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Carlos Menendez-Castro, Dörte Nitz, Nada Cordasic, Jutta Jordan, Tobias Bäuerle, Fabian B Fahlbusch, Wolfgang Rascher, Karl F Hilgers, Andrea Hartner
Neonatal nephron loss may follow hypoxic-ischemic events or nephrotoxic medications. Its long-term effects on the kidney are still unclear. Unlike term infants, preterm neonates less than 36 weeks gestational age show ongoing nephrogenesis. We hypothesized that nephron loss during nephrogenesis leads to more severe renal sequelae than nephron loss shortly after the completion of nephrogenesis. Rats show nephrogenesis until day 10 of life resembling the situation of preterm infants. Animals were uninephrectomized at day 1 (UNX d1) resulting in nephron reduction during nephrogenesis and at day 14 of life (UNX d14) inducing nephron loss after the completion of nephrogenesis...
March 14, 2018: Scientific Reports
Věra Čertíková Chábová, Petr Kujal, Petra Škaroupková, Zdeňka Varňourková, Šárka Vacková, Zuzana Husková, Soňa Kikerlová, Janusz Sadowski, Elzbieta Kompanowska-Jezierska, Iwona Baranowska, Sung Hee Hwang, Bruce D Hammock, John D Imig, Vladimír Tesař, Ludek Červenka
BACKGROUND/AIMS: We found recently that increasing renal epoxyeicosatrienoic acids (EETs) levels by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, shows renoprotective actions and retards the progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). This prompted us to examine if additional protection is provided when sEH inhibitor is added to the standard renin-angiotensin system (RAS) blockade, specifically in rats with established CKD...
March 6, 2018: Kidney & Blood Pressure Research
Jiye Sun, Xuemei Chen, Ting Liu, Xushun Jiang, Yue Wu, Shan Yang, Wei Hua, Zhengdong Li, Huizhe Huang, Xiongzhong Ruan, Xiaogang Du
BACKGROUND Increased lipid accumulation in renal tubular epithelial cells (TECs) contributes to their injury and dysfunction and progression of tubulointerstitial fibrosis. Berberine (BBR), a natural plant alkaloid isolated from traditional medicine herbs, is effective in lowing serum lipid, and has a protective effect on chronic kidney disease (CKD) with dyslipidemia, including diabetic nephropathy. The aim of this study was to investigate the effect of BBR on palmitate (PA)-induced lipid accumulation and apoptosis in TECs...
March 12, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
B Handan Özdemir, Şebnem Ayva, Gökçe Özdemir, Alev Ok Atılgan, Eda Akçay, F Nurhan Özdemir, Mehmet Haberal
OBJECTIVES: The interaction between calcium oxalate deposition and urinary tract infection is not well established. We aimed to identify the association between these and to determine the role of calcium oxalate deposition on interstitial fibrosis development. MATERIALS AND METHODS: Renal allograft biopsies of 967 patients were reviewed to identify those with calcium oxalate deposition in the renal allograft, with 27 (2.8%) identified. Follow-up biopsies were conducted to reevaluate for calcium oxalate presence and interstitial fibrosis development...
March 2018: Experimental and Clinical Transplantation
Saori Kataoka, Toshio Norikura, Shin Sato
Maternal malnutrition is known to increase the risk of obesity in offspring. We investigated whether green tea extract (GTE) intake during lactation affects obesity-related fibrosis and inflammation in the kidney of high-fat-diet-fed adult offspring of protein-restricted-diet-fed dams during pregnancy and lactation. Pregnant Wistar rats received diets containing 20% (normal-protein, NP) or 8% (low-protein, LP) casein, and they received 0%-, 0.12%- or 0.24%-GTE-containing LP diets (LP/LP, LP/LGT and LP/HGT, respectively) during lactation...
February 9, 2018: Journal of Nutritional Biochemistry
J S Lawson, H M Syme, C P D Wheeler-Jones, J Elliott
BACKGROUND: Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1...
March 9, 2018: BMC Veterinary Research
Andrea Wenzel, Janine Altmueller, Arif B Ekici, Bernt Popp, Kurt Stueber, Holger Thiele, Alois Pannes, Simon Staubach, Eduardo Salido, Peter Nuernberg, Richard Reinhardt, André Reis, Patrick Rump, Franz-Georg Hanisch, Matthias T F Wolf, Michael Wiesener, Bruno Huettel, Bodo B Beck
Recently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel sequencing methods due to the complexity of the VNTR. We established long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay. Our approach allows complete VNTR assembly, thereby enabling the detection of all variants residing within the VNTR and simultaneous determination of VNTR length...
March 8, 2018: Scientific Reports
L B Lopes, C C Abreu, C F Souza, L E R Guimaraes, A A Silva, F Aguiar-Alves, K O Kidd, S Kmoch, A J Bleyer, J R Almeida
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is characterized by autosomal dominant inheritance, progressive chronic kidney disease, and a bland urinary sediment. ADTKD is most commonly caused by mutations in the UMOD gene encoding uromodulin (ADTKD-UMOD). We herein report the first confirmed case of a multi-generational Brazilian family with ADTKD-UMOD, caused by a novel heterozygous mutation (c.163G>A, GGC→AGC, p.Gly55Ser) in the UMOD gene. Of 41 family members, 22 underwent genetic analysis, with 11 individuals found to have this mutation...
March 1, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Julia Wijkström, Channa Jayasumana, Rajeewa Dassanayake, Nalin Priyawardane, Nimali Godakanda, Sisira Siribaddana, Anneli Ring, Kjell Hultenby, Magnus Söderberg, Carl-Gustaf Elinder, Annika Wernerson
In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies...
2018: PloS One
Chao-Yi Wu, Huang-Yu Yang, Hui-Ping Chien, Min-Hua Tseng, Jing-Long Huang
BACKGROUND: Lupus nephritis (LN) is a major risk factor for systemic lupus erythematous (SLE)-related morbidity and mortality. With the aim of bypassing renal biopsy, we analyzed urinary biomarkers for their ability to predict renal histopathologic features and end-stage kidney disease (ESKD). METHODS: Urinary albumin, ß2-microglobulin (B2M), cystatin C, kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), clusterin, calbindin, interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), trefoil factor 3 (TFF3), osteopontin, and glutathione S-transferase π (GST-π) levels were measured at time of renal biopsy...
March 6, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Orestes Foresto-Neto, Victor Ferreira Ávila, Simone Costa Alarcon Arias, Fernanda Florencia Fregnan Zambom, Lisienny Campoli Tono Rempel, Viviane Dias Faustino, Flavia Gomes Machado, Denise Maria Avancini Costa Malheiros, Hugo Abensur, Niels Olsen Saraiva Camara, Roberto Zatz, Clarice Kazue Fujihara
Recent studies suggest that NLRP3 inflammasome activation is involved in the pathogenesis of chronic kidney disease (CKD). Allopurinol (ALLO) inhibits xanthine oxidase (XOD) activity, and, consequently, reduces the production of uric acid (UA) and reactive oxygen species (ROS), both of which can activate the NLRP3 pathway. Thus, ALLO can contribute to slow the progression of CKD. We investigated whether inhibition of XOD by ALLO reduces NLRP3 activation and renal injury in the 5/6 renal ablation (Nx) model...
March 6, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Naro Ohashi, Shinsuke Isobe, Takashi Matsuyama, Sayaka Ishigaki, Naoko Tsuji, Tomoyuki Fujikura, Takayuki Tsuji, Akihiko Kato, Hideo Yasuda
Intrarenal renin-angiotensin system (RAS) activation plays an important role in the development of hypertension and renal damage. However, the association between daytime and night-time intrarenal RAS activation and renal structural damage in normotensive IgA nephropathy patients is unclear. We investigated the relationships between urinary angiotensinogen (U-AGT) excretion, which reflects intrarenal RAS activity, and renal structural damage (i.e., endocapillary and mesangial cell hypercellularity, arteriolar hyalinosis and arteriosclerosis levels, and global glomerulosclerosis and tubulointerstitial fibrosis percentages) in 27 normotensive IgA nephropathy patients (age 39...
March 5, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Hisato Shima, Manabu Tashiro, Satoshi Yamada, Motokazu Matsuura, Kazuyoshi Okada, Toshio Doi, Jun Minakuchi, Shu Kawashima
BACKGROUND: Cilostazol is an antiplatelet drug that is widely prescribed for the prevention of secondary stroke. Adverse reactions to cilostazol include headaches, palpitations, and diarrhea. Little is known about the nephrotoxicity of cilostazol, such as acute kidney injury. We report a biopsy-proven case of diffuse tubulointerstitial nephritis induced by cilostazol. CASE PRESENTATION: A 69-year-old woman prescribed cilostazol was hospitalized for acute kidney injury...
March 5, 2018: BMC Nephrology
Wen-Qi Yang, Shan Mou, Li Xu, Feng-Hua Li, Hong-Li Li
The goal of the study described here was to evaluate the degree of tubulointerstitial injury in patients with chronic kidney disease (CKD) using a more accurate model that combines renal sonographic parameters and laboratory biomarkers. A total of 308 patients were enrolled. The study protocol included conventional ultrasound, contrast-enhanced ultrasonography and renal biopsy. CKD patients were divided into normal and mild (≤25%), moderate (26%-50%) and severe (>50%) tubulointerstitial injury groups. We created a model comprising peak intensity, time to peak, urinary retinol-binding protein and β2 -microglobulin that could discriminate severe (>50%) tubulointerstitial injury...
March 1, 2018: Ultrasound in Medicine & Biology
Alexander J Gallan, W James Chon, Michelle A Josephson, Patrick N Cunningham, Kammi J Henriksen, Anthony Chang
Acute T cell-mediated rejection (TCMR) is an important cause of renal allograft loss. The Banff classification for tubulointerstitial (type I) rejection is based on the extent of both interstitial inflammation and tubulitis. Lymphocytes may also be present between parietal epithelial cells and Bowman capsules in this setting, which we have termed "capsulitis." We conducted this study to determine the clinical significance of capsulitis. We identified 42 patients from the pathology archives at the University of Chicago with isolated Banff type I TCMR from 2010-2015...
February 28, 2018: Human Pathology
XingMei Liu, YingYing Zhang, MingJun Shi, YuanYuan Wang, Fan Zhang, Rui Yan, LingLing Liu, Ying Xiao, Bing Guo
Diabetic nephropathy (DN) is a serious clinical microvascular complication of diabetes mellitus. DN is characterized by the accumulation of extracellular matrix, resulting in progressive fibrosis leading to the loss of renal function. Notch1 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) signaling have been associated with fibrosis. Autophagy serves as an essential regulator of tubular cellular homeostasis. However, how these molecules control the balance between fibrosis and autophagy, the main homeostatic mechanism regulating fibrosis, is not well understood...
February 26, 2018: Biochemical and Biophysical Research Communications
Imari Mimura, Yosuke Hirakawa, Yasuharu Kanki, Ryo Nakaki, Yutaka Suzuki, Tetsuhiro Tanaka, Hiroyuki Aburatani, Masaomi Nangaku
Tubulointerstitial fibrosis has been recently reported to be caused by the collapse of the epigenetic regulation of kidney diseases. We examined whether pharmacological inhibition of histone modification is effective against renal fibrosis. DZNep (3-deazaneplanocin A) was originally developed as an anti-cancer drug to inhibit the repressive histone mark, H3K27me3. We used a model of chronic tubulointerstitial fibrosis induced by unilateral ischaemia/reperfusion and administered DZNep intravenously to the mice for 8 weeks...
February 28, 2018: Scientific Reports
Keizo Kanasaki
Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine...
February 28, 2018: Clinical Science (1979-)
Ryo Koda, Hirofumi Watanabe, Masafumi Tsuchida, Noriaki Iino, Kazuo Suzuki, Go Hasegawa, Naofumi Imai, Ichiei Narita
BACKGROUND: Acute tubulointerstitial nephritis (ATIN) has been increasingly recognized as an important manifestation of kidney injury associated with the use of immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4). While the exact pathophysiology remains unknown, corticosteroids are the mainstay of management. CASE PRESENTATION: We describe a 67-year-old man with stage IV non-small-cell lung cancer who developed kidney injury during treatment with the anti-PD-1 antibody nivolumab...
February 27, 2018: BMC Nephrology
Xiao Li, Liting Xu, Xiaoyan Hou, Jian Geng, Jianwei Tian, Xiaoting Liu, Xiaoyan Bai
AIMS: Diabetic nephropathy (DN) is the most common microvascular complications and the principal cause of mortality and morbidity in patients with diabetes. The expression of advanced oxidation protein products (AOPPs) has been found in vacuolated renal tubules in DN and correlated with patients' decreased renal function. The accumulation of AOPPs is regarded as an initiating factor in podocyte injuries via the protein kinase C (PKC) signaling, which plays a critical role in triggering oxidative stress and mitochondrial injuries in diseases including DN...
February 26, 2018: Antioxidants & Redox Signaling
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