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Sample records for murine renal transcriptoma

  1. Chinese medicinal herbs inhibit growth of murine renal cell carcinoma.

    PubMed

    Lau, B H; Ruckle, H C; Botolazzo, T; Lui, P D

    1994-01-01

    Tumors are known to produce factors suppressing immune functions. We previously showed that a murine renal cell carcinoma (Renca) suppressed macrophage function in vitro and that this suppression was abolished by co-incubation with extracts of two Chinese medicinal herbs. We now report that these phytochemicals are capable of inhibiting growth of Renca in vivo. BALB/c mice were transplanted intraperitoneally (IP) with 1-2 x 10(5) Renca cells. One day after tumor transplant, mice were randomized into two groups. One group was treated IP, daily for 10 days, with 100 microliters of phytochemicals containing 500 micrograms each of Astragalus membranaceus and Ligustrum lucidum, while the other group received saline as controls. A cure rate of 57% was obtained with these phytochemicals when the initial tumor load was 2 x 10(5), and 100% when the initial tumor load was 1 x 10(5). Additional experiments were performed to investigate the mechanisms involved in this protection. Splenic macrophages from tumor-bearing mice were shown to have depressed chemiluminescent oxidative burst activity, and this depression was restored with phytochemical treatment. Splenocytes from mice transplanted with Renca responded less favorably to interleukin-2 (IL-2) in generating lymphokine-activated killer (LAK) cells; again this depression was restored with phytochemical treatment. Our data suggest that these phytochemicals may have exerted their antitumor effects via augmentation of phagocyte and LAK cell activities. PMID:7812364

  2. Development of renal atrophy in murine 2 kidney 1 clip hypertension is strain independent.

    PubMed

    Kashyap, Sonu; Boyilla, Rajendra; Zaia, Paula J; Ghossan, Roba; Nath, Karl A; Textor, Stephen C; Lerman, Lilach O; Grande, Joseph P

    2016-08-01

    The murine 2-kidney 1-clip (2K1C) model has been used to identify mechanisms underlying chronic renal disease in human renovascular hypertension. Although this model recapitulates many of the features of human renovascular disease, strain specific variability in renal outcomes and animal-to-animal variation in the degree of arterial stenosis are well recognized limitations. In particular, the C57BL/6J strain is considered to be resistant to chronic renal damage in other models. Our objectives were to determine strain dependent variations in renal disease progression and to identify parameters that predict renal atrophy in murine 2K1C hypertension. We used a 0.20mm polytetrafluoroethylene cuff to establish RAS in 3 strains of mice C57BL/6J (N=321), C57BLKS/J (N=177) and129Sv (N=156). The kidneys and hearts were harvested for histopathologic analysis after 3days or after 1, 2, 4, 6, 7, 11 or 17weeks. We performed multivariate analysis to define associations between blood pressure, heart and kidney weights, ratio of stenotic kidney/contralateral kidney (STK/CLK) weight, percent atrophy (% atrophy) and plasma renin content. The STK of all 3 strains showed minimal histopathologic alterations after 3days, but later developed progressive interstitial fibrosis, tubular atrophy, and inflammation. The STK weight negatively correlated with maximum blood pressure and % atrophy, and positively correlated with STK/CLK ratio. RAS produces severe chronic renal injury in the STK of all murine strains studied, including C57BL/6J. Systolic blood pressure is negatively associated with STK weight, STK/CLK ratio and positively with atrophy and may be used to assess adequacy of vascular stenosis in this model. PMID:27473991

  3. Targeting Sirtuin-1 prolongs murine renal allograft survival and function.

    PubMed

    Levine, Matthew H; Wang, Zhonglin; Xiao, Haiyan; Jiao, Jing; Wang, Liqing; Bhatti, Tricia R; Hancock, Wayne W; Beier, Ulf H

    2016-05-01

    Current immunosuppressive medications used after transplantation have significant toxicities. Foxp3(+) T-regulatory cells can prevent allograft rejection without compromising protective host immunity. Interestingly, inhibiting the class III histone/protein deacetylase Sirtuin-1 can augment Foxp3(+) T-regulatory suppressive function through increasing Foxp3 acetylation. Here we determined whether Sirtuin-1 targeting can stabilize biological allograft function. BALB/c kidney allografts were transplanted into C57BL/6 recipients with a CD4-conditional deletion of Sirtuin-1 (Sirt1(fl/fl)CD4(cre)) or mice treated with a Sirtuin-1-specific inhibitor (EX-527), and the native kidneys removed. Blood chemistries and hematocrit were followed weekly. Sirt1(fl/fl)CD4(cre) recipients showed markedly longer survival and improved kidney function. Sirt1(fl/fl)CD4(cre) recipients exhibited donor-specific tolerance, accepted BALB/c, but rejected third-party C3H cardiac allografts. C57BL/6 recipients of BALB/c renal allografts that were treated with EX-527 showed improved survival and renal function at 1, but not 10 mg/kg/day. Pharmacologic inhibition of Sirtuin-1 also improved renal allograft survival and function with dosing effects having relevance to outcome. Thus, inhibiting Sirtuin-1 can be a useful asset in controlling T-cell-mediated rejection. However, effects on non-T cells that could adversely affect allograft survival and function merit consideration. PMID:27083279

  4. Regulation of TLR2 and NLRP3 in Primary Murine Renal Tubular Epithelial Cells

    PubMed Central

    Kasimsetty, Sashi G.; DeWolf, Sean E.; Shigeoka, Alana A.; McKay, Dianne B.

    2016-01-01

    Pattern recognition receptors (PRRs) are now recognized to be key triggers of injury in a variety of renal diseases. Several families of these receptors are present in the kidney, and recent data suggest that they are differentially expressed and regulated in the kidney. This study evaluated the interaction between two distinct PRRs that are expressed in the kidney, i.e. TLR2 (Toll-like receptor 2) and the NLRP3 inflammasome. The regulation and activation of these receptors in primary renal tubular epithelial (RTE) cells from murine kidneys were evaluated. RTE cells were extracted from WT and NLRP3-mutant mice and treated ex vivo with ligands specific for TLR2 or NLRP3. We found that TLR2 upregulated NLRP3 as well as its substrate IL-1β, and that signaling through the NLRP3 inflammasome induced RTE cell necrosis. The results of this study suggest a previously unknown interaction between TLR2 and NLRP3 in primary RTE cells and highlight the importance of the cross talk that occurs in kidney-related PRRs. Understanding how PRRs are regulated is important for the design of rationale therapeutic strategies to modulate these receptors in renal disease. PMID:25343834

  5. Nephroprotective Effect of Ursolic Acid in a Murine Model of Gentamicin-Induced Renal Damage

    PubMed Central

    Pai, Preethi G.; Chamari Nawarathna, Savindika; Kulkarni, Avdhooth; Habeeba, Umma; Reddy C., Sudarshan; Teerthanath, Srinivas; Shenoy, Jnaneshwara P.

    2012-01-01

    The present study evaluates the nephroprotective effects of ursolic acid in a murine model of gentamicin induced renal damage. Wistar albino rats of either sex, weighing 150–200 g were divided into 5 groups; normal saline, gentamicin 80 mg/kg, intraperitoneally for 8 days, ursolic acid at 2, 5, and 10 mg/kg, per oral for 8 days, ursolic acid administered 3 days prior and concurrently with gentamicin for 5 days. Blood urea, serum creatinine, uric acid and blood urea nitrogen analyses and microscopic examination of kidney were performed. Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in serum urea, serum uric acid, serum creatinine and blood urea nitrogen (162.33 ± 9.92 mg/dL, 3.13 ± 0.12 mg/dL, 6.85 ± 0.35 mg/dL and 75.86 ± 4.64 mg/dL; resp.) when compared to the saline treated groups. Co-administration of ursolic acid with gentamicin decreased the rise in these parameters in a dose dependent manner. Histopathological analysis revealed epithelial loss with intense granular degeneration in gentamicin treated rats, whereas ursolic acid mitigated the severity of gentamicin-induced renal damage. To conclude, our data suggest that ursolic acid exhibits renoprotective effect in gentamicin induced renal damage and further studies on its mechanis of action are warranted. PMID:22811930

  6. Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro

    SciTech Connect

    Morizane, Ryuji; Monkawa, Toshiaki; Itoh, Hiroshi

    2009-12-25

    Embryonic stem (ES) cells which have the unlimited proliferative capacity and extensive differentiation potency can be an attractive source for kidney regeneration therapies. Recent breakthroughs in the generation of induced pluripotent stem (iPS) cells have provided with another potential source for the artificially-generated kidney. The purpose of this study is to know how to differentiate mouse ES and iPS cells into renal lineage. We used iPS cells from mouse fibroblasts by transfection of four transcription factors, namely Oct4, Sox2, c-Myc and Klf4. Real-time PCR showed that renal lineage markers were expressed in both ES and iPS cells after the induction of differentiation. It also showed that a tubular specific marker, KSP progressively increased to day 18, although the differentiation of iPS cells was slower than ES cells. The results indicated that renal lineage cells can be differentiated from both murine ES and iPS cells. Several inducing factors were tested whether they influenced on cell differentiation. In ES cells, both of GDNF and BMP7 enhanced the differentiation to metanephric mesenchyme, and Activin enhanced the differentiation of ES cells to tubular cells. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. ES and iPS cells have a potential to differentiate to renal lineage cells, and they will be an attractive resource of kidney regeneration therapy. This differentiation is enhanced by Activin in both ES and iPS cells.

  7. Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells.

    PubMed

    Tan, Thian Kui; Zheng, Guoping; Hsu, Tzu-Ting; Wang, Ying; Lee, Vincent W S; Tian, Xinrui; Wang, Yiping; Cao, Qi; Wang, Ya; Harris, David C H

    2010-03-01

    As a rich source of pro-fibrogenic growth factors and matrix metalloproteinases (MMPs), macrophages are well-placed to play an important role in renal fibrosis. However, the exact underlying mechanisms and the extent of macrophage involvement are unclear. Tubular cell epithelial-mesenchymal transition (EMT) is an important contributor to renal fibrosis and MMPs to induction of tubular cell EMT. The aim of this study was to investigate the contribution of macrophages and MMPs to induction of tubular cell EMT. The murine C1.1 tubular epithelial cell line and primary tubular epithelial cells were cultured in activated macrophage-conditioned medium (AMCM) derived from lipopolysaccharide-activated J774 macrophages. MMP-9, but not MMP-2 activity was detected in AMCM. AMCM-induced tubular cell EMT in C1.1 cells was inhibited by broad-spectrum MMP inhibitor (GM6001), MMP-2/9 inhibitor, and in AMCM after MMP-9 removal by monoclonal Ab against MMP-9. AMCM-induced EMT in primary tubular epithelial cells was inhibited by MMP-2/9 inhibitor. MMP-9 induced tubular cell EMT in both C1.1 cells and primary tubular epithelial cells. Furthermore, MMP-9 induced tubular cell EMT in C1.1 cells to an extent similar to transforming growth factor-beta. Transforming growth factor-beta-induced tubular cell EMT in C1.1 cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence that MMPs, specifically MMP-9, secreted by effector macrophages can induce tubular cell EMT and thereby contribute to renal fibrosis. PMID:20075196

  8. Blockade of CCR2 reduces macrophage influx and development of chronic renal damage in murine renovascular hypertension.

    PubMed

    Kashyap, Sonu; Warner, Gina M; Hartono, Stella P; Boyilla, Rajendra; Knudsen, Bruce E; Zubair, Adeel S; Lien, Karen; Nath, Karl A; Textor, Stephen C; Lerman, Lilach O; Grande, Joseph P

    2016-03-01

    Renovascular hypertension (RVH) is a common cause of both cardiovascular and renal morbidity and mortality. In renal artery stenosis (RAS), atrophy in the stenotic kidney is associated with an influx of macrophages and other mononuclear cells. We tested the hypothesis that chemokine receptor 2 (CCR2) inhibition would reduce chronic renal injury by reducing macrophage influx in the stenotic kidney of mice with RAS. We employed a well-established murine model of RVH to define the relationship between macrophage infiltration and development of renal atrophy in the stenotic kidney. To determine the role of chemokine ligand 2 (CCL2)/CCR2 signaling in the development of renal atrophy, mice were treated with the CCR2 inhibitor RS-102895 at the time of RAS surgery and followed for 4 wk. Renal tubular epithelial cells expressed CCL2 by 3 days following surgery, a time at which no significant light microscopic alterations, including interstitial inflammation, were identified. Macrophage influx increased with time following surgery. At 4 wk, the development of severe renal atrophy was accompanied by an influx of inducible nitric oxide synthase (iNOS)+ and CD206+ macrophages that coexpressed F4/80, with a modest increase in macrophages coexpressing arginase 1 and F4/80. The CCR2 inhibitor RS-102895 attenuated renal atrophy and significantly reduced the number of dual-stained F4/80+ iNOS+ and F4/80+ CD206+ but not F4/80+ arginase 1+ macrophages. CCR2 inhibition reduces iNOS+ and CD206+ macrophage accumulation that coexpress F4/80 and renal atrophy in experimental renal artery stenosis. CCR2 blockade may provide a novel therapeutic approach to humans with RVH. PMID:26661648

  9. Glomerular parietal epithelial cells of adult murine kidney undergo EMT to generate cells with traits of renal progenitors.

    PubMed

    Swetha, G; Chandra, Vikash; Phadnis, Smruti; Bhonde, Ramesh

    2011-02-01

    Glomerular parietal epithelial cells (GPECs) are known to revert to embryonic phenotype in response to renal injury. However, the mechanism of de-differentiation in GPECs and the underlying cellular processes are not fully understood. In the present study, we show that cultured GPECs of adult murine kidney undergo epithelial-mesenchymal transition (EMT) to generate cells, which express CD24, CD44 and CD29 surface antigens. Characterization by qRT-PCR and immunostaining of these clonogenic cells demonstrate that they exhibit metastable phenotype with co-expression of both epithelial (cytokeratin-18) and mesenchymal (vimentin) markers. Transcript analysis by qRT-PCR revealed high expression of metanephric mesenchymal (Pax-2, WT-1, Six-1, Eya-1, GDNF) and uteric bud (Hoxb-7, C-Ret) genes in these cells, indicating their bipotent progenitor status. Incubation of GPECs with EMT blocker Prostaglandin E2, resulted in low expression of renal progenitor markers reflecting the correlation between EMT and acquired stemness in these cells. Additional in vitro renal commitment assays confirmed their functional staminality. When injected into E13.5 kidney rudiments, the cells incorporated into the developing kidney primordia and co-culture with E13.5 spinal cord resulted in branching and tubulogenesis in these cells. When implanted under renal capsule of unilaterally nephrectomized mice, these cells differentiated into immature glomeruli and vascular ducts. Our study demonstrates that EMT plays a major role in imparting plasticity to terminally differentiated GPECs by producing metastable cells with traits of kidney progenitors. The present study would improve our understanding on epithelial cell plasticity, furthering our knowledge of its role in renal repair and regeneration. PMID:19840197

  10. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  11. Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease

    PubMed Central

    Fox, Christopher; Cocchiaro, Pasquale; Oakley, Fiona; Howarth, Rachel; Callaghan, Krystena; Leslie, Jack; Luli, Saimir; Wood, Katrina M.; Genovese, Federica; Sheerin, Neil S.; Moles, Anna

    2016-01-01

    During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for cathepsins in CKD. CtsD and B were located in distal and proximal tubular cells respectively in human disease. Administration of CtsD (Pepstatin A) but not B inhibitor (Ca074-Me), in two mouse CKD models, UUO and chronic ischemia reperfusion injury, led to a reduction in fibrosis. No changes in collagen transcription or myofibroblasts numbers were observed. Pepstatin A administration resulted in increased extracellular urokinase and collagen degradation. In vitro and in vivo administration of chloroquine, an endo/lysosomal inhibitor, mimicked Pepstatin A effect on renal fibrosis. Therefore, we propose a mechanism by which CtsD inhibition leads to increased collagenolytic activity due to an impairment in lysosomal recycling. This results in increased extracellular activity of enzymes such as urokinase, triggering a proteolytic cascade, which culminates in more ECM degradation. Taken together these results suggest that inhibition of lysosomal proteases, such as CtsD, could be a new therapeutic approach to reduce renal fibrosis and slow progression of CKD. PMID:26831567

  12. Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease.

    PubMed

    Fox, Christopher; Cocchiaro, Pasquale; Oakley, Fiona; Howarth, Rachel; Callaghan, Krystena; Leslie, Jack; Luli, Saimir; Wood, Katrina M; Genovese, Federica; Sheerin, Neil S; Moles, Anna

    2016-01-01

    During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for cathepsins in CKD. CtsD and B were located in distal and proximal tubular cells respectively in human disease. Administration of CtsD (Pepstatin A) but not B inhibitor (Ca074-Me), in two mouse CKD models, UUO and chronic ischemia reperfusion injury, led to a reduction in fibrosis. No changes in collagen transcription or myofibroblasts numbers were observed. Pepstatin A administration resulted in increased extracellular urokinase and collagen degradation. In vitro and in vivo administration of chloroquine, an endo/lysosomal inhibitor, mimicked Pepstatin A effect on renal fibrosis. Therefore, we propose a mechanism by which CtsD inhibition leads to increased collagenolytic activity due to an impairment in lysosomal recycling. This results in increased extracellular activity of enzymes such as urokinase, triggering a proteolytic cascade, which culminates in more ECM degradation. Taken together these results suggest that inhibition of lysosomal proteases, such as CtsD, could be a new therapeutic approach to reduce renal fibrosis and slow progression of CKD. PMID:26831567

  13. Increased renal catabolism of 1,25-dihydroxyvitamin D3 in murine X-linked hypophosphatemic rickets.

    PubMed Central

    Tenenhouse, H S; Yip, A; Jones, G

    1988-01-01

    The hypophosphatemic (Hyp) mouse, a murine homologue of human X-linked hypophosphatemic rickets, is characterized by renal defects in brush border membrane phosphate transport and vitamin D3 metabolism. The present study was undertaken to examine whether elevated renal 25-hydroxyvitamin D3-24-hydroxylase activity in Hyp mice is associated with increased degradation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by side chain oxidation. Metabolites of 1,25(OH)2D3 were separated by HPLC on Zorbax SIL and identified by comparison with standards authenticated by mass spectrometry. Production of 1,24,25-trihydroxyvitamin D3, 24-oxo-1,25-dihydroxyvitamin D3, and 24-oxo-1,23,25-trihydroxyvitamin D3 was twofold greater in mitochondria from mutant Hyp/Y mice than from normal +/Y littermates. Enzyme activities, estimated by the sum of the three products synthesized per milligram mitochondrial protein under initial rate conditions, were used to estimate kinetic parameters. The apparent Vmax was significantly greater for mitochondria from Hyp/Y mice than from +/Y mice (0.607 +/- 0.064 vs. 0.290 +/- 0.011 pmol/mg per protein per min, mean +/- SEM, P less than 0.001), whereas the apparent Michaelis-Menten constant (Km) was similar in both genotypes (23 +/- 2 vs. 17 +/- 5 nM). The Km for 1,25(OH)2D3 was approximately 10-fold lower than that for 25-hydroxyvitamin D3 [25(OH)D3], indicating that 1,25(OH)2D3 is perhaps the preferred substrate under physiological conditions. In both genotypes, apparent Vmax for 25(OH)D3 was fourfold greater than that for 1,25(OH)2D3, suggesting that side chain oxidation of 25(OH)D3 may operate at pharmacological concentrations of substrate. The present results demonstrate that Hyp mice exhibit increased renal catabolism of 1,25(OH)2D3 and suggest that elevated degradation of vitamin D3 hormone may contribute significantly to the clinical phenotype in this disorder. PMID:3339128

  14. Genome-wide analysis of murine renal distal convoluted tubular cells for the target genes of mineralocorticoid receptor

    SciTech Connect

    Ueda, Kohei; Fujiki, Katsunori; Shirahige, Katsuhiko; Gomez-Sanchez, Celso E.; Fujita, Toshiro; Nangaku, Masaomi; Nagase, Miki

    2014-02-28

    Highlights: • We define a target gene of MR as that with MR-binding to the adjacent region of DNA. • We use ChIP-seq analysis in combination with microarray. • We, for the first time, explore the genome-wide binding profile of MR. • We reveal 5 genes as the direct target genes of MR in the renal epithelial cell-line. - Abstract: Background and objective: Mineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). Methods: We analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10{sup −7} M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10{sup −7} M aldosterone for 3 h by microarray. Results: 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10{sup −9} M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. Conclusions: We, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases.

  15. BMP-7 is an efficacious treatment of vascular calcification in a murine model of atherosclerosis and chronic renal failure.

    PubMed

    Davies, Matthew R; Lund, Richard J; Hruska, Keith A

    2003-06-01

    Chronic renal failure is complicated by high cardiovascular mortality. One key contributor to this mortality is vascular calcification, for which no therapy currently exists. Bone morphogenetic protein 7 is an essential renal morphogen that maintains renal tubular differentiation in the adult and is downregulated in renal failure. Several studies have demonstrated its efficacy in treating various renal diseases in rodents, and it was hypothesized that it would also be an effective treatment of vascular calcification in this setting. Uremia was imposed on LDL receptor null mice (a model of atherosclerosis), which were then treated with bone morphogenetic protein 7 for 15 wk. Uremic animals had increased vascular calcification by histology and chemical analysis. Calcification in treated animals was similar to or less than non-uremic control animals. Cells exhibiting an osteoblast-like phenotype in the vessel wall may be important in the etiology of vascular calcification. Expression of osteocalcin was assessed as a marker of osteoblastic function, and it is shown that it is increased in untreated uremic animals but downregulated to levels similar to non-uremic control animals with treatment. The data are compatible with bone morphogenetic protein 7 deficiency as a pathophysiologic factor in chronic renal failure, and they demonstrate its efficacy as a potential treatment of vascular calcification. PMID:12761256

  16. Chemokine gene expression in the murine renal cell carcinoma, RENCA, following treatment in vivo with interferon-alpha and interleukin-2.

    PubMed Central

    Sonouchi, K.; Hamilton, T. A.; Tannenbaum, C. S.; Tubbs, R. R.; Bukowski, R.; Finke, J. H.

    1994-01-01

    The expression of three chemoattractant cytokine (chemokine) messenger (m)RNAs in the murine renal cell carcinoma (RENCA) from mice treated with a combination of interferon-alpha (IFN-alpha) and interleukin-2 was examined and related to tumor infiltration by inflammatory leukocytes. Using a semi-quantitative reverse transcriptase polymerase chain reaction assay, mRNAs encoding the KC, JE, and IP-10 genes were all elevated in tumor tissue from mice treated systemically with IFN-alpha/interleukin-2 for 4 days. Similarly, the mRNA for tumor necrosis factor-alpha (TNF-alpha) was also increased in tumors from treated as compared to control animals. The same tumors showed a significant increase in Mac-1+ leukocytes, which correlated well with the increase in chemokine and TNF-alpha gene expression. The renal cell carcinoma tumor itself may be responsible for the expression of chemokine genes in the tumor bed following cytokine therapy. Cultures of freshly explanted RENCA cells expressed significant levels of chemokine mRNAs when stimulated in vitro with IFN alpha, IFN gamma, and/or interleukin-2, demonstrating that this tumor cell has potential for expression of these genes in vivo. In contrast, TNF-alpha expression was not detected in cultured tumor cells. Thus TNF-alpha may be expressed by infiltrating monocytes following exposure to recombinant cytokine therapy. Images Figure 1 Figure 2 Figure 4 PMID:8160774

  17. Role of MHC-Linked Genes in Autoantigen Selection and Renal Disease in a Murine Model of Systemic Lupus Erythematosus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously described a renal protective effect of factor B deficiency in MRL/lpr mice. Factor B is in the MHC cluster; thus, the deficient mice were H2b, the haplotype on which the knockout was derived, whereas the wild-type littermates were H2k, the H2 of MRL/lpr mice. To determine which protect...

  18. TLR9 Deficiency Leads to Accelerated Renal Disease and Myeloid Lineage Abnormalities in Pristane-Induced Murine Lupus.

    PubMed

    Bossaller, Lukas; Christ, Anette; Pelka, Karin; Nündel, Kerstin; Chiang, Ping-I; Pang, Catherine; Mishra, Neha; Busto, Patricia; Bonegio, Ramon G; Schmidt, Reinhold Ernst; Latz, Eicke; Marshak-Rothstein, Ann

    2016-08-15

    Systemic lupus erythematosus (SLE) is a chronic, life-threatening autoimmune disorder, leading to multiple organ pathologies and kidney destruction. Analyses of numerous murine models of spontaneous SLE have revealed a critical role for endosomal TLRs in the production of autoantibodies and development of other clinical disease manifestations. Nevertheless, the corresponding TLR9-deficient autoimmune-prone strains consistently develop more severe disease pathology. Injection of BALB/c mice with 2,6,10,14-tetramethylpentadecane (TMPD), commonly known as pristane, also results in the development of SLE-like disease. We now show that Tlr9(-/-) BALB/c mice injected i.p. with TMPD develop more severe autoimmunity than do their TLR-sufficient cohorts. Early indications include an increased accumulation of TLR7-expressing Ly6C(hi) inflammatory monocytes at the site of injection, upregulation of IFN-regulated gene expression in the peritoneal cavity, and an increased production of myeloid lineage precursors (common myeloid progenitors and granulocyte myeloid precursors) in the bone marrow. TMPD-injected Tlr9(-/-) BALB/c mice develop higher autoantibody titers against RNA, neutrophil cytoplasmic Ags, and myeloperoxidase than do TMPD-injected wild-type BALB/c mice. The TMP-injected Tlr9(-/-) mice, and not the wild-type mice, also develop a marked increase in glomerular IgG deposition and infiltrating granulocytes, much more severe glomerulonephritis, and a reduced lifespan. Collectively, the data point to a major role for TLR7 in the response to self-antigens in this model of experimental autoimmunity. Therefore, the BALB/c pristane model recapitulates other TLR7-driven spontaneous models of SLE and is negatively regulated by TLR9. PMID:27354219

  19. A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model.

    PubMed

    Guo, Kai; Huang, Peng; Xu, Naijin; Xu, Peng; Kaku, Haruki; Zheng, Shaobo; Xu, Abai; Matsuura, Eiji; Liu, Chunxiao; Kumon, Hiromi

    2015-08-28

    YM155, a small molecule inhibitor of the antiapoptotic protein survivin, has been developed as a potential anti-cancer drug. We investigated a combination therapy of YM155 and interleukin-2 (IL-2) in a mouse model of renal cell carcinoma (RCC). YM155 caused cell cycle arrest and apoptosis in renal cancer (RENCA) cells. Next, luciferase-expressing RENCA cells were implanted in the left kidney and the lung of BALB/c mice to develop RCC metastatic model. In this orthotopic renal and metastatic lung tumors models, YM155 and IL-2 additively decreased tumor weight, lung metastasis, and luciferin-stained tumor images. Also, the combination significantly suppressed regulatory T cells and myeloid-derived suppressor cells compared with single agent treatment. We suggest that a combination of YM155 and IL-2 can be tested as a potential therapeutic modality in patients with RCC. PMID:26023798

  20. A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model

    PubMed Central

    Huang, Peng; Xu, Peng; Kaku, Haruki; Zheng, Shaobo; Xu, Abai; Matsuura, Eiji; Liu, Chunxiao; Kumon, Hiromi

    2015-01-01

    YM155, a small molecule inhibitor of the antiapoptotic protein survivin, has been developed as a potential anti-cancer drug. We investigated a combination therapy of YM155 and interleukin-2 (IL-2) in a mouse model of renal cell carcinoma (RCC). YM155 caused cell cycle arrest and apoptosis in renal cancer (RENCA) cells. Next, luciferase-expressing RENCA cells were implanted in the left kidney and the lung of BALB/c mice to develop RCC metastatic model. In this orthotopic renal and metastatic lung tumors models, YM155 and IL-2 additively decreased tumor weight, lung metastasis, and luciferin-stained tumor images. Also, the combination significantly suppressed regulatory T cells and myeloid-derived suppressor cells compared with single agent treatment. We suggest that a combination of YM155 and IL-2 can be tested as a potential therapeutic modality in patients with RCC. PMID:26023798

  1. Murine Typhus

    PubMed Central

    Dzul-Rosado, Karla R; Zavala Velázquez, Jorge Ernesto; Zavala-Castro, Jorge

    2012-01-01

    Rickettsia typhi: is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against Rickettsia typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of R. typhi are rats (some species belonging the Rattus Genus) and fleas (Xenopsylla cheopis) are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi. PMID:24893060

  2. Renal arteriography

    MedlinePlus

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Update Date 4/7/2014 Updated by: Jason ... Failure Kidney Tests X-Rays Browse the Encyclopedia A. ...

  3. Renal venogram

    MedlinePlus

    ... 2008:chap 6. Rankin S. Renal parenchymal disease, including renal failure, renovascular disease and transportation. In: Grainger RC, Allison D, Adam, Dixon AK, eds. Diagnostic Radiology: A Textbook of Medical Imaging . 5th ed. New York, NY: Churchill Livingstone; 2008:chap 39. Read ... arteriography Renal vein thrombosis Tumor Venogram Wilms ...

  4. [Renal elastography].

    PubMed

    Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

    2016-04-01

    Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. PMID:26976058

  5. Cloning of murine ferrochelatase.

    PubMed Central

    Brenner, D A; Frasier, F

    1991-01-01

    Ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) catalyzes the last step in the heme biosynthetic pathway, the chelation of ferrous iron and protoporphyrin to form heme. The activity of ferrochelatase is deficient in the inherited disease protoporphyria. In this study, murine ferrochelatase cDNAs were obtained by screening cDNA libraries with an oligonucleotide probe. The derived amino acid sequence of murine ferrochelatase has 47% identity with the recently cloned Saccharomyces cerevisiae ferrochelatase, but it is not significantly similar to other published sequences. Results of Southern blotting are consistent with a single murine ferrochelatase gene, while Northern blotting demonstrates two ferrochelatase transcripts in all tissues examined. The ferrochelatase protein and mRNAs have different relative concentrations in different tissues. The cloning of murine ferrochelatase cDNAs provides the basis for future studies on ferrochelatase gene expression and on the identification of the molecular defect in protoporphyria. Images PMID:1704134

  6. [Renal colic].

    PubMed

    Pinheiro, J M

    1999-01-01

    The appropriate approach to renal colic, which should be known by the family doctor, is presented. The incidence of this condition in the emergency department of a large general hospital is described as well as the physiopathology of pain, its clinical aspects and the therapeutic attitudes. Renal colic is frequent, it is often possible to diagnose the clinical aspects and general practitioners have the competence for treatment. The use of analgesic drugs, in the correct dosage, is enough to relieve pain and suffering in most of the patients. PMID:10423866

  7. [Renal disease].

    PubMed

    Espinosa-Cuevas, María de Los Ángeles

    2016-09-01

    Chronic renal failure in its various stages, requires certain nutritional restrictions associated with the accumulation of minerals and waste products that cannot be easily eliminated by the kidneys. Some of these restrictions modify the intake of proteins, sodium, and phosphorus. Milk and dairy products are sources of these nutrients. This article aims to inform the reader about the benefits including milk and dairy products relying on a scientific and critical view according to the clinical conditions and the stage of renal disease in which the patient is. PMID:27603894

  8. Renal organogenesis

    PubMed Central

    2011-01-01

    The increasing prevalence of chronic kidney disease in the absence of new treatment modalities has become a strong driver for innovation in nephrology. An increasing understanding of stem cell biology has kindled the prospects of regenerative options for kidney disease. However, the kidney itself is not a regenerative organ, as all the nephrons are formed during embryonic development. Here, we will investigate advances in the molecular genetics of renal organogenesis, including what this can tell us about lineage relationships, and discuss how this may serve to inform us about both the normal processes of renal repair and options for regenerative therapies. PMID:22198432

  9. Human and murine erythropoiesis

    PubMed Central

    An, Xiuli; Schulz, Vincent P.; Mohandas, Narla; Gallagher, Patrick G.

    2015-01-01

    Purpose of review Research into the fundamental mechanisms of erythropoiesis has provided critical insights into inherited and acquired disorders of the erythrocyte. Studies of human erythropoiesis have primarily utilized in-vitro systems, whereas murine models have provided insights from in-vivo studies. This report reviews recent insights into human and murine erythropoiesis gained from transcriptome-based analyses. Recent findings The availability of high-throughput genomic methodologies has allowed attainment of detailed gene expression data from cells at varying developmental and differentiation stages of erythropoiesis. Transcriptome analyses of human and murine reveal both stage and species-specific similarities and differences across terminal erythroid differentiation. Erythroid-specific long noncoding RNAs exhibit poor sequence conservation between human and mouse. Genome-wide analyses of alternative splicing reveal that complex, dynamic, stage-specific programs of alternative splicing program are utilized during terminal erythroid differentiation. Transcriptome data provide a significant resource for understanding mechanisms of normal and perturbed erythropoiesis. Understanding these processes will provide innovative strategies to detect, diagnose, prevent, and treat hematologic disease. Summary Understanding the shared and different mechanisms controlling human and murine erythropoiesis will allow investigators to leverage the best model system to provide insights in normal and perturbed erythropoiesis. PMID:25719574

  10. Renal Calculi

    PubMed Central

    Yendt, E. R.

    1970-01-01

    The pathogenesis of renal calculi is reviewed in general terms followed by the results of investigation of 439 patients with renal calculi studied by the author at Toronto General Hospital over a 13-year period. Abnormalities of probable pathogenetic significance were encountered in 76% of patients. Idiopathic hypercalciuria was encountered in 42% of patients, primary hyperparathyroidism in 11%, urinary infection in 8% and miscellaneous disorders in 8%. The incidence of uric acid stones and cystinuria was 5% and 2% respectively. In the remaining 24% of patients in whom no definite abnormalities were encountered the mean urinary magnesium excretion was less than normal. Of 180 patients with idiopathic hypercalciuria, only 24 were females. In the diagnosis of hyperparathyroidism, the importance of detecting minimal degrees of hypercalcemia is stressed; attention is also drawn to the new observation that the upper limit of normal for serum calcium is slightly lower in females than in males. The efficacy of various measures advocated for the prevention of renal calculi is also reviewed. In the author's experience the administration of thiazides has been particularly effective in the prevention of calcium stones. Thiazides cause a sustained reduction in urinary calcium excretion and increase in urinary magnesium excretion. These agents also appear to affect the skeleton by diminishing bone resorption and slowing down bone turnover. PMID:5438766

  11. Renal Fibrosis

    PubMed Central

    Zeisberg, Michael; Maeshima, Yohei; Mosterman, Barbara; Kalluri, Raghu

    2002-01-01

    During progression of chronic renal disease, qualitative and quantitative changes in the composition of tubular basement membranes (TBMs) and interstitial matrix occur. Transforming growth factor (TGF)-β1-mediated activation of tubular epithelial cells (TECs) is speculated to be a key contributor to the progression of tubulointerstitial fibrosis. To further understand the pathogenesis associated with renal fibrosis, we developed an in vitro Boyden chamber system using renal basement membranes that partially mimics in vivo conditions of TECs during health and disease. Direct stimulation of TECs with TGF-β1/epithelial growth factor results in an increased migratory capacity across bovine TBM preparations. This is associated with increased matrix metalloproteinase (MMP) production, namely MMP-2 and MMP-9. Indirect chemotactic stimulation by TGF-β1/EGF or collagen type I was insufficient in inducing migration of untreated TECs across bovine TBM preparation, suggesting that basement membrane integrity and composition play an important role in protecting TECs from interstitial fibrotic stimuli. Additionally, neutralization of MMPs by COL-3 inhibitor dramatically decreases the capacity of TGF-β1-stimulated TECs to migrate through bovine TBM preparation. Collectively, these results demonstrate that basement membrane structure, integrity, and composition play an important role in determining interstitial influences on TECs and subsequent impact on potential aberrant cell-matrix interactions. PMID:12057905

  12. Proximal renal tubular acidosis

    MedlinePlus

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  13. Renal Denervation

    PubMed Central

    Persu, Alexandre; Renkin, Jean; Thijs, Lutgarde; Staessen, Jan A.

    2013-01-01

    The term “ultima ratio” has multiple, though related, meanings. The motto “ultima ratio regum,” cast on the cannons of the French army of King Louis XIV, meant that war is the last argument of kings, that is, the one to be used after all diplomatic arguments have failed. Along similar lines, we propose that, given the current evidence, renal denervation should be used as a last resort, after state-of-the-art drug treatment optimized at expert centers failed to control blood pressure. PMID:22851728

  14. [Renal physiology].

    PubMed

    Gueutin, Victor; Deray, Gilbert; Isnard-Bagnis, Corinne

    2012-03-01

    The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status, acid-base status, calcium and phosphate metabolism or erythropoiesis. They adapt quantitative and qualitative composition of the urine to keep these systems in balance. The flow of plasma is filtered in the range of 120 mL/min, and depends on the systemic and renal hemodynamics which is subject to self-regulation. The original urine will then be modified in successive segments of the nephron. The proximal nephron is to lead the massive reabsorption of water and essential elements such as sodium, bicarbonates, amino-acids and glucose. The distal nephron includes the distal convoluted tubule, the connector tube and the collecting duct. Its role is to adapt the quality composition of urine to the needs of the body. PMID:22157516

  15. Inherited renal cystic diseases.

    PubMed

    Kim, Bohyun; King, Bernard F; Vrtiska, Terri J; Irazabal, Maria V; Torres, Vicente E; Harris, Peter C

    2016-06-01

    A number of inherited renal diseases present with renal cysts and often lead to end-stage renal disease. With recent advances in genetics, increasing number of genes and mutations have been associated with cystic renal diseases. Although genetic testing can provide a definite diagnosis, it is often reserved for equivocal cases or for ongoing investigational research. Therefore, imaging findings are essential in the routine diagnosis, follow-up, and detection of complications in patients with inherited cystic renal diseases. In this article, the most recent classification, genetic analysis, clinical presentations, and imaging findings of inherited cystic renal diseases will be discussed. PMID:27167233

  16. Tubular Overexpression of Angiopoietin-1 Attenuates Renal Fibrosis.

    PubMed

    Singh, Sudhir; Manson, Scott R; Lee, Heedoo; Kim, Yeawon; Liu, Tuoen; Guo, Qiusha; Geminiani, Julio J; Austin, Paul F; Chen, Ying Maggie

    2016-01-01

    Emerging evidence has highlighted the pivotal role of microvasculature injury in the development and progression of renal fibrosis. Angiopoietin-1 (Ang-1) is a secreted vascular growth factor that binds to the endothelial-specific Tie2 receptor. Ang-1/Tie2 signaling is critical for regulating blood vessel development and modulating vascular response after injury, but is dispensable in mature, quiescent vessels. Although dysregulation of vascular endothelial growth factor (VEGF) signaling has been well studied in renal pathologies, much less is known about the role of the Ang-1/Tie2 pathway in renal interstitial fibrosis. Previous studies have shown contradicting effects of overexpressing Ang-1 systemically on renal tubulointerstitial fibrosis when different engineered forms of Ang-1 are used. Here, we investigated the impact of site-directed expression of native Ang-1 on the renal fibrogenic process and peritubular capillary network by exploiting a conditional transgenic mouse system [Pax8-rtTA/(TetO)7 Ang-1] that allows increased tubular Ang-1 production in adult mice. Using a murine unilateral ureteral obstruction (UUO) fibrosis model, we demonstrate that targeted Ang-1 overexpression attenuates myofibroblast activation and interstitial collagen I accumulation, inhibits the upregulation of transforming growth factor β1 and subsequent phosphorylation of Smad 2/3, dampens renal inflammation, and stimulates the growth of peritubular capillaries in the obstructed kidney. Our results suggest that Ang-1 is a potential therapeutic agent for targeting microvasculature injury in renal fibrosis without compromising the physiologically normal vasculature in humans. PMID:27454431

  17. Tubular Overexpression of Angiopoietin-1 Attenuates Renal Fibrosis

    PubMed Central

    Lee, Heedoo; Kim, Yeawon; Liu, Tuoen; Guo, Qiusha; Geminiani, Julio J.; Austin, Paul F.; Chen, Ying Maggie

    2016-01-01

    Emerging evidence has highlighted the pivotal role of microvasculature injury in the development and progression of renal fibrosis. Angiopoietin-1 (Ang-1) is a secreted vascular growth factor that binds to the endothelial-specific Tie2 receptor. Ang-1/Tie2 signaling is critical for regulating blood vessel development and modulating vascular response after injury, but is dispensable in mature, quiescent vessels. Although dysregulation of vascular endothelial growth factor (VEGF) signaling has been well studied in renal pathologies, much less is known about the role of the Ang-1/Tie2 pathway in renal interstitial fibrosis. Previous studies have shown contradicting effects of overexpressing Ang-1 systemically on renal tubulointerstitial fibrosis when different engineered forms of Ang-1 are used. Here, we investigated the impact of site-directed expression of native Ang-1 on the renal fibrogenic process and peritubular capillary network by exploiting a conditional transgenic mouse system [Pax8-rtTA/(TetO)7 Ang-1] that allows increased tubular Ang-1 production in adult mice. Using a murine unilateral ureteral obstruction (UUO) fibrosis model, we demonstrate that targeted Ang-1 overexpression attenuates myofibroblast activation and interstitial collagen I accumulation, inhibits the upregulation of transforming growth factor β1 and subsequent phosphorylation of Smad 2/3, dampens renal inflammation, and stimulates the growth of peritubular capillaries in the obstructed kidney. Our results suggest that Ang-1 is a potential therapeutic agent for targeting microvasculature injury in renal fibrosis without compromising the physiologically normal vasculature in humans. PMID:27454431

  18. Downregulating Hedgehog Signaling Reduces Renal Cystogenic Potential of Mouse Models

    PubMed Central

    Talbott, George C.; Turbe-Doan, Annick; Jacobs, Damon T.; Schonfeld, Michael P.; Silva, Luciane M.; Chatterjee, Anindita; Prysak, Mary; Allard, Bailey A.; Beier, David R.

    2014-01-01

    Renal cystic diseases are a leading cause of renal failure. Mutations associated with renal cystic diseases reside in genes encoding proteins that localize to primary cilia. These cystoproteins can disrupt ciliary structure or cilia-mediated signaling, although molecular mechanisms connecting cilia function to renal cystogenesis remain unclear. The ciliary gene, Thm1(Ttc21b), negatively regulates Hedgehog signaling and is most commonly mutated in ciliopathies. We report that loss of murine Thm1 causes cystic kidney disease, with persistent proliferation of renal cells, elevated cAMP levels, and enhanced expression of Hedgehog signaling genes. Notably, the cAMP-mediated cystogenic potential of Thm1-null kidney explants was reduced by genetically deleting Gli2, a major transcriptional activator of the Hedgehog pathway, or by culturing with small molecule Hedgehog inhibitors. These Hedgehog inhibitors acted independently of protein kinase A and Wnt inhibitors. Furthermore, simultaneous deletion of Gli2 attenuated the renal cystic disease associated with deletion of Thm1. Finally, transcripts of Hedgehog target genes increased in cystic kidneys of two other orthologous mouse mutants, jck and Pkd1, and Hedgehog inhibitors reduced cystogenesis in jck and Pkd1 cultured kidneys. Thus, enhanced Hedgehog activity may have a general role in renal cystogenesis and thereby present a novel therapeutic target. PMID:24700869

  19. Renal vein thrombosis

    MedlinePlus

    ... the kidneys. Possible Complications Complications may include: Acute renal failure (especially if thrombosis occurs in a dehydrated child) ... Saunders; 2012:chap 34. Read More Acute kidney failure Arteriogram Blood ... embolus Renal Tumor Update Date 5/19/2015 Updated by: ...

  20. Renal papillary necrosis

    MedlinePlus

    ... your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Ruggenenti P, Cravedi P, Remuzzi G. Microvascular and macrovascular diseases of the kidney. In: Taal MW, Chertow GM, ...

  1. Kidney (Renal) Failure

    MedlinePlus

    ... renal function using ureteral stenting, nephrostomy, surgery or dialysis. What is kidney (renal) failure? How is kidney ... as a urinary stent or kidney stone removal. Dialysis , including hemodialysis and peritoneal dialysis: These procedures remove ...

  2. Renal papillary necrosis

    MedlinePlus

    ... renal papillary necrosis, especially after taking over-the-counter pain medicines ... diabetes or sickle cell anemia may reduce your risk. To prevent renal ... over-the-counter pain relievers. Do not take more than the ...

  3. Cardio-renal syndrome

    PubMed Central

    Gnanaraj, Joseph; Radhakrishnan, Jai

    2016-01-01

    Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome.

  4. Renal Denervation

    PubMed Central

    Pan, Tao; Guo, Jin-he; Teng, Gao-jun

    2015-01-01

    Abstract Type 2 diabetes mellitus (T2DM) is a group of metabolic diseases of multiple etiologies. Although great progress has been made, researchers are still working on the pathogenesis of T2DM and how to best use the treatments available. Aside from several novel pharmacological approaches, catheter-based sympathetic renal denervation (RDN) has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. In this article, we will summarize herein the role sympathetic activation plays in the progression of T2DM and review the recent clinical RDN experience in glucose metabolism. We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2015. Studies were included if a statistical relationship was investigated between RDN and T2DM. The quality of each included study was assessed by Newcastle–Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did meta-regression analysis. Finally, we identified 4 eligible articles. In most studies, RDN achieved via novel catheter-based approach using radiofrequency energy has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. But the DREAMS-Study showed that RDN did not change median insulin sensitivity nor systemic sympathetic activity. Firstly, the current published studies lacked a proper control group, along with the sample capacity was small. Also, data obtained in the subgroups of diabetic patients were not separately analyzed and the follow-up period was very short. In addition, a reduction in blood pressure accounts for the improvements in glucose metabolism and insulin resistance cannot be excluded. If the favorable result of better glucose metabolism is confirmed in large-scale, randomized studies

  5. Murine typhus in travelers returning from Indonesia.

    PubMed Central

    Parola, P.; Vogelaers, D.; Roure, C.; Janbon, F.; Raoult, D.

    1998-01-01

    We report the first three documented cases of murine typhus imported into Europe from Indonesia, discuss clues for the diagnosis of the disease, and urge that murine fever be considered in the diagnosis of febrile disease in travelers. PMID:9866749

  6. Antibacterial activity of recombinant murine beta interferon.

    PubMed Central

    Fujiki, T; Tanaka, A

    1988-01-01

    Recombinant murine beta interferon was protective and therapeutic for mice against Listeria monocytogenes infection in vivo. The recombinant murine beta interferon caused enhanced H2O2 release by macrophages in vivo, but not in vitro. PMID:3343048

  7. Immunosuppressive effect of murine cytomegalovirus.

    PubMed Central

    Loh, L; Hudson, J B

    1980-01-01

    Murine cytomegalovirus suppressed the ability of spleen cells to respond to mitogens in vitro. The degree of suppression was proportional to the multiplicity of infection. This effect could not be explained by cytolysis of lymphocytes, an alteration in the kinetics of the response to mitogen, or a direct competition between virions and mitogen molecules for cell-surface receptors. Nor was it due to simple contact between cell and virus, since ultraviolet-inactivated murine cytomegalovirus failed to suppress the response to mitogens. Reconstitution experiments were performed which involved mixing various combinations of infected and uninfected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages had an impaired capacity to mediate the response ot T lymphocytes to concanavalin A. This suggests that murine cytomegalovirus may cause immunosuppression indirectly by interfering with macrophage function. PMID:6244228

  8. Recurrent renal giant leiomyosarcoma

    PubMed Central

    Öziş, Salih Erpulat; Gülpınar, Kamil; Şahlı, Zafer; Konak, Baha Burak; Keskin, Mete; Özdemir, Süleyman; Ataoğlu, Ömür

    2016-01-01

    Primary renal leiomyosarcomas are rare, aggressive tumors. They constitute 1–2% of adult malignant renal tumors. Although leiomyosarcomas are the most common histological type (50–60%) of renal sarcomas, information on renal leiomyosarcoma is limited. Local or systemic recurrences are common. The radiological appearance of renal leiomyosarcomas is not specific, therefore renal leiomyosarcoma cannot be distinguished from renal cell carcinoma by imaging methods in all patients. A 74-year-old female patient presented to our clinic complaining of a palpable mass on the right side of her abdomen in November 2012. The abdominal magnetic resonance imaging revealed a mass, 25 × 24 × 23 cm in size. Her past medical history revealed that she has undergone right radical nephrectomy in 2007, due to a 11 × 12 × 13 cm renal mass that was then reported as renal cell carcinoma on abdominal magnetic resonance imaging, but the pathological diagnosis was low-grade renal leiomyosarcoma. The most recent follow-up of the patient was in 2011, with no signs of local recurrence or distant metastases within this four-year period. The patient underwent laparotomy on November 2012, and a 35 cm retroperitoneal mass was excised. The pathological examination of the mass was reported as high-grade leiomyosarcoma. The formation of this giant retroperitoneal mass in 1 year can be explained by the transformation of the lesion’s pathology from low-grade to a high-grade tumor.

  9. In vivo formation of polyphosphoinositide isomers and association with progression of murine polycystic kidney disease.

    PubMed

    Aukema, H M; Chapkin, R S; Tomobe, K; Takahashi, H; Holub, B J

    1992-08-01

    Polyphosphoinositide isomers have been demonstrated to be important mediators of cell proliferation in vitro. The present study demonstrates, for the first time, the in vivo formation of the novel isomer, phosphatidylinositol(3)phosphate, in the kidney and liver of intact animals following intraperitoneal administration of [3H]myo-inositol. The formation of renal [3H]phosphatidylinositol(3)phosphate relative to total [3H]phosphatidylinositol-phosphate was positively correlated with cyst proliferation and renal enlargement in a murine model of polycystic kidney disease. Furthermore, despite no difference in the formation of renal [3H]phosphatidylinositol(4)phosphate, a markedly lower accumulation (by 48%) of [3H]phosphatidylinositol(4,5)bisphosphate was observed in the diseased animals as compared to controls. These results indicate that further studies on the in vivo formation of specific polyphosphoinositide isomers in disease states characterized by abnormal growth and oncogene expression are warranted. PMID:1327862

  10. Renal Artery Embolization

    PubMed Central

    Sauk, Steven; Zuckerman, Darryl A.

    2011-01-01

    Renal artery embolization (RAE) is an effective minimally invasive alternative procedure for the treatment of a variety of conditions. Since the 1970s when RAE was first developed, technical advances and growing experience have expanded the indications to not only include treatment of conditions such as symptomatic hematuria and palliation for metastatic renal cancer, but also preoperative infarction of renal tumors, treatment of angiomyolipomas, vascular malformations, medical renal disease, and complications following renal transplantation. With the drastically improved morbidity associated with this technique in part due to the introduction of more precise embolic agents and smaller delivery catheters, RAE continues to gain popularity for various urologic conditions. The indications and techniques for renal artery embolization are reviewed in the following sections. PMID:23204638

  11. Renal cystic disease

    SciTech Connect

    Hartman, D.S.

    1988-01-01

    The book begins with an overview of renal cystic disease and a presentation of simple renal cysts. Subsequent chapters cover cystic disease in association with renal neoplasms and medullary sponge kidney. The chapters addressing autosomal-dominant and autosomal-recessive polycystic kidney disease discuss and differentiate the infantile and adult forms of the disease. There are also separate discussions of medullary cystic disease, multicystic dysplastic kidney, and cysts of the renarenal sinus.

  12. Calcified renal oncocytoma

    SciTech Connect

    Wasserman, N.F.; Ewing, S.L.

    1983-10-01

    Renal oncocytoma, a neoplasm thought to derive from cells of the proximal convoluted tubules, exhibits benign clinical features. Its preoperative distinction from typical renal cell carcinoma would enable the surgeon to perform a more limited procedure. In a patient who is a poor operative candidate, surgery might be deferred. However, preoperative diagnosis has been elusive. A rare case of bilateral renal oncocytoma is reported. One of these tumors represents the first reported oncocytoma showing radiologically demonstrable calcification.

  13. Antimicrobial proteins of murine macrophages.

    PubMed Central

    Hiemstra, P S; Eisenhauer, P B; Harwig, S S; van den Barselaar, M T; van Furth, R; Lehrer, R I

    1993-01-01

    Three murine microbicidal proteins (MUMPs) were purified from cells of the murine macrophage cell line RAW264.7 that had been activated by gamma interferon. Similar proteins were also present in nonactivated RAW264.7 cells, in cells of the murine macrophage cell line J774A.1, and in resident and activated murine peritoneal macrophages. MUMP-1, MUMP-2, and MUMP-3 killed Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Mycobacterium fortuitum, and Cryptococcus neoformans in vitro. MUMP-1 resembled an H1 histone but was unusual because its N-terminal residue (serine) was not N acetylated. Although MUMP-2 was N terminally blocked, its high lysine/arginine ratio and its reactivity with an antibody to H1 histones suggested that it also belonged to the H1 histone family. MUMP-3 was identical to histone H2B in 30 of 30 amino-terminal residues. Although the antimicrobial properties of histones have been recognized for decades, this is the first evidence that such proteins may endow the lysosomal apparatus of macrophages with nonoxidative antimicrobial potential. Other MUMPs, including some with a more restricted antimicrobial spectrum and one that appeared to be induced in RAW264.7 cells after gamma interferon stimulation, were noted but remain to be characterized. Images PMID:8514411

  14. [Hereditary renal cell carcinomas].

    PubMed

    Hartmann, A; Stöhr, C G; Junker, K

    2010-10-01

    Renal cell carcinomas occur in several hereditary tumor syndromes. These renal tumors frequently have a specific histopathological appearance which can be a sign for a hereditary cause of the disease. The genetic alterations responsible for most of these tumor syndromes were identified in recent years. Interestingly, renal cell carcinomas show specific histopathological features in each of the hereditary renal cancer syndromes. Clear cell and often cystic renal cell carcinomas occur in von Hippel-Lindau syndrome (VHL), while oncocytomas and chromophobe renal cell carcinomas are found in the Birt-Hugg-Dube syndrome, often also as hybrid tumors. Well differentiated papillary carcinomas (Type 1 according to the WHO) are found in the hereditary papillary renal cell carcinoma (HPRC). In contrast, poorly diffentiated papillary renal cell carcinomas (Type 2 according to the WHO) occur in combination with leiomyomas and leiomyosarcomas of the skin and uterus in hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC). The various genetic causes for these hereditary tumor syndromes open up new therapeutic possibilities, some of which are already being investigated in clinical studies. PMID:20960197

  15. Tuberous Sclerosis Complex Renal Disease

    PubMed Central

    Dixon, Bradley P.; Hulbert, John C.; Bissler, John J.

    2010-01-01

    Although not as common as other genetic renal diseases such as autosomal dominant polycystic kidney disease, patients with tuberous sclerosis complex frequently have significant renal involvement. Recent revelations in the cell biology of these renal disease manifestations as well as effective therapies for tuberous sclerosis complex-related renal issues have heralded hope of improved renal survival and improved quality of life for the TSC patient. This review specifically addresses some of the major renal manifestations of this disease. PMID:21071977

  16. Synchronized renal tubular cell death involves ferroptosis

    PubMed Central

    Skouta, Rachid; Himmerkus, Nina; Mulay, Shrikant R.; Dewitz, Christin; De Zen, Federica; Prokai, Agnes; Zuchtriegel, Gabriele; Krombach, Fritz; Welz, Patrick-Simon; Weinlich, Ricardo; Vanden Berghe, Tom; Vandenabeele, Peter; Pasparakis, Manolis; Bleich, Markus; Weinberg, Joel M.; Reichel, Christoph A.; Bräsen, Jan Hinrich; Kunzendorf, Ulrich; Anders, Hans-Joachim; Stockwell, Brent R.; Green, Douglas R.; Krautwald, Stefan

    2014-01-01

    Receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is thought to be the pathophysiologically predominant pathway that leads to regulated necrosis of parenchymal cells in ischemia–reperfusion injury (IRI), and loss of either Fas-associated protein with death domain (FADD) or caspase-8 is known to sensitize tissues to undergo spontaneous necroptosis. Here, we demonstrate that renal tubules do not undergo sensitization to necroptosis upon genetic ablation of either FADD or caspase-8 and that the RIPK1 inhibitor necrostatin-1 (Nec-1) does not protect freshly isolated tubules from hypoxic injury. In contrast, iron-dependent ferroptosis directly causes synchronized necrosis of renal tubules, as demonstrated by intravital microscopy in models of IRI and oxalate crystal-induced acute kidney injury. To suppress ferroptosis in vivo, we generated a novel third-generation ferrostatin (termed 16-86), which we demonstrate to be more stable, to metabolism and plasma, and more potent, compared with the first-in-class compound ferrostatin-1 (Fer-1). Even in conditions with extraordinarily severe IRI, 16-86 exerts strong protection to an extent which has not previously allowed survival in any murine setting. In addition, 16-86 further potentiates the strong protective effect on IRI mediated by combination therapy with necrostatins and compounds that inhibit mitochondrial permeability transition. Renal tubules thus represent a tissue that is not sensitized to necroptosis by loss of FADD or caspase-8. Finally, ferroptosis mediates postischemic and toxic renal necrosis, which may be therapeutically targeted by ferrostatins and by combination therapy. PMID:25385600

  17. Activation of Sirtuin-1 Promotes Renal Fibroblast Activation and Aggravates Renal Fibrogenesis.

    PubMed

    Ponnusamy, Murugavel; Zhuang, Michelle A; Zhou, Xiaoxu; Tolbert, Evelyn; Bayliss, George; Zhao, Ting C; Zhuang, Shougang

    2015-08-01

    Although activation of sirtuin-1 (SIRT1) has been shown to protect the kidney from acute injury, its role in renal fibrosis remains controversial since both inhibition and activation of SIRT1 have been reported to attenuate renal fibrosis. To resolve this conflict, we further examined the effect of SIRT1 activators on the activation of renal interstitial fibroblasts and development of renal fibrosis in vivo and in vitro. In a murine model of renal fibrosis induced by unilateral ureteral obstruction, administration of SRT1720 (N-[2-[3-(piperazin-1-ylmethyl)imidazo[2,1-b][1,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide), a potent activator of SIRT1, accelerated deposition of collagen fibrils and increased expression of fibroblast activation markers (α-smooth muscle actin [α-SMA], collagen I, and fibronectin) in the obstructive kidney of mice. In cultured rat renal interstitial fibroblasts (NRK-49F), exposure of cells to SRT1720 or YK-3-237 (B-[2-methoxy-5-[(1E)-3-oxo-3-(3,4,5-trimethoxyphenyl)-1-propen-1-yl]phenyl]-boronic acid), another SIRT1 activator, also resulted in enhanced expression of α-SMA and fibronectin. Mechanistic studies showed that augmentation of renal fibrogenesis by SRT1720 is associated with elevated phosphorylation of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor β (PDGFRβ). SRT1720 treatment also increased the phosphorylation of signal transducer and activator of transcription 3 and protein kinase B in the fibrotic kidney and NRK-49F cells. However, SRT1720 treatment did not affect expression of proliferating cell nuclear protein, a proliferation marker and activation of extracellular signal regulated kinase 1/2 in vitro and in vivo. These results indicate that SIRT1-activating compounds can provoke renal fibrogenesis through a mechanism involved in the activation of EGFR and PDGFR signaling pathways and suggest that long-term use of SIRT1 activators risks the development and progression of chronic

  18. Peptidyl arginine deiminase-4-deficient mice are protected against kidney and liver injury after renal ischemia and reperfusion.

    PubMed

    Rabadi, May; Kim, Mihwa; D'Agati, Vivette; Lee, H Thomas

    2016-08-01

    We previously demonstrated that renal peptidyl arginine deiminase-4 (PAD4) is induced after renal ischemia and reperfusion (I/R) injury and exacerbates acute kidney injury (AKI) by increasing the renal tubular inflammatory response. Here, we tested whether genetic ablation of PAD4 attenuates renal injury and inflammation after I/R in mice. After renal I/R, PAD4 wild-type mice develop severe AKI with large increases in plasma creatinine, neutrophil infiltration, as well as significant renal tubular necrosis, apoptosis, and proinflammatory cytokine generation. In contrast, PAD4-deficient mice are protected against ischemic AKI with reduced real tubular neutrophil infiltration, renal tubular necrosis, and apoptosis. In addition, hepatic injury and inflammation observed in PAD4 wild-type mice after renal I/R are significantly attenuated in PAD4-deficient mice. We also show that increased renal tubular PAD4 expression after renal I/R is associated with translocation of PAD4 from the nucleus to the cytosol. Consistent with PAD4 cytosolic translocation, we show increased renal tubular cytosolic peptidyl-citrullination after ischemic AKI. Mechanistically, recombinant PAD4 treatment increased nuclear translocation of NF-κB in cultured human as well as murine proximal tubule cells that is inhibited by a PAD4 inhibitor (2-chloroamidine). Taken together, our studies further support the hypothesis that renal tubular PAD4 plays a critical role in renal I/R injury by increasing the renal tubular inflammatory response and neutrophil infiltration after renal I/R perhaps by interacting with the proinflammatory transcription factor NF-κB in the cytosol and promoting its nuclear translocation. PMID:27335376

  19. Deregulated Renal Calcium and Phosphate Transport during Experimental Kidney Failure

    PubMed Central

    van Loon, Ellen P.; van de Sluis, Bart; Vervloet, Mark G.; Hoenderop, Joost G.; Bindels, René J.

    2015-01-01

    Impaired mineral homeostasis and inflammation are hallmarks of chronic kidney disease (CKD), yet the underlying mechanisms of electrolyte regulation during CKD are still unclear. Here, we applied two different murine models, partial nephrectomy and adenine-enriched dietary intervention, to induce kidney failure and to investigate the subsequent impact on systemic and local renal factors involved in Ca2+ and Pi regulation. Our results demonstrated that both experimental models induce features of CKD, as reflected by uremia, and elevated renal neutrophil gelatinase-associated lipocalin (NGAL) expression. In our model kidney failure was associated with polyuria, hypercalcemia and elevated urinary Ca2+ excretion. In accordance, CKD augmented systemic PTH and affected the FGF23-αklotho-vitamin-D axis by elevating circulatory FGF23 levels and reducing renal αklotho expression. Interestingly, renal FGF23 expression was also induced by inflammatory stimuli directly. Renal expression of Cyp27b1, but not Cyp24a1, and blood levels of 1,25-dihydroxy vitamin D3 were significantly elevated in both models. Furthermore, kidney failure was characterized by enhanced renal expression of the transient receptor potential cation channel subfamily V member 5 (TRPV5), calbindin-D28k, and sodium-dependent Pi transporter type 2b (NaPi2b), whereas the renal expression of sodium-dependent Pi transporter type 2a (NaPi2a) and type 3 (PIT2) were reduced. Together, our data indicates two different models of experimental kidney failure comparably associate with disturbed FGF23-αklotho-vitamin-D signalling and a deregulated electrolyte homeostasis. Moreover, this study identifies local tubular, possibly inflammation- or PTH- and/or FGF23-associated, adaptive mechanisms, impacting on Ca2+/Pi homeostasis, hence enabling new opportunities to target electrolyte disturbances that emerge as a consequence of CKD development. PMID:26566277

  20. [Atherosclerotic renal artery stenosis].

    PubMed

    Sauguet, A; Honton, B

    2014-12-01

    Atherosclerotic renal artery stenosis can cause ischaemic nephropathy and arterial hypertension. Renal artery stenosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Many patients with RAS may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the cardiovascular outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of RAS for cardiologists in the context of recent randomized clinical trials. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary edema, rapidly declining renal function and severe resistant hypertension. PMID:25450992

  1. Targeted inactivation of fh1 causes proliferative renal cyst development and activation of the hypoxia pathway.

    PubMed

    Pollard, Patrick J; Spencer-Dene, Bradley; Shukla, Deepa; Howarth, Kimberley; Nye, Emma; El-Bahrawy, Mona; Deheragoda, Maesha; Joannou, Maria; McDonald, Stuart; Martin, Alison; Igarashi, Peter; Varsani-Brown, Sunita; Rosewell, Ian; Poulsom, Richard; Maxwell, Patrick; Stamp, Gordon W; Tomlinson, Ian P M

    2007-04-01

    Germline mutations in the fumarate hydratase (FH) tumor suppressor gene predispose to leiomyomatosis, renal cysts, and renal cell cancer (HLRCC). HLRCC tumors overexpress HIF1alpha and hypoxia pathway genes. We conditionally inactivated mouse Fh1 in the kidney. Fh1 mutants developed multiple clonal renal cysts that overexpressed Hif1alpha and Hif2alpha. Hif targets, such as Glut1 and Vegf, were upregulated. We found that Fh1-deficient murine embryonic stem cells and renal carcinomas from HLRCC showed similar overexpression of HIF and hypoxia pathway components to the mouse cysts. Our data have shown in vivo that pseudohypoxic drive, resulting from HIF1alpha (and HIF2alpha) overexpression, is a direct consequence of Fh1 inactivation. Our mouse may be useful for testing therapeutic interventions that target angiogenesis and HIF-prolyl hydroxylation. PMID:17418408

  2. Cadmium and renal cancer

    SciTech Connect

    Il'yasova, Dora; Schwartz, Gary G. . E-mail: gschwart@wfubmc.edu

    2005-09-01

    Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine.

  3. Multicystic renal dysplasia.

    PubMed

    Nagaraj, V P; Ratnakar, K S

    2001-07-01

    Multicystic renal dysplasia, the most common form of cystic renal disease in the newborn period, is a clinically important consequence of abnormal nephrogenesis. It usually presents as an abdominal mass. The dysplasias are usually unilateral, but it can be bilateral, segmental or focal. The clinical presentation usually depends on the extent of the dysplastic involvement and the degree of the associated urinary obstruction. Here, we present a case of histologically multicystic renal dysplasia, which is ?bilateral. The left kidney showed typical radiological, gross and histopathological features of multicystic dysplasia, but the right kidney showed only radiological features of dysplastic cystic kidney. PMID:11479648

  4. Renal Replacement Therapy.

    PubMed

    Villa, Gianluca; Ricci, Zaccaria; Ronco, Claudio

    2015-10-01

    Renal replacement therapy (RRT) is a cornerstone in the clinical management of patients with acute kidney injury. Results from different studies agree that early renal support therapy (aimed to support the residual kidney function during early phases of organ dysfunction) may reduce mortality with respect to late RRT (aimed to substitute the complete loss of function during the advanced kidney insufficiency). Although it seems plausible that a timely initiation of RRT may be associated with improved renal and nonrenal outcomes in these patients, there is scarce evidence in literature to exactly identify the most adequate onset timing for RRT. PMID:26410148

  5. Role of TREM1-DAP12 in renal inflammation during obstructive nephropathy.

    PubMed

    Tammaro, Alessandra; Stroo, Ingrid; Rampanelli, Elena; Blank, Froilan; Butter, Loes M; Claessen, Nike; Takai, Toshiyuki; Colonna, Marco; Leemans, Jaklien C; Florquin, Sandrine; Dessing, Mark C

    2013-01-01

    Tubulo-interstitial damage is a common finding in the chronically diseased kidney and is characterized by ongoing inflammation and fibrosis leading to renal dysfunction and end-stage renal disease. Upon kidney injury, endogenous ligands can be released which are recognized by innate immune sensors to alarm innate immune system. A new family of innate sensors is the family of TREM (triggering receptor expressed on myeloid cell). TREM1 is an activating receptor and requires association with transmembrane adapter molecule DAP12 (DNAX-associated protein 12) for cell signaling. TREM1-DAP12 pathway has a cross-talk with intracellular signaling pathways of several Toll-like receptors (TLRs) and is able to amplify TLR signaling and thereby contributes to the magnitude of inflammation. So far, several studies have shown that TLRs play a role in obstructive nephropathy but the contribution of TREM1-DAP12 herein is unknown. Therefore, we studied TREM1 expression in human and murine progressive renal diseases and further investigated the role for TREM1-DAP12 by subjecting wild-type (WT), TREM1/3 double KO and DAP12 KO mice to murine unilateral ureter obstruction (UUO) model. In patients with hydronephrosis, TREM1 positive cells were observed in renal tissue. We showed that in kidneys from WT mice, DAP12 mRNA and TREM1 mRNA and protein levels were elevated upon UUO. Compared to WT mice, DAP12 KO mice displayed less renal MCP-1, KC and TGF-β1 levels and less influx of macrophages during progression of UUO, whereas TREM1/3 double KO mice displayed less renal MCP-1 level. Renal fibrosis was comparable in WT, TREM1/3 double KO and DAP12 KO mice. We conclude that DAP12, partly through TREM1/3, is involved in renal inflammation during progression of UUO. PMID:24358193

  6. Renal Mitochondrial Cytopathies

    PubMed Central

    Emma, Francesco; Montini, Giovanni; Salviati, Leonardo; Dionisi-Vici, Carlo

    2011-01-01

    Renal diseases in mitochondrial cytopathies are a group of rare diseases that are characterized by frequent multisystemic involvement and extreme variability of phenotype. Most frequently patients present a tubular defect that is consistent with complete De Toni-Debré-Fanconi syndrome in most severe forms. More rarely, patients present with chronic tubulointerstitial nephritis, cystic renal diseases, or primary glomerular involvement. In recent years, two clearly defined entities, namely 3243 A > G tRNALEU mutations and coenzyme Q10 biosynthesis defects, have been described. The latter group is particularly important because it represents the only treatable renal mitochondrial defect. In this paper, the physiopathologic bases of mitochondrial cytopathies, the diagnostic approaches, and main characteristics of related renal diseases are summarized. PMID:21811680

  7. Temperature-dependent elaboration of collagenase by the renal adenocarcinoma of the leopard frog, Rana pipiens.

    PubMed

    Ogilvie, D J; McKinnell, R G; Tarin, D

    1984-08-01

    Naturally occurring renal adenocarcinoma in North American leopard frogs, Rana pipiens, metastasize frequently (77%) when these ectothermic animals are kept in a warm environment but not when they are kept cold. We have found that explants of these tumors secrete collagenase, an enzyme capable of dissolving connective tissue fibers and found previously to be closely correlated with metastatic colony-forming capability of murine mammary tumors, and that the amount released sequentially rises and falls as the ambient temperature is shifted between metastasis-permissive and -inhibitory levels. In contrast, normal frog renal tissue has low collagenase output, unaffected by temperature changes. PMID:6331646

  8. 'Transcollateral' Renal Angioplasty for a Completely Occluded Renal Artery

    SciTech Connect

    Chandra, Subash; Chadha, Davinder S. Swamy, Ajay

    2011-02-15

    Percutaneous transluminal renal angioplasty with stenting has been effective in the control of hypertension, renal function, and pulmonary edema caused by atherosclerotic renal artery stenosis. However, the role of the procedure has not been fully established in the context of chronic total occlusion of renal artery. We report the successful use of this procedure in 57-year-old male patient who reported for evaluation of a recent episode of accelerated hypertension. A renal angiogram in this patient showed ostial stenosis of the right renal artery, which was filling by way of the collateral artery. Renal angioplasty for chronic total occlusion of right renal artery was successfully performed in a retrograde fashion through a collateral artery, thereby leading to improvement of renal function and blood pressure control.

  9. Disappearing renal calculus

    PubMed Central

    Cui, Helen; Thomas, Johanna; Kumar, Sunil

    2013-01-01

    We present a case of a renal calculus treated solely with antibiotics which has not been previously reported in the literature. A man with a 17 mm lower pole renal calculus and concurrent Escherichia coli urine infection was being worked up to undergo percutaneous nephrolithotomy. However, after a course of preoperative antibiotics the stone was no longer seen on retrograde pyelography or CT imaging. PMID:23580676

  10. Hereditary Renal Cancer Syndromes

    PubMed Central

    Haas, Naomi B.

    2013-01-01

    Inherited susceptibility to kidney cancer is a fascinating and complex topic. Our knowledge about types of genetic syndromes associated with an increased risk of disease is continually expanding. Currently, there are 10 syndromes associated with an increased risk of all types of renal cancer, which are reviewed herein. Clear cell renal cancer is associated with von Hippel Lindau disease, chromosome 3 translocations, PTEN hamartomatous syndrome and mutations in BAP1, as well as several of the genes encoding the proteins comprising the succinate dehydrogenase complex (SDHB/C/D). Type 1 papillary renal cancers arise in conjunction with germline mutations in MET and type 2 as part of Hereditary Leiomyomatosis and Renal Cell Cancer (FH mutations). Chromophone and oncocytic renal cancers are predominantly associated with Birt Hogg Dubé syndrome. Angiomyolipomas are commonly and their malignant counterpart epitheliod angiomyolipomas rarely are found in patients with Tuberous Sclerosis Complex. The targeted therapeutic options for the renal cancer associated with these diseases are just starting to expand, and are an area of active clinical research. PMID:24359990

  11. Murine Typhus, Reunion, France, 2011–2013

    PubMed Central

    Camuset, Guillaume; Socolovschi, Cristina; Moiton, Marie-Pierre; Kuli, Barbara; Foucher, Aurélie; Poubeau, Patrice; Borgherini, Gianandrea; Wartel, Guillaume; Audin, Héla; Raoult, Didier; Filleul, Laurent; Parola, Philippe; Pagès, Fréderic

    2015-01-01

    Murine typhus case was initially identified in Reunion, France, in 2012 in a tourist. Our investigation confirmed 8 autochthonous cases that occurred during January 2011–January 2013 in Reunion. Murine typhus should be considered in local patients and in travelers returning from Reunion who have fevers of unknown origin. PMID:25625653

  12. Improved renal ischemia tolerance in females influences kidney transplantation outcomes

    PubMed Central

    Aufhauser, David D.; Wang, Zhonglin; Murken, Douglas R.; Bhatti, Tricia R.; Wang, Yanfeng; Ge, Guanghui; Redfield, Robert R.; Abt, Peter L.; Wang, Liqing; Reese, Peter P.; Hancock, Wayne W.; Levine, Matthew H.

    2016-01-01

    Experimentally, females show an improved ability to recover from ischemia-reperfusion injury (IRI) compared with males; however, this sex-dependent response is less established in humans. Here, we developed a series of murine renal ischemia and transplant models to investigate sex-specific effects on recovery after IRI. We found that IRI tolerance is profoundly increased in female mice compared with that observed in male mice and discovered an intermediate phenotype after neutering of either sex. Transplantation of adult kidneys from either sex into a recipient of the opposite sex followed by ischemia at a remote time resulted in ischemia recovery that reflected the sex of the recipient, not the donor, revealing that the host sex determines recovery. Likewise, renal IRI was exacerbated in female estrogen receptor α–KO mice, while female mice receiving supplemental estrogen before ischemia were protected. We examined data from the United Network for Organ Sharing (UNOS) to determine whether there is an association between sex and delayed graft function (DGF) in patients who received deceased donor renal transplants. A multivariable logistic regression analysis determined that there was a greater association with DGF in male recipients than in female recipients. Together, our results demonstrate that sex affects renal IRI tolerance in mice and humans and indicate that estrogen administration has potential as a therapeutic intervention to clinically improve ischemia tolerance. PMID:27088798

  13. Regulatory T cells in immune-mediated renal disease.

    PubMed

    Ghali, Joanna R; Wang, Yuan Min; Holdsworth, Stephen R; Kitching, A Richard

    2016-02-01

    Regulatory T cells (Tregs) are CD4+ T cells that can suppress immune responses by effector T cells, B cells and innate immune cells. This review discusses the role that Tregs play in murine models of immune-mediated renal diseases and acute kidney injury and in human autoimmune kidney disease (such as systemic lupus erythematosus, anti-glomerular basement membrane disease, anti-neutrophil cytoplasmic antibody-associated vasculitis). Current research suggests that Tregs may be reduced in number and/or have impaired regulatory function in these diseases. Tregs possess several mechanisms by which they can limit renal and systemic inflammatory immune responses. Potential therapeutic applications involving Tregs include in vivo induction of Tregs or inducing Tregs from naïve CD4+ T cells or expanding natural Tregs ex vivo, to use as a cellular therapy. At present, the optimal method of generating a phenotypically stable pool of Tregs with long-lasting suppressive effects is not established, but human studies in renal transplantation are underway exploring the therapeutic potential of Tregs as a cellular therapy, and if successful may have a role as a novel therapy in immune-mediated renal diseases. PMID:26206106

  14. [Hereditary renal cancer].

    PubMed

    Sanz-Ortega, Julián; Olivier, Carlos; Pérez Segura, Pedro; Galante Romo, Isabel; San José Mansó, Luis; Saez, Mamen

    2009-02-01

    Kidney cancer is the tenth most common cause of cancer death. There are a growing number of genes known to be associated with an increased risk of specific types of kidney cancer. People with Von Hippel-Lindau syndrome have about a 40% risk of developing multiple bilateral clear cell kidney cancers. They can also develop retinal and brain hemangioblastoma, kidneys or pancreas cysts, pheochromocytoma and endolymphatic sac tumor. Four phenotypes with different renal cancer and pheocromocitoma risk have been described depending on the germline mutation. Hereditary papillary renal cell carcinoma syndrome has type 1 papillary renal cell carcinomas associated with protooncogene c-MET germline mutations. Birt-Hogg-Dubé syndrome has FLCN gene mutations associated with fibrofolliculomas, lung cysts with a high risk for spontaneous pneumothorax, and a 15% to 30% risk of kidney cancer (most classified as chromophobe carcinoma, oncocytoma or oncocytic hybrid, but clear cell and papillary kidney cancers have also been reported). Histopathological findings such as oncocytosis and oncocytic hybrids are very unusual outside the syndrome. Hereditary leiomyomatosis and renal cell cancer syndrome shows mutations of Fumarate hydratase gene and cutaneous leiomyomata in 76% of affected individuals, uterine leiomyomata in 100% of females, and unilateral, solitary, and aggressive papillary renal cancer in 10 to 16% of patients. A specific histopathological change is eosinophilic prominent nucleoli with a perinucleolar halo. Tuberous sclerosis complex is one of the most prevalent (1/5.800) hereditary syndromes where renal disease is the second leading cause of death, associated with angiomyolipomas (70%), renal cysts, oncocytomas or clear cell cancer. PMID:19418834

  15. Pharmacokinetics in renal disease.

    PubMed

    Levy, G

    1977-04-01

    The physiologic perturbations associated with renal disease can have a pronounced effect on the kinetics of elimination of drugs and their metabolites from the body. Drugs are ordinarily cleared from the body by a number of routes, each of which can be characterized by a clearance value. The sum of these clearances (renal, hepatic, etc.) is the total or body clearance which is inversely proportional to the steady-state plasma concentration produced by a given drug dosage regimen. The quantitative contribution of each route of elimination to the metabolic fate of a drug is proportional to the clearance value of that route relative to the body clearance. As a first approximation, the reduction in the renal clearance of a drug caused by renal disease is proportional to the reduction in the renal clearance of creatinine. The metabolic (biotransformation) clearance of many extensively plasma protein bound drugs is proportional to their free fraction (ratio of concentrations of free to total drug) in plasma. Since severe renal disease causes a reduction in the plasma protein binding of many drugs, the metabolic clearance of such drugs will be increased. The contribution of hemodialysis to the total clearance of a drug depends on the magnitude of the clearance obtained by hemodialysis relative to the magnitude of the body clearance of the drug on a day between dialyses. To compensate for the increased elimination of a drug during hemodialysis, the dosing rate (i.e., the dose per unit of time) must be increased by the factor (hemodialysis clearance and body clearance):body clearance, where body clearance is that during a day between dialyses. Further dosage compensation may be needed if body clearance is increased during hemodialysis due to decreased plasma protein binding of the drug. Under certain conditions, an increased accumulation of pharmacologically active drug metabolites during renal failure becomes a matter of serious concern. PMID:851113

  16. Renal consequences of obesity.

    PubMed

    Naumnik, Beata; Myśliwiec, Michał

    2010-08-01

    The worldwide prevalence of obesity and its associated metabolic and cardiovascular disorders has risen dramatically within the past 2 decades. Our objective is to review the mechanisms that link obesity with altered kidney function. Current evidence suggests that excess weight gain may be responsible for 65-75% of the risk for arterial hypertension. Impaired renal pressure natriuresis, initially due to increased renal tubular sodium reabsorption, is a key factor linking obesity with hypertension. Obesity increases renal sodium reabsorption by activating the renin-angiotensin and sympathetic nervous systems, and by altering intrarenal physical forces. Adipose tissue functions as an endocrine organ, secreting hormones/cytokines (e.g., leptin) which may trigger sodium retention and hypertension. Additionally, excess visceral adipose tissue may physically compress the kidneys, increasing intrarenal pressures and tubular reabsorption. Eventually, sustained obesity via hyperinsulinemia, due to resistance to insulin, causes hyperfiltration, resulting in structural changes in the kidneys--glomerular hyperthrophy and occasionally focal segmental glomerulosclerosis. The consequences of kidney injury are continuous loss of glomerular filtration rate, further increase of arterial pressure and escalation of cardiovascular morbidity and mortality. There is a growing awareness of the renal consequences of obesity, and considerable progress is being made in understanding its pathophysiology. Weight reduction results in lowered proteinuria. Aside from low sodium diet and exercises, more widespread use of renoprotective therapy (e.g., ACE inhibitors and statins) in treatment of hypertension in obese subjects should be advocated. Renal protection should result in reducing the cardiovascular complications of obesity. PMID:20671624

  17. Renal disease in Colombia.

    PubMed

    Gómez, Rafael Alberto

    2006-01-01

    Chronic renal disease represents a problem of public health in Colombia. Its prevalence has increased in last decade, with a prevalence of 44.7 patients per million (ppm) in 1993 to 294.6 ppm in 2004, considering that only 56.2% of the population has access to the health. This increase complies with the implementation of Law 100 of 1993, offering greater coverage of health services to the Colombian population. The cost of these pathologies is equivalent to the 2.49% of the budget for health of the nation. The three most common causes of renal failure are diabetes mellitus (DM; 30%), arterial hypertension (30%), and glomerulonephritis (7.85%). In incident patients, the DM accounts for 32.9%. The rate of global mortality is 15.8%, 17.4% in hemodialysis and 15.1% in peritoneal dialysis. In 2004, 467 renal transplants were made, 381 of deceased donor with an incidence of 10.3 ppm. The excessive cost of these pathologies can cause the nation's health care system to collapse if preventative steps are not taken. In December of 2004, the Colombian Association of Nephrology with the participation of the Latin American Society of Nephrology and Arterial Hypertension wrote the "Declaration of Bogotá," committing the state's scientific societies and promotional health companies to develop a model of attention for renal health that, in addition to implementing national registries, continues to manage renal disease. PMID:17162422

  18. Renal Tumor Biopsy Technique

    PubMed Central

    Zhang, Lei; Li, Xue-Song; Zhou, Li-Qun

    2016-01-01

    Objective: To review hot issues and future direction of renal tumor biopsy (RTB) technique. Data Sources: The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015. Study Selection: We included all the relevant articles on RTB technique in English, with no limitation of study design. Results: Computed tomography and ultrasound were usually used for guiding RTB with respective advantages. Core biopsy is more preferred over fine needle aspiration because of superior accuracy. A minimum of two good-quality cores for a single renal tumor is generally accepted. The use of coaxial guide is recommended. For biopsy location, sampling different regions including central and peripheral biopsies are recommended. Conclusion: In spite of some limitations, RTB technique is relatively mature to help optimize the treatment of renal tumors. PMID:27174334

  19. Tofacitinab in Renal Transplantation

    PubMed Central

    Zand, Martin S.

    2013-01-01

    Tofacitinib (tositinib, CP-690,550) is a small molecule inhibitor of Janus associated kinases, primarily JAK3 and JAK2, which inhibits cytokine signaling through the IL-2Rγ chain. In this article, we review the mechanism of action of tofacitinib, and pre-clinical and clinical data regarding its use in solid organ transplantation thus far. It is hoped that tofacitinib may form the basis for calcineurin-free immunosuppression, improving renal function while eliminating calcineurin inhibitor renal toxicity. Current studies suggest that tofacitinib is an effective immunosuppressive agent for renal transplantation, but it's use in current protocols carries an increased risk of CMV, BK, and EBV viral infection, anemia and leukopenia, and post-transplant lymphoproliferative disorder. PMID:23849222

  20. Contemporary Management of Renal Trauma

    PubMed Central

    Shoobridge, Jennifer J; Corcoran, Niall M; Martin, Katherine A; Koukounaras, Jim; Royce, Peter L; Bultitude, Matthew F

    2011-01-01

    In the management of renal trauma, surgical exploration inevitably leads to nephrectomy in all but a few specialized centers. With current management options, the majority of hemodynamically stable patients with renal injuries can be successfully managed nonoperatively. Improved radiographic techniques and the development of a validated renal injury scoring system have led to improved staging of injury severity that is relatively easy to monitor. This article reviews a multidisciplinary approach to facilitate the care of patients with renal injury. PMID:21941463

  1. Renal denervation and hypertension.

    PubMed

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  2. Autophagy in renal diseases.

    PubMed

    De Rechter, Stéphanie; Decuypere, Jean-Paul; Ivanova, Ekaterina; van den Heuvel, Lambertus P; De Smedt, Humbert; Levtchenko, Elena; Mekahli, Djalila

    2016-05-01

    Autophagy is the cell biology process in which cytoplasmic components are degraded in lysosomes to maintain cellular homeostasis and energy production. In the healthy kidney, autophagy plays an important role in the homeostasis and viability of renal cells such as podocytes and tubular epithelial cells and of immune cells. Recently, evidence is mounting that (dys)regulation of autophagy is implicated in the pathogenesis of various renal diseases, and might be an attractive target for new renoprotective therapies. In this review, we provide an overview of the role of autophagy in kidney physiology and kidney diseases. PMID:26141928

  3. Renal adaptation during hibernation

    PubMed Central

    Martin, Sandra L.; Jain, Swati; Keys, Daniel; Edelstein, Charles L.

    2013-01-01

    Hibernators periodically undergo profound physiological changes including dramatic reductions in metabolic, heart, and respiratory rates and core body temperature. This review discusses the effect of hypoperfusion and hypothermia observed during hibernation on glomerular filtration and renal plasma flow, as well as specific adaptations in renal architecture, vasculature, the renin-angiotensin system, and upregulation of possible protective mechanisms during the extreme conditions endured by hibernating mammals. Understanding the mechanisms of protection against organ injury during hibernation may provide insights into potential therapies for organ injury during cold storage and reimplantation during transplantation. PMID:24049148

  4. Physiology of the Renal Interstitium

    PubMed Central

    2015-01-01

    Long overlooked as the virtual compartment and then strictly characterized through descriptive morphologic analysis, the renal interstitium has finally been associated with function. With identification of interstitial renin- and erythropoietin-producing cells, the most prominent endocrine functions of the kidney have now been attributed to the renal interstitium. This article reviews the functional role of renal interstitium. PMID:25813241

  5. IL-10 regulates murine lupus.

    PubMed

    Yin, Zhinan; Bahtiyar, Gul; Zhang, Na; Liu, Lanzhen; Zhu, Ping; Robert, Marie E; McNiff, Jennifer; Madaio, Michael P; Craft, Joe

    2002-08-15

    MRL/MpJ-Tnfrsf6(lpr) (MRL/MpJ-Fas(lpr); MRL-Fas(lpr)) mice develop a spontaneous lupus syndrome closely resembling human systemic lupus erythematosus. To define the role of IL-10 in the regulation of murine lupus, IL-10 gene-deficient (IL-10(-/-)) MRL-Fas(lpr) (MRL-Fas(lpr) IL-10(-/-)) mice were generated and their disease phenotype was compared with littermates with one or two copies of an intact IL-10 locus (MRL-Fas(lpr) IL-10(+/-) and MRL-Fas(lpr) IL-10(+/+) mice, respectively). MRL-Fas(lpr) IL-10(-/-) mice developed severe lupus, with earlier appearance of skin lesions, increased lymphadenopathy, more severe glomerulonephritis, and higher mortality than their IL-10-intact littermate controls. The increased severity of lupus in MRL-Fas(lpr) IL-10(-/-) mice was closely associated with enhanced IFN-gamma production by both CD4(+) and CD8(+) cells and increased serum concentration of IgG2a anti-dsDNA autoantibodies. The protective effect of IL-10 in this lupus model was further supported by the observation that administration of rIL-10 reduced IgG2a anti-dsDNA autoantibody production in wild-type MRL-Fas(lpr) animals. In summary, our results provide evidence that IL-10 can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses. Modulation of the level of IL-10 may be of potential therapeutic benefit for human lupus. PMID:12165544

  6. Ablative therapies for renal tumors

    PubMed Central

    Ramanathan, Rajan; Leveillee, Raymond J.

    2010-01-01

    Owing to an increased use of diagnostic imaging for evaluating patients with other abdominal conditions, incidentally discovered kidney masses now account for a majority of renal tumors. Renal ablative therapy is assuming a more important role in patients with borderline renal impairment. Renal ablation uses heat or cold to bring about cell death. Radiofrequency ablation and cryoablation are two such procedures, and 5-year results are now emerging from both modalities. Renal biopsy at the time of ablation is extremely important in order to establish tissue diagnosis. Real-time temperature monitoring at the time of radiofrequency ablation is very useful to ensure adequacy of ablation. PMID:21789083

  7. Metabolomics and Renal Disease

    PubMed Central

    Rhee, Eugene P.

    2015-01-01

    Purpose of review This review summarizes recent metabolomics studies of renal disease, outlining some of the limitations of the literature to date. Recent findings The application of metabolomics in nephrology research has expanded from initial analyses of uremia to include both cross-sectional and longitudinal studies of earlier stages of kidney disease. Although these studies have nominated several potential markers of incident CKD and CKD progression, lack of overlap in metabolite coverage has limited the ability to synthesize results across groups. Further, direct examination of renal metabolite handling has underscored the substantial impact kidney function has on these potential markers (and many other circulating metabolites). In experimental studies, metabolomics has been used to identify a signature of decreased mitochondrial function in diabetic nephropathy and a preference for aerobic glucose metabolism in PKD; in each case, these studies have outlined novel therapeutic opportunities. Finally, as a complement to the longstanding interest in renal metabolite clearance, the microbiome has been increasingly recognized as the source of many plasma metabolites, including some with potential functional relevance to CKD and its complications. Summary The high-throughput, high-resolution phenotyping enabled by metabolomics technologies has begun to provide insight on renal disease in clinical, physiologic, and experimental contexts. PMID:26050125

  8. Renal imaging techniques.

    PubMed

    Hierholzer, K; Hierholzer, J

    1997-01-01

    The ancient approach to obtain an image of the kidneys (and other internal organs) was 'section-inspection-imaging' by drawing, painting, sculpturing, and modelling. The present study follows chronologically the development and use of sectioning techniques from ancient (often forbidden) methods to modern microdissection and maceration of silicone-rubber-injected tubules. Inspection evolved from the use of the naked eye to magnifying lenses, microscopes and finally electron microscopy. Pertinent examples such as the description of the kidneys as the site of urine formation, the visualization of loop structures in the renal medulla and the imaging of tight junction strands are discussed. Inspection or visualization of renal structure and function has been revolutionized by modern noninvasive techniques, such as X-ray imaging, imaging by radioisotopes, ultrasound, computer tomography and nuclear magnetic resonance. Pertinent examples are given demonstrating the potency of the various techniques. The contribution of computerized data evaluation is discussed. The development of micropuncture and microperfusion techniques has opened the field for direct imaging not only of renal (sub)structural details but also of functional parameters such as transtubular reabsorption rates, single glomerular capillary filtration and conductance of the paracellular pathway. We focus particularly on techniques specifically designed to visualize renal hemodynamic and transport parameters. PMID:9189257

  9. Malignancy after renal transplantation.

    PubMed

    Zeier, Martin; Hartschuh, Wolfgang; Wiesel, Manfred; Lehnert, Thomas; Ritz, Eberhard

    2002-01-01

    Malignancy following renal transplantation is an important medical problem during the long-term follow-up. The overall incidence of malignancy at this time is 3 to 5 times higher than in the general population. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). The type of malignancy is different in various countries and dependent on genetic and environmental factors. Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse are additional risk factors. Malignancy may even be transplanted by the graft. Previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and postmalignancy screening. Finally, every dialysis patient on the waiting list should undergo a regular screening program before and after renal transplantation to detect a potentially malignant tumor in an early stage. In addition to specific oncological treatment, managing a malignancy after renal transplantation should include modification of immunosuppression. PMID:11774131

  10. CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

    PubMed Central

    Sánchez-López, Elsa; Rayego, Sandra; Rodrigues-Díez, Raquel; Rodriguez, Javier Sánchez; Rodrigues-Díez, Raúl; Rodríguez-Vita, Juan; Carvajal, Gisselle; Aroeira, Luiz Stark; Selgas, Rafael; Mezzano, Sergio A.; Ortiz, Alberto; Egido, Jesús; Ruiz-Ortega, Marta

    2009-01-01

    Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-κB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-κB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-γ, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-κB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-κB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-κB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-κB pathway. PMID:19423687

  11. CTGF promotes inflammatory cell infiltration of the renal interstitium by activating NF-kappaB.

    PubMed

    Sánchez-López, Elsa; Rayego, Sandra; Rodrigues-Díez, Raquel; Rodriguez, Javier Sánchez; Rodrigues-Díez, Raúl; Rodríguez-Vita, Juan; Carvajal, Gisselle; Aroeira, Luiz Stark; Selgas, Rafael; Mezzano, Sergio A; Ortiz, Alberto; Egido, Jesús; Ruiz-Ortega, Marta

    2009-07-01

    Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-kappaB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-kappaB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-gamma, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-kappaB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-kappaB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-kappaB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-kappaB pathway. PMID:19423687

  12. RENAL INSUFFICIENCY FOLLOWING TRYPSIN INJECTION INTO THE RENAL ARTERIES.

    PubMed

    Friedman, M; Katz, L N

    1938-09-30

    1. The injection of trypsin into both renal arteries of the dog was found to cause an acute necrosis of large sections of the kidney, an immediate excretory insufficiency, and a transient hypertension. 2. Dogs surviving the acute phase of the trypsin injection, developed a chronic renal excretory insufficiency with no hypertension, despite the severity and duration of the renal excretory insufficiency. 3. The application of a Goldblatt clamp to the renal artery of one of the two kidneys, previously injected with trypsin, led to a rise in blood pressure which returned at once to normal when the ischemic kidney was removed, even though the pre-existing renal excretory insufficiency was augmented. This experience demonstrated unequivocally that chronic renal excretory insufficiency and hypertension are not directly related. 4. The application of a Goldblatt clamp to the renal artery of one kidney and the simultaneous injection of trypsin into the other led to a hypertension. The later removal of the ischemic kidney led to a severe renal excretory insufficiency, at the same time the pre-existing hypertension disappeared. This indicated again that renal excretory insufficiency and renal ischemia produced different phenomena and that the former had no direct relation to hypertension. PMID:19870800

  13. Murine retroviral vector producer cells survival and toxicity in the dog liver.

    PubMed

    Link, C J; Seregina, T; Levy, J P; Martin, M; Ackermann, M; Moorman, D W

    2000-01-01

    To develop a safe method to target gene delivery into intrahepatic tumors, we examined the toxicity of intrahepatic (IH) injection of retroviral vector producer cells (VPC) into the canine liver. VPC have been demonstrated to effectively transfer genes in vivo. To evaluate for adverse effects form xenogeneic cell transplantation, mongrel dogs were injected IH with 1 x 10(9) murine LTKOSN.2 VPC divided into three aliquots. The animals were then monitored for acute toxicity induced by the VPC. The intraoperative IH injections of the cells were tolerated without difficulty. Starting 7 days after IH injection, the dogs then received intravenous ganciclovir (GCV) twice daily (5 mg/kg) for 7 days. GCV treatment did not cause significant toxicities. Dogs underwent serial blood tests to evaluate bone marrow, renal, liver and immunological function. Complete blood counts, electrolytes, liver function and renal function tests remained normal except for mild elevations of alkaline phosphatase. Histologic examination of liver tissues from the IH injection site revealed no apparent normal tissue destruction induced by the VPC. Two of the four treated dogs underwent liver biopsy on day 3. These biopsy specimens were cultured and persistent, viable VPC were recovered. The dogs mounted an antibody response to the murine VPC that was first demonstrated 5 days post injection. PCR analysis demonstrated low level gene transfer into dog liver tissue. Overall, our results demonstrate that IH xenogeneic VPC injections are not accompanied by significant adverse effects over a 1 month period following administration into the canine liver. These data support the safety aspects of using murine VPC in Phase I clinical trials. PMID:11212842

  14. Expression of intronic miRNAs and their host gene Igf2 in a murine unilateral ureteral obstruction model

    PubMed Central

    Li, N.Q.; Yang, J.; Cui, L.; Ma, N.; Zhang, L.; Hao, L.R.

    2015-01-01

    The objective of this study was to determine the expression of miR-483 and miR-483* and the relationship among them, their host gene (Igf2), and other cytokines in a murine model of renal fibrosis. The extent of renal fibrosis was visualized using Masson staining, and fibrosis was scored 3 days and 1 and 2 weeks after unilateral ureteral obstruction (UUO). Expression of miR-483, miR-483* and various cytokine mRNAs was detected by real-time polymerase chain reaction (PCR). Expression of miR-483 and miR-483* was significantly upregulated in the UUO model, particularly miR-483 expression was the greatest 2 weeks after surgery. Additionally, miR-483 and miR-483* expression negatively correlated with Bmp7 expression and positively correlated with Igf2, Tgfβ, Hgf, and Ctgf expression, as determined by Pearson's correlation analysis. Hgf expression significantly increased at 1 and 2 weeks after the surgery compared to the control group. This study showed that miR-483 and miR-483* expression was upregulated in a murine UUO model. These data suggest that miR-483 and miR-483* play a role in renal fibrosis and that miR-483* may interact with miR-483 in renal fibrosis. Thus, these miRNAs may play a role in the pathogenesis of renal fibrosis and coexpression of their host gene Igf2. PMID:25831208

  15. Dental management of people with renal disease and renal transplants.

    PubMed

    Ferguson, C A; Whyman, R A

    1998-09-01

    Chronic renal failure is the result of progressive loss of functioning nephrons leading to loss of renal function and accumulation of excretory products. Loss of the regulatory and excretory functions of the kidneys causes oral manifestations and multiple complications which have implications for dental care. Dental management of patients with renal failure and renal transplants involves consideration of specific haematological and cardiovascular effects, and implications for the prescribing and use of pharmaceuticals. It also requires the dentist to appreciate the potential for involvement of multiple organ systems in the disease process and the implications this has for dental care. The orofacial manifestations of chronic renal failure are secondary to systemic manifestations and are not specific to the diagnosis of end-stage renal disease. PMID:9775650

  16. Apoptosis in irradiated murine tumors.

    PubMed

    Stephens, L C; Ang, K K; Schultheiss, T E; Milas, L; Meyn, R E

    1991-09-01

    Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors. PMID:1886987

  17. Chemoimmunotherapy of murine bladder cancer.

    PubMed

    Stogdill, B J; Lamm, D L; Livingston, R B

    1981-11-01

    The lethality of invasive transitional cell carcinoma (TCC) has prompted a search for effective, minimally toxic, adjuvant therapy. Such agents were evaluated in a murine bladder cancer (MBT2) model which parallels the clinical disease. One hundred C3H/He mice were inoculated i.d. with 2.5 x 10(4) viable MBT2 tumor cells and randomized to receive either normal saline (control), cis-Platinum (CPT), cyclophosphamide (CY), methotrexate (MTX), BCG, (CY + MTX), or (CY + MTX + BCG). Chemotherapy was given intraperitoneally weekly starting on day 7 after inoculation. Immunotherapy was given intralesionally on days 1 and 10 only. All mice were treated for 5 weeks followed by 5 weeks of observation. At 5 weeks, tumors of mice receiving cyclophosphamide alone or either of the combinations of therapy were smaller (P less than 0.01) than tumors of controls or other single agents alone. Each regimen increased survival, but only the combination regimen increase survival significantly (P less than 0.01). In the doses and schedule used in this model. Combination chemotherapy and chemoimmunotherapy significantly delay tumor growth and increase duration of survival (P less than 0.01) when compared with controls or single agent groups. PMID:7298287

  18. Improvement of renal function after opening occluded atherosclerotic renal arteries.

    PubMed

    Kanamori, Hiroshi; Toma, Masanao; Fukatsu, Atsushi

    2009-09-01

    Percutaneous transluminal renal angioplasty (PTRA) with stenting has been effective in the control of hypertension, renal function and pulmonary edema caused by atherosclerotic renal artery stenosis (ARAS). However, concerning the viability of renal function, this procedure has not been fully established, especially in the presence of renal atrophy or severe renal parenchymal disease. We report a dramatically improved case of acute renal failure caused by acute worsening ARAS treated by stenting. A 72-year-old female was admitted for accelerated renal dysfunction (serum ceatinine; 1.2-2.3 mg/dl) and hypertension (190/100 mmHg). At 10 days after admission, the patient's serum ceatinine increased to 6.7 mg/dl, her pulmonary edema was exaggerated and hemodialysis was required. Ultrasonography showed bilateral high-echoic kidneys, but no apparent finding of renal artery stenosis (RAS). At day 15, computed tomographic angiography indicated bilateral ostial RAS. Renal angiography demonstrated total occlusion of the right and severe (90%) disease in the left. ARAS was diagnosed by intravascular ultrasonography. The guidewire was inserted in both renal arteries, PTRA with stenting was performed in the right and a stent was directly implanted in the left. Immediately, each kidney enlarged to almost normal size, leading to satisfactory urination. She was released from hemodialysis the next day since her serum creatinine was normal and the pulmonary edema was improved. Although there is still no reliable prognostic factor including resistive index or kidney size, it is important that PTRA with stenting in ARAS should be considered in a case of accelerated renal dysfunction because of the possible improvement. PMID:19726830

  19. Bilateral renal calculi

    PubMed Central

    Sreenevasan, G

    1974-01-01

    Bilateral renal calculi were present in 114 (10.7%) of 1,070 cases of proved urinary calculus admitted to the Urological Department of the General Hospital, Kuala Lumpur, during the period November 1968—May 1973. The management of bilateral renal calculi is discussed with reference to the first 100 cases in this series. The introduction of renography has greatly facilitated the decision as to which kidney should be operated on first. The management of patients with and without uraemia is discussed and the use of the modified V and V—Y incisions for the removal of staghorn calculi is described. Complications and results are briefly reviewed. ImagesFig. 1Fig. 4Fig. 6Fig. 7 PMID:4845653

  20. Inherited renal carcinomas.

    PubMed

    Kawashima, Akira; Young, Scott W; Takahashi, Naoki; King, Bernard F; Atwell, Thomas D

    2016-06-01

    Hereditary forms of kidney carcinoma account for 5-8% of all malignant kidney neoplasms. The renal tumors are often multiple and bilateral and occur at an earlier age. Each of the hereditary kidney carcinoma syndromes is associated with specific gene mutations as well as a specific histologic type of kidney carcinoma. The presence of associated extrarenal manifestations may suggest a hereditary kidney cancer syndrome. Radiology is most commonly used to screen and manage patients with hereditary kidney cancer syndromes. This manuscript reviews the clinical and imaging findings of well-defined inherited kidney cancer syndromes including von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, hereditary papillary renal carcinoma syndrome, hereditary leiomyomatosis and RCC syndrome, tuberous sclerosis complex, and Lynch syndrome. PMID:27108134

  1. Renal injury in sport.

    PubMed

    Holmes, F Clarke; Hunt, Jeremy J; Sevier, Thomas L

    2003-04-01

    Hematuria is the most common presenting sign of renal injury. Its presence in athletes may indicate a benign entity such as exercise-induced hematuria or a more serious injury in the presence of trauma. Exercise-induced hematuria can originate in the kidney, bladder, urethra, or prostate. The type of activity, as well as activity duration and intensity, contributes to its development. A wide differential diagnosis must be considered if hematuria persists longer than 24 to 72 hours. Trauma to the kidney can occur from a direct blow or deceleration; contact and collision sports are most commonly involved. Fortunately, most sports-related renal trauma is mild, and can be managed expectantly. A sporting injury rarely results in nephrectomy. Determining return to play for the athlete with a single kidney remains a controversial issue that requires patient education and an individualized approach. PMID:12831667

  2. Renal stones in pregnancy

    PubMed Central

    Gibbons, Norma; DasGupta, Ranan

    2014-01-01

    Diagnosis and treatment of renal stones during pregnancy is a complex problem. Risks to the fetus from ionising radiation and interventional procedures need to be balanced with optimising clinical care for the mother. Management of such patients requires a clear understanding of available options, with a multidisciplinary team approach. In this review, we discuss the role of different diagnostic tests including ultrasound, magnetic resonance urography, and computerized tomography. We also provide an update on recent developments in the treatment of renal stones during pregnancy. Expectant management remains first-line treatment. Where definitive treatment of the stone is required, new evidence suggests that ureteroscopic stone removal may be equally safe, and possibly better than traditional temporising procedures.

  3. Renal Medullary Interstitial Cells

    NASA Astrophysics Data System (ADS)

    Rao, Reena; Hao, Chuan-Ming; Breyer, Matthew D.

    2007-04-01

    Renal medullary interstitial cells (RMICs) are specialized fibroblast-like cells that reside in the renal medulla among the vasa recta, the thin limbs of Henle's loop, and medullary collecting ducts. These cells are characterized by abundant lipid droplets in the cytoplasm. The lipid droplets are composed of triglycerides, cholesterol esters and free long-chain fatty acids, including arachidonic acid. RMICs are also a major site of cyclooxygenase2 (COX-2) expression, and thus a major site of COX-2 derived prostanoid biosynthesis. RMICs are also a potential target of hormones such as angiotensin II and endothelin. The RMIC COX-2 expression and the abundance of lipid droplets change with salt and water intake. These properties of RMICs are consistent with an important role of these cells in modulating physiologic and pathologic processes of the kidney.

  4. Renal Clearance of Nanoparticles

    PubMed Central

    Choi, Hak Soo; Liu, Wenhao; Misra, Preeti; Tanaka, Eiichi; Zimmer, John P.; Ipe, Binil Itty; Bawendi, Moungi G.; Frangioni, John V.

    2008-01-01

    SUMMARY The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using quantum dots (QDs) as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter (HD) by over 15 nm and prevented renal excretion. A final HD smaller than 5.5 nm resulted in rapid and efficient urinary excretion, and elimination of QDs from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications. PMID:17891134

  5. Effects of sodium fluoride on immune response in murine macrophages.

    PubMed

    De la Fuente, Beatriz; Vázquez, Marta; Rocha, René Antonio; Devesa, Vicenta; Vélez, Dinoraz

    2016-08-01

    Excessive fluoride intake may be harmful for health, producing dental and skeletal fluorosis, and effects upon neurobehavioral development. Studies in animals have revealed effects upon the gastrointestinal, renal and reproductive systems. Some of the disorders may be a consequence of immune system alterations. In this study, an in vitro evaluation is made of fluoride immunotoxicity using the RAW 264.7 murine macrophage line over a broad range of concentrations (2.5-75mg/L). The results show that the highest fluoride concentrations used (50-75mg/L) reduce the macrophage population in part as a consequence of the generation of reactive oxygen and/or nitrogen species and consequent redox imbalance, which in turn is accompanied by lipid peroxidation. A decrease in the expression of the antiinflammatory cytokine Il10 is observed from the lowest concentrations (5mg/L). High concentrations (50mg/L) in turn produce a significant increase in the proinflammatory cytokines Il6 and Mip2 from 4h of exposure. In addition, cell phagocytic capacity is seen to decrease at concentrations of ≥20mg/L. These data indicate that fluoride, at high concentrations, may affect macrophages and thus immune system function - particularly with regard to the inflammation autoregulatory processes, in which macrophages play a key role. PMID:26965474

  6. Renal Infarction Caused by Isolated Spontaneous Renal Artery Intramural Hematoma

    PubMed Central

    Park, Sihyung; Lee, Ga Hee; Jin, Kyubok; Park, Kang Min; Kim, Yang Wook; Park, Bong Soo

    2015-01-01

    Patient: Male, 46 Final Diagnosis: Renal infarction Symptoms: Flank pain Medication: — Clinical Procedure: CT Specialty: Nephrology Objective: Rare disease Background: Acute renal infarction is an uncommon condition resulting from an obstruction or a decrease in renal arterial blood flow. Isolated spontaneous renal artery intramural hematoma is a rare cause of renal infarction. Case Report: A 46-year-old healthy man presented to our emergency room because of sudden onset of severe right flank pain. An enhanced abdominal computed tomography scan showed a low-attenuated lesion in the lateral portion of the right kidney but no visible thromboembolisms in the main vessels. Computed tomography angiography revealed acute infarction resulting from intramural hematoma of the anterior segmental artery of the right kidney, with distal occlusion. Conclusions: The rarity and non-specific clinical presentation of renal infarction often lead to a delayed diagnosis that may result in impaired renal function. Clinical suspicion is important in the early diagnosis, and intramural hematoma of the renal artery should be considered the cause of renal infarction even in healthy patients without pre-disposing factors. PMID:26596500

  7. Simvastatin prevents vascular complications in the chronic reactive oxygen species murine model of systemic sclerosis.

    PubMed

    Bitto, Alessandra; Bagnato, Gian Luca; Pizzino, Gabriele; Roberts, William Neal; Irrera, Natasha; Minutoli, Letteria; Russo, Giuseppina; Squadrito, Francesco; Saitta, Antonino; Bagnato, Gian Filippo; Altavilla, Domenica

    2016-05-01

    Aims Systemic sclerosis (SSc) is characterized by vasculopathy and organ fibrosis. Although microvascular alterations are very well characterized, structural and functional abnormalities of large vessels are not well defined. Therefore, we evaluated the effect of simvastatin administration on aortic and small renal arteries thickening, and on myofibroblasts differentiation in a murine model of SSc. Methods and results SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl, 100 μl) for 6 weeks. Mice (n = 23) were randomized to receive: HOCl (n = 10); HOCl plus simvastatin (40 mg/kg; n = 8); or vehicle (n = 5). Simvastatin administration started 30 min after HOCl injection, and up to week 6. Aortic and small renal arteries intima-media thickness was evaluated by histological analysis. Immunostaining for α-smooth muscle actin (SMA), vascular endothelial growth factor receptor 2 (VEGFR2), and CD31 in aortic tissues was performed to evaluate myofibroblast differentiation and endothelial markers.In HOCl-treated mice, intima-media thickening with reduced lumen diameter was observed in the aorta and in small renal arteries and simvastatin administration prevented this increase. Aortic and renal myofibroblasts count, as expressed by α-SMA + density, was lower in the group of mice treated with simvastatin compared to HOCl-treated mice. Simvastatin prevented the reduction in VEGFR2 and CD31 expression induced by HOCl. Conclusions The administration of simvastatin regulates collagen deposition in the aortic tissues and in the small renal arteries by modulating myofibroblasts differentiation and vascular markers. Further studies are needed to better address the effect of statins in the macrovascular component of SSc. PMID:26846205

  8. Renal Replacement Therapy.

    PubMed

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients' clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the "Tower of Babel" of critical care nephrology. PMID:26918174

  9. Renal Replacement Therapy

    PubMed Central

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology. PMID:26918174

  10. Drug-induced renal disorders.

    PubMed

    Ghane Shahrbaf, Fatemeh; Assadi, Farahnak

    2015-01-01

    Drug-induced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acid-base and fluid electrolytes disorders. Certain drugs can cause alteration in intraglomerular hemodynamics, inflammatory changes in renal tubular cells, leading to acute kidney injury (AKI), tubulointerstitial disease and renal scarring. Drug-induced nephrotoxicity tends to occur more frequently in patients with intravascular volume depletion, diabetes, congestive heart failure, chronic kidney disease, and sepsis. Therefore, early detection of drugs adverse effects is important to prevent progression to end-stage renal disease. Preventive measures requires knowledge of mechanisms of drug-induced nephrotoxicity, understanding patients and drug-related risk factors coupled with therapeutic intervention by correcting risk factors, assessing baseline renal function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations. PMID:26468475

  11. Percutaneous renal cryoablation: current status.

    PubMed

    Mazaris, Evangelos M; Varkarakis, Ioannis M; Solomon, Stephen B

    2008-04-01

    Over the last 13 years, renal cryoablation has emerged as a promising technique for the treatment of solid renal tumors. The improvement in imaging modalities such as ultrasound, computed tomography and MRI, as well as the introduction of thinner probes, has led to the spread of the minimally invasive percutaneous approach. We review the historical background of percutaneous renal cryoablation (PRC), present its basic principles, mention the contemporary clinical data and outcomes of this technique and suggest future directions for its wider application in renal tumors. Early results have demonstrated that it may offer an alternative for the treatment of small renal masses with the advantages of minimal complications, spared renal function, decreased overall costs and equivalent oncologic efficacy. Long-term results are required in order to apply this minimally invasive technique to a broader spectrum of patients. PMID:18407738

  12. Anatomy and nomenclature of murine lymph nodes: Descriptive study and nomenclatory standardization in BALB/cAnNCrl mice.

    PubMed

    Van den Broeck, Wim; Derore, Annie; Simoens, Paul

    2006-05-30

    Murine lymph nodes are intensively studied but often assigned incorrectly in scientific papers. In BALB/cAnNCrl mice, we characterized a total of 22 different lymph nodes. Peripheral nodes were situated in the head and neck region (mandibular, accessory mandibular, superficial parotid, cranial deep cervical nodes), and at the forelimb (proper axillary, accessory axillary nodes) and hindlimb (subiliac, sciatic, popliteal nodes). Intrathoracic lymph nodes included the cranial mediastinal, tracheobronchal and caudal mediastinal nodes. Abdominal lymph nodes were associated with the gastrointestinal tract (gastric, pancreaticoduodenal, jejunal, colic, caudal mesenteric nodes) or were located along the major intra-abdominal blood vessels (renal, lumbar aortic, lateral iliac, medial iliac and external iliac nodes). Comparative and nomenclative aspects of murine lymph nodes are discussed. The position of the lymph nodes of BALB/cAnNCrl mice is summarized and illustrated in an anatomical chart containing proposals for both an official nomenclature according to the Nomina Anatomica Veterinaria and English terms. PMID:16624319

  13. Multiple oncocytomas and renal carcinoma

    SciTech Connect

    Velasquez, G.; Glass, T.A.; D'Souza, V.J.; Formanek, A.G.

    1984-01-01

    Renal oncocytoma, although rare, is being diagnosed more frequently, and criteria to differentiate it from other tumors have been described. Multiple oncocytomas have been reported, but an association between multiple oncocytomas and renal carcinoma in the same kidney has not been described. The authors report a case with two oncocytomas and a renal carcinoma in the right kidney as well as a right adrenal adenoma.

  14. INCREASED SUSCEPTIBILITY TO PARATHION POISONING FOLLOWING MURINE CYTOMEGALOVIRUS INFECTION

    EPA Science Inventory

    Increased Susceptibility to Parathion Poisoning Following Murine Cytomegalovirus Infection. Fifty to 100 percent mortality occurred in mice treated with ordinarily sublethal doses of parathion 2 to 5 days post infection with murine cytomegalovirus (MCMV). These mortalities appear...

  15. Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury.

    PubMed

    Zhao, Wen-Yu; Zhang, Lei; Sui, Ming-Xing; Zhu, You-Hua; Zeng, Li

    2016-01-01

    Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD(+) dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model. SIRT3 deletion increased the CLP-induced upregulation of the NLRP3 inflammasome and apoptosis-associated speck-like protein, resulting in the activation of oxidative stress, increased production of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and the enhancement of apoptosis, and these effects were reversed by antioxidant NAC. Our results suggest that SIRT3 plays a protective role against mitochondrial damage in the kidney by attenuating ROS production, inhibiting the NRLP3 inflammasome, attenuating oxidative stress, and downregulating IL-1β and IL-18. PMID:27620507

  16. Murine typhus in Kuwait in 1978

    PubMed Central

    Al-Awadi, Abdul Rahman; Al-Kazemi, Nouri; Ezzat, Gaafar; Saah, Alfred J.; Shepard, Charles; Zaghloul, Talaat; Gherdian, Beatriz

    1982-01-01

    Murine typhus occurred in 254 individuals in Kuwait between April and August 1978; 81% of patients were aged between 15 and 44 years, and 63% were male. The highest attack rate occurred among people in the lowest socioeconomic class. The outbreak coincided with a period of high rat and flea density. A study of the first 104 cases suggested that infection was acquired in the home, but a case — control study revealed no significant differences between patients and control subjects in terms of exposure to rats or domestic animals, and other factors. This suggests that murine typhus is hyperendemic rather than epidemic in Kuwait. The disease is being controlled through reduction of both flea and rat populations. Murine typhus may be much more common in many areas than is generally realized, and its status should be re-evaluated regularly in all known and potential foci. PMID:6980739

  17. Murine Norovirus: Propagation, Quantification and Genetic Manipulation

    PubMed Central

    Hwang, Seungmin; Alhatlani, Bader; Arias, Armando; Caddy, Sarah L; Christodoulou, Constantina; Cunha, Juliana; Emmott, Ed; Gonzalez-Hernandez, Marta; Kolawole, Abimbola; Lu, Jia; Rippinger, Christine; Sorgeloos, Frédéric; Thorne, Lucy; Vashist, Surender; Goodfellow, Ian

    2014-01-01

    Murine norovirus (MNV) is a positive-sense, plus-stranded RNA virus in the Caliciviridae family. It is the most common pathogen in biomedical research colonies. MNV is also related to the human noroviruses, which cause the majority of non-bacterial gastroenteritis worldwide. Like the human noroviruses, MNV is an enteric virus that replicates in the intestine and is transmitted by the fecal-oral route. MNV replicates in murine macrophages and dendritic cells in cells in culture and in the murine host. This virus is often used to study mechanisms in norovirus biology, because the human noroviruses are refractory to growth in cell culture. MNV combines the availability of a cell culture and reverse genetics system with the ability to study infection in the native host. Herein, we describe a panel of techniques that are commonly used to study MNV biology. PMID:24789596

  18. The renal scan in pregnant renal transplant patients

    SciTech Connect

    Goldstein, H.A.; Ziessman, H.A.; Fahey, F.H.; Collea, J.V.; Alijani, M.R.; Helfrich, G.B.

    1985-05-01

    With the greater frequency of renal transplant surgery, more female pts are becoming pregnant and carrying to term. In the renal allograft blood vessels and ureter may be compressed resulting in impaired renal function and/or, hypertension. Toxemia of pregnancy is seen more frequently than normal. Radionuclide renal scan monitoring may be of significant value in this high risk obstetrical pt. After being maintained during the pregnancy, renal function may also deteriorate in the post partum period. 5 pregnant renal transplant pts who delivered live babies had renal studies with Tc-99m DTPA to assess allograft perfusion and function. No transplanted kidney was lost during or after pregnancy as a result of pregnancy. No congenital anomalies were associated with transplant management. 7 studies were performed on these 5 pts. The 7 scans all showed the uterus/placenta. The bladder was always distorted. The transplanted kidney was rotated to a more vertical position in 3 pts. The radiation dose to the fetus is calculated at 0.024 rad/mCi administered. This study demonstrates the anatomic and physiologic alterations expected in the transplanted kidney during pregnancy when evaluated by renal scan and that the radiation burden may be acceptable in management of these pts.

  19. Early diagnosis of renal disease and renal failure.

    PubMed

    Lees, George E

    2004-07-01

    The main goal of early diagnosis of renal disease and renal failure in dogs and cats is to enable timely application of therapeutic interventions that may slow or halt disease progression. Strategies for early diagnosis of renal disease use urine tests that detect proteinuria that is a manifestation of altered glomerular permselectivity or impaired urine-concentrating ability as well blood tests to evaluate plasma creatinine concentration. Animals with progressive renal disease should be carefully investigated and treated appropriately. Animals with mild, possibly nonprogressive, renal disease should be monitored adequately to detect any worsening trends,which should lead to further investigation and treatment even if the increments of change are small. PMID:15223206

  20. Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies.

    PubMed

    Waters, Alicia M; Stewart, Jerry E; Atigadda, Venkatram R; Mroczek-Musulman, Elizabeth; Muccio, Donald D; Grubbs, Clinton J; Beierle, Elizabeth A

    2016-05-01

    Rare tumors of solid organs remain some of the most difficult pediatric cancers to cure. These difficult tumors include rare pediatric renal malignancies, such as malignant rhabdoid kidney tumors (MRKT) and non-osseous renal Ewing sarcoma, and hepatoblastoma, a pediatric liver tumor that arises from immature liver cells. There are data in adult renal and hepatic malignancies demonstrating the efficacy of retinoid therapy. The investigation of retinoic acid therapy in cancer is not a new strategy, but the widespread adoption of this therapy has been hindered by toxicities. Our laboratory has been investigating a novel synthetic rexinoid, UAB30, which exhibits a more favorable side-effect profile. In this study, we hypothesized that UAB30 would diminish the growth of tumor cells from both rare renal and liver tumors in vitro and in vivo We successfully demonstrated decreased cellular proliferation, invasion and migration, cell-cycle arrest, and increased apoptosis after treatment with UAB30. Additionally, in in vivo murine models of human hepatoblastoma or rare human renal tumors, there were significantly decreased tumor xenograft growth and increased animal survival after UAB30 treatment. UAB30 should be further investigated as a developing therapeutic in these rare and difficult-to-treat pediatric solid organ tumors. Mol Cancer Ther; 15(5); 911-21. ©2016 AACR. PMID:26873726

  1. Contemporary Renal Cell Cancer Epidemiology

    PubMed Central

    Chow, Wong-Ho; Devesa, Susan S.

    2010-01-01

    We analyzed renal cell cancer incidence patterns in the United States and reviewed recent epidemiologic evidence with regard to environmental and host genetic determinants of renal cell cancer risk. Renal cell cancer incidence rates continued to rise among all racial/ethnic groups in the United States, across all age groups, and for all tumor sizes, with the most rapid increases for localized stage disease and small tumors. Recent cohort studies confirmed the association of smoking, excess body weight, and hypertension with an elevated risk of renal cell cancer, and suggested that these factors can be modified to reduce the risk. There is increasing evidence for an inverse association between renal cell cancer risk and physical activity and moderate intake of alcohol. Occupational exposure to TCE has been positively associated with renal cell cancer risk in several recent studies, but its link with somatic mutations of the VHL gene has not been confirmed. Studies of genetic polymorphisms in relation to renal cell cancer risk have produced mixed results, but genome-wide association studies with larger sample size and a more comprehensive approach are underway. Few epidemiologic studies have evaluated risk factors by subtypes of renal cell cancer defined by somatic mutations and other tumor markers. PMID:18836333

  2. UNITED STATES RENAL DATA SYSTEM

    EPA Science Inventory

    The United States Renal Data System (USRDS) is a national data system that collects, analyzes, and distributes information about end-stage renal disease (ESRD) in the United States. The USRDS is funded directly by the National Institute of Diabetes and Digestive and Kidney Diseas...

  3. Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

    PubMed Central

    Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

    2012-01-01

    Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

  4. Renal biopsy: methods and interpretation.

    PubMed

    Vaden, Shelly L

    2004-07-01

    Renal biopsy most often is indicated in the management of dogs and cats with glomerular disease or acute renal failure. Renal biopsy can readily be performed in dogs and cats via either percutaneous or surgical methods. Care should be taken to ensure that proper technique is used. When proper technique is employed and patient factors are properly addressed, renal biopsy is a relatively safe procedure that minimally affects renal function. Patients should be monitored during the post biopsy period for severe hemorrhage, the most common complication. Accurate diagnosis of glomerular disease, and therefore, accurate treatment planning,requires that the biopsy specimens not only be evaluated by light microscopy using special stains but by electron and immunofluorescent microscopy. PMID:15223207

  5. Renal failure after ruptured aneurysm.

    PubMed

    Abbott, W M; Abel, R M; Beck, C H; Fischer, J E

    1975-09-01

    The effectiveness of an intravenous nutritional program plus aggressive dialysis was studied in 32 patients with renal failure following ruptured abdominal aortic aneurysm. Each patient was managed postoperatively with a renal failure fluid regimen, consisting of the eight essential amino acids plus dextrose in conjunction with peritoneal dialysis and hemodialysis. This regimen induced salutary metabolic effects temporarily improving the patient's condition in most instances. No technical or septic complications associated with the intravenous dietary therapy occurred. However, the incidence of recovery of renal function was low, and the overall patient survival was only 12.5%. The experience indicates that although this program has been shown to be efficacious in some patients with acute renal failure, it seems of little benefit in those whose renal failure follows ruptured aortic aneurysm. PMID:808197

  6. Renal Denervation: Where to Now?

    PubMed

    Wimmer, Neil J; Mauri, Laura

    2015-12-01

    Resistant hypertension remains a growing problem worldwide. Renal sympathetic denervation was thought to be a new method for the treatment for resistant hypertension. Early studies demonstrated a marked benefit in patients who underwent renal denervation procedures, but the pivotal SYMPLICITY 3-HTN trial, the only sham-controlled randomized trial performed, did not show a benefit for patients treated with the procedure compared to sham. There is still much to learn about the physiology and anatomy of renal sympathetic pathways as well as careful attention to medication adherence in order to understand the role of renal sympathetic denervation in treating hypertensive patients. While renal denervation technology remains available in clinical practice outside of the USA, we expect further development of this technology in the upcoming years and the continued evaluation of this technology in patients with hypertension as well as other disease states to fully understand its role. PMID:26482759

  7. Renal transplantation in infants.

    PubMed

    Jalanko, Hannu; Mattila, Ilkka; Holmberg, Christer

    2016-05-01

    Renal transplantation (RTx) has become an accepted mode of therapy in infants with severe renal failure. The major indications are structural abnormalities of the urinary tract, congenital nephrotic syndrome, polycystic diseases, and neonatal kidney injury. Assessment of these infants needs expertise and time as well as active treatment before RTx to ensure optimal growth and development, and to avoid complications that could lead to permanent neurological defects. RTx can be performed already in infants weighing around 5 kg, but most operations occur in infants with a weight of 10 kg or more. Perioperative management focuses on adequate perfusion of the allograft and avoidance of thrombotic and other surgical complications. Important long-term issues include rejections, infections, graft function, growth, bone health, metabolic problems, neurocognitive development, adherence to medication, pubertal maturation, and quality of life. The overall outcome of infant RTx has dramatically improved, with long-term patient and graft survivals of over 90 and 80 %, respectively. PMID:26115617

  8. A Polymeric Nanomedicine Diminishes Inflammatory Events in Renal Tubular Cells

    PubMed Central

    Ocaña-Salceda, Carlos; Sancho, Mónica; Orzáez, Mar; Messeguer, Angel; Ruiz-Ortega, Marta; Egido, Jesús; Vicent, María J.; Ortiz, Alberto; Ramos, Adrián M.

    2013-01-01

    The polyglutamic acid/peptoid 1 (QM56) nanoconjugate inhibits apoptosis by interfering with Apaf-1 binding to procaspase-9. We now describe anti-inflammatory properties of QM56 in mouse kidney and renal cell models. In cultured murine tubular cells, QM56 inhibited the inflammatory response to Tweak, a non-apoptotic stimulus. Tweak induced MCP-1 and Rantes synthesis through JAK2 kinase and NF-κB activation. Similar to JAK2 kinase inhibitors, QM56 inhibited Tweak-induced NF-κB transcriptional activity and chemokine expression, despite failing to inhibit NF-κB-p65 nuclear translocation and NF-κB DNA binding. QM56 prevented JAK2 activation and NF-κB-p65(Ser536) phosphorylation. The anti-inflammatory effect and JAK2 inhibition by QM56 were observed in Apaf-1−/− cells. In murine acute kidney injury, QM56 decreased tubular cell apoptosis and kidney inflammation as measured by down-modulations of MCP-1 and Rantes mRNA expression, immune cell infiltration and activation of the JAK2-dependent inflammatory pathway. In conclusion, QM56 has an anti-inflammatory activity which is independent from its role as inhibitor of Apaf-1 and apoptosis and may have potential therapeutic relevance. PMID:23300960

  9. Murine neonatal intravascular injections: Modeling newborn disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability to perform murine neonatal intravascular injections likely will prove useful in studying many newborn-specific disease states that are modeled in mice. Unfortunately, effective intravascular injection in the neonatal mouse has been limited by developmental immaturity and small size. To e...

  10. Renal disease and chronic renal failure in dental practice.

    PubMed

    Fitzpatrick, J J; Wilson, M H; McArdle, N S; Stassen, L F A

    2008-01-01

    Patients with renal diseases are increasingly common in dental practice. This is due to advances in medicine, and the increasing life expectancy of western populations. Chronic renal failure is a serious condition that general dental practitioners may see in their practice. This article discusses the functions of the kidney, and the causes and medical management of chronic renal failure, as well as considerations in the dental management of these patients. Common complications such as infection and bleeding are discussed. General recommendations are made, based on current evidence with respect to prescribing of medications. PMID:18986093

  11. Renal Glucose Handling

    PubMed Central

    Ferrannini, Ele; Veltkamp, Stephan A.; Smulders, Ronald A.; Kadokura, Takeshi

    2013-01-01

    OBJECTIVE Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, stimulates glycosuria and lowers glycemia in patients with type 2 diabetes (T2DM). The objective of this study was to assess the pharmacodynamics of ipragliflozin in T2DM patients with impaired renal function. RESEARCH DESIGN AND METHODS Glycosuria was measured before and after a single ipragliflozin dose in 8 nondiabetic subjects and 57 T2DM patients (age 62 ± 9 years, fasting glucose 133 ± 39 mg/dL, mean ± SD) with normal renal function (assessed as the estimated glomerular filtration rate [eGFR]) (eGFR1 ≥90 mL · min–1 · 1.73 m−2), mild (eGFR2 ≥60 to <90), moderate (eGFR3 ≥30 to <60), or severe reduction in eGFR (eGFR4 ≤15 to <30). RESULTS Ipragliflozin significantly increased urinary glucose excretion in each eGFR class (P < 0.0001). However, ipragliflozin-induced glycosuria declined (median [IQR]) across eGFR class (from 46 mg/min [33] in eGFR1 to 8 mg/min [7] in eGFR4, P < 0.001). Ipragliflozin-induced fractional glucose excretion (excretion/filtration) was 39% [27] in the T2DM patients (pooled data), similar to that of the nondiabetic subjects (37% [17], P = ns). In bivariate analysis of the pooled data, ipragliflozin-induced glycosuria was directly related to eGFR and fasting glucose (P < 0.0001 for both, r2 = 0.55), predicting a decrement in 24-h glycosuria of 15 g for each 20 mL/min decline in eGFR and an increase of 7 g for each 10 mg/dL increase in glucose above fasting normoglycemia. CONCLUSIONS In T2DM patients, ipragliflozin increases glycosuria in direct, linear proportion to GFR and degree of hyperglycemia, such that its amount can be reliably predicted in the individual patient. Although absolute glycosuria decreases with declining GFR, the efficiency of ipragliflozin action (fractional glucose excretion) is maintained in patients with severe renal impairment. PMID:23359360

  12. Patterning the Renal Vascular Bed

    PubMed Central

    Herzlinger, Doris; Hurtado, Romulo

    2015-01-01

    The renal vascular bed has a stereotypic architecture that is essential for the kidney’s role in excreting metabolic waste and regulating the volume and composition of body fluids. The kidney’s excretory functions are dependent on the delivery of the majority of renal blood flow to the glomerular capillaries, which filter plasma removing from it metabolic waste, as well as vast quantities of solutes and fluids. The renal tubules reabsorb from the glomerular filtrate solutes and fluids required for homeostasis, while the post-glomerular capillary beds return these essential substances back into the systemic circulation. Thus, the kidney’s regulatory functions are dependent on the close proximity or alignment of the post-glomerular capillary beds with the renal tubules. This review will focus on our current knowledge of the mechanisms controlling the embryonic development of the renal vasculature. An understanding of this process is critical for developing novel therapies to prevent vessel rarefaction and will be essential for engineering renal tissues suitable for restoring kidney function to the ever-increasing population of patients with end stage renal disease. PMID:25128732

  13. The Synthetic Tie2 Agonist Peptide Vasculotide Protects Renal Vascular Barrier Function In Experimental Acute Kidney Injury

    PubMed Central

    Rübig, Eva; Stypmann, Jörg; Van Slyke, Paul; Dumont, Daniel J; Spieker, Tilmann; Buscher, Konrad; Reuter, Stefan; Goerge, Tobias; Pavenstädt, Hermann; Kümpers, Philipp

    2016-01-01

    Microvascular barrier dysfunction plays a major role in the pathophysiology of acute kidney injury (AKI). Angiopoietin-1, the natural agonist ligand for the endothelial-specific Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor. Here we evaluate the efficacy of a polyethylene glycol-clustered Tie2 agonist peptide, vasculotide (VT), to protect against endothelial-cell activation with subsequent microvascular dysfunction in a murine model of ischemic AKI. Renal ischemia reperfusion injury (IRI) was induced by clamping of the renal arteries for 35 minutes. Mice were treated with VT or PEGylated cysteine before IRI. Sham-operated animals served as time-matched controls. Treatment with VT significantly reduced transcapillary albumin flux and renal tissue edema after IRI. The protective effects of VT were associated with activation of Tie2 and stabilization of its downstream effector, VE-cadherin in renal vasculature. VT abolished the decline in renal tissue blood flow, attenuated the increase of serum creatinine and blood urea nitrogen after IRI, improved recovery of renal function and markedly reduced mortality compared to PEG [HR 0.14 (95% CI 0.05–0.78) P < 0.05]. VT is inexpensive to produce, chemically stable and unrelated to any Tie2 ligands. Thus, VT may represent a novel therapy to prevent AKI in patients. PMID:26911791

  14. [Cystic renal pathology].

    PubMed

    Rosi, P; Cesaroni, M; Bracarda, S; Rociola, W; Virgili, G

    1993-08-01

    Ultrasonography has a great interest in diagnosis of cystic kidney disorders for typical eco-pattern of this pathology. In this work we show the eco-pattern of the most common cystic kidney disorders. Particularly we examine simple cysts (typical, atypical, complicated), multicystic kidney dysplasia, autosomal recessive polycystic kidney disease (infantile) autosomal dominant polycystic kidney disease (adult age). The so-called neoplastic cysts (multiloculated cysts, multiloculated cysts nephroma, cystic nephroblastoma), medullar cysts (medullary sponge kidney, medullary cystic disease), parapyelic cysts, acquired cystic kidney disease in renal failure patients, parasitic cysts, epidermoid cysts. About this disorders we present the more typical and expressive ultrasonographic appearance and we define the role and the opportunity of diagnostic setting by echography, moreover ultrasonography allows us to make a differential diagnosis between cystic kidney disorders and other kidney disease. PMID:8353538

  15. Renal Ablation Update

    PubMed Central

    Khiatani, Vishal; Dixon, Robert G.

    2014-01-01

    Thermal ablative technologies have evolved considerably in the recent past and are now an important component of current clinical guidelines for the treatment of small renal masses. Both radiofrequency ablation and cryoablation have intermediate-term oncologic control that rivals surgical options, with favorable complication profiles. Studies comparing cryoablation and radiofrequency ablation show no significant difference in oncologic control or complication profile between the two modalities. Early data from small series with microwave ablation have shown similar promising results. Newer technologies including irreversible electroporation and high-intensity–focused ultrasound have theoretical advantages, but will require further research before becoming a routine part of the ablation armamentarium. The purpose of this review article is to discuss the current ablative technologies available, briefly review their mechanisms of action, discuss technical aspects of each, and provide current data supporting their use. PMID:25049445

  16. Hyperparathyroidism of Renal Disease

    PubMed Central

    Yuen, Noah K; Ananthakrishnan, Shubha; Campbell, Michael J

    2016-01-01

    Renal hyperparathyroidism (rHPT) is a common complication of chronic kidney disease characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Patients with rHPT experience increased rates of cardiovascular problems and bone disease. The Kidney Disease: Improving Global Outcomes guidelines recommend that screening and management of rHPT be initiated for all patients with chronic kidney disease stage 3 (estimated glomerular filtration rate, < 60 mL/min/1.73 m2). Since the 1990s, improving medical management with vitamin D analogs, phosphate binders, and calcimimetic drugs has expanded the treatment options for patients with rHPT, but some patients still require a parathyroidectomy to mitigate the sequelae of this challenging disease. PMID:27479950

  17. [Cilia and renal cysts].

    PubMed

    Paces-Fessy, Mélanie

    2014-11-01

    Advances in genomics, bioinformatics and the creation of model organisms have identified many genes associated with polycystic kidney diseases. Historically, these genes were not necessarily associated with ciliopathies, but it appeared that many connections can be made between the cystic kidney disease and function of the primary cilium. Indeed, the proteins encoded by these genes are localized to the cilium itself, to the basal body or are known to regulate the expression and localization of ciliary proteins. The goal of this article is to describe the multiple cellular processes that may lead to the development of renal cysts if they are deregulated. These include changes in proliferation rate, cell polarity or signaling pathways involved in embryonic kidney development. To highlight the role of the primary cilium in cystogenesis, I will discuss several studies investigating the function of ciliary genes and cilia in the kidneys of different model organisms. PMID:25388585

  18. Renal ablation update.

    PubMed

    Khiatani, Vishal; Dixon, Robert G

    2014-06-01

    Thermal ablative technologies have evolved considerably in the recent past and are now an important component of current clinical guidelines for the treatment of small renal masses. Both radiofrequency ablation and cryoablation have intermediate-term oncologic control that rivals surgical options, with favorable complication profiles. Studies comparing cryoablation and radiofrequency ablation show no significant difference in oncologic control or complication profile between the two modalities. Early data from small series with microwave ablation have shown similar promising results. Newer technologies including irreversible electroporation and high-intensity-focused ultrasound have theoretical advantages, but will require further research before becoming a routine part of the ablation armamentarium. The purpose of this review article is to discuss the current ablative technologies available, briefly review their mechanisms of action, discuss technical aspects of each, and provide current data supporting their use. PMID:25049445

  19. Renal Cancer in the Elderly.

    PubMed

    González León, Tania; Morera Pérez, Maricela

    2016-01-01

    The increase of the aging population corresponds with the rise of renal cancer in elderly patients. The distinction between functional and chronological age, quality of life, and survival estimate are important issues, among others, that should be considered in the management of renal cancer in elderly patients. We made this review with the purpose of synthesizing the most updated criteria regarding indications and outcomes of the different therapeutic options in the management of elderly patients with renal cancer, beginning from the physiologic considerations that characterize them, their capacity to tolerate different therapeutic possibilities, and the prognosis of the patients' risks and comorbidity assessment. PMID:26715222

  20. Unusual renal tumour: multilocular cystic renal cell carcinoma.

    PubMed

    Palmeiro, Marta Morna; Niza, João Luz; Loureiro, Ana Luisa; Conceição e Silva, João Paulo

    2016-01-01

    Multilocular cystic renal cell carcinoma (MCRCC) is a rare presentation of renal cell carcinoma. Most patients are asymptomatic and frequently MCRCCs are detected incidentally. MCRCCs have good prognosis because of their low malignant potential. We report a case of a 39-year-old woman who presented with mild right flank pain and normal laboratory data. On imaging examinations, a Bosniak III cystic lesion was detected in the lower third of the right kidney. She underwent right partial nephrectomy and histopathology showed a multilocular cystic renal cell carcinoma Fuhrman grade 1. In this article, we also present a review of the literature on MCRCC, highlight the correlation of the pathological and imaging characteristics of these low aggressive renal lesions, and underscore the importance of their recognition to prevent unnecessary radical surgery. PMID:26957035

  1. Reduction of Renal Superoxide Dismutase in Progressive Diabetic Nephropathy

    PubMed Central

    Fujita, Hiroki; Fujishima, Hiromi; Chida, Shinsuke; Takahashi, Keiko; Qi, Zhonghua; Kanetsuna, Yukiko; Breyer, Matthew D.; Harris, Raymond C.; Yamada, Yuichiro; Takahashi, Takamune

    2009-01-01

    Superoxide excess plays a central role in tissue damage that results from diabetes, but the mechanisms of superoxide overproduction in diabetic nephropathy (DN) are incompletely understood. In the present study, we investigated the enzyme superoxide dismutase (SOD), a major defender against superoxide, in the kidneys during the development of murine DN. We assessed SOD activity and the expression of SOD isoforms in the kidneys of two diabetic mouse models (C57BL/6-Akita and KK/Ta-Akita) that exhibit comparable levels of hyperglycemia but different susceptibility to DN. We observed down-regulation of cytosolic CuZn-SOD (SOD1) and extracellular CuZn-SOD (SOD3), but not mitochondrial Mn-SOD (SOD2), in the kidney of KK/Ta-Akita mice which exhibit progressive DN. In contrast, we did not detect a change in renal SOD expression in DN-resistant C57BL/6-Akita mice. Consistent with these findings, there was a significant reduction in total SOD activity in the kidney of KK/Ta-Akita mice compared with C57BL/6-Akita mice. Finally, treatment of KK/Ta-Akita mice with a SOD mimetic, tempol, ameliorated the nephropathic changes in KK/Ta-Akita mice without altering the level of hyperglycemia. Collectively, these results indicate that down-regulation of renal SOD1 and SOD3 may play a key role in the pathogenesis of DN. PMID:19470681

  2. Hypohyperparathyroidism: a model for renal osteodystrophy?

    PubMed

    Junor, B J; Edward, N

    1981-06-01

    A child who presented with features of renal osteodystrophy but with normal renal function is described. Improvement occurred both on large doses of vitamin D and small doses of 1, alpha-hydroxy-vitamin D3 (1, alpha-OHD3). Investigations suggested that the primary defect was an impaired renal response to parathyroid hormone. The relationship between renal osteodystrophy, abnormalities of vitamin D metabolism and hypohyperparathyroidism is discussed and an alternative hypothesis for the development of renal bone disease suggested. PMID:7301683

  3. Familial renal glycosuria and modifications of glucose renal excretion.

    PubMed

    Prié, D

    2014-12-01

    Under physiological conditions, the kidneys contribute to glucose homoeostasis by producing glucose by gluconeogenesis and preventing glucose loss in urine. The glucose filtered by the glomeruli is completely reabsorbed in the renal proximal tubule. Renal gluconeogenesis produces 25% of the circulating glucose in the postabsorptive state, while the amount of glucose reabsorbed by the kidneys largely exceeds the quantity synthesized by kidney gluconeogenesis. Sodium-glucose cotransporter type 2 (SGLT-2) and glucose transporter 2 (GLUT2) carry out more than 90% of renal glucose uptake. In diabetes, both gluconeogenesis and renal glucose reabsorption are increased. The augmentation of glucose uptake in diabetes is due to the overexpression of renal glucose transporters SGLT-2 and GLUT2 in response to the increase in expression of transcription activator hepatic nuclear factor 1-alpha (HNF1α). The rise in glucose uptake contributes to hyperglycaemia and induces glomerular hyperfiltration by increasing sodium and water reabsorption in the proximal tubule that, in turn, modifies urine flux at the macula densa. SGLT-2 inhibitors improve glycaemic control and prevent renal hyperfiltration in diabetes. Loss of SGLT-2 transporter function is a benign state characterized by glycosuria. In contrast, mutations of other glucose transporters expressed in the kidney are responsible for severe disorders. PMID:25554066

  4. Murine retroviral vector producer cells survival and toxicity in the peritoneal cavity of dogs.

    PubMed

    Link, C J; Moorman, D W; Ackerman, M; Levy, J P; Seregina, T

    2000-01-01

    Retroviral vector producer cells (VPC) can effectively transfer genes in vivo. To develop a safe method to target gene delivery into intraperitoneal tumors, we have examined the toxicity of intraperitoneal (i.p.) infusion of retroviral VPC in a xenogeneic canine model. Mongrel dogs were injected intraperitoneally (i.p.) with 2 x 10(9) murine LTKOSN.2 VPC. The animals did not demonstrate acute toxicity and tolerated the i.p. infusion of the cells without difficulty. Starting 7 days after i.p. injection, the dogs received intravenous injections of ganciclovir (GCV) twice daily (5 mg/kg) for 7 days. The treatment dogs underwent peritoneal washings on days 3, 7 and 14 after their initial infusion of cells to study the persistence of the VPC. GCV treatment did not cause significant toxicities. Dogs underwent serial blood tests to evaluate bone marrow, renal, liver and immunological function. Complete blood counts, electrolytes and renal function remained normal throughout the study. Although, transient mild elevations occurred of serum alkaline phosphate, the remaining hepatic enzymes remained normal. Histologic examination of tissues from animals sacrificed after the i.p. administration of the VPC revealed no tissue destruction of the normal peritoneal lining. The dogs mounted an antibody response to the murine VPC that was first observed 7 days post injection. PCR analysis of selected tissues after GCV administration did not reveal persistent vector sequences. These results demonstrated that the injection of xenogeneic VPC is not accompanied by significant adverse effects over a 1 month period following administration into the canine peritoneal cavity. These data support the potential clinical application of the VPC in Phase I clinical trials in humans. PMID:11212841

  5. The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

    PubMed Central

    Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

    2015-01-01

    Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

  6. Taurine and the renal system

    PubMed Central

    2010-01-01

    Taurine participates in a number of different physiologic and biologic processes in the kidney, often reflected by urinary excretion patterns. The kidney is key to aspects of taurine body pool size and homeostasis. This review will examine the renal-taurine interactions relative to ion reabsorption; renal blood flow and renal vascular endothelial function; antioxidant properties, especially in the glomerulus; and the role of taurine in ischemia and reperfusion injury. In addition, taurine plays a role in the renal cell cycle and apoptosis, and functions as an osmolyte during the stress response. The role of the kidney in adaptation to variations in dietary taurine intake and the regulation of taurine body pool size are described. Finally, the protective function of taurine against several kidney diseases is reviewed. PMID:20804616

  7. Renal Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  8. Renal protection in cardiovascular surgery

    PubMed Central

    Di Tomasso, Nora; Monaco, Fabrizio; Landoni, Giovanni

    2016-01-01

    Acute kidney injury (AKI) is one of the most relevant complications after major surgery and is a predictor of mortality. In Western countries, patients at risk of developing AKI are mainly those undergoing cardiovascular surgical procedures. In this category of patients, AKI depends on a multifactorial etiology, including low ejection fraction, use of contrast media, hemodynamic instability, cardiopulmonary bypass, and bleeding. Despite a growing body of literature, the treatment of renal failure remains mainly supportive (e.g. hemodynamic stability, fluid management, and avoidance of further damage); therefore, the management of patients at risk of AKI should aim at prevention of renal damage. Thus, the present narrative review analyzes the pathophysiology underlying AKI (specifically in high-risk patients), the preoperative risk factors that predispose to renal damage, early biomarkers related to AKI, and the strategies employed for perioperative renal protection. The most recent scientific evidence has been considered, and whenever conflicting data were encountered possible suggestions are provided. PMID:26998249

  9. Urea distribution in renal failure

    PubMed Central

    Blackmore, D. J.; Elder, W. J.; Bowden, C. H.

    1963-01-01

    An assessment of intracellular urea removed during haemodialysis has been made from urea extraction and plasma urea estimations. An apparent wide variation in the movement of intracellular urea in patients with acute renal failure from obstetric and traumatic causes and with chronic renal failure is reported. A method for the estimation of red cell water urea is presented. In two patients with chronic renal failure the red cell urea level was much higher than would have been expected from the plasma urea level before dialysis. In two obstetric patients there was no such discrepancy. The conclusion is drawn that research should be directed to variations of intracellular metabolism in renal failure before a more rational approach can be made to its management. PMID:16811009

  10. The renal mononuclear phagocytic system.

    PubMed

    Nelson, Peter J; Rees, Andrew J; Griffin, Matthew D; Hughes, Jeremy; Kurts, Christian; Duffield, Jeremy

    2012-02-01

    The renal mononuclear phagocytic system, conventionally composed of macrophages (Mø) and dendritic cells (DCs), plays a central role in health and disease of the kidney. Overlapping definitions of renal DCs and Mø, stemming from historically separate research tracks and the lack of experimental tools to specifically study the roles of these cells in vivo, have generated confusion and controversy, however, regarding their immunologic function in the kidney. This brief review provides an appraisal of the current state of knowledge of the renal mononuclear phagocytic system interpreted from the perspective of immunologic function. Physical characteristics, ontogeny, and known functions of the main subsets of renal mononuclear phagocytes as they relate to homeostasis, surveillance against injury and infection, and immune-mediated inflammatory injury and repair within the kidney are described. Gaps and inconsistencies in current knowledge are used to create a roadmap of key questions to be answered in future research. PMID:22135312

  11. Primary carcinoma of renal calyx.

    PubMed

    Williams, Phillip A; Mai, Kien T

    2013-10-01

    Renal calyx carcinoma (RCXC) may mimic collecting duct carcinoma (CDC) or urothelial carcinoma (UC) of the renal pelvis. RCXC is distinguished from CDC and UC of the renal pelvis as having the tumor epicenter in the renal calyx, with limited involvement of the surrounding renal pelvis surface urothelium. In this study, we summarize our experience with this entity. Ten cases of RCXC, including 9 cases with urothelial differentiation (RCXC-UC) and 1 case with salivary gland-type differentiation (RCXC-SC), were identified. Ten consecutive cases of UC were selected for comparison, with extensive renal pelvis involvement and with secondary renal parenchymal invasion. Two cases of collecting duct carcinoma (CDC) were also examined. Immunohistochemistry (IHC) was performed on representative tissue blocks for PAX8, PAX2, CK5, CK7, CK20, p63, GATA3, AMACR, RCC, CD10, vimentin, S100, and MSA. The 10 cases of RCXC (M:F=4:6, ages: 62-91 years, mean: 76) presented with renal masses of 3-6cm. Ureteroscopic studies and renal pelvic washings showed atypical/malignant cells in three cases. Seven patients were treated with nephrectomy followed by radiation±chemotherapy, and all cases developed metastases to lymph nodes or liver/lung/bone. In all 7 cases with nephrectomy, there was extensive renal parenchymal involvement with infiltrating borders and diffuse spread along collecting ducts. Six RCXC-UC contained focal squamous differentiation. The RCXC-SC displayed features of adenoid cystic and basaloid features. In situ UC, with or without papillary components, was identified in the calyces in all 7 nephrectomy cases with remaining renal pelvis harboring small tumor burden in 5 cases, and no tumor in another 2 cases. Of the three cases without nephrectomy, no tumor in the renal pelvis could be visualized with endoscopy, however one case was associated with UC of the urinary bladder. Of 10 control UC cases, tumor was limited to the tip of renal papilla in 7 cases, extensive in 3

  12. Expression and localization of GPR91 and GPR99 in murine organs.

    PubMed

    Diehl, Julia; Gries, Barbara; Pfeil, Uwe; Goldenberg, Anna; Mermer, Petra; Kummer, Wolfgang; Paddenberg, Renate

    2016-05-01

    Energy substrates and metabolic intermediates are proven ligands of a growing number of G-protein coupled receptors. In 2004, GPR91 and GPR99 were identified as receptors for the citric acid cycle intermediates, succinate and α-ketoglutarate, respectively. GPR91 seems to act as a first responder to local stress and GPR99 participates in the regulation of the acid-base balance through an intrarenal paracrine mechanism. However, a systematic analysis of the distribution of both receptors in mouse organs is still missing. The aim of this study was to examine the expression of GPR91 and GPR99 in a large number of different murine organs both at mRNA and protein level. Whereas GPR91 mRNA was detectable in almost all organs, GPR99 mRNA was mainly expressed in neuronal tissues. Widespread expression of GPR91 was also detected at the protein level by western blotting and immunohistochemistry. In addition to neuronal cells, GPR99 protein was found in renal intercalated cells and epididymal narrow cells. Double-labeling immunohistochemistry demonstrated the colocalization of GPR99 with the B1 subunit isoform of vacuolar H(+)-ATPases which is expressed only by a very limited number of cell types. In summary, our detailed expression analysis of GPR91 and GPR99 in murine tissues will allow a more directed search for additional functions of both receptors. PMID:26590824

  13. Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients

    ClinicalTrials.gov

    2015-12-23

    Chronic Allograft Nephropathy; Chronic Kidney Disease; Chronic Renal Failure; Disordered Mineral Metabolism; End Stage Renal Disease; Hyperparathyroidism; Hypophosphatemia; Kidney Disease; Kidney Transplantation; Post Renal Transplantation

  14. Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition

    PubMed Central

    Taylor, A.M.; Preston, A.J.; Paulk, N.K.; Sutherland, H.; Keenan, C.M.; Wilson, P.J.M.; Wlodarski, B.; Grompe, M.; Ranganath, L.R.; Gallagher, J.A.; Jarvis, J.C.

    2012-01-01

    Objective Alkaptonuria (AKU) is a rare genetic disease which results in severe early onset osteoarthropathy. It has recently been shown that the subchondral interface is of key significance in disease pathogenesis. Human surgical tissues are often beyond this initial stage and there is no published murine model of pathogenesis, to study the natural history of the disease. The murine genotype exists but it has been reported not to demonstrate ochronotic osteoarthropathy consistent with the human disease. Recent anecdotal evidence of macroscopic renal ochronosis in a mouse model of tyrosinaemia led us to perform histological analysis of tissues of these mice that are known to be affected in human AKU. Design The homogentisate 1,2-dioxygenase Hgd+/−Fah−/− mouse can model either hereditary tyrosinaemia type I (HT1) or AKU depending on selection conditions. Mice having undergone Hgd reversion were sacrificed at various time points, and their tissues taken for histological analysis. Sections were stained with haematoxylin eosin (H&E) and Schmorl’s reagent. Results Early time point observations at 8 months showed no sign of macroscopic ochronosis of tissues. Macroscopic examination at 13 months revealed ochronosis of the kidneys. Microscopic analysis of the kidneys revealed large pigmented nodules displaying distinct ochre colouration. Close microscopic examination of the distal femur and proximal fibula at the subchondral junctions revealed the presence of numerous pigmented chondrocytes. Conclusions Here we present the first data showing ochronosis of tissues in a murine model of AKU. These preliminary histological observations provide a stimulus for further studies into the natural history of the disease to provide a greater understanding of this class of arthropathy. PMID:22542924

  15. Cystic renal neoplasms and renal neoplasms associated with cystic renal diseases in adults: cross-sectional imaging findings.

    PubMed

    Katabathina, Venkata S; Garg, Deepak; Prasad, Srinivasa R; Vikram, Raghu

    2012-01-01

    Cystic renal neoplasms in adults are a heterogeneous group of tumors with characteristic histogenesis, pathological findings, and variable biological profiles. They include disparate entities that are either biologically benign (lymphangioma, cystic nephroma, and mixed epithelial and stromal tumor) or malignant (cystic renal cell carcinoma, multilocular cystic renal cell carcinoma, and primary renal synovial sarcoma). Renal cystic diseases are characterized by cystic changes of the kidneys due to hereditary, developmental, or acquired etiology. Cystic renal diseases such as acquired cystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis are associated with the development of a wide spectrum of benign and malignant renal neoplasms. Most cystic renal tumors and cystic disease-associated renal neoplasms show characteristic cross-sectional imaging findings that permit accurate diagnosis. In addition, cross-sectional imaging is pivotal in the follow-up and surveillance of adult cystic tumors of the kidney. PMID:23192202

  16. Metoclopramide and renal vascular resistance.

    PubMed

    Manara, A R; Bolsin, S; Monk, C R; Hartnell, G; Harris, R A

    1991-01-01

    We have studied the effect of i.v. metoclopramide on renal vascular resistance in nine healthy volunteers. Peak systolic and end-diastolic frequencies were measured using duplex Doppler ultrasound of a renal interlobar artery, before and after the administration of i.v. metoclopramide 10 mg, and the resistance index derived. There was no significant change in mean arterial pressure or resistance index following metoclopramide. PMID:1997046

  17. Management of acute renal failure

    PubMed Central

    Fry, A C; Farrington, K

    2006-01-01

    Acute renal failure is a common condition, frequently encountered in both community practice and hospital inpatients. While it remains a heterologous condition, following basic principles makes investigation straightforward, and initial management follows a standard pathway in most patients. This article shows this, advises on therapeutic strategies, including those in special situations, and should help the clinician in deciding when to refer to a nephrologist, and when to consider renal replacement therapy. PMID:16461473

  18. Oxygen radicals and renal diseases.

    PubMed

    Klahr, S

    1997-01-01

    Reactive oxygen metabolites (superoxide, hydrogen peroxide, hydroxyl radical, and hypochlorous acid) are important mediators of renal damage in acute renal failure and glomerular and tubulointerstitial diseases. The role of these oxygen metabolites in the above entities is discussed, and the effects of antioxidants and scavengers of O2 radicals are considered. The role of oxygen radicals in the regulation of gene transcription is also considered. PMID:9387104

  19. Renal Ammonia Metabolism and Transport

    PubMed Central

    Weiner, I. David; Verlander, Jill W.

    2015-01-01

    Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3− for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3−-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. PMID:23720285

  20. [Renal injury in Takayasu's arteritis].

    PubMed

    Boubaker, Karima; Kaaroud, Hayet; Goucha, Rim; Kheder, Adel

    2014-11-01

    Renal involvement in Takayasu's arteritis is frequent and worsens the progression of the disease. This is primarily a renal artery stenosis causing renovascular hypertension. The glomerular disease is exceptional. This study was undertaken to determine the clinical, radiological, biological features and therapeutic response in patients with kidney disease associated with Takayasu arteritis. A retrospective chart review was conducted on 11 patients (five men and six females), with a mean age of 31.1 years (19-40 years). The discovery of kidney disease preceded the diagnosis of Takayasu's arteritis in eight cases. Ten patients developed hypertension. Laboratory finding showed proteinuria in five cases of which one case was due to nephrotic syndrome. Renal failure was found in six cases including four cases in stage of terminal chronic renal failure. Impairment of the renal artery was present in nine patients, proximal in seven cases and distal in two cases, bilateral in five cases and unilateral in four cases. Narrowing renal artery was found in seven cases. The renal biopsy revealed membranoproliferative glomerulonephritis in one case and nephrosclerosis in another case. Eleven patients were followed for an average period of 155 months (3-335 months). Remission of nephrotic syndrome was concomitant with the remission of the disease. Seven patients developed outbreaks of Takayasu's arteritis of which six were in care. Relapse of nephrotic syndrome was concomitant with the outbreak of the disease followed by spontaneous remission of both diseases. Improved pressure was obtained in 5 cases and worsening renal function in seven cases. Death was observed in two cases. PMID:25440941

  1. CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders

    PubMed Central

    Bai, Xiuying; Miao, Dengshun; Xiao, Sophia; Qiu, Dinghong; St-Arnaud, René; Petkovich, Martin; Gupta, Ajay; Goltzman, David; Karaplis, Andrew C.

    2016-01-01

    CYP24A1 (hereafter referred to as CYP24) enzymatic activity is pivotal in the inactivation of vitamin D metabolites. Basal renal and extrarenal CYP24 is usually low but is highly induced by its substrate 1,25-dihydroxyvitamin D. Unbalanced high and/or long-lasting CYP24 expression has been proposed to underlie diseases like chronic kidney disease, cancers, and psoriasis that otherwise should favorably respond to supplemental vitamin D. Using genetically modified mice, we have shown that renal phosphate wasting hypophosphatemic states arising from high levels of fibroblast growth factor 23 (FGF23) are also associated with increased renal Cyp24 expression, suggesting that elevated CYP24 activity is pivotal to the pathophysiology of these disorders. We therefore crossed 2 mouse strains, each with distinct etiology for high levels of circulating FGF23, onto a Cyp24-null background. Specifically, we evaluated Cyp24 deficiency in Hyp mice, the murine homolog of X-linked dominant hypophosphatemic rickets, and transgenic mice that overexpress a mutant FGF23 (FGF23R176Q) that is associated with the autosomal dominant form of hypophosphatemic rickets. Loss of Cyp24 in these murine models of human disease resulted in near-complete recovery of rachitic/osteomalacic bony abnormalities in the absence of any improvement in the serum biochemical profile. Moreover, treatment of Hyp and FGF23R1760-transgenic mice with the CYP24 inhibitor CTA102 also ameliorated their rachitic bones. Our results link CYP24 activity to the pathophysiology of FGF23-dependent renal phosphate wasting states and implicate pharmacologic CYP24 inhibition as a therapeutic adjunct for their treatment. PMID:26784541

  2. CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders.

    PubMed

    Bai, Xiuying; Miao, Dengshun; Xiao, Sophia; Qiu, Dinghong; St-Arnaud, René; Petkovich, Martin; Gupta, Ajay; Goltzman, David; Karaplis, Andrew C

    2016-02-01

    CYP24A1 (hereafter referred to as CYP24) enzymatic activity is pivotal in the inactivation of vitamin D metabolites. Basal renal and extrarenal CYP24 is usually low but is highly induced by its substrate 1,25-dihydroxyvitamin D. Unbalanced high and/or long-lasting CYP24 expression has been proposed to underlie diseases like chronic kidney disease, cancers, and psoriasis that otherwise should favorably respond to supplemental vitamin D. Using genetically modified mice, we have shown that renal phosphate wasting hypophosphatemic states arising from high levels of fibroblast growth factor 23 (FGF23) are also associated with increased renal Cyp24 expression, suggesting that elevated CYP24 activity is pivotal to the pathophysiology of these disorders. We therefore crossed 2 mouse strains, each with distinct etiology for high levels of circulating FGF23, onto a Cyp24-null background. Specifically, we evaluated Cyp24 deficiency in Hyp mice, the murine homolog of X-linked dominant hypophosphatemic rickets, and transgenic mice that overexpress a mutant FGF23 (FGF23R176Q) that is associated with the autosomal dominant form of hypophosphatemic rickets. Loss of Cyp24 in these murine models of human disease resulted in near-complete recovery of rachitic/osteomalacic bony abnormalities in the absence of any improvement in the serum biochemical profile. Moreover, treatment of Hyp and FGF23R1760-transgenic mice with the CYP24 inhibitor CTA102 also ameliorated their rachitic bones. Our results link CYP24 activity to the pathophysiology of FGF23-dependent renal phosphate wasting states and implicate pharmacologic CYP24 inhibition as a therapeutic adjunct for their treatment. PMID:26784541

  3. Caspase deficiency alters the murine gut microbiome

    PubMed Central

    Brinkman, B M; Hildebrand, F; Kubica, M; Goosens, D; Del Favero, J; Declercq, W; Raes, J; Vandenabeele, P

    2011-01-01

    Caspases are aspartate-specific cysteine proteases that have an essential role in apoptosis and inflammation, and contribute to the maintenance of homeostasis in the intestine. These facts, together with the knowledge that caspases are implicated in host-microbe crosstalk, prompted us to investigate the effect of caspase (Casp)1, -3 and -7 deficiency on the composition of the murine gut microbiota. We observed significant changes in the abundance of the Firmicutes and Bacteroidetes phyla, in particular the Lachnospiraceae, Porphyromonodaceae and Prevotellacea families, when comparing Casp-1, -7 and -3 knockout mice with wild-type mice. Our data point toward an intricate relationship between these caspases and the composition of the murine gut microflora. PMID:22012254

  4. Retroviral Transduction of Murine Primary T Lymphocytes

    PubMed Central

    Lee, James; Sadelain, Michel; Brentjens, Renier

    2016-01-01

    Summary In comparison to human T cells, efficient retroviral gene transfer and subsequent expansion of murine primary T cells is more difficult to achieve. Herein, we describe an optimized gene transfer protocol utilizing an ecotropic viral vector to transduce primary murine T cells activated with magnetic beads coated with agonistic anti-CD3 and CD28 antibodies. Activated T cells are subsequently centrifuged (spinoculated) on RetroNectin-coated tissue culture plates in the context of retroviral supernatant. Variables found to be critical to high gene transfer and subsequent efficient T cell expansion included CD3/CD28 magnetic bead to cell ratio, time from T cell activation to initial spinoculation, frequency of T cell spinoculation, interleukin-2 concentration in the medium, and the initial purity of the T cell preparation. PMID:19110621

  5. Myositis in a Child with Murine Typhus

    PubMed Central

    Seshadri, Sheshashree; Fergie, Jaime

    2014-01-01

    A 12-year-old boy presented with fever, lower extremity pain and weakness. Examination revealed paraparesis, thigh and calf tenderness. Labs showed high creatinine phosphokinase and Rickettsia typhi titers. This case illustrates endemic typhus should be considered in the differential diagnosis of myositis especially in areas with high prevalence of the disease. To our knowledge, this is the first reported case of myositis and paraparesis associated with a case of murine typhus. PMID:24757508

  6. Cone inputs to murine striate cortex

    PubMed Central

    Ekesten, Björn; Gouras, Peter

    2008-01-01

    Background We have recorded responses from single neurons in murine visual cortex to determine the effectiveness of the input from the two murine cone photoreceptor mechanisms and whether there is any unique selectivity for cone inputs at this higher region of the visual system that would support the possibility of colour vision in mice. Each eye was stimulated by diffuse light, either 370 (strong stimulus for the ultra-violet (UV) cone opsin) or 505 nm (exclusively stimulating the middle wavelength sensitive (M) cone opsin), obtained from light emitting diodes (LEDs) in the presence of a strong adapting light that suppressed the responses of rods. Results Single cells responded to these diffuse stimuli in all areas of striate cortex. Two types of responsive cells were encountered. One type (135/323 – 42%) had little to no spontaneous activity and responded at either the on and/or the off phase of the light stimulus with a few impulses often of relatively large amplitude. A second type (166/323 – 51%) had spontaneous activity and responded tonically to light stimuli with impulses often of small amplitude. Most of the cells responded similarly to both spectral stimuli. A few (18/323 – 6%) responded strongly or exclusively to one or the other spectral stimulus and rarely in a spectrally opponent manner. Conclusion Most cells in murine striate cortex receive excitatory inputs from both UV- and M-cones. A small fraction shows either strong selectivity for one or the other cone mechanism and occasionally cone opponent responses. Cells that could underlie chromatic contrast detection are present but extremely rare in murine striate cortex. PMID:19014590

  7. Renal artery injury during robot-assisted renal surgery.

    PubMed

    Lee, Jae Won; Yoon, Young Eun; Kim, Dae Keun; Park, Sung Yul; Moon, Hong Sang; Lee, Tchun Yong

    2010-07-01

    Laparoscopic partial nephrectomy (LPN) is becoming the standard of care for incidentally diagnosed, small renal tumors. With its seven degrees of freedom and three-dimensional vision, the DaVinci robotic surgical system has been used to assist in LPNs. The main disadvantage of robot-assisted surgery, however, is the lack of tactile feedback. We present a case of renal artery injury during robot-assisted renal surgery. Robot-assisted partial nephrectomy (RPN) was planned for 47-year-old man with a 3.5-cm right renal mass. After standard bowel mobilization, renal hilar dissection was performed. In the attempt to complete the dissection posteriorly, however, there was sudden profuse bleeding. The intraperitoneal pressure immediately increased to 20 mm Hg, and an additional suction device was inserted through the 5-mm liver retractor port. On inspection, there was an injury at the takeoff of the posterior segmental artery. A decision was made to convert to robot-assisted laparoscopic radical nephrectomy. The main renal artery and renal vein were controlled with Hem-o-Lok clips. The estimated blood loss was 2,000 mL. Four units of packed red blood cells were transfused intraoperatively. The post-transfusion hemoglobin level was 12.6 g/dL. There were no other perioperative complications. The surgeon should keep in mind that the robotic arms are very powerful and can easily injure major vessels because of lack of tactile feedback. A competent and experienced tableside surgeon is very important in robot-assisted surgery because the unsterile console surgeon cannot immediately react to intraoperative complications. PMID:20590468

  8. Pathophysiology and management of progressive renal disease.

    PubMed

    Brown, S A; Crowell, W A; Brown, C A; Barsanti, J A; Finco, D R

    1997-09-01

    Recently, the hypothesis that all renal diseases are inherently progressive and self-perpetuating has focused attention on adaptive changes in renal structure and function that occur whenever renal function is reduced. These glomerular adaptations to renal disease include increases in filtration rate, capillary pressure and size, and are referred to as glomerular hyperfiltration, glomerular hypertension and glomerular hypertrophy, respectively. Extrarenal changes, such as dietary phosphate excess, systemic hypertension, hyperlipidaemia, acidosis and hyperparathyroidism occur in animals with renal disease and may be contributors to progression of renal disease. Emphasis in the management of companion animals with renal disease has shifted to identifying, understanding and controlling those processes that play a role in the progression from early to end-stage renal failure. Advances made by veterinary nephrologists in the past 15 years permit resolution of old controversies, formulation of new hypotheses and discussion of unresolved issues about the nature of progressive renal disease in dogs and cats. PMID:9308397

  9. Renal Ischemia/Reperfusion Injury in Soluble Epoxide Hydrolase-Deficient Mice

    PubMed Central

    Zhu, Ye; Blum, Maximilian; Hoff, Uwe; Wesser, Tim; Fechner, Mandy; Westphal, Christina; Gürgen, Dennis; Catar, Rusan Ali; Philippe, Aurelie; Wu, Kaiyin; Bubalo, Gordana; Rothe, Michael; Weldon, Steven M.; Dragun, Duska; Schunck, Wolf-Hagen

    2016-01-01

    Aim 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP)-dependent eicosanoids that play opposite roles in the regulation of vascular tone, inflammation, and apoptosis. 20-HETE aggravates, whereas EETs ameliorate ischemia/reperfusion (I/R)-induced organ damage. EETs are rapidly metabolized to dihydroxyeicosatrienoic acids (DHETs) by the soluble epoxide hydrolase (sEH). We hypothesized that sEH gene (EPHX2) deletion would increase endogenous EET levels and thereby protect against I/R-induced acute kidney injury (AKI). Methods Kidney damage was evaluated in male wildtype (WT) and sEH-knockout (KO)-mice that underwent 22-min renal ischemia followed by two days of reperfusion. CYP-eicosanoids were analyzed by liquid chromatography tandem mass spectrometry. Results Contrary to our initial hypothesis, renal function declined more severely in sEH-KO mice as indicated by higher serum creatinine and urea levels. The sEH-KO-mice also featured stronger tubular lesion scores, tubular apoptosis, and inflammatory cell infiltration. Plasma and renal EET/DHET-ratios were higher in sEH-KO than WT mice, thus confirming the expected metabolic consequences of sEH deficiency. However, CYP-eicosanoid profiling also revealed that renal, but not plasma and hepatic, 20-HETE levels were significantly increased in sEH-KO compared to WT mice. In line with this finding, renal expression of Cyp4a12a, the murine 20-HETE-generating CYP-enzyme, was up-regulated both at the mRNA and protein level, and Cyp4a12a immunostaining was more intense in the renal arterioles of sEH-KO compared with WT mice. Conclusion These results indicate that the potential beneficial effects of reducing EET degradation were obliterated by a thus far unknown mechanism leading to kidney-specific up-regulation of 20-HETE formation in sEH-KO-mice. PMID:26727266

  10. [Renal transplantation: ethical issues].

    PubMed

    Mamzer-Bruneel, Marie-France; Laforêt, Emmanuelle Grand; Kreis, Henri; Thervet, Éric; Martinez, Frank; Snanoudj, Renaud; Hervé, Christian; Legendre, Christophe

    2012-12-01

    One of the most significant advances in medicine during the last 50 years is the development of organ transplantation. In the context of chronic kidney diseases, renal transplantation offers patients a better clinical outcome than other treatment options. However, the benefits of organ transplantation have not been maximized due to an inadequate supply of organs for transplantation. Despite the establishment of elaborate legal rules for organs procurement, both on deceased and living donors in numerous countries, ethical concerns remain. Most of them are consequences of the strategies implemented or proposed to address the so-called organ shortage. The involvement of society in these complex problems is crucial as numerous questions emerge: could actual state of organ procurement change? Is it possible and/or realistic to increase the number of organs, with respects to living donors or deceased persons? Is the shortage an indicator to limit the use of kidney transplantation? How do we maintain efficiency and justice, in this context. PMID:23168353

  11. Renal cell carcinoma

    PubMed Central

    Gao, Jianjun; Rathmell, W Kimryn

    2014-01-01

    The treatment of renal cell carcinoma (RCC) has changed greatly over the past 15 years. Progress in the surgical management of the primary tumor and increased understanding of the molecular biology and genomics of the disease have led to the development of new therapeutic agents. The management of the primary tumor has changed owing to the realization that clean margins around the primary lesion are sufficient to prevent local recurrence, as well as the development of more sophisticated tools and techniques that increase the safety of partial nephrectomy. The management of advanced disease has altered even more dramatically as a result of new agents that target the tumor vasculature or that attenuate the activation of intracellular oncogenic pathways. This review summarizes data from prospective randomized phase III studies on the surgical management and systemic treatment of RCC, and provides an up to date summary of the histology, genomics, staging, and prognosis of RCC. It describes the management of the primary tumor and offers an overview of systemic agents that form the mainstay of treatment for advanced disease. The review concludes with an introduction to the exciting new class of immunomodulatory agents that are currently in clinical trials and may form the basis of a new therapeutic approach for patients with advanced RCC. PMID:25385470

  12. The scintigraphic pattern of renal angiomyolipoma

    SciTech Connect

    Jaikishen, P.; Oster, Z.H.; Atkins, H.L. )

    1990-03-01

    The patterns of renal and gallium scintigraphy in a patient with renal angiomyolipoma are presented. Renal study with Tc-99m DTPA demonstrated a photopenic area in the flow and delayed images. Ga-67 citrate imaging did not show any evidence of increased activity. Although this pattern is also seen in renal cysts, scintigraphy seems to be valuable in the evaluation of angiomyolipoma. It helps differentiate it from renal carcinoma or renal abscess (which may be gallium avid), especially when the tumor is characterized by a paucity of adipose tissue and complicated by hemorrhage, in which case CT and ultrasonographic patterns are not diagnostic.

  13. The HIV matrix protein p17 induces hepatic lipid accumulation via modulation of nuclear receptor transcriptoma

    PubMed Central

    Renga, Barbara; Francisci, Daniela; Carino, Adriana; Marchianò, Silvia; Cipriani, Sabrina; Chiara Monti, Maria; Del Sordo, Rachele; Schiaroli, Elisabetta; Distrutti, Eleonora; Baldelli, Franco; Fiorucci, Stefano

    2015-01-01

    Liver disease is the second most common cause of mortality in HIV-infected persons. Exactly how HIV infection per se affects liver disease progression is unknown. Here we have investigated mRNA expression of 49 nuclear hormone receptors (NRs) and 35 transcriptional coregulators in HepG2 cells upon stimulation with the HIV matrix protein p17. This viral protein regulated mRNA expression of some NRs among which LXRα and its transcriptional co-activator MED1 were highly induced at mRNA level. Dissection of p17 downstream intracellular pathway demonstrated that p17 mediated activation of Jak/STAT signaling is responsible for the promoter dependent activation of LXR. The treatment of both HepG2 as well as primary hepatocytes with HIV p17 results in the transcriptional activation of LXR target genes (SREBP1c and FAS) and lipid accumulation. These effects are lost in HepG2 cells pre-incubated with a serum from HIV positive person who underwent a vaccination with a p17 peptide as well as in HepG2 cells pre-incubated with the natural LXR antagonist gymnestrogenin. These results suggest that HIV p17 affects NRs and their related signal transduction thus contributing to the progression of liver disease in HIV infected patients. PMID:26469385

  14. Genetics Home Reference: action myoclonus-renal failure syndrome

    MedlinePlus

    ... Action Myoclonus - Renal Failure Syndrome Genetic Testing Registry: Epilepsy, progressive myoclonic 4, with or without renal failure ... failure syndrome action myoclonus–renal failure syndrome AMRF epilepsy, progressive myoclonic 4, with or without renal failure ...

  15. Hyperdense renal masses: a CT manifestation of hemorrhagic renal cysts

    SciTech Connect

    Sussman, S.; Cochran, S.T.; Pagani, J.J.; McArdle, C.; Wong, W.; Austin, R.; Curry, N.; Kelly, K.M.

    1984-01-01

    Eleven patients with sharply circumscribed round to ovoid renal cysts measuring 70-90 H on CT are reported. The cysts were hyperdense on unenhanced scans, measuring 30-60 H greater than the adjacent parenchyma, and either hypodense, isodense, or hyperdense on enhanced scans. Four patients had polycystic kidney disease; of the other 7 patients, the cysts were cortical in 6 and parapelvic in 1. Eight patients had a solitary cyst and 3 had multiple cysts. Sonography demonstrated internal echoes and/or lack of increased through-transmission in 6 patients. Pathological analysis was available in 6 cases and indicated a benign, hemorrhagic renal cyst. This hyperdense CT appearance is characteristic of some hemorrhagic renal cysts, though differentiation between benign and malignant cysts requires cyst puncture and/or surgery.

  16. The role of renal biopsy in small renal masses

    PubMed Central

    Burruni, Rodolfo; Lhermitte, Benoit; Cerantola, Yannick; Tawadros, Thomas; Meuwly, Jean-Yves; Berthold, Dominik; Jichlinski, Patrice; Valerio, Massimo

    2016-01-01

    Renal biopsy is being increasingly proposed as a diagnostic tool to characterize small renal masses (SRM). Indeed, the wide adoption of imaging in the diagnostic workup of many diseases had led to a substantial increased incidence of SRM (diameter ≤4 cm). While modern ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) techniques have high sensitivity for detecting SRM, none is able to accurately and reliably characterize them in terms of histological features. This is currently of key importance in guiding clinical decision-making in some situations, and in these cases renal biopsy should be considered. In this review, we aim to summarize the technique, diagnostic performance, and predicting factors of nondiagnostic biopsy, as well as the future perspectives. PMID:26858784

  17. Murine strain differences and the effects of zinc on cadmium concentrations in tissues after acute cadmium exposure.

    PubMed

    King, L M; Anderson, M B; Sikka, S C; George, W J

    1998-10-01

    The role of strain differences in cadmium tissue distribution was studied using sensitive (129/J) and resistant (A/J) mice. These murine strains have previously been shown to differ in their susceptibility to cadmium-induced testicular toxicity. Cadmium concentration was measured in testis, epididymis, seminal vesicle, liver, and kidney at 24 h after cadmium chloride exposure (4, 10, and 20 micromol/kg CdCl2). The 129/J mice exhibited a significant increase in cadmium concentration in testis, epididymis, and seminal vesicle at all cadmium doses used, compared to A/J mice. However, cadmium concentrations in liver and kidney were not different between the strains, at any dose, indicating that cadmium uptake is similar in these organs at 24 h. These murine strains demonstrate similar hepatic and renal cadmium uptake but significantly different cadmium accumulation in the reproductive organs at 24 h. The mechanism of the protective effect of zinc on cadmium toxicity was studied by assessing the impact of zinc acetate (ZnAc) treatment on cadmium concentrations in 129/J mice after 24 h. Zinc pretreatment (250 micromol/kg ZnAc), given 24 h prior to 20 micromol/kg CdCl2 administration, significantly decreased the amount of cadmium in the testis, epididymis, and seminal vesicle of 129/J mice, and significantly increased the cadmium content of the liver after 24 h. Cadmium levels in the kidney were unaffected at this time. Zinc pretreatment also prevented the cadmium-induced decrease in testicular sperm concentration and epididymal sperm motility seen in 129/J mice. These findings suggest that the differences in the two murine strains may be attributed partly to the differential accumulation of cadmium in murine gonads. This may be caused by strain differences in the specificity of cadmium transport mechanisms. The protective role of zinc in cadmium-induced testicular toxicity in the sensitive strain may be due to an interference in the cadmium uptake by susceptible

  18. Circadian regulation of renal function.

    PubMed

    Firsov, Dmitri; Bonny, Olivier

    2010-10-01

    Urinary excretion of water and all major electrolytes exhibit robust circadian oscillations. The 24-h periodicity has been well documented for several important determinants of urine formation, including renal blood flow, glomerular filtration, tubular reabsorption, and tubular secretion. Disturbance of the renal circadian rhythms is increasingly recognized as a risk factor for hypertension, polyuria, and other diseases and may contribute to renal fibrosis. The origin of these rhythms has been attributed to the reactive response of the kidney to circadian changes in volume and/or in the composition of extracellular fluids that are entrained by rest/activity and feeding/fasting cycles. However, numerous studies have shown that most of the renal excretory rhythms persist for long periods of time, even in the absence of periodic environmental cues. These observations led to the hypothesis of the existence of a self-sustained mechanism, enabling the kidney to anticipate various predictable circadian challenges to homeostasis. The molecular basis of this mechanism remained unknown until the recent discovery of the mammalian circadian clock made of a system of autoregulatory transcriptional/translational feedback loops, which have been found in all tissues studied, including the kidney. Here, we present a review of the growing evidence showing the involvement of the molecular clock in the generation of renal excretory rhythms. PMID:20664559

  19. Drugs Approved for Kidney (Renal Cell) Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs ... that are not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) ...

  20. Radiographic Kinetics of Sarcomatoid Renal Cell Carcinoma.

    PubMed

    Syed, Ali; Raval, Amar; Pridjian, Andrew; Birbe, Ruth; Trabulsi, Edouard J

    2016-07-01

    Renal cell carcinoma is a common entity often managed surgically with excellent survival benefits. We report a rare case of sarcomatoid renal cell carcinoma with aggressive growth kinetics after palliative resection captured radiographically. PMID:27041470

  1. General Information about Renal Cell Cancer

    MedlinePlus

    ... Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  2. Genetics Home Reference: renal coloboma syndrome

    MedlinePlus

    ... 1 link) The Kidney and Urology Foundation of America GeneReviews (1 link) Renal Coloboma Syndrome Genetic Testing Registry (1 link) Renal coloboma syndrome Scientific articles on PubMed (1 link) PubMed OMIM (1 ...

  3. Paraneoplastic Cough and Renal Cell Carcinoma

    PubMed Central

    Sullivan, Stephen

    2016-01-01

    A case of patient with intractable cough due to renal cell carcinoma is reported. The discussion reviews the literature regarding this unusual paraneoplastic manifestation of renal malignancy. PMID:27445553

  4. Parasites and chronic renal failure

    PubMed Central

    Mohammadi Manesh, Reza; Hosseini Safa, Ahmad; Sharafi, Seyedeh Maryam; Jafari, Rasool; Bahadoran, Mehran; Yousefi, Morteza; Nasri, Hamid; Yousofi Darani, Hossein

    2014-01-01

    Suppression of the human immune system results in an increase in susceptibility to infection by various infectious agents. Conditions such as AIDS, organ transplantation and chronic renal insufficiency (CRI) are the most important cause of insufficient immune response against infections. Long term renal disorders result in uremia, which can suppress human immune system. Parasitic infections are one of the most important factors indicating the public health problems of the societies. These infections can be more hostile and life threatening in susceptible individuals than in the normal people. In these patients some parasitic infections such as blastocystiosis, cryptosporidiosis and toxoplasmosis have been reported to be more prevalent. This review aimed to give an overview about parasitic infections in patients with renal disorders. PMID:25610885

  5. Primary renal primitive neuroectodermal tumor

    PubMed Central

    Goel, V; Talwar, V; Dodagoudar, C; Singh, S; Sharma, A; Patnaik, N

    2015-01-01

    Primitive Neuroectodermal Tumor of the kidney is a rare entity. Very few cases of primary renal PNET have been reported to date. Most literature about rPNET is isolated case reports. We report a case of rPNET in a 39-year-old male with a pre-operative diagnosis of renal cell carcinoma with renal vein thrombosis. The patient underwent radical nephrectomy with thrombolectomy, and histopathological examination revealed a highly aggressive tumor composed of monotonous sheets of round cells. Tumor cells were positive for CD 99 and FLI-1, hence confirming the diagnosis of Primitive Neuroectodermal Tumor. Post-surgery, patient was given VAC/IE-based adjuvant chemotherapy. In view of highly aggressive nature of this tumor, prompt diagnosis and imparting effective chemotherapy regimen to the patient is required, and it is important to differentiate PNET from other small round-cell tumors because of different therapeutic approach. PMID:25766349

  6. Future challenges in renal transplantation.

    PubMed

    Whalen, H; Clancy, M; Jardine, A

    2012-02-01

    There is a worldwide increase in the incidence of end-stage renal disease. Renal transplantation has been shown to be cost effective, prolong survival and provide a better quality of life in comparison to dialysis. Consequently, there has been a steady increase in demand for organs leading to a shortage of available kidneys, and an increase in transplant waiting lists. Renal transplantation is therefore an expanding field with a number of unique future challenges to address. This article outlines strategies that may be employed to expand organ supply in order to meet increased demand. The ethical issues surrounding this are also summarized. Furthermore, we highlight techniques with the potential to minimize peri-transplant injury to the kidney on its journey from donor to recipient. Current and potential future management strategies to optimize graft and patient survival are also discussed. PMID:22361673

  7. Management of diabetic renal disease

    PubMed Central

    Eboh, Cecil

    2015-01-01

    Diabetic nephropathy is the leading cause of end stage renal failure (ESRF) worldwide, representing over 50% of patients on renal replacement therapy in some parts of the world. The condition is common in people with type 1 and type 2 diabetes, although the incidence appears to be declining, especially in type 1 diabetes. More than 1 in 3 people with type 2 diabetes have impaired kidney function. Advances in our understanding of the pathogenesis and natural history of the condition have enabled us to consider earlier therapy aimed at renal preservation and reduction in cardiovascular morbidity. Microalbuminuria is now established as the earliest risk marker for nephropathy in type 1 diabetes and cardiovascular disease in type 2 diabetes. This review examines the current concepts in the pathogenesis and management of diabetic nephropathy. PMID:26244141

  8. Renal calculus complicated with squamous cell carcinoma of renal pelvis: Report of two cases.

    PubMed

    Xiao, Jiantao; Lei, Jun; He, Leye; Yin, Guangming

    2015-01-01

    Longstanding renal calculus is a risk factor of squamous cell carcinoma (SCC) of the renal pelvis. It is highly aggressive and usually diagnosed at advanced stages with a poor prognosis. We present two cases of kidney stone complications with renal pelvic SCC. These two patients had a radical nephrectomy and the dissected tissues were renal pelvic SCC. Our cases further emphasize that renal pelvic SCC should be considered in patients with longstanding renal calculus. These cases contribute greatly to an early diagnosis and early treatment, both of which will significantly minimize the damage of, and markedly improve the prognosis of, renal pelvic SCC. PMID:26029303

  9. Renal calculus complicated with squamous cell carcinoma of renal pelvis: Report of two cases

    PubMed Central

    Xiao, Jiantao; Lei, Jun; He, Leye; Yin, Guangming

    2015-01-01

    Longstanding renal calculus is a risk factor of squamous cell carcinoma (SCC) of the renal pelvis. It is highly aggressive and usually diagnosed at advanced stages with a poor prognosis. We present two cases of kidney stone complications with renal pelvic SCC. These two patients had a radical nephrectomy and the dissected tissues were renal pelvic SCC. Our cases further emphasize that renal pelvic SCC should be considered in patients with longstanding renal calculus. These cases contribute greatly to an early diagnosis and early treatment, both of which will significantly minimize the damage of, and markedly improve the prognosis of, renal pelvic SCC. PMID:26029303

  10. Renal tubular secretion of pramipexole.

    PubMed

    Knop, Jana; Hoier, Eva; Ebner, Thomas; Fromm, Martin F; Müller, Fabian

    2015-11-15

    The dopamine agonist pramipexole is cleared predominantly by the kidney with a major contribution of active renal secretion. Previously the organic cation transporter 2 (OCT2) was shown to be involved in the uptake of pramipexole by renal tubular cells, while the mechanism underlying efflux into tubular lumen remains unclear. Cimetidine, a potent inhibitor of multidrug and toxin extrusion proteins 1 (MATE1) and 2-K (MATE2-K), decreases renal pramipexole clearance in humans. We hypothesized that, in addition to OCT2, pramipexole may be a substrate of MATE-mediated transport. Pramipexole uptake was investigated using MDCK or HEK cells overexpressing OCT2, MATE1 or MATE2-K and the respective vector controls (Co). Transcellular pramipexole transport was investigated in MDCK cells single- or double-transfected with OCT2 and/or MATE1 and in Co cells, separating a basal from an apical compartment in a model for renal tubular secretion. Pramipexole uptake was 1.6-, 1.1-, or 1.6-folds in cells overexpressing OCT2, MATE1 or MATE2-K, respectively as compared to Co cells (p<0.05). In transcellular transport experiments, intracellular pramipexole accumulation was 1.7-folds in MDCK-OCT2 (p<0.001), and transcellular pramipexole transport was 2.2- and 4.0-folds in MDCK-MATE1 and MDCK-OCT2-MATE1 cells as compared to Co cells (p<0.001). Transcellular pramipexole transport was pH dependent and inhibited by cimetidine with IC50 values of 12μM and 5.5μM in MATE1 and OCT2-MATE1 cells, respectively. Taken together, coordinate activity of OCT2-mediated uptake and MATE-mediated efflux determines pramipexole renal secretion. Reduced OCT2 or MATE transport activity due to genetic variation or drug-drug interactions may affect pramipexole renal secretion. PMID:26360835

  11. Renal pelvis urothelial carcinoma of the upper moiety in complete right renal duplex: a case report

    PubMed Central

    Zhang, Yiran; Yu, Quanfeng; Zhang, Zhihong; Liu, Ranlu; Xu, Yong

    2015-01-01

    Urothelial carcinoma (UC) originated from renal pelvis is the common tumor of the urinary system, however, neoplasia of the renal pelvis in duplex kidneys is extremely rare, especially in the complete renal and ureteral duplex cases. We present the first case of renal pelvis UC of the upper moiety in a complete right renal duplex. This male patient has bilateral complete renal and ureteral duplex. To the best of our knowledge, this is the first reported case of renal pelvis UC in a complete renal duplex system. After this experience we feel that the diagnosis of renal pelvis UC in duplex kidneys is not so easy, and once the diagnosis is determined, the whole renal duplex units and bladder cuff or ectopic orifice should be excised radically. PMID:26823906

  12. Papillary adenocarcinoma of the renal pelvis with renal calculus: A rare case report

    PubMed Central

    LI, JIANLONG; LI, QING; YU, YI

    2016-01-01

    Papillary adenocarcinoma of the renal pelvis is a rare clinicopathology of a kidney tumor with renal calculus. In the present case report, percutaneous renal biopsy, nephroscope lithotripsy and radical nephroureterectomy within a papillary adenocarcinoma of the renal pelvis accompanied with renal calculus was performed on a 65-year-old patient, also including a report on the patient's data and a literature review. The histopathological features confirmed the diagnosis of papillary adenocarcinoma of the renal pelvis. Tumors of the renal pelvis are uncommon features of urothelial carcinoma, and papillary adenocarcinoma of the renal pelvis is a very unusual entity. The present case report describes papillary adenocarcinoma of the renal pelvis with renal calculus, which has rarely been previously reported. PMID:27123287

  13. Effect of Ceftriaxone on the Outcome of Murine Pyelonephritis Caused by Extended-Spectrum-β-Lactamase-Producing Escherichia coli

    PubMed Central

    Tratselas, A.; Simitsopoulou, M.; Giannakopoulou, A.; Dori, I.; Saoulidis, S.; Kollios, K.; Papaioannidou, P.; Pournaras, S.

    2014-01-01

    Urinary tract infections (UTIs) due to extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae in children are becoming more frequent, and they are commonly treated initially with a second- or third-generation cephalosporin. We developed a murine model of ascending UTI caused by ESBL-producing Escherichia coli. Using this model, we investigated the renal bacterial burden, interleukin-6 (IL-6) expression, and histopathological alterations caused by ESBL- and non-ESBL-producing bacteria after 1, 2, or 6 days with or without ceftriaxone therapy. The renal bacterial burden, IL-6 concentration, and histological inflammatory lesions were not significantly different between mice infected with ESBL- and non-ESBL-producing bacteria without treatment at any of the time points examined. Following ceftriaxone administration, the bacterial burden was eliminated in the kidneys of mice infected with ESBL- and non-ESBL-producing bacteria on the 6th postinfection day. The histological analysis demonstrated that among mice treated with ceftriaxone, those infected with ESBL-producing bacteria had more profound renal alterations than those infected with non-ESBL-producing bacteria on the 6th day (P < 0.001). In comparison, microbiological outcomes did not differ significantly between mice infected with ESBL- and non-ESBL-producing bacteria at any of the time points examined. The effectiveness of ceftriaxone in mice with UTIs due to ESBL-producing E. coli may have therapeutic implications; it is, however, hampered by limited activity on the histopathological lesions, a finding that needs further investigation. PMID:25224003

  14. Irradiation Design for an Experimental Murine Model

    SciTech Connect

    Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

    2010-12-07

    In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

  15. Efficacy of Posaconazole in Murine Experimental Sporotrichosis

    PubMed Central

    Fernández-Silva, Fabiola; Capilla, Javier; Mayayo, Emilio

    2012-01-01

    We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology. PMID:22330929

  16. Imaging patients with renal impairment.

    PubMed

    Mathur, Mahan; Weinreb, Jeffrey C

    2016-06-01

    Imaging with intravascular contrast media is generally considered safe, particularly in patients without renal failure. However, as renal function deteriorates, the potential risk of nonallergic-type adverse events increases. This presents a unique challenge, particularly when the use of intravenous contrast media is deemed essential for diagnostic purposes. Following a discussion regarding the definition and epidemiology of kidney injury, this review focuses on the evolving understanding of both contrast-induced nephropathy and nephrogenic systemic fibrosis and discusses preventative strategies aimed at minimizing the risk of developing these entities. Alternative non-contrast imaging techniques are also discussed. PMID:27015867

  17. Emerging Entities in Renal Neoplasia.

    PubMed

    Mehra, Rohit; Smith, Steven C; Divatia, Mukul; Amin, Mahul B

    2015-12-01

    This article reviews emerging entities in renal epithelial neoplasia, including tubulocystic carcinoma, clear-cell-papillary renal cell carcinoma (RCC), thyroid-like follicular RCC, ALK-related RCC, translocation RCC, acquired cystic disease-related RCC, succinate dehydrogenase-deficient RCC, and hereditary leiomyomatosis-RCC syndrome-associated RCC. Many of these rarer subtypes of RCC were recently studied in more depth and are included in the upcoming version of the World Health Organization classification of tumors. Emphasis is placed on common gross and morphologic features, differential diagnoses, use of ancillary studies for making accurate diagnoses, molecular alterations, and predicted biologic behavior based on previous studies. PMID:26612218

  18. Isolation of renal brush borders.

    PubMed

    Morré, D James; Hammond, Timothy

    2007-03-01

    Methods are described to isolate intact brush borders and brush border membranes from renal cell homogenates. A rapid method yields sealed vesicles that reconstitute renal brush border transport. In one variation of this protocol, 10 to 20 mM CaCl2 or MgCl2 is added to aggregate non-brush border structures for subsequent removal by centrifugation. For analytical studies, guidance is provided for subsequent purification steps including preparative free-flow and aqueous two-phase partition. Marker enzymes and morphological parameters are included for assessment of yield and fraction purity. PMID:18228514

  19. Mass spectrometry and renal calculi

    PubMed Central

    Purcarea, VL; Sisu, I; Sisu, E

    2010-01-01

    The present review represents a concise and complete survey of the literature covering 2004–2009, concerning the mass spectrometric techniques involved in the structural investigation of renal calculi. After a short presentation of the fundamental mass spectrometric techniques (MALDI–TOF, QTOF, MS–MS) as well as hyphenated methods (GC–MS, LC–MS, CE–MS), an extensive study of the urinary proteome analysis as well as the detection and quantification by mass spectrometry of toxins, drugs and metabolites from renal calculi is presented. PMID:20968197

  20. Reemergence of Murine Typhus in Galveston, Texas, USA, 2013

    PubMed Central

    Vohra, Rahat F.; Bouyer, Donald H.; Walker, David H.

    2015-01-01

    Twelve patients with murine typhus were identified in Galveston, Texas, USA, in 2013. An isolate from 1 patient was confirmed to be Rickettsia typhi. Reemergence of murine typhus in Galveston emphasizes the importance of vector control and awareness of this disease by physicians and public health officials. PMID:25695758

  1. Acute Renal Failure after Uterine Artery Embolization

    SciTech Connect

    Rastogi, Sachin; Wu, Yu-Hsin; Shlansky-Goldberg, Richard D.; Stavropoulos, S. William

    2004-09-15

    Renal failure is a potential complication of any endovascular procedure using iodinated contrast, including uterine artery embolization (UAE). In this report we present a case of acute renal failure (ARF) following UAE performed as a treatment for uterine fibroids. The likely causes of ARF in this patient are explored and the possible etiologies of renal failure in patients undergoing UAE are reviewed.

  2. Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure

    PubMed Central

    Konkalmatt, Prasad R.; Asico, Laureano D.; Zhang, Yanrong; Yang, Yu; Drachenberg, Cinthia; Zheng, Xiaoxu; Han, Fei; Jose, Pedro A.; Armando, Ines

    2016-01-01

    Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing of Drd2 using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue of Drd2 expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vector with DRD2. Renal Drd2 siRNA treatment decreased the renal expression of DRD2 protein by 55%, and DRD2 AAV treatment increased the renal expression of DRD2 protein by 7.5- to 10-fold. Renal-selective DRD2 rescue reduced the expression of proinflammatory factors and kidney injury, preserved renal function, and normalized systolic and diastolic blood pressure. These results demonstrate that the deleterious effects of renal-selective Drd2 silencing on renal function and blood pressure were rescued by renal-selective overexpression of DRD2. Moreover, the deleterious effects of 45-minute bilateral ischemia/reperfusion on renal function and blood pressure in mice were ameliorated by a renal-selective increase in DRD2 expression by the retrograde ureteral infusion of DRD2 AAV immediately after the induction of ischemia/reperfusion injury. Thus, 14 days after ischemia/reperfusion injury, the renal expression of profibrotic factors, serum creatinine, and blood pressure were lower in mice infused with DRD2 AAV than in those infused with control AAV. These results indicate an important role of renal DRD2 in limiting renal injury and preserving normal renal function and blood pressure. PMID:27358912

  3. Renal functional reserve and renal recovery after acute kidney injury.

    PubMed

    Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio

    2014-01-01

    Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use. PMID:25343829

  4. Chemical Renal Denervation in the Rat

    SciTech Connect

    Consigny, Paul M. Davalian, Dariush; Donn, Rosy Hu, Jie; Rieser, Matthew Stolarik, DeAnne

    2013-12-03

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  5. Protective effect of lyophilized recombinant human brain natriuretic peptide on renal ischemia/reperfusion injury in mice.

    PubMed

    Cao, X; Xia, H Y; Zhang, T; Qi, L C; Zhang, B Y; Cui, R; Chen, X; Zhao, Y R; Li, X Q

    2015-01-01

    Brain natriuretic peptide (BNP) has a protective effect on acute injury of the heart, brain, and lung. However, its role in acute kidney injury (AKI) remains unclear. The aim of this study was to investigate the effect of lyophilized recombinant human BNP (lrh-BNP) on AKI and the underlying molecular mechanisms. An experimental model for AKI was established using an ischemia/reperfusion (I/R) procedure. Healthy adult BALB/c mice were randomized to the sham, I/R, and lrh-BNP-treated post-I/R (BNP + I/R) groups. Post-operatively, the BNP + I/R group was subcutaneously injected with lrh-BNP (0.03 μg·kg(-1)·min(-1)), whereas the other groups received saline at the same dose. Serum creatinine (Scr) and blood urea nitrogen levels were examined; tissue staining was performed to evaluate the degree of I/R injury (IRI). Ki67 positive staining of renal tubular epithelial cells was observed using immunofluorescence confocal laser scanning to assess the effect of BNP on cell proliferation after IRI. Inflammatory factor expression levels were detected to evaluate the effect of BNP on renal inflammation. Compared with the sham group, the I/R group showed increased Scr levels, severe tubular injury of the renal outer medulla, increased Kim-1 mRNA expression, an increased number of infiltrative macrophages in the renal interstitium, and increased TNF-α, IL- 1β, IL-6, MCP-1, and HIF-1α mRNA expression. BNP delivery significantly reduced all pathological changes in the I/R group. The protective role of BNP in murine renal IRI may be associated with its inhibition of renal interstitial inflammation and hypoxia and its promotion of renal tubule repair. PMID:26535643

  6. Sexual dimorphism of Murine Masticatory Muscle Function

    PubMed Central

    Daniels, David W.; Tian, Zuozhen; Barton, Elisabeth R.

    2008-01-01

    (1) Objective To determine if gender distinctions of force generating capacity existed in murine masticatory muscles. (2) Design In order to investigate the effect of sex on force generating capacity in this muscle group, an isolated muscle preparation was developed utilizing the murine anterior deep masseter. Age-matched male and female mice were utilized to assess function, muscle fiber type and size in this muscle. (3) Results Maximum isometric force production was not different between age-matched male and female mice. However, the rate of force generation and relaxation was slower in female masseter muscles. Assessment of fiber type distribution by immunohistochemistry revealed a threefold decrease in the proportion of myosin heavy chain 2b positive fibers in female masseters, which correlated with the differences in contraction kinetics. (4) Conclusions These results provide evidence that masticatory muscle strength in mice is not affected by sex, but there are significant distinctions in kinetics associated with force production between males and females. PMID:18028868

  7. Renal effects of percutaneous stone removal

    SciTech Connect

    Eshghi, M.; Schiff, R.G.; Smith, A.D.

    1989-02-01

    Preoperative and postoperative renography with 99mTechnetium-diethylene-triamine pentaacetic acid was performed on 33 patients who were free of renal scarring, infection, and obstruction and who underwent percutaneous renal stone removal. Although there was a transient decrease in renal function postoperatively in some patients, statistically significant reductions in renal function occurred only in 1 patient with an arteriovenous malformation that was embolized and in 1 patient who had a postoperative ureteropelvic junction stricture. The creation of more than one nephrostomy tract did not affect the results. In the absence of serious complications, percutaneous nephrostomy does not have a significant effect on renal function.

  8. Renal function in diabetic nephropathy.

    PubMed

    Dabla, Pradeep Kumar

    2010-05-15

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease. PMID:21537427

  9. [Great moments in renal transplantation].

    PubMed

    Ghossain, Antoine

    2015-01-01

    A selective review of some great moments in renal transplantation experienced or witnessed with some of the great architects of this epic. The path was strewn with hazards, sometimes halts or changes of attitude that harmed or helped some patients. PMID:26591188

  10. Emphysema in the renal allograft

    SciTech Connect

    Potter, J.L.; Sullivan, B.M.; Fluornoy, J.G.; Gerza, C.

    1985-04-01

    Two diabetic patients in whom emphysematous pyelonephritis developed after renal transplantation are described. Clinical recognition of this unusual and serious infection is masked by the effects of immunosuppression. Abdominal radiographic, ultrasound, and computed tomography findings are discussed. The clinical presentation includes urinary tract infection, sepsis, and acute tubular malfunction of the allograft in insulin-dependent diabetics.

  11. Renal leiomyosarcoma in a cat.

    PubMed

    Evans, Dawn; Fowlkes, Natalie

    2016-05-01

    Renal leiomyosarcoma was diagnosed in a 10-year-old Domestic Shorthair cat with a 3-year history of clinically managed, chronic renal disease. Sudden death was preceded by a brief episode of mental dullness and confusion. At postmortem examination, the gross appearance of the left kidney was suggestive of hydronephrosis, and a nephrolith was present in the contralateral kidney. However, histology revealed an infiltrative, poorly differentiated, spindle cell sarcoma bordering the grossly cavitated area. Neoplastic cells were immunoreactive for vimentin and smooth muscle actin, which led to a diagnosis of renal leiomyosarcoma; neoplastic cells were not immunoreactive for desmin. Leiomyosarcoma arising in the kidney is a rare occurrence in humans and an even rarer occurrence in veterinary medicine with no prior cases being reported in cats in the English literature. The macroscopic appearance of the tumor at postmortem examination was misleadingly suggestive of hydronephrosis as a result of the large cavitation and may be similar to particularly unusual cases of renal leiomyosarcomas in humans that have a cystic or cavitated appearance. PMID:26975352

  12. [Renal failure and cystic kidney diseases].

    PubMed

    Correas, J-M; Joly, D; Chauveau, D; Richard, S; Hélénon, O

    2011-04-01

    Cystic kidney diseases often are discovered at the time of initial work-up of renal failure through ultrasound or family history, or incidentally at the time of an imaging test. Hereditary diseases include autosomal dominant or recessive polycystic kidney disease (PKD), tuberous sclerosis (TS) and medullary cystic kidney disease (MCKD). Autosomal dominant PKD is characterized by large renal cysts developing in young adults. Renal failure is progressive and becomes severe around 50-60 years of age. Atypical cysts (hemorrhagic or hyperdense) are frequent on CT and MRI examinations. Imaging plays a valuable role in the management of acute complications such as cyst hemorrhage or infection. Autosomal recessive PKD is often detected in neonates, infants or young adults. It is characterized by renal enlargement due to the presence of small cysts and liver disease (fibrosis and biliary ductal dilatation). Late manifestation or slow progression of autosomal recessive PKD may be more difficult to distinguish from autosomal dominant PKD. These cystic kidney diseases should not be confused with non-hereditary incidental multiple renal cysts. In tuberous sclerosis, renal cysts are associated with angiomyolipomas and sometimes pulmonary lymphangioleiomyomatosis. Renal failure is inconstant. Other hereditary cystic kidney diseases, including MCKD and nephronophtisis, are usually associated with renal failure. Non-hereditary cystic kidney diseases include multicystic renal dysplasia (due to complete pelvi-ureteric atresia or hydronephrosis), acquired multicystic kidney disease (chronic renal failure, chronic hemodialysis) and varied cystic kidney diseases (multicystic renal disease, glomerulocystic kidney disease, microcystic kidney disease). PMID:21549887

  13. Renal lesions of nondomestic felids.

    PubMed

    Newkirk, K M; Newman, S J; White, L A; Rohrbach, B W; Ramsay, E C

    2011-05-01

    To comprehensively evaluate the occurrence of renal lesions in a variety of nondomestic felids, necropsy cases from 1978 to 2008 were reviewed from a municipal zoo and a large cat sanctuary for those in which the kidneys were examined histologically. Seventy exotic felids were identified (25 tigers, 18 lions, 6 cougars, 5 leopards, 3 snow leopards, 3 clouded leopards, 3 Canadian lynx, 2 ocelots, 2 bobcats, 2 cheetahs, 1 jaguar), and their histologic renal lesions were evaluated and compared. The most common lesion was tubulointerstitial nephritis (TIN); 36 of 70 (51%) cats were affected to some degree. Lymphocytic interstitial nephritis was the most common lesion in the tigers (9 of 25, 36%) and was rarely seen in other species. Although the renal pelvis was not available for all cats, 28 of 47 (60%) had some degree of lymphocytic pyelitis. There was no significant association between the presence of pyelitis and that of TIN. Only 1 cat had pyelonephritis. Renal papillary necrosis was present in 13 of 70 (19%) cats and was significantly associated with historical nonsteroidal anti-inflammatory drug treatment (odds ratio, 7.1; 95% confidence interval, 1.9 to 26.8). Only 1 cat (lion) had amyloid accumulation, and it was restricted to the corticomedullary junction. Primary glomerular lesions were absent in all cats. Intraepithelial pigment was identified in many of the cats but was not correlated with severity of TIN. Despite several previous reports describing primary glomerular disease or renal amyloidosis in exotic felids, these lesions were rare to absent in this population. PMID:20876911

  14. Propranolol disposition in renal failure.

    PubMed Central

    Wood, A J; Vestal, R E; Spannuth, C L; Stone, W J; Wilkinson, G R; Shand, D G

    1980-01-01

    1 Previous studies of propranolol disposition in renal failure have been conflicting. 2 Using simultaneous administration of [3H]-propranolol intravenously and unlabelled propranolol orally the principal determinants of drug distribution were calculated in normals, patients with severe renal impairment (creatinine clearance 14.5 +/- 2.8 ml/min) but not on haemodialysis and patients on haemodialysis (creatinine clearance less than 5 ml/min). 3 The effect of haemodialysis on propranolol binding and free fraction was also examined. The percentage of propranolol unbound rose from 7.1% to 9.9%. (P less than 0.001) 20 min following heparinization and beginning haemodialysis. This was accompanied by a large rise in free fatty acids from 0.567 +/- 0.059 to 3.326 +/- 0.691 mumol/ml (P less than 0.005). 4 The blood to plasma concentration ratios of propranolol were significantly higher in patients with renal failure (P less than 0.02) and on haemodialysis (P less than 0.001) and were significantly negatively correlated (P less than 0.001) with the haematocrit. 5 Although the half-life propranolol was significantly shortened in the patients with renal failure (P less than 0.02), there was no change in the apparent liver blood flow, extraction ratio or the principal determinants of steady-state drug concentrations in blood namely oral and intravenous clearance from blood. 6 There is, therefore, no pharmacokinetic basis to adjust the dosage of propranolol in patients with renal failure. PMID:7470370

  15. Renal interventions during endovascular aneurysm repair.

    PubMed

    Davies, Mark G

    2013-12-01

    Renal insufficiency is a risk factor for mortality and morbidity during endovascular aneurysm repair. Multiple changes in practice have occurred to mitigate renal injury and renal dysfunction. Transrenal fixation does carry an increased risk of a decline in renal function in the medium term. Renal stenting for athero-occlusive disease during endovascular aneurysm repair needs careful consideration, as indications have changed and there are unexpected consequences with early vessel occlusion. The growing number of renal interventions during complex endovascular aneurysm repair with the advent of chimney snorkel/periscope techniques and the introduction of fenestrated grafts has shown the resilience of the intervention with relatively low renal issues (approximately 10%), but has also illustrated the need for additional device development. PMID:25220325

  16. Imaging of haemodialysis: renal and extrarenal findings.

    PubMed

    Degrassi, Ferruccio; Quaia, Emilio; Martingano, Paola; Cavallaro, Marco; Cova, Maria Assunta

    2015-06-01

    Electrolyte alterations and extra-renal disorders are quite frequent in patients undergoing haemodialysis or peritoneal dialysis. The native kidneys may be the site of important pathologies in patients undergoing dialysis, especially in the form of acquired renal cystic disease with frequent malignant transformation. Renal neoplasms represents an important complication of haemodialysis-associated acquired cystic kidney disease and imaging surveillance is suggested. Extra-renal complications include renal osteodistrophy, brown tumours, and thoracic and cardiovascular complications. Other important fields in which imaging techniques may provide important informations are arteriovenous fistula and graft complications. Teaching points • Renal neoplasms represent a dreaded complication of haemodialysis.• In renal osteodystrophy bone resorption typically manifests along the middle phalanges.• Brown tumours are well-defined lytic lesions radiographically, possibly causing bone expansion.• Vascular calcifications are very common in patients undergoing haemodialysis.• Principal complications of the AV fistula consist of thrombosis, aneurysms and pseudoaneurysms. PMID:25680325

  17. Renal relevant radiology: renal functional magnetic resonance imaging.

    PubMed

    Ebrahimi, Behzad; Textor, Stephen C; Lerman, Lilach O

    2014-02-01

    Because of its noninvasive nature and provision of quantitative measures of a wide variety of physiologic parameters, functional magnetic resonance imaging (MRI) shows great potential for research and clinical applications. Over the past decade, application of functional MRI extended beyond detection of cerebral activity, and techniques for abdominal functional MRI evolved. Assessment of renal perfusion, glomerular filtration, interstitial diffusion, and parenchymal oxygenation turned this modality into an essential research and potentially diagnostic tool. Variations in many renal physiologic markers can be detected using functional MRI before morphologic changes become evident in anatomic magnetic resonance images. Moreover, the framework of functional MRI opened a window of opportunity to develop novel pathophysiologic markers. This article reviews applications of some well validated functional MRI techniques, including perfusion, diffusion-weighted imaging, and blood oxygen level-dependent MRI, as well as some emerging new techniques such as magnetic resonance elastography, which might evolve into clinically useful tools. PMID:24370767

  18. Modulating the Adhesion of Haematopoietic Stem Cells with Chemokines to Enhance Their Recruitment to the Ischaemically Injured Murine Kidney

    PubMed Central

    White, Rebecca L.; Nash, Gerard; Kavanagh, Dean P. J.; Savage, Caroline O. S.; Kalia, Neena

    2013-01-01

    Introduction Renal disease affects over 500 million people worldwide and is set to increase as treatment options are predominately supportive. Evidence suggests that exogenous haematopoietic stem cells (HSCs) can be of benefit but due to the rarity and poor homing of these cells, benefits are either minor or transitory. Mechanisms governing HSC recruitment to injured renal microcirculation are poorly understood; therefore this study determined (i) the adhesion molecules responsible for HSC recruitment to the injured kidney, (ii) if cytokine HSC pre-treatment can enhance their homing and (iii) the molecular mechanisms accountable for any enhancement. Methods Adherent and free-flowing HSCs were determined in an intravital murine model of renal ischaemia-reperfusion injury. Some HSCs and animals were pre-treated prior to HSC infusion with function blocking antibodies, hyaluronidase or cytokines. Changes in surface expression and clustering of HSC adhesion molecules were determined using flow cytometry and confocal microscopy. HSC adhesion to endothelial counter-ligands (VCAM-1, hyaluronan) was determined using static adhesion assays in vitro. Results CD49d, CD44, VCAM-1 and hyaluronan governed HSC adhesion to the IR-injured kidney. Both KC and SDF-1α pre-treatment strategies significantly increased HSC adhesion within injured kidney, whilst SDF-1α also increased numbers continuing to circulate. SDF-1α and KC did not increase CD49d or CD44 expression but increased HSC adhesion to VCAM-1 and hyaluronan respectively. SDF-1α increased CD49d surface clustering, as well as HSC deformability. Conclusion Increasing HSC adhesive capacity for its endothelial counter-ligands, potentially through surface clustering, may explain their enhanced renal retention in vivo. Furthermore, increasing HSC deformability through SDF-1α treatment could explain the prolonged systemic circulation; the HSC can therefore continue to survey the damaged tissue instead of becoming entrapped

  19. Bay11-7082 attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation.

    PubMed

    Zhao, Jijun; Zhang, Hui; Huang, Yuefang; Wang, Hongyue; Wang, Shuang; Zhao, Chunmei; Liang, Yingjie; Yang, Niansheng

    2013-09-01

    Nuclear factor-kappa B (NF-κB) and NLRP3 inflammasome are involved in inflammation and autoimmunity. In vitro data have shown that Bay11-7082 selectively inhibits NLRP3 inflammasome activity independent of NF-κB activity. In this study, we evaluated the therapeutic effects of Bay11-7082 on murine lupus nephritis (LN) in vivo. Twelve-week-old MRL/lpr mice were treated with either Bay11-7082 (5mg/kg) or vehicle (DMSO/PBS buffer) by intraperitoneal injection thrice per week for 8 weeks. NLRP3 inflammasome formation and NF-κB activation were measured. Histopathology, immune complex deposits, proteinuria, renal function and production of anti-dsDNA antibody as well as inflammatory markers were evaluated. Bay11-7082 treatment inhibited renal NLRP3 inflammasome formation and NF-κB activation in vivo. Bay11-7082 decreased proteinuria, blood urea nitrogen, resulting in dramatically attenuated renal damage. Bay11-7082-treated mice had decreased serum anti-dsDNA level and less renal immune complex deposition. The IL-1β, TNF-α and chemokine (C-C Motif) ligand 2 (CCL2) levels and infiltration of macrophages as well as the mortality were significantly reduced by Bay11-7082 treatment. This study suggests that dual inhibition of NLRP3 inflammasome and NF-κB activation using Bay11-7082 or its analogues may be a promising therapeutic strategy for preventing the progression of LN. PMID:23770281

  20. Diagnostic value of routine bone scintigraphy renal imaging in renal cell carcinoma

    SciTech Connect

    Chancellor, M.B.; Konnak, J.W.; Grossman, H.B.

    1989-05-01

    Technetium-99m-phosphate compounds used in bone scanning are excreted by the kidney, and excellent renal images can be obtained on routine bone scintigrams. The preoperative bone scans of 49 patients who underwent radical nephrectomy for renal cell carcinoma between 1981 and 1985 were reviewed for renal imaging. Ninety-four percent of the patients had abnormal bone scan renal images (82% had focal decreased uptake, and 12% had focal increased uptake). Six percent of the renal images were symmetrical bilaterally. When bone scans are employed in the postoperative follow-up of patients with renal cancer, they can be used to assess the status of the remaining kidney.

  1. Renal Cell Carcinoma Arising From Renal Allograft Detected by 18F-FDG PET-CT.

    PubMed

    Guo, Yuehong; Wang, Tie

    2016-05-01

    Renal cell carcinoma arising from renal allograft is a rare condition. A 56-year-old man with a history of 3 renal transplantation due to renal failure presented poor appetite and weight loss for 3 months. Possibility of tumor of unknown origin was suspected. For this reason, an FDG PET/CT was performed, and the images showed a hypermetabolic focus in the lower pole of the left renal transplant, suggestive of a malignant lesion. Subsequent pathological examination following allograft nephrectomy confirmed grade 4 renal cell carcinoma. PMID:26825198

  2. Screen-based identification and validation of four new ion channels as regulators of renal ciliogenesis

    PubMed Central

    Slaats, Gisela G.; Wheway, Gabrielle; Foletto, Veronica; Szymanska, Katarzyna; van Balkom, Bas W. M.; Logister, Ive; Den Ouden, Krista; Keijzer-Veen, Mandy G.; Lilien, Marc R.; Knoers, Nine V.; Johnson, Colin A.; Giles, Rachel H.

    2015-01-01

    ABSTRACT To investigate the contribution of ion channels to ciliogenesis, we carried out a small interfering RNA (siRNA)-based reverse genetics screen of all ion channels in the mouse genome in murine inner medullary collecting duct kidney cells. This screen revealed four candidate ion channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4. We show that these four ion channels localize to renal tubules, specifically to the base of primary cilia. We report that human KCNQ1 Long QT syndrome disease alleles regulate renal ciliogenesis; KCNQ1-p.R518X, -p.A178T and -p.K362R could not rescue ciliogenesis after Kcnq1-siRNA-mediated depletion in contrast to wild-type KCNQ1 and benign KCNQ1-p.R518Q, suggesting that the ion channel function of KCNQ1 regulates ciliogenesis. In contrast, we demonstrate that the ion channel function of KCNJ10 is independent of its effect on ciliogenesis. Our data suggest that these four ion channels regulate renal ciliogenesis through the periciliary diffusion barrier or the ciliary pocket, with potential implication as genetic contributors to ciliopathy pathophysiology. The new functional roles of a subset of ion channels provide new insights into the disease pathogenesis of channelopathies, which might suggest future therapeutic approaches. PMID:26546361

  3. Increasing reactive oxygen species as a therapeutic approach to treat hereditary leiomyomatosis and renal cell carcinoma.

    PubMed

    Sourbier, Carole; Valera-Romero, Vladimir; Giubellino, Alessio; Yang, Youfeng; Sudarshan, Sunil; Neckers, Len; Linehan, W Marston

    2010-10-15

    Hereditary leiomyomatosis renal cell carcinoma (HLRCC)-associated renal tumors are aggressive and tend to metastasize early. There are currently no effective forms of therapy for patients with advanced HLRCC-associated kidney cancer. We have previously shown that HLRCC cells express a high level of reactive oxygen species (ROS). In the present study we investigated the cytotoxic effects of increasing ROS level using bortezomib in combination with cisplatin on HLRCC cells in vitro and in an in vivo xenograft model. The cytotoxic effect of several ROS inducers on FH-deficient cells was assessed by synthetic lethality. ROS inducers had a pronounced impact on the viability of FH-deficient cells. Because of its high potency, the proteasome inhibitor bortezomib was further investigated. Bortezomib induced apoptosis in vitro in HLRCC cells and inhibited HLRCC tumour growth in vivo. Bortezomib-associated cytotoxicity was highly correlated with cellular ROS level: combining bortezomib with other ROS inducers enhanced cytotoxicity, while combining bortezomib with a ROS scavenger inhibited its cytotoxic effect. Finally, HLRCC murine xenografts were treated with bortezomib and cisplatin, another ROS inducer. This regimen induced HLRCC tumour regression in vivo. These findings suggest that increasing ROS level in HLRCC above a certain threshold can induce HLRCC-tumor cell death. Increasing tumor ROS with bortezomib in combination with cisplatin represents a novel targeted therapeutic approach to treat advanced HLRCC-associated renal tumors. PMID:20953139

  4. Mechanisms of HO-1 mediated attenuation of renal immune injury: a gene profiling study.

    PubMed

    Duann, Pu; Lianos, Elias A

    2011-10-01

    Using a mouse model of immune injury directed against the renal glomerular vasculature and resembling human forms of glomerulonephritis (GN), we assessed the effect of targeted expression of the cytoprotective enzyme heme oxygenase (HO)-1. A human (h) HO-1 complementary DNAN (cDNA) sequence was targeted to glomerular epithelial cells (GECs) using a GEC-specific murine nephrin promoter. Injury by administration of antibody against the glomerular basement membrane (anti-GBM) to transgenic (TG) mice with GEC-targeted hHO-1 was attenuated compared with wild-type (WT) controls. To explore changes in the expression of genes that could mediate this salutary effect, we performed gene expression profiling using a microarray analysis of RNA isolated from the renal cortex of WT or TG mice with or without anti-GBM antibody-induced injury. Significant increases in expression were detected in 9 major histocompatibility complex (MHC)-class II genes, 2 interferon-γ (IFN-γ)-inducible guanosine triphosphate (GTP)ases, and 3 genes of the ubiquitin-proteasome system. The increase in MHC-class II and proteasome gene expression in TG mice with injury was validated by real-time polymerase chain reaction (PCR) or Western blot analysis. The observations point to novel mechanisms underlying the cytoprotective effect of HO-1 in renal immune injury. PMID:21925121

  5. Renal outcome of children with unilateral renal agenesis.

    PubMed

    Doğan, Çağla Serpil; Torun Bayram, Meral

    2013-01-01

    The aim of this study was to evaluate associated urological anomalies and renal outcome in children with unilateral renal agenesis (URA). Medical records of 51 cases of URA followed at Şanlıurfa Children 's Hospital between January 2009 and December 2012 were reviewed retrospectively. In all patients, diagnosis was made by abdominal ultrasound (US) and confirmed by a radionuclide scan. The children were between 3 months and 17 years of age (median age: 5 years). There were 31 males (60.8%) and 20 females (39.2%). In 33 patients (67.3%), the left kidney was absent. Urological anomalies were found in 12/51 patients (23.5%), including ureterovesical junction obstruction in 4 (7.8%), bladder dysfunction in 2 (3.9%), and vesicoureteral reflux (VUR), ureteropelvic junction obstruction, ureterovesical and ureteropelvic junction obstruction, duplicated collecting system plus grade IV VUR, ectopic kidney plus grade V VUR, and ectopic kidney in 1 patient (2%) each. Chronic renal insufficiency (CRI) developed in 5/51 patients (9.8%) (stage III in 3 patients and stage IV in 2), 4 of whom had additional urological anomaly; in the remaining 1 patient, a 17-year-old female, imaging studies were normal except for a small and hyperechogenic solitary kidney determined on US. A total of 3 patients (5.8%) developed hypertension, and all except one had an associated urological anomaly. Proteinuria was seen in 2 patients (3.8%) with stage IV CRI, one of whom was also hypertensive. In conclusion, urological anomalies usually accompany URA and should be followed closely to decrease the risk of renal failure. PMID:24577979

  6. Does Renal Artery Supply Indicate Treatment Success of Renal Denervation?

    SciTech Connect

    Schmid, Axel; Ditting, Tilmann; Sobotka, Paul A.; Veelken, Roland Schmieder, Roland E.; Uder, Michael; Ott, Christian

    2013-08-01

    PurposeRenal denervation (RDN) emerged as an innovative interventional antihypertensive therapy. With the exception of pretreatment blood pressure (BP) level, no other clear predictor for treatment efficacy is yet known. We analyzed whether the presence of multiple renal arteries has an impact on BP reduction after RDN.MethodsFifty-three patients with treatment-resistant hypertension (office BP {>=} 140/90 mmHg and 24-h ambulatory BP monitoring ({>=}130/80 mmHg) underwent bilateral catheter-based RDN. Patients were stratified into one-vessel (OV) (both sides) and at least multivessel (MV) supply at one side. Both groups were treated on one vessel at each side; in case of multiple arteries, only the dominant artery was treated on each side.ResultsBaseline clinical characteristics (including BP, age, and estimated glomerular filtration rate) did not differ between patients with OV (n = 32) and MV (n = 21). Office BP was significantly reduced in both groups at 3 months (systolic: OV -15 {+-} 23 vs. MV -16 {+-} 20 mmHg; diastolic: OV -10 {+-} 12 vs. MV -8 {+-} 11 mmHg, both p = NS) as well as 6 months (systolic: OV -18 {+-} 18 vs. MV -17 {+-} 22 mmHg; diastolic: OV -10 {+-} 10 vs. -10 {+-} 12 mmHg, both p = NS) after RDN. There was no difference in responder rate (rate of patients with office systolic BP reduction of at least 10 mmHg after 6 months) between the groups.ConclusionIn patients with multiple renal arteries, RDN of one renal artery-namely, the dominant one-is sufficient to induce BP reduction in treatment-resistant hypertension.

  7. A returned traveller with persistent fever due to murine typhus.

    PubMed

    Ng, C P; Lo, C B; Wong, K K; Chung, C H

    2002-12-01

    Murine (endemic) typhus is a notifiable disease in Hong Kong, but its diagnosis can be difficult. We report a case of murine typhus in a middle-aged man who presented with persistent fever, headache, and skin rash 2 weeks after returning from a visit to China. The diagnosis of murine typhus requires a high index of suspicion for a febrile patient with a history of potential exposure to the disease vector (rat flea) in an endemic area. The importance of early recognition lies in the potential for early therapeutic intervention, leading to decreases in morbidity and duration of stay in hospital. PMID:12459604

  8. Glucocorticoid receptors in murine erythroleukaemic cells

    SciTech Connect

    Hammond, K.D.; Torrance, J.M.; DiDomenico, M.

    1987-01-01

    Glucocorticoid receptors in murine erythroleukaemic cells were studied in relation to hexamethylene bisacetamide (HMBA) induced differentiation. Specific binding of dexamethasone was measured. A single class of saturable, high affinity binding sites was demonstrated in intact cells; with cell homogenates or fractions binding was low and could not be reliably quantified. Receptor binding in whole cell suspensions was lower in cells which had been treated with HMBA (36.5 +/- 8.2 pmol/g protein) than in untreated controls (87.9 +/- 23.6 pmol/g protein); dissociation constants were similar in treated (2.7 nM) and untreated cells (2.5 nM). Dexamethasone, hydrocortisone, corticosterone and progesterone competed with tritium-labelled dexamethasone for receptor binding sites; cortisone, deoxycorticosterone and oestradiol had little effect.

  9. Renal Clearance of Mineral Metabolism Biomarkers.

    PubMed

    van Ballegooijen, Adriana J; Rhee, Eugene P; Elmariah, Sammy; de Boer, Ian H; Kestenbaum, Bryan

    2016-02-01

    CKD leads to disturbances in multiple interrelated hormones that regulate bone and mineral metabolism. The renal handling of mineral metabolism hormones in humans is incompletely understood. We determined the single-pass renal clearance of parathyroid hormone, fibroblast growth factor 23, vitamin D metabolites, and phosphate from paired blood samples collected from the abdominal aorta and renal vein in 17 participants undergoing simultaneous right and left heart catheterization and estimated associations of eGFR with the renal elimination of metabolites. The mean age ±SD of the study population was 71.4±10.0 years and 11 participants (65%) were male. We found a relatively large mean±SD single-pass renal extraction of parathyroid hormone (44.2%±10.3%) that exceeded the extraction of creatinine (22.1%±7.9%). The proportionate renal extraction of parathyroid hormone correlated with eGFR. The renal extraction of fibroblast growth factor 23 was, on average, lower than that of parathyroid hormone with greater variability across individuals (17.1%±19.5%). There were no differences in the mean concentrations of vitamin D metabolites across the renal vein and artery. In summary, we demonstrate substantial single-pass renal extraction of parathyroid hormone at a rate that exceeds glomerular filtration. Impaired renal clearance of parathyroid hormone may contribute to secondary hyperparathyroidism in CKD. PMID:26047790

  10. Focus on renal congestion in heart failure

    PubMed Central

    Afsar, Baris; Ortiz, Alberto; Covic, Adrian; Solak, Yalcin; Goldsmith, David; Kanbay, Mehmet

    2016-01-01

    Hospitalizations due to heart failure are increasing steadily despite advances in medicine. Patients hospitalized for worsening heart failure have high mortality in hospital and within the months following discharge. Kidney dysfunction is associated with adverse outcomes in heart failure patients. Recent evidence suggests that both deterioration in kidney function and renal congestion are important prognostic factors in heart failure. Kidney congestion in heart failure results from low cardiac output (forward failure), tubuloglomerular feedback, increased intra-abdominal pressure or increased venous pressure. Regardless of the cause, renal congestion is associated with increased morbidity and mortality in heart failure. The impact on outcomes of renal decongestion strategies that do not compromise renal function should be explored in heart failure. These studies require novel diagnostic markers that identify early renal damage and renal congestion and allow monitoring of treatment responses in order to avoid severe worsening of renal function. In addition, there is an unmet need regarding evidence-based therapeutic management of renal congestion and worsening renal function. In the present review, we summarize the mechanisms, diagnosis, outcomes, prognostic markers and treatment options of renal congestion in heart failure. PMID:26798459

  11. Blackwater fever like in murine malaria.

    PubMed

    Rivera, Norma; Romero, Samanta E; Menchaca, Angeles; Zepeda, Armando; García, Luis E; Salas, Gerardo; Romero, Laura; Malagón, Filiberto

    2013-03-01

    Blackwater fever (BWF) is the term used to designate the occurrence of hemoglobin pigments in the urine of patients infected with malaria parasites. BWF is more often associated with Plasmodium falciparum infection in man. The pathogenesis of BWF has not been explained satisfactorily. In the present study, the clinical and pathological observations made upon CD1 mice infected with Plasmodium yoelii yoelii lethal strain with clinical signs of hemoglobinuria and acute renal failure were evaluated. From the 40 P. yoelii yoelii-infected mice, 14 presented hemoglobinuria. In the observations, it was emphasized that hemoglobinuria occurred in the animals 1-2 days before they die. At 6 days post-infection, infected hemoglobinuric mice (HM) exhibited clinical signs such as dark red urine, apnea, and evident oliguria and hematuria; urine microscopical examination showed very few red blood cells. The entire non hemoglobinuric infected mice had a high parasitemia preceding the time of death, while the HM parasitemia was just detectable. In HM, marked hepatosplenomegaly, anemia, and renal and hepatic dysfunction were observed with the blood chemistry analysis at 6 days post-infection. Severe renal lesions were demonstrated in histopathological and scanning electron microscopy samples. Occlusion and necrosis of convoluted tubules were the main lesions found. The conditions required for the experimental production of hemoglobinuria in CD1 mouse infected by P. yoelii yoelii is still unknown. The clinical picture of a BWF, like in our rodents, was produced exclusively by the interaction between the parasite and its host. Results showed that hemoglobinuria in CD1 mice infected with P. yoelii yoelii and BWF in man infected with P. falciparum are similar in their pathogenesis. PMID:23254588

  12. Renal calculi and their management.

    PubMed

    Melick, R A

    1976-03-01

    Any patient presenting with renal colic requires the taking of a detailed history-- with inquiries about diet and drugs, an examination of the urine, intravenous pyelography and measurement of the calcium concentration in serum and urine. Any stone passed should be analysed. Recurrent stone formation warrants more comprehensive metabolic investigation. The cause of renal calculi in most patients is still not known. When a cause is found, specific treatment can prevent or control stone formation. For the majority in whom no abnormality is detected, various methods of reducing stone formation have been tried but results are disappointing. The most important points in management are the early detection and effective treatment of urinary tract infection or obstruction and the maintenance of a high fluid intake. PMID:1272102

  13. Leiomyosarcoma of the renal vein.

    PubMed

    Imao, Tetsuya; Amano, Toshiyasu; Takemae, Katsurou

    2011-02-01

    A 43-year-old woman was referred to our clinic for evaluation of a left retroperitoneal mass. She presented to our internal medicine department complaining of back pain. Computed tomography (CT) scan revealed a left retroperitoneal mass 55 mm in size in the hilum of the left kidney. Enhanced CT scan and magnetic resonance imaging (MRI) disclosed a poorly staining mass. Metaiodobenzylguanidine scintigraphy demonstrated no accumulation in the mass; moreover, endocrinologic examination was normal. Laparoscopic resection of the left retroperitoneal tumor was attempted; however, strong adhesion between the tumor and the left renal vein was encountered. Thus, left nephrectomy after open conversion was performed. Histological findings indicated leiomyosarcoma originating from the left renal vein. The postoperative course has been uneventful; neither recurrence nor metastasis is evident 2 years postsurgery. PMID:20694494

  14. Mesalazine-induced renal calculi

    PubMed Central

    Jacobsson, Henrik; Eriksen, Jaran; Karlén, Per

    2013-01-01

    Patient: Female, 32 Final Diagnosis: Renal colic Symptoms: Acute colic pain • macrohematuria Medication: Mesalazine Clinical Procedure: CT scan of urinary tract • cystoscopy • gynecological consultation • stone analysis Specialty: Gastroenterology and Hepatology • Clinical Pharmacology Objective: Unexpected drug reaction Background: Mesalazine, a 5-aminosalicylic acid compound, is one of the cornerstones in modern treatment regimens of ulcerative colitis. It is generally well tolerated, although adverse reactions such as nephrotoxicity, perimyocarditis, and pancreatitis have been reported. Case Report: We report the case of a 32-year-old woman with colitis who developed recurrent episodes of renal colic after introduction of mesalazine to her treatment. Biochemical analysis of the stones showed that they were composed of crystalized drug material. Conclusions: To our knowledge this is the first report of mesalazine precipitation in the urinary tract. We believe that it is vital for physicians to recognize this potentially severe adverse effect in the use of this treatment. PMID:24478817

  15. Radiocontrast-induced renal failure

    SciTech Connect

    Misson, R.T.; Cutler, R.E.

    1985-05-01

    Review of the literature concerning contrast-induced renal dysfunction shows that the currently used agents are remarkably safe with careful patient selection. Clinically apparent kidney failure after their use is essentially nonexistent in those without preexistent renal insufficiency. The incidence rises rapidly in those with azotemia from any cause, however, and diabetic persons with nephropathy are perhaps at special risk. Vigorous volume expansion is possibly effective as a preventive measure and may attenuate adverse effects in those in whom postcontrast dysfunction occurs. New agents are becoming available. It is not yet known if these will prove safer or cost-effective. They have some experimentally demonstrated and theoretical advantages over the presently used agents. 58 references, 1 figure, 2 tables.

  16. Leiomyoma in a Renal Allograft.

    PubMed

    Li, Yan Jun; Siriwardana, Amila Rohan; Symons, James Lawrence Penn; O'Neill, Gordon Francis; Qiu, Min Ru; Furlong, Timothy John

    2016-01-01

    Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year. PMID:27195169

  17. Asymptomatic hyperuricemia following renal transplantation

    PubMed Central

    Bellomo, Gianni

    2015-01-01

    Evidence is accumulating indicating a role for uric acid in the genesis and progression of kidney disease, and a few studies are beginning to show a possible beneficial effect of urate-lowering therapy. Whether this holds true for renal allograft recipients is not clear. In this short review evidence from epidemiological as well as intervention studies is summarized and discussed, with some practical considerations presented at the end. PMID:26167455

  18. Asymptomatic hyperuricemia following renal transplantation.

    PubMed

    Bellomo, Gianni

    2015-07-01

    Evidence is accumulating indicating a role for uric acid in the genesis and progression of kidney disease, and a few studies are beginning to show a possible beneficial effect of urate-lowering therapy. Whether this holds true for renal allograft recipients is not clear. In this short review evidence from epidemiological as well as intervention studies is summarized and discussed, with some practical considerations presented at the end. PMID:26167455

  19. Leiomyoma in a Renal Allograft

    PubMed Central

    Li, Yan Jun; Siriwardana, Amila Rohan; Symons, James Lawrence Penn; O'Neill, Gordon Francis; Qiu, Min Ru; Furlong, Timothy John

    2016-01-01

    Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year. PMID:27195169

  20. Identification and immune regulation of 25-hydroxyvitamin D-1-α-hydroxylase in murine macrophages

    PubMed Central

    Overbergh, L; Decallonne, B; Valckx, D; Verstuyf, A; Depovere, J; Laureys, J; Rutgeerts, O; Saint-Arnaud, R; Bouillon, R; Mathieu, C

    2000-01-01

    Receptors for 1,25(OH)2vitaminD3 are found in most immune cells and important immunological effects have been described in vitro, reflected by its capacity to prevent autoimmunity and to prolong graft survival. The aim of this study was to examine the presence and nature of the enzyme responsible for final activation of the molecule, 1-α-hydroxylase, in murine macrophages and to analyse its regulation and possible role in the immune system. Peritoneal macrophages from C57Bl/6 mice were incubated with lipopolysaccharide (LPS; 100 μg/ml), interferon-gamma (IFN-γ; 500 U/ml) or a combination of both. By quantitative reverse transcriptase-polymerase chain reaction, using primers based on the murine renal cDNA sequence, low levels of 1-α-hydroxylase mRNA were detected in freshly isolated cells (18 ± 7 × 10−6 copies/β-actin copies). Analysis of the cDNA sequence of the gene revealed identical coding sequences for the macrophage and renal enzymes. mRNA levels rose three-fold with LPS (NS), but a six-fold increase was seen after IFN-γ stimulation (P < 0·05). Combining LPS and IFN-γ did not result in a major additional increase, but addition of cyclosporin A further increased levels 2·5-fold both in IFN-γ- and combination-stimulated cells (P < 0·05). Time course analysis revealed that up-regulation of 1-α-hydroxylase was a late phenomenon, preceded by the up-regulation of activating macrophage products such as IL-1 and tumour necrosis factor-alpha. Finally, a defect in 1-α-hydroxylase up-regulation by immune stimuli was found in autoimmune non-obese diabetic mice. In conclusion, we propose that the up-regulation of 1-α-hydroxylase in activated macrophages, resulting in the synthesis of 1,25(OH)2D3, might be a negative feedback loop in inflammation. A defect in this system might be an additional element in tipping the balance towards autoimmunity. PMID:10759775

  1. New perspectives on the renal slit diaphragm protein podocin

    PubMed Central

    Relle, Manfred; Cash, Hannes; Brochhausen, Christoph; Strand, Dennis; Menke, Julia; Galle, Peter R; Schwarting, Andreas

    2011-01-01

    Podocin is a critical component of the glomerular filtration barrier, its mutations causing recessive steroid-resistant nephrotic syndrome. A GenBank analysis of the human podocin (NPHS2) gene resulted in the possible existence of a new splice variant of podocin in the kidney, missing the in-frame of exon 5, encoding the prohibitin homology domain. Using RT–polymerase chain reaction and immunoblotting followed by sequence analysis, we are for the first time able to prove the expression of a novel podocin isoform (isoform 2), exclusively and constitutively expressed in human podocytes. Furthermore, we reveal singular extrarenal podocin expression in human and murine testis. Our data show the Sertoli cells of the seminiferous tubules to be the origin of testicular podocin. Confocal laser microscopy illustrates the co-localization of podocin with filamentous actin within Sertoli cells, suggesting a role of podocin in the blood/testis barrier. These results led to the rationale to examine podocin expression in testes of men with Sertoli cell-only syndrome, a disorder characterized by azoospermia. Interestingly, we observed a complete down-regulation of podocin mRNA in Sertoli cell-only syndrome, indicating a possible role of podocin in the pathogenesis of this germinal aplasia. Men with Sertoli cell-only syndrome show normal renal podocin expression, suggesting an alternate regulation of the testicular promoter. Our findings may change the perception of podocin and give new insights into the ultrastructure of glomerular slit diaphragm and the blood/testis barrier. PMID:21499232

  2. Immunotherapy in renal cell carcinoma.

    PubMed

    Bukowski, R M

    1999-06-01

    Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy include the observations of spontaneous tumor regression, the presence of a T-cell-mediated immune response, and the tumor responses observed in patients receiving cytokine therapy. Analysis of prognostic factors in these patients demonstrates that clinical responses occur most frequently in individuals with good performance status. The cytokines interleukin-2 (IL-2, aldesleukin [Proleukin], interferon-alfa (Intron A, Roferon-A), or the combination produce responses in 15% to 20% of patients. Randomized trials suggest that administration of interferon-alfa may result in a modest improvement in median survival. Investigation of the molecular genetics of renal cell carcinoma and the presence of T-lymphocyte immune dysregulation have suggested new therapeutic strategies. Further preclinical and clinical studies investigating inhibitors of angiogenesis or pharmacologic methods to reverse immune dysregulation are ongoing. Therapeutic results in patients with renal cell carcinoma remain limited, and investigational approaches are warranted. PMID:10378218

  3. Mechanisms of compensatory renal growth.

    PubMed

    Cleper, Roxana

    2012-11-01

    Congenitally reduced renal mass- as with agenesis of one kidney, unilateral multicystic dysplastic kidney or with premature birth with early arrest of nephrogenesis- as well as acquired loss of a significant part of kidney tissue- as with kidney donation, after surgery for tumor etc- set in motion compensatory processes with main target to meet metabolic body needs. The sensors for reduced renal mass have not yet been identified. The effectors of the compensatory process include a wide range of growth factors- IGF1, TGF-b1, HGF- and signaling molecules-mTOR- which has intricate reciprocal interactions. As nephrogenesis stops at 34-36 weeks of gestation and can't be restarted thereafter, the main result of this compensatory process is increase in glomerular size (glomerulomegaly) and tubular hypertrophy. Renal volume evaluation by ultrasound is a practical noninvasive tool for assessment of compensatory kidney growth. The increased nephron and kidney size induced by the compensatory process have potential detrimental long-term effect through stretch-induced glomerular cell activation of profibrogenic and vasoconstrictor pathways as well as tubular cell nephrotoxicity caused by abnormal activation of reabsorptive mechanisms including GLUT1 and megalin. Deep understanding of these potentially damage process might help in timely implementation of protective strategies. PMID:23469392

  4. Cultured Human Renal Cortical Cells

    NASA Technical Reports Server (NTRS)

    1998-01-01

    During the STS-90 shuttle flight in April 1998, cultured renal cortical cells revealed new information about genes. Timothy Hammond, an investigator in NASA's microgravity biotechnology program was interested in culturing kidney tissue to study the expression of proteins useful in the treatment of kidney diseases. Protein expression is linked to the level of differentiation of the kidney cells, and Hammond had difficulty maintaining differentiated cells in vitro. Intrigued by the improvement in cell differentiation that he observed in rat renal cells cultured in NASA's rotating wall vessel (a bioreactor that simulates some aspects of microgravity) and during an experiment performed on the Russian Space Station Mir, Hammond decided to sleuth out which genes were responsible for controlling differentiation of kidney cells. To do this, he compared the gene activity of human renal cells in a variety of gravitational environments, including the microgravity of the space shuttle and the high-gravity environment of a centrifuge. Hammond found that 1,632 genes out of 10,000 analyzed changed their activity level in microgravity, more than in any of the other environments. These results have important implications for kidney research as well as for understanding the basic mechanism for controlling cell differentiation.

  5. [Immune tolerance after renal transplantation].

    PubMed

    Krajewska, Magdalena; Weyde, Wacław; Klinger, Marian

    2006-01-01

    Progress in immunosuppressive therapy has improved short-term survival of renal allografts by decreasing the frequency of acute rejections. However, the long-term survival of renal grafts has not improved. Transplanted kidneys are lost in the late period after transplantation as a result of vasculopathy and chronic rejection. Immunological tolerance means the lack of immunological activity towards certain antigens while the response towards others remains correct. The induction of immunological tolerance of donor antigens (transplant tolerance) is examined intensively to work out treatment methods which will allow prevention of chronic allograft rejection. The paper includes an overview of current knowledge on allograft tolerance. Immune response to alloantigens is described and the mechanisms of immunological tolerance induction (including clonal deletion, anergy connected with the microchimerism phenomenon, and active suppression caused by regulatory lymphocytes) are characterized. The role of dendritic cells in the process of inducing and maintaining tolerance is highlighted. Tolerance-inducing strategies in renal transplant recipients and clinically applied evaluation methods are presented. At present, optimizing recipient matching is used to decrease the risk of graft rejection. Hopefully, gene therapy will be possible in the near future. However, before introducing such a procedure into clinical studies, optimal therapy conditions and risk evaluation must be defined in tests on animals. PMID:16552396

  6. Dimethylarginine Dimethylaminohydrolase1 Is an Organ-Specific Mediator of End Organ Damage in a Murine Model of Hypertension

    PubMed Central

    Sydow, Karsten; Schmitz, Christine; von Leitner, Eike-Christin; von Leitner, Robin; Klinke, Anna; Atzler, Dorothee; Krebs, Christian; Wieboldt, Hartwig; Ehmke, Heimo; Schwedhelm, Edzard; Meinertz, Thomas; Blankenberg, Stefan; Böger, Rainer H.; Magnus, Tim

    2012-01-01

    Background The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular and overall mortality. Moreover, elevated ADMA plasma concentrations are associated with the extent of hypertension. However, data from small-sized clinical trials and experimental approaches using murine transgenic models have revealed conflicting results regarding the impact of ADMA and its metabolizing enzyme dimethylarginine dimethylaminohydrolase (DDAH) in the pathogenesis of hypertension. Methodology/Principal Findings Therefore, we investigated the role of ADMA and DDAH1 in hypertension-induced end organ damage using the uninephrectomized, deoxycorticosterone actetate salt, and angiotensin II-induced hypertension model in human DDAH1 (hDDAH1) overexpressing and wild-type (WT) mice. ADMA plasma concentrations differed significantly between hDDAH1 and WT mice at baseline, but did not significantly change during the induction of hypertension. hDDAH1 overexpression did not protect against hypertension-induced cardiac fibrosis and hypertrophy. In addition, the hypertension-induced impairment of the endothelium-dependent vasorelaxation of aortic segments ex vivo was not significantly attenuated by hDDAH1 overexpression. However, hDDAH1 mice displayed an attenuated hypertensive inflammatory response in renal tissue, resulting in less hypertensive renal injury. Conclusion/Significance Our data reveal that hDDAH1 organ-specifically modulates the inflammatory response in this murine model of hypertension. The lack of protection in cardiac and aortic tissues may be due to DDAH1 tissue selectivity and/or the extent of hypertension by the used combined model. However, our study underlines the potency of hDDAH1 overexpression in modulating inflammatory processes as a crucial step in the pathogenesis of hypertension, which needs further experimental and clinical investigation. PMID:23110194

  7. Novel Microbial Virulence Factor Triggers Murine Lyme Arthritis

    PubMed Central

    Yang, Xiuli; Qin, Jinhong; Promnares, Kamoltip; Kariu, Toru; Anderson, John F.; Pal, Utpal

    2013-01-01

    Borrelia burgdorferi bba57 is a conserved gene encoding a potential lipoprotein of unknown function. Here we show that bba57 is up-regulated in vivo and is required for early murine infection and potential spirochete transmission process. Although BBA57 is dispensable for late murine infection, the mutants were unable to induce disease. We show that BBA57, an outer membrane and surface-exposed antigen, is a major trigger of murine Lyme arthritis; even in cases of larger challenge inocula, which allow their persistence in joints at a level similar to wild-type spirochetes, bba57 mutants are unable to induce joint inflammation. We further showed that BBA57 deficiency reduces the expression of selected “neutrophil-recruiting” chemokines and associated receptors, causing significant impairment of neutrophil chemotaxis. New approaches to combat Lyme disease may include strategies to interfere with BBA57, a novel virulence factor and a trigger of murine Lyme arthritis. PMID:23303811

  8. Acute renal failure due to falciparum malaria.

    PubMed

    Habte, B

    1990-01-01

    Seventy-two patients with severe falciparum malaria are described. Twenty-four (33.3%) were complicated by acute renal failure. Comparing patients with renal failure and those without, statistically significant differences occurred regarding presence of cerebral malaria (83% vs 46%), jaundice (92% vs 33%), and death (54% vs 17%). A significantly higher number of patients with renal failure were nonimmune visitors to malaria endemic regions. Renal failure was oliguric in 45% of cases. Dialysis was indicated in 38%, 29% died in early renal failure, and 33% recovered spontaneously. It is concluded that falciparum malaria is frequently complicated by cerebral malaria and renal failure. As nonimmune individuals are prone to develop serious complications, malaria prophylaxis and vigorous treatment of cases is mandatory. PMID:2236718

  9. [Current management of renal artery stenosis].

    PubMed

    Lenz, T

    2013-12-01

    Severe renal artery stenosis may cause renovascular hypertension; in case of bilateral narrowing or in a stenotic solitary kidney, renal insufficiency (ischemic kidney disease) or rarely pulmonary flush edema may occur. Renal artery stenosis may be treated by revascularization, using either percutaneous (balloon angioplasty, stenting) or less common open surgical procedures, both with excellent primary patency rates. However, randomized trials of renal artery angioplasty or stenting have failed to demonstrate a longer-term benefit with regard to blood pressure control and renal function over medical management alone (except for fibromuscular disease). Furthermore, endovascular procedures are associated with substantial risks. It has not yet been demonstrated that renal revascularization leads to a prolongation of event-free survival. Careful patient selection is essential to maximize the potential benefit. PMID:24217529

  10. Renal dysplasia in boxers and Finnish harriers.

    PubMed

    Hoppe, A; Karlstam, E

    2000-09-01

    Puppies from two litters of dogs were found to have severe polyuria and polydipsia. Four of the dogs were investigated by means of clinical examination, haematological and biochemical analysis, and urinalysis. A modified water deprivation response test was also performed in two of the dogs. Renal changes on postmortem examination in three of the dogs were found to be consistent with renal dysplasia. A possible explanation for the finding of hyposthenuria and the extreme polyuria and polydipsia in association with renal dysplasia may be lack of response to antidiuretic hormone owing to anomalous maturation of the renal tubules. Six other puppies from the two litters of dogs did not show any clinical signs of polyuria and polydipsia, although postmortem examination in one of them also revealed renal dysplasia. The clinical features of renal dysplasia may therefore vary greatly between individuals. PMID:11023130