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Journal articles on the topic 'Kidney glomerulus Diseases'
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1
Beeman, Scott C., Min Zhang, Lina Gubhaju, Teresa Wu, John F. Bertram, David H. Frakes, Brian R. Cherry, and Kevin M. Bennett. "Measuring glomerular number and size in perfused kidneys using MRI." American Journal of Physiology-Renal Physiology 300, no. 6 (June 2011): F1454—F1457. http://dx.doi.org/10.1152/ajprenal.00044.2011.
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The goal of this work was to nondestructively measure glomerular (and thereby nephron) number in the whole kidney. Variations in the number and size of glomeruli have been linked to many renal and systemic diseases. Here, we develop a robust magnetic resonance imaging (MRI) technique based on injection of cationic ferritin (CF) to produce an accurate measurement of number and size of individual glomeruli. High-field (19 Tesla) gradient-echo MR images of perfused rat kidneys after in vivo intravenous injection of CF showed specific labeling of individual glomeruli with CF throughout the kidney. We developed a three-dimensional image-processing algorithm to count every labeled glomerulus. MRI-based counts yielded 33,786 ± 3,753 labeled glomeruli ( n = 5 kidneys). Acid maceration counting of contralateral kidneys yielded an estimate of 30,585 ± 2,053 glomeruli ( n = 6 kidneys). Disector/fractionator stereology counting yielded an estimate of 34,963 glomeruli ( n = 2). MRI-based measurement of apparent glomerular volume of labeled glomeruli was 4.89 × 10−4mm3( n = 5) compared with the average stereological measurement of 4.99 × 10−4mm3( n = 2). The MRI-based technique also yielded the intrarenal distribution of apparent glomerular volume, a measurement previously unobtainable in histology. This work makes it possible to nondestructively measure whole-kidney glomerular number and apparent glomerular volumes to study susceptibility to renal diseases and opens the door to similar in vivo measurements in animals and humans.
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KITAMURA, MASANORI. "Renal Transfer of Genetically Engineered Cells." Journal of the American Society of Nephrology 11, suppl 2 (November 2000): S154—S158. http://dx.doi.org/10.1681/asn.v11suppl_2s154.
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Abstract. For many years, ex vivo gene transfer has been used for genetic manipulation of various organs. In the kidney, ex vivo gene transfer was reported using mesangial cells and macrophages. In rats, cultured cells injected into the renal artery are accumulated selectively in the glomerulus. With this approach, it is possible to transfer genetically engineered cells to normal and diseased glomeruli. The transfer of genetically engineered cells to glomeruli can be used for several purposes. With the use of resident glomerular cells engineered in vitro, it is possible to examine how the cells that overexpress certain genes behave differently in normal and diseased glomeruli. Both gain-of-function and loss-of-function strategies are useful for this purpose. For the latter, stable expression of antisense cDNA, ribosomes, or dominant-negative mutants is available. By transfer of engineered cells producing secretory, recombinant proteins, it is possible to modify glomerular microenvironment in vivo. Transfer of genes encoding therapeutically relevant molecules could be useful for therapeutic intervention. Transfer of engineered leukocytes to the glomerulus also allows investigation of cross talk between leukocytes and resident cells. Transfer of stimulated leukocytes is useful for investigation of the pathologic actions of infiltrating cells on glomerular structure and function. Leukocytes in which certain gene functions are selectively reinforced or deleted would be useful for elucidation of the exact functions of leukocyte-associated genes in glomerular diseases. This article summarizes current experience with the adoptive transfer of engineered cells to the glomerulus for investigation of and therapy for glomerular diseases.
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Wang, Honglian, Jingyi Sheng, Huijun He, Xiaocui Chen, Jinhong Li, Ruizhi Tan, Li Wang, and Hui-Yao Lan. "A simple and highly purified method for isolation of glomeruli from the mouse kidney." American Journal of Physiology-Renal Physiology 317, no. 5 (November 1, 2019): F1217—F1223. http://dx.doi.org/10.1152/ajprenal.00293.2019.
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Highly purified mouse glomeruli are of great value for studying glomerulus-associated kidney diseases. Here, we developed a simple and rapid procedure for mouse glomerular isolation with large quantity and high purity based on the combination of size-selective sieving and differential adhesion techniques, which we termed the “differential adhesion method.” In this method, mouse renal cortices were minced and digested with collagenase. Glomeruli were disassociated from tubules by successive sieving through 105-, 75-, and 40-μm cell strainers. The retained glomeruli-rich preparation on the 40-μm strainer was rinsed into a cell culture dish to allow tubules to adhere quickly to the dish while leaving most glomeruli floating (termed “differential adhesion”). The floating glomerular fraction was then subjected to another wash through the 40-μm strainer followed by an additional differential adhesion step to obtain highly purified glomeruli with yields of 8,357 ± 575 and purity of 96.1 ± 1.8% from one adult C57BL/6 mouse. The purity of the isolated glomeruli was further confirmed by high expression of the podocyte marker nephrin without detectable tubular marker cadherin-16. Importantly, we also found that although both the quantity and purity of the isolated glomeruli by this and the established Dynabeads method were comparable, glomeruli isolated by the current method showed much less inflammatory stress in terms of proinflammatory cytokine expression than the Dynabeads method. In conclusion, we established a newly mouse glomerular isolation method that is simple, rapid, cost effective, and productive. It provides an advanced methodology for research into glomerulus-related kidney diseases in the mouse.
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Yoshida, Yutaka, Masahito Miyamoto, Izumi Taguchi, Bo Xu, Ying Zhang, Eishin Yaoita, Hidehiko Fujinaka, and Tadashi Yamamoto. "Human kidney glomerulus proteome and biomarker discovery of kidney diseases." PROTEOMICS – CLINICAL APPLICATIONS 2, no. 3 (March 2008): 420–27. http://dx.doi.org/10.1002/prca.200780016.
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Zhu, D., Y. Kim, M. W. Steffes, T. J. Groppoli, R. J. Butkowski, and S. M. Mauer. "Application of electron microscopic immunocytochemistry to the human kidney: distribution of type IV and type VI collagen in normal human kidney." Journal of Histochemistry & Cytochemistry 42, no. 5 (May 1994): 577–84. http://dx.doi.org/10.1177/42.5.8157929.
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We used immunogold electron microscopic (IEM) techniques with periodate-lysine-paraformaldehyde-fixed and Lowicryl-embedded or cryopreserved tissues to study the distribution of alpha 1(IV) and alpha 3(IV) chains of Types IV and VI collagen in glomerular basement membrane (GBM) and mesangial matrix of glomeruli in normal human kidneys. Monoclonal antibodies to alpha 1(IV) and alpha 3(IV) collagen chains and Type VI collagen could be detected only with cryoultramicrotomy, whereas polyclonal anti-Type IV collagen antibody was detectable in Lowicryl-embedded tissue. Ultrastructural detail was better preserved in the Lowicryl-embedded tissue. IEM labeling provided more detailed information as to the site-specific array of these extracellular matrix molecules in glomeruli than did immunofluorescent microscopy. The labeling of alpha 1(IV) collagen chain was distributed mainly along the endothelial side of glomerular basement membrane and the mesangial matrix. Mesangial GBM was relatively poorly labeled compared with that of mesangial matrix. In contrast, the alpha 3(IV) chain was detected throughout the thickness of the GBM, but there was no labeling of mesangial matrix. Type VI collagen distribution was identical to that of the alpha 1(IV) chain within the glomerulus but was also associated with interstitial collagen fibrils. This study documents and details the heterogeneous distribution of Type IV and VI collagen chains within the normal human glomerulus and provides the framework for the study of these matrix components in human glomerular diseases.
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PATRAKKA, JAAKKO, VESA RUOTSALAINEN, ILKKA KETOLA, CHRISTER HOLMBERG, MARKKU HEIKINHEIMO, KARL TRYGGVASON, and HANNU JALANKO. "Expression of Nephrin in Pediatric Kidney Diseases." Journal of the American Society of Nephrology 12, no. 2 (February 2001): 289–96. http://dx.doi.org/10.1681/asn.v122289.
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Abstract. Nephrin is a podocyte cell adhesion protein located at the slit diaphragm area of the kidney glomerulus. Mutations in the nephrin gene (NPHS1) lead to congenital nephrosis, suggesting that nephrin is essential for the glomerular filtration barrier. This prompted this study of the expression of nephrin in acquired pediatric kidney diseases usingin situhybridization and immunohistochemistry.In situhybridization for nephrin mRNA was performed in biopsy samples from patients with proteinuria caused by minimal change nephrosis, focal segmental glomerulosclerosis, and membranous nephropathy. The expression of nephrin mRNA was evaluated by grading the signal intensity visually and by counting the number of grains in separate glomeruli. No significant difference was observed in these samples as compared with controls. Immunostaining for nephrin was performed using antibodies directed against extra- and intracellular parts of the molecule. Nephrin staining gave a linear pattern along the glomerular capillary loops. In minimal change nephrosis, focal segmental glomerulosclerosis, and membranous nephropathy, the distribution of nephrin was similar to that in controls. In proliferative forms of glomerulonephritides (Henoch-Schönlein nephritis, IgA nephropathy, postinfectious and membranoproliferative glomerulonephritis), crescents and sclerotic lesions were negative for nephrin, and mesangial proliferation led to a scattered and sparse staining pattern. The staining pattern of nephrin was compared to that of ZO-1, a component of the cytoplasmic face of the slit diaphragm. The distributions of these two proteins in capillary tufts were similar in all disease entities studied. In conclusion, immunohistochemistry andin situhybridization did not reveal major alterations in the expression of nephrin in proteinuric kidney diseases in children. Further studies are needed for more precise evaluation of the role of nephrin in these diseases.
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SUZUKI, DAISUKE, TOSHIO MIYATA, MASAOMI NANGAKU, HIDEO TAKANO, NOBORU SAOTOME, MASAO TOYODA, YASUO MORI, et al. "Expression of Megsin mRNA, a Novel Mesangium-Predominant Gene, in the Renal Tissues of Various Glomerular Diseases." Journal of the American Society of Nephrology 10, no. 12 (December 1999): 2606–13. http://dx.doi.org/10.1681/asn.v10122606.
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Abstract. Mesangial cells play an important role in maintaining a structure and function of the glomerulus and in the pathogenesis of glomerular diseases. Recently, we discovered a new mesangium-predominant gene termed “megsin.” Megsin is a novel protein that belongs to the serine protease inhibitor (serpin) superfamily. To elucidate the pathophysiologic role of megsin in the kidney, the expression and localization of megsin mRNA in renal tissues of patients with IgA nephropathy (IgA-N), diabetic nephropathy (DN), minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN), and normal human kidney (NHK) was evaluated by in situ hybridization using digoxigenin-labeled oligonucleotide. Individual cells positive for megsin mRNA were observed only in glomeruli in all renal tissues. Their localization coincided with those of mesangial cells. The percentage of positive cells for megsin mRNA in total glomerular cells was significantly greater in IgA-N than in MCNS, MN, and NHK. It was also significantly greater in DN than in MCNS and NHK. In IgA-N, the percentage of megsin mRNA-positive cells was greater in tissues from those with mesangial cell proliferation and slightly mesangial matrix expansion (periodic acid-Schiff-positive area in the total glomerulus area, <30%; cell number in mesangial matrix area, >30; assessed in cross-sections through their vascular poles) than in tissues from those with severe mesangial matrix expansion (periodic acid-Schiff-positive area in total glomerulus area, >30%; cell number in mesangial matrix area, <30). In conclusion, megsin mRNA was predominantly expressed in glomerular mesangial cells in all renal tissues. The expression of megsin mRNA was upregulated in IgA-N and DN, both of which are diseases accompanied with mesangial cell proliferation and/or mesangial matrix expansion. These data suggest a link of megsin expression to the pathogenesis of IgA-N and DN, two major causes of end-stage renal failure.
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Rodriguez, Patricia Q., Asmundur Oddsson, Lwaki Ebarasi, Bing He, Kjell Hultenby, Annika Wernerson, Christer Betsholtz, Karl Tryggvason, and Jaakko Patrakka. "Knockdown of Tmem234 in zebrafish results in proteinuria." American Journal of Physiology-Renal Physiology 309, no. 11 (December 1, 2015): F955—F966. http://dx.doi.org/10.1152/ajprenal.00525.2014.
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Podocytes are highly specialized epithelial cells located at the outer aspects of the glomerular capillary tuft and critical components of the kidney filtration barrier. To maintain their unique features, podocytes express a number of proteins that are only sparsely found elsewhere in the body. In this study, we have identified four (Tmem234, Znf185, Lrrc49, and Slfn5) new highly podocyte-enriched proteins. The proteins are strongly expressed by podocytes, while other parts of the kidney show only weak or no expression. Tmem234, Slfn5, and Lrrc49 are located in foot processes, whereas Znf185 is found in both foot and major processes. Expressional studies in developing kidneys show that these proteins are first expressed at the capillary stage glomerulus, the same stage when the formation of major and foot processes begins. We identified zebrafish orthologs for Tmem234 and Znf185 genes and knocked down their expression using morpholino technology. Studies in zebrafish larvae indicate that Tmem234 is essential for the organization and functional integrity of the pronephric glomerulus filtration barrier, as inactivation of Tmem234 expression results in foot process effacement and proteinuria. In summary, we have identified four novel highly podocyte-enriched proteins and show that one of them, Tmem234, is essential for the normal filtration barrier in the zebrafish pronephric glomerulus. Identification of new molecular components of the kidney filtration barrier opens up possibilities to study their role in glomerulus biology and diseases.
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Beck, Karl-Friedrich, and Josef Pfeilschifter. "The Pathophysiology of H2S in Renal Glomerular Diseases." Biomolecules 12, no. 2 (January 26, 2022): 207. http://dx.doi.org/10.3390/biom12020207.
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Renal glomerular diseases such as glomerulosclerosis and diabetic nephropathy often result in the loss of glomerular function and consequently end-stage renal disease. The glomerulus consists of endothelial cells, mesangial cells and glomerular epithelial cells also referred to as podocytes. A fine-tuned crosstalk between glomerular cells warrants control of growth factor synthesis and of matrix production and degradation, preserving glomerular structure and function. Hydrogen sulfide (H2S) belongs together with nitric oxide (NO) and carbon monoxide (CO) to the group of gasotransmitters. During the last three decades, these higher concentration toxic gases have been found to be produced in mammalian cells in a well-coordinated manner. Recently, it became evident that H2S and the other gasotransmitters share common targets as signalling devices that trigger mainly protective pathways. In several animal models, H2S has been demonstrated as a protective factor in the context of kidney disorders, in particular of diabetic nephropathy. Here, we focus on the synthesis and action of H2S in glomerular cells, its beneficial effects in the glomerulus and its action in the context of the other gaseous signalling molecules NO and CO.
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Lee, Hsi-Chieh, and Ahmad Fauzan Aqil. "Combination of Transfer Learning Methods for Kidney Glomeruli Image Classification." Applied Sciences 12, no. 3 (January 20, 2022): 1040. http://dx.doi.org/10.3390/app12031040.
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The rising global incidence of chronic kidney disease necessitates the development of image categorization of renal glomeruli. COVID-19 has been shown to enter the glomerulus, a tissue structure in the kidney. This study observes the differences between focal-segmental, normal and sclerotic renal glomerular tissue diseases. The splitting and combining of allied and multivariate models was accomplished utilizing a combined technique using existing models. In this study, model combinations are created by using a high-accuracy accuracy-based model to improve other models. This research exhibits excellent accuracy and consistent classification results on the ResNet101V2 combination using a mix of transfer learning methods, with the combined model on ResNet101V2 showing an accuracy of up to 97 percent with an F1-score of 0.97, compared to other models. However, this study discovered that the anticipated time required was higher than the model employed in general, which was mitigated by the usage of high-performance computing in this study.
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Puelles, Victor G., Luise A. Cullen-McEwen, Georgina E. Taylor, Jinhua Li, Michael D. Hughson, Peter G. Kerr, Wendy E. Hoy, and John F. Bertram. "Human podocyte depletion in association with older age and hypertension." American Journal of Physiology-Renal Physiology 310, no. 7 (April 1, 2016): F656—F668. http://dx.doi.org/10.1152/ajprenal.00497.2015.
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Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease.
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Lay, Abigail C., A. Fern Barrington, Jenny A. Hurcombe, Raina D. Ramnath, Mark Graham, Philip A. Lewis, Marieangela C. Wilson, et al. "A role for NPY-NPY2R signaling in albuminuric kidney disease." Proceedings of the National Academy of Sciences 117, no. 27 (June 19, 2020): 15862–73. http://dx.doi.org/10.1073/pnas.2004651117.
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Albuminuria is an independent risk factor for the progression to end-stage kidney failure, cardiovascular morbidity, and premature death. As such, discovering signaling pathways that modulate albuminuria is desirable. Here, we studied the transcriptomes of podocytes, key cells in the prevention of albuminuria, under diabetic conditions. We found thatNeuropeptide Y (NPY)was significantly down-regulated in insulin-resistant vs. insulin-sensitive mouse podocytes and in human glomeruli of patients with early and late-stage diabetic nephropathy, as well as other nondiabetic glomerular diseases. This contrasts with the increased plasma and urinary levels of NPY that are observed in such conditions. Studying NPY-knockout mice, we found that NPY deficiency in vivo surprisingly reduced the level of albuminuria and podocyte injury in models of both diabetic and nondiabetic kidney disease. In vitro, podocyte NPY signaling occurred via the NPY2 receptor (NPY2R), stimulating PI3K, MAPK, and NFAT activation. Additional unbiased proteomic analysis revealed that glomerular NPY-NPY2R signaling predicted nephrotoxicity, modulated RNA processing, and inhibited cell migration. Furthermore, pharmacologically inhibiting the NPY2R in vivo significantly reduced albuminuria in adriamycin-treated glomerulosclerotic mice. Our findings suggest a pathogenic role of excessive NPY-NPY2R signaling in the glomerulus and that inhibiting NPY-NPY2R signaling in albuminuric kidney disease has therapeutic potential.
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Okabe, Masahiro, Yoichi Miyazaki, Fumio Niimura, Ira Pastan, Akira Nishiyama, Takashi Yokoo, Iekuni Ichikawa, and Taiji Matsusaka. "Unilateral ureteral obstruction attenuates intrarenal angiotensin II generation induced by podocyte injury." American Journal of Physiology-Renal Physiology 308, no. 8 (April 15, 2015): F932—F937. http://dx.doi.org/10.1152/ajprenal.00444.2014.
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The renal tissue renin-angiotensin system is activated in chronic kidney diseases. We previously demonstrated that intrarenal ANG II is synthesized primarily from liver-derived angiotensinogen filtered through the glomerulus and that podocyte injury increases the passage of angiotensinogen into the tubular lumen and generation of ANG II. In the present study, we tested the effect of cessation of glomerular filtration by ureteral obstruction on renal ANG II generation in kidneys with podocyte injury under two experimental conditions. Ureteral obstruction is known to activate the renin-angiotensin system in nonproteinuric kidneys. Transgenic mice expressing hCD25 in podocyte (NEP25) were injected with 1.25 or 10 ng/g body wt of LMB2, a hCD25-targeted immunotoxin, subjected to unilateral ureteral ligation on the following day, and euthanized 7 and 4 days later, respectively. In both experiments, compared with the kidney in untreated wild-type mice, renal angiotensinogen protein, as assessed by immunostaining and Western blot analysis, was increased in the contralateral unobstructed kidney. However, it was markedly decreased in the obstructed kidney. Whereas intrarenal ANG II content was increased in the contralateral kidney compared with the untreated kidney (248 ± 83 vs. 106 ± 21 and 298 ± 185 vs. 64.8 ± 20 fmol/g kidney, respectively), this increase was suppressed in the obstructed kidney (161 ± 75 and 113 ± 34 fmol/g kidney, respectively), a pattern opposite to what we expected in obstructed kidneys without podocyte injury. Thus, our study indicates that the major source of increased renal ANG II in podocyte injury is filtered angiotensinogen.
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Scott, Rizaldy P., and Susan E. Quaggin. "The cell biology of renal filtration." Journal of Cell Biology 209, no. 2 (April 27, 2015): 199–210. http://dx.doi.org/10.1083/jcb.201410017.
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The function of the kidney, filtering blood and concentrating metabolic waste into urine, takes place in an intricate and functionally elegant structure called the renal glomerulus. Normal glomerular function retains circulating cells and valuable macromolecular components of plasma in blood, resulting in urine with just trace amounts of proteins. Endothelial cells of glomerular capillaries, the podocytes wrapped around them, and the fused extracellular matrix these cells form altogether comprise the glomerular filtration barrier, a dynamic and highly selective filter that sieves on the basis of molecular size and electrical charge. Current understanding of the structural organization and the cellular and molecular basis of renal filtration draws from studies of human glomerular diseases and animal models of glomerular dysfunction.
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Trimarchi, H., M. Paulero, T. Rengel, I. González-Hoyos, M. Forrester, F. Lombi, V. Pomeranz, R. Iriarte, and A. Iotti. "Mucin-1 Gene Mutation and the Kidney: The Link between Autosomal Dominant Tubulointerstitial Kidney Disease and Focal and Segmental Glomerulosclerosis." Case Reports in Nephrology 2018 (July 31, 2018): 1–5. http://dx.doi.org/10.1155/2018/9514917.
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Glomerular diseases are one of the most frequent causes of chronic kidney disease, focal and segmental glomerulosclerosis being one of the commonest glomerulopathies. However, the etiology of this glomerular entity, which merely depicts a morphologic pattern of disease, is often not established and, in most of the patients, remains unknown. Nephrologists tend to assume focal and segmental glomerulosclerosis as a definitive diagnosis. However, despite the increasing knowledge developed in the field, genetic causes of glomerular diseases are currently identified in fewer than 10% of chronic kidney disease subjects. Moreover, unexplained familial clustering among dialysis patients suggests that genetic causes may be underrecognized. Secondary focal and segmental glomerulosclerosis due to genetic mutations mainly located in the podocyte and slit diaphragm can occur from childbirth to adulthood with different clinical presentations, ranging from mild proteinuria and normal renal function to nephrotic syndrome and renal failure. However, this histopathological pattern can also be due to primary defects outside the glomerulus. The present report illustrates an adult case of secondary focal and segmental glomerulosclerosis with a dominant tubulointerstitial damage that led to the pursue of its cause at the tubular level. In this patient with an undiagnosed family history of adult kidney disease, a genetic study unraveled a mutation in the mucin-1 gene and a final diagnosis of adult dominant tubular kidney disease-MUC1 was made.
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Kramer, Holly. "Diet and Chronic Kidney Disease." Advances in Nutrition 10, Supplement_4 (November 1, 2019): S367—S379. http://dx.doi.org/10.1093/advances/nmz011.
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ABSTRACT Kidney disease affects almost 15% of the US population, and prevalence is anticipated to grow as the population ages and the obesity epidemic continues due to Western dietary practices. The densely caloric Western diet, characterized by high animal protein and low fruit and vegetable content, has fueled the growth of chronic diseases, including chronic kidney disease. The glomerulus or filtering unit of the kidney is very susceptible to barotrauma, and diets high in animal protein impede the glomerulus’ ability to protect itself from hemodynamic injury. High animal protein intake combined with low intake of fruits and vegetables also leads to a high net endogenous acid production requiring augmentation of ammonium excretion in order to prevent acidosis. This higher workload of the kidney to maintain a normal serum bicarbonate level may further exacerbate kidney disease progression. This article reviews the potential mechanisms whereby several key characteristics of the typical Western diet may impact kidney disease incidence and progression. Reducing animal protein intake and egg yolk and increasing intake of fruits and vegetables and fiber may prevent or delay end-stage renal disease, but few clinical trials have examined vegetarian diets for management of chronic kidney disease. More research is needed to determine optimal dietary patterns for the prevention of kidney disease and its progression.
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Shah, Hitesh H., Nupur N. Uppal, and Mark A. Perazella. "Cancer drugs and the glomerulus." Journal of Onco-Nephrology 2, no. 2-3 (June 2018): 78–91. http://dx.doi.org/10.1177/2399369318815418.
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Several chemotherapeutics including novel immunotherapies and targeted therapies have recently been approved for the treatment of various cancers. Several nephrotoxicities secondary to treatment with chemotherapeutics have been described in patients with cancer. Acute kidney injury from acute tubular necrosis and acute interstitial nephritis is commonly reported nephrotoxicities following treatment with cancer drugs. Although less common, several glomerular lesions include minimal change disease, collapsing and non-collapsing focal segmental glomerulosclerosis secondary to chemotherapy-related podocyte injury have been reported in the literature. In addition to conventional chemotherapeutics, several novel cancer drugs including immune point check inhibitors, anti-vascular endothelial growth factor inhibitors, and tyrosine kinase inhibitors have also been associated with various glomerular lesions. While the occurrence of glomerular toxicities related to cancer drugs is less common than tubular injury, failure to recognize these associations may lead to poor renal outcome. In this article, we review several chemotherapy-related glomerular diseases including thrombotic microangiopathy.
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Patel, Sanket, Kalyani Kulkarni, and Tahir Hussain. "Protecting glomerulus: role of angiotensin-II type 2 receptor." Clinical Science 136, no. 20 (October 2022): 1467–70. http://dx.doi.org/10.1042/cs20220396.
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Abstract Podocyte injury due to either drug, toxin, infection, or metabolic abnormality is a great concern as it increases the risk of developing focal segmental glomerulosclerosis (FSGS) and proteinuric kidney diseases. The direct podocyte injury due to doxorubicin is associated with an increase in proinflammatory cytokines and induction of cathepsin L. The increased activity of cathepsin L in turn may degrade the glomerular slit diaphragm resulting in proteinuric kidney injury. The angiotensin-II type 2 receptor (AT2R) has earlier been reported to be associated with the preservation of slit diaphragm proteins and prevention of proteinuria. Recent in vivo findings by Zhang and colleagues further support the anti-proteinuric role of AT2R in preventing podocyte injury via down-regulating cytokines ccl2, and hence, cathepsin L, thereby, limiting the progression of FSGS.
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Schreiner, G. F., and D. E. Kohan. "Regulation of renal transport processes and hemodynamics by macrophages and lymphocytes." American Journal of Physiology-Renal Physiology 258, no. 4 (April 1, 1990): F761—F767. http://dx.doi.org/10.1152/ajprenal.1990.258.4.f761.
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Inflammatory diseases of the renal glomerulus and interstitium are characterized by numerous alterations in renal glomerular hemodynamics and tubule transport processes. The cellular mechanisms underlying these changes have been theoretically attributed to nephron toxicity and destruction. However, recent studies suggest that many of the alterations in renal physiology may be mediated by specific immune cell-derived factors. Macrophages release a variety of cytokines on activation. One of these monokines, interleukin 1, induces a natriuresis by direct inhibition of collecting duct sodium reabsorption. Glomerular macrophages release highly vasoconstrictive compounds, including leukotriene D4 and thromboxane A2. Macrophages have now been demonstrated to migrate into the renal interstitium in diseases not previously considered to have an immunological component. Acute ureteral obstruction is characterized by a rapid infiltration of macrophages and lymphocytes into the kidney. Removal of the immune cell infiltrate in ureteral obstruction by irradiation markedly improves glomerular filtration rate and renal blood flow and partially corrects sodium and water excretion. Such immune modulation of renal function is likely to occur in a wide variety of diseases of the kidney, many of which do not involve a primary immunological insult. We propose that the abnormalities in renal hemodynamics and in the transport of fluid and electrolytes observed in states characterized by coexistence of immune cells among renal parenchymal cells may reflect a complex immune modulation of renal cell physiology.
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Liang, Chun-ling, Jun-biao Wu, Jie-mei Lai, Shu-fang Ye, Jin Lin, Hui Ouyang, Janis Ya-xian Zhan, and Jiu-yao Zhou. "Protection Effect of Zhen-Wu-Tang on Adriamycin-Induced Nephrotic Syndrome via Inhibiting Oxidative Lesions and Inflammation Damage." Evidence-Based Complementary and Alternative Medicine 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/131604.
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Zhen-wu-tang (ZWT), a well-known formula in China, is widely used to treat chronic kidney diseases. However, very little information on ZWT’s mechanism of action is currently available. In this study, we investigated the possible protective role and underlying mechanism of ZWT on nephrotic syndrome (NS) induced by Adriamycin (intravenous injection, 6.0 mg/kg) in rats using biochemical and histopathological approaches. ZWT decreased urine protein excretion and the serum levels of total cholesterol, triglycerides, blood urea nitrogen, and creatinine significantly in diseased rats. A decrease in plasma levels of total protein and albumin was also recorded in nephropathic rats. Pathological results show an improved pathological state and recovering glomerular structure in ZWT treatment groups. ZWT decreased renal IL-8 level but increased renal IL-4 level. In addition, rats subjected to ZWT exhibited less IgG deposition in glomerulus compared with model group. RT-PCR results showed that ZWT decreased the mRNA expression of NF-κB p65 and increased the mRNA expression of IκB. Furthermore, ZWT reduced the level of MDA and increased SOD activity. These results demonstrated that ZWT ameliorated Adriamycin-induced NS in rats possibly by inhibiting Adriamycin-induced inflammation damage, enhancing body’s antioxidant capacity, thereby protecting glomerulus from injury.
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Endres, Bradley T., Ruben M. Sandoval, George J. Rhodes, Silvia B. Campos-Bilderback, Malgorzata M. Kamocka, Christopher McDermott-Roe, Alexander Staruschenko, Bruce A. Molitoris, Aron M. Geurts, and Oleg Palygin. "Intravital imaging of the kidney in a rat model of salt-sensitive hypertension." American Journal of Physiology-Renal Physiology 313, no. 2 (August 1, 2017): F163—F173. http://dx.doi.org/10.1152/ajprenal.00466.2016.
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Hypertension is one of the most prevalent diseases worldwide and a major risk factor for renal failure and cardiovascular disease. The role of albuminuria, a common feature of hypertension and robust predictor of cardiorenal disorders, remains incompletely understood. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate the complex renal physiological changes that occur during salt-induced hypertension. Following a high-salt diet, SS rats exhibited elevated blood pressure, increased glomerular sieving of albumin (GSCalb = 0.0686), relative permeability to albumin (+Δ16%), and impaired volume hemodynamics (−Δ14%). Serum albumin but not serum globulins or creatinine concentration was decreased (−0.54 g/dl), which was concomitant with increased filtration of albumin (3.7 vs. 0.8 g/day normal diet). Pathologically, hypertensive animals had significant tubular damage, as indicated by increased prevalence of granular casts, expansion and necrosis of PT epithelial cells (+Δ2.20 score/image), progressive augmentation of red blood cell velocity (+Δ269 µm/s) and micro vessel diameter (+Δ4.3 µm), and increased vascular injury (+Δ0.61 leakage/image). Therefore, development of salt-induced hypertension can be triggered by fast and progressive pathogenic remodeling of PT epithelia, which can be associated with changes in albumin handling. Collectively, these results indicate that both the glomerulus and the PT contribute to albuminuria, and dual treatment of glomerular filtration and albumin reabsorption may represent an effective treatment of salt-sensitive hypertension.
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Wenderfer, Scott. "Endothelial Cells Bind Immune Complexes in the Kidney (172.39)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 172.39. http://dx.doi.org/10.4049/jimmunol.188.supp.172.39.
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Abstract Inflammatory kidney diseases often involve the deposition of antibodies (Ab) or antibody-antigen immune complexes (IC). The glomerulus is a highly evolved vascular system which filters blood to produce urine. Ab-mediated glomerular injury can lead to bleeding into the urine, protein wasting, hypertension, decreased urine output, edema, and kidney failure. However, the mechanisms by which IC deposit and the means by which they are cleared remain unclear. In order to model endothelium-Ab interactions, kidney endothelial cells (KEnCs) were isolated from C57BL/6 mice and cultured in vitro. Immuno-phenotyping was performed to assess expression of CD31, VEGF receptors, von Willebrand factor (vWF), and alpha smooth muscle actin. CD31+ vWF+ VEGF-R2+ KEnCs displayed a phenotype in culture similar to other microvascular cells. Monomeric and heat aggregated Ig (HA-IgG) and peroxidase-antiperoxidase IC (PAP-IC) were used for binding and stimulation assays. Effects of stimulation of KEnCs were identified using PCR arrays and multiplex cytokine analysis. KEnCs stained brightly with HA-IgG and PAP-IC, but only dimly with monomeric IgG. KEnCs responded to IC with robust chemokine and cytokine responses in a dose dependent manner. Competitive binding studies mapped the interaction to the Fc-portion of IgG, but suggest that the KEnCs bind independently of classical Fc-receptors. Results support an important role for KEnCs in the pathogenesis of IC kidney diseases.
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Bautista-García, Pablo, José L. Reyes, Dolores Martín, María C. Namorado, Bibiana Chavez-Munguía, Elizabeth Soria-Castro, Otmar Huber, and Lorenza González-Mariscal. "Zona occludens-2 protects against podocyte dysfunction induced by ADR in mice." American Journal of Physiology-Renal Physiology 304, no. 1 (January 1, 2013): F77—F87. http://dx.doi.org/10.1152/ajprenal.00089.2012.
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Zona occludens-2 (ZO-2) is a protein present at the tight junction and nucleus of epithelial cells. ZO-2 represses the transcription of genes regulated by the Wnt/β-catenin pathway. This pathway plays a critical role in podocyte injury and proteinuria. Here, we analyze whether the overexpression of ZO-2 in the glomerulus, by hydrodynamics transfection, prevents podocyte injury mediated by the Wnt/β-catenin pathway in the mouse model of adriamycin (ADR) nephrosis. By immunofluorescence and immunogold electron microscopy, we show that ZO-2 is present in mice glomerulus, not at the slit diaphragms where nephrin concentrates, but in the cytoplasm and at processes of podocytes. Our results indicate that in the glomeruli of mice treated with ADR, ZO-2 overexpression increases the amount of phosphorylated β-catenin, inhibits the expression of the transcription factor snail, prevents nephrin and podocalyxin loss, reduces podocyte effacement and massive fusions, restrains proteinuria, and supports urea and creatinine clearance. These results suggest that ZO-2 could be a new target for the regulation of hyperactive Wnt/β-catenin signaling in proteinuric kidney diseases.
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Pérez, Aurora, Isidro Torregrosa, Luis D’Marco, Isabel Juan, Liria Terradez, Miguel Ángel Solís, Francesc Moncho, Carmen Carda-Batalla, María J. Forner, and Jose Luis Gorriz. "IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection." Viruses 13, no. 4 (March 31, 2021): 587. http://dx.doi.org/10.3390/v13040587.
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The renal involvement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported. The etiology of kidney injury appears to be tubular, mainly due to the expression of angiotensin-converting enzyme 2, the key joint receptor for SARS-CoV-2; however, cases with glomerular implication have also been documented. The multifactorial origin of this renal involvement could include virus-mediated injury, cytokine storm, angiotensin II pathway activation, complement dysregulation, hyper-coagulation, and microangiopathy. We present the renal histological findings from a patient who developed acute kidney injury and de novo nephrotic syndrome, highly suggestive of acute IgA-dominant infection-associated glomerulonephritis (IgA-DIAGN) after SARS-CoV-2 infection, as evidenced by the presence of this virus detected in the renal tissue of the patient via immunohistochemistry assay. In summary, we document the first case of IgA-DIAGN associated to SARS-CoV-2. Thus, SARS-CoV-2 S may act as a super antigen driving the development of multisystem inflammatory syndrome as well as cytokine storm in patients affected by COVID-19, reaching the glomerulus and leading to the development of this novel IgA-DIAGN.
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Garg, Puneet. "A Review of Podocyte Biology." American Journal of Nephrology 47, Suppl. 1 (2018): 3–13. http://dx.doi.org/10.1159/000481633.
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Background: Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature of multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked to mechanistic dysfunctions in the renal glomerulus involving the function of podocyte epithelial cells, including podocyte foot process effacement. Summary: Developments in imaging technology are improving knowledge of the detailed structure of the human renal glomerulus and cortex. Podocyte foot processes attach themselves to the glomerular capillaries at the glomerular basement membrane (GBM) forming intercellular junctions that form slit diaphragm filtration barriers that help maintain normal renal function. Damage in this area has been implicated in glomerular disease. Injured podocytes undergo effacement whereby they lose their structure and spread out, leading to a reduction in filtration barrier function. Effacement is typically associated with the presence of proteinuria in focal segmental glomerulosclerosis, minimal change disease, and diabetes. It is thought to be due to a breakdown in the actin cytoskeleton of the foot processes, complex contractile apparatuses that allow podocytes to dynamically reorganize according to changes in filtration requirements. The process of podocyte depletion correlates with the development of glomerular sclerosis and chronic kidney disease. Focal adhesion complexes that interact with the underlying GBM bind the podocytes within the glomerular structure and prevent their detachment. Key Messages: Knowledge of glomerular podocyte biology is helping to advance our understanding of the science and mechanics of the glomerular filtering process, opening the way to a variety of new potential applications for clinical targeting.
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Reiser, Jochen, and Mehmet M. Altintas. "Podocytes." F1000Research 5 (January 28, 2016): 114. http://dx.doi.org/10.12688/f1000research.7255.1.
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Podocytes are highly specialized cells of the kidney glomerulus that wrap around capillaries and that neighbor cells of the Bowman’s capsule. When it comes to glomerular filtration, podocytes play an active role in preventing plasma proteins from entering the urinary ultrafiltrate by providing a barrier comprising filtration slits between foot processes, which in aggregate represent a dynamic network of cellular extensions. Foot processes interdigitate with foot processes from adjacent podocytes and form a network of narrow and rather uniform gaps. The fenestrated endothelial cells retain blood cells but permit passage of small solutes and an overlying basement membrane less permeable to macromolecules, in particular to albumin. The cytoskeletal dynamics and structural plasticity of podocytes as well as the signaling between each of these distinct layers are essential for an efficient glomerular filtration and thus for proper renal function. The genetic or acquired impairment of podocytes may lead to foot process effacement (podocyte fusion or retraction), a morphological hallmark of proteinuric renal diseases. Here, we briefly discuss aspects of a contemporary view of podocytes in glomerular filtration, the patterns of structural changes in podocytes associated with common glomerular diseases, and the current state of basic and clinical research.
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Fine, L. G., and J. T. Norman. "Renal growth responses to acute and chronic injury: routes to therapeutic intervention." Journal of the American Society of Nephrology 2, no. 10 (April 1992): S206. http://dx.doi.org/10.1681/asn.v210s206.
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Knowledge of the control of cell growth and extracellular matrix deposition has assumed center stage in the understanding of how the diseased kidney responds to injury. After acute tubular injury, there may be reversible, partial depolarization of renal cells or cell necrosis. The latter requires a regenerative response, which could be under the control of growth factors such as epidermal growth factor (EGF). Up-regulation of EGF receptors on viable cells provides the cell with an enhanced growth response despite a reduction in EGF production by the kidney. Acute glomerular injury involves a highly complex network of cytokines and growth inhibitors, the most important of which appear to be platelet-derived growth factor as a mitogen and transforming growth factor beta as an activator of extracellular matrix deposition. The long-term growth responses of the kidney to injury, reflected by chronic renal diseases, include tubular hypertrophy in those nephrons which are less affected by the primary disease. Tubular cell enlargement appears to proceed along a pathway that is different from the growth in cell size which precedes cell division, at least as indicated by a fundamentally different pattern of early gene expression. This pattern is not suggestive of a classical growth factor-initiated process. Other chronic changes that seem to correlate well with the progression of human disease are tubular atrophy and interstitial fibrosis. Growth factors produced by tubular cells may cause proliferation and matrix deposition by adjacent interstitial fibroblasts. A scheme is proposed in which low-grade ischemic injury to tubular cells, secondary to microvascular injury, leads to tubular atrophy, the release of growth factors, interstitial fibrosis, and the obliteration of peritubular capillaries. This would aggravate primary glomerular injury by compromising the vascular outflow from the glomerulus and would account for the long-recognized association between tubulo-interstitial injury and the progression of a variety of renal diseases. The use of growth factors to stimulate specific growth responses, antibodies, or inhibitory molecules to inhibit scarring generated by cytokines and the potential for genetic manipulation of the kidney provide future avenues for manipulating the growth response of the diseased kidney.
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Sato, Alex Yuri Simões, Eliane Antonioli, Rodrigo Tambellini, and Alexandre Holthausen Campos. "ID1 inhibits USF2 and blocks TGF-β-induced apoptosis in mesangial cells." American Journal of Physiology-Renal Physiology 301, no. 6 (December 2011): F1260—F1269. http://dx.doi.org/10.1152/ajprenal.00128.2011.
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Mesangial cells (MC) play an essential role in normal function of the glomerulus. Phenotypic changes in MC lead to the development of glomerular diseases such as diabetic nephropathy and glomerulosclerosis. The late phase of diabetic glomerulopathy is characterized by MC death and fibrosis. Current data highlight the transforming growth factor (TGF)-β as a trigger of the pathological changes observed in MC, including death by apoptosis. However, the mechanisms and mediators involved in this process are still poorly understood. Identification of novel elements involved in MC death may provide a better understanding of the pathophysiology of glomerular diseases. Here, we show that bone morphogenetic proteins (BMPs; known antagonists of the profibrotic effects of TGF-β in the kidney) strongly induce inhibitor of DNA binding (ID1) mRNA transcription and protein expression in human MC. ID genes have been implicated in cell survival control and are constitutively expressed in MC. We show that BMPs and ID1 exert an anti-apoptotic effect in MC by inhibition of USF2 transcriptional activity. On the other hand, TGF-β upregulates USF2, increasing BAX (proapoptotic gene) levels and apoptosis rates. Taken together, our results point to a novel molecular pathway that modulates MC apoptosis, which is potentially involved in the pathogenesis of glomerular diseases.
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Schindler, Maximilian, Antje Blumenthal, Marcus Johannes Moeller, Karlhans Endlich, and Nicole Endlich. "Adriamycin does not damage podocytes of zebrafish larvae." PLOS ONE 15, no. 11 (November 13, 2020): e0242436. http://dx.doi.org/10.1371/journal.pone.0242436.
Full textAbstract:
Podocytes are highly specialized epithelial cells that are essential for an intact glomerular filtration barrier in the kidney. Several glomerular diseases like focal segmental glomerulosclerosis (FSGS) are initially due to podocyte injury and loss. Since causative treatments for FSGS are not available until today, drug screening is of great relevance. In order to test a high number of drugs, FSGS needs to be reliably induced in a suitable animal model. The zebrafish larva is an ideal model for kidney research due to the vast amount of offsprings, the rapid development of a simple kidney and a remarkable homology to the mammalian glomerulus. Zebrafish larvae possess a size-selective glomerular filtration barrier at 4 days post fertilization including podocytes with interdigitating foot processes that are connected by a slit membrane. Adriamycin is an anthracycline which is often used in mice and rats to induce a FSGS-like phenotype. In this study, we aimed to induce a similar phenotype to zebrafish larvae by adding adriamycin to the tank water in different concentrations. Surprisingly, zebrafish larvae did not develop glomerular injury and displayed an intact filtration barrier after treatment with adriamycin. This was shown by (immuno-) histology, our filtration assay, in vivo imaging by 2-photon microcopy, RT-(q)PCR as well as transmission electron microscopy. To summarize, adriamycin is unable to induce a podocyte-related damage in zebrafish larvae and therefore major effort must be made to establish FSGS in zebrafish larvae to identify effective drugs by screenings.
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Leung, Nelson, Maria E. Drosou, and Samih H. Nasr. "Dysproteinemias and Glomerular Disease." Clinical Journal of the American Society of Nephrology 13, no. 1 (November 7, 2017): 128–39. http://dx.doi.org/10.2215/cjn.00560117.
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Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein–related kidney diseases.
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Seccia, Teresa, Brasilina Caroccia, Maria Piazza, and Gian Paolo Rossi. "The Key Role of Epithelial to Mesenchymal Transition (EMT) in Hypertensive Kidney Disease." International Journal of Molecular Sciences 20, no. 14 (July 21, 2019): 3567. http://dx.doi.org/10.3390/ijms20143567.
Full textAbstract:
Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT), originally described as a key process for organ development and metastasis budding in cancer, plays a key role in the development of renal fibrosis in several diseases, including hypertensive nephroangiosclerosis. We herein reviewed the concept of EMT and its role in renal diseases, with particular focus on hypertensive kidney disease, the second leading cause of end-stage renal disease after diabetes mellitus. After discussing the pathophysiology of hypertensive nephropathy, the ‘classic’ view of hypertensive nephrosclerosis entailing hyalinization, and sclerosis of interlobular and afferent arterioles, we examined the changes occurring in the glomerulus and tubulo-interstitium and the studies that investigated the role of EMT and its molecular mechanisms in hypertensive kidney disease. Finally, we examined the reasons why some studies failed to provide solid evidence for renal EMT in hypertension.
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Roselli, Séverine, Laurence Heidet, Mireille Sich, Anna Henger, Matthias Kretzler, Marie-Claire Gubler, and Corinne Antignac. "Early Glomerular Filtration Defect and Severe Renal Disease in Podocin-Deficient Mice." Molecular and Cellular Biology 24, no. 2 (January 15, 2004): 550–60. http://dx.doi.org/10.1128/mcb.24.2.550-560.2004.
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ABSTRACT Podocytes are specialized epithelial cells covering the basement membrane of the glomerulus in the kidney. The molecular mechanisms underlying the role of podocytes in glomerular filtration are still largely unknown. We generated podocin-deficient (Nphs2 −/−) mice to investigate the function of podocin, a protein expressed at the insertion of the slit diaphragm in podocytes and defective in a subset of patients with steroid-resistant nephrotic syndrome and focal and segmental glomerulosclerosis. Nphs2 −/− mice developed proteinuria during the antenatal period and died a few days after birth from renal failure caused by massive mesangial sclerosis. Electron microscopy revealed the extensive fusion of podocyte foot processes and the lack of a slit diaphragm in the remaining foot process junctions. Using real-time PCR and immunolabeling, we showed that the expression of other slit diaphragm components was modified in Nphs2 −/− kidneys: the expression of the nephrin gene was downregulated, whereas that of the ZO1 and CD2AP genes appeared to be upregulated. Interestingly, the progression of the renal disease, as well as the presence or absence of renal vascular lesions, depends on the genetic background. Our data demonstrate the crucial role of podocin in the establishment of the glomerular filtration barrier and provide a suitable model for mapping and identifying modifier genes involved in glomerular diseases caused by podocyte injuries.
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Conti, F. G., L. J. Striker, S. J. Elliot, D. Andreani, and G. E. Striker. "Synthesis and release of insulinlike growth factor I by mesangial cells in culture." American Journal of Physiology-Renal Physiology 255, no. 6 (December 1, 1988): F1214—F1219. http://dx.doi.org/10.1152/ajprenal.1988.255.6.f1214.
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Mesangial cell proliferation is a common hallmark of many glomerular diseases. The exact mechanisms inducing cell proliferation in glomerulosclerosis are not completely understood, and it remains to be determined whether growth factors play a role in this process. Insulinlike growth factor I (IGF I) has been shown to be synthesized in the kidney, and glomerular mesangial cells have receptors for and exhibit mitogenic response to IGF I. We found that mouse glomerular mesangial cells in culture synthesized and released into the culture medium a molecule with immunological and biological features of IGF I. This molecule specifically bound to mesangial cell IGF I receptors; high-pressure liquid chromatographic analysis provided further evidence of its similarity to human recombinant IGF I. Mesangial cells released into the culture medium 6 ng/10(6) cells of IGF I-like material per 24 h in a time-dependent and actinomycin-D inhibitable fashion. These data suggest that IGF I might be locally released by mesangial cells in the glomerulus and act in an autocrine and paracrine fashion.
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Petrosyan, E. K., V. A. Gavrilova, B. L. Kushnir, and P. E. Povilaitite. "ANСA-associated vasculitis and IGG4-associated disease - the same or different diseases?" Nephrology (Saint-Petersburg) 25, no. 2 (February 13, 2021): 73–78. http://dx.doi.org/10.36485/1561-6274-2021-25-2-73-78.
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IgG4-related disease (IgG4-AD), is a fibro-inflammatory condition characterized by an increase of serum IgG4 and infiltration of the tissue of affected organs by IgG4-positive plasma cells. There is a significant cross between IgG4-AB and antineutrophilic cytoplasmic antibodies (ANCA) – associated vasculitis (AAV) because of clinical and morphological features of both pathologies. A positive ANCA test is considered highly specific for AAV and excludes other forms of systemic diseases. However, a number of recent publications have demonstrated a combination of IgG4-AD with positive serum ANCA in patients, which suggests a revision of the role of ANCA as a diagnostic criterion for AAV. In this work, we describe a clinical case of a combination of clinical and morphological markers of IgG4-AD and positive serum ANCA in an 8-year-old girl. She had a combination of lung and kidney injury. Kidney disease was manifested as pyelonephritis and incomplete nephrotic syndrome. Histologically, it was identified a combination of tubulointerstitial nephritis and membranous nephropathy, with severe IgG4 infiltration in the glomerulus. The search for serological markers of systemic diseases revealed a positive test for myeloperoxidase ANCA, which suggested the existence of AAV in the patient. However, the presence of membranous nephropathy, which is an uncharacteristic morphological pattern of AAV, and massive deposition of IgG4 in the kidney tissue suggests a different pathogenetic mechanism in this patient.
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Pandey, Kaushlendra Kumar, Wilma Delphine Silvia CR, Aparna Pandey, and Asha Agarwal. "Evaluation of renal biopsies in various kidney diseases with reference to staining." IP Archives of Cytology and Histopathology Research 6, no. 4 (December 15, 2021): 269–74. http://dx.doi.org/10.18231/j.achr.2021.058.
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Renal diseases of different origin and nature may produce essentially similar disturbances of renal functions and may have clinical similarities and hence there was a need to classify renal diseases more scientifically. The basic approach was to correlate clinical signs and symptoms with histological changes in the tissue, using both simple and special staining techniques so as to reach to a definitive diagnosis.The present study was conducted on renal biopsy referred to pathology department. Criteria for successful biopsy were as follows-Adequate biopsy sample size, correct processing of specimen, informed interpretation and issue of an accurate report. A total of 29 renal biopsies were examined. In minimal change disease, only in 4 patients the glomerulus was sclerosed. Membranous glomerulonephritis comprised of the maximum number of cases (9/30). Total of 3 cases of renal biopsies revealed amyloidosis. Focal amyloid deposits with deposits either near the hilum or perivascular areas were found in 33.3% of cases, while extensive amyloid deposits were found in 33.3% of the cases.It is necessary to determine both the type of renal disease and the cause of the primary disorder in order to make the diagnosis and various staining techniques play a very helpful role. The likelihood that the biopsy specimen accurately reflects the type and severity of the underlying disease is directly related to both the diffuseness of the disease process and the amount of tissue examined.
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Adnani, Nitish Basant, and Sudung O. Pardede. "Laju Filtrasi Glomerulus pada Anak: Metode Apa yang Digunakan?" Majalah Kedokteran UKI 36, no. 1 (May 27, 2021): 33–41. http://dx.doi.org/10.33541/mk.v36i1.2990.
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Abstrak
Laju filtrasi glomerulus (LFG) adalah kecepatan filtrasi volume plasma melalui ginjal per unit waktu per luas permukaan tubuh (LPB) dan merupakan salah satu indikator utama untuk pemantauan fungsi ginjal. Standar baku emas untuk menentukan LFG saat ini adalah dengan menghitung klirens inulin ginjal. Akan tetapi, karena prosedur tersebut dinilai kompleks, maka klirens inulin tidak digunakan dalam praktik klinik. Estimasi LFG menggunakan penanda eksogen lainnya seperti kreatinin serum dan sistatin C merupakan pilihan praktis yang dapat menggantikan perhitungan klirens inulin ginjal. Penentuan LFG pada anak berbeda dengan pada dewasa karena tidak mudah mengumpulkan urin per hari pada anak, sehingga diperlukan formula untuk mempermudah menentukan LFG. Berbagai peneliti telah melakukan penelitian untuk menemukan rumus untuk menentukan LFG dengan mudah dan praktis. Pemeriksaan LFG biasanya dilakukan berbasis klirens kreatinin dan belakangan ini dilakukan degan pemeriksaan sistatin C. Beberapa penanda yang digunakan untuk pengukuran LFG antara lain zat radiofarmaka seperti chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), technetium 99-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA), iodine 125-labeled iothalamate (125I-iothalamate), dan zat kontras radiografik. Dari berbagai rumus estimasi LFG, salah satu yang kini direkomendasikan untuk digunakan pada praktik klinis sehari-hari adalah rumus Schwartz yang dimodifikasi, karena dinilai sederhana, relatif akurat, tidak invasif, dan tidak membutuhkan biaya yang mahal.
Kata kunci: laju filtrasi glomerulus, penyakit ginjal pada anak, kreatinin, sistatin C
Abstract
Glomerular filtration rate (GFR), which represents the plasma volume filtered through the kidney for each time unit and body surface area (BSA) unit, is one of the main indicators for renal function. The current gold standard for determining GFR is by calculating the renal inulin clearance. However, because this involves a complex procedure, inulin clrearance was not used in clinical practice. GFR estimation using other exogenous markers such as serum creatinine and cystatin C can be considered as practical alternatives. Determining GFR in children is difference with in adult because difficulty of 24 hours urine collection in children, so iti is needed a simple formula for determining GFR. Some researchers performed studies for determining easy and practical formula. GFR examinations usually based on creatinine clearance and nowadays by cyatatin C examination. Some markers are used in measuring of GFR such as chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), technetium 99-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA), iodine 125-labeled iothalamate (125I-iothalamate), and radiographic contrast. Among the various existing formulas to estimate GFR, one of the most commonly recommended in daily clinical practice is the modified Schwartz formula, as it is thought to be simple, relatively accurate, non-invasive, and inexpensive.
Keywords: glomerular filtration rate, pediatric kidney diseases, creatinine, cystatin C
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Kim, Jin-Ju, Sydney S. Wilbon, and Alessia Fornoni. "Podocyte Lipotoxicity in CKD." Kidney360 2, no. 4 (February 26, 2021): 755–62. http://dx.doi.org/10.34067/kid.0006152020.
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CKD represents the ninth most common cause of death in the United States but, despite this large health burden, treatment options for affected patients remain limited. To remedy this, several relevant pathways have been identified that may lead to novel therapeutic options. Among them, altered renal lipid metabolism, first described in 1982, has been recognized as a common pathway in clinical and experimental CKD of both metabolic and nonmetabolic origin. This observation has led many researchers to investigate the cause of this renal parenchyma lipid accumulation and its downstream effect on renal structure and function. Among key cellular components of the kidney parenchyma, podocytes are terminally differentiated cells that cannot be easily replaced when lost. Clinical and experimental evidence supports a role of reduced podocyte number in the progression of CKD. Given the importance of the podocytes in the maintenance of the glomerular filtration barrier and the accumulation of TG and cholesterol-rich lipid droplets in the podocyte and glomerulus in kidney diseases that cause CKD, understanding the upstream cause and downstream consequences of lipid accumulation in podocytes may lead to novel therapeutic opportunities. In this review, we hope to consolidate our understanding of the causes and consequences of dysregulated renal lipid metabolism in CKD development and progression, with a major focus on podocytes.
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Deng, Aihua, Kirk Conrad, and Chris Baylis. "Relaxin-mediated renal vasodilation in the rat is associated with falls in glomerular blood pressure." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 314, no. 2 (February 1, 2018): R147—R152. http://dx.doi.org/10.1152/ajpregu.00148.2017.
Full textAbstract:
Relaxin (RLX) is a pleiotropic peptide hormone with marked renal vasodilatory actions that are physiologically important during pregnancy. RLX also has potent antifibrotic actions and is being tested therapeutically in various fibrotic diseases, including chronic kidney disease (CKD). Since renal vasodilation may expose the glomerulus to increased blood pressure [glomerular capillary pressure (PGC)], which exacerbates progression of CKD, we assessed the glomerular hemodynamic actions of acute (0.89 µg·100 g body wt−1·h−1 iv over 75 min) and chronic (1.5 µg·100 g body wt−1·h−1 sc) administration of RLX. Both acute and chronic RLX produced marked renal vasodilation and increased renal plasma flow (RPF) in euvolemic, anesthetized male rats. Glomerular filtration rate also increased with RLX, but the magnitude of the rise was much less than the increase in RPF due to concomitant decreases in filtration fraction. The fall in filtration fraction was the result of significant decreases in PGC, despite a slight increase in mean arterial blood pressure (MAP) with acute RLX and no net change in MAP with chronic RLX. This fall in PGC occurred because of the “in-series” arrangement of the afferent and efferent arteriolar resistance vessels, which can regulate PGC independently of MAP. With both acute and chronic RLX, efferent arteriolar resistance vessels relaxed to a greater extent than afferent arteriolar resistance vessels, thus producing falls in PGC. Based on this finding, RLX has a beneficial hemodynamic impact on the kidney, which, together with the antifibrotic actions of RLX, suggests a strong therapeutic potential for use in CKD.
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Sen, Utpal, and Suresh C. Tyagi. "Homocysteine and Hypertension in Diabetes: Does PPARγHave a Regulatory Role?" PPAR Research 2010 (2010): 1–12. http://dx.doi.org/10.1155/2010/806538.
Full textAbstract:
Dysfunction of macro- and microvessels is a major cause of morbidity and mortality in patients with cardio-renovascular diseases such as atherosclerosis, hypertension, and diabetes. Renal failure and impairment of renal function due to vasoconstriction of the glomerular arteriole in diabetic nephropathy leads to renal volume retention and increase in plasma homocysteine level. Homocysteine, which is a nonprotein amino acid, at elevated levels is an independent cardio-renovascular risk factor. Homocysteine induces oxidative injury of vascular endothelial cells, involved in matrix remodeling through modulation of the matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) axis, and increased formation and accumulation of extracellular matrix protein, such as collagen. In heart this leads to increased endothelial-myocyte uncoupling resulting in diastolic dysfunction and hypertension. In the kidney, increased matrix accumulation in the glomerulus causes glomerulosclerosis resulting in hypofiltration, increased renal volume retention, and hypertension. PPARγagonist reduces tissue homocysteine levels and is reported to ameliorate homocysteine-induced deleterious vascular effects in diabetes. This review, in light of current information, focuses on the beneficial effects of PPARγagonist in homocysteine-associated hypertension and vascular remodeling in diabetes.
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Chen, Xiwu, Tristin D. Abair, Maria R. Ibanez, Yan Su, Mark R. Frey, Rebecca S. Dise, D. Brent Polk, et al. "Integrin α1β1 Controls Reactive Oxygen Species Synthesis by Negatively Regulating Epidermal Growth Factor Receptor-Mediated Rac Activation." Molecular and Cellular Biology 27, no. 9 (March 5, 2007): 3313–26. http://dx.doi.org/10.1128/mcb.01476-06.
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ABSTRACT Integrins control many cell functions, including generation of reactive oxygen species (ROS) and regulation of collagen synthesis. Mesangial cells, found in the glomerulus of the kidney, are able to produce large amounts of ROS via the NADPH oxidase. We previously demonstrated that integrin α1-null mice develop worse fibrosis than wild-type mice following glomerular injury and this is due, in part, to excessive ROS production by α1-null mesangial cells. In the present studies, we describe the mechanism whereby integrin α1-null mesangial cells produce excessive ROS. Integrin α1-null mesangial cells have constitutively increased basal levels of activated Rac1, which result in its increased translocation to the cell membrane, excessive ROS production, and consequent collagen IV deposition. Basal Rac1 activation is a direct consequence of ligand-independent increased epidermal growth factor receptor (EGFR) phosphorylation in α1-null mesangial cells. Thus, our study demonstrates that integrin α1β1-EGFR cross talk is a key step in negatively regulating Rac1 activation, ROS production, and excessive collagen synthesis, which is a hallmark of diseases characterized by irreversible fibrosis.
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Lucero, Claudia M., Juan Prieto-Villalobos, Lucas Marambio-Ruiz, Javiera Balmazabal, Tanhia F. Alvear, Matías Vega, Paola Barra, Mauricio A. Retamal, Juan A. Orellana, and Gonzalo I. Gómez. "Hypertensive Nephropathy: Unveiling the Possible Involvement of Hemichannels and Pannexons." International Journal of Molecular Sciences 23, no. 24 (December 14, 2022): 15936. http://dx.doi.org/10.3390/ijms232415936.
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Hypertension is one of the most common risk factors for developing chronic cardiovascular diseases, including hypertensive nephropathy. Within the glomerulus, hypertension causes damage and activation of mesangial cells (MCs), eliciting the production of large amounts of vasoactive and proinflammatory agents. Accordingly, the activation of AT1 receptors by the vasoactive molecule angiotensin II (AngII) contributes to the pathogenesis of renal damage, which is mediated mostly by the dysfunction of intracellular Ca2+ ([Ca2+]i) signaling. Similarly, inflammation entails complex processes, where [Ca2+]i also play crucial roles. Deregulation of this second messenger increases cell damage and promotes fibrosis, reduces renal blood flow, and impairs the glomerular filtration barrier. In vertebrates, [Ca2+]i signaling depends, in part, on the activity of two families of large-pore channels: hemichannels and pannexons. Interestingly, the opening of these channels depends on [Ca2+]i signaling. In this review, we propose that the opening of channels formed by connexins and/or pannexins mediated by AngII induces the ATP release to the extracellular media, with the subsequent activation of purinergic receptors. This process could elicit Ca2+ overload and constitute a feed-forward mechanism, leading to kidney damage.
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Mertowski, Sebastian, Ewelina Grywalska, Jarosław Ludian, Agnieszka Grafka, Barbara Pęksa, Jacek Roliński, and Wojciech Załuska. "The significance of Toll-like receptors in selected nephropathies." Diagnostyka Laboratoryjna 55, no. 2 (April 5, 2019): 107–12. http://dx.doi.org/10.5604/01.3001.0013.7445.
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The diseases associated with kidney damage are an increasingly common problem in modern society and complications of chronic renal failure can result in death. Research conducted by many scientific centers, both Polish and foreign, concern the search for possible factors involved in the pathogenesis of glomerulonephritis. One of the possible causes of nephropathy may include the dysfunction of Toll-like receptors (TLRs), which constitute a “bridge” between innate and acquired response. TLRs are involved in receiving signals related to pathogen associated molecular patterns (PAMPs) as well as receiving information related to the danger associated molecular patterns (DAMP). The stimulation of these receptors activates a cascade of reactions in the course of which various mediators, including pro-inflammatory mediators, are produced. The resulting long-lasting inflammation that develops within the glomerulus may cause kidney damage. In both nephropathies caused by excessive production of antibodies in the IgA class, as well as nephropathy induced by diabetes or lupus, the expression of individual TLRs may indicate an inducer of an inflammatory reaction cascade that leads to kidney damage. This article focuses on literature reports that present current views on the role of TLRs in the pathogenesis of the most common nephropathies.
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Kasztan, Małgorzata, Agnieszka Piwkowska, Ewelina Kreft, Dorota Rogacka, Irena Audzeyenka, Mirosława Szczepanska-Konkel, and Maciej Jankowski. "Extracellular purines' action on glomerular albumin permeability in isolated rat glomeruli: insights into the pathogenesis of albuminuria." American Journal of Physiology-Renal Physiology 311, no. 1 (July 1, 2016): F103—F111. http://dx.doi.org/10.1152/ajprenal.00567.2015.
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Purinoceptors (adrengeric receptors and P2 receptors) are expressed on the cellular components of the glomerular filtration barrier, and their activation may affect glomerular permeability to albumin, which may ultimately lead to albuminuria, a well-established risk factor for the progression of chronic kidney disease and development of cardiovascular diseases. We investigated the mechanisms underlying the in vitro and in vivo purinergic actions on glomerular filter permeability to albumin by measuring convectional albumin permeability ( Palb) in a single isolated rat glomerulus based on the video microscopy method. Primary cultured rat podocytes were used for the analysis of Palb, cGMP accumulation, PKG-Iα dimerization, and immunofluorescence. In vitro, natural nucleotides (ATP, ADP, UTP, and UDP) and nonmetabolized ATP analogs (2-meSATP and ATP-γ-S) increased Palb in a time- and concentration-dependent manner. The effects were dependent on P2 receptor activation, nitric oxide synthase, and cytoplasmic guanylate cyclase. ATP analogs significantly increased Palb, cGMP accumulation, and subcortical actin reorganization in a PKG-dependent but nondimer-mediated route in cultured podocytes. In vivo, 2-meSATP and ATP-γ-S increased Palb but did not significantly affect urinary albumin excretion. Both agonists enhanced the clathrin-mediated endocytosis of albumin in podocytes. A product of adenine nucleotides hydrolysis, adenosine, increased the permeability of the glomerular barrier via adrenergic receptors in a dependent and independent manner. Our results suggest that the extracellular nucleotides that stimulate an increase of glomerular Palb involve nitric oxide synthase and cytoplasmic guanylate cyclase with actin reorganization in podocytes.
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Kombe, Afdriansyah L., Cerelia E. C. Sugeng, and Bisuk P. Sedli. "Korelasi Lama Menyandang Diabetes Melitus dan HbA1c dengan Estimasi Laju Filtrasi Glomerulus pada Pasien Diabetes Melitus Tipe 2." Medical Scope Journal 4, no. 1 (January 29, 2023): 89–92. http://dx.doi.org/10.35790/msj.v4i1.44732.
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Abstract: Diabetes mellitus (DM) is a group of metabolic diseases characterized by high blood sugar levels (hyperglycemia) that occur due to abnormalities in insulin secretion, insulin action, or both. Poor blood sugar control in the long term can cause various diseases, one of which is chronic kidney disease. This study aimed to determine the correlation between duration of DM and HbA1c (glycated hemoglobin) with estimated glomerular filtration rate (eGFR) in type 2 DM patients. This was an analytical study with a retrospective approach and a cross-sectional design. were taken by using consecutive sampling technique. Data of HbA1c and eGFR were obtained from the patient's medical record. Duration of suffering from diabetes mellitus was carried out by interviewing the patients. Data were analyzed using the Pearson and Spearman correlation statistical tests. The results obtained 38 type 2 DM patients as respondents. The correlation test between duration of DM and eGFR showed a significant negative correlation (r=-0.411; p=0.01), and the correlation test between HbA1c correlation test and eLFG showed a non-significant negative correlation (r=-0.109; p=0.516). In conclusion, there is a significant negative correlation between duration of DM and eGFR and a non-significant negative correlation between HbA1c and eGFR. Keywords: duration of diabetes mellitus; glycated hemoglobin; estimated glomerular filtration rate Abstrak: Diabetes melitus merupakan kelompok penyakit metabolik yang memiliki karakteristik kadar gula tinggi (hiperglikemia) yang terjadi karena kelainan sekresi insluin, kerja insulin atau keduanya. Kontrol gula darah yang buruk secara jangka panjang dapat menimbulkan berbagai penyakit salah satunya penyakit ginjal kronik. Penelitian ini bertujuan untuk untuk mengetahui korelasi lama menyandang DM dan HbA1c (glycated hemoglobin) dengan eLFG (estimasi laju filtrasi glomerulus) pada pasien DM tipe 2. Jenis penelitian ialah analitik dengan pendekatan retrospektif serta menggunakan desain potong lintang. Responden penelitian diambil dengan teknik consecutive sampling. Data HbA1c dan eLFG diperoleh melalui rekam medik pasien. Pengambilan data lama menyandang DM dilakukan dengan wawancara pada pasien. Pada penelitian ini digunakan uji statistik korelasi Pearson dan Spearman. Hasil penelitian mendapatkan sebanyak 38 responden. Hasil uji korelasi antara lama menyandang DM dengan eLFG menunjukkan korelasi negatif bermakna (r=-0,411; p=0,01), dan hasil uji korelasi HbA1c dengan eLFG menunjukkan korelasi negatif tidak bermakna (r=-0,109; p=0,516). Simpulan penelitian ini ialah terdapat korelasi negatif yang bermakna antara lama menyandang diabetes melitus dengan eLFG dan korelasi negatif tidak bermakna antara HbA1c dengan eLFG. Kata kunci: lama menyandang diabetes melitus; glycated hemoglobin; estimasi laju filtrasi glomerulus
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Cho, H., and E. B. Jeung. "204 A COMPARATIVE ANALYSIS OF CALCIUM TRANSPORT GENES EXPRESSION IN HOLSTEIN AND HANWOO (KOREAN CATTLE) IN THE DUODENUM AND KIDNEY." Reproduction, Fertility and Development 27, no. 1 (2015): 193. http://dx.doi.org/10.1071/rdv27n1ab204.
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Transmembranous calcium (Ca2+) channels such as Trpv5/6,Ncx1,Pmca1b are known to play an important role in maintaining homeostasis and metabolizing Ca2+ ions. Transient receptor potential cation channel subfamily V members 5 and 6 (Trpv5/6) play an important role in Ca2+ absorption. Na+/Ca2+ exchanger 1 (Ncx1) and plasma membrane Ca2+-transporting ATPase1 (Pmca1b) play a role in Ca2+ excretion. Holstein cattle are known to provide higher milk production than other cattle breeds. In this respect, a higher susceptibility to hypocalcaemia that is a risk factor for many of calcium-related diseases such as milk fever has been observed. In contrary, Hanwoo cattle are relatively resistant to the calcium-related diseases. The aim of this study was to evaluate the expression of calcium transport genes in the duodenum and kidney of Hanwoo (Korean cattle) and Holstein cattle. All samples were obtained from Holstein and Hanwoo cattle from 36 to 60 months of age at a local slaughterhouse. The collected duodenum and kidney were rapidly excised and washed in cold sterile saline (0.9% NaCl). Total RNA was prepared from duodenum and kidney tissues using TRIzol Reagent (Invitrogen, Carlsbad, CA, USA), according to the manufacturer's protocol. Protein was extracted using Pro-prep (iNtRON Bio), according to the manufacturer's protocol. Expression of Trpv5/6, Ncx1 and Pmca1b was analysed by real-time RT–PCR, Western blot analysis, and immunohistochemistry. In dairy cattle's kidney (Holstein), the level of Trpv5 mRNA was ~3-fold more than Hanwoo's kidney while Pmca1b mRNA was one-fifth less than Hanwoo's kidney. However, no difference in Trpv6 and Ncx1 mRNA expression was observed in the kidney of Holstein compared with Hanwoo. Duodenal Trpv5 and Trpv6 mRNA were scarcely expressed in both Hanwoo and Holstein cattle. In addition, the mRNA expression of Pmca1b and Ncx1 were also not different between Hanwoo and Holstein. The protein expression of calcium transport genes were similar to the mRNA levels of calcium transport genes in both Hanwoo and Holstein. Localization of calcium transporter genes were identified, the glomerulus, and proximal and distal convoluted tubules expressed TRPV5, 6, Pmca1b, and Ncx1 in the kidney. These four calcium transport genes may play an important role in the bovine duodenum and kidney. The difference between Holstein and Hanwoo animals which express different gene expression patterns may be helpful in studying diseases associated with calcium metabolism, e.g. milk fever.
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Radajewska, Anna, Jakub Szyller, Joanna Niewiadomska, Agnieszka Noszczyk-Nowak, and Iwona Bil-Lula. "Punica granatum L. Polyphenolic Extract as an Antioxidant to Prevent Kidney Injury in Metabolic Syndrome Rats." Oxidative Medicine and Cellular Longevity 2023 (January 5, 2023): 1–14. http://dx.doi.org/10.1155/2023/6144967.
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Introduction. Obesity and metabolic syndrome (MetS) constitute a rapidly increasing health problem and contribute to the development of multiple comorbidities like acute and chronic kidney disease. Insulin resistance, inappropriate lipolysis, and excess of free fatty acids (FFAs) are associated with glomerulus hyperfiltration and atherosclerosis. The important component of MetS, oxidative stress, is also involved in the destabilization of kidney function and the progression of kidney injury. Natural polyphenols have the ability to reduce the harmful effect of reactive oxygen and nitrogen species (ROS/RNS). Extract derived from Punica granatum L. is rich in punicalagin that demonstrates positive effects in MetS and its associated diseases. The aim of the study was to investigate the effect of bioactive substances of pomegranate peel to kidney damage associated with the MetS. Methods. In this study, we compared biomarkers of oxidative stress in kidney tissue of adult male Zucker Diabetic Fatty (ZDF) rats with MetS and healthy controls that were treated with Punica granatum L. extract at a dose of 100 or 200 mg/kg. Additionally, we evaluated the effect of polyphenolic extract on kidney injury markers and remodeling. The concentration of ROS/RNS, oxLDL, glutathione (GSH), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), metalloproteinase 2 and 9 (MMP-2, MMP-9), and the activity of superoxide dismutase (SOD) and catalase (CAT) were measured. Results. The data showed significant differences in oxidative stress markers between treated and untreated MetS rats. ROS/RNS levels, oxLDL concentration, and SOD activity were lower, whereas CAT activity was higher in rats with MetS receiving polyphenolic extract. After administration of the extract, markers for kidney injury (NGAL, KIM-1) decreased. Conclusion. Our study confirmed the usefulness of pomegranate polyphenols in the treatment of MetS and the prevention of kidney damage. However, further, more detailed research is required to establish the mechanism of polyphenol protection.
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Brem, Andrew S., and Rujun Gong. "Therapeutic targeting of aldosterone: a novel approach to the treatment of glomerular disease." Clinical Science 128, no. 9 (January 27, 2015): 527–35. http://dx.doi.org/10.1042/cs20140432.
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Numerous studies have established a role for mineralocorticoids in the development of renal fibrosis. Originally, the research focus for mineralocorticoid-induced fibrosis was on the collecting duct, where ‘classical’ mineralocorticoid receptors (MRs) involved with electrolyte transport are present. Epithelial cells in this segment can, under selected circumstances, also respond to MR activation by initiating pro-fibrotic pathways. More recently, ‘non-classical’ MRs have been described in kidney cells not associated with electrolyte transport, including mesangial cells and podocytes within the glomerulus. Activation of MRs in these cells appears to lead to glomerular sclerosis. Mechanistically, aldosterone induces excess production of reactive oxygen species (ROS) and oxidative stress in glomerular cells through activation of NADPH oxidase. In mesangial cells, aldosterone also has pro-apoptotic, mitogenic and pro-fibrogenic effects, all of which potentially promote active remodelling and expansion of the mesangium. Although mitochondrial dysfunction seems to mediate the aldosterone-induced mesangial apoptosis, the ROS dependent epithelial growth factor receptor (EGFR) transactivation is probably responsible for aldosterone-induced mesangial mitosis and proliferation. In podocytes, mitochondrial dysfunction elicited by oxidative stress is an early event associated with aldosterone-induced podocyte injury. Both the p38 MAPK (p38 mitogen-activated protein kinase) signalling and the redox-sensitive glycogen synthase kinase (GSK)3β pathways are centrally implicated in aldosterone-induced podocyte death. Aldosterone-induced GSK3β over-activity could potentially cause hyperphosphorylation and over-activation of putative GSK3β substrates, including structural components of the mitochondrial permeability transition (MPT) pore, all of which lead to cell injury and death. Clinically, proteinuria significantly decreases when aldosterone inhibitors are included in the treatment of many glomerular diseases further supporting the view that mineralocorticoids are important players in glomerular pathology.
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Talyan, Sweta, Samantha Filipów, Michael Ignarski, Magdalena Smieszek, He Chen, Lucas Kühne, Linus Butt, et al. "CALINCA—A Novel Pipeline for the Identification of lncRNAs in Podocyte Disease." Cells 10, no. 3 (March 20, 2021): 692. http://dx.doi.org/10.3390/cells10030692.
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Diseases of the renal filtration unit—the glomerulus—are the most common cause of chronic kidney disease. Podocytes are the pivotal cell type for the function of this filter and focal-segmental glomerulosclerosis (FSGS) is a classic example of a podocytopathy leading to proteinuria and glomerular scarring. Currently, no targeted treatment of FSGS is available. This lack of therapeutic strategies is explained by a limited understanding of the defects in podocyte cell biology leading to FSGS. To date, most studies in the field have focused on protein-coding genes and their gene products. However, more than 80% of all transcripts produced by mammalian cells are actually non-coding. Here, long non-coding RNAs (lncRNAs) are a relatively novel class of transcripts and have not been systematically studied in FSGS to date. The appropriate tools to facilitate lncRNA research for the renal scientific community are urgently required due to a row of challenges compared to classical analysis pipelines optimized for coding RNA expression analysis. Here, we present the bioinformatic pipeline CALINCA as a solution for this problem. CALINCA automatically analyzes datasets from murine FSGS models and quantifies both annotated and de novo assembled lncRNAs. In addition, the tool provides in-depth information on podocyte specificity of these lncRNAs, as well as evolutionary conservation and expression in human datasets making this pipeline a crucial basis to lncRNA studies in FSGS.
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Cojocaru, Manole, Inimioara Cojocaru, Isabela Silosi, and Camelia Vrabie. "Kidney Damage in Autoimmune Diseases." Journal of Medical Biochemistry 29, no. 2 (April 1, 2010): 61–65. http://dx.doi.org/10.2478/v10011-010-0007-x.
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Kidney Damage in Autoimmune DiseasesRenal involvement in autoimmunity has many facets. Glomerular, tubular and vascular structures are targeted and damaged as a consequence of autoimmune processes. Immunologically mediated kidney diseases represent the third most common cause of end-stage renal failure (after diabetic and hypertensive nephropathies). Appropriate evalution of patients with immune-mediated kidney diseases requires a meticulous history and physical examination, with particular attention to the urinalysis, tests of renal function and often renal biopsy. The thorough clinician should personally review microscopic urinalysis in any case in which there is a reasonable index of suspicion of immune-mediated renal disease. In this article we propose to highlight recent developments, with particular reference to renal autoimmunity. Systemic lupus erythe-matosus affects many parts of the body: primarily the skin and joints, but also the kidneys. Goodpasture's syndrome involves an autoantibody that specifically targets the kidneys and the lungs. IgA nephropathy is a form of glomerular disease that results when immunoglobulin A (IgA) forms deposits in the glomeruli, where it creates inflammation. Future research could look for how the disease occurs, and how to easily test for its presence so that early treatment could be started.
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Machado, Soraia Goretti Rocha, Thiago Quadros, Yoshimi Watanabe, Cecília F. Aquino, Alba Otoni, and Sérgio Wyton Pinto. "Most common histopathological patterns of the Minas Gerais Association of the Centers of Nephrology." Revista da Associação Médica Brasileira 65, no. 3 (March 2019): 441–45. http://dx.doi.org/10.1590/1806-9282.65.3.441.
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SUMMARY INTRODUCTION: We analyzed the distribution and frequency of glomerular diseases in patients biopsied between 1992 and 2016 in centers that make up the AMICEN (Minas Gerais Association of Nephrology Centers). METHODS: We analyzed the biopsy reports of patients from 9 AMICEN nephrology centers. We took note of their age, gender, ultrasound use, post-biopsy resting time, whether the kidney was native or a graft, number of glomeruli and indication for the biopsy. The kidney biopsy findings were broken down into four categories: glomerular and non-glomerular diseases, normal kidneys and insufficient material for analysis. Those patients diagnosed with glomerular diseases were further divided into having primary or secondary glomerular diseases. RESULTS: We obtained 582 biopsy reports. The median age was 38 years (1 to 85). The number of glomeruli varied between 0 and 70 (median = 13.0). In total, 97.8% of the biopsies were ultrasound guided. The main indication was nephrotic syndrome (36.9%), followed by hematuria-proteinuria association (16.2%). Primary glomerular diseases proved to be the most frequent (75.3%), followed by secondary diseases (24.7%). Among the primary glomerular diseases, FSGS was found at a higher frequency (28.8%), while among the secondary diseases, SLE was the most prevalent (42.4%). Regarding prevalence findings, those for both primary and secondary diseases were similar to those found in the large Brazilian registries published thus far. CONCLUSION: Glomerular disease registries are an important tool to identify the prevalence of such disease in regions of interest and can serve as an instrument to guide public policy decisions concerning the prevention of terminal kidney diseases.