Vecihi Batuman

Background: Cardiorenal syndrome (CRS) is associated with poor outcomes. Risk factors for progressive CRS are not understood in patients with chronic kidney disease (CKD). Objectives: This study aimed to determine the incidence of progressive CRS and risk factors in individuals with CKD. Methods: Adults with CKD in the Chronic Renal Insufficiency Cohort (CRIC) study excluding those with heart failure (HF) at baseline were included (n = 3,557). We defined progressive CRS as developing HF and end-stage kidney disease (ESKD) within 12 months. ESKD was defined as needing renal replacement therapy or renal transplant. The associations of baseline risk factors with progressive CRS were examined using Cox proportional hazards models. A sensitivity analysis assessed risk factors in those who developed HF before ESKD and vice versa. Results: 161 patients (4.5%) developed progressive CRS. Traditional risk factors [multivariable-adjusted hazard ratios (HR) (95% CI)] associated with progressive CRS in multivariable models included lower education [1.90 (1.28,2.83)], cardiovascular disease [1.53 (1.07,2.18)], lower estimated glomerular filtration rate [0.64 (0.51,0.82)] and higher albumin to creatinine ratio [2.44 (1.98,3.02)]. Novel risk factors associated included higher levels of alkaline phosphatase, brain natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-?), growth differentiation factor 15 (GDF-15), hemoglobin A1C, and lower hemoglobin. Risk factors associated with both ESKD before HF and HF before ESKD were kidney dysfunction, albuminuria, and mineral bone disorder (higher alkaline phosphatase and PTH), inflammation (TNF-?), fibrotic factor (GDF-15), and anemia. Diabetes, CVD, systolic blood pressure, waist circumference, HbA1c, and BNP were more strongly associated when HF preceded ESKD. Conclusions: Both traditional risk factors and novel risk factors associated with inflammation, mineral bone disorder, anemia, diabetes control, albuminuria, worse kidney function, and fibrotic factors are associated with progressive CRS in individuals with CKD. Many of these risk factors are modifiable representing potential areas for intervention.

Aristolochic acids (AAs) are extracted from certain plants as folk remedies for centuries until their nephrotoxicity and carcinogenicity were recognized. Aristolochic acid I (AAI) is one of the main pathogenic compounds, and it has nephrotoxic, carcinogenic and mutagenic effects. Previous studies have shown that AAI acts mainly on proximal renal tubular epithelial cells; however, the mechanisms of AAI‐induced proximal tubule cell damage are still not fully characterized. We exposed human kidney proximal tubule cells (PTCs; HK2 cell line) to AAI in vitro at different time/dose conditions and assessed cell proliferation, reactive oxygen species (ROS) generation, nitric oxide (NO) production, m‐RNA/ protein expressions and mitochondrial dysfunction. AAI exposure decreased proliferation and increased apoptosis, ROS generation / NO production in PTCs significantly at 24 h. Gene/ protein expression studies demonstrated activation of innate immunity (TLRs 2, 3, 4 and 9, HMGB1), inflammatory (IL6, TNFA, IL1B, IL18, TGFB and NLRP3) and kidney injury (LCN2) markers. AAI also induced epithelial‐mesenchymal transition (EMT) and mitochondrial dysfunction in HK2 cells. TLR9 knock‐down and ROS inhibition were able to ameliorate the toxic effect of AAI. In conclusion, AAI treatment caused injury to PTCs through ROS‐HMGB1/mitochondrial DNA (mt DNA)‐mediated activation of TLRs and inflammatory response.

Renal Anatomi Orçun ALTUNÖREN Garip BEKFİLAVİOĞLU Renal Fizyoloji Ceren ÖNAL Bülent ALTUN Öykü ve Fizik İnceleme Tekin AKPOLAT Klirens Kavramı ve Glomerüler Filtrasyon Hızı Ölçüm Metotları Ebru SEVİNÇ OK İdrar Analizi ve Yorumlanması Çiğdem MENGÜŞ Ahmet Uğur YALÇIN Renal Görüntüleme Kenan TURGUTALP Caner ÖZER Renal Biyopsi ve Temel Patolojik İncelemeler Gökhan TEMİZ İlter BOZACI İdrar Miktarı Değişiklikleri (Poliüri, Oligüri, Anüri) Aydın ÜNAL İşeme Bozuklukları (Noktüri-Pollaküri-Dizüri-İdrar İnkontinansı) Murat Hayri SİPAHİOĞLU Sümeyra KOYUNCU Hematüriye Yaklaşım Cenk GÖKALP Soner DUMAN Proteinüriye Yaklaşım Serkan AKTÜRK Fatih DEDE Hücre Dışı Sıvı Volümü Düzenlenmesi ve Bozuklukları Seyhun KÜRŞAT Su ve Sodyum Metabolizması Bozuklukları Tevfik ECDER Potasyum Metabolizması ve Bozuklukları Bülent TOKGÖZ Cihan UYSAL Kalsiyum Metabolizması ve Bozuklukları Engin ONAN Özkan GÜNGÖR Fosfor Metabolizması ve Bozuklukları Aysel GÜRKAN TOÇOĞLU Savaş SİPAHİ Magnezyum Metabolizması ve Bozuklukları Eyüp KÜLAH Asit-Baz Dengesi Zeki AYDIN Metabolik Asidoz Özant HELVACI Galip GÜZ Metabolik Alkaloz Aykut SİFİL Solunumsal Asit-Baz Bozuklukları Halil AYDAR Garip ŞAHİN Karma Asit-Baz Bozuklukları Meltem SEZİŞ DEMİRCİ Gökhan ATAY Glomerüler Hastalıkların Patogenezi ve Sınıflaması Serhan TUĞLULAR Primer Glomerüler Hastalıkların Epidemiyolojisi Egemen CEBECİ Nefritik Sendrom İzzet Hakkı ARIKAN Nefrotik Sendrom Ferruh ARTUNÇ Minimal Değişim Hastalığı Meltem GÜRSU Membranöz Nefropati Savaş ÖZTÜRK İmmünglobülin A Nefropatisi Zerrin BİCİK BAHÇEBAŞI Fokal Segmental Glomerüloskleroz Abdülmecit YILDIZ Membranoproliferatif Glomerülonefrit ve C3 Glomerülopatisi Ahmet Burak DİRİM Yaşar ÇALIŞKAN Hızlı İlerleyen Glomerülonefritler Hayriye SAYARLIOĞLU Enfeksiyon İlişkili Glomerülonefritler Beyza ALGÜL DURAK Emre TUTAL İnce Bazal Membran Hastalığı Kamil DİLEK Diğer Glomerülonefritler Necmi EREN Serkan BAKIRDÖĞEN Lupus Nefriti Mustafa GÜLLÜLÜ Diğer Bağ Dokusu Hastalıkları ve Böbrek Didem TURGUT Diabetes Mellitus Epidemiyolojisi, Tanısı, Patogenezi, Kliniği ve Tedavisi Kültigin TÜRKMEN İsmail BALOĞLU Diyabetik Böbrek Hastalığı Neriman Sıla KOÇ Mustafa ARICI Gebelikte Böbrek Fizyolojisi Kübra KAYNAR Gebelikte Böbrek İlişkili Sorunlar Dilek TORUN Böbrek Hastalıklarında Gebelik Saime PAYDAŞ Üriner Sistem Enfeksiyonlarına Yaklaşım Faruk Hilmi TURGUT Kan Basıncı Kontrolü ve Hipertansiyon Fizyopatolojisi Ercan TÜRKMEN Nurol ARIK Primer Hipertansiyon ve Tedavisi Şükrü ULUSOY Gülsüm ÖZKAN Renovasküler Hipertansiyon Hadim AKOĞLU Endokrin Hipertansiyon Ayşa HACIOĞLU Züleyha KARACA Diğer Sekonder Hipertansiyon Nedenleri Ali Rıza UÇAR Halil YAZICI Hipertansif Aciller Kürşad ÖNEÇ Ülver BOZTEPE DERİCİ Ozmotik Diüretikler Özgür Akın OTO Tiazid ve Benzeri Diüretikler Ayça İNCİ Loop Diüretikleri Fatma AYERDEN EBİNÇ Diğer Diüretikler Yasemin COŞKUN YAVUZ Akuaretikler İrem PEMBEGÜL Kistik Böbrek Hastalıkları İsmail KOÇYİĞİT Eray EROĞLU Kalıtsal Tübüler Hastalıklar Ramazan ÇETİNKAYA Fabry Hastalığı Nurhan SEYAHİ Şeyda GÜL ÖZCAN Alport Hastalığı Ali Kemal KADİROĞLU Akut İnterstisyel Nefrit Ali GÜREL Ayhan DOĞUKAN Kronik İnterstisyel Nefrit Hakan AKDAM FMF ve Amiloidoz Harun AKAR Paraproteinemiler ve Miyelom Böbreği Vecihi BATUMAN Ürolojik Testler ve Değerlendirilmesi Aydın GÜÇLÜ Vezikoüreteral Reflü Funda SAĞLAM Böbrek Taş Hastalıkları Neslihan TEZCAN Rüya MUTLUAY Üriner Sistem Obstrüksiyonu Funda SARI Akut Böbrek Hasarının Tanımı ve Epidemiyolojisi Belda DURSUN Akut Böbrek Hasarında Klinik ve Komplikasyonlar Yelda GÜN Yavuz YENİÇERİOĞLU Akut Böbrek Hasarı Tedavisi Abdülmecit YILDIZ Alp İKİZLER Ezilme (Crush) Sendromu Mehmet Şükrü SEVER Trombotik Mikroanjiyopatiler Tuncay ŞAHUTOĞLU Ekrem KARA Yoğun Bakım Ünitesinde Akut Böbrek Hasarı ve Hemodinamik Destek Özlem USALAN Orhan ÖZDEMİR Yoğun Bakım Ünitesinde Renal Replasman Tedavileri Cuma Bülent GÜL Hepatitler ve Böbrek Alper AZAK Hepatorenal Sendrom Sinan KAZAN Sena ULU Kardiyorenal Sendrom: Patogenez ve Tanı Bülent HÜDDAM Kardiyorenal Sendrom: Tedavi İlter BOZACI Erhan TATAR Ürik Asitin Sistemik Hastalıklar ve Hipertansiyon Gelişimindeki Rolü Sidar ÇOPUR Mehmet KANBAY Gut ve Ürik Asit Nefropatisi Ender HÜR Aysun TORAMAN Kronik Böbrek Hastalığının Epidemiyolojisi ve Fizyopatolojisi...

Free light chains (FLCs) induce inflammatory pathways in proximal tubule cells (PTCs). The role of TLRs in these responses is unknown. Here we present findings on the role of TLRs in FLC-induced PTC injury. We exposed human kidney PTC cultures to κ and λ FLCs and used cell supernatants and pellets for ELISA and gene expression studies. We also analyzed tissues from Stat1 ^–/– and littermate control mice treated with daily i.p. injections of a κ FLC for 10 days. FLCs increased the expression of TLR2, TLR4, and TLR6 via HMGB1, a damage-associated molecular pattern. Countering TLR2, TLR4, and TLR6 through GIT-27 or specific TLR siRNAs reduced downstream cytokine responses. Blocking HMGB1 through siRNA or pharmacologic inhibition, or via STAT1 inhibition, reduced FLC-induced TLR2, TLR4, and TLR6 expression. Blocking endocytosis of FLCs through silencing of megalin/cubilin, with bafilomycin A1 or hypertonic sucrose, attenuated FLC-induced cytokine responses in PTCs. IHC showed decreased TLR4 and TLR6 expression in kidney sections from Stat1 ^–/– mice compared with their littermate controls. PTCs exposed to FLCs released HMGB1, which induced expression of TLR2, TLR4, and TLR6 and downstream inflammation. Blocking FLCs’ endocytosis, Stat1 knockdown, HMGB1 inhibition, and TLR knockdown each rescued PTCs from FLC-induced injury.

Anemia is common among patients with chronic kidney disease (CKD) but its health consequences are poorly defined. The aim of this study was to determine the relationship between anemia and cognitive decline in older adults with CKD. We studied a subgroup of 762 adults age ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) study. Anemia was defined according to the World Health Organization criteria (hemoglobin <13 g/dL for men and <12 g/dL for women). Cognitive function was assessed annually with a battery of six tests. We used logistic regression to determine the association between anemia and baseline cognitive impairment on each test, defined as a cognitive score more than one standard deviation from the mean, and mixed effects models to determine the relation between anemia and change in cognitive function during follow-up after adjustment for demographic and clinical characteristics. Of 762 participants with mean estimated glomerular filtration rate of 42.7 ± 16.4 ml/min/1.73 m2, 349 (46 %) had anemia. Anemia was not independently associated with baseline cognitive impairment on any test after adjustment for demographic and clinical characteristics. Over a median 2.9 (IQR 2.6–3.0) years of follow-up, there was no independent association between anemia and change in cognitive function on any of the six cognitive tests. Among older adults with CKD, anemia was not independently associated with baseline cognitive function or decline.