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Kidney International

Ming-Zhi Zhang, Xin Wang, Yinqiu Wang, Aolei Niu, Suwan Wang, Chenhang Zou, Raymond C Harris
Cytokines IL-4 and IL-13 play important roles in polarization of macrophages/dendritic cells to an M2 phenotype, which is important for recovery from acute kidney injury. Both IL-4 and IL-13 activate JAK3/STAT6 signaling. In mice with diphtheria toxin receptor expression in proximal tubules (selective injury model), a relatively selective JAK3 inhibitor, tofacitinib, led to more severe kidney injury, delayed recovery from acute kidney injury, increased inflammatory M1 phenotype markers and decreased reparative M2 phenotype markers of macrophages/dendritic cells, and development of more severe renal fibrosis after diphtheria toxin administration...
October 10, 2016: Kidney International
Yun Pang, Ying Tan, Yongzhe Li, Jianchun Zhang, Yongbing Guo, Zhiling Guo, Chengying Zhang, Feng Yu, Ming-Hui Zhao
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by overproduction of numerous autoantibodies. Many studies have sought to identify such biomarkers to distinguish patients with active lupus nephritis from SLE patients without renal involvement. Because antibodies to complement C1q appear to be prevalent in patients with active lupus nephritis, we analyzed the frequency of antigenic epitopes of C1q and their clinical significance in a large multicenter study of Chinese patients. The lupus cohort consisted of 210 patients with active lupus nephritis as a discovery cohort, 130 active patients as a validation cohort along with 130 SLE patients without clinical renal involvement, and 100 healthy controls...
October 10, 2016: Kidney International
Nisha Bansal, Charles E McCulloch, Feng Lin, Cassianne Robinson-Cohen, Mahboob Rahman, John W Kusek, Amanda H Anderson, Dawei Xie, Raymond R Townsend, Claudia M Lora, Jackson Wright, Alan S Go, Akinlolu Ojo, Arnold Alper, Eva Lustigova, Magda Cuevas, Radhakrishna Kallem, Chi-Yuan Hsu
Blood pressure is a modifiable risk for cardiovascular disease (CVD). Among hemodialysis patients, there is a U-shaped association between blood pressure and risk of death. However, few studies have examined the association between blood pressure and CVD in patients with stage 4 and 5 chronic kidney disease. Here we studied 1795 Chronic Renal Insufficiency Cohort (CRIC) Study participants with estimated glomerular filtration rate <30 ml/min per 1.73 m(2) and not on dialysis. The association of systolic (SBP), diastolic (DBP), and pulse pressure with the risk of physician-adjudicated atherosclerotic CVD (stroke, myocardial infarction, or peripheral arterial disease) and heart failure was tested using Cox regression adjusted for demographics, comorbidity and medications...
October 4, 2016: Kidney International
Paul Pang, Molly Abbott, Steven L Chang, Malyun Abdi, Nikita Chauhan, Murti Mistri, Joshua Ghofrani, Quynh-Anh Fucci, Colleen Walker, Corey Leonardi, Samuel Grady, Arvin Halim, Ryan Hoffman, Tzongshi Lu, Huixia Cao, Stefan G Tullius, Sayeed Malek, Sanjaya Kumar, Graeme Steele, Adam Kibel, Benjamin S Freedman, Sushrut S Waikar, Andrew M Siedlecki
Vascular progenitor cells show promise for the treatment of microvasculature endothelial injury. We investigated the function of renal artery progenitor cells derived from radical nephrectomy patients, in animal models of acute ischemic and hyperperfusion injuries. Present in human adventitia, CD34positive/CD105negative cells were clonal and expressed transcription factors Sox2/Oct4 as well as surface markers CXCR4 (CD184)/KDR(CD309) consistent with endothelial progenitor cells. Termed renal artery-derived vascular progenitor cells (RAPC), injected cells were associated with decreased serum creatinine after ischemia/reperfusion, reduced albuminuria after hyperperfusion, and improved blood flow in both models...
September 29, 2016: Kidney International
Sahir Kalim, Eugene P Rhee
The high-throughput, high-resolution phenotyping enabled by metabolomics has been applied increasingly to a variety of questions in nephrology research. This article provides an overview of current metabolomics methodologies and nomenclature, citing specific considerations in sample preparation, metabolite measurement, and data analysis that investigators should understand when examining the literature or designing a study. Furthermore, we review several notable findings that have emerged in the literature that both highlight some of the limitations of current profiling approaches, as well as outline specific strengths unique to metabolomics...
September 28, 2016: Kidney International
A Richard Kitching, Joshua D Ooi
The generation of inbred mouse strains in the late 19th and early 20th centuries, coupled with the later establishment of specific pathogen-free animal research facilities created a powerful biological platform for exploration of the immune system in health and disease. Studies in this setting have been responsible for huge advances in our understanding of immunobiology and disease, including immune-mediated kidney disease. However, whereas this reductionist and relatively standardized approach allows us to make sense of complex disease biology, it takes place in controlled environments that clearly differ from those that we humans encounter in everyday life...
September 28, 2016: Kidney International
Steven T Haller, Sivarajan Kumarasamy, David A Folt, Leah M Wuescher, Stanislaw Stepkowski, Manish Karamchandani, Harshal Waghulde, Blair Mell, Muhammad Chaudhry, Kyle Maxwell, Siddhi Upadhyaya, Christopher A Drummond, Jiang Tian, Wanda E Filipiak, Thomas L Saunders, Joseph I Shapiro, Bina Joe, Christopher J Cooper
High blood pressure is a common cause of chronic kidney disease. Because CD40, a member of the tumor necrosis factor receptor family, has been linked to the progression of kidney disease in ischemic nephropathy, we studied the role of Cd40 in the development of hypertensive renal disease. The Cd40 gene was mutated in the Dahl S genetically hypertensive rat with renal disease by targeted-gene disruption using zinc-finger nuclease technology. These rats were then given low (0.3%) and high (2%) salt diets and compared...
September 28, 2016: Kidney International
Marcel P B Jansen, Diba Emal, Gwendoline J D Teske, Mark C Dessing, Sandrine Florquin, Joris J T H Roelofs
Acute kidney injury is often the result of ischemia reperfusion injury, which leads to activation of coagulation and inflammation, resulting in necrosis of renal tubular epithelial cells. Platelets play a central role in coagulation and inflammatory processes, and it has been shown that platelet activation exacerbates acute kidney injury. However, the mechanism of platelet activation during ischemia reperfusion injury and how platelet activation leads to tissue injury are largely unknown. Here we found that renal ischemia reperfusion injury in mice leads to increased platelet activation in immediate proximity of necrotic cell casts...
September 27, 2016: Kidney International
Björn Tampe, Ulrike Steinle, Désirée Tampe, Julienne L Carstens, Peter Korsten, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Michael Zeisberg
Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression...
September 27, 2016: Kidney International
Qin Zhang, Lin Liu, Wenjun Lin, Shasha Yin, Aiping Duan, Zhihong Liu, Wangsen Cao
Rhein is an anthraquinone compound isolated from the medicinal plant rhubarb and mainly used in the clinical treatment of diabetic nephropathy. Rhein exhibits various renoprotective functions, but the underlying mechanisms are not fully determined. However, its renoprotective properties recapitulate the role of Klotho, a renal-specific antiaging protein critical for maintaining kidney homeostasis. Here we explored the connections between rhein renoprotection and Klotho in a mouse model of adenine-induced chronic kidney disease...
September 27, 2016: Kidney International
Emiel Hendrik Post, John A Kellum, Rinaldo Bellomo, Jean-Louis Vincent
The pathogenesis of sepsis-associated acute kidney injury is complex and likely involves perfusion alterations, a dysregulated inflammatory response, and bioenergetic derangements. Although global renal hypoperfusion has been the main target of therapeutic interventions, its role in the development of renal dysfunction in sepsis is controversial. The implications of renal hypoperfusion during sepsis probably extend beyond a simple decrease in glomerular filtration pressure, and targeting microvascular perfusion deficits to maintain tubular epithelial integrity and function may be equally important...
September 27, 2016: Kidney International
Janka Bábíčková, Barbara M Klinkhammer, Eva M Buhl, Sonja Djudjaj, Mareike Hoss, Felix Heymann, Frank Tacke, Jürgen Floege, Jan U Becker, Peter Boor
Progressive renal diseases are associated with rarefaction of peritubular capillaries, but the ultrastructural and functional alterations of the microvasculature are not well described. To study this, we analyzed different time points during progressive kidney damage and fibrosis in 3 murine models of different disease etiologies. These models were unilateral ureteral obstruction, unilateral ischemia-reperfusion injury, and Col4a3-deficient mice, we analyzed ultrastructural alterations in patient biopsy specimens...
September 24, 2016: Kidney International
Ania Stefanska, Christopher Kenyon, Helen C Christian, Charlotte Buckley, Isaac Shaw, John J Mullins, Bruno Péault
Pericytes, perivascular cells embedded in the microvascular wall, are crucial for vascular homeostasis. These cells also play diverse roles in tissue development and regeneration as multi-lineage progenitors, immunomodulatory cells and as sources of trophic factors. Here, we establish that pericytes are renin producing cells in the human kidney. Renin was localized by immunohistochemistry in CD146 and NG2 expressing pericytes, surrounding juxtaglomerular and afferent arterioles. Similar to pericytes from other organs, CD146(+)CD34(-)CD45(-)CD56(-) renal fetal pericytes, sorted by flow cytometry, exhibited tri-lineage mesodermal differentiation potential in vitro...
September 24, 2016: Kidney International
Toshifumi Sugatani, Olga A Agapova, Yifu Fang, Alycia G Berman, Joseph M Wallace, Hartmut H Malluche, Marie-Claude Faugere, William Smith, Victoria Sung, Keith A Hruska
Dysregulation of skeletal remodeling is a component of renal osteodystrophy. Previously, we showed that activin receptor signaling is differentially affected in various tissues in chronic kidney disease (CKD). We tested whether a ligand trap for the activin receptor type 2A (RAP-011) is an effective treatment of the osteodystrophy of the CKD-mineral bone disorder. With a 70% reduction in the glomerular filtration rate, CKD was induced at 14 weeks of age in the ldlr-/- high fat-fed mouse model of atherosclerotic vascular calcification and diabetes...
September 22, 2016: Kidney International
Jean-Michel Correas, Dany Anglicheau, Dominique Joly, Jean-Luc Gennisson, Mickael Tanter, Olivier Hélénon
In recent years, several novel ultrasound (US)-based techniques have emerged for kidney diagnostic imaging, including tissue stiffness assessment with elastography, Ultrasensitive Doppler techniques, and contrast-enhanced ultrasonography to assess renal microvascularization. Renal elastography has become available with the development of noninvasive quantitative techniques, following the rapidly growing field of liver fibrosis diagnosis. With the increased incidence of chronic kidney disease, noninvasive diagnosis of renal fibrosis can be of critical value...
September 21, 2016: Kidney International
Jochen Friedemann, Ralf Heinrich, Yury Shulhevich, Matthias Raedle, Lena William-Olsson, Johannes Pill, Daniel Schock-Kusch
Transcutaneous measurement of the glomerular filtration rate (tGFR) is now frequently used in animal studies. tGFR allows consecutive measurements on the same animal, including multiple measurements on a daily basis, because no blood sampling is required. Here we derive and validate a novel kinetic model for the description of transcutaneously measured FITC-Sinistrin excretion kinetics. In contrast to standard 1- to 3-compartment models, our model covers the complete kinetic, including injection and distribution of the tracer in the plasma compartment...
September 21, 2016: Kidney International
Pieter Evenepoel, Jordi Bover, Pablo Ureña Torres
Circulating parathyroid hormone (PTH) shows a complex relationship with hard outcomes in subjects with chronic kidney disease (CKD). Moreover, intervention studies directly targeting PTH failed to yield unequivocal results. Disturbed PTH metabolism, posttranslational modifications of PTH, and end-organ hyporesponsiveness to PTH may explain the poor performance of PTH as an outcome biomarker and precise target of therapy in the setting of CKD, at least in the gray middle target zone. PTH fragments accumulate in CKD patients and may exert effects that are distinct from, if not opposite to biointact (1-84)PTH...
September 18, 2016: Kidney International
Sally El-Kateb, Sivakumar Sridharan, Ken Farrington, Stanley Fan, Andrew Davenport
Dialysis adequacy is traditionally based on urea clearance, adjusted for total body volume (Kt/Vurea), and clinical guidelines recommend a Kt/Vurea target for peritoneal dialysis. We wished to determine whether adjusting dialysis dose by resting and total energy expenditure would alter the delivered dialysis dose. The resting and total energy expenditures were determined by equations based on doubly labeled isotopic water studies and adjusted Kturea for resting energy expenditure and total energy expenditure in 148 peritoneal dialysis patients (mean age, 60...
September 18, 2016: Kidney International
Jiangling Dong, Yanjun Dong, Zihong Chen, William E Mitch, Liping Zhang
Fibrosis in skeletal muscle develops after injury or in response to chronic kidney disease (CKD), but the origin of cells becoming fibrous tissue and the initiating and sustaining mechanisms causing muscle fibrosis are unclear. We identified muscle fibro/adipogenic progenitor cells (FAPs) that potentially differentiate into adipose tissues or fibrosis. We also demonstrated that CKD stimulates myostatin production in muscle. Therefore, we tested whether CKD induces myostatin, which stimulates fibrotic differentiation of FAPs leading to fibrosis in skeletal muscles...
September 18, 2016: Kidney International
Anissa Moktefi, Shao-Yu Zhang, Pauline Vachin, Virginie Ory, Carole Henique, Vincent Audard, Catherine Rucker-Martin, Elodie Gouadon, Michael Eccles, Andreas Schedl, Laurence Heidet, Mario Ollero, Djillali Sahali, Andre Pawlak
The WT1 (Wilm's tumor suppressor) gene is expressed throughout life in podocytes and is essential for the functional integrity of the glomerular filtration barrier. We have previously shown that CMIP (C-Maf inducing protein) is overproduced in podocyte diseases and alters intracellular signaling. Here we isolated the proximal region of the human CMIP promoter and showed by chromatin immunoprecipitation assays and electrophoretic-mobility shift that Wilm's tumor protein (WT1) bound to 2 WT1 response elements, located at positions -290/-274 and -57/-41 relative to transcription start site...
September 17, 2016: Kidney International
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