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Kidney International

Nimrit Goraya, Jan Simoni, Lauren N Sager, Nicolaos E Madias, Donald E Wesson
Acid (H+ ) retention appears to contribute to progressive decline in glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD), including some patients without metabolic acidosis. Identification of patients with H+ retention but without metabolic acidosis could facilitate targeted alkali therapy; however, current methods to assess H+ retention are invasive and have little clinical utility. We tested the hypothesis that urine excretion of the pH-sensitive metabolite citrate can identify H+ retention in patients with reduced GFR but without overt metabolic acidosis...
March 1, 2019: Kidney International
Jessica M Vanslambrouck, Lauren E Woodard, Norseha Suhaimi, Felisha M Williams, Sara E Howden, Sean B Wilson, Andrew Lonsdale, Pei X Er, Joan Li, Jovana Maksimovic, Alicia Oshlack, Matthew H Wilson, Melissa H Little
All nephrons in the mammalian kidney arise from a transient nephron progenitor population that is lost close to the time of birth. The generation of new nephron progenitors and their maintenance in culture are central to the success of kidney regenerative strategies. Using a lentiviral screening approach, we previously generated a human induced nephron progenitor-like state in vitro using a pool of six transcription factors. Here, we sought to develop a more efficient approach for direct reprogramming of human cells that could be applied in vivo...
February 28, 2019: Kidney International
Pilar Sanchis, Chin Yee Ho, Yiwen Liu, Leilani E Beltran, Sadia Ahmad, Anne P Jacob, Malgorzata Furmanik, Joanne Laycock, David A Long, Rukshana Shroff, Catherine M Shanahan
Children on dialysis have a cardiovascular mortality risk equivalent to older adults in the general population, and rapidly develop medial vascular calcification, an age-associated pathology. We hypothesized that premature vascular ageing contributes to calcification in children with advanced chronic kidney disease (CKD). Vessels from children with Stage 5 CKD with and without dialysis had evidence of increased oxidative DNA damage. The senescence markers p16 and p21 were also increased in vessels from children on dialysis...
February 28, 2019: Kidney International
Titi Chen, Qi Cao, Yiping Wang, David C H Harris
Tissue macrophages are crucial players in homeostasis, inflammation, and immunity. They are characterized by heterogeneity and plasticity, due to which they display a continuum of phenotypes with M1/M2 presenting 2 extremes of this continuum. M2 macrophages are usually termed in the literature as anti-inflammatory and wound healing. Substantial progress has been made in elucidating the biology of M2 macrophages and their potential for clinical translation. In this review we discuss the current state of knowledge in M2 macrophage research with an emphasis on kidney disease...
February 28, 2019: Kidney International
Claudia R C van Roeyen, Ina V Martin, Ana Drescher, Katharina A Schuett, Daniela Hermert, Ute Raffetseder, Stephanie Otten, Eva M Buhl, Gerald S Braun, Christoph Kuppe, Elisa Liehn, Peter Boor, Ralf Weiskirchen, Ulf Eriksson, Oliver Gross, Frank Eitner, Jürgen Floege, Tammo Ostendorf
Platelet-derived growth factors (PDGF) have been implicated in kidney disease progression. We previously found that PDGF-C is upregulated at sites of renal fibrosis and that antagonism of PDGF-C reduces fibrosis in the unilateral ureteral obstruction model. We studied the role of PDGF-C in collagen 4A3-/- ("Alport") mice, a model of progressive renal fibrosis with greater relevance to human kidney disease. Alport mice were crossbred with PDGF-C-/- mice or administered a neutralizing PDGF-C antibody...
February 28, 2019: Kidney International
Takaya Tajima, Ayumi Yoshifuji, Ayumi Matsui, Tomoaki Itoh, Kiyotaka Uchiyama, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh
Ketone bodies including β-hydroxybutyrate (β-OHB) have been shown to protect against ischemic tissue injury when present at low concentrations. We evaluated the impact of β-OHB on renal ischemia/reperfusion injury (IRI). Mice were treated with a continuous infusion of β-OHB using an osmotic mini-pump before and after IRI. We also tested the effects of increasing endogenous serum β-OHB levels by fasting. Renal IRI was attenuated by β-OHB treatment compared to saline control, with similar results in the fasting condition...
February 27, 2019: Kidney International
Jevin Z Clark, Lihe Chen, Chung-Lin Chou, Hyun Jun Jung, Jae Wook Lee, Mark A Knepper
Bulk-tissue RNA-Seq is increasingly being used in the study of physiological and pathophysiological processes in the kidney; however, the presence of multiple cell types in kidney tissue complicates data interpretation. We addressed the question of which cell types are represented in whole-kidney RNA-Seq data in order to identify circumstances in which bulk-kidney RNA-Seq can be successfully interpreted. We carried out RNA-Seq in mouse whole kidneys and in microdissected renal tubule segments. To aid in the interpretation of the data, we compiled a database of cell-type selective protein markers for 43 cell types believed to be present in kidney tissue...
February 25, 2019: Kidney International
Irma Tchokhonelidze, Alexander Zemchenkov
No abstract text is available yet for this article.
February 25, 2019: Kidney International
François Gaillard, Marie Courbebaisse, Nassim Kamar, Lionel Rostaing, Lola Jacquemont, Maryvonne Hourmant, Arnaud Del Bello, Lionel Couzi, Pierre Merville, Paolo Malvezzi, Benedicte Janbon, Bruno Moulin, Nicolas Maillard, Laurence Dubourg, Sandrine Lemoine, Cyril Garrouste, Hans Pottel, Christophe Legendre, Pierre Delanaye, Christophe Mariat
While direct measurements of glomerular filtration rate (GFR) provide the most accurate evaluation of pre-donation kidney function, guidelines do not systematically require the use of a reference method. We evaluated whether and to what extent relying upon creatinine-based estimating equations (eGFR) rather than direct measurement of GFR (mGFR) alters the selection of potential living donors. We compared the impact of 4 equations (the MDRD study equation, the CKD-EPI equation, the revised Lund-Malmö equation, and the full age spectrum [FAS] equation) on the evaluation of 2733 potential donors with GFR measured by reference methods...
February 25, 2019: Kidney International
Nirupama Ramkumar, Donald E Kohan
The (pro)renin receptor (PRR) is a multifunctional protein that is expressed in multiple organs. Binding of prorenin/renin to the PRR activates angiotensin II-dependent and angiotensin II-independent pathways. The PRR is also involved in autophagy and Wnt/ß catenin signaling, functions that are not contingent on prorenin binding. Emerging evidence suggests that the PRR plays an important role in blood pressure regulation and glucose and lipid metabolism. Herein, we review PRR function in health and disease, with particular emphasis on hypertension and the metabolic syndrome...
February 25, 2019: Kidney International
Harlan G Sparrow, Joshua T Swan, Linda W Moore, A Osama Gaber, Wadi N Suki
The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline classifies acute kidney injury (AKI) into 3 stages defined by serum creatinine elevation or urine output decline. We evaluated the potential impact of further categorizing AKI stage 1 into two stages based on serum creatinine criteria, with a focus on how the resulting 4-stage classification would affect the association of AKI stages with clinical outcomes. We defined AKI stage 1a as an absolute increase in serum creatinine of 0...
February 25, 2019: Kidney International
Theresa M Wewers, Anna B Mayer, Alexander Pfleiderer, Katrin Beul, Rene Schmidt, Barbara Heitplatz, Veerle Van Marck, Ingo Nolte, Hermann Pavenstädt, Stefan Reuter, Marcus Brand, Giovana S Di Marco
Renal ischemia reperfusion injury (IRI) adversely affects clinical outcomes following kidney transplantation. Understanding the cellular mechanisms and the changes in gene/protein expression following IRI may help to improve these outcomes. Serum soluble fms-like tyrosine kinase 1 (sFlt-1), a circulating antiangiogenic protein, is increased in the first week following kidney transplantation. We evaluated the casual relationship of elevated sFlt-1 levels with renal microvascular dysfunction following IRI in a longitudinal study of 93 kidney transplant recipients and in several animal models...
February 22, 2019: Kidney International
Ming Liang, Qunying Guo, Fengzhang Huang, Guofeng Han, Ke Song, Jinlong Luo, Hunter Cheng, Hongzhen Hu, Eric K Peden, Changyi Chen, William E Mitch, Jie Du, Xiaodong Fu, Luan Truong, Jizhong Cheng
Neointima formation is a major contributor to arteriovenous fistula (AVF) failure. We have previously shown that activation of the Notch signaling pathway contributes to neointima formation by promoting the migration of vascular smooth muscle cells (VSMCs) into the venous anastomosis. In the current study we investigated the mechanisms underlying the dedifferentiation and migration of VSMCs, and in particular the role of bone marrow-derived fibroblast specific protein 1 (FSP-1)+ cells, another cell type found in models of vascular injury...
February 16, 2019: Kidney International
Kan Kikuchi, Takayuki Hamano, Atsushi Wada, Shigeru Nakai, Ikuto Masakane
On-line hemodiafiltration is an increasingly common alternative to chronic hemodialysis in some countries, based on the results of randomized controlled trials of post-dilution on-line hemodiafiltration. There are now more than 60,000 patients treated with on-line hemodialfiltration in Japan, over 95% of whom use predilution on-line hemodiafiltration; however, large-scale data on clinical outcomes with this modality are lacking. We created a propensity-matched cohort of 5,000 pairs of patients treated with conventional hemodialysis or predilution on-line hemodiafiltration, using the Japanese Society for Dialysis Therapy Renal Data Registry database from December 31, 2012 to December 31, 2013...
February 16, 2019: Kidney International
Eric Rondeau, Valerie A Luyckx, Hans-Joachim Anders, Kai-Uwe Eckardt, Sandrine Florquin, Hans-Peter Marti, Klaus Ølgaard, Paul Harden
No abstract text is available yet for this article.
February 16, 2019: Kidney International
Naim M Maalouf, John R Poindexter, Beverley Adams-Huet, Orson W Moe, Khashayar Sakhaee
Idiopathic uric acid nephrolithiasis is characterized by an overly acidic urine pH caused by the combination of increased acid production and inadequate buffering of urinary protons by ammonia. A large proportion of uric acid stone formers exhibit features of the metabolic syndrome. We previously demonstrated that thiazolidinediones improved the urinary biochemical profile in an animal model of the metabolic syndrome. In this proof-of-concept study, we examined whether the thiazolidinedione pioglitazone can also ameliorate the overly acidic urine in uric acid stone formers...
February 15, 2019: Kidney International
Sang Jun Han, Hongmei Li, Mihwa Kim, Vivette D'Agati, H Thomas Lee
Intestinal Paneth cells play a critical role in ischemic acute kidney injury (AKI) by releasing interleukin 17A (IL-17A). Because Toll-like receptor 9 (TLR9) activation degranulates Paneth cells and necrotic tubular epithelial cells release several damage associated molecular patterns that target TLR9, we tested the hypothesis that intestinal TLR9 deficiency would protect against ischemic AKI and associated remote intestinal and hepatic dysfunction by decreasing Paneth cell degranulation. We generated mice lacking TLR9 in intestinal epithelia (TLR9fl/fl Villin Cre mice) and compared them to wild type (TLR9fl/fl) mice following right nephrectomy and left ischemia/reperfusion...
February 15, 2019: Kidney International
Xianghui Chen, Yachun Han, Peng Gao, Ming Yang, Li Xiao, Xiaofen Xiong, Hao Zhao, Chengyuan Tang, Guochun Chen, Xuejing Zhu, Shuguang Yuan, Fuyou Liu, Lily Q Dong, Feng Liu, Yashpal S Kanwar, Lin Sun
Ectopic fat deposition (EFD) in the kidney has been shown to play a causal role in diabetic nephropathy; however, the mechanism underlying EFD remains elusive. By transcriptome analysis, we found decreased expression levels of disulfide-bond A oxidoreductase-like protein (DsbA-L) in the kidneys of diabetic mice (induced by high-fat diet plus Streptozotocin) compared with control mice. Increased expression of adipocyte differentiation-related protein and abnormal levels of collagen I, fibronectin, and phosphorylated 5'AMP-activated kinase (p-AMPK), adipose triglyceride lipase (p-ATGL), and HMG-CoA reductase (p-HMGCR) were also observed in diabetic mice...
February 12, 2019: Kidney International
Dervla M Connaughton, Claire Kennedy, Shirlee Shril, Nina Mann, Susan L Murray, Patrick A Williams, Eoin Conlon, Makiko Nakayama, Amelie T van der Ven, Hadas Ityel, Franziska Kause, Caroline M Kolvenbach, Rufeng Dai, Asaf Vivante, Daniela A Braun, Ronen Schneider, Thomas M Kitzler, Brona Moloney, Conor P Moran, John S Smyth, Alan Kennedy, Katherine Benson, Caragh Stapleton, Mark Denton, Colm Magee, Conall M O'Seaghdha, William D Plant, Matthew D Griffin, Atif Awan, Clodagh Sweeney, Shrikant M Mane, Richard P Lifton, Brenda Griffin, Sean Leavey, Liam Casserly, Declan G de Freitas, John Holian, Anthony Dorman, Brendan Doyle, Peter J Lavin, Mark A Little, Peter J Conlon, Friedhelm Hildebrandt
Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features...
February 12, 2019: Kidney International
Manaswita Jain, Rainer W J Kaiser, Katrin Bohl, Martin Hoehne, Heike Göbel, Malte P Bartram, Sandra Habbig, Roman-Ulrich Müller, Agnes B Fogo, Thomas Benzing, Bernhard Schermer, Katja Höpker, Gisela G Slaats
Recent human genetic studies have suggested an intriguing link between ciliary signaling defects and altered DNA damage responses in nephronophthisis (NPH) and related ciliopathies. However, the molecular mechanism and the role of altered DNA damage response in kidney degeneration and fibrosis have remained elusive. We recently identified the kinase-regulated DNA damage response target Apoptosis Antagonizing Transcription Factor (AATF) as a master regulator of the p53 response. Here, we characterized the phenotype of mice with genetic deletion of Aatf in tubular epithelial cells...
February 12, 2019: Kidney International
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