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Katarina Leyba, Brent Wagner
PURPOSE OF REVIEW: The hegemony of gadolinium-based contrast agent-induced adverse events stretches beyond those who have renal impairment. 'Nephrogenic' systemic fibrosis is a misnomer: gadolinium-based contrast agents are the known trigger for the disease; kidney impairment is a risk factor. Impaired (true) glomerular filtration may be one catalyst for gadolinium-based contrast agent-induced adverse events, but it is increasingly evident that the same cluster of symptoms occurs in patients with normal renal function...
December 3, 2018: Current Opinion in Nephrology and Hypertension
Lori L O'Brien, Alexander N Combes, Kieran M Short, Nils O Lindström, Peter H Whitney, Luise A Cullen-McEwen, Adler Ju, Ahmed Abdelhalim, Odyssé Michos, John F Bertram, Ian M Smyth, Melissa H Little, Andrew P McMahon
A normal endowment of nephrons in the mammalian kidney requires a balance of nephron progenitor self-renewal and differentiation throughout development. Here, we provide evidence for a novel action of ureteric branch tip-derived Wnt11 in progenitor cell organization and interactions within the nephrogenic niche, ultimately determining nephron endowment. In Wnt11 mutants, nephron progenitors dispersed from their restricted niche, intermixing with interstitial progenitors. Nephron progenitor differentiation was accelerated, kidneys were significantly smaller, and the nephron progenitor pool was prematurely exhausted, halving the final nephron count...
December 5, 2018: ELife
Mariane Le Fur, Peter Caravan
Gadolinium-based contrast agents (GBCAs) are widely used with clinical magnetic resonance imaging (MRI), and 10 s of millions of doses of GBCAs are administered annually worldwide. GBCAs are hydrophilic, thermodynamically stable and kinetically inert gadolinium chelates. In clinical MRI, 5-10 millimoles of Gd ion is administered intravenously and the GBCA is rapidly eliminated intact primarily through the kidneys into the urine. It is now well-established that the Gd3+ ion, in some form(s), is partially retained in vivo...
December 5, 2018: Metallomics: Integrated Biometal Science
Donat Peter Sarlos, Daniel Banyai, Lehel Peterfi, Arpad Szanto, Gyula Kovacs
BACKGROUND/AIM: The association of Wilms' tumor (WT), papillary renal cell tumor (PRCT) and mucinous tubular and spindle cell carcinoma (MTSCC) with embryonal rests has already been documented, but the cellular origin of metanephric adenoma (MA) is not yet known. The aim of this study was to understand their developmental evolution and find diagnostic markers. MATERIALS AND METHODS: CD57, KRT7, AMACR, SCEL, WT1 and CDH17 expression was analysed by immunohistochemistry in the four types of tumors and the associated pre-neoplastic lesions...
December 2018: Anticancer Research
Kohei Kawaguchi, Juma Obayashi, Takuya Kawaguchi, Junki Koike, Yasuji Seki, Kunihide Tanaka, Kei Ohyama, Hideki Nagae, Shigeyuki Furuta, Masayuki Takagi, Kevin C Pringle, Hiroaki Kitagawa
BACKGROUND: The kidney develops from an intimate interaction between the ureteric bud and the metanephric mass. We attempted to differentially stain the derivatives of the ureteric bud and the metanephric mass in ovine fetuses. METHODS: After appropriate approval, 47 fetal lambs' kidneys at 50 (4), 60 (6), 70 (5), 80 (4), 100 (10), 110 (8), 145 (10) days' gestation (term is 140-145 days) were obtained. After confirming the pregnancy, the sheep were anesthetized, and the fetuses sacrificed...
December 2018: Journal of Pediatric Surgery
Tatyana Lyapustina, Charlotte Goldfine, Sean Rhyee, Kavita M Babu, Matthew K Griswold
INTRODUCTION: Gadolinium-based contrast agents (GBCAs) have been increasingly used in clinical practice since their introduction in the 1980s. Recently, increased public attention has been given to patients who report new symptoms following GBCA exposure. This review details the current knowledge surrounding GBCAs, with a focus on the known and proposed disease states that may be associated with GBCAs. Recommendations for the appropriate clinical workup of a patient suspected of having symptoms attributable to gadolinium exposure are included...
November 29, 2018: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
Kristen Kurtzeborn, Cristina Cebrian, Satu Kuure
Classically, trophic factors are considered as proteins which support neurons in their growth, survival, and differentiation. However, most neurotrophic factors also have important functions outside of the nervous system. Especially essential renal growth and differentiation regulators are glial cell line-derived neurotrophic factor (GDNF), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs). Here we discuss how trophic factor-induced signaling contributes to the control of ureteric bud (UB) branching morphogenesis and to maintenance and differentiation of nephrogenic mesenchyme in embryonic kidney...
2018: Frontiers in Physiology
Riccarda Delfino, Matteo Biasotto, Riccardo Candido, Matteo Altissimo, Marco Stebel, Murielle Salomè, Johannes T van Elteren, Katarina Vogel Mikuš, Cristina Zennaro, Martin Šala, Riccardo Addobbati, Giuliana Tromba, Lorella Pascolo
Gadolinium deposition in tissue is linked to nephrogenic systemic fibrosis (NSF): a rare disorder occurring in patients with severe chronic kidney disease and associated with administration of Gd-based contrast agents (GBCAs) for Magnetic Resonance Imaging (MRI). It is suggested that the GBCAs prolonged permanence in blood in these patients may result in a Gd precipitation in peripheral or central organs, where it initiates a fibrotic process. In this study we investigated new sites of retention/precipitation of Gd in a mouse model of renal disease (5/6 nephrectomy) receiving two doses (closely after each other) of a linear GBCA...
November 23, 2018: Toxicology Letters
Richard C Semelka, John P Prybylski, Miguel Ramalho
BACKGROUND: The molecular structure, charge, thermodynamic and kinetic stability are approximately the same for gadodiamide and gadoversetamide, the main substantive difference is that gadodiamide is manufactured with 5% free ligand to form Omniscan® and gadoversetamide with 10% free ligand to form OptiMARK®. PURPOSE: To determine the relative risk of Nephrogenic Systemic Fibrosis (NSF) between gadodiamide (Omniscan®) and gadoversetamide (OptiMARK®) and to explore the potential contribution of the amount of excess ligand added to their commercial formulations...
November 21, 2018: Magnetic Resonance Imaging
Catherine Kavanagh, Natalie S Uy
Nephrogenic diabetes insipidus (NDI) results from the inability of the late distal tubules and collecting ducts to respond to vasopressin. The lack of ability to concentrate urine results in polyuria and polydipsia. Primary and acquired forms of NDI exist in children. Congenital NDI is a result of mutation in AVPR2 or AQP2 genes. Secondary NDI is associated with electrolyte abnormalities, obstructive uropathy, or certain medications. Management of NDI can be difficult with only symptomatic treatment available, using low-solute diet, diuretics, and prostaglandin inhibitors...
February 2019: Pediatric Clinics of North America
Iryna V Sorokina, Mykhailo S Myroshnychenko, Nataliia V Kapustnyk, Alla V Simachova, Alona A Ivanova
OBJECTIVE: Introduction: Kidneys in fetuses and newborns play an important role in the homeostasis regulation and are the most vulnerable to the action of damaging factors from the mother organism, therefore it is important to timely assess their morphofunctional state. The aim: The purpose of the study was to reveal the morphometrical features of fetuses and newborns kidneys from mothers, whose pregnancy was complicated by iron deficiency anemia of varying degrees of severity. PATIENTS AND METHODS: Materials and methods: The material of the study was the tissue of kidneys of mature fetuses and newborns from mothers with physiological pregnancy (28 cases), as well as from mothers whose pregnancy was complicated by iron deficiency anemia of varying degrees of severity (85 cases)...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Anyi Wang, Takuo Hirose, Yusuke Ohsaki, Chika Takahashi, Emiko Sato, Ikuko Oba-Yabana, Satoshi Kinugasa, Yoshikazu Muroya, Sadayoshi Ito, Takefumi Mori
BACKGROUND: Tolvaptan is an effective treatment for polycystic kidney disease (PKD), but also causes unfortunate polyuria. Hydrochlorothiazide (HCTZ) has been shown to reduce urine volume in nephrogenic diabetes insipidus, raising the possibility that HCTZ could also be effective in reducing tolvaptan-induced polyuria. In this study, we examined the combined administration of HCTZ and tolvaptan. METHODS: Male PCK rats were divided into four groups of normal chow (Cont), normal chow plus tolvaptan, gavage HCTZ treatment, and tolvaptan + HCTZ...
November 13, 2018: Clinical and Experimental Nephrology
X H Wang, X Lu, B He, Y X Jiang, W J Yu, H Wang, W Zhang, Y J Li
Objective: To investigate the clinicopathologic characteristics, diagnostic features and prognosis of primary renal neuroendocrine carcinoma (NEC). Methods: The clinicopathologic data of eight cases of renal NEC was collected from January 2008 to December 2017 from Affiliated Hospital of Qingdao University. Immunohistochemical staining was performed, and follow-up information was analyzed, and the relevant literature reviewed. Results: The patients' mean age at diagnosis was 45 years (range, 27-66 years); five were women, and three were men...
November 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Anna Caliò, Kathleen A Warfel, John N Eble
The aim of this work was to study small neoplasms of the epithelium of the renal tubules; kidneys from 402 unselected autopsies were sectioned at 1 to 2 mm intervals. All lesions were examined histologically. A total of 232 papillary adenomas were found in 76 patients (19%), ranging from 1 to 35 adenomas/patient (mean: 3, median: 2). Patients with papillary adenomas were older (range: 27 to 90 y) (P<0.0001), more commonly smokers (P=0.01), and more frequently had glomerulosclerosis (P=0.0001) than those without...
November 9, 2018: American Journal of Surgical Pathology
Ismail Elbeshlawi, Mohamed S AbdelBaki
The introduction of paramagnetic contrast in the late 1980s constituted a paradigm shift boosting the efficacy of magnetic resonance imaging. Due to its high magnetic moment, gadolinium-based contrast agent made its way smoothly as the flagship paramagnetic contrast. With the widespread application, reports of untoward effects started to surface. Allergic reactions, nephrogenic systemic sclerosis, and deposition in brain tissue dented the safety profile of gadolinium-based contrast agent. Better understanding of these adverse effects prompted preventive measures...
September 2018: Pediatric Neurology
J Davis, M Desmond, M Berk
BACKGROUND: Despite lithium being the most efficacious treatment for bipolar disorder, its use has been decreasing at least in part due to concerns about its potential to cause significant nephrotoxicity. Whilst the ability of lithium to cause nephrogenic diabetes insipidus is well established, its ability to cause chronic kidney disease is a much more vexing issue, with various studies suggesting both positive and negative causality. Despite these differences, the weight of evidence suggests that lithium has the potential to cause end stage kidney disease, albeit over a prolonged period...
November 3, 2018: BMC Nephrology
Nozomu Kurose, Michiho Takenaka, Manabu Yamashita, Chie Shimaguchi, Mariko Nakano, Bryant Britni, Xin Guo, Chizuru Futatsuya, Akihiro Shioya, Sohsuke Yamada
BACKGROUND: Nephroblastoma (NB) is a malignant embryonal neoplasm derived from nephrogenic blastemal cells. NB usually forms a solid mass, but in extremely rare cases, it may show cystic changes. CASE PRESENTATION: A six-month-old girl with persistent high fevers was found to have pyuria and bacteriuria. Ultrasonography revealed multilocular cysts in the right kidney. Right nephrectomy was performed with cyst wall rupture during surgery. An intraoperative rapid diagnosis, based on peritoneal fluid cytology, confirmed three components of blastemal, stromal, and epithelial cells...
October 27, 2018: Diagnostic Pathology
Bin Li, Yanan Zhu, Haiyun Chen, Hui Gao, Hangyuan He, Na Zuo, Linguo Pei, Wen Xie, Liaobin Chen, Ying Ao, Hui Wang
This study aimed to demonstrate that prenatal dexamethasone exposure (PDE) can induce kidney dysplasia in utero and adult glomerulosclerosis in male offspring, and to explore the underlying intrauterine programming mechanisms. Pregnant rats were subcutaneously administered dexamethasone 0.2 mg/kg.d from gestational day (GD) 9 to GD20. The male fetus on GD20 and the adult offspring at age of postnatal week 28 were analyzed. The adult offspring kidneys in the PDE group displayed glomerulosclerosis, elevated levels of serum creatinine and urine protein, ultrastructural damage of podocytes, the reduced expression levels of podocyte marker genes, nephrin and podocin...
October 22, 2018: Toxicology
Will W Minuth
In healthy newborn babies, nephrogenesis proceeds unnoticed until birth. With start of the perinatal period, morphogenetic activity in the renal outer cortex consisting of an inner maturation zone and an outer nephrogenic zone is downregulated by unknown signals. One of the results is that the entire nephrogenic zone as well as the contained progenitor cells and niches disintegrate. In contrast, a too early inactivation of the nephrogenic zone takes place in the kidneys of preterm and low birth weight babies...
October 18, 2018: Cell and Tissue Research
Krithika Hariharan, Harald Stachelscheid, Bella Rossbach, Su-Jun Oh, Nancy Mah, Kai Schmidt-Ott, Andreas Kurtz, Petra Reinke
Human pluripotent stem cells (hPSCs) provide a source for the generation of defined kidney cells and renal organoids applicable in regenerative medicine, disease modeling, and drug screening. These applications require the provision of hPSC-derived renal cells by reproducible, scalable, and efficient methods. We established a chemically defined protocol by application of Activin A, BMP4, and Retinoic acid followed by GDNF, which steered hPSCs to the renal lineage and resulted in populations of SIX2+ /CITED1+ metanephric mesenchyme- (MM) and of HOXB7+ /GRHL2+ ureteric bud (UB)-like cells already by 6 days...
October 11, 2018: Cellular and Molecular Life Sciences: CMLS
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