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Renal Tissue (renal + tissue)
Selected AbstractsCan Renal Acute Tubular Necrosis Be Differentiated from Autolysis at Autopsy?,JOURNAL OF FORENSIC SCIENCES, Issue 2 2009Linda Kocovski B.Sc. Abstract:, We investigate the morphological characteristics that may differentiate between ischemic acute tubular necrosis (ATN) and autolysis in postmortem samples. Renal tissue from 57 postmortem cases with an antemortem diagnosis of ATN and 57 age-/sex-matched control cases were examined for 10 morphological characteristics: epithelial proliferation (Ki-67 immunoperoxidase positivity), fibrin thrombi, tubular epithelial whorls, mitoses, casts, autolysis, tubulorrhexis, epithelial flattening, interstitial inflammation, and interstitial expansion. Tubular epithelial whorls were found in 16 ATN cases and were absent in controls. These findings suggest that specific morphological criteria may distinguish ischemic ATN from autolysis. Diagnoses of ATN may be confirmed using these combined criteria as contributing to cause of death and/or to ascertain previously undiagnosed cases of ATN postmortem. [source] Renal pathology of polycystic kidney disease and concurrent hereditary nephritis in Bull TerriersAUSTRALIAN VETERINARY JOURNAL, Issue 6 2002CA O'LEARY Objective To describe the renal lesions in Bull Terrier poly-cystic kidney disease (BTPKD), to confirm that the renal cysts in BTPKD arise from the nephron or collecting tubule, and to identify lesions consistent with concurrent BTPKD and Bull Terrier hereditary nephritis (BTHN). Design Renal tissue from five Bull Terriers with BTPKD and eight control dogs was examined by light and transmission electron microscopy. Clinical data were collected from all dogs, and family history of BTPKD and BTHN for all Bull Terriers. Results In BTPKD the renal cysts were lined by epithelial cells of nephron or collecting duct origin that were usually squamous or cuboidal, with few organelles. They had normal junctional complexes, and basal laminae of varying thicknesses. Glomeruli with small, atrophic tufts and dilated Bowman's capsules, tubular loss and dilation, and interstitial inflammation and fibrosis were common. Whereas the lesions seen in BTHN by light microscope were nonspecific, the presence of characteristic ultrastructural glomerular basement membrane (GMB) lesions and a family history of this disease indicated concurrent BTHN was likely in three of five cases of BTPKD. Conclusion This paper provides evidence that renal cysts in BTPKD are of nephron or collecting duct origin. In addition, GBM lesions are described that strongly suggest that BTPKD and BTHN may occur simultaneously. [source] Increasing renal mass improves survival in anephric rats following metanephros transplantationEXPERIMENTAL PHYSIOLOGY, Issue 1 2007Damian Marshall Renal failure and end-stage renal disease are prevalent diseases associated with high levels of morbidity and mortality, the preferred treatment for which is kidney transplantation. However, the gulf between supply and demand for kidneys remains high and is growing every year. A potential alternative to the transplantation of mature adult kidneys is the transplantation of the developing renal primordium, the metanephros. It has been shown previously, in rodent models, that transplantation of a metanephros can provide renal function capable of prolonging survival in anephric animals. The aim of the present study was to determine whether increasing the mass of transplanted tissue can prolong survival further. Embryonic day 15 rat metanephroi were transplanted into the peritoneum of anaesthetized adult rat recipients. Twenty-one days later, the transplanted metanephroi were anastomosed to the recipient's urinary system, and 35 days following anastomosis the animal's native renal mass was removed. Survival times and composition of the excreted fluid were determined. Rats with single metanephros transplants survived 29 h longer than anephric controls (P < 0.001); animals with two metanephroi survived 44 h longer (P < 0.001). A dilute urine was formed, with low concentrations of sodium, potassium and urea; potassium and urea concentrations were elevated in terminal serum samples, but sodium concentration and osmolality were comparable to control values. These data show that survival time is proportional to the mass of functional renal tissue. While transplanted metanephroi cannot currently provide life-sustaining renal function, this approach may have therapeutic benefit in the future. [source] Acetyl-CoA:1- O -alkyl- sn -glycero-3-phosphocholine acetyltransferase (lyso-PAF AT) activity in cortical and medullary human renal tissueFEBS JOURNAL, Issue 14 2003Tzortzis N Nomikos Platelet-activating factor (PAF) is one of the most potent inflammatory mediators. It is biosynthesized by either the de novo biosynthesis of glyceryl ether lipids or by remodeling of membrane phospholipids. PAF is synthesized and catabolized by various renal cells and tissues and exerts a wide range of biological activities on renal tissue suggesting a potential role during renal injury. The aim of this study was to identify whether cortex and medulla of human kidney contain the acetyl-CoA:1- O -alkyl- sn -glycero-3-phosphocholine acetyltransferase (lyso-PAF AT) activity which catalyses the last step of the remodeling biosynthetic route of PAF and is activated in inflammatory conditions. Cortex and medulla were obtained from nephrectomized patients with adenocarcinoma and the enzymatic activity was determined by a trichloroacetic acid precipitation method. Lyso-PAF AT activity was detected in both cortex and medulla and distributed among the membrane subcellular fractions. No statistical differences between the specific activity of cortical and medullary lyso-PAF AT was found. Both cortical and medullary microsomal lyso-PAF ATs share similar biochemical properties indicating common cellular sources. [source] Ethanol-induced alterations of the antioxidant defense system in rat kidneyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2006Diana Dinu Abstract We report here the effects of chronic ethanol consumption on the antioxidant defense system in rat kidney. Thirty-two male Wistar rats were randomly divided in two identical groups and were treated as follows: control group (water for fluid) and the ethanol-fed group (2 g/kg body weight/24 h). The animals were sacrificed after 10 weeks, and respectively 30 weeks of ethanol consumption, and the renal tissue was isolated and analyzed. Results revealed that kidney alcohol dehydrogenase activities increased significantly after ethanol administration, but the electrophoretic pattern of alcohol dehydrogenase isoforms was unmodified. The SDS polyacrylamidegel electrophoretic study of kidney proteins has revealed the appearance of two new protein bands after long-term ethanol consumption. The kidney reduced glutathione/oxidized glutathione ratio decreased, indicating an oxidative stress response due to ethanol ingestion. The malondialdehyde contents and xanthine oxidase activities were unchanged. The antioxidant enzymatic defense system showed a different response during the two periods of ethanol administration. After 10 weeks, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase were activated, while superoxide dismutase, glutathione transferase, and ,-glutamyltranspeptidase levels were stationary. After 30 weeks, superoxide dismutase and glutathione peroxidase activities were unmodified, but catalase, glutathione transferase, ,-glutamyltranspeptidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities were significantly increased. Remarkable changes have been registered after 30 weeks of ethanol administration for glutathione reductase and glucose-6-phosphate dehydrogenase activities, including an increase by 106 and 216' of control values, respectively. These results showed specific changes in rat kidney antioxidant system and glutathione status as a consequence of long-term ethanol administration. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:386-395, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20101 [source] Genotyping of the JC virus in urine samples of healthy Korean individualsJOURNAL OF MEDICAL VIROLOGY, Issue 2 2004Byung-Hoon Jeong Abstract A human polyomavirus, JC virus (JCV) is ubiquitous in humans and infects children asymptomatically. It persists in renal tissue and is excreted progeny in urine. DNAs from urine samples of 100 healthy Korean individuals were screened for the presence of JCV by polymerase chain reaction (PCR). Twenty of the samples were positive for JCV. JCV DNA was found in one individual (4%) in the 1,19-year group, two individuals (9%) in the 20,39-year group, ten individuals (38%) in the 40,59-year group, seven individuals (28%) in the over 60-year group. The prevalence of JC viral DNA was the highest in the 40,59-year-old Korean population. To investigate genotypes of JCV in Korea, the genotypes were determined by DNA sequence analysis of the regulatory region (333 bp) and the VT-intergenic region (656 bp) of DNA from the 20 JCV isolates. We have identified three distinctive JCV strains in the regulatory region and ten distinctive JCV strains in the VT-intergenic region of DNA from the 20 isolates. Based on restriction fragment length polymorphism (RFLP) analysis and phylogenetic analysis of the VT-intergenic region of JCV, two distinct subtypes, CY and type 2A (MY), were found to be prevalent in this Korean population. CY and type 2A of JCV were identified in 13 individuals (65%) and four individuals (20%), respectively. Interestingly, type 1, which was distributed mostly in Europe, was found in 3 (15%) isolates from healthy Korean individuals. J. Med. Virol. 72:281,289, 2004. © 2004 Wiley-Liss, Inc. [source] Melatonin reduces uranium-induced nephrotoxicity in ratsJOURNAL OF PINEAL RESEARCH, Issue 1 2007Montserrat Bellés Abstract:, The protective role of exogenous melatonin on U-induced nephrotoxicity was investigated in rats. Animals were given single doses of uranyl acetate dihydrate (UAD) at 5 mg/kg (subcutaneous), melatonin at 10 or 20 mg/kg (intraperitoneal), and UAD (5 mg/kg) plus melatonin (10 or 20 mg/kg), or vehicle (control group). In comparison with the UAD-treated group only, significant beneficial changes were noted in some urinary and serum parameters of rats concurrently exposed to UAD and melatonin. The increase of U excretion after UAD administration was accompanied by a significant reduction in the renal content of U when melatonin was given at a dose of 20 mg/kg. Melatonin also reduced the severity of the U-induced histological alterations in kidney. In renal tissue, the activity of the superoxide dismutase (SOD) and the thiobarbituric acid reactive substances (TBARS) levels increased significantly as a result of UAD exposure. Following UAD administration, oxidative stress markers in erythrocytes showed a reduction in SOD activity and an increase in TBARS levels, which were significantly restored by melatonin administration. In plasma, reduced glutathione (GSH) and its oxidized form (GSSG) were also altered in UAD-exposed rats. However, only the GSSG/GSH ratio was restored to control levels after melatonin treatment. Oxidative damage was observed in kidneys. Melatonin administration partially restored these adverse effects. It is concluded that melatonin offers some benefit as a potential agent to treat acute U-induced nephrotoxicity. [source] Osteopontin expression correlates with prognostic variables and survival in clear cell renal cell carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2006Koviljka Matusan MD Abstract Background and Objectives Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Recently, it has been detected in a growing number of human tumors, and assessed as a potential prognostic marker. The aim of this study was to analyze the expression of OPN in normal renal tissue and clear cell renal cell carcinomas (CRCCs), and to assess its prognostic significance. Methods The expression of OPN protein was immunohistochemically analyzed in 171 CRCCs and compared to usual clinicopathological parameters such as tumor size, nuclear grade, pathological stage, Ki-67 proliferation index, and cancer-specific survival. Results In normal renal parenchyma, the expression of OPN was seen in distal tubular epithelial cells, calcifications, and some stromal cells. The upregulation of OPN was observed in 61 CRCCs (35.7%) in the form of cytoplasmic granular staining of various intensities. Statistical analysis showed correlation of the OPN expression with tumor size (P,<,0.001), Fuhrman nuclear grade (P,<,0.001), pathological stage (P,=,0.011), and Ki-67 proliferation index (P,<,0.001). Moreover, patients with OPN-positive tumors had significantly worse prognosis in comparison to patients with tumors lacking OPN protein (P,=,0.004). Conclusion Our results suggest that overexpression of OPN is involved in the progression of CRCC. J. Surg. Oncol. 2006;94:325,331. © 2006 Wiley-Liss, Inc. [source] Occurrence of the African subgroup (Ia) of BK polyomavirus in younger Japanese childrenMICROBIOLOGY AND IMMUNOLOGY, Issue 6 2009Kaori Tanaka ABSTRACT BK polyomavirus (BKV) is ubiquitous among humans, usually infecting them asymptomatically during childhood. BKV persists in renal tissue of individuals and their progeny are excreted in urine, particularly in immunocompromised patients. JC virus, another human polyomavirus, has been considered to be transmitted from parents to children during prolonged cohabitation. However, BKV has been supposed to be transmitted not only within but also outside the family. In the present study, to clarify this possibility, we analyzed phylogenetically 35 BKV which were excreted in the urine by Japanese children and adults undergoing stem cell transplantation. Subtypes I, III and IV were detected in 15, two and one children and in 15, one and one adults, respectively. Among 15 subtype I isolates from children, three, four and eight belonged to subgroups Ia, Ib-1 and Ic, respectively. All the three children from whom Ia was detected were less than 9 years old. In contrast in the adults, three subtype I belonged to Ib-1 and the other 12 to Ic. These findings may reflect the recent transmission of BKV Ia strains to Japanese children. [source] Comparison of the distribution patterns of BK polyomavirus lineages among China, Korea and Japan: Implications for human migrations in northeast AsiaMICROBIOLOGY AND IMMUNOLOGY, Issue 5 2009Shan Zhong ABSTRACT BKV is widespread among humans, infecting children asymptomatically and then persisting in renal tissue. Based on the serological or phylogenetic method, BKV isolates worldwide are classified into four subtypes (I,IV), with subtypes I and IV further divided into several genetically-distinct subgroups. Since, similarly to JCV, a close relationship exists between BKV lineages and human populations, BKV should be useful as a marker to trace human migrations. To elucidate ancient human migrations in northeast Asia, urine samples were collected from immunocompetent elderly patients in Shanghai, China; Anyang, South Korea; and various locations in Japan. Partial and complete BKV genomes from these samples were amplified and sequenced using PCR, and the determined sequences were classified into subtypes and subgroups by phylogenetic and SNP analyses. In addition, based on an SNP analysis, the major subtype I subgroup (I/c) was classified into two subdivisions, I/c/Ch and I/c/KJ. The distribution patterns of BKV subgroups and subdivisions among the three regions were compared. Some aspects of the subgroup and subdivision distribution were more similar between Korea and Japan, but others were more similar between China and Korea or between China and Japan. Based on these findings, we inferred various northeast Asian migrations. Most of the JCV-based inferences of northeastern Asian migrations were consistent with those based on BKV, but the previously suggested migration route from the Asian continent to the Japanese archipelago seemed to need revision. [source] IgA nephropathy and mesangial cell proliferation: shared global gene expression profilesNEPHROLOGY, Issue 2002Hideto SAKAI SUMMARY: It is well established that mesangial cell proliferation plays a major role in glomerular injury and progressive renal injury. the expression of a number of different genes has been reported in proliferative mesangial cells in culture. However, the relevance of these genes to renal injury in general and IgA nephropathy (IgAN) remains to be established. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed molecular strategy to expand the scope of clinical investigation from a single gene to studying all genes at once in a systematic pattern. Capitalizing on the recently developed methodology of high cDNA array hybridization, the simultaneous expression of thousands of genes in primary human proliferating mesangial cells was monitored and compared with renal tissue of IgAN. Complex [,- 33P]-labelled cDNA targets were prepared from cultured mesangial cells, remnant tissue from five IgAN renal biopsies and four nephrectomies (controls). Each target was hybridized to a high-density array of 18 326 paired target genes. the radioactive hybridization signals were analysed by phosphorimager. Approximately 8212±530 different gene transcripts were detected per target. Close to 5% (386±90 genes) were full-length mRNA human transcripts (HT) and the remainder were expressed sequence tags (EST). Using a relational database, electronic subtraction was performed and matching was carried out to allow identification of 203 HT with shared expression in proliferative mesangial cells and IgAN renal biopsies. In addition hierarchical clustering analysis was performed on the HT of IgAN and controls to establish differential expression profiles of mesangial HT in IgAN and controls. Collectively the presented data constitutes a preliminary renal bioinformatics database of the transcriptional profiles in IgAN. More importantly, the information may help to speed up the discovery of genes underlying human IgAN. [source] Kinetics of PME/Pi in pig kidneys during cold ischemiaNMR IN BIOMEDICINE, Issue 7 2007Dominik von Elverfeldt Abstract Quality assessment of renal grafts via 31P magnetic resonance spectroscopy (MRS) has been investigated since 1986. As ATP concentrations decay rapidly during cold ischemia, the ratio of phosphomonoesters (PME) to inorganic phosphate (PiO) within the organ (PME/PiO) is commonly used as a quality marker and is considered to be the most reliable parameter. MRS did not lead to any delay in the transplantation procedure since it was performed during the time necessary for immunological matching (cross-match). Differences in the time period until transplantation call for extrapolation of the measured ratio to the end of cold ischemia before correlating with graft performance after transplantation. Therefore, quantitative determination of PME/PiO kinetics is essential. As a model for metabolite decay in human renal grafts, pig kidneys obtained from a slaughterhouse were monitored for up to 80,h via 31P MRS at 2,T. By employing chemical shift imaging (CSI) with a spatial resolution of approximately 1,×,1,×,4,cm3, it was possible to reduce partial volume effects significantly. The improved spectral resolution gained through CSI enabled reliable PME/PiO ratios to be determined only from those voxels containing renal tissue. Spectra were fitted automatically using the magnetic resonance user interface (MRUI), with prior knowledge obtained from unlocalized spectra when necessary. A monoexponential time dependence of PME/PiO for histidine,tryptophane,alpha-ketoglutarate (HTK)-perfused kidneys during cold ischemia was observed, and the determined value of the decay constant , was 0.0099,±,0.0012,h,1. In University of Wisconsin solution (UW)-perfused kidneys, an , of 0.0183,±,0.0053,h,1 was determined. Determination of the decay constant enables a usable extrapolation of PME/PiO for quality assessment of UW perfusion and a reliable extrapolation for HTK-perfused human renal grafts. Copyright © 2007 John Wiley & Sons, Ltd. [source] Prophylaxis effect of Trigonella foenum graecum L. seeds on renal stone formation in ratsPHYTOTHERAPY RESEARCH, Issue 10 2007Amine Laroubi Abstract Despite considerable progress in medical therapy, there is no satisfactory drug to treat kidney stones. Therefore, the current study aimed to look for an alternative by using Trigonella foenum graecum (Tfg) on nephrolithiasic rats as a preventive agent against the development of kidney stones, which is commonly used in Morocco as a phytotherapeutic agent. The inhibitory effect of the aqueous extract of Tfg seeds was examined on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) with ammonium chloride. At the end of the experiment all kidneys were removed and examined microscopically for possible crystal/stone locations and the total calcium amount in the renal tissue was evaluated. The blood was recovered to determine the levels of calcium, phosphorus, creatinine and urea. The results showed that the amount of calcification in the kidneys and the total calcium amount of the renal tissue in rats treated with Tfg were significantly reduced compared with the untreated group. Consequently, Tfg may be a useful agent in the treatment of patients with calcic urolithiasis. Copyright © 2007 John Wiley & Sons, Ltd. [source] Glomerular and tubular induction of the transcription factor c-Jun in human renal disease,THE JOURNAL OF PATHOLOGY, Issue 2 2007MH De Borst Abstract The transcription factor c-Jun regulates the expression of genes involved in proliferation and inflammation in many cell types but its role in human renal disease is largely unclear. In the current study we investigated whether c-Jun activation is associated with human renal disease and if c-Jun activation regulates pro-inflammatory and pro-fibrotic genes in renal cells. Activation of c-Jun was quantified by scoring renal expression of phosphorylated c-Jun (pc-Jun) in control human renal tissue and in biopsies from patients with various renal diseases (diabetic nephropathy, focal glomerulosclerosis, hypertension, IgA nephropathy, membranous glomerulopathy, minimal change disease, membranoproliferative glomerulonephritis, systemic lupus erythematosus, acute rejection, and Wegener's granulomatosis); this was correlated with parameters of renal damage. Furthermore, we studied the functional role of c-Jun activation in human tubular epithelial cells (HK-2) stimulated with TGF-,. Activated c-Jun was present in nuclei of glomerular and tubular cells in all human renal diseases, but only sporadically in controls. Across the diseases, the extent of pc-Jun expression correlated with the degree of focal glomerulosclerosis, interstitial fibrosis, cell proliferation, kidney injury molecule-1 (Kim-1) expression, macrophage accumulation, and impairment of renal function. In HK-2 cells, TGF-, induced c-Jun activation after 1 h (+40%, p < 0.001) and 24 h (+160%, p < 0.001). The specific c-Jun N-terminal kinase (JNK) inhibitor SP600125 abolished c-Jun phosphorylation at all time points and blunted TGF-,- or BSA-induced procollagen-1, 1 and MCP-1 gene expression in HK-2 cells. We conclude that in human renal disease, the transcription factor c-Jun is activated in glomerular and tubular cells. Activation of c-Jun may be involved in the regulation of inflammation and/or fibrosis in human renal disease. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Renal ACE2 expression in human kidney disease,THE JOURNAL OF PATHOLOGY, Issue 5 2004AT Lely Abstract Angiotensin-converting enzyme 2 (ACE2) is a recently discovered homologue of angiotensin-converting enzyme (ACE) that is thought to counterbalance ACE. ACE2 cleaves angiotensin I and angiotensin II into the inactive angiotensin 1,9, and the vasodilator and anti-proliferative angiotensin 1,7, respectively. ACE2 is known to be present in human kidney, but no data on renal disease are available to date. Renal biopsies from 58 patients with diverse primary and secondary renal diseases were studied (hypertensive nephropathy n = 5, IgA glomerulopathy n = 8, minimal change nephropathy n = 7, diabetic nephropathy n = 8, focal glomerulosclerosis n = 5, vasculitis n = 7, and membranous glomerulopathy n = 18) in addition to 17 renal transplants and 18 samples from normal renal tissue. Immunohistochemical staining for ACE2 was scored semi-quantitatively. In control kidneys, ACE2 was present in tubular and glomerular epithelium and in vascular smooth muscle cells and the endothelium of interlobular arteries. In all primary and secondary renal diseases, and renal transplants, neo-expression of ACE2 was found in glomerular and peritubular capillary endothelium. There were no differences between the various renal disorders, or between acute and chronic rejection and control transplants. ACE inhibitor treatment did not alter ACE2 expression. In primary and secondary renal disease, and in transplanted kidneys, neo-expression of ACE2 occurs in glomerular and peritubular capillary endothelium. Further studies should elucidate the possible protective mechanisms involved in the de novo expression of ACE2 in renal disease. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] FOXP3 Expression in Human Kidney Transplant Biopsies Is Associated with Rejection and Time Post Transplant but Not with Favorable OutcomesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2008S. Bunnag Expression of the transcription factor forkhead box P3 (FOXP3) in transplant biopsies is of interest due to its role in a population of regulatory T cells. We analyzed FOXP3 mRNA expression using RT-PCR in 83 renal transplant biopsies for cause in relationship to histopathology, clinical findings and expression of pathogenesis-based transcript sets assessed by microarrays. FOXP3 mRNA was higher in rejection (T-cell and antibody-mediated) than nonrejection. Surprisingly, some native kidney controls also expressed FOXP3 mRNA. Immunostaining for FOXP3 was consistent with RT-PCR, showing interstitial FOXP3+ lymphocytes, even in some native kidney controls. FOXP3 expression correlated with interstitial inflammation, tubulitis, interstitial fibrosis, tubular atrophy, C4d positivity, longer time posttransplant, younger donors, class II panel reactive antibody >20% and transcript sets reflecting inflammation and injury, but unlike these features was time dependent. In multivariate analysis, higher FOXP3 mRNA was independently associated with rejection, T-cell-associated transcripts, younger donor age and longer time posttransplant. FOXP3 expression did not correlate with favorable graft outcomes, even when the analysis was restricted to biopsies with rejection. Thus FOXP3 mRNA expression is a time-dependent feature of inflammatory infiltrates in renal tissue. We hypothesize that time-dependent entry of FOXP3-positive cells represents a mechanism for stabilizing inflammatory sites. [source] Early Presence of Calcium Oxalate Deposition in Kidney Graft Biopsies is Associated with Poor Long-Term Graft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2005Hélady Sanders Pinheiro Accumulated oxalate will be excreted after renal transplantation, creating an increased risk of tubular precipitation, especially in the presence of allograft dysfunction. We evaluated calcium oxalate (CaOx) deposition in renal allograft biopsies with early dysfunction, its association with acute tubular necrosis (ATN) and graft survival. We studied 97 renal transplant patients, submitted to a graft biopsy within 3 months post-transplant, and reanalyzed them after 10 years. We analyzed renal tissue under polarized light and quantified CaOx deposits. CaOx deposits were detected in 52.6% of the patients; 26.8% were of mild and 25.8% of moderate intensity. The deposits were more frequent in biopsies performed within 3 weeks post-transplant (82.4 vs. 63.0%, p < 0.05) and in allografts with more severe renal dysfunction (creatinine 5.6 mg/dL vs. 3.4 mg/dL, p < 0.001). ATN incidence was also higher in patients with CaOx deposits (47% vs. 24%, p < 0.001). Twelve-year graft survival was strikingly worse in patients with CaOx deposits compared to those free of deposits (49.7 vs. 74.1%, p = 0.013). Our study shows a high incidence of CaOx deposits in kidney allografts with early dysfunction, implying an additional risk for acute tubular injury, with a negative impact on graft survival. [source] Renal tubular expression of Toll-like receptor 4 in cyclosporine nephrotoxicityAPMIS, Issue 8 2009BEOM JIN LIM Lim BJ, Hong SW, Jeong HJ. Renal tubular expression of Toll-like receptor 4 in cyclosporine nephrotoxicity. APMIS 2009; 117: 583,91. Exploring the expression of Toll-like receptor (TLR) in cyclosporine (CsA)-induced renal injury in humans, we evaluated the expression of TLR4 in both biopsied renal tissue and cultured tubular cells. Immunohistochemical stains for TLR4, heat shock protein (HSP) 47, and HSP70 were performed in both pre- and post-treatment biopsies obtained from 18 patients of minimal change nephrotic syndrome or IgA nephropathy treated with CsA, and the percentage of positive tubules was compared in each case. For in vitro experiments, HK-2 cells were treated with CsA (2, 5, and 10 ,g/ml) for 24, 48, and 72 h. TLR4 mRNA and protein were measured using real-time RT-PCR and Western blot. In addition, hypoxic effect was added by GasPak System. The tubular expressions of TLR4 (2.2 ± 1.2% vs 4.4 ± 2.0%, p < 0.001) and HSP70 (2.6 ± 2.8% vs 6.1 ± 4.2%, p = 0.002) were increased after CsA treatment. TLR4 mRNA and protein expression were also increased in a dose-dependent manner. Hypoxia enormously increased TLR4 expression. In summary, CsA increased tubular expression of TLR4 and its ligand HSP70. As hypoxia was shown to be a strong stimulus for TLR4 expression, it can be said that TLR4 is influenced by both direct toxicity and impediment of renal microcirculation in human CsA nephrotoxicity. [source] Secondary effects induced by the colon carcinogen azoxymethane in BDIX rats,APMIS, Issue 6 2004MORTEN KOBÆK-LARSEN Azoxymethane (AOM) is claimed to be a colon-specific carcinogen. In our studies, AOM was administered to adult BDIX/OrlIco rats by four weekly subcutaneous injections of 15 mg/kg body weight each , two periods of 2 weeks of AOM treatment separated by a one-week break. This treatment schedule resulted in colon carcinomas with a high frequency (75,100%) and with a high reproducibility. However, some serious side effects are associated with this carcinogen treatment. In addition to the colorectal tumours, we found small intestinal tumours, hepatic lesions and a high frequency of mesenchymal renal tumours which increased with longer latency periods. The renal tumours were only found in female rats, and this indicates a possible relation to sex hormones. We therefore analyzed both male and female kidneys for the expression of estrogen and progesterone receptors by immunohistochemical methods. A positive nuclear reaction for estrogen receptor was present in most tumour cells in all tumours and occasionally in nuclei of entrapped tubular cells, but never in glomeruli. Normal appearing renal tissue from female rats showed no positive reaction, but in male rats a slight nuclear reaction was seen in tubuli in the peripheral part of the medulla. A similar pattern was seen for progesterone receptors, but less pronounced. No rats developed tumours in the external ear canal, which is in contrast to studies performed in other rat strains. This may therefore be strain related. In order to reduce the secondary effects of the induction of colon cancer by AOM, it is advisable to use male rats only and a maximum latency period of 32 weeks. [source] Genetic, immunologic, and immunohistochemical analysis of the programmed death 1/programmed death ligand 1 pathway in human systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 1 2009George K. Bertsias Objective A putative regulatory intronic polymorphism (PD1.3) in the programmed death 1 (PD-1) gene, a negative regulator of T cells involved in peripheral tolerance, is associated with increased risk for systemic lupus erythematosus (SLE). We undertook this study to determine the expression and function of PD-1 in SLE patients. Methods We genotyped 289 SLE patients and 256 matched healthy controls for PD1.3 by polymerase chain reaction,restriction fragment length polymorphism analysis. Expression of PD-1 and its ligand, PDL-1, was determined in peripheral blood lymphocytes and in renal biopsy samples by flow cytometry and immunohistochemistry. A crosslinker of PD-1 was used to assess its effects on anti-CD3/anti-CD28,induced T cell proliferation and cytokine production. Results SLE patients had an increased frequency of the PD1.3 polymorphism (30.1%, versus 18.4% in controls; P = 0.006), with the risk A allele conferring decreased transcriptional activity in transfected Jurkat cells. Patients homozygous for PD1.3,but not patients heterozygous for PD1.3,had reduced basal and induced PD-1 expression on activated CD4+ T cells. In autologous mixed lymphocyte reactions (AMLRs), SLE patients had defective PD-1 induction on activated CD4+ cells; abnormalities were more pronounced among homozygotes. PD-1 was detected within the glomeruli and renal tubules of lupus nephritis patients, while PDL-1 was expressed by the renal tubules of both patients and controls. PD-1 crosslinking suppressed proliferation and cytokine production in both normal and lupus T cells; addition of serum from patients with active SLE significantly ameliorated this effect on proliferation. Conclusion SLE patients display aberrant expression and function of PD-1 attributed to both direct and indirect effects. The expression of PD-1/PDL-1 in renal tissue and during AMLRs suggests an important role in regulating peripheral T cell tolerance. [source] A Thermoreversible Polymer Mediates Controlled Release of Glial Cell Line-Derived Neurotrophic Factor to Enhance Kidney RegenerationARTIFICIAL ORGANS, Issue 8 2010Yousof Gheisari Abstract Previously, we reported that human mesenchymal stem cells (hMSCs) that were cultivated in growing embryos differentiated in an appropriate developmental milieu, thereby facilitating the development of a functional renal unit. However, this approach required transfection with an adenovirus that expressed glial cell line-derived neurotrophic factor (GDNF) to enhance the development of hMSC-derived renal tissue, and safety issues restrict the clinical use of such viral vectors. To circumvent this problem, we tested an artificial polymer as a means to diffuse GDNF. This GDNF-polymer, which exists in liquid form at 4°C but becomes a hydrogel upon heating to 37°C, was used as a thermoreversible switch, allowing the injection of hMSCs at low viscosity using a mouth pipette, with subsequent slow diffusion of GDNF as it solidified. The polymer, which was dissolved in a solution of GDNF at 4°C and then maintained at 37°C, acted as a diffuser of GDNF for more than 48 h. LacZ -transfected hMSCs and the GDNF-polymer (at 4°C) were placed in the nephrogenic sites of growing rat embryos that were maintained at 37°C. Forty-eight hours later, the resultant kidney anlagen were dissected out and allowed to continue developing for 6 days in vitro. Whole-organ X-Gal staining and fluorescence activated cell sorter analysis showed that the number of hMSC-derived cells was significantly increased in developed anlagen that have been generated from hMSCs plus GDNF-polymer compared with those from hMSCs plus GDNF-containing medium and was comparable to those from adenovirus-transfected hMSCs. These findings suggest that the GDNF-polymer can be used as a diffuser of GDNF for kidney organogenesis. [source] Sulphated Polysaccharides: New Insight in the Prevention of Cyclosporine A-Induced Glomerular InjuryBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2007Anthony Josephine Nephrotoxicity induced by cyclosporine A continues to be a major problem despite its potent immunosuppressive action. Adult male albino rats of Wistar strain were categorized into four groups. Two groups (II and IV) were administered cyclosporine A (25 mg/kg body weight, orally) for 21 days, in which Group IV rats were also treated simultaneously with sulphated polysaccharides (5 mg/kg body weight, subcutaneously) for the same period. A significant loss in body weight was noted in the cyclosporine A-induced rats. Renal damage was assessed in terms of decreased creatinine clearance and increased activity of lysosomal enzymes. The levels of glycoproteins were found to be decreased in the renal tissue, and a noticeable rise in glycosaminoglycanuria coupled with marked proteinuria was more prominent in the cyclosporine A-induced animals. Furthermore, the extent of kidney damage was assessed by histopathological findings. Toxic manifestations were also confirmed by transmission electron microscopic studies. These morphological abnormalities and other alterations in the renal tissue were significantly offset by sulphated polysaccharides supplementation. These findings underline that restoration of normal cells accredits sulphated polysaccharides, from Sargassum wightii, with nephroprotective role, against cyclosporine A-induced renal injury. [source] Ectopic renal tissue in the gubernaculum associated with undescended testisBJU INTERNATIONAL, Issue 3 2002T. Shono No abstract is available for this article. [source] INTRAPERITONEAL GLYCEROL INDUCES OXIDATIVE STRESS IN RAT KIDNEYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2008Elenara Rieger SUMMARY 1Glycerol has been used for the treatment of intracranial hypertension, cerebral oedema and glaucoma. Experimentally, intramuscular administration of hypertonic glycerol solution is used to produce acute renal failure. In this model, glycerol causes rhabdomyolysis and myoglobinuria, resulting in the development of renal injury. The pathogenesis is thought to involve vascular congestion, the formation of casts and oxidative stress. However, the effect of glycerol itself independent of rhabdomyolysis has not been investigated. Therefore, the aim of the present study was to investigate the effects of i.p. glycerol on some biochemical and oxidative stress parameters in the kidney of young rats. 2Rats received 10 mL/kg, i.p., hypertonic glycerol solution (50% v/v) or saline (NaCl 0.85 g%) followed by 24 h water deprivation. Twenty-four hours after the administration of glycerol, rats were killed. Creatinine levels and the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined in the plasma. In addition, CK, pyruvate kinase and LDH activity and oxidative stress parameters (free radical formation, lipid peroxidation and protein carbonylation) were measured in renal tissue. 3Glycerol did not alter plasma CK activity and increased plasma creatinine levels, suggesting renal insufficiency and the absence of rhabdomyolysis. Renal CK and pyruvate kinase activity was decreased, suggesting diminution of energy homeostasis in the kidney. Plasma and renal LDH activity was decreased, whereas the formation of free radicals, lipid peroxidation and protein carbonylation were increased, suggesting oxidative stress. 4These results are similar to those described after the intramuscular administration of glycerol. Therefore, it is possible that glycerol may provoke renal lesions by mechanisms other than those induced by rhabdomyolysis. [source] Patterning the embryonic kidney: BMP signaling mediates the differentiation of the pronephric tubules and duct in Xenopus laevisDEVELOPMENTAL DYNAMICS, Issue 1 2008Christina M. Bracken Abstract The Bone morphogenetic proteins (BMPs) mediate a wide range of diverse cellular behaviors throughout development. Previous studies implicated an important role for BMP signaling during the differentiation of the definitive mammalian kidney, the metanephros. In order to examine whether BMP signaling also plays an important role during the patterning of earlier renal systems, we examined the development of the earliest nephric system, the pronephros. Using the amphibian model system Xenopus laevis, in combination with reagents designed to inhibit BMP signaling during specific stages of nephric development, we revealed an evolutionarily conserved role for this signaling pathway during renal morphogenesis. Our results demonstrate that conditional BMP inhibition after specification of the pronephric anlagen is completed, but prior to the onset of morphogenesis and differentiation of renal tissues, results in the severe malformation of both the pronephric duct and tubules. Importantly, the effects of BMP signaling on the developing nephron during this developmental window are specific, only affecting the developing duct and tubules, but not the glomus. These data, combined with previous studies examining metanephric development in mice, provide further support that BMP functions to mediate morphogenesis of the specified renal field during vertebrate embryogenesis. Specifically, BMP signaling is required for the differentiation of two types of nephric structures, the pronephric tubules and duct. Developmental Dynamics 237:132,144, 2008. © 2007 Wiley-Liss, Inc. [source] Regional DNA hypermethylation and DNA methyltransferase (DNMT) 1 protein overexpression in both renal tumors and corresponding nontumorous renal tissuesINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Eri Arai Abstract To evaluate the significance of altered DNA methylation during renal tumorigenesis, tumorous tissues (T) and corresponding nontumorous renal tissues (N) from 94 patients with renal tumors, and normal renal tissues (C) from 16 patients without renal tumors were investigated. DNA methylation status on CpG islands of the p16, human MutL homologue 1 (hMLH1), von-Hippel Lindau (VHL) and thrombospondin-1 (THBS-1) genes and the methylated in tumor (MINT) -1, -2, -12, -25 and -31 clones and DNA methyltransferase (DNMT) 1 expression were examined by bisulfite modification and immunohistochemistry, respectively. The average number of methylated CpG islands was significantly higher in N than in C, and was even higher in T. The average number of methylated CpG islands in N was significantly correlated with a higher histological grade of corresponding conventional renal cell carcinomas (RCCs). The average number of methylated CpG islands in RCCs was significantly correlated with macroscopic configuration with extranodular or multinodular growth, higher histological grade, infiltrating growth pattern and vascular involvement. The recurrence-free survival rate of patients with RCCs showing accumulation of DNA methylation was significantly lower than that of patients not showing this feature. The incidence of nuclear immunoreactivity for DNMT1 tended to be higher in proximal tubules from N than in those from C, and was significantly higher in RCCs. From the viewpoint of altered DNA methylation, N is at the precancerous stage, and N showing accumulation of DNA methylation may generate more malignant RCCs. Regional DNA hypermethylation may be associated with renal tumorigenesis from a precancerous condition to malignant progression and become a predictor of patient prognosis. © 2006 Wiley-Liss, Inc. [source] Haematological, hepatic and renal alterations after repeated oral or intraperitoneal administration of monoisoamyl DMSA.JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2002Abstract Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a vicinal thiol chelator, is gaining recognition recently as a better chelator than meso 2,3-dimercaptosuccinic acid (DMSA) in decreasing heavy metal burden in tissues because of its lipophilic character. There is, however, little information available on the toxicological properties of this chelator after repeated administration in animals. In the present study, we investigated the dose-dependent effect of MiADMSA on various biochemical parameters suggestive of alterations in haem biosynthesis and hepatic, renal and brain oxidative stress after 21 days of repeated intraperitoneal (i.p.) or oral (p.o.) administration to rats. The concentration of essential metals in blood and soft tissues was determined along with histopathological observations of hepatic and renal tissues. The results suggest that MiADMSA administration had no effect on blood ,-aminolevulinic acid dehydratase activity. However, an increase in zinc protoporphyrin and a decrease in haemoglobin levels were noted in animals given MiADMSA i.p. A moderate increase in serum alkaline phosphatase suggested mild hepatotoxicity at the highest dose (100 mg kg,1, i.p.). This was confirmed by histopathological examinations, which identified basophilic stippling, granulation of the cytoplasm, haemorrhage and congestion. At the highest dose, levels of hepatic thiobarbituric acid reactive substance and oxidized glutathione were increased above those of control values. Levels of hepatic reduced glutathione were decreased. Taken together, these observations point to oxidative stress. In animals administered MiADMSA i.p. there was an increase in the brain malondialdehyde levels at the two higher doses (50 and 100 mg kg,1). Essential metal status revealed a significant effect of MiADMSA (p.o.) in increasing blood zinc while significantly decreasing the kidney zinc level. The most significant adverse effect of MiADMSA was on copper concentration, which showed significant depletion from almost all major organs. Magnesium levels in blood decreased but increased in liver of MiADMSA-administered rats. Histopathological observations of liver and kidneys suggest few moderate lesions. It can be concluded that repeated administration of MiADMSA is compromised with some mild toxic effect, particularly the loss of copper. The effects during oral administration are comparatively less pronounced than by the i.p. route. Copyright © 2002 John Wiley & Sons, Ltd. [source] Calotte morphology in the phylum Dicyemida: niche separation and convergenceJOURNAL OF ZOOLOGY, Issue 4 2003Hidetaka Furuya Abstract The renal sacs of a diversity of cephalopod molluscs were examined to study the morphology of dicyemid mesozoans. Most of the dicyemid species studied were found to be host specific. Typically, two or more species of dicyemids were present in each host species or each host individual. When dicyemid species co-occurred, their calotte shapes were distinctly different. The following variations in calotte shapes were usually detected within a given host individual: (1) when two species of dicyemids were present, two distinct calotte shapes, conical and discoidal, were observed; (2) when three species of dicyemids were present, three types of calotte configurations were observed, conical (two grades) and discoidal; (3) when more than four species of dicyemids were present, at least one species was characterized by its rare irregularly shaped calotte. As a rule, when more than two dicyemid species were present in a single host individual, calotte shapes were dissimilar. Calotte shapes in dicyemid species from different host species more closely resemble each other than those of dicyemids observed within the same host species. Dicyemids with conical or dome-shaped calottes are found within the convolutions or folds of the renal appendages, whereas those with flat, discoidal calottes attach to the surface of the renal appendages. In the dicyemids, calotte morphology seems to result from adaptation to the structure of host renal tissues and helps to facilitate niche separation of coexisting species. [source] METHODS FOR STUDYING THE PHYSIOLOGY OF KIDNEY OXYGENATIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2008Roger G Evans SUMMARY 1An improved understanding of the regulation of kidney oxygenation has the potential to advance preventative, diagnostic and therapeutic strategies for kidney disease. Here, we review the strengths and limitations of available and emerging methods for studying kidney oxygen status. 2To fully characterize kidney oxygen handling, we must quantify multiple parameters, including renal oxygen delivery (DO2) and consumption (VO2), as well as oxygen tension (Po2). Ideally, these parameters should be quantified both at the whole-organ level and within specific vascular, tubular and interstitial compartments. 3Much of our current knowledge of kidney oxygen physiology comes from established techniques that allow measurement of global kidney DO2 and VO2, or local tissue Po2. When used in tandem, these techniques can help us understand oxygen mass balance in the kidney. Po2 can be resolved to specific tissue compartments in the superficial cortex, but not deep below the kidney surface. We have limited ability to measure local kidney tissue DO2 and VO2. 4Mathematical modelling has the potential to provide new insights into the physiology of kidney oxygenation, but is limited by the quality of the information such models are based on. 5Various imaging techniques and other emerging technologies have the potential to allow Po2 mapping throughout the kidney and/or spatial resolution of Po2 in specific renal tissues, even in humans. All currently available methods have serious limitations, but with further refinement should provide a pathway through which data obtained from experimental animal models can be related to humans in the clinical setting. [source] | |||||||||||||||||||||||||