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Kidney International

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https://www.readbyqxmd.com/read/28233612/unique-molecular-changes-in-kidney-allografts-after-simultaneous-liver-kidney-compared-with-solitary-kidney-transplantation
#1
Timucin Taner, Walter D Park, Mark D Stegall
Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match-positive simultaneous liver-kidney transplants...
February 20, 2017: Kidney International
https://www.readbyqxmd.com/read/28233611/identification-of-the-activating-cytotoxicity-receptor-nkg2d-as-a-senescence-marker-in-zero-hour-kidney-biopsies-is-indicative-for-clinical-outcome
#2
Julia Günther, Thomas Resch, Hubert Hackl, Arne Sattler, Susanne Ebner, Paul Viktor Ritschl, Matthias Biebl, Robert Öllinger, Stefan Schneeberger, Gerald Brandacher, Hubert Schwelberger, Bettina Zelger, Diana Stauch, Andreas Pascher, Johann Pratschke, Katja Kotsch
The definition of biological donor organ age rather than chronological age seems obvious for the establishment of a valid pre-transplant risk assessment. Therefore, we studied gene expression for candidate markers in 60 zero-hour kidney biopsies. Compared with 29 younger donors under age 55, 31 elderly donors age 55 and older had significant mRNA expression for immunoproteasome subunits (PSMB8, PSMB9 and PSMB10), HLA-DRB, and transcripts of the activating cytotoxicity receptor NKG2D. Gene expression was validated in an independent donor cohort consisting of 37 kidneys from donors 30 years and under (Group I), 75 kidneys from donors age 31-54 years (Group II) and 75 kidneys from donors age 55 and older (Group III)...
February 20, 2017: Kidney International
https://www.readbyqxmd.com/read/28233610/the-genetic-and-clinical-spectrum-of-a-large-cohort-of-patients-with-distal-renal-tubular-acidosis
#3
Viviana Palazzo, Aldesia Provenzano, Francesca Becherucci, Giulia Sansavini, Benedetta Mazzinghi, Valerio Orlandini, Laura Giunti, Rosa Maria Roperto, Marilena Pantaleo, Rosangela Artuso, Elena Andreucci, Sara Bargiacchi, Giovanna Traficante, Stefano Stagi, Luisa Murer, Elisa Benetti, Francesco Emma, Mario Giordano, Francesca Rivieri, Giacomo Colussi, Silvana Penco, Emanuela Manfredini, Maria Rosa Caruso, Livia Garavelli, Simeone Andrulli, Gianluca Vergine, Nunzia Miglietti, Elena Mancini, Cristina Malaventura, Antonio Percesepe, Enrico Grosso, Marco Materassi, Paola Romagnani, Sabrina Giglio
Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly described in association with mutations in one gene instead of the others. Nevertheless, the diagnosis of distal renal tubular acidosis is essentially based on clinical and laboratory findings, and the series of patients described so far are usually represented by small cohorts...
February 20, 2017: Kidney International
https://www.readbyqxmd.com/read/28233609/nephrotic-syndrome-in-pregnancy-poses-risks-with-both-maternal-and-fetal-complications
#4
Iris De Castro, Thomas R Easterling, Nisha Bansal, J Ashley Jefferson
In the absence of uncontrolled hypertension or renal insufficiency, many consider the perinatal outcomes in pregnant women with nephrotic syndrome to be good. To further investigate this we performed a retrospective chart review of women with biopsy-proven nephrotic syndrome due to primary glomerular disease during pregnancy at a single tertiary center. Our review determined characteristics, presentation, management, pathologic diagnoses, and associated renal and maternal-fetal outcomes of 19 individuals with 26 pregnancies and 26 offspring...
February 20, 2017: Kidney International
https://www.readbyqxmd.com/read/28222898/strategies-for-the-optimal-timing-to-start-renal-replacement-therapy-in-critically-ill-patients-with-acute-kidney-injury
#5
REVIEW
Sean M Bagshaw, Ron Wald
Renal replacement therapy (RRT) is increasingly utilized to support critically ill patients with severe acute kidney injury (AKI). The question of whether and when to start RRT for a critically ill patient with AKI has long troubled clinicians. When severe complications of AKI develop, the need to commence RRT is unambiguous. In the absence of such complications but in the presence of severe AKI, the optimal time and thresholds for starting RRT are uncertain. The majority of existing data have largely been derived from observational studies...
February 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28215666/expansion-of-polymorphonuclear-myeloid-derived-suppressor-cells-in-patients-with-end-stage-renal-disease-may-lead-to-infectious-complications
#6
Yan-Fang Xing, Rui-Ming Cai, Qu Lin, Qing-Jian Ye, Jian-Hua Ren, Liang-Hong Yin, Xing Li
Myeloid-derived suppressor cells (MDSCs) are recently identified immune suppressive cells in multiple chronic inflammations. Here, we investigated MDSCs in patients with end-stage renal disease (ESRD) and their clinical significance in these patients and healthy individuals (49 each). Polymorphonuclear and mononuclear MDSCs were investigated by flow cytometry. Patients with ESRD before hemodialysis presented a significantly higher level of polymorphonuclear MDSCs. Depletion of polymorphonuclear-MDSCs resolved T cell IFN-γ responses...
February 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28214022/circulating-il-6-upregulates-il-10-production-in-splenic-cd4-t-cells-and-limits-acute-kidney-injury-induced-lung-inflammation
#7
Ana Andres-Hernando, Kayo Okamura, Rhea Bhargava, Carol M Kiekhaefer, Danielle Soranno, Lara A Kirkbride-Romeo, Hyo-Wook Gil, Chris Altmann, Sarah Faubel
Although it is well established that acute kidney injury (AKI) is a proinflammatory state, little is known about the endogenous counter-inflammatory response. IL-6 is traditionally considered a pro-inflammatory cytokine that is elevated in the serum in both human and murine AKI. However, IL-6 is known to have anti-inflammatory effects. Here we sought to investigate the role of IL-6 in the counter-inflammatory response after AKI, particularly in regard to the anti-inflammatory cytokine IL-10. Ischemic AKI was induced by bilateral renal pedicle clamping...
February 14, 2017: Kidney International
https://www.readbyqxmd.com/read/28209335/impact-of-fluid-status-and-inflammation-and-their-interaction-on-survival-a-study-in-an-international-hemodialysis-patient-cohort
#8
Marijke J E Dekker, Daniele Marcelli, Bernard J Canaud, Paola Carioni, Yuedong Wang, Aileen Grassmann, Constantijn J A M Konings, Peter Kotanko, Karel M Leunissen, Nathan W Levin, Frank M van der Sande, Xiaoling Ye, Vaibhav Maheshwari, Len A Usvyat, Jeroen P Kooman
In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein...
February 13, 2017: Kidney International
https://www.readbyqxmd.com/read/28209334/pregnancy-in-chronic-kidney-disease-and-kidney-transplantation
#9
REVIEW
Philip Webster, Liz Lightstone, Dianne B McKay, Michelle A Josephson
Chronic kidney disease (CKD) affects up to 6% of women of childbearing age in high income countries, and is estimated to affect 3% of pregnant women. Advanced renal dysfunction, proteinuria, hypertension, and poorly controlled underlying primary renal disease are all significant risks for adverse maternal, fetal, and renal outcomes. In order to achieve the best outcomes, it is therefore of paramount importance that these pregnancies are planned, where possible, to allow the opportunity to counsel women and their partners in advance and to optimize these risks...
February 13, 2017: Kidney International
https://www.readbyqxmd.com/read/28187985/a-systematic-review-and-meta-analysis-suggests-obesity-predicts-onset-of-chronic-kidney-disease-in-the-general-population
#10
Carlo Garofalo, Silvio Borrelli, Roberto Minutolo, Paolo Chiodini, Luca De Nicola, Giuseppe Conte
Obesity and chronic kidney disease (CKD) are public health priorities that share core pathophysiological mechanisms. However, whether high body mass index (BMI) increases risk of CKD de novo remains ill-defined. To evaluate the role of BMI in predicting CKD onset in the general adult population, we performed a systematic review and meta-analysis of PubMed and ISI Web of Science databases articles published between January 2000 and August 2016 without language restriction. We selected studies in adult individuals from a general population with normal renal function at baseline that reported the risk of low estimated glomerular filtration (eGFR) (under 60 mL/min/1...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28187984/construction-of-a-viral-t2a-peptide-based-knock-in-mouse-model-for-enhanced-cre-recombinase-activity-and-fluorescent-labeling-of-podocytes
#11
Sybille Koehler, Sebastian Brähler, Fabian Braun, Henning Hagmann, Markus M Rinschen, Martin R Späth, Martin Höhne, F Thomas Wunderlich, Bernhard Schermer, Thomas Benzing, Paul T Brinkkoetter
Podocyte injury is a key event in glomerular disease leading to proteinuria and opening the path toward glomerular scarring. As a consequence, glomerular research strives to discover molecular mechanisms and signaling pathways affecting podocyte health. The hNphs2.Cre mouse model has been a valuable tool to manipulate podocyte-specific genes and to label podocytes for lineage tracing and purification. Here we designed a novel podocyte-specific tricistronic Cre mouse model combining codon improved Cre expression and fluorescent cell labeling with mTomato under the control of the endogenous Nphs2 promoter using viral T2A-peptides...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28187983/intensified-multifactorial-intervention-in-type-2-diabetics-with-microalbuminuria-leads-to-long-term-renal-benefits
#12
Jens Oellgaard, Peter Gæde, Peter Rossing, Frederik Persson, Hans-Henrik Parving, Oluf Pedersen
In the present post hoc analyses we studied the impact of intensified, multifactorial treatment on renal outcomes in patients with type 2 diabetes and microalbuminuria enrolled in the Steno-2 Study. Outcome measures were progression to macroalbuminuria, decline in the glomerular filtration rate (GFR), and development of end stage renal disease (ESRD). In total, 160 patients with type 2 diabetes and microalbuminuria were recruited and assigned to conventional or intensified therapy targeting multiple risk factors...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28187982/the-renal-trpv4-channel-is-essential-for-adaptation-to-increased-dietary-potassium
#13
Mykola V Mamenko, Nabila Boukelmoune, Viktor N Tomilin, Oleg L Zaika, V Behrana Jensen, Roger G O'Neil, Oleh M Pochynyuk
To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28187981/deglycosylation-of-myeloperoxidase-uncovers-its-novel-antigenicity
#14
Jun-Tao Yu, Jian-Nan Li, Jia Wang, Xiao-Yu Jia, Zhao Cui, Ming-Hui Zhao
Myeloperoxidase (MPO) is a common target antigen of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and is recognized in one-third of patients with anti-glomerular basement membrane (GBM) disease. Our previous study identified over 60% of patients with anti-GBM disease recognizing linear peptides of MPO heavy chain. Here we tested whether aberrant glycosylation alters MPO antigenicity through exposure of neo-epitopes on MPO molecules. Atypical glycosylated MPO molecules, including all possible glycosylation types, were prepared by exoglycosidase and endoglycosidase treatments...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28187980/patients-with-hypertension-associated-thrombotic%C3%A2-microangiopathy-may-present-with%C3%A2-complement-abnormalities
#15
Sjoerd A M E G Timmermans, Myrurgia A Abdul-Hamid, Joris Vanderlocht, Jan G M C Damoiseaux, Chris P Reutelingsperger, Pieter van Paassen
Thrombotic microangiopathy (TMA) is a pattern of endothelial damage that can be found in association with diverse clinical conditions such as malignant hypertension. Although the pathophysiological mechanisms differ, accumulating evidence links complement dysregulation to various TMA syndromes and in particular the atypical hemolytic uremic syndrome. Here, we evaluated the role of complement in nine consecutive patients with biopsy-proven renal TMA attributed to severe hypertension. Profound hematologic symptoms of TMA were uncommon...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28159318/circulating-fibronectin-contributes-to-mesangial-expansion-in-a-murine-model-of-type-1-diabetes
#16
Verena Klemis, Hiba Ghura, Giuseppina Federico, Carina Würfel, Anke Bentmann, Norbert Gretz, Tatsuhiko Miyazaki, Hermann-Joseph Gröne, Inaam A Nakchbandi
Fibronectin is ubiquitously expressed in the extracellular matrix, and its accumulation in the glomerular mesangium in diabetic nephropathy is associated with deterioration of renal function in these patients. However, the exact role of fibronectin in the pathogenesis of diabetic nephropathy remains unknown. To clarify this, we administered fluorescent-labeled plasma fibronectin to wild-type mice and found it to accumulate in the mesangium. Using liver-specific conditional-knockout mice to decrease circulating fibronectin, we reduced circulating fibronectin by more than 90%...
January 31, 2017: Kidney International
https://www.readbyqxmd.com/read/28159317/novel-treatment-protocol-for-ameliorating-refractory-chronic-pain-in-patients-with-autosomal-dominant-polycystic-kidney-disease
#17
Niek F Casteleijn, Maatje D A van Gastel, Peter J Blankestijn, Joost P H Drenth, Rosa L de Jager, Anna M Leliveld, Ruud Stellema, Andreas P Wolff, Gerbrand J Groen, Ron T Gansevoort
Autosomal dominant polycystic kidney disease (ADPKD) patients can suffer from chronic pain that can be refractory to conventional treatment, resulting in a wish for nephrectomy. This study aimed to evaluate the effect of a multidisciplinary treatment protocol with sequential nerve blocks on pain relief in ADPKD patients with refractory chronic pain. As a first step a diagnostic, temporary celiac plexus block with local anesthetics was performed. If substantial pain relief was obtained, the assumption was that pain was relayed via the celiac plexus and major splanchnic nerves...
January 31, 2017: Kidney International
https://www.readbyqxmd.com/read/28143656/bone-marrow-transplantation-improves-proximal-tubule-dysfunction-in-a-mouse-model-of-dent-disease
#18
Sarah S Gabriel, Hendrica Belge, Alkaly Gassama, Huguette Debaix, Alessandro Luciani, Thomas Fehr, Olivier Devuyst
Dent disease is a rare X-linked tubulopathy caused by mutations in the endosomal chloride-proton exchanger (ClC-5) resulting in defective receptor-mediated endocytosis and severe proximal tubule dysfunction. Bone marrow transplantation has recently been shown to preserve kidney function in cystinosis, a lysosomal storage disease causing proximal tubule dysfunction. Here we test the effects of bone marrow transplantation in Clcn5(Y/-) mice, a faithful model for Dent disease. Transplantation of wild-type bone marrow in Clcn5(Y/-) mice significantly improved proximal tubule dysfunction, with decreased low-molecular-weight proteinuria, glycosuria, calciuria, and polyuria four months after transplantation, compared to Clcn5(Y/-) mice transplanted with ClC-5 knockout bone marrow...
January 28, 2017: Kidney International
https://www.readbyqxmd.com/read/28139295/hypercalcemia-induces-targeted-autophagic-degradation-of-aquaporin-2-at-the-onset-of-nephrogenic-diabetes-insipidus
#19
Sookkasem Khositseth, Komgrid Charngkaew, Chatikorn Boonkrai, Poorichaya Somparn, Panapat Uawithya, Nusara Chomanee, D Michael Payne, Robert A Fenton, Trairak Pisitkun
Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased...
January 27, 2017: Kidney International
https://www.readbyqxmd.com/read/28139294/c5-inhibition-prevents-renal-failure-in-a-mouse-model-of-lethal-c3-glomerulopathy
#20
Allison Lesher Williams, Damodar Gullipalli, Yoshiyasu Ueda, Sayaka Sato, Lin Zhou, Takashi Miwa, Kenneth S Tung, Wen-Chao Song
C3 glomerulopathy is a potentially life-threatening disease of the kidney caused by dysregulated alternative pathway complement activation. The specific complement mediator(s) responsible for kidney injury in C3 glomerulopathy are yet to be defined and no specific therapy is currently available. We previously developed a mouse model of lethal C3 glomerulopathy with factor H and properdin gene double mutations. Therefore, we used this model to examine the role of C5 and C5a receptor (C5aR) in the pathogenesis of the disease...
January 27, 2017: Kidney International
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