Journal of the American Society of Nephrology : JASN This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor Signaling
In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCB11, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2. We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) enco...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Santana Machado, T., Poitevin, S., Paul, P., McKay, N., Jourde-Chiche, N., Legris, T., Mouly-Bandini, A., Dignat-George, F., Brunet, P., Masereeuw, R., Burtey, S., Cerini, C. Tags: Basic Research Source Type: research

Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction
In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles du...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Furini, G., Schroeder, N., Huang, L., Boocock, D., Scarpellini, A., Coveney, C., Tonoli, E., Ramaswamy, R., Ball, G., Verderio, C., Johnson, T. S., Verderio, E. A. M. Tags: Basic Research Source Type: research

ApoL1 Overexpression Drives Variant-Independent Cytotoxicity
Coding variants in the APOL1 gene are associated with kidney diseases in African ancestral populations; yet, the underlying biologic mechanisms remain uncertain. Variant-dependent autophagic and cytotoxic cell death have been proposed as pathogenic pathways mediating kidney injury. To examine this possibility, we conditionally expressed APOL1-G0 (reference), -G1, and -G2 (variants) using a tetracycline-regulated system in HEK293 cells. Autophagy was monitored biochemically and cell death was measured using multiple assays. We measured intracellular Na+ and K+ content with atomic absorption spectroscopy and APOL1-dependent ...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: O'Toole, J. F., Schilling, W., Kunze, D., Madhavan, S. M., Konieczkowski, M., Gu, Y., Luo, L., Wu, Z., Bruggeman, L. A., Sedor, J. R. Tags: Basic Research Source Type: research

GRHL2 Is Required for Collecting Duct Epithelial Barrier Function and Renal Osmoregulation
Collecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions composed of barrier-enforcing claudins and exhibits a higher transepithelial resistance than other segments of the renal tubule exhibit. However, the functional relevance of this s...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Hinze, C., Ruffert, J., Walentin, K., Himmerkus, N., Nikpey, E., Tenstad, O., Wiig, H., Mutig, K., Yurtdas, Z. Y., Klein, J. D., Sands, J. M., Branchi, F., Schumann, M., Bachmann, S., Bleich, M., Schmidt-Ott, K. M. Tags: Basic Research Source Type: research

Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney
Tamm–Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loop of Henle. Although predominantly secreted apically into the urine, where it becomes highly polymerized, THP is also released basolaterally, toward the interstitium and circulation, to inhibit tubular inflammatory signaling. Whether, through this latter route, THP can also regulate the function of renal interstitial mononuclear phagocytes (MPCs) remains unclear, however. Here, we show that THP is primarily in a monomeric form in human serum. Compared with wild-type mice, THP&nda...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Micanovic, R., Khan, S., Janosevic, D., Lee, M. E., Hato, T., Srour, E. F., Winfree, S., Ghosh, J., Tong, Y., Rice, S. E., Dagher, P. C., Wu, X.-R., El-Achkar, T. M. Tags: Basic Research Source Type: research

Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron Patterning
The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal–distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity. Moreover, we identified a novel ne...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Lindström, N. O., Tran, T., Guo, J., Rutledge, E., Parvez, R. K., Thornton, M. E., Grubbs, B., McMahon, J. A., McMahon, A. P. Tags: Basic Research Source Type: research

Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney
This study provides a benchmark for the mesenchymal progenitors in the human nephrogenic niche and highlights species-variability in kidney developmental programs. (Source: Journal of the American Society of Nephrology : JASN)
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Lindström, N. O., Guo, J., Kim, A. D., Tran, T., Guo, Q., De Sena Brandine, G., Ransick, A., Parvez, R. K., Thornton, M. E., Basking, L., Grubbs, B., McMahon, J. A., Smith, A. D., McMahon, A. P. Tags: Basic Research Source Type: research

Conserved and Divergent Features of Human and Mouse Kidney Organogenesis
Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34–37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined hu...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Lindström, N. O., McMahon, J. A., Guo, J., Tran, T., Guo, Q., Rutledge, E., Parvez, R. K., Saribekyan, G., Schuler, R. E., Liao, C., Kim, A. D., Abdelhalim, A., Ruffins, S. W., Thornton, M. E., Basking, L., Grubbs, B., Kesselman, C., McMahon, A. P Tags: Basic Research Source Type: research

Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca Fusion
The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion....
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Hoshi, M., Reginensi, A., Joens, M. S., Fitzpatrick, J. A. J., McNeill, H., Jain, S. Tags: Brief Communication Source Type: research

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach
FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasses of FSGS include primary, genetic, and secondary forms, the latter comprising maladaptive, viral, and drug-induced FSGS. Despite sharing certain clinical and histologic features, these subclasses differ noticeably in management and prognosis. Without an accepted nongenetic biomarker that discriminates among these FSGS types, classification of patients is often challenging. This review summarizes the clinical and histologic features, including the onset and severity of proteinuria as w...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: De Vriese, A. S., Sethi, S., Nath, K. A., Glassock, R. J., Fervenza, F. C. Tags: Brief Reviews Source Type: research

Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives
The unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody-mediated transplant rejection permits insight into the pathogenetic effect of these cells. Notwithstanding the limitations of preclinical models and clinical studies (h...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Schrezenmeier, E., Jayne, D., Dörner, T. Tags: Brief Reviews Source Type: research

Salt-Losing Tubulopathies in Children: Whats New, Whats Controversial?
Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual physicians and centers and is based mainly on understanding of renal physiology, reported clinical observations, and individual experiences. Salt-losing tubulopathies can affect al...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Kleta, R., Bockenhauer, D. Tags: Brief Reviews Source Type: research

The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease
The identification of genetic factors associated with kidney disease has the potential to provide critical insights into disease mechanisms. Genome-wide association studies have uncovered genomic regions associated with renal function metrics and risk of CKD. UMOD is among the most outstanding loci associated with CKD in the general population, because it has a large effect on eGFR and CKD risk that is consistent across different ethnic groups. The relevance of UMOD for CKD is clear, because the encoded protein, uromodulin (Tamm–Horsfall protein), is exclusively produced by the kidney tubule and has specific biochemi...
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Devuyst, O., Pattaro, C. Tags: Brief Reviews Source Type: research

The Benefits of Tubular Proteinuria: An Evolutionary Perspective
(Source: Journal of the American Society of Nephrology : JASN)
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Simons, M. Tags: Perspective Source Type: research

Evolution and Kidney Development: A Rosetta Stone for Nephrology
(Source: Journal of the American Society of Nephrology : JASN)
Source: Journal of the American Society of Nephrology : JASN - February 28, 2018 Category: Urology & Nephrology Authors: Chevalier, R. L. Tags: Editorials Source Type: research