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Kidney International

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https://www.readbyqxmd.com/read/29779709/a-mutation-in-transcription-factor-mafb-causes-focal-segmental-glomerulosclerosis-with-duane-retraction-syndrome
#1
Yoshinori Sato, Hiroyasu Tsukaguchi, Hiroyuki Morita, Koichiro Higasa, Mai Thi Nhu Tran, Michito Hamada, Toshiaki Usui, Naoki Morito, Shoichiro Horita, Takao Hayashi, Junko Takagi, Izumi Yamaguchi, Huan Thanh Nguyen, Masayo Harada, Kiyoko Inui, Yuichi Maruta, Yoshihiko Inoue, Fumihiko Koiwa, Hiroshi Sato, Fumihiko Matsuda, Shinya Ayabe, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Ashio Yoshimura
Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease in children and adults. Genetic factors significantly contribute to early-onset FSGS, but the etiologies of most adult cases remain unknown. Genetic studies of monogenic syndromic FSGS exhibiting extra-renal manifestations have uncovered an unexpected biological role for genes in the development of both podocytes and other cellular lineages. To help define these roles, we studied two unrelated families with FSGS associated with Duane Retraction Syndrome, characterized by impaired horizontal eye movement due to cranial nerve malformation...
May 17, 2018: Kidney International
https://www.readbyqxmd.com/read/29779708/imaging-mass-spectrometry-reveals-direct-albumin-fragmentation-within-the-diabetic-kidney
#2
Kerri J Grove, Nichole M Lareau, Paul A Voziyan, Fenghua Zeng, Raymond C Harris, Billy G Hudson, Richard M Caprioli
Albumin degradation in the renal tubules is impaired in diabetic nephropathy such that levels of the resulting albumin fragments increase with the degree of renal injury. However, the mechanism of albumin degradation is unknown. In particular, fragmentation of the endogenous native albumin has not been demonstrated in the kidney and the enzymes that may contribute to fragmentation have not been identified. To explore this we utilized matrix-assisted laser desorption/ionization imaging mass spectrometry for molecular profiling of specific renal regions without disturbing distinct tissue morphology...
May 17, 2018: Kidney International
https://www.readbyqxmd.com/read/29776756/sex-hormone-binding-globulin-is-a-biomarker-associated-with-nonvertebral-fracture-in-men-on-dialysis-therapy
#3
Jasna Aleksova, Phillip Wong, Robert McLachlan, Kay Weng Choy, Peter R Ebeling, Frances Milat, Grahame J Elder
Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation...
May 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29776755/neutral-ph-and-low-glucose-degradation-product-dialysis-fluids-induce-major-early-alterations-of-the-peritoneal-membrane-in-children-on-peritoneal-dialysis
#4
Betti Schaefer, Maria Bartosova, Stephan Macher-Goeppinger, Peter Sallay, Peter Vörös, Bruno Ranchin, Karel Vondrak, Gema Ariceta, Ariane Zaloszyc, Aysun K Bayazit, Uwe Querfeld, Rimante Cerkauskiene, Sara Testa, Christina Taylan, Johan VandeWalle, YokChin Yap, Rafael T Krmar, Rainer Büscher, Anne K Mühlig, Dorota Drozdz, Salim Caliskan, Felix Lasitschka, Sahar Fathallah-Shaykh, Enrico Verrina, Günter Klaus, Klaus Arbeiter, Raj Bhayadia, Anette Melk, Philipp Romero, Bradley A Warady, Franz Schaefer, Akos Ujszaszi, Claus Peter Schmitt
The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products...
May 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29759420/lysyl-oxidase-like-2-contributes-to-renal-fibrosis-in-col4%C3%AE-3-alport-mice
#5
Dominic Cosgrove, Brianna Dufek, Daniel T Meehan, Duane Delimont, Michael Hartnett, Gina Samuelson, Michael Anne Gratton, Grady Phillips, Deidre A MacKenna, Gretchen Bain
Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lung fibrosis, little is known regarding its role in renal fibrosis. Here we determine whether LOXL2 influences kidney disease in COL4A3 (-/-) Alport mice. These mice were treated with a small molecule inhibitor selective for LOXL2 or with vehicle and assessed for glomerular sclerosis and fibrosis, albuminuria, blood urea nitrogen, lifespan, pro-fibrotic gene expression and ultrastructure of the glomerular basement membrane...
May 11, 2018: Kidney International
https://www.readbyqxmd.com/read/29759419/circulating-complement-factor-h-related-protein-5-levels-contribute-to-development-and-progression-of-iga-nephropathy
#6
Li Zhu, Wei-Yi Guo, Su-Fang Shi, Li-Jun Liu, Ji-Cheng Lv, Nicholas R Medjeral-Thomas, Hannah J Lomax-Browne, Matthew C Pickering, Hong Zhang
IgA nephropathy (IgAN) is a disease associated with activation of the complement system. But the factors influencing complement activation in IgAN are not fully understood. Complement factor H (FH) is an essential negative regulator of complement C3 activation. Complement factor H-related protein (FHR)-5 shares high sequence similarity with factor H. However, unlike factor H, on binding to activated C3 it enables further activation to proceed. Previously, we reported the contribution of rare variants of the CFHR5 gene to IgAN susceptibility...
May 11, 2018: Kidney International
https://www.readbyqxmd.com/read/29759418/a-clone-directed-approach-may-improve-diagnosis-and-treatment-of-proliferative-glomerulonephritis-with-monoclonal-immunoglobulin-deposits
#7
Ramnika Gumber, Jordana B Cohen, Matthew B Palmer, Sidney M Kobrin, Dan T Vogl, Alan G Wasserstein, Sunita D Nasta, Melissa B Bleicher, Roy D Bloom, Laura Dember, Adam Cohen, Brendan M Weiss, Jonathan J Hogan
The optimal treatment for the monoclonal gammopathies of renal significance is not known, but there is consensus among experts that treatment should be specific for the underlying clone. The majority of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) do not have an identifiable clone, and prior studies have found poor renal outcomes for patients with PGNMID treated with a variety of regimens. Here we present a retrospective case series of 19 patients with PGNMID with a more uniform, clone-directed approach...
May 11, 2018: Kidney International
https://www.readbyqxmd.com/read/29751972/notch3-orchestrates-epithelial-and-inflammatory-responses-to-promote-acute-kidney-injury
#8
Panagiotis Kavvadas, Zela Keuylian, Niki Prakoura, Sandrine Placier, Aude Dorison, Christos E Chadjichristos, Jean-Claude Dussaule, Christos Chatziantoniou
Acute kidney injury is a major risk factor for subsequent chronic renal and/or cardiovascular complications. Previous studies have shown that Notch3 was de novo expressed in the injured renal epithelium in the early phases of chronic kidney disease. Here we examined whether Notch3 is involved in the inflammatory response and the epithelial cell damage that typifies ischemic kidneys using Notch3 knockout mice and mice with short-term activated Notch3 signaling (N3ICD) in renal epithelial cells. After ischemia/reperfusion, N3ICD mice showed exacerbated infiltration of inflammatory cells and severe tubular damage compared to control mice...
May 8, 2018: Kidney International
https://www.readbyqxmd.com/read/29751971/cardiac-hypertrophy-elevates-serum-levels-of-fibroblast-growth-factor-23
#9
Isao Matsui, Tatsufumi Oka, Yasuo Kusunoki, Daisuke Mori, Nobuhiro Hashimoto, Ayumi Matsumoto, Karin Shimada, Satoshi Yamaguchi, Keiichi Kubota, Sayoko Yonemoto, Tomoaki Higo, Yusuke Sakaguchi, Yoshitsugu Takabatake, Takayuki Hamano, Yoshitaka Isaka
Several experimental studies have shown that fibroblast growth factor 23 (FGF23) induces left ventricular hypertrophy (LVH). However, the opposite directional relationship, namely a potential effect of LVH on FGF23, remains uncertain. Here we evaluated the effects of LVH on FGF23 using cardiomyocyte-specific calcineurin A transgenic mice. At six weeks, these mice showed severe LVH, with elevated levels of serum intact FGF23. FGF23 levels were elevated in cardiomyocytes, but not osteocytes, of the transgenic animals...
May 8, 2018: Kidney International
https://www.readbyqxmd.com/read/29735310/factors-leading-to-the-discard-of-deceased-donor-kidneys-in-the-united-states
#10
Sumit Mohan, Mariana C Chiles, Rachel E Patzer, Stephen O Pastan, S Ali Husain, Dustin J Carpenter, Geoffrey K Dube, R John Crew, Lloyd E Ratner, David J Cohen
The proportion of deceased donor kidneys procured for transplant but subsequently discarded has been growing steadily in the United States, but factors contributing to the rising discard rate remain unclear. To assess the reasons for and probability of organ discard we assembled a cohort of 212,305 deceased donor kidneys recovered for transplant from 2000-2015 in the SRTR registry that included 36,700 kidneys that were discarded. 'Biopsy Findings' (38.2%) was the most commonly reported reason for discard. The median Kidney Donor Risk Index of discarded kidneys was significantly higher than transplanted organs (1...
May 5, 2018: Kidney International
https://www.readbyqxmd.com/read/29735309/the-elevation-of-circulating-fibroblast-growth-factor-23-without-kidney-disease-does-not-increase-cardiovascular-disease-risk
#11
Eva-Maria Pastor-Arroyo, Nicole Gehring, Christiane Krudewig, Sarah Costantino, Carla Bettoni, Thomas Knöpfel, Sibylle Sabrautzki, Bettina Lorenz-Depiereux, Johanne Pastor, Tim M Strom, Martin Hrabě de Angelis, Giovanni G Camici, Francesco Paneni, Carsten A Wagner, Isabel Rubio-Aliaga
High circulating fibroblast growth factor 23 (FGF23) levels are probably a major risk factor for cardiovascular disease in chronic kidney disease. FGF23 interacts with the receptor FGFR4 in cardiomyocytes inducing left ventricular hypertrophy. Moreover, in the liver FGF23 via FGFR4 increases the risk of inflammation which is also found in chronic kidney disease. In contrast, X-linked hypophosphatemia is characterized by high FGF23 circulating levels due to loss of function mutations of the phosphate-regulating gene with homologies to an endopeptidase on the X chromosome (PHEX), but is not characterized by high cardiovascular morbidity...
May 5, 2018: Kidney International
https://www.readbyqxmd.com/read/29735308/grazoprevir-plus-elbasvir-in-hcv-genotype-1-or-4-infected-patients-with-stage-4-5-severe-chronic-kidney-disease-is-safe-and-effective
#12
Laurent Alric, Isabelle Ollivier-Hourmand, Emilie Bérard, Sophie Hillaire, Maeva Guillaume, Anais Vallet-Pichard, Brigitte Bernard-Chabert, Veronique Loustaud-Ratti, Marc Bourlière, Victor de Ledinghen, Isabelle Fouchard-Hubert, Valerie Canva, Anne Minello, Eric Nguyen-Khac, Vincent Leroy, David Saadoun, Dominique Trias, Stanislas Pol, Nassim Kamar
Patients with advanced chronic kidney disease who receive direct-acting antiviral drugs require special consideration regarding comorbid conditions. Here we assessed the efficacy and safety of grazoprevir plus elbasvir in 93 patients infected with HCV genotype 1 or 4 and with advanced chronic kidney disease in a non-randomized, multicenter, nationwide observational survey. Twenty patients with HCV genotype 1a, 51 patients with 1b, four unclassified genotype 1, 17 with genotype 4 and one with genotype 6 received grazoprevir plus elbasvir (100/50 mg) once daily...
May 5, 2018: Kidney International
https://www.readbyqxmd.com/read/29735307/combination-of-pediatric-and-adult-formulas-yield-valid-glomerular-filtration-rate-estimates-in-young-adults-with-a-history-of-pediatric-chronic-kidney-disease
#13
Derek K Ng, George J Schwartz, Michael F Schneider, Susan L Furth, Bradley A Warady
As patients with chronic kidney disease (CKD) transition from pediatric nephrology care to adult care, their kidney function is clinically assessed by estimated glomerular filtration rate (eGFR) using both pediatric and adult equations, which may not be congruent. Here we evaluated commonly used eGFR equations and directly measured iohexol GFR (iGFR) among participants between ages 18 and 26 with a diagnosis of pediatric CKD in the Chronic Kidney Disease in Children (CKiD) cohort. The bedside serum creatinine (SCr)-only equation (CKiDSCr ), the SCr-only CKD-EPI (CKD-EPISCr ), the cystatin C (Cys)-only CKD-EPI (CKD-EPICys ) and the combined SCr and Cys CKD-EPI (CKD-EPISCr-Cys ) were compared with a) 279 measured iGFRs obtained from 187 participants and b) 548 eGFRs from the SCr and Cys-based CKiD equation (CKiDSCr-Cys ) obtained from 219 participants...
May 5, 2018: Kidney International
https://www.readbyqxmd.com/read/29735306/renoprotective-effects-of-sodium-glucose-cotransporter-2-inhibitors
#14
REVIEW
Hiddo J L Heerspink, Mikhail Kosiborod, Silvio E Inzucchi, David Z I Cherney
Over the past two years, our understanding of anti-hyperglycemic medications used to treat patients with type 2 diabetes (T2D) has fundamentally changed. Before the EMPA-REG OUTCOME trial, agents used to lower blood glucose were felt to prevent or delay the development of microvascular complications, but were not known to definitively reduce cardiovascular risk or mortality. Previous studies with then novel sodium-glucose cotransport-2 (SGLT2) inhibitors demonstrated improvements in several cardiovascular and renal risk factors, including HbA1c, blood pressure, weight, renal hyperfiltration, and albuminuria...
May 5, 2018: Kidney International
https://www.readbyqxmd.com/read/29731111/kidney-targeted-inhibition-of-protein-kinase-c-%C3%AE-ameliorates-nephrotoxic-nephritis-with-restoration-of-mitochondrial-dysfunction
#15
Nino Kvirkvelia, Malgorzata McMenamin, Marie Warren, Ravirajsinh N Jadeja, Sai Karthik Kodeboyina, Ashok Sharma, Wenbo Zhi, Paul M O'Connor, Raghavan Raju, Rudolf Lucas, Michael P Madaio
To investigate the role of protein kinase C-α (PKC-α) in glomerulonephritis, the capacity of PKC-α inhibition to reverse the course of established nephrotoxic nephritis (NTN) was evaluated. Nephritis was induced by a single injection of nephrotoxic serum and after its onset, a PKC-α inhibitor was administered either systemically or by targeted glomerular delivery. By day seven, all mice with NTN had severe nephritis, whereas mice that received PKC-α inhibitors in either form had minimal evidence of disease...
May 4, 2018: Kidney International
https://www.readbyqxmd.com/read/29729982/c3-glomerulopathy-associated-with-monoclonal-ig-is-a-distinct-subtype
#16
Aishwarya Ravindran, Fernando C Fervenza, Richard J H Smith, Sanjeev Sethi
Monoclonal immunoglobulins (MIg) may play a causal role in C3 glomerulopathy (C3G) by impairing regulation of the alternative pathway of complement. Ninety-five patients with C3G were tested for MIg of which 36 were positive. Their mean age at diagnosis was 60 years and among patient 50 years and older, 65.1% had a MIg. At presentation, median serum creatinine and proteinuria were 1.9 mg/dL and 3.0 g/24 hours. Hematuria was present in 32 (88.9%) patients. Twelve (34.3%) patients had low C3 levels. C3 nephritic factor was detected in 45...
May 2, 2018: Kidney International
https://www.readbyqxmd.com/read/29728257/automated-acute-kidney-injury-alerts
#17
REVIEW
Kianoush B Kashani
Acute kidney injury (AKI) is one of the most common and probably one of the more consequential complications of critical illnesses. Recent information indicates that it is at least partially preventable; however, progress in its prevention, management, and treatment has been hindered by the scarcity of knowledge for effective interventions, inconsistencies in clinical practices, late identification of patients at risk for or with AKI, and limitations of access to best practices for prevention and management of AKI...
May 2, 2018: Kidney International
https://www.readbyqxmd.com/read/29716796/protein-carbamylation-exacerbates-vascular-calcification
#18
Daisuke Mori, Isao Matsui, Akihiro Shimomura, Nobuhiro Hashimoto, Ayumi Matsumoto, Karin Shimada, Satoshi Yamaguchi, Tatsufumi Oka, Keiichi Kubota, Sayoko Yonemoto, Yusuke Sakaguchi, Atsushi Takahashi, Yasunori Shintani, Seiji Takashima, Yoshitsugu Takabatake, Takayuki Hamano, Yoshitaka Isaka
Protein carbamylation is a posttranslational modification that can occur non-enzymatically in the presence of high concentrations of urea. Although carbamylation is recognized as a prognostic biomarker, the contribution of protein carbamylation to organ dysfunction remains uncertain. Because vascular calcification is common under carbamylation-prone situations, we investigated the effects of carbamylation on this pathologic condition. Protein carbamylation exacerbated the calcification of human vascular smooth muscle cells (hVSMCs) by suppressing the expression of ectonucleotide pyrophosphate/phosphodiesterase 1 (ENPP1), a key enzyme in the generation of pyrophosphate, which is a potent inhibitor of ectopic calcification...
April 28, 2018: Kidney International
https://www.readbyqxmd.com/read/29716795/metformin-prevents-the-development-of-severe-chronic-kidney-disease-and-its-associated-mineral-and-bone-disorder
#19
Ellen Neven, Benjamin Vervaet, Kerstin Brand, Ulrike Gottwald-Hostalek, Britt Opdebeeck, Annelies De Maré, Anja Verhulst, Jean-Daniel Lalau, Said Kamel, Marc E De Broe, Patrick C D'Haese
Chronic kidney disease (CKD) causes dysregulation of mineral metabolism, vascular calcification and renal osteodystrophy, an entity called 'CKD-Mineral and Bone Disorder' (CKD-MBD). Here we determine whether metformin, an anti-diabetic drug, exerts favorable effects on progressive, severe CKD and concomitant mineral metabolism disturbances. Rats with CKD-MBD, induced by a 0.25% adenine diet for eight weeks, were treated with 200 mg/kg/day metformin or vehicle from one week after CKD induction onward. Severe, stable CKD along with marked hyperphosphatemia and hypocalcemia developed in these rats which led to arterial calcification and high bone turnover disease...
April 28, 2018: Kidney International
https://www.readbyqxmd.com/read/29716794/proliferative-glomerulonephritis-with-monoclonal-immunoglobulin-g-deposits-is-associated-with-high-rate-of-early-recurrence-in-the-allograft
#20
Samar M Said, Fernando G Cosio, Anthony M Valeri, Nelson Leung, Sanjeev Sethi, Hassan Salameh, Lynn D Cornell, Mary E Fidler, Mariam P Alexander, Fernando C Fervenza, Maria Eleni Drosou, Da Zhang, Vivette D D'Agati, Samih H Nasr
The characteristics of allograft proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) are not well defined. To better characterize this disease we retrospectively identified 26 patients with allograft PGNMID, including 16 followed with early protocol biopsies. PGNMID was found to be a recurrent disease in most (89%) patients. A diagnostic biopsy was done for proteinuria and/or increased creatinine in most patients. Median time from transplant to diagnostic biopsy was 5.5 months, with detection within three to four months post-transplant in 86% of patients...
April 28, 2018: Kidney International
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