Publications by authors named "Nur Canpolat"

79 Publications

Hemodiafiltration maintains a sustained improvement in blood pressure compared to conventional hemodialysis in children-the HDF, heart and height (3H) study.

Pediatr Nephrol 2021 Feb 24. Epub 2021 Feb 24.

University College London Great Ormond Street Hospital for Children and Institute of Child Health, London, UK.

Background: Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1 year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF).

Methods: This is a post hoc analysis of the "3H - HDF-Hearts-Height" dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1 year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) ≥95th percentile.

Results: Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12 months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality (β = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (β = 0.13 [95%CI 0.06-0.19]; p = 0.0003).

Conclusions: Children on HD had a significant and sustained increase in BP over 1 year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups.
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http://dx.doi.org/10.1007/s00467-021-04930-2DOI Listing
February 2021

Rituximab treatment for difficult-to-treat nephrotic syndrome in children: a multicenter, retrospective study.

Turk J Med Sci 2021 Feb 14. Epub 2021 Feb 14.

Background/aim This study aimed to evaluate the efficacy of rituximab in children with difficult-to-treat nephrotic syndrome, considering the type of disease (steroid-sensitive or ?resistant) and the dosing regimen. Materials and methods This multicenter retrospective study enrolled children with difficult-to-treat nephrotic syndrome on rituximab treatment from 13 centers. The patients were classified based on the steroid response and initial dose of rituximab as low (single dose of 375 mg/m2) or high (2-4 doses of 375 mg/m2). Clinical outcomes were compared. Results Data from 42 children [20 steroid-sensitive (frequent relapsing / steroid-dependent) and 22 steroid-resistant nephrotic syndrome, aged 1.9-17.3 years] were analyzed. Eleven patients with steroid-sensitive nephrotic syndrome (55%) had a relapse following initial rituximab therapy, with the mean time to first relapse of 8.4±5.2 months. Complete remission was achieved in 41% and 36% of steroid-resistant patients, with the median remission time of 3.65 months. At Year 2, eight patients in steroid-sensitive group (40%) and four in steroid-resistant group (18%) were drug-free. Total cumulative doses of rituximab were higher in steroid-resistant group (p=001). Relapse rates and time to first relapse in steroid-sensitive group or remission rates in steroid-resistant group did not differ between the low and high initial dose groups. Conclusions The current study reveals that rituximab therapy may provide a lower relapse rate and prolonged relapse-free survival in the steroid-sensitive group, increased remission rates in the steroid-resistant group, and a significant number of drug-free patients in both groups. The optimal regimen for initial treatment and maintenance needs to be determined.
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http://dx.doi.org/10.3906/sag-2012-297DOI Listing
February 2021

Influenza and pneumococcus vaccination rates in pediatric dialysis patients in Europe: Recommendations vs reality A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group Study.

Turk J Med Sci 2021 Feb 4. Epub 2021 Feb 4.

Background: Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although, vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers.

Methods: In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during one year of observation period between 01.01.2014 and 01.01.2015.

Results: In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). 50% of centers recommended pneumococcal polysaccharide vaccine following routine PCV series. Significantly higher pneumococcal vaccination rate (43.9 %) was seen in PD patients compared to those on HD (32.9 %) (p=0.035), while the rates for influenza were similar (42.4 % and 46.1 respectively, p=0.496). Among all dialysis patients, 2,2 % (n=8) developed pneumonia and 6.4 % (n=23) infected by influenza. Pneumococcic pneumonia rate was 5 % for 140 patients who received anti-pneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p=0.007). The influenza virus infection rates were similar for patients vaccinated and non-vaccinated (7 % and 6 %, respectively).

Conclusions: Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.
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http://dx.doi.org/10.3906/sag-2012-26DOI Listing
February 2021

Strong mesangial IgA staining-does it always refer to IgA nephropathy in a patient with proteinuria and hematuria? Answers.

Pediatr Nephrol 2021 Jan 18. Epub 2021 Jan 18.

Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-020-04899-4DOI Listing
January 2021

Strong mesangial IgA staining-does it always refer to IgA nephropathy in a patient with proteinuria and hematuria? Questions.

Pediatr Nephrol 2021 Jan 18. Epub 2021 Jan 18.

Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-020-04886-9DOI Listing
January 2021

Telemedicine Applications in a Tertiary Pediatric Hospital in Turkey During COVID-19 Pandemic.

Telemed J E Health 2020 Dec 9. Epub 2020 Dec 9.

Division of Pediatric Nephrology, Department of Pediatrics, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

A novel type of Coronavirus emerged at Wuhan in late 2019 involving preferentially the respiratory system. Owing to the rapid spread, almost 22 million people became infected and 700,000 died. Similar to other countries, the need for additional hospital beds and intensive care units required diversion of health care resources toward the care for those with COVID-19 in Turkey. Telemedicine appeared as a safe and low-cost alternative for the maintainability of pediatric health services during the pandemics. Within this context, we aimed to deliver the health services through telemedicine during the follow-up of chronic childhood diseases. This prospective study included five pediatric subspecialties, including allergy immunology, hematology and oncology, nephrology, rheumatology, and inborn metabolic disorders. After the interview, patients and involved physicians were requested to fill out a questionnaire designed to measure the level of satisfaction and the quality of the service we offered. Of the 263 interviews, overall patient and physician satisfaction was 99% and 87%, respectively. As results of the interviews, 250 routine visits were performed, 181 acute complaints were assessed, drug changes were made in 118 patients, 9 patients were determined to be unable to get their drugs, and 12 who misused their drugs. The main advantage of the telemedicine declared by the patients was "not to waste time for transportation." The main concerns of the participants were inability to perform physical and laboratory examinations. Consequently, we considered telemedicine as a feasible alternative not only during pandemics but also in daily practice in Turkey.
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http://dx.doi.org/10.1089/tmj.2020.0381DOI Listing
December 2020

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

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

Predictors of poor kidney outcome in children with C3 glomerulopathy.

Pediatr Nephrol 2020 Oct 31. Epub 2020 Oct 31.

Department of Pediatric Nephrology, Erciyes University, Faculty of Medicine, Kayseri, Turkey.

Background: C3 glomerulopathy (C3G) is characterized by heterogeneous clinical presentation, outcome, and predominant C3 accumulation in glomeruli without significant IgG. There is scarce outcome data regarding childhood C3G. We describe clinical and pathological features, treatment and outcomes, and risk factors for progression to chronic kidney disease stage 5 (CKD5) in the largest pediatric series with biopsy-proven C3G.

Methods: Sixty pediatric patients with C3G from 21 referral centers in Turkey were included in this retrospective study. Patients were categorized according to CKD stage at last visit as CKD5 or non-CKD5. Demographic data, clinicopathologic findings, treatment, and outcome data were compared and possible risk factors for CKD5 progression determined using Cox proportional hazards model.

Results: Mean age at diagnosis was 10.6 ± 3.0 years and follow-up time 48.3 ± 36.3 months. Almost half the patients had gross hematuria and hypertension at diagnosis. Nephritic-nephrotic syndrome was the commonest presenting feature (41.6%) and 1/5 of patients presented with nephrotic syndrome. Membranoproliferative glomerulonephritis was the leading injury pattern, while 40 patients had only C3 staining. Patients with DDD had significantly lower baseline serum albumin compared with C3GN. Eighteen patients received eculizumab. Clinical remission was achieved in 68.3%. At last follow-up, 10 patients (16.6%) developed CKD5: they had lower baseline eGFR and albumin and higher frequency of nephrotic syndrome and dialysis requirement than non-CKD5 patients. Lower serum albumin and eGFR at diagnosis were independent predictors for CKD5 development.

Conclusions: Children with C3G who have impaired kidney function and hypoalbuminemia at diagnosis should be carefully monitored for risk of progression to CKD5. Graphical abstract.
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http://dx.doi.org/10.1007/s00467-020-04799-7DOI Listing
October 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

Efficacy of tolterodine in children with overactive bladder.

Turk Pediatri Ars 2020 23;55(3):284-289. Epub 2020 Sep 23.

Department of Pediatric Nephrology, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul, Turkey.

Aim: Tolterodine is an anticholinergic drug used for the treatment of overactive bladder. We evaluated the effects of tolterodine on clinical symptoms and compared its efficacy with that of oxybutynin in terms of bladder capacity, bladder wall thickness, and post-void residual volume in children with overactive bladder.

Material And Methods: Twenty-six patients who were treated with tolterodine for overactive bladder (20 girls, mean age 8.0±2.2 years) were evaluated retrospectively. Twenty patients with overactive bladder who had undergone oxybutynin treatment (15 girls, mean age 7.6±1.8 years) served as the control group. Dysfunctional voiding symptom scoring was used to evaluate the clinical response to tolterodine. To investigate the effect of treatment on the bladder, ultrasonographic data at baseline and the third month were compared with the oxybutynin group.

Results: The dysfunctional voiding symptom scores significantly decreased after the third month of tolterodine treatment (p<0.001). Bladder capacity significantly increased (p<0.001), and filled bladder wall thickness decreased (p=0.007); however, post-void residual volumes significantly increased (p<0.001) at the third month. No serious adverse effects were recorded during tolterodine treatment. The increase in bladder capacity at the third month in the tolterodine group was similar to that in the oxybutynin group (p=0.77), but the decrease in filled bladder wall thickness was significantly greater in the tolterodine group (p=0.019).

Conclusion: Tolterodine remarkably ameliorates the clinical symptoms of overactive bladder in a short time, and seems to be as effective as oxybutynin for the treatment of overactive bladder in children. Its effect on reduction of bladder wall thickness appears to be superior to that of oxybutynin.
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http://dx.doi.org/10.14744/TurkPediatriArs.2020.98215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536450PMC
September 2020

Natural history of patients with infantile nephrolithiasis: what are the predictors of surgical intervention?

Pediatr Nephrol 2021 Apr 2;36(4):939-944. Epub 2020 Oct 2.

Department of Urology, Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, 34098, Istanbul, Turkey.

Background: We evaluated the risk factors for the requirement of surgical intervention in infants with nephrolithiasis.

Methods: The medical records of 122 (156 kidney units (KU)) infants were reviewed. The clinical features, stone characteristics, changes in stone status, and treatment protocols were noted. The stone status of the KU was categorized into 3 groups according to the change in size between the first and last ultrasound: resolution, unchanged, and growth.

Results: The median age was 8 months (r: 2-12). The median length of follow-up was 16 months (r: 10-36). Resolution was detected in 94 KUs (60%). Stone growth was detected in 39 KUs (25%), and stone size was unchanged in 23 KUs (15%). Surgical intervention was required in 26 patients (17%). A history of intensive care unit (ICU) follow-up and a stone size > 5 mm at time of diagnosis were defined as independent risk factors for stone growth (p = 0.005, < 0.001, respectively). The surgical intervention rate was higher in stones > 5 mm and stones with pelvic localization (p = 0.018, 0.021, respectively). Stone resolution was higher in patients with stone size ≤ 5 mm (p = 0.018).

Conclusion: A stone size > 5 mm at the time of diagnosis and a history of ICU follow-up are independent risk factors for stone growth. Pelvic localization of stones and stones > 5 mm are associated with an increased risk of surgical intervention.
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http://dx.doi.org/10.1007/s00467-020-04781-3DOI Listing
April 2021

Anemia after kidney transplantation: Does its basis differ from anemia in chronic kidney disease?

Pediatr Transplant 2020 12 14;24(8):e13818. Epub 2020 Aug 14.

Department of Pediatric Nephrology, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Background: Although similar factors play a role in both PTA and anemia in patients with CKD, additional risk factors exist in the pathogenesis of PTA. The present study aimed at comparing anemia and inflammation-related parameters between RTx recipients and CKD patients and elucidating the risk factors of PTA.

Methods: This single-centered, cross-sectional study consisted of 68 participants: 48 were in the RTx group and 20 were in the CKD group. The CKD patients were comparable to the RTx recipients in terms of age, gender, and eGFR. Serum levels of EPO, hepcidin, and IL-6 were measured by enzyme-linked immunosorbent assays. The ratio of EPO/Hb was calculated to estimate endogenous EPO resistance.

Results: The prevalence of anemia was 46% in the RTx group and 30% in the CKD group (P = .23). RTx recipients had significantly lower Hb (P = .04), higher EPO (P < .001), and ferritin levels (P = .001), and higher EPO/Hb ratios (P < .001); however, CKD patients showed a higher frequency of absolute iron deficiency (P = .008). Neither hepcidin nor IL-6 levels differed between the two groups. Hb level of RTx recipients was correlated with only eGFR (r = .437, P = .002) but not with any of the transplantation-related factors, while Fe level was the only parameter to be correlated with Hb level of CKD patients (r = .622, P = .01).

Conclusion: In the present study comparing GFR-matched RTx and CKD patients, lower GFR level appears to be the factor most strongly associated with anemia, and endogenous EPO resistance is among the contributing factors to PTA.
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http://dx.doi.org/10.1111/petr.13818DOI Listing
December 2020

Is the burden of late hypertension and cardiovascular target organ damage in children and adolescents with coarctation of the aorta after early successful repair different to healthy controls?

Cardiol Young 2020 Sep 22;30(9):1305-1312. Epub 2020 Jul 22.

Department of Pediatric Cardiology, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Objective: Cardiovascular morbidity is high in patients with coarctation of aorta even after successful repair. This study aimed to assess the frequency of late hypertension and the relationship between ambulatory hypertension and cardiovascular target organ damage in children and adolescents after early and successful repair of coarctation of the aorta.

Methods: Twenty-five children and adolescents (mean age 13.5 ± 3.43 years) with repaired coarctation of the aorta (median age at repair 4 months, arm-leg gradient <20 mmHg) and 16 healthy controls were included. Office and ambulatory blood pressure, pulse wave velocity, and left ventricular mass index were assessed.

Results: Both day- and night-time systolic blood pressure standard deviation score and left ventricular mass index were significantly higher in patients compared to controls (p ≤ 0.001 for all), whereas pulse wave velocity did not differ. The prevalence of masked hypertension, isolated nocturnal hypertension, and left ventricular hypertrophy were 40, 28, and 24%, respectively. Left ventricular mass index was higher in patients with sustained hypertension, masked hypertension, and normotension compared to controls (p < 0.05). In multivariate analysis, higher night-time systolic blood pressure standard deviation score was the only independent predictor of left ventricular mass index.

Conclusion: The present study reveals a high prevalence of masked hypertension, isolated nocturnal hypertension, and left ventricular hypertrophy in children and adolescents with coarctation of the aorta even after early and successful repair. Ambulatory blood pressure monitoring should be considered to diagnose hypertension. All coarctation of aorta patients should be followed up lifelong and encouraged to establish a healthy lifestyle starting from childhood.
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http://dx.doi.org/10.1017/S104795112000205XDOI Listing
September 2020

A homozygous HOXA11 variation as a potential novel cause of autosomal recessive congenital anomalies of the kidney and urinary tract.

Clin Genet 2020 10;98(4):390-395

Nephrogenetics Laboratory, Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Congenital anomalies of the kidney and urinary tract (CAKUT) is the leading cause of end-stage kidney disease in children. Until now, more than 50 monogenic causes for CAKUT have been described, all of which only explain 10% to 20% of all patients with CAKUT, suggesting the presence of additional genes that cause CAKUT when mutated. Herein, we report two siblings of a consanguineous family with CAKUT, both of which rapidly progressed to chronic kidney disease in early childhood. Whole-exome sequencing followed by homozygosity mapping identified a homozygous variation in HOXA11. We therefore showed for the first time an association between a homozygous HOXA11 variation with CAKUT in humans, expanding the genetic spectrum of the disease.
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http://dx.doi.org/10.1111/cge.13813DOI Listing
October 2020

Renal Biopsy Prognostic Findings in Children With Atypical Hemolytic Uremic Syndrome.

Pediatr Dev Pathol 2020 Sep-Oct;23(5):362-371. Epub 2020 May 14.

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

Background: The aim of this study was to investigate the histopathological findings in kidney biopsies in children with atypical hemolytic uremic syndrome (aHUS) and to determine whether specific pathological findings in aHUS have a prognostic value.

Methods: Renal biopsy specimens of 29 patients who were recorded in the national Turkish aHUS registry database were available for review. Histopathological findings were compared with the clinical and laboratory features at the presentation and the final outcome.

Results: The mean age at presentation and follow-up period was 4.9 ± 3.9 and 3.9 ± 3.0 years, respectively. The median time interval from the first symptom to biopsy was 10 days. Vascular thrombosis and interstitial fibrosis were significantly related to chronic kidney disease (CKD) requiring dialysis or kidney transplantation during follow-up (5.6-fold, for both). Glomerular necrosis, cortical necrosis, and glomerular sclerosis were markedly associated with CKD without dialysis (6.2-fold, 13.3-fold, and 8.8-fold, respectively). However, presence of endothelial swelling, subendothelial widening, and fragmented erythrocytes was found to be correlated with a favorable final outcome.

Conclusions: Presence of vascular thrombosis, cortical necrosis, and glomerular sclerosis in histopathological evaluation correlated with developing CKD. Chronic changes in the interstitial compartment were also related to poor prognosis, a finding that has been shown for the first time in pediatric aHUS cases.
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http://dx.doi.org/10.1177/1093526620925947DOI Listing
May 2020

Mercury intoxication resembling pediatric rheumatic diseases: case series and literature review.

Rheumatol Int 2020 Aug 27;40(8):1333-1342. Epub 2020 Apr 27.

Cerrahpasa Medical School, Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Mercury is the only metal that remains in liquid form at the room temperature. It is a very toxic metal and even short-term exposure can lead to poisoning. Mercury intoxication can affect many systems such as skin, cardiovascular, genitourinary, central and peripheral nervous, respiratory, and musculoskeletal system. Consequently, the diagnosis of mercury intoxication can be challenging due to its non-specific and multisystemic presentation. Herein, we report five pediatric cases with mercury intoxication from two families that were initially misdiagnosed as rheumatic disorders. We also performed a literature review about pediatric cases with mercury intoxication to investigate the clinical findings in children, the source of intoxication, and the current treatment preferences. As in our cases, reported patients were previously misdiagnosed as various infectious and/or rheumatic diseases before the diagnosis of mercury intoxication was established. A delay in diagnosis and treatment can cause serious morbidities and even mortality. We report this case series to emphasize the multisystemic presentation of mercury intoxication, and to remind and provide clues for physicians to recognize this rare toxicologic syndrome.
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http://dx.doi.org/10.1007/s00296-020-04589-2DOI Listing
August 2020

Discontinuation of RAAS Inhibition in Children with Advanced CKD.

Clin J Am Soc Nephrol 2020 05 6;15(5):625-632. Epub 2020 Apr 6.

Division of Pediatric Nephrology, University Hospital Heidelberg, Heidelberg, Germany.

Background And Objectives: Although renin-angiotensin-aldosterone system inhibition (RAASi) is a cornerstone in the treatment of children with CKD, it is sometimes discontinued when kidney function declines. We studied the reasons of RAASi discontinuation and associations between RAASi discontinuation and important risk markers of CKD progression and on eGFR decline in the Cardiovascular Comorbidity in Children with CKD study.

Design, Setting, Participants, & Measurements: In this study, 69 children with CKD (67% male, mean age 13.7 years, mean eGFR 27 ml/min per 1.73 m) who discontinued RAASi during prospective follow-up were included. Initial change in BP, albuminuria, and potassium after discontinuation were assessed (median time 6 months). Rate of eGFR decline (eGFR slope) during a median of 1.9 years before and 1.2 years after discontinuation were estimated using linear mixed effects modeling.

Results: Physician-reported reasons for RAASi discontinuation were increase in serum creatinine, hyperkalemia, and symptomatic hypotension. After discontinuation of RAASi, BP and albuminuria increased, whereas potassium decreased. eGFR declined more rapidly after discontinuation of RAASi (-3.9 ml/min per 1.73 m per year; 95% confidence interval, -5.1 to -2.6) compared with the slope during RAASi treatment (-1.5 ml/min per 1.73 m per year; 95% confidence interval, -2.4 to -0.6; =0.005). In contrast, no change in eGFR slope was observed in a matched control cohort of patients in whom RAASi was continued.

Conclusions: Discontinuation of RAASi in children with CKD is associated with an acceleration of kidney function decline, even in advanced CKD.
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http://dx.doi.org/10.2215/CJN.09750819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269205PMC
May 2020

Factors influencing blood pressure and microalbuminuria in children with type 1 diabetes mellitus: salt or sugar?

Pediatr Nephrol 2020 07 24;35(7):1267-1276. Epub 2020 Mar 24.

Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098, Istanbul, Turkey.

Background: The aim of the study is to identify the effect of salt intake and diabetes itself on blood pressure (BP) profile and microalbuminuria in children with type one diabetes mellitus (T1DM). Our hypothesis is that higher amount of salt consumption and/or hyperglycemia may impair blood pressure pattern in children with T1DM.

Methods: This cross-sectional study included 84 children and adolescents with T1DM (62% females, age 13.9 ± 3.2 years, disease duration 7.3 ± 3.1 years, 43% poorly controlled diabetes) and 54 aged- and sex-matched healthy children with an adequately collected 24-h urine samples. Urine sodium, creatinine, and microalbumin were measured and salt intake was assessed on the basis of sodium excretion in 24-h urine. Blood pressure profile of the children with T1DM was evaluated with 24-h ambulatory blood pressure monitoring.

Results: Compared to the children with well-controlled diabetes, children with poorly controlled diabetes had significantly higher standard deviation scores (SDS) of nighttime systolic BP (0.22 ± 1.28 vs - 0.87 ± 0.76, p = 0.003) and lower dipping in diastole (13.4 ± 5.9 vs 18.4 ± 8.1, p = 0.046). Among T1DM group, children with the highest quartile of salt intake had higher nighttime systolic and diastolic BP-SDS (0.53 ± 1.25 vs - 0.55 ± 0.73, p = 0.002 and 0.89 ± 1.19 vs 0.25 ± 0.63, p = 0.038, respectively) and lower dipping in systole compared to their counterparts (7.7 ± 5.0 vs 11.5 ± 6.1, p = 0.040). High averaged HbA1c was independently associated with higher both daytime and nighttime systolic BP-SDS (p = 0.010, p < 0.001) and nighttime diastolic BP-SDS (p = 0.001), and lower diastolic dipping (p = 0.001). High salt intake was independently associated with higher nighttime systolic BP-SDS (p = 0.002) and lower systolic dipping (p = 0.019). A 24-h MAP-SDS was the only independent risk factor for microalbuminuria (p = 0.035).

Conclusion: Beside poor diabetic control, high salt consumption appears to be an important modifiable risk factor for impaired BP pattern, which contributes to the development of diabetic kidney disease in children with T1DM.
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http://dx.doi.org/10.1007/s00467-020-04526-2DOI Listing
July 2020

The Frequency of Familial Congenital Anomalies of the Kidney and Urinary Tract: Should We Screen Asymptomatic First-Degree Relatives Using Urinary Tract Ultrasonography?

Nephron 2020 7;144(4):170-175. Epub 2020 Jan 7.

Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey.

Introduction: The objectives of this study were to determine the incidence of congenital anomalies of the kidney and urinary tract (CAKUT) in asymptomatic first-degree relatives of patients with a CAKUT diagnosis and to evaluate the benefits of such screening.

Methods: Files of patients who were followed up at Cerrahpaşa Faculty of Medicine, Pediatric Nephrology Outpatient Clinic, Istanbul University-Cerrahpaşa between 1998 and 2016 were examined retrospectively and those with CAKUT were identified. These patients, and their asymptomatic first-degree relatives, were invited to participate in this study. Ultrasonography of the urinary tract was performed in siblings and parents of 145 CAKUT patients (index cases) who could be reached by phone and agreed to participate.

Results: A total of 412 asymptomatic first-degree relatives of 145 index patients were screened by ultrasound. CAKUT was diagnosed in 23 individuals among the family members of 21 index subjects. Anomalies detected in asymptomatic first-degree relatives were renal agenesis (RA) and grade 3 hydronephrosis (n = 1), RA (n = 7), renal hypodysplasia (n = 7), grade 2 hydronephrosis (n = 1), and grade 1 hydronephrosis (n = 7). The frequency of familial CAKUT was 14.4%. Familial RA was found in 3 of the 5 families of index cases with RA.

Conclusion: The ratio of familial CAKUT was 14.4%. The findings of the present study could not support a systematic family screening to all asymptomatic first-degree relatives; however, family screening with ultrasonography can be considered for children with RA.
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http://dx.doi.org/10.1159/000505402DOI Listing
January 2020

A rare cause of hypertension in childhood: Answers.

Pediatr Nephrol 2020 01 20;35(1):79-82. Epub 2019 Sep 20.

Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, Fevzi Çakmak Mahallesi, Muhsin Yazıcıoğlu Caddesi, No: 10 34899 Pendik, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-019-04329-0DOI Listing
January 2020

A rare cause of hypertension in childhood: Questions.

Pediatr Nephrol 2020 01 20;35(1):77-78. Epub 2019 Sep 20.

Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, Fevzi Çakmak Mahallesi, Muhsin Yazıcıoğlu Caddesi, No:10 34899 Pendik, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-019-04326-3DOI Listing
January 2020

Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease.

Pediatr Nephrol 2019 12 19;34(12):2571-2582. Epub 2019 Aug 19.

Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University Children's Hospital Heidelberg, Heidelberg, Germany.

Background: Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients.

Methods: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6-17 years with initial eGFR of 10-60 ml/min per 1.73 m.

Results: The median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 μmol/l (8.7) and 17.0 μmol/l (21.6), respectively. In a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors.

Conclusions: Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort.
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http://dx.doi.org/10.1007/s00467-019-04331-6DOI Listing
December 2019

Haemodiafiltration does not lower protein-bound uraemic toxin levels compared with haemodialysis in a paediatric population.

Nephrol Dial Transplant 2020 04;35(4):648-656

Department of Internal Medicine & Pediatrics, Ghent University, Ghent, Belgium.

Background: Haemodiafiltration (HDF) is accepted to effectively lower plasma levels of middle molecules in the long term, while data are conflicting with respect to the additive effect of convection on lowering protein-bound uraemic toxins (PBUTs). Here we compared pre-dialysis β2-microglobulin (β2M) and PBUT levels and the percentage of protein binding (%PB) in children on post-dilution HDF versus conventional high- (hf) or low-flux (lf) haemodialysis (HD) over 12 months of treatment.

Methods: In a prospective multicentre, non-randomized parallel-arm intervention study, pre-dialysis levels of six PBUTs and β2M were measured in children (5-20 years) on post-HDF (n = 37), hf-HD (n = 42) and lf-HD (n = 18) at baseline and after 12 months. Analysis of variance was used to compare levels and %PB in post-HDF versus conventional hf-HD and lf-HD cross-sectionally at 12 months and longitudinal from baseline to 12 months.

Results: For none of the PBUTs, no difference was found in either total and free plasma levels or %PB between post-HDF versus the hf-HD and lf-HD groups. Children treated with post-HDF had lower pre-dialysis β2M levels [median 23.2 (21.5; 26.6) mg/dL] after 12 months versus children on hf-HD [P<0.01; 35.2 (29.3; 41.2) mg/dL] and children on lf-HD [P<0.001; 47.2 (34.3; 53.0) mg/dL]. While β2M levels remained steady in the hf-HD and lf-HD group, a decrease in β2M was demonstrated for children on post-HDF (P<0.01).

Conclusions: While post-HDF successfully decreased β2M, no additive effect on PBUT over 12 months of treatment was found. PBUT removal is complex and hampered by several factors. In children, these factors might be different from adults and should be explored in future research.
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http://dx.doi.org/10.1093/ndt/gfz132DOI Listing
April 2020

The Relationship between the Waist Circumference and Increased Carotid Intima Thickness in Obese Children.

Child Obes 2019 10 27;15(7):468-475. Epub 2019 Jun 27.

Department of Pediatric Nephrology, Faculty of Cerrahpasa Medical, Istanbul University, Istanbul, Turkey.

This study aimed to evaluate the cardiometabolic risk factors in normotensive obese and hypertensive obese (HT-obese) children by comparison of anthropomorphic measurements, fat distribution, carotid artery intima-media thickness (CIMT), and inflammatory markers. Fifty-three obese patients 10-18 years of age with a BMI-for-age/gender >95th percentile and 20 age- and gender-matched healthy volunteers enrolled in the study. Obese patients were divided into two groups according to the presence of hypertension (HT), as follows: HT-obese subgroup ( = 30) and nonhypertensive obese (non-HT-obese) subgroup ( = 23). Weight standard deviation score (SDS), BMI-SDS, waist circumference (WC) SDS, and the fat tissue -score were significantly higher ( < 0.001 for all) in the obese patients than the control groups. Obese patients had higher 24-hour systolic blood pressure (SBP) SDS and leptin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 levels. Furthermore, CIMT and CIMT-SDS were significantly higher in them. HT-obese patients ( = 30) had significantly higher WC-SDS and lower serum leptin and adiponectin levels than those of non-HT-obese group ( = 23). Finally, an association between increased CIMT-SDS and WC-SDS ( = 0.399,  = 0.002) and 24-hour SBP-SDS ( = 0.272,  = 0.009) was shown. Association between increased WC and HT implies the importance of central obesity in atherosclerosis. We concluded that WC measurement could be used to define risk groups since it is related to cardiometabolic complications.
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http://dx.doi.org/10.1089/chi.2019.0022DOI Listing
October 2019

Isolated nocturnal and isolated daytime hypertension associate with altered cardiovascular morphology and function in children with chronic kidney disease: findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease study.

J Hypertens 2019 11;37(11):2247-2255

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

Introduction: Prevalence of isolated nocturnal hypertension (INH) and isolated daytime hypertension (IDH) is around 10% in adults. Data in children, especially in chronic kidney disease (CKD), are lacking. The aim of this cross-sectional multicenter cohort study was to define the prevalence of INH and IDH and its association with cardiovascular morphology and function, that is, pulse wave velocity (PWV), carotid intima-media thickness (cIMT), or left ventricular mass index (LVMI) in children with CKD.

Methods: Ambulatory blood pressure (BP) monitoring profiles were analyzed in 456 children with CKD stages III-V participating in the Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study (64.3% males, 71.3% congenital anomaly of the kidney and urinary tract, age 12.5 ± 3.2 years, estimated glomerular filtration rate 29 ± 12 ml/min per 1.73 m). Baseline PWV, cIMT, and LVMI were compared in normotension, INH, IDH, or sustained 24-h hypertension.

Results: Prevalence of sustained hypertension was 18.4%, of INH 13.4%, and of IDH 3.7%. PWV SDS (SD score) and cIMT SDS were significantly higher in sustained hypertension and INH, and PWV SDS was significantly higher in IDH, compared with normotension. LVMI was significantly increased in sustained hypertension, but not in INH or IDH. Determinants of INH were smallness for gestational age, older age, higher height SDS and parathyroid hormone, and shorter duration of CKD. In logistic regression analysis, day/night-time hypertension or ambulatory BP monitoring pattern (normal, INH, IDH, sustained hypertension) were independently associated with cardiovascular outcome measures: elevated night-time BP was associated with increased cIMT, PWV, and left ventricular hypertrophy; INH was associated with cIMT.

Conclusion: INH is present in almost one out of seven children with predialysis CKD; INH and nocturnal hypertension in general are associated with alterations of arterial morphology and function.
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http://dx.doi.org/10.1097/HJH.0000000000002160DOI Listing
November 2019

A rare cause of proteinuria after kidney transplantation: Answers.

Pediatr Nephrol 2019 11 30;34(11):2333-2335. Epub 2019 Apr 30.

Cerrahpaşa Faculty of Medicine, Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-019-04263-1DOI Listing
November 2019

A rare cause of proteinuria after kidney transplantation: Questions.

Pediatr Nephrol 2019 11 30;34(11):2331-2332. Epub 2019 Apr 30.

Cerrahpaşa Faculty of Medicine, Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-019-04262-2DOI Listing
November 2019

Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population.

Toxins (Basel) 2019 04 24;11(4). Epub 2019 Apr 24.

Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort ( = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4-5 ( = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4-5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF ( -0.2 to -0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4-5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population.
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http://dx.doi.org/10.3390/toxins11040235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521157PMC
April 2019

Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children.

Kidney Int 2019 07 20;96(1):214-221. Epub 2019 Mar 20.

Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany. Electronic address:

Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6-17 years with baseline estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m. uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m, and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m, or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69-0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD.
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http://dx.doi.org/10.1016/j.kint.2019.01.035DOI Listing
July 2019