Publications by authors named "Esra Baskin"

108 Publications

Transplantation in pediatric aHUS within the era of eculizumab therapy.

Pediatr Transplant 2020 Nov 20:e13914. Epub 2020 Nov 20.

Department of Pediatrics, Division of Pediatric Nephrology, Gazi University School of Medicine, Ankara, Turkey.

aHUS is caused by the over-activation and dysregulation of the alternative complement pathway. Data regarding outcomes of pediatric aHUS patients after kidney transplantation are still very scarce. Accordingly, the aim of this study was to describe the clinical findings and outcomes of pediatric aHUS patients after renal transplantation. This is a retrospective, multicenter study including 12 patients from the national registry system. Among the 12 patients, eight had received prophylactic eculizumab and none of those patients (except one) had experienced aHUS recurrence during a median follow-up period of 58.5 (min-max, 4-94) months. Although eculizumab had been started on the day before transplantation in one of them, aHUS recurrence occurred during the transplantation procedure. Eculizumab had been stopped in only one patient who had no complement gene mutation after 35 months of therapy, and recurrence had not been observed during the 19 months of follow-up. In three patients, maintenance doses had been spaced out without any recurrence. One additional patient with anti-CFH antibody received only two doses of eculizumab for transplantation and had been followed for 46 months without aHUS recurrence. The remaining three patients had not received anti-C5 therapy and none of those patients experienced aHUS recurrence during a median follow-up period of 21 (min-max, 9-42) months. Prophylactic eculizumab is a safe and effective treatment for the prevention of aHUS recurrence. Eculizumab interval prolongation, discontinuation, and transplantation without eculizumab prophylaxis can be tried in selected patients with close follow-up.
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http://dx.doi.org/10.1111/petr.13914DOI Listing
November 2020

Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children.

PLoS One 2020 27;15(10):e0240446. Epub 2020 Oct 27.

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

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3-0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240446PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591021PMC
December 2020

Impact of Matrix Metalloproteinases 2 and 9 and Tissue Inhibitor of Metalloproteinase 2 Gene Polymorphisms on Allograft Rejection in Pediatric Renal Transplant Recipients.

Exp Clin Transplant 2020 Aug 14. Epub 2020 Aug 14.

From the Baskent University Faculty of Medicine Department of Medical Genetics, Ankara, Turkey.

Objectives: Acute and chronic allograft rejection have been continuously an important obstacle in the follow-up of renal transplant recipients. During clinical management, several factors acting simultaneously result in acute rejection and chronic allograft nephropathy. Matrix metalloproteinases and tissue inhibitors of metalloproteinases are responsible for the organization of the extracellular matrix and play roles in cell proliferation and cellular invasion. Changes in matrix metalloproteinase expression levels have been reported to be associated with renal allograft rejection and interstitial fibrosis. In this study, we aimed to investigate functional polymorphisms of MMP2, MMP9, and TIMP2 genes in pediatric renal transplant recipients.

Materials And Methods: Our study included 68 kidney transplant recipients and 58 control patients. The kidney transplant recipient group was further divided into 2 subgroups: no graft rejection (n = 47) and graft rejection (n =21). MMP2 -735C >T (rs2285053), MMP2 -1306C >T (rs243865), MMP2 -1575G >A (rs243866), MMP9 c.-1562C >T (rs3918242), TIMP2 -418G >C (rs8179090), and TIMP2 303C > T (rs2277698) polymorphisms were analyzed with the use of polymerase chain reaction and restriction fragment-length polymorphism methods. Allele prevalence was compared with reference values of the control group, and Hardy-Weinberg equilibrium was tested.

Results: Mean ages were 16.7 ± 3.9 years for the study group and 14.8 ± 5.6 years for the control group. The mean follow-up time after transplant was 37.7 ± 7.9 months. We compared allele frequencies in the 2 groups and calculated a statistically significant difference in rs2285053, rs243865, rs243866, rs3918242, rs8179090, and rs2277698 polymorphism frequencies between the transplant recipients and control patients. When the transplant recipient group was compared in itself with regard to allograft rejection, all investigated polymorphisms except TIMP2 -418G >C (rs8179090) revealed a statistically significant difference between those with and without rejection (P < .05).

Conclusions: Matrix metalloproteinases and their tissue inhibitors could be important predictive biological markers for the follow-up of kidney transplant recipients.
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http://dx.doi.org/10.6002/ect.2020.0036DOI Listing
August 2020

Recurrence and Outcomes of Complement-Related Renal Disease After Pediatric Renal Transplantation.

Exp Clin Transplant 2020 01;18(Suppl 1):82-83

From the Department of Pediatric Nephrology, Baskent University, Ankara, Turkey.

Complement dysregulation is related to different glomerular pathologies. Patients with complement dysregulation have high recurrence risk after transplant; however, with trough-effective therapeutics, renal transplant can be an option for these patients. Here, we present 2 boys with renal disease related to complement dysregulation and their outcomes after renal transplant. Patient 1 had atypical hemolytic uremic syndrome, which was treated with eculizumab before renal transplant; eculizumab therapy was also continued after transplant as preventive therapy. Eculizumab therapy was stopped at year 2 post-transplant. At year 4 post-transplant, his serum creatinine level was 0.87 mg/dL. Patient 2, who had chronic renal disease related to C3 glomerulopathy, was not responsive to eculizumab before renal transplant. At month 4 posttransplant, C3 glomerulopathy recurrence was demonstrated with biopsy, and serum creatinine level was 1.96 mg/dL at this time. Eculizumab was started as a rescue therapy. At year 4 posttransplant, his serum creatinine level was 2.07 mg/dL. In our 2 patients with complement dysregulation, eculizumab was an effective and preventive therapy after renal transplant. However, more studies are needed to understand the long-term efficacy and safety of eculizumab after renal transplant.
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http://dx.doi.org/10.6002/ect.TOND-TDTD2019.P28DOI Listing
January 2020

Importance of Hypomagnesemia on New-Onset Diabetes Mellitus in Pediatric Renal Transplant Patients.

Exp Clin Transplant 2020 01;18(Suppl 1):78-81

From the Department of Pediatric Nephrology, Baskent University, Ankara, Turkey.

Objectives: Hypomagnesemia is considered as an independent risk factor for new-onset diabetes mellitus after kidney transplant. New-onset diabetes mellitus is an important comorbidity associated with allograft failure. In this study, our aim was to investigate the correlation between hypomagnesemia and preva-lence of posttransplant diabetes mellitus.

Materials And Methods: We retrospectively evaluated 189 pediatric renal transplant recipients who underwent their first renal transplant. A patient with type 1 diabetes mellitus before transplant was excluded from the analysis. Hypomagnesemia was defined as having serum magnesium levels lower than 1.7 mg/dL. Diabetes was defined according to American Diabetes Association criteria. Serum magnesium and glucose levels at month 1 after transplant were recorded.

Results: We evaluated the records of 188 patients. New-onset diabetes mellitus was diagnosed in 7 patients (3.7%). Hypomagnesemia was shown in 50% of patients (64/120). Mean glucose levels were higher in those with hypomagnesemia than in patients without hypomagnesemia (119.2 vs 91.56 mg/dL, respectively; P = .01) A significant negative correlation was observed between serum magnesium and glucose levels (r = -0.53; P < .05). Mean serum magnesium level in patients with new-onset diabetes mellitus was lower than in patients without diabetes (1.56 ± 0.21 vs 1.75 ± 0.26 mg/dL; P = .052).

Conclusions: Hypomagnesemia is a common problem in pediatric renal transplant. The relationship between serum magnesium and glucose levels suggests that hypomagnesemia plays a role in the development of new-onset diabetes mellitus after transplant. Compre-hensive studies are needed to support this association.
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http://dx.doi.org/10.6002/ect.TOND-TDTD2019.P27DOI Listing
January 2020

Lower Urinary Tract Dysfunction and Pediatric Renal Transplant.

Exp Clin Transplant 2020 01;18(Suppl 1):41-43

From the Department of Pediatric Nephrology, Başkent University, Ankara, Turkey.

Objectives: Lower urinary tract abnormalities have been considered to be contraindications for renal transplant. However, advancements in diagnosis and treatment in this area have allowed renal transplant as a treatment choice in selected cases. We evaluated clinical outcomes of pediatric renal transplant in patients with lower urinary tract dysfunction.

Materials And Methods: We retrospectively evaluated data from 165 pediatric renal transplant patients, and data were compared between patients with and without lower urinary tract dysfunction. Patient demographics, cause of chronic renal failure, acute rejection episodes, and graft loss were included in our analyses.

Results: Seventeen patients had lower urinary tract dysfunction, and the remaining 148 patients had functional lower urinary tracts. Patients with lower urinary tract dysfunction were younger than the other patient group at diagnosis of chronic renal failure. The mean follow-up after renal transplant in the 2 groups was similar. Differences with regard to donor type, immunosuppressive treatment, and acute rejection episodes were not significant between the 2 groups. Eight patients had lost their grafts during follow-up; however, only 1 of these patients was in the lower urinary tract dysfunction group. Graft loss rate was similar between the groups.

Conclusions: Pediatric patients with lower urinary tract dysfunction had similar graft outcomes versus other pediatric renal transplant patients. Careful evaluation and preparation of the lower urinary tract are important factors for renal transplant success.
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http://dx.doi.org/10.6002/ect.TOND-TDTD2019.O21DOI Listing
January 2020

Effectiveness of the Gamma Probe in Childhood Parathyroidectomy: Retrospective Study.

Cureus 2020 Jan 11;12(1):e6629. Epub 2020 Jan 11.

Pediatric Nephrology, Baskent University, Ankara, TUR.

Background There are few reports about parathyroidectomy due to secondary hyperparathyroidism in patients with end-stage renal failure in the literature. We aimed to evaluate the surgical treatment methods and the results of patients who were operated for secondary hyperparathyroidism with end-stage renal disease in our center. Method Sixteen patients with the diagnosis of secondary hyperparathyroidism were treated surgically in our center. Demographical data, laboratory findings, and imagining methods were all examined. The effect of the Technetium 99m methoxyisobutylisonitrile (Tc-99m-MIBI) probe sensitive to gamma rays detection was also evaluated to locate and identify all the parathyroid glands during the operation. Results Eleven of the patients underwent intravenous (IV) Tc-99m MIBI preoperatively and a gamma probe was detected during surgery. The gamma probe was not used in five patients. Four parathyroid glands were removed in eight (72.7%) out of 11 patients with gamma probes and three parathyroid glands were found in three patients. Total parathyroidectomy and parathyroid autoimplantation were made to eight patients who had removed four glands, subtotal parathyroidectomy was done for the other patients. On a comparison of laboratory findings before and after the surgery, there was a significant relationship between the decrease of serum parathyroid hormone and calcium levels (p<0.05). Conclusion Total parathyroidectomy and parathyroid autoimplantation is the most efficient and safe mode of management for secondary parathyroidism patients. During the surgery, using a probe sensitive to gamma rays detection may also help the surgeon. Thus, unnecessary dissections to prevent the presence of atypical parathyroid glands are prevented.
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http://dx.doi.org/10.7759/cureus.6629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957029PMC
January 2020

The Clinical Characteristics of Pediatric Non-Infectious Uveitis in Two Tertiary Referral Centers in Turkey.

Ocul Immunol Inflamm 2019 Nov 5:1-8. Epub 2019 Nov 5.

Department of Ophthalmology, Ankara University, Ankara, Turkey.

: To report the manifestations, patterns of disease, treatment strategies and outcomes in pediatric patients with noninfectious uveitis.: Demographic information of 76 cases was recorded. Symptoms, anatomic location, laterality, visual acuity (VA), intraocular pressure, associated systemic diseases, therapeutic strategies, side effects, complications were reviewed.: Thirty-one patients were diagnosed as uveitis on routine surveillance because of underlying systemic disease. The most common anatomic location was intermediate uveitis (34.2%). Juvenile idiopathic arthritis (JIA) was the most common underlying systemic disease (25%). Glaucoma was the most common complication (7.7%). The patients with refractory uveitis received adalimumab (26.5%), infliximab (4.6%) and tocilizumab (3.1%). The mean first-year VA was between 20/32 and 20/20 in 116/140 eyes.: Most pediatric noninfectious uveitis cases have bilateral intermediate uveitis. JIA was the most common systemic association. The first-year VA was good in most eyes which may be due to early use of corticosteroid-sparing agents.
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http://dx.doi.org/10.1080/09273948.2019.1674890DOI Listing
November 2019

Extra-Renal manifestations of atypical hemolytic uremic syndrome in children.

Pediatr Nephrol 2018 08 2;33(8):1395-1403. Epub 2018 Apr 2.

Gazi University, School of Medicine, Department of Pediatric Nephrology, Istanbul, Turkey.

Background: Atypical hemolytic uremic syndrome (aHUS) is a chronic disease characterized by thrombotic microangiopathy and a high risk of end-stage kidney disease. Dysregulation and/or excessive activation of the complement system results in thrombotic microangiopathy. Interest in extrarenal manifestations of aHUS is increasing. This study aimed to determine the clinical characteristics of patients with extrarenal manifestations of aHUS in childhood.

Methods: This study included 70 children with extrarenal manifestations of HUS from the national Turkish aHUS Registry. The demographics, clinical characteristics, genetic test results, all treatments, and renal/hematologic status of aHUS patients with extrarenal involvement were recorded.

Results: The most common extrarenal manifestation was neurological system involvement (n = 46 [27.2%]), followed by gastrointestinal (n = 20 [11.8%]), cardiovascular (n = 12 [7%]), and respiratory (n = 12 [7%]) involvement. The patients with neurological involvement had a higher mortality rate and a lower estimated glomerular filtration rate (eGFR) than the other patients at last follow-up. Eculizumab (with or without plasma exchange/plasma infusion) treatment increased the renal and hematologic recovery rates.

Conclusions: The most common and serious extrarenal manifestation of aHUS is neurological involvement and treatment outcome findings presented herein are important to all relevant clinicians.
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http://dx.doi.org/10.1007/s00467-018-3933-3DOI Listing
August 2018

Agreement Between Integrated Management of Childhood Illness and Final Diagnosis in Acute Respiratory Tract Infections.

Indian J Pediatr 2018 Dec 19;85(12):1086-1089. Epub 2018 Feb 19.

Department of Pediatric Nephrology, Baskent University Faculty of Medicine, Ankara, Turkey.

Objective: To evaluate the agreement between integrated management of childhood illness (IMCI) and final diagnosis in patients presenting with cough at the second and third level health institutions.

Methods: This cross-sectional study included 373 children aged 2-60 mo who presented with cough at the pediatric emergency and outpatient clinics in the Department of Pediatrics. After clinical examination of children, body temperature, respiratory rate, saturation, presence or absence of the chest indrawing, rales, wheezing and laryngeal stridor were recorded. Cases were categorized according to IMCI algorithm regarding the severity using the color code, such as red (urgent treatment), yellow (treatment in the hospital), or green (treatment at home). Final diagnosis after physical examination, laboratory analysis and chest X-ray was compared with the IMCI algorithm.

Results: Study agreement between IMCI classification and final diagnosis was 74.3% with kappa value 0.55 (moderate agreement). Similar agreement values were detected in both the second and third level health institutions. Health condition and gender did not affect agreement value. Agreement were found to be high in patients <24 mo of age (ĸ = 0.67), presence of fever and cough (ĸ = 0.54), tachypnea (ĸ = 0.93), chest indrawing (ĸ = 1.00) and oxygen saturation of <94%(ĸ = 0.90).

Conclusions: Adding saturation level to the IMCI algorithmic diagnosis may increase agreement between IMCI classification and final diagnosis.
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http://dx.doi.org/10.1007/s12098-018-2637-9DOI Listing
December 2018

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

The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis.

Clin J Am Soc Nephrol 2017 Aug 9. Epub 2017 Aug 9.

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

Background And Objectives: Infantile nephropathic cystinosis is a severe disease that occurs due to mutations in the cystinosis gene, and it is characterized by progressive dysfunction of multiple organs; >100 cystinosis gene mutations have been identified in multiple populations. Our study aimed to identify the clinical characteristics and spectrum of cystinosis gene mutations in Turkish pediatric patients with cystinosis.

Design, Setting, Participants, & Measurements: We identified the clinical characteristics and spectrum of cystinosis gene mutations in Turkish patients with cystinosis in a multicenter registry that was established for data collection. The data were extracted from this registry and analyzed.

Results: In total, 136 patients (75 men and 61 women) were enrolled in the study. The most common clinical findings were growth retardation, polyuria, and loss of appetite. None of the patients had the 57-kb deletion, but seven novel mutations were identified. The most common mutations identified were c.681G>A (p.Glu227Glu; 31%), c.1015G>A (p.Gly339Arg; 22%), and c.18_21 del (p.Thr7Phefs*7; 14%). These mutations were associated with earlier age of disease onset than the other mutations. To understand the effects of these allelic variants on clinical progression, the mutations were categorized into two major groups (missense versus deletion/duplication/splice site). Although patients with missense mutations had a better eGFR at the last follow-up visit, the difference was not significant. Patients in whom treatment began at age <2 years old had later onset of ESRD (=0.02). Time to ESRD did not differ between the patients with group 1 and group 2 mutations.

Conclusions: The most common cystinosis gene mutations identified in Turkey were c.681G>A (p.Glu227Glu), c.1015G>A (p.Gly339Arg), and c.18_21 del (p.Thr7Phefs*7). Patients with less severe cystinosis gene mutations tend to have better kidney outcome.
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http://dx.doi.org/10.2215/CJN.00180117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628704PMC
August 2017

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

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis.

Lancet 2017 May 20;389(10084):2128-2137. Epub 2017 Mar 20.

ESPN/ERA-EDTA Registry, Amsterdam, Netherlands.

Background: We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors.

Methods: In this registry analysis, we extracted patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (aHR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy.

Findings: Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate was 15·8 deaths per 1000 patient-years (IQR 6·4-16·4). France had a mortality rate (9·2) of more than 3 SDs better, and Russia (35·2), Poland (39·9), Romania (47·4), and Bulgaria (68·6) had mortality rates more than 3 SDs worse than the European average. Public health expenditure was inversely associated with mortality risk (per SD increase, aHR 0·69, 95% CI 0·52-0·91) and explained 67% of the variation in renal replacement therapy mortality rates between countries. Child mortality rates showed a significant association with renal replacement therapy mortality, albeit mediated by macroeconomics (eg, neonatal mortality reduced from 1·31 [95% CI 1·13-1·53], p=0·0005, to 1·21 [0·97-1·51], p=0·10). After accounting for country distributions of patient age, the variation in renal replacement therapy mortality rates between countries increased by 21%.

Interpretation: Substantial international variation exists in paediatric renal replacement therapy mortality rates across Europe, most of which was explained by disparities in public health expenditure, which seems to limit the availability and quality of paediatric renal care. Differences between countries in their ability to accept and treat the youngest patients, who are the most complex and costly to treat, form an important source of disparity within this population. Our findings can be used by policy makers and health-care providers to explore potential strategies to help reduce these health disparities.

Funding: ERA-EDTA and ESPN.
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http://dx.doi.org/10.1016/S0140-6736(17)30063-6DOI Listing
May 2017

Micronuclei and other nuclear anomalies in buccal epithelial cells of children with chronic kidney disease.

Arh Hig Rada Toksikol 2016 Dec;67(4):317-325

The objective of this study was to reveal the likely genomic instability in children with chronic kidney disease (CKD) using micronucleus (MN) assay on buccal epithelial cells (BEC). We investigated the frequencies of micronuclei and other nuclear anomalies, such as nuclear buds, binucleated cells, condensed chromatin, and karyorrhectic and pyknotic cells in BEC. Children with CKD were grouped as follows: children in the pre-dialysis (PreD) stage (N=17), children on regular haemodialysis (HD) (N=14), and children who have undergone transplantation (Tx) (N=17). As a control group, twenty age- and gender-matched healthy children were selected. The MN frequency in BEC of all groups of children with CKD was significantly elevated (5- to 7-fold) as compared to the control group (p<0.001). In contrast, the frequencies of nuclear buds were not significantly higher in the study groups compared to the control group. The frequencies of binucleated cells and condensed chromatin cells were significantly higher in all subgroups of children with CKD relative to the control group (p<0.001). Our results show that the BEC of pediatric PreD, HD, and Tx patients with CKD display increased cytogenetic, cytokinetic, and cytotoxic effects. They also point to the sensitivity and usefulness of the BEC MN assay in the assessment of genetic susceptibility of patients with CKD.
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http://dx.doi.org/10.1515/aiht-2016-67-2851DOI Listing
December 2016

The predictive value of resistive index obtained by Doppler ultrasonography early after renal transplantation on long-term allograft function.

Pediatr Transplant 2017 Mar 29;21(2). Epub 2016 Nov 29.

Division of General Surgery, Baskent University, Ankara, Turkey.

DUSG is a useful diagnostic tool for the follow-up of renal transplant recipients. The measurement of intrarenal arterial RI by DUSG has been proven to predict short-term AF. The aim of the study was to evaluate the predictive value of DUSG performed during the early after RTx on long-term AF. Seventy patients were enrolled into study. DUSG was performed at third and seventh days after RTx. Patients were divided into two groups according to rate of recovery of graft function as patients with normal graft function and abnormal graft function. Although the RI values were correlated with the AF early after transplantation, they were not correlated with long-term AF. However, the rate of recovery of graft function at early period after RTx was correlated with creatinine level at first year and with glomerular filtration rate at first year and last visit. Although the RI has no predictive value for long-term AF, the rate of recovery of graft function at early post-transplantation period has predictive value for long-term AF; patients with higher RI values early after RTx should be followed carefully for the development of chronic allograft injury.
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http://dx.doi.org/10.1111/petr.12860DOI Listing
March 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.
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http://dx.doi.org/10.2215/CJN.01090216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220645PMC
January 2017

Timing for Removal of Peritoneal Dialysis Catheters in Pediatric Renal Transplant Patients.

Exp Clin Transplant 2016 11;14(Suppl 3):74-77

From the Department of Pediatric Nephrology, Baskent University, Ankara, Turkey; and the Department of Pediatric Nephrology, Cukurova University, Adana, Turkey.

Objectives: Peritoneal dialysis, the preferred long-term renal replacement modality in the pediatric population, can also be used during the post transplant period. Although it is well known that peritonitis or other complications may occur related to the peritoneal dialysis catheter, less is known about complications related to the peritoneal dialysis during the posttransplant period. Our objective was to evaluate the complications related to use of a peritoneal dialysis catheter during the posttransplant period and to determine the optimum time for removal of the peritoneal dialysis catheter.

Materials And Methods: We retrospectively analyzed 33 chronic peritoneal dialysis patients. Pretransplant and posttransplant demographics and clinical and laboratory data for each patient were recorded, including incidence of peritonitis and incidence of peritoneal dialysis catheter requirement after transplant.

Results: Mean age of patients at transplant was 12.8 ± 4.0 years (range, 3.5-18.0 y). Mean catheter removal time was 81.1 ± 36.2 days (range, 22.0-152.0 d). The peritoneal dialysis catheter was used in 6 of 33 patients (18.2%); none of these patients developed peritonitis. In contrast, 2 of the 27 patients who did not use the peritoneal dialysis catheter developed peritonitis. Our data suggest that the need for catheter use occurs predominantly during the first month, and infectious complications usually happen later.

Conclusions: Previously, the trend was to not remove the peritoneal dialysis catheter at the time of transplant. However, in light of recent literature and our present study, we recommend that the time of catheter removal should be modified and decided for each patient on an individual basis.
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November 2016

Favorable Outcomes of Renal Transplant in Children With Abnormal Lower Urinary Tract.

Exp Clin Transplant 2016 05 2. Epub 2016 May 2.

From the Department of Pediatric Nephrology, Baskent University School of Medicine, Ankara, Turkey.

Objectives: Chronic kidney disease caused by lower urinary tract abnormalities is a significant complication in pediatric care. Although there are conflicting reports about clinical outcomes in the past, favorable outcomes have been reported in recent years. Despite this, many centers still refrain from performing renal transplant in these patients. Here, we compared clinical outcomes of renal transplant recipients with and without lower urinary tract abnormalities.

Materials And Methods: Our study included 71 renal transplant recipients who were divided into 3 groups: 17 patients with abnormal lower urinary tracts having vesicoureteral reflux (group 1), 7 patients with abnormal lower urinary tracts having bladder dysfunction (group 2), and 47 patients with anatomically and functionally normal lower urinary tracts (group 3). We retrospectively compared demographic features, clinical course, graft survival, pre- and posttransplant incidence of urinary tract infections, and final graft function among the groups.

Results: There were no statistically significant differences among groups regarding median age at time of transplant, graft survival, median creatinine level, and median glomerular filtration rate (P > .05). Significant differences were shown in incidence of urinary tract infections between patients in groups 1 and 2 (abnormal lower urinary tracts) and group 3 (normal lower urinary tracts) before transplant (P < .05). Although frequency of urinary tract infections in groups 1 and 2 were moderately higher than shown in group 3 after transplant, this difference was not statistically significant.

Conclusions: Although the children with abnormal lower urinary tracts had slightly higher incidence of urinary tract infections, there were no differences between patients with abnormal and normal lower urinary tracts regarding allograft survival and function. In addition, proper follow-up of patients before and after transplant, based on our experience, should include educating patients and their parents about potential complications after transplant for the best outcome of renal transplant.
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http://dx.doi.org/10.6002/ect.2016.0120DOI Listing
May 2016

Abnormal circadian blood pressure regulation in children with nocturnal enuresis.

Ren Fail 2016 Jul 7;38(6):899-905. Epub 2016 Apr 7.

a Department of Pediatric Nephrology , University of Başkent , Ankara , Turkey.

Introduction: To investigate autonomic nervous system function in enuretic children by performing ambulatory blood pressure monitor (ABPM) for 24 h.

Methods: Twenty-eight children ranging in age from 6 to 15 years with primary nocturnal enuresis and 27 age-matched healthy controls were enrolled and they get 24 h ABPM. Hypertension was defined as standard deviation score (SDS) > 1.64 (i.e., >95th percentile) adjusted for gender and height. Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were carried out in all children. They have also requested to have a diary about daily fluid intake and urine volume.

Results: Although the mean 24-h and daytime diastolic blood pressure (BP) did not differ between the groups, systolic BP (SBP) was significantly higher in enuretic children (p < 0.05). The mean night-time SBP, DBP values, SDS and BP loads were found to be significantly higher than those in the controls (p < 0.01). A lack of nocturnal decrease was more prevalent in the enuretic children compared with the control subjects, the difference was statistically significant for DBP but not for SBP. Patients with elevated night-time BP load was found to have higher frequency of urinary incontinence per week as well as per night when compared with enuretic children with normal night-time BP load (r = 0.72, r = 0.69, p < 0.01, respectively).

Conclusion: Subtle abnormalities of circadian BP regulation in enuretic children indicated by a selective elevation of nocturnal SBP, DBP, and MAP, and attenuated nocturnal dipping may reflect sympathetic hyper activation and its possible role in pathogenesis of enuresis.
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http://dx.doi.org/10.3109/0886022X.2016.1164064DOI Listing
July 2016

Rituximab Therapy and Infection Risk in Pediatric Renal Transplant Patients.

Exp Clin Transplant 2016 Apr 8;14(2):172-5. Epub 2016 Jan 8.

From the Department of Pediatric Nephrology, Baskent University, Ankara, Turkey.

Objectives: Rituximab is a monoclonal antibody directed against the CD20 molecule on pre-B and mature B cells and is used in transplant recipients for the prevention and treatment of alloantibody-mediated rejection or for the treatment of disease recurrence after transplant. In most patients, rituximab has been safe and well-tolerated, but the long-term adverse effects of rituximab are currently unknown.

Materials And Methods: We retrospectively evaluated 78 pediatric renal transplant recipients for the occurrence of infectious disease. Patients who received rituximab therapy were divided into 2 groups: those who developed an infection and those who did not. The 2 groups were compared for serious infections, hospitalization, graft loss, and death rates.

Results: Eighteen transplant patients received rituximab therapy for various causes. The number of rituximab courses given varied according to the cause and ranged from 1 to 8 courses. The dose at each course was 375 mg/m(2). Median age of all recipients was 16.00 years (min-max:, 5.00-22.00 y), and median follow-up time was 2.00 years (min-max:, 1.00-3.00 y). Serious infections (bacterial sepsis, tuberculosis, Cytomegalovirus infection, varicella-zoster virus infection, Polyomavirus-associated nephropathy, and acute pyelonephritis) were observed in 8 patients who received rituximab therapy. We observed that patients with antibody-mediated rejection had significantly increased infection rate. Patients who had used rituximab combined with antithymocyte globulin and higher rituximab course number and higher pretreatment CD19 and CD20 levels had higher risk of infection (P < .05).

Conclusions: The combined use of rituximab with additional treatments such as antithymocyte globulin, intravenous immunoglobulin, and repeated plasma exchange may be associated with high risk of infectious disease. Especially for those patients who required intensive and repetitive treatment, such as antibody-mediated rejection, rituximab treatment should be used with caution. Infection risk should be closely monitored, although mainly in patients who receive T-cell-depleting agents.
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http://dx.doi.org/10.6002/ect.2014.0156DOI Listing
April 2016

Low-Grade Persistent Hyperparathyroidism After Pediatric Renal Transplant.

Exp Clin Transplant 2016 06 17;14(3):294-8. Epub 2015 Nov 17.

From the Pediatric Nephrology Department, Baskent University, Ankara, Turkey.

Objectives: Hyperparathyroidism, a frequent complication of chronic kidney disease, persists after renal transplant. Our aims were to examine the status of parathyroid hormone levels and to determine the clinical and biochemical risk factors of persistent hyperparathyroidism after transplant.

Materials And Methods: Our study included 44 pediatric renal transplant recipients with stable graft function. Median follow-up after transplant was 17.5 months (range, 12-126 mo). Patients did not receive routine vitamin D or calcium supplements after transplant, and none had undergone previous parathyroidectomy. Bone mineral densitometry of the lumbar spine was measured.

Results: Fifteen patients (34%) had parathyroid hormone levels greater than 70 pg/mL (normal range, 10-70 pg/mL). Duration of dialysis before transplant was longer in patients with persistent hyperparathyroidism. Mean serum bicarbonate levels were significantly lower in patients with persistent hyperparathyroidism than in patients without persistent hyperparathyroidism after transplant. A significant negative correlation was noted between parathyroid hormone level and serum bicarbonate level. Another significant negative correlation was shown between parathyroid hormone level and z score.

Conclusions: We found that persistent hyperparathyroidism is related to longer dialysis duration, lower serum bicarbonate level, and lower z score. Pretransplant dialysis duration is an important predictor of persistent hyperparathyroidism. Early identification of factors that contribute to persistent hyperparathyroidism after transplant could lead to treatment strategies to minimize or prevent its detrimental effects on bone health and growth in pediatric transplant recipients.
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http://dx.doi.org/10.6002/ect.2014.0157DOI Listing
June 2016

Parvovirus B19-induced acute bilateral carpal tunnel syndrome in twin girls.

Acta Orthop Traumatol Turc 2015 ;49(5):568-70

Başkent University Faculty of Medicine, Department of Neurology, Konya, Turkey.

We describe 2 cases of 6-year-old twin girls presenting with acute carpal tunnel syndrome (CTS) associated with human parvovirus B19 (HPV-B19) infection, as evidenced by serological data and detection of HPV-B19 DNA in blood with use of polymerase chain reaction (PCR). To our knowledge, this is the first time that HPV-B19 infection has been suggested as the causal agent of simultaneous acute bilateral CTS in twins, thus presenting the possibility that similar immunologic responses can be observed in twins during viral infections.
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http://dx.doi.org/10.3944/AOTT.2015.13.0020DOI Listing
July 2016

Five-year assessment of causative agents and antibiotic resistances in urinary tract infections.

Turk Pediatri Ars 2014 Jun 1;49(2):124-9. Epub 2014 Jun 1.

Division of Pediatric Neurology, Başkent University Faculty of Medicine, Ankara, Turkey.

Aim: To show the distribution and changes of causative agents of urinary tract infections in children and resistance rates by years and select the most appropriate antibiotics.

Material And Methods: In this study, the Başkent University Alanya Research and Application Hospital automation system microbiology recording book was screened retrospectively. Growth of a single microorganism above 105 colonies (cfu/mL) was included in the assessment. Throughout the study, 10 691 urinary cultures were studies and growth was found in 392 (3.7%).

Results: Three hundred and nine (78.8%) of the samples with growth belonged to girls. Growth was found in the neonatal period in 32 patients (8.2%). The most commonly isolated microorganism was Escherichia coli (E. coli) which was found in 68.4% of the patients. Klebsiella spp. were found with a rate of 12.0%; Enterobacter spp. were found with a rate of 10.7% and proteus spp. were found with a rate of 5.1%. Resistance to cefalotin (62.1%), trimethoprim-sulfamethoxasole (43.1%), amoxycillin-clavulanate (34.8%), ampicillin (30.4%), cefixim (26.3%) and nitrofurantoin (3.6%) was found in E. coli species. The antibiotic which had the highest resistance rate was ampicillin with a rate of 93.2% for klebsiella and 83.4% for enterobacter. Klebsiella spp. were the most commonly grown pathogens in newborns (40.6%). In a follow-up period of 5 years, the resistance of E. coli to amoxycillin-clavulanate regressed from 40.3% to 31.3%, while the resistance to trimethoprim-sulfamethoxasole (TMP-SMX) regressed from 45.6% to 34.7%.

Conclusions: A high resistance against first-generation cephalosporins, ampicillin, amoxycillin-clavulanate and TMP-SMX which are the first-line antibiotics in childhood urinary tract infections was found. Carbapenem (meropenem, imipenem) resistance was not found in our center. Nitrofurantoin, aminoglycosides and cefixime can be recommended for empirical treatment in our hospital because of low resistance. Antibiotic treatment should be redecided according to in vitro antibiotic sensitivity results.
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http://dx.doi.org/10.5152/tpa.2014.1505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462286PMC
June 2014

Familial Mediterranean fever with a single MEFV mutation: comparison of rare and common mutations in a Turkish paediatric cohort.

Clin Exp Rheumatol 2015 Nov-Dec;33(6 Suppl 94):S152-5. Epub 2015 May 25.

Department of Paediatric Nephrology and Rheumatology, School of Medicine, Ankara University, Ankara, Turkey.

Objectives: Presence of common MEFV gene mutations strengthened the diagnosis of FMF in addition to the typical clinical characteristics of FMF. However, there are also rare mutations. P369S, A744S, R761H, K695R, F479L are the main rare mutations in Turkish population. We aimed to evaluate FMF patients with a single allele MEFV mutation and to compare patients with common and rare mutations.

Methods: We retrospectively reviewed the medical records of FMF patients with a single allele mutation who were followed up between 2008 and 2013 in six centres. We compared the patients with rare and common mutations for disease severity score, frequent exacerbations ( >1 attack per month), long attack period (>3 day), symptoms, age at the onset of symptoms, gender, consanguinity, and family history.

Results: Two hundred and seventeen patients (M/F=101/116) with the diagnosis of FMF and single mutation were included. Heterozygote mutations were defined as common (M694V, V726A, M68OI) and rare mutations (A744S, P369S, K695R, R761H, F479L). Sixty-seven patients (27 males, 40 females) had one single rare mutation and 150 (74 males, 76 females) had one single common mutation. No difference was found between the rare and common mutations with respect to the disease severity score. There was no significant difference between common and rare heterozygote form of mutations in terms of disease severity.

Conclusions: Patients with typical characteristics of FMF, with some rare mutations (A744S, P369S) should be treated in the same manner as patients with a common mutation.
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January 2016

HPSE2 mutations in urofacial syndrome, non-neurogenic neurogenic bladder and lower urinary tract dysfunction.

Nephron 2015 28;130(1):54-8. Epub 2015 Apr 28.

Department of Pediatric Nephrology, Ankara University School of Medicine, Ankara, Turkey.

Background: Urofacial syndrome (UFS) is characterised by congenital bladder dysfunction accompanied by a characteristic abnormal grimace upon smiling and crying. In recent years, biallelic mutations of HPSE2 and LRIG2 have been reported in UFS patients. Non-neurogenic neurogenic bladder (NNNB) has a bladder identical to UFS without typical facial features. The aim of this study was to analyse HPSE2 mutations in patients with UFS and NNNB or severe lower urinary tract dysfunction (LUTD) without abnormal facial expression.

Methods: Patients with UFS, NNNB and severe LUTD were enrolled in the study. We examined a total of 35 patients from 33 families. There were seven UFS patients from five different families, 21 patients with NNNB and seven with LUTD. HPSE2 gene mutation analysis was performed using the polymerase chain reaction protocol followed by Sanger sequencing in these patients.

Results: A twin pair with UFS was found to be homozygous for c.457C>T (p.Arg153*) mutation. No other pathogenetic variant was detected.

Conclusion: HPSE2 mutations were found in one UFS family but not detected in patients with NNNB and severe LUTD. Considering the increasingly recognised cases of NNNB that were diagnosed in early childhood period, genetic factors appear to be responsible. Thus, further genetic studies are needed to discover novel associated gene variants in these bladder anomalies.
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http://dx.doi.org/10.1159/000381465DOI Listing
February 2016

Effects of hyperuricemia on renal function in pediatric renal transplant recipients.

Exp Clin Transplant 2015 Apr;13 Suppl 1:247-50

From the Department of Family Medicine, Baskent University Faculty of Medicine, Ankara, Turkey.

Objectives: Hyperuricemia is common in pediatric renal transplant recipients, and it is associated with poor allograft outcomes. Hyperuricemia occurs early after transplant and is associated with use of diuretics, cyclosporine therapy, a history of hyperuricemia, and decreased glomerular filtration rate. We aimed to investigate causes and effects of hyperuricemia on allograft outcomes in our patients.

Materials And Methods: There were 81 pediatric transplant patients (41 female and 40 male) included in the study. Demographic characteristics and laboratory parameters were recorded. Risk factors for hyperuricemia and the effects of plasma uric acid levels at 3, 6, 12, and 36 months on allograft outcomes were evaluated.

Results: Mean age was 16.9 ± 5.6 years. Mean follow-up after transplant was 3.5 ± 0.47 years. Hyperuricemia was detected in 17.6% patients. A significant negative correlation was observed between 6-month uric acid level and 36-month glomerular filtration rate (r = -0.33, P = .04; r = -0.33, P = .017). A significant positive correlation between 3- and 6-month uric acid levels and 36-month plasma creatinine level was observed (r = -0.44, P = .01; r = -0.51, P = .001). There was no significant correlation between plasma uric acid level and body mass index, plasma lipid levels, use of diuretics, or immunosuppressive treatment (tacrolimus or cyclosporine).

Conclusions: Uric acid levels may have predictive value in the long-term assessment of renal function. Posttransplant hyperuricemia can be used as a long-term prognostic marker of poor renal outcome. Patients with hyperuricemia should be monitored closely for renal function.
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April 2015

Liver and kidney transplant in primary hyperoxaluria: a single center experience.

Exp Clin Transplant 2015 Apr;13 Suppl 1:145-7

From the Department of General Surgery, Baskent University, School of Medicine, Ankara, Turkey.

Objectives: Primary hyperoxaluria, especially type 1, is a severe disease with multisystem morbidity and high mortality. We present 3 primary hyperoxaluria type 1 patients who underwent liver transplant, including living-donor liver transplant or combined liver and kidney transplant in our institution.

Case Reports: Patients who underwent liver transplant or combined liver/kidney transplant at our institution were evaluated, retrospectively. Between January 2002 and 2013, there were 3 patients who underwent transplant for primary hyperoxaluria. All 3 patients had disease onset in childhood, and the definitive diagnosis was established at age < 1, 6, and 8 years. Although early diagnosis was made, primary hyperoxaluria resulted in end-stage renal disease in 2 patients, and hemodialysis was introduced before liver transplant. All 3 patients underwent living-donor liver transplant. Case 1 was a 10-year-old girl who had an uneventful course after living-donor liver transplant, and she received a living-donor kidney transplant from the same donor 4 months after living-donor liver transplant. Case 2 was a 7-yearold boy who was the younger brother of the first patient; he did not have end-stage renal disease or any renal disorder after successful living-donor liver transplant. Case 3 was a 3-year-old boy who was diagnosed at age 2 months with renal disorders; although he was discharged from the hospital after living-donor liver transplant, he was readmitted because of unconsciousness that developed 1 day after discharge, and he died because of intracranial hemorrhage 2 months after liver transplant, unable to receive a kidney transplant.

Conclusions: Primary hyperoxaluria is a rare disorder that is difficult to diagnose until end-organ damage is severe. Outcomes may be improved with early and accurate diagnosis, aggressive supportive treatment, and correction of the enzyme defect by liver transplant before systemic oxalosis develops. However, kidney transplant or combined liver and kidney transplant is required in many primary hyperoxaluria type 1 patients because of the delayed diagnosis or long organ waiting time.
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April 2015

Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.

Clin J Am Soc Nephrol 2015 Apr 29;10(4):592-600. Epub 2015 Jan 29.

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

Background And Objectives: Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome.

Design, Setting, Participants, & Measurements: Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal.

Results: Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis.

Conclusions: The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.
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http://dx.doi.org/10.2215/CJN.06260614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386250PMC
April 2015

Success of eculizumab in the treatment of atypical hemolytic uremic syndrome.

Pediatr Nephrol 2015 May 11;30(5):783-9. Epub 2014 Nov 11.

Pediatric Nephrology Department, Baskent University, 54. Cadde N:72/3, Bahcelievler, Cankaya, Ankara, 06340, Turkey.

Background: Disorders of complement regulation are the most important etiology of atypical hemolytic uremic syndrome (aHUS). Recent studies demonstrate that eculizumab is beneficial in long-term aHUS treatment. We present a series of children with aHUS resistant to/dependent on plasma exchange (PE) who were treated with eculizumab.

Methods: This was a retrospective study in which data were retrieved from the medical files of children who had received PE as treatment for aHUS. The data retrieved included age, sex, presenting symptoms, presence of diarrhea/vomiting, hospitalization duration, laboratory data on admission and follow-up, need for transfusion or dialysis, response to PE, response to eculizumab and outcome.

Results: Of the 15 children diagnosed with aHUS in 2011 and 2012 in our departments, ten were resistant to, or dependent on, plasma therapy and treated with eculizumab; these children were enrolled in the study. Three patients had relapses, and seven had a new diagnosis. Nine children had oliguria or anuria, and eight required dialysis. Hypertension was observed in six patients. Neurologic involvement developed in six patients, with the symptoms including seizures, loss of balance, vision loss and severe confusion. Five and five patients were resistant to and dependent on plasma therapy, respectively. Following the start of eculizumab treatment, all patients achieved full recovery of renal function and hematologic parameters.

Conclusions: In our ten pediatric patients with aHUS who did not respond to PE, eculizumab was a lifesaving therapy and improved their quality of life. Early eculizumab use was a rescue therapy for renal function. Our results show that eculizumab is an effective treatment for aHUS. However, more studies are needed on the long-term efficacy and safety of eculizumab in children with aHUS and to determine the optimal duration of treatment.
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http://dx.doi.org/10.1007/s00467-014-3003-4DOI Listing
May 2015