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tubulointerstitial disease

Lucas L Falke, Jan Willem Leeuwis, Karen M Lyons, Christine L Mummery, Tri Q Nguyen, Roel Goldschmeding
Treatment with rhBMP7 exerts profound protective effects in a wide variety of experimental models of renal disease. However, little is known about how these protective effects are mediated, and which cells in the kidney are targeted by exogenous rhBMP7 treatment. To determine if rhBMP7 increases glomerular and tubulointerstitial canonical BMP signaling, we performed Unilateral Ureteral Obstruction (UUO, a widely used obstructive nephropathy model) in mice reporting transcriptional activity downstream of canonical BMP signaling by the expression of GFP under the BMP Responsive Element of the Id1 promoter (BRE:gfp mice)...
October 20, 2016: Journal of Cell Communication and Signaling
Hui Han, Jinzhou Zhu, Yaqiong Wang, Zhengbin Zhu, Yanjia Chen, Lin Lu, Wei Jin, Xiaoxiang Yan, Ruiyan Zhang
Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B cell-deficient μMT mice or CD20 antibody-mediated B cell depleted mice...
October 20, 2016: Journal of Pathology
Shinichi Hikasa, Megumi Yasuda, Kyoko Hideta, Mai Kawakami, Satoshi Higasa, Akihiro Sawada, Tazuko Tokugawa, Takeshi Kimura
BACKGROUND: Renal dysfunction is recognized with increasing frequency among the noninfectious comorbidities associated with human immunodeficiency virus (HIV) infection. Urinary liver-type fatty acid-binding protein (L-FABP) has been shown to be a new biomarker to screen for not only tubulointerstitial damage but also kidney dysfunction. METHODS: We performed a cross-sectional study to determine the association between the urinary L-FABP and chronic kidney disease (CKD) among 77 HIV-infected Japanese patients by backward-stepwise multivariable logistic regression...
October 19, 2016: Clinical and Experimental Nephrology
Naro Ohashi, Shinsuke Isobe, Sayaka Ishigaki, Takahisa Suzuki, Masafumi Ono, Tomoyuki Fujikura, Takayuki Tsuji, Akihiko Kato, Seiichiro Ozono, Hideo Yasuda
Circulating renin-angiotensin system (RAS) activation is maintained after renal function has deteriorated. The activation of the intrarenal RAS plays a critical role in the pathophysiology of chronic kidney disease (CKD), independently of the circulating RAS. However, the activation of intrarenal RAS and the chymase-dependent pathway after initiation of dialysis has not been clarified. We recruited 19 CKD patients (10 without dialysis and 9 with dialysis) who underwent a heminephrectomy. Circulating RAS was investigated before nephrectomy...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Birong Li, Babitha Haridas, Ashley R Jackson, Hanna Cortado, Nicholas Mayne, Rebecca Kohnken, Brad Bolon, Kirk M McHugh, Andrew L Schwaderer, John D Spencer, Christina B Ching, David S Hains, Sheryl S Justice, Santiago Partida-Sanchez, Brian Becknell
Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis...
October 19, 2016: American Journal of Physiology. Renal Physiology
Agnes Gardet, Wei C Chou, Taylor L Reynolds, Diana B Velez, Kai Fu, Julia M Czerkowicz, Jeffrey Bajko, Ann M Ranger, Normand Allaire, Hannah M Kerns, Sarah Ryan, Holly M Legault, Robert W Dunstan, Robert Lafyatis, Matvey Lukashev, Joanne L Viney, Jeffrey L Browning, Dania Rabah
Mouse models lupus nephritis (LN) have provided important insights into disease pathogenesis, although none have been able to recapitulate all features of the human disease. Using comprehensive longitudinal analyses, we characterized a novel accelerated mouse model of lupus using pristane treatment in SNF1 (SWR X NZB F1) lupus prone mice (pristane-SNF1 mice). Pristane treatment in SNF1 mice accelerated the onset and progression of proteinuria, autoantibody production, immune complex deposition and development of renal lesions...
2016: PloS One
Youri van Berkel, Michael Ludwig, Joanna A E van Wijk, Arend Bökenkamp
BACKGROUND: Dent disease is a rare X-linked recessive proximal tubulopathy caused by mutations in CLCN5 (Dent-1) or OCRL (Dent-2). As a rule, total protein excretion (TPE) is low in tubular proteinuria compared with glomerular disease. Several authors have reported nephrotic-range proteinuria (NP) and glomerulosclerosis in Dent disease. Therefore, we aimed to analyze protein excretion in patients with documented CLCN5 or OCRL mutations in a systematic literature review. DESIGN: PubMed and Embase were searched for cases with documented CLCN5 or OCRL mutations and (semi-)quantitative data on protein excretion...
October 18, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Omar Al Dhaybi, George Bakris
PURPOSE OF REVIEW: Current evidence showcases the pathologic effects of excess aldosterone in promoting glomerular and tubulointerstitial inflammation and fibrosis through various pathways. The place for mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD) progression is unclear. RECENT FINDINGS: MRAs further reduce albuminuria and blood pressure in CKD patients when used in conjunction with angiotensin-converting enzyme inhibitor or angiotensin receptor blockers...
October 7, 2016: Current Opinion in Nephrology and Hypertension
Huei-Fen Jheng, Motohiko Hirotsuka, Tsuyoshi Goto, Masayuki Shibata, Yasuki Matsumura, Teruo Kawada
SCOPE: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Here, we examined the effect of long-term consumption of a low-fat soy milk powder (LFSMP) on the diabetic kidney structure and function. METHODS AND RESULTS: KKAy mice were fed a casein- LFSMP-or high-fat soy mixture powder (HFSMP)-based diet for 4 months. Plasma and urine were subjected to a biochemical assay every 2-4 weeks. Renal morphology and protein expression were evaluated by histochemical staining and western blots...
October 17, 2016: Molecular Nutrition & Food Research
Shinya Kawamoto, Ryo Koda, Atsunori Yoshino, Tetsuro Takeda, Yoshihiko Ueda
Medullary cystic kidney disease (MCKD) is a hereditary disease associated with bilateral medullary polycysts and interstitial fibrosis. MCKD is typically associated with slowly progressive renal dysfunction. We herein report two rare elderly cases with enlarged kidneys and rapidly progressive renal dysfunction without myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), PR3-ANCA, or anti-glomerular basement membrane (GBM) antibodies. Renal biopsies revealed extensive tubular dilatation and atrophy with interstitial fibrosis consistent with MCKD...
2016: Internal Medicine
Rafael Coimbra Ferreira Beltrame, Maurício Friderichs, Bárbara Rayanne Fior, Pedro Guilherme Schaefer, Gustavo Gomes Thomé, Dirceu Reis da Silva, Elvino José Guardão Barros, Renato Seligman, Francisco Veríssimo Veronese
The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%...
July 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Zhi Su, Deborah Widomski, Ji Ma, Marian Namovic, Arthur Nikkel, Laura Leys, Lauren Olson, Katherine Salte, Diana Donnelly-Roberts, Timothy Esbenshade, Steve McGaraughty
BACKGROUND: Obese ZSF-1 rats display many features of human type II diabetes including nephropathy (DN). The study aimed to further understand the relevance of this model to DN, for which glomerular filtration rate (GFR), renal fibrosis and several urinary/tissue biomarkers was followed over 24 weeks in ZSF-1 rats. METHODS: Intact/sham or uninephrectomized male and female ZSF-1 rats were studied. GFR was measured by transdermal clearance of fluorescein isothiocyanate-sinistrin...
October 14, 2016: American Journal of Nephrology
Ningning Liu, Lailai Li, Xin Zhu, Zhiqiang Ling, Jianguo Feng, Ying Hu, Yi Wang, Lijun Mou, Yi Wang
Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images...
October 10, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hideki Yokoi, Masashi Mukoyama
Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis. Transforming growth factor-β (TGF-β) is postulated to play a central role in the development of both fibrotic processes. Extracellular matrix proteins, particularly type I collagen and fibronectin, accumulate in the tissue during renal fibrogenesis. CCN2, also known as connective tissue growth factor (CTGF), is increased in the setting of fibrosis and modulates a number of downstream signaling pathways involved in the fibrogenic properties of TGF-β...
2017: Methods in Molecular Biology
Robin Satanovskij, Alhaddad Bader, Matthias Block, Victor Herbst, Wolfgang Schlumberger, Tobias Haack, Wolfgang Andreas Nockher, Uwe Heemann, Lutz Renders, Christoph Schmaderer, Susanne Angermann, Ming Wen, Thomas Meitinger, Jürgen Scherberich, Dominik Steubl
BACKGROUND: Uromodulin-associated Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD-UMOD) belongs to a group of autosomal dominant inherited diseases caused by mutations in the UMOD gene, which codes for uromodulin, a protein exclusively expressed in renal tubular cells of the ascending limb of the loop of Henle. The diagnosis is hampered by non-specific clinical, laboratory and histological findings. In this study, we evaluated serum uromodulin as diagnostic marker for ADTKD-UMOD in a family with a novel mutation in UMOD...
October 10, 2016: Clinical Biochemistry
Eun-Sil Park, Michio Suzuki, Masanobu Kimura, Hiroshi Mizutani, Ryuichi Saito, Nami Kubota, Youko Hasuike, Jungo Okajima, Hidemi Kasai, Yuko Sato, Noriko Nakajima, Keiji Maruyama, Koichi Imaoka, Shigeru Morikawa
BACKGROUND: Feline morbillivirus (FmoPV) is a novel paramyxovirus found to infect domestic cats. FmoPV has been isolated in several countries in Asia and Europe and is considered to have genetic diversity. Also, it is suspected to be associated with feline renal diseases including tubulointerstitial nephritis (TIN), which affects domestic cats with a high incidence rate. RESULTS: To clarify the state of FmoPV infection among domestic cats in Japan, an epidemiological survey was conducted...
October 11, 2016: BMC Veterinary Research
Susanne Muehlich, Margot Rehm, Astrid Ebenau, Margarete Goppelt-Struebe
Changes in cell morphology that involve alterations of the actin cytoskeleton are a hallmark of diseased renal tubular epithelial cells. While the impact of actin remodeling on gene expression has been analyzed in many model systems based on cell lines, this study investigated human primary tubular epithelial cells isolated from healthy parts of tumor nephrectomies. Latrunculin B (LatB) and cytochalasin D (CytoD) were used to modulate G-actin levels in a receptor-independent manner. Both compounds (at 0.5μM) profoundly altered F-actin structures in a Rho kinase-dependent manner, but only CytoD strongly induced the pro-fibrotic factor CTGF (connective tissue growth factor)...
October 7, 2016: Cellular Signalling
Laura Penna Rocha, Samuel Cavalcante Xavier, Fernanda Rodrigues Helmo, Juliana Reis Machado, Fernando Silva Ramalho, Marlene Antônia Dos Reis, Rosana Rosa Miranda Corrêa
INTRODUCTION: Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells may express mesenchymal cell markers with subsequent change in their functions, and it may be part of the etiopathogenesis of kidney disease. OBJECTIVE: The aim of this study was to evaluate the immunexpression of some EMT inducers and markers in frequent nephropathies in pediatric patients. METHODS: 59 patients aged 2-18 years old were selected and divided into 6 groups of frequent nephropathies in children and adolescents, as well as one control group...
September 22, 2016: Pathology, Research and Practice
Payaswini Vasanth, Michelle Parmley, Jose Torrealba, Tamim Hamdi
Tubulointerstitial nephritis in patients with inflammatory bowel disease has been linked to the use of 5-ASA derivatives. Various aspects of this theory have been challenged with a potential role for the underlying autoimmune disorder. Steroids are the mainstay of treatment and mycophenolate mofetil might be an effective alternative. We report a patient who responded well to mycophenolate despite continuing mesalamine, the suspected offending agent.
2016: Case Reports in Nephrology
Giuseppina Federico, Michael Meister, Daniel Mathow, Gunnar H Heine, Gerhard Moldenhauer, Zoran V Popovic, Viola Nordström, Annette Kopp-Schneider, Thomas Hielscher, Peter J Nelson, Franz Schaefer, Stefan Porubsky, Danilo Fliser, Bernd Arnold, Hermann-Josef Gröne
Renal tubular atrophy and interstitial fibrosis are common hallmarks of etiologically different progressive chronic kidney diseases (CKD) that eventually result in organ failure. Even though these pathological manifestations constitute a major public health problem, diagnostic tests, as well as therapeutic options, are currently limited. Members of the dickkopf (DKK) family, DKK1 and -2, have been associated with inhibition of Wnt signaling and organ fibrosis. Here, we identify DKK3 as a stress-induced, tubular epithelia-derived, secreted glycoprotein that mediates kidney fibrosis...
January 21, 2016: JCI Insight
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