atherosclerosis markers should be used along with activation criteria of primary diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-017-3741-3DOI Listing
May 2018

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

J Am Soc Nephrol 2017 Oct 31;28(10):3055-3065. Epub 2017 May 31.

Division of Pediatric Nephrology, University Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany;

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2016101121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619960PMC
October 2017

Peritoneal Dialysis Access Revision in Children: Causes, Interventions, and Outcomes.

Clin J Am Soc Nephrol 2017 01 29;12(1):105-112. Epub 2016 Nov 29.

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Background And Objectives: Little published information is available about access failure in children undergoing chronic peritoneal dialysis. Our objectives were to evaluate frequency, risk factors, interventions, and outcome of peritoneal dialysis access revision.

Design, Setting, Participants, & Measurements: Data were derived from 824 incident and 1629 prevalent patients from 105 pediatric nephrology centers enrolled in the International Pediatric Peritoneal Dialysis Network Registry between 2007 and 2015.

Results: In total, 452 access revisions were recorded in 321 (13%) of 2453 patients over 3134 patient-years of follow-up, resulting in an overall access revision rate of 0.14 per treatment year. Among 824 incident patients, 186 (22.6%) underwent 188 access revisions over 1066 patient-years, yielding an access revision rate of 0.17 per treatment year; 83% of access revisions in incident patients were reported within the first year of peritoneal dialysis treatment. Catheter survival rates in incident patients were 84%, 80%, 77%, and 73% at 12, 24, 36, and 48 months, respectively. By multivariate logistic regression analysis, risk of access revision was associated with younger age (odds ratio, 0.93; 95% confidence interval, 0.92 to 0.95; P<0.001), diagnosis of congenital anomalies of the kidney and urinary tract (odds ratio, 1.28; 95% confidence interval, 1.03 to 1.59; P=0.02), coexisting ostomies (odds ratio, 1.42; 95% confidence interval, 1.07 to 1.87; P=0.01), presence of swan neck tunnel with curled intraperitoneal portion (odds ratio, 1.30; 95% confidence interval, 1.04 to 1.63; P=0.02), and high gross national income (odds ratio, 1.10; 95% confidence interval, 1.02 to 1.19; P=0.01). Main reasons for access revisions included mechanical malfunction (60%), peritonitis (16%), exit site infection (12%), and leakage (6%). Need for access revision increased the risk of peritoneal dialysis technique failure or death (hazard ratio, 1.35; 95% confidence interval, 1.10 to 1.65; P=0.003). Access dysfunction due to mechanical causes doubled the risk of technique failure compared with infectious causes (hazard ratio, 1.95; 95% confidence interval, 1.20 to 2.30; P=0.03).

Conclusions: Peritoneal dialysis catheter revisions are common in pediatric patients on peritoneal dialysis and complicate provision of chronic peritoneal dialysis. Attention to potentially modifiable risk factors by pediatric nephrologists and pediatric surgeons should be encouraged.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.05270516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220659PMC
January 2017

Cardiovascular Phenotypes in Children with CKD: The 4C Study.

Clin J Am Soc Nephrol 2017 01 8;12(1):19-28. Epub 2016 Nov 8.

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Background And Objectives: Cardiovascular disease is the most important comorbidity affecting long-term survival in children with CKD.

Design, Setting, Participants, & Measurements: The Cardiovascular Comorbidity in Children with CKD Study is a multicenter, prospective, observational study in children ages 6-17 years old with initial GFR of 10-60 ml/min per 1.73 m. The cardiovascular status is monitored annually, and subclinical cardiovascular disease is assessed by noninvasive measurements of surrogate markers, including the left ventricular mass index, carotid intima-media thickness, and central pulse wave velocity. We here report baseline data at study entry and an explorative analysis of variables associated with surrogate markers.

Results: A total of 737 patients were screened from October of 2009 to August of 2011 in 55 centers in 12 European countries, and baseline data were analyzed in 688 patients. Sixty-four percent had congenital anomalies of the kidney and urinary tract; 26.1% of children had uncontrolled hypertension (24-hour ambulatory BP monitoring; n=545), and the prevalence increased from 24.4% in CKD stage 3 to 47.4% in CKD stage 5. The prevalence of left ventricular hypertrophy was higher with each CKD stage, from 10.6% in CKD stage 3a to 48% in CKD stage 5. Carotid intima-media thickness was elevated in 41.6%, with only 10.8% of patients displaying measurements below the 50th percentile. Pulse wave velocity was increased in 20.1%. The office systolic BP SD score was the single independent factor significantly associated with all surrogate markers of cardiovascular disease. The intermediate end point score (derived from the number of surrogate marker measurements >95th percentile) was independently associated with a diagnosis of congenital anomalies of the kidney and urinary tract, time since diagnosis of CKD, body mass index, office systolic BP, serum phosphorus, and the hemoglobin level.

Conclusions: The baseline data of this large pediatric cohort show that surrogate markers for cardiovascular disease are closely associated with systolic hypertension and stage of CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.01090216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220645PMC
January 2017

Can Urinary Nerve Growth Factor and Brain-Derived Neurotrophic Factor be used in the Diagnosis and Follow-Up of Voiding Dysfunction in Children?

Urol J 2016 Jun 28;13(3):2690-6. Epub 2016 Jun 28.

Department of Pediatric Nephrology, Ege University School of Medicine, İzmir 3500, Turkey.

Purpose: We investigated the utility of urinary nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels as non-invasive markers for diagnosis and evaluation of treatment efficacy in children with overactive bladder (OAB).

Materials And Methods: This prospective study included 24 children with OAB and 30 healthy controls. At the time of diagnosis, micturition disorder symptom scores (MDSS) were determined, blood and urine samples were collected, and anticholinergic therapy was initiated. Clinical responses were evaluated, at the third and sixth month of treatment, by MDSS and urinary NGF, BDNF, and creatinine levels.

Results: The patient group had significantly higher urine NGF/Cr ratio (975 ± 827 and 159 ± 84, respectively, P < .001) and BDNF/Cr ratio (5.98 ± 5.78 and 0.81 ± 0.70, respectively, P < .001) before treatment. Significantly decreased BDNF/Cr ratio was found at the sixth month (5.98 ± 5.78 and 2.24 ± 0.98, respectively, P = .004). NGF/Cr > 360 was found to have 87.5% sensitivity and 100% specificity, and BDNF/Cr > 1.288 was found to have 87.5% sensitivity and 83.3% specificity for OAB diagnosis.

Conclusion: In conclusion, urine NGF/Cr and BDNF/Cr ratios may be useful markers for diagnosis of OAB. The BDNF/Cr ratio was found to be more significant in monitoring treatment response. .
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2016

Genetic, Environmental, and Disease-Associated Correlates of Vitamin D Status in Children with CKD.

Clin J Am Soc Nephrol 2016 07 16;11(7):1145-53. Epub 2016 Jun 16.

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Background And Objectives: Vitamin D deficiency is endemic in children with CKD. We sought to investigate the association of genetic disposition, environmental factors, vitamin D supplementation, and renal function on vitamin D status in children with CKD.

Design, Setting, Participants, & Measurements: Serum 25-hydroxy-vitamin D, 1,25-dihydroxy-vitamin D, and 24,25-dihydroxy-vitamin D concentrations were measured cross-sectionally in 500 children from 12 European countries with CKD stages 3-5. All patients were participants of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study, had CKD stage 3-5, and were age 6-18 years old. Patients were genotyped for single-nucleotide polymorphisms in the genes encoding 25-hydroxylase, vitamin D binding protein, 7-dehydrocholesterol reductase, and 24-hydroxylase. Associations of genetic status, season, local solar radiation, oral vitamin D supplementation, and disease-associated factors with vitamin D status were assessed.

Results: Two thirds of patients were vitamin D deficient (25-hydroxy-vitamin D <16 ng/ml). 25-Hydroxy-vitamin D concentrations varied with season and were twofold higher in vitamin D-supplemented patients (21.6 [14.1] versus 10.4 [10.1] ng/ml; P<0.001). Glomerulopathy, albuminuria, and girls were associated with lower 25-hydroxy-vitamin D levels. 24,25-dihydroxy-vitamin D levels were closely correlated with 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D (r=0.87 and r=0.55; both P<0.001). 24,25-dihydroxy-vitamin D concentrations were higher with higher c-terminal fibroblast growth factor 23 and inversely correlated with intact parathyroid hormone. Whereas 25-hydroxy-vitamin D levels were independent of renal function, 24,25-dihydroxy-vitamin D levels were lower with lower eGFR. Vitamin D deficiency was more prevalent in Turkey than in other European regions independent of supplementation status and disease-related factors. Single-nucleotide polymorphisms in the vitamin D binding protein gene were independently associated with lower 25-hydroxy-vitamin D and higher 24,25-dihydroxy-vitamin D.

Conclusions: Disease-related factors and vitamin D supplementation are the main correlates of vitamin D status in children with CKD. Variants in the vitamin D binding protein showed weak associations with the vitamin D status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.10210915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934841PMC
July 2016

Assessment of vascular function in systemic onset juvenile idiopathic arthritis.

Clin Rheumatol 2016 Jul 13;35(7):1699-703. Epub 2016 Apr 13.

Department of Pediatric Nephrology, Ege University Faculty of Medicine, Izmir, Turkey.

An increased incidence of cardiovascular disease has been found in rheumatic disorders. Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Prolonged immunological inflammatory process leads these patients to an early onset of atherosclerosis. We aimed to assess the presence of early vascular dysfunction in patients with systemic onset juvenile idiopathic arthritis (sJIA) and investigate the role of therapy sJIA in vascular health. Thirty-three patients (22 males, 11 females) diagnosed with sJIA according to the International League of Associations for Rheumatology criteria were compared to 72 age- and sex-matched controls. None of the participants was overweight, obese, or had a history of hypertension, dyslipidemia, diabetes mellitus, or cardiovascular disease. Arterial stiffness (As) was evaluated by measurement of carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) with a Vicorder. The mean age of patients in this study was 9.96 ± 3.71 years (range 4-16 years) and the mean age of controls was 10.9 ± 3.52 years (range 4-19 years). These two groups were well matched for age, sex, and BMI. The mean age of patients at the onset of disease was 7.06 ± 3.9 years (range 3-15 years). The mean duration of disease and active disease was 79 ± 45 months (range 6-162 months) and 58 ± 49 months (range 1-101 months), respectively. The highest levels of PWV and AIx were found in the patient group. Seven patients had had macrophage activation syndrome at presentation. In these patients, vascular changes were higher than other patients (6.30 ± 0.42 m/s vs 5.17 ± 0.55 m/s, p = 0.01, respectively). The corticosteroid therapy was found associated with higher PWV, (p < 0.05), while there was no difference between vascular parameters and use of non-steroid therapies (methotrexate (MTX), anti-TNF alfa agents). We also find statistically significant correlation between PWV and disease duration (p = 0.003, r = 0.45). Vascular function is impaired in patients with sJIA at a very young age. Vascular dysfunction may be partly attributed to the effects of disease-related characteristics (inflammation, disease activity, and medications).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-016-3254-5DOI Listing
July 2016

Growth evaluation in children with vesicoureteral reflux.

Minerva Pediatr 2017 Apr 17;69(2):129-134. Epub 2015 Sep 17.

Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Ege University, İzmir, Turkey.

Background: Vesicoureteral reflux and urinary tract infection predispose children to retardation of growth, hypertension, renal scarring and renal failure. The aim of this study was to evaluate growth pattern in children with vesicoureteral reflux before and after medical/surgical treatment.

Methods: This study was a retrospective cross-sectional study. The study population included 97 children aged 0.5 to 17 years (8.8±5.5). Body weight, height and bone age of the children were measured. Weight Z score and height Z score were calculated during first visits and after medical and/or surgical treatment. Distribution, mean and standard deviation score were evaluated for the descriptive data. T-test and Mann-Whitney U test and Wilcoxon test were used for statistical analysis.

Results: Sixty-five percent of 97 children enrolled in this study were girls. About 48.5% of the children had unilateral and mild reflux, while 16.5% had bilateral and severe reflux. The bone age was 8.6 years. Differentiation with chronological age and bone age were not significant (P=0.294). At admission, 54.6% and 50.5% of children had negative Weight Z score and height Z score, respectively. After medical and surgical treatment, Weight Z score and height Z score were increased, however, only the increase in Weight Z score was significant (P=0.039, P=0.031, respectively). A significant reduction in bone age was found in children with renal scars compared to those without renal scars (P=0.048).

Conclusions: High-grade vesicoureteral reflux had a negative impact on indices of growth in children. Medical and/or surgical treatment had positive effect on weight gain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4946.16.04132-3DOI Listing
April 2017

The long-term outlook to final outcome and steroid treatment results in children with idiopathic nephrotic syndrome.

Ren Fail 2015 27;37(8):1267-72. Epub 2015 Aug 27.

c Department of Pediatric Nephrology, Medical Faculty , Ege University , Izmir , Turkey.

Idiopathic Nephrotic Syndrome (INS) was defined as combination of a nephrotic syndrome and non-specific histological abnormalities of the kidney. Among these abnormalities, minimal change nephrotic syndrome (MCNS) is the most common. We report our experience with MCNS; its clinical course, treatments and outcomes. One-hundred twenty children (66 male, 54 female) with MCNS, admitted to Nephrology Department between 1987-2009 was assessed. Their clinical presentations, treatment and disease courses were reviewed. The mean duration of follow-up was 11.5 ± 1.9 years. Initially, all patients given prednisone 2 mg/kg/ day single dose per four weeks a followed by eight weeks of the same daily dose given every other day. After week 12, prednisone was progressively tapered off at the rate of 0.5 mg/kg per 15 daily intervals until complete discontinuation had been achieved by week 16. Steroid resistance was accepted as no achievement of remission following four weeks of prednisone 2 mg/kg/day followed by three intravenous pulses of corticosteroids. At the end of the initial steroid treatment, 106 (88.3%) patients were determinate steroid responsive while 14 (11.7%) patients were steroid resistance. Thirty-eight patients underwent biopsy. At the end of study recovery rate was increased from 88.3% to 94.1%. In conclusion, most of patients entered remission by our therapy end of follow up time. With the support of our satisfactory results among the whole study group, long-term prednisolone treatment still remains valid.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/0886022X.2015.1073051DOI Listing
June 2016

The long-term outlook to final outcome and steroid treatment results in children with idiopathic nephrotic syndrome.

Ren Fail 2015 Aug 14:1-6. Epub 2015 Aug 14.

Department of Pediatric Nephrology, Ankara Children Health and Research Hematology Oncology Education Research Hospital , Ankara , Turkey .

Idiopathic Nephrotic Syndrome (INS) was defined as combination of a nephrotic syndrome and non-specific histological abnormalities of the kidney. Among these abnormalities, minimal change nephrotic syndrome (MCNS) is the most common. We report our experience with MCNS; its clinical course, treatments and outcomes. One-hundred twenty children (66 male, 54 female) with MCNS, admitted to Nephrology Department between 1987-2009 was assessed. Their clinical presentations, treatment and disease courses were reviewed. The mean duration of follow-up was 11.5 ± 1.9 years. Initially, all patients given prednisone 2 mg/kg/ day single dose per four weeks a followed by eight weeks of the same daily dose given every other day. After week 12, prednisone was progressively tapered off at the rate of 0.5 mg/kg per 15 daily intervals until complete discontinuation had been achieved by week 16. Steroid resistance was accepted as no achievement of remission following four weeks of prednisone 2 mg/kg/day followed by three intravenous pulses of corticosteroids. At the end of the initial steroid treatment, 106 (88.3%) patients were determinate steroid responsive while 14 (11.7%) patients were steroid resistance. Thirty-eight patients underwent biopsy. At the end of study recovery rate was increased from 88.3% to 94.1%. In conclusion, most of patients entered remission by our therapy end of follow up time. With the support of our satisfactory results among the whole study group, long-term prednisolone treatment still remains valid.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2015

Is Daytime Systolic Load an Important Risk Factor for Target Organ Damage in Pediatric Hypertension?

J Clin Hypertens (Greenwich) 2015 Oct 3;17(10):760-6. Epub 2015 Jul 3.

Department of Pediatric Nephrology, Ege University Medical Faculty, Izmir, Turkey.

The aim of this study was to compare ambulatory blood pressure (BP) monitoring (ABPM) data and determine which hypertension type is a risk factor in target organ damage. A total of 82 children (47 boys) with suspected hypertension based on office BP measurements and considered hypertensive by ABPM were studied. Target organ damage included the following: 35.3% hypertensive retinopathy, 25.6% microalbuminuria, 15.8% increased left ventricular mass index, 29.2% increased carotid intima-media thickness (cIMT), 24.3% high augmentation index (AIx), and 19.5% high pulse wave velocity (PWV). The association between BP load, PWV, and cIMT was statistically significant. There were significant correlations between daytime systolic BP load, PWV, AIx, and cIMT. A statistically significant difference was also detected between nighttime systolic BP load, PWV, and cIMT values and nighttime diastolic BP load levels and values of AIx and cIMT. There was also a statistically significant difference between the high level of nighttime diastolic BP load and cIMT. The authors found that target organ damage was seen more often in children with primary hypertension who had systolic loads.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jch.12608DOI Listing
October 2015

ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS.

J Am Soc Nephrol 2016 Jan 12;27(1):63-8. Epub 2015 May 12.

Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany;

Hereditary defects of coenzyme Q10 biosynthesis cause steroid-resistant nephrotic syndrome (SRNS) as part of multiorgan involvement but may also contribute to isolated SRNS. Here, we report 26 patients from 12 families with recessive mutations in ADCK4. Mutation detection rate was 1.9% among 534 consecutively screened cases. Patients with ADCK4 mutations showed a largely renal-limited phenotype, with three subjects exhibiting occasional seizures, one subject exhibiting mild mental retardation, and one subject exhibiting retinitis pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 14.1 years) with nephrotic-range proteinuria in 44% of patients and advanced CKD in 46% of patients at time of diagnosis. Renal biopsy specimens uniformly showed FSGS. Whereas 47% and 36% of patients with mutations in WT1 and NPHS2, respectively, progressed to ESRD before 10 years of age, ESRD occurred almost exclusively in the second decade of life in ADCK4 nephropathy. However, CKD progressed much faster during adolescence in ADCK4 than in WT1 and NPHS2 nephropathy, resulting in similar cumulative ESRD rates (>85% for each disorder) in the third decade of life. In conclusion, ADCK4-related glomerulopathy is an important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD of unknown origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2014121240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696579PMC
January 2016

Association of clearance of middle- and large-molecular-weight substance with arterial stiffness and left ventricular mass in children receiving renal replacement therapy.

Minerva Pediatr 2017 Dec 30;69(6):495-502. Epub 2015 Apr 30.

Department of Pediatric Nephrology, Ege University School of Medicine, İzmir, Turkey.

Background: The prominent cause of mortality in children receiving dialysis treatment is cardiovascular diseases. Risk factors related to chronic renal disease, are effective in the development of cardiovascular diseases. The aim of study was to investigate cardiovascular system (CVS) involvement for functional and structural alterations in children receiving dialysis, and display any association between cardiovascular morbidity and uremic toxins.

Methods: 20 dialysis patients and 20 healthy controls were included to the study. Clearance of small, middle and large molecular-weight uremic toxins was evaluated in blood samples collected 30 minutes before (D0) and 2 hour after dialysis (D2), and change value was calculated as D0-D2/D0. Cardiovascular involvement was determined by comparing arterial stiffness, carotid intima-media thickness (CIMT) and Left Ventricular Mass Index (LVMI) with the control group.

Results: Four patients receiving hemodialysis and two patients in continuous ambulatory peritoneal dialysis (CAPD) group who have significant differences in all functional and structural parameters were detected. Four dialysis patients with detected cardiovascular disease have distinctively lower beta-2 microglobulin and homocysteine clearances compared to the patients with no CVS involvement.

Conclusions: The clearance of middle and large molecular-weight substances should be closely monitored in children receiving dialysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4946.16.04253-5DOI Listing
December 2017