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Journal of the American Society of Nephrology: JASN

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https://www.readbyqxmd.com/read/28923914/new-ultrasound-techniques-promise-further-advances-in-aki-and-ckd
#1
REVIEW
Travis D Hull, Anupam Agarwal, Kenneth Hoyt
AKI and CKD are important clinical problems because they affect many patients and the associated diagnostic and treatment paradigms are imperfect. Ultrasound is a cost-effective, noninvasive, and simple imaging modality that offers a multitude of means to improve the diagnosis, monitoring, and treatment of both AKI and CKD, especially considering recent advances in this technique. Ultrasound alone can attenuate AKI and prevent CKD by stimulating the splenic cholinergic anti-inflammatory pathway. Additionally, microbubble contrast agents are improving the sensitivity and specificity of ultrasound for diagnosing kidney disease, especially when these agents are conjugated to ligand-specific mAbs or peptides, which make the dynamic assessment of disease progression and response to treatment possible...
September 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28923913/variations-in-microrna-25-expression-influence-the-severity-of-diabetic-kidney-disease
#2
Yunshuang Liu, Hongzhi Li, Jieting Liu, Pengfei Han, Xuefeng Li, He Bai, Chunlei Zhang, Xuelian Sun, Yanjie Teng, Yufei Zhang, Xiaohuan Yuan, Yanhui Chu, Binghai Zhao
Diabetic nephropathy is characterized by persistent albuminuria, progressive decline in GFR, and secondary hypertension. MicroRNAs are dysregulated in diabetic nephropathy, but identification of the specific microRNAs involved remains incomplete. Here, we show that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of microRNA-25 (miR-25) compared with those of their nondiabetic counterparts. Furthermore, treatment with high glucose decreased the expression of miR-25 in cultured kidney cells...
September 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28912373/the-association-of-sleep-duration-and-quality-with-ckd-progression
#3
Ana C Ricardo, Kristen Knutson, Jinsong Chen, Lawrence J Appel, Lydia Bazzano, Eunice Carmona-Powell, Janet Cohan, Manjula Kurella Tamura, Susan Steigerwalt, John Daryl Thornton, Matthew Weir, Nicolas F Turek, Mahboob Rahman, Eve Van Cauter, James P Lash
Evidence suggests that sleep disorders are common in individuals with CKD, but the influence of sleep duration and quality on CKD progression is unknown. We examined the association of habitual sleep duration and quality with CKD progression in 431 Chronic Renal Insufficiency Cohort (CRIC) Study participants, of whom 48% were women and 50% had diabetes (mean age of 60 years old, mean eGFR =38 ml/min per 1.73 m(2), and median urine protein-to-creatinine ratio [UPCR] =0.20 g/g). We assessed sleep duration and quality by 5-7 days of wrist actigraphy and self-report...
September 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28904002/assessing-microvascular-function-in-humans-from-a-chronic-disease-perspective
#4
Alfons J H M Houben, Remy J H Martens, Coen D A Stehouwer
Microvascular dysfunction (MVD) is considered a crucial pathway in the development and progression of cardiometabolic and renal disease and is associated with increased cardiovascular mortality. MVD often coexists with or even precedes macrovascular disease, possibly due to shared mechanisms of vascular damage, such as inflammatory processes and oxidative stress. One of the first events in MVD is endothelial dysfunction. With the use of different physiologic or pharmacologic stimuli, endothelium-dependent (micro)vascular reactivity can be studied...
September 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28874403/new-insights-into-fuel-choices-of-nephron-progenitor-cells
#5
EDITORIAL
Leif Oxburgh, Clifford J Rosen
No abstract text is available yet for this article.
September 5, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28874402/transplantation-of-kidneys-from-hcv-positive-donors-how-to-best-use-a-scarce-resource
#6
David Roth, Marco Ladino
No abstract text is available yet for this article.
September 5, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28864466/the-evolving-complexity-of-the-podocyte-cytoskeleton
#7
Christoph Schell, Tobias B Huber
Podocytes exhibit a unique cytoskeletal architecture that is fundamentally linked to their function in maintaining the kidney filtration barrier. The cytoskeleton regulates podocyte shape, structure, stability, slit diaphragm insertion, adhesion, plasticity, and dynamic response to environmental stimuli. Genetic mutations demonstrate that even slight impairment of the podocyte cytoskeletal apparatus results in proteinuria and glomerular disease. Moreover, mechanisms underpinning all acquired glomerular pathologies converge on disruption of the cytoskeleton, suggesting that this subcellular structure could be targeted for therapeutic purposes...
September 1, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28860163/proximal-tubular-cannabinoid-1-receptor-regulates-obesity-induced-ckd
#8
Shiran Udi, Liad Hinden, Brian Earley, Adi Drori, Noa Reuveni, Rivka Hadar, Resat Cinar, Alina Nemirovski, Joseph Tam
Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB1R) induces nephropathy, whereas CB1R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB1R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis...
August 31, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28848001/the-trauma-of-dialysis-initiation
#9
Gavril Hercz
No abstract text is available yet for this article.
August 28, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28838955/bosutinib-versus-placebo-for-autosomal-dominant-polycystic-kidney-disease
#10
Vladimir Tesar, Kazimierz Ciechanowski, York Pei, Irina Barash, Megan Shannon, Ray Li, Jason H Williams, Matteo Levisetti, Steven Arkin, Andreas Serra
Overactivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR≥60 ml/min per 1.73 m(2), and total kidney volume ≥750 ml were randomized 1:1:1 to bosutinib 200 mg/d, bosutinib 400 mg/d, or placebo for ≤24 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for ≥2 weeks who had at least one postbaseline magnetic resonance imaging scan that was preceded by a 30-day washout (modified intent-to-treat population)...
August 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28827403/targeting-anti-tgf-%C3%AE-therapy-to-fibrotic-kidneys-with-a-dual-specificity-antibody-approach
#11
Steve McGaraughty, Rachel A Davis-Taber, Chang Z Zhu, Todd B Cole, Arthur L Nikkel, Meha Chhaya, Kelly J Doyle, Lauren M Olson, Gregory M Preston, Christine M Grinnell, Katherine M Salte, Anthony M Giamis, Yanping Luo, Victor Sun, Andrew D Goodearl, Murali Gopalakrishnan, Susan E Lacy
Targeted delivery of a therapeutic agent to a site of pathology to ameliorate disease while limiting exposure at undesired tissues is an aspirational treatment scenario. Targeting diseased kidneys for pharmacologic treatment has had limited success. We designed an approach to target an extracellular matrix protein, the fibronectin extra domain A isoform (FnEDA), which is relatively restricted in distribution to sites of tissue injury. In a mouse unilateral ureteral obstruction (UUO) model of renal fibrosis, injury induced significant upregulation of FnEDA in the obstructed kidney...
August 21, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28821571/why-diuretics-fail-failing-hearts
#12
EDITORIAL
Evan C Ray, Cary R Boyd-Shiwarski, Thomas R Kleyman
No abstract text is available yet for this article.
August 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28814511/targeting-phospholipase-d4-attenuates-kidney-fibrosis
#13
Priyanka Trivedi, Ramya K Kumar, Ashwin Iyer, Sarah Boswell, Casimiro Gerarduzzi, Vivekkumar P Dadhania, Zach Herbert, Nikita Joshi, James P Luyendyk, Benjamin D Humphreys, Vishal S Vaidya
Phospholipase D4 (PLD4), a single-pass transmembrane glycoprotein, is among the most highly upregulated genes in murine kidneys subjected to chronic progressive fibrosis, but the function of PLD4 in this process is unknown. Here, we found PLD4 to be overexpressed in the proximal and distal tubular epithelial cells of murine and human kidneys after fibrosis. Genetic silencing of PLD4, either globally or conditionally in proximal tubular epithelial cells, protected mice from the development of fibrosis. Mechanistically, global knockout of PLD4 modulated innate and adaptive immune responses and attenuated the upregulation of the TGF-β signaling pathway and α1-antitrypsin protein (a serine protease inhibitor) expression and downregulation of neutrophil elastase (NE) expression induced by obstructive injury...
August 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28814510/a-heterologous-model-of-thrombospondin-type-1-domain-containing-7a-associated-membranous-nephropathy
#14
Nicola M Tomas, Catherine Meyer-Schwesinger, Hanning von Spiegel, Ahmed M Kotb, Gunther Zahner, Elion Hoxha, Udo Helmchen, Nicole Endlich, Friedrich Koch-Nolte, Rolf A K Stahl
Thrombospondin type 1 domain-containing 7A (THSD7A) is a target for autoimmunity in patients with membranous nephropathy (MN). Circulating autoantibodies from patients with THSD7A-associated MN have been demonstrated to cause MN in mice. However, THSD7A-associated MN is a rare disease, preventing the use of patient antibodies for larger experimental procedures. Therefore, we generated antibodies against the human and mouse orthologs of THSD7A in rabbits by coimmunization with the respective cDNAs. Injection of these anti-THSD7A antibodies into mice induced a severe nephrotic syndrome with proteinuria, weight gain, and hyperlipidemia...
August 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28808078/relationship-of-kidney-injury-biomarkers-with-long-term-cardiovascular-outcomes-after-cardiac-surgery
#15
Chirag R Parikh, Jeremy Puthumana, Michael G Shlipak, Jay L Koyner, Heather Thiessen-Philbrook, Eric McArthur, Kathleen Kerr, Peter Kavsak, Richard P Whitlock, Amit X Garg, Steven G Coca
Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB)...
August 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28801314/macrophage-migration-inhibitory-factor-limits-renal-inflammation-and-fibrosis-by-counteracting-tubular-cell-cycle-arrest
#16
Sonja Djudjaj, Ina V Martin, Eva M Buhl, Nina J Nothofer, Lin Leng, Marta Piecychna, Jürgen Floege, Jürgen Bernhagen, Richard Bucala, Peter Boor
Renal fibrosis is a common underlying process of progressive kidney diseases. We investigated the role of macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine, in this process. In mice subjected to unilateral ureteral obstruction, genetic deletion or pharmacologic inhibition of MIF aggravated fibrosis and inflammation, whereas treatment with recombinant MIF was beneficial, even in established fibrosis. In two other models of progressive kidney disease, global Mif deletion or MIF inhibition also worsened fibrosis and inflammation and associated with worse kidney function...
August 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28794148/tubulointerstitial-nephritis-with-igm-positive-plasma-cells
#17
Naoki Takahashi, Takako Saeki, Atsushi Komatsuda, Chishio Munemura, Takeaki Fukui, Naofumi Imai, Noriyuki Homma, Tsuguru Hatta, Ken-Ichi Samejima, Takashi Fujimoto, Hiroki Omori, Yumi Ito, Yudai Nishikawa, Mamiko Kobayashi, Yukie Morikawa, Sachiko Fukushima, Seiji Yokoi, Daisuke Mikami, Kenji Kasuno, Hideki Kimura, Tomoyuki Nemoto, Yasunari Nakamoto, Kiyonao Sada, Manabu Sugai, Hironobu Naiki, Haruyoshi Yoshida, Ichiei Narita, Yoshihiko Saito, Masayuki Iwano
Infiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected...
August 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28790143/structural-and-functional-changes-in-human-kidneys-with-healthy-aging
#18
REVIEW
Musab S Hommos, Richard J Glassock, Andrew D Rule
Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR...
August 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28784700/serum-iron-protects-from-renal-postischemic-injury
#19
Céline Vaugier, Mariane T Amano, Jonathan M Chemouny, Michael Dussiot, Claire Berrou, Marie Matignon, Sanae Ben Mkaddem, Pamella H M Wang, Aurélie Fricot, Thiago T Maciel, Damien Grapton, Jacques R R Mathieu, Carole Beaumont, Marie-Noëlle Peraldi, Carole Peyssonnaux, Laurent Mesnard, Eric Daugas, François Vrtovsnik, Renato C Monteiro, Olivier Hermine, Yelena Z Ginzburg, Marc Benhamou, Niels O S Camara, Martin Flamant, Ivan C Moura
Renal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients (n=169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation...
August 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28784698/kidney-disease-in-hiv-moving-beyond-hiv-associated-nephropathy
#20
REVIEW
Vasantha Jotwani, Mohamed G Atta, Michelle M Estrella
In developed countries, remarkable advances in antiretroviral therapy have transformed HIV infection into a chronic condition. As a result, HIV-associated nephropathy, the classic HIV-driven kidney lesion among individuals of African descent, has largely disappeared in these regions. However, HIV-positive blacks continue to have much higher rates of ESRD than HIV-positive whites, which could be attributed to the APOL1 renal risk variants. Additionally, HIV-positive individuals face adverse consequences beyond HIV itself, including traditional risk factors for CKD and nephrotoxic effects of antiretroviral therapy...
August 7, 2017: Journal of the American Society of Nephrology: JASN
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