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By Isabel Acosta-Ochoa Nephrology senior staff. Valladolid. Spain
H Wiig, F C Luft, J M Titze
The role of salt in the pathogenesis of arterial hypertension is not well understood. According to the current understanding, the central mechanism for blood pressure (BP) regulation relies on classical studies linking BP and Na+ balance, placing the kidney at the very centre of long-term BP regulation. To maintain BP homeostasis, the effective circulating fluid volume and thereby body Na+ content has to be maintained within very narrow limits. From recent work in humans and rats, the notion has emerged that Na+ could be stored somewhere in the body without commensurate water retention to buffer free extracellular Na+ and that previously unidentified extrarenal, tissue-specific regulatory mechanisms are operative regulating the release and storage of Na+ from a kidney-independent reservoir...
November 28, 2017: Acta Physiologica
Dario R Lemos, Graham Marsh, Angela Huang, Gabriela Campanholle, Takahide Aburatani, Lan Dang, Ivan Gomez, Ken Fisher, Giovanni Ligresti, Janos Peti-Peterdi, Jeremy S Duffield
Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1(+) mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice...
December 1, 2016: American Journal of Physiology. Renal Physiology
Sandeep K Mallipattu, John C He
The Centers for Disease Control and Prevention estimates more than 10% of adults in the United States, over 20 million Americans, have chronic kidney disease (CKD). A failure to maintain the glomerular filtration barrier directly contributes to the onset of CKD. The visceral epithelial cells, podocytes, are integral to the maintenance of this renal filtration barrier. Direct podocyte injury contributes to the onset and progression of glomerular diseases such as minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), diabetic nephropathy, and HIV-associated nephropathy (HIVAN)...
July 1, 2016: American Journal of Physiology. Renal Physiology
Ellen F Carney
No abstract text is available yet for this article.
June 2016: Nature Reviews. Nephrology
A Richard Kitching, Holly L Hutton
Glomerular diseases are common and important. They can arise from systemic inflammatory or metabolic diseases that affect the kidney. Alternately, they are caused primarily by local glomerular abnormalities, including genetic diseases. Both intrinsic glomerular cells and leukocytes are critical to the healthy glomerulus and to glomerular dysregulation in disease. Mesangial cells, endothelial cells, podocytes, and parietal epithelial cells within the glomerulus all play unique and specialized roles. Although a specific disease often primarily affects a particular cell type, the close proximity, and interdependent functions and interactions between cells mean that even diseases affecting one cell type usually indirectly influence others...
September 7, 2016: Clinical Journal of the American Society of Nephrology: CJASN
Wilna Oosthuyzen, Kathleen M Scullion, Jessica R Ivy, Emma E Morrison, Robert W Hunter, Philip J Starkey Lewis, Eoghan O'Duibhir, Jonathan M Street, Andrea Caporali, Christopher D Gregory, Stuart J Forbes, David J Webb, Matthew A Bailey, James W Dear
Extracellular vesicles (ECVs) facilitate intercellular communication along the nephron, with the potential to change the function of the recipient cell. However, it is not known whether this is a regulated process analogous to other signaling systems. We investigated the potential hormonal regulation of ECV transfer and report that desmopressin, a vasopressin analogue, stimulated the uptake of fluorescently loaded ECVs into a kidney collecting duct cell line (mCCDC11) and into primary cells. Exposure of mCCDC11 cells to ECVs isolated from cells overexpressing microRNA-503 led to downregulated expression of microRNA-503 target genes, but only in the presence of desmopressin...
November 2016: Journal of the American Society of Nephrology: JASN
David A Ferenbach, Joseph V Bonventre
PURPOSE OF REVIEW: The kidney mediates the excretion or conservation of water and electrolytes in the face of changing fluid and salt intake and losses. To ultrafilter and reabsorb the exact quantities of free water and salts to maintain euvolemia a range of endocrine, paracrine, and hormonal signaling systems have evolved linking the tubules, capillaries, glomeruli, arterioles, and other intrinsic cells of the kidney. Our understanding of these systems remains incomplete. RECENT FINDINGS: Recent work has provided new insights into the workings of the communication pathways between tubular segments and the glomeruli and vasculature, with novel therapeutic agents in development...
May 2016: Current Opinion in Nephrology and Hypertension
Jerome Lowenstein, Jared J Grantham
The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured...
June 1, 2016: American Journal of Physiology. Renal Physiology
Giovanni Ligresti, Ryan J Nagao, Jun Xue, Yoon Jung Choi, Jin Xu, Shuyu Ren, Takahide Aburatani, Susan K Anderson, James W MacDonald, Theo K Bammler, Stephen M Schwartz, Kimberly A Muczynski, Jeremy S Duffield, Jonathan Himmelfarb, Ying Zheng
Human kidney peritubular capillaries are particularly susceptible to injury, resulting in dysregulated angiogenesis, capillary rarefaction and regression, and progressive loss of kidney function. However, little is known about the structure and function of human kidney microvasculature. Here, we isolated, purified, and characterized human kidney peritubular microvascular endothelial cells (HKMECs) and reconstituted a three-dimensional human kidney microvasculature in a flow-directed microphysiologic system...
August 2016: Journal of the American Society of Nephrology: JASN
Sanjay K Nigam, Wei Wu, Kevin T Bush, Melanie P Hoenig, Roland C Blantz, Vibha Bhatnagar
The proximal tubule of the kidney plays a crucial role in the renal handling of drugs (e.g., diuretics), uremic toxins (e.g., indoxyl sulfate), environmental toxins (e.g., mercury, aristolochic acid), metabolites (e.g., uric acid), dietary compounds, and signaling molecules. This process is dependent on many multispecific transporters of the solute carrier (SLC) superfamily, including organic anion transporter (OAT) and organic cation transporter (OCT) subfamilies, and the ATP-binding cassette (ABC) superfamily...
November 6, 2015: Clinical Journal of the American Society of Nephrology: CJASN
R Tyler Miller, Paul A Janmey
PURPOSE OF REVIEW: Cells and tissues must respond to physical stresses. Cells exist in an elastic environment determined by their matrix, matrix contacts, cell-cell contacts, and cytoskeletal structure. We discuss the determinants of the elastic environment of cells and its potential roles in glomerular disease. RECENT FINDINGS: Control of the mechanical environment is sufficient to induce and maintain the differentiated state of cells including myofibroblasts. New experimental techniques permit precise measurement of the elastic characteristics of normal and diseased tissues and cells, and analysis of cell behavior and cytoskeletal structure in response to mechanical and elastic stimuli...
July 2015: Current Opinion in Nephrology and Hypertension
Tarek M El-Achkar, Pierre C Dagher
The mammalian kidney is an organ composed of numerous functional units or nephrons. Beyond the filtering glomerulus of each nephron, various tubular segments with distinct populations of epithelial cells sequentially span the kidney from cortex to medulla. The highly organized folding of the tubules results in a spatial distribution that allows intimate contact between various tubular subsegments. This unique arrangement can promote a newly recognized type of horizontal epithelial-to-epithelial cross talk. In this review, we discuss the importance of this tubular cross talk in shaping the response of the kidney to acute injury in a sense and sensibility model...
June 15, 2015: American Journal of Physiology. Renal Physiology
Victor G Puelles, John F Bertram
PURPOSE OF REVIEW: There is currently much interest in the numbers of both glomeruli and podocytes. This interest stems from a greater understanding of the effects of suboptimal fetal events on nephron endowment, the associations between low nephron number and chronic cardiovascular and kidney disease in adults, and the emergence of the podocyte depletion hypothesis. RECENT FINDINGS: Obtaining accurate and precise estimates of glomerular and podocyte number has proven surprisingly difficult...
May 2015: Current Opinion in Nephrology and Hypertension
Jae Wook Lee, Chung-Lin Chou, Mark A Knepper
The function of each renal tubule segment depends on the genes expressed therein. High-throughput methods used for global profiling of gene expression in unique cell types have shown low sensitivity and high false positivity, thereby limiting the usefulness of these methods in transcriptomic research. However, deep sequencing of RNA species (RNA-seq) achieves highly sensitive and quantitative transcriptomic profiling by sequencing RNAs in a massive, parallel manner. Here, we used RNA-seq coupled with classic renal tubule microdissection to comprehensively profile gene expression in each of 14 renal tubule segments from the proximal tubule through the inner medullary collecting duct of rat kidneys...
November 2015: Journal of the American Society of Nephrology: JASN
Michael Zeisberg, Raghu Kalluri
Long overlooked as the virtual compartment and then strictly characterized through descriptive morphologic analysis, the renal interstitium has finally been associated with function. With identification of interstitial renin- and erythropoietin-producing cells, the most prominent endocrine functions of the kidney have now been attributed to the renal interstitium. This article reviews the functional role of renal interstitium.
October 7, 2015: Clinical Journal of the American Society of Nephrology: CJASN
Florian Grahammer, Thomas Benzing, Tobias B Huber
Glomerular kidney diseases are a major cause of end-stage renal disease (ESRD). Thus, it comes as wonderful news that glomerular research is advancing at a remarkable pace. Researchers from around the world met at the 10th International Podocyte Conference in Freiburg, Germany, to discuss the latest developments and findings in this innovative field of kidney research. The meeting highlighted the tremendous progress in our understanding of podocyte-related disorders and promised a rapid transfer of this knowledge into novel treatment options for proteinuric kidney diseases...
May 2015: Kidney International
Albert Q Lam, Joseph V Bonventre
PURPOSE OF REVIEW: Nephrogenesis in humans is limited to the period of embryonic kidney development in utero, with no new nephrons formed after birth. Although the kidneys possess the capacity to self-repair segments of the nephron, nephron loss from acute or chronic kidney injury is irreversible and results in impaired function. Human pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, are an attractive source of cells to regenerate nephron progenitor cells (NPCs) and ultimately functional kidney tissue...
April 2015: Current Opinion in Organ Transplantation
Moin A Saleem
The podocyte is a highly specialized cell, forming within the developing glomerulus from a mesenchymal origin, acquiring some but not complete features of an epithelial cell as it matures. Once mature, this cell has the potential to receive signals from several different directions and sits within a dynamic microenvironment. By taking an overview of many lines of evidence, it is clear that we already know many signals that are tightly controlled in keeping the podocyte healthy. For example, vascular endothelial growth factor, insulin and integrins are all known to have bidirectional effects on podocyte functionality, depending on whether there is too much or too little...
August 2015: Nephrology, Dialysis, Transplantation
Ankita Roy, Mohammad M Al-bataineh, NĂºria M Pastor-Soler
Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the function of the intercalated cell has become greatly enhanced and has shaped a new model for how the distal segments of the kidney tubule integrate salt and water reabsorption, potassium homeostasis, and acid-base status. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on the species. They are most abundant in the collecting duct, where they can be detected all the way from the cortex to the initial part of the inner medulla...
February 6, 2015: Clinical Journal of the American Society of Nephrology: CJASN
Enriko D Klootwijk, Markus Reichold, Robert J Unwin, Robert Kleta, Richard Warth, Detlef Bockenhauer
Renal Fanconi syndrome (RFS) refers to the generalized dysfunction of the proximal tubule (PT) (Kleta R. Fanconi or not Fanconi? Lowe syndrome revisited. Clin J Am Soc Nephrol 2008; 3: 1244-1245). In its isolated form, RFS only affects the PT, but not the other nephron segments. The study of isolated RFS can thus provide specific insights into the function of the PT. In a recent paper, Klootwijk et al. investigated one such form of isolated RFS and revealed the underlying molecular basis (Klootwijk ED, Reichold M, Helip-Wooley A et al...
September 2015: Nephrology, Dialysis, Transplantation
2014-12-12 10:13:15
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