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    Childhood vasculitides in Turkey: A nationwide survey
    (2007) Ozen S.; Bakkaloglu A.; Dusunsel R.; Soylemezoglu O.; Ozaltin F.; Poyrazoglu H.; Kasapcopur O.; Ozkaya O.; Yalcinkaya F.; Balat A.; Kural N.; Donmez O.; Alpay H.; Anarat A.; Mir S.; Gur-Guven A.; Sonmez F.; Gok F.
    Aim: The aims of this study were to evaluate the characteristics of childhood vasculitides and to establish the first registry in Turkey, an eastern Mediterranean country with a white population. Patients and methods: A questionnaire was distributed to the main referral centers asking for the registration of the Henoch-Schönlein purpura (HSP) patients in the last calendar year only and 5 years for other vasculitides. Demographic, clinical, and laboratory data were assessed. Results: Vasculitic diseases were registered from 15 pediatric centers. These centers had a fair representation throughout the country. In the last calendar year, incidences were as follows: HSP 81.6%, Kawasaki disease (KD) 9.0%, childhood polyarteritis nodosa (C-PAN) 5.6%, Takayasu arteritis (TA) 1.5%, Wegener's granulomatosis 0.4%, and Behçet disease 1.9%. There was no clear gender dominance. The mean age was 11.05±4.89 years. Acute phase reactants were elevated in almost all, highest figures being in C-PAN. Renal involvement was present in 28.6% of HSP and 53% of the C-PAN patients. Abdominal aorta was involved in all TA patients. Among the C-PAN patients, 25% had microscopic PAN with necrotizing glomerulonephritis; antineutrophil cytoplasmic antibody was positive in those who were studied. Among the patients, 12.5% and 15% had classic PAN and cutaneous PAN, respectively. The remaining majority were classified as systemic C-PAN diagnosed with biopsies and/or angiograms demonstrating small to midsize artery involvement. The overall prognosis was better than reported in adult series. Conclusion: This is the largest multicenter study defining the demographic data for childhood vasculitides. The distribution of childhood vasculitides was different in our population where KD is much less frequent, whereas HSP constitutes an overwhelming majority. C-PAN was more frequent as well. © Clinical Rheumatology 2006.
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    Early proteinuria lowering by angiotensin-converting enzyme inhibition predicts renal survival in children with CKD
    (American Society of Nephrology, 2018) Van Den Belt S.M.; Heerspink H.J.L.; Gracchi V.; De Zeeuw D.; Wühl E.; Schaefer F.; Anarat A.; Bakkaloglu A.; Ozaltin F.; Peco-Antic A.; Querfeld U.; Gellermann J.; Sallay P.; Drozdz D.; Bonzel K.-E.; Wingen A.-M.; Zurowska A.; Balasz I.; Trivelli A.; Perfumo F.; Müller-Wiefel D.E.; Möller K.; Offner G.; Enke B.; Wühl E.; Gimpel C.; Mehls O.; Schaefer F.; Emre S.; Caliskan S.; Mir S.; Wygoda S.; Hohbach-Hohenfellner K.; Jeck N.; Klaus G.; Ardissino G.; Testa S.; Montini G.; Charbit M.; Niaudet P.; Caldas-Afonso A.; Fernandes-Teixeira A.; Dušek J.; Matteucci M.C.; Picca S.; Mastrostefano A.; Wigger M.; Berg U.B.; Celsi G.; Fischbach M.; Terzic J.; Fydryk J.; Urasinski T.; Coppo R.; Peruzzi L.; Arbeiter K.; Jankauskiené A.; Grenda R.; Litwin M.; Janas R.; Laube G.; Neuhaus T.J.
    Background Although pharmacotherapeutic proteinuria lowering was found to be nephroprotective in adults, the predictive value of early drug-induced proteinuria reduction for long-term renal survival in pediatric CKD is unknown. We analyzed data from the ESCAPE Trial for a potential association between initial antiproteinuric effect of standardized angiotensin-converting enzyme (ACE) inhibition and renal disease progression in children with CKD. Methods In total, 280 eligible children with CKD stages 2-4 (mean age 11.7 years old, median eGFR 46 ml/min per 1.73 m2, 71% congenital renal malformations) received a fixed dose of ramipril (6 mg/m2 per day) and were subsequently randomized to conventional or intensified BP control. We assessed initial proteinuria reduction from baseline to first measurement on ramipril (at 2.561.3 months). We used multivariable Cox modeling to estimate the association between initial proteinuria reduction and the risk of reaching a renal end point (50% eGFR decline or ESRD), which occurred in 80 patients during 5 years of observation. Results Ramipril therapy lowered proteinuria by a mean of 43.5% (95% confidence interval, 36.3% to 49.9%). Relative to proteinuria reduction,30%, 30%-60% and .60% reduction resulted in hazard ratios (95% confidence intervals) of 0.70 (0.40 to 1.22) and 0.42 (0.22 to 0.79), respectively. This association was independent of age, sex, CKD diagnosis, baseline eGFR, baseline proteinuria, initial BP, and concomitant BP reduction. Conclusions The early antiproteinuric effect of ACE inhibition is associated with long-term preservation of renal function in children with CKD. Proteinuria lowering should be considered an important target in the management of pediatric CKD. Copyright © 2018 by the American Society of Nephrology.
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    Familial Mediterranean Fever (FMF) in Turkey: Results of a nationwide multicenter study
    (Lippincott Williams and Wilkins, 2005) Tunca M.; Ozdogan H.; Kasapcopur O.; Yalcinkaya F.; Tutar E.; Topaloglu R.; Yilmaz E.; Arici M.; Bakkaloglu A.; Besbas N.; Akpolat T.; Dinc A.; Erken E.; Tirpan K.; Ozer H.T.E.; Soyturk M.; Senturk T.; Balci B.; Ozguc M.; Dundar M.; Akar E.; Ozel D.; Dundar M.; Gunesacar R.; Booth D.R.; Hawkins P.N.; Touitou I.; Aksentijevich I.; Matzner Y.; Arslan S.; Balaban Y.; Batman F.; Bayraktar Y.; Apras S.; Calguneri M.; Duzova A.; Kav T.; Ozaltin F.; Simsek H.; Sivri B.; Tatar G.; Akkoc N.; Kavukcu S.; Soylu A.; Turkmen M.; Unsal E.; Arisoy N.; Caliskan S.; Gogus F.; Masatlioglu S.; Sever L.; Akkok N.; Cakar N.; Kara N.; Kocak H.; Ozalp S.; Bilge I.; Sevinc E.; Gul A.; Kamali S.; Sadikoglu B.; Selcukbiricik F.; Sirin A.; Sucu A.; Bek K.; Bulbul M.; Delibas A.; Demircin G.; Erdogan O.; Oner A.; Mesiha M.; Ozkaya N.; Tekin M.; Demirkaya E.; Erdem H.; Gok F.; Pay S.; Islek I.; Kabasakal Y.; Keser G.; Ozmen M.; Akoglu E.; Atagunduz P.; Direskeneli H.; Temel M.; Tuglular S.; Buyan N.; Bakkaloglu S.; Derici U.; Goker B.; Kalman S.; Ozkaya O.; Dusunsel R.; Gunduz Z.; Poyrazoglu M.H.; Korkmaz C.; Baskin E.; Koseoglu H.K.; Saatci U.; Yucel E.; Coban E.; Yakupoglu G.; Oktem F.; Tunc E.; Cobankara V.
    Familial Mediterranean fever (FMF) is an autosomal recessive disease that is prevalent among eastern Mediterranean populations, mainly non-Ashkenazi Jews, Armenians, Turks, and Arabs. Since a large proportion of all the FMF patients in the world live in Turkey, the Turkish FMF Study Group (FMF-TR) was founded to develop a patient registry database and analyze demographic, clinical, and genetic features. The cohort was composed of 2838 patients (mean age, 23.0 ± 13.33 yr; range, 2-87 yr), with a male:female ratio of 1.2:1. There was a mean period of 6.9 ± 7.65 years from disease onset to diagnosis; the period was about 2 years shorter for each decade since 1981. Ninety-four percent of patients were living in the central-western parts of the country; however, their familial origins (70% from the central-eastern and Black Sea regions) reflected not only the ongoing east to west migration, but also the historical roots of FMF in Turkey. Patients' clinical features included peritonitis (93.7%), fever (92.5%), arthritis (47.4%), pleuritis (31.2%), myalgia (39.6%), and erysipelas-like erythema (20.9%). Arthritis, arthralgia, myalgia, and erysipelas-like erythema were significantly more frequent (p < 0.001) among patients with disease onset before the age of 18 years. Genetic analysis of 1090 patients revealed that M694V was the most frequent mutation (51.4%), followed by M680I (14.4%) and V726A (8.6%). Patients with the M694V/M694V genotype were found to have an earlier age of onset and higher frequencies of arthritis and arthralgia compared with the other groups (both p < 0.001). In contrast to other reported studies, there was no correlation between amyloidosis and M694V homozygosity in this cohort. However, amyloidosis was still remarkably frequent in our patients (12.9%), and it was prevalent (27.8%) even among the 18 patients with a disease onset after age 40 years. Twenty-two patients (0.8%) had nonamyloid glomerular diseases. The high prevalence of vasculitides (0.9% for polyarteritis nodosa and 2.7% for Henoch-Schönlein purpura) and high frequency of pericarditis (1.4%) were striking findings in the cohort. Phenotype II cases (those patients with amyloidosis as the presenting or only manifestation of disease) were rare (0.3% or less). There was a high rate of a past diagnosis of acute rheumatic fever, which suggested a possible misdiagnosis in children with FMF presenting with recurrent arthritis. To our knowledge, this is the largest series of patients with FMF reported from 1 country. We describe the features of the disease in the Turkish population and show that amyloidosis is still a substantial problem.
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    Henoch-schönlein nephritis: A nationwide study
    (2009) Soylemezoglu O.; Ozkaya O.; Ozen S.; Bakkaloglu A.; Dusunsel R.; Peru H.; Çetinyurek A.; Yildiz N.; Donmez O.; Buyan N.; Mir S.; Arisoy N.; Gur-Guven A.; Alpay H.; Ekim M.; Aksu N.; Soylu A.; Gok F.; Poyrazoglu H.; Sonmez F.
    Background/Aim: The aim of this retrospective study was to evaluate the presentation, clinical and pathological manifestations and outcome of the Henoch-Schönlein purpura (HSP) nephritis in children. Methods: Clinical and laboratory data of 443 children with HSP nephritis aged between 3 and 16 years from 16 pediatric nephrology reference centers were analyzed retrospectively. The biopsy findings were graded according to the classification developed by the International Study of Kidney Disease in Children (ISKDC). Results: Renal biopsy was performed in 179 of the patients with HSP nephritis. The most common presenting clinical finding in patients who were biopsied was nephrotic range proteinuria (25%) which was followed by nephritic-nephrotic syndrome (23.5%). The biopsy findings according to the ISKDC were as follows: class I: 8.3%; II: 44.1%; III: 36.3%; IV: 6.7%; V: 3.3%; VI: 1.1%. All of the patients who developed end-stage renal disease had nephritic-nephrotic syndrome at presentation. Of 443 patients, 87.2% had a favorable outcome and 12.8% had an unfavorable outcome. The overall percentage of children who developed end-stage renal disease at follow-up was 1.1%. Logistic regression analysis did not show any association of initial symptoms and histology with outcome. Conclusion: In the presented cohort, the presence of crescents in the first biopsy or presenting clinical findings did not seem to predict the outcome of HSP nephritis in children. We conclude that children with HSP nephritis even with isolated microscopic hematuria and/or mild proteinuria should be followed closely. © 2009 S. Karger AG, Basel.
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    Normal 25-Hydroxyvitamin D Levels Are Associated with Less Proteinuria and Attenuate Renal Failure Progression in Children with CKD
    (American Society of Nephrology, 2016) Shroff R.; Aitkenhead H.; Costa N.; Trivelli A.; Litwin M.; Picca S.; Anarat A.; Sallay P.; Ozaltin F.; Zurowska A.; Jankauskiene A.; Montini G.; Charbit M.; Schaefer F.; Wühl E.; Bakkaloglu A.; Peco-Antic A.; Querfeld U.; Gellermann J.; Drozdz D.; Bonzel K.-E.; Wingen A.-M.; Balasz I.; Perfumo F.; Müller-Wiefel D.E.; Möller K.; Offner G.; Enke B.; Gimpel C.; Mehls O.; Emre S.; Caliskan S.; Mir S.; Wygoda S.; Hohbach-Hohenfellner K.; Jeck N.; Klaus G.; Ardissino G.; Testa S.; Niaudet P.; Caldas-Afonso A.; Fernandes-Teixeira A.; Duek J.; Matteucci M.C.; Mastrostefano A.; Wigger M.; Berg U.B.; Celsi G.; Fischbach M.; Terzic J.; Fydryk J.; Urasinski T.; Coppo R.; Peruzzi L.; Arbeiter K.; Jankauskiené A.; Grenda R.; Janas R.; Laube G.; Neuhaus T.J.
    Angiotensin-converting enzyme inhibitors (ACEi) for renin-angiotensin-aldosterone system (RAAS) blockade are routinely used to slow CKD progression. However, Vitamin D may also promote renoprotection by suppressing renin transcription through cross-talk between RAAS and Vitamin D -fibroblast growth factor-23 (FGF-23)-Klotho pathways. To determine whether Vitamin D levels influence proteinuria and CKD progression in children, we performed a post hoc analysis of the Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of CKD in Pediatric Patients (ESCAPE) cohort. In 167 children (median EGFR 51 ml/min per 1.73 m2), serum 25-hydroxyvitaminD(25(OH)D),FGF-23, andKlotho levelsweremeasuredatbaselineandafteramedian8months onACEi.Childrenwith lower 25(OH)D levels had higher urinary protein/creatinine ratios at baseline (P=0.03) and at follow-up (P=0.006). Levels of 25(OH)D and serum Vitamin D -binding protein were not associated, but 25(OH)D #50 nmol/L associated with higher diastolicBP(P=0.004).ACEi therapy alsoassociatedwith increasedKlotho levels (P<0.001). The annualized loss of EGFR was inversely associated with baseline 25(OH)D level (P<0.001, r=0.32). Five-year renal survivalwas 75%in patientswith baseline 25(OH)D$50 nmol/L and 50%in thosewith lower 25(OH) D levels (P<0.001). This renoprotective effect remained significant but attenuated with ACEi therapy (P=0.05). Renal survival increased 8.2% per 10 nmol/L increase in 25(OH)D (P=0.03), independent of EGFR; proteinuria, BP, and FGF-23 levels; and underlying renal diagnosis. In children with CKD, 25(OH)D?50 nmol/L was associatedwith greater preservation of renal function. This effect was present but attenuated with concomitant ACEi therapy. © 2016 by the American Society of Nephrology.