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Kidney International

Juan M Díaz-Tocados, María E Rodríguez-Ortiz, Yolanda Almadén, Carmen Pineda, Julio M Martínez-Moreno, Carmen Herencia, Noemi Vergara, M Victoria Pendón-Ruiz de Mier, Rafael Santamaría, Cristian Rodelo-Haad, Antonio Casado-Díaz, Víctor Lorenzo, Catarina Carvalho, João M Frazão, Arnold J Felsenfeld, William G Richards, Escolástico Aguilera-Tejero, Mariano Rodríguez, Ignacio López, Juan R Muñoz-Castañeda
Calcimimetics decrease parathyroid hormone (PTH) secretion in patients with secondary hyperparathyroidism. The decrease in PTH should cause a reduction in bone turnover; however, the direct effect of calcimimetics on bone cells, which express the calcium-sensing receptor (CaSR), has not been defined. In this study, we evaluated the direct bone effects of CaSR activation by a calcimimetic (AMG 641) in vitro and in vivo. To create a PTH "clamp," total parathyroidectomy was performed in rats with and without uremia induced by 5/6 nephrectomy, followed by a continuous subcutaneous infusion of PTH...
March 12, 2019: Kidney International
Neil A Roberts, Emma N Hilton, Filipa M Lopes, Subir Singh, Michael J Randles, Natalie J Gardiner, Karl Chopra, Riccardo Coletta, Zunera Bajwa, Robert J Hall, Wyatt W Yue, Franz Schaefer, Stefanie Weber, Roger Henriksson, Helen M Stuart, Håkan Hedman, William G Newman, Adrian S Woolf
Mutations in leucine-rich-repeats and immunoglobulin-like-domains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome...
March 8, 2019: Kidney International
Haiyan Fu, Dong Zhou, Haili Zhu, Jinlin Liao, Lin Lin, Xue Hong, Fan Fan Hou, Youhua Liu
Matrix metalloproteinase-7 (MMP-7) is a secreted endopeptidase that degrades a broad range of substrates. Recent studies have identified MMP-7 as an early biomarker to predict severe acute kidney injury (AKI) and poor outcomes after cardiac surgery; however, the role of MMP-7 in the pathogenesis of AKI is unknown. In this study, we investigated the expression of MMP-7 and the impact of MMP-7 deficiency in several models of AKI. MMP-7 was induced in renal tubules following ischemia/ reperfusion injury or cisplatin administration, and in folic acid-induced AKI...
March 8, 2019: Kidney International
Tsuyoshi Inoue, Hiroshi Maekawa, Reiko Inagi
Organelle damage can cause various kidney diseases. In particular, organelle stress such as decreased proteostatic activity in the endoplasmic reticulum (ER) and altered energy metabolism in mitochondria contribute to glomerular and tubulointerstitial damage, resulting in the progression and development of kidney diseases. The ER regulates protein quality control via the unfolded protein response (UPR) pathway. Pathogenic ER stress leads to dysregulation of this pathway, and a maladaptive UPR is highly deleterious to renal cell function, and thereby has been implicated in the pathophysiology of various kidney diseases...
March 4, 2019: 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
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