bromochloroacetic-acid and Kidney-Failure--Chronic

Topics: alpha-Fetoproteins; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Humans; Keratin-19; Keratins; Kidney Failure, Chronic; Male; Neoplasms; Peptide Fragments; Peptides; Peritoneal Dialysis; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Protein Precursors; Prothrombin; Recombinant Proteins; Renal Dialysis; Serpins; Tissue Polypeptide Antigen

Pre-neoplastic lesions and renal cell tumors of distinct pheno- and genotypes occur frequently in end-stage kidneys. The aim of this study was to investigate the role of KRT7 and KRT19 in this process, the expression of which was previously detected by Affymetrix GeneChip analysis.. Twelve end-stage kidneys were analyzed to find pre-neoplastic lesions and tumors and expression of KRT7 and KRT19 was examined by immunohistochemistry.. A total of 17 tumors, 149 pre-neoplastic lesions, 179 simple or proliferative cysts >2 mm were identified. Diffuse expression of KRT7 and KRT19 was seen in all end-stage kidneys as well as in the vast majority of cysts, pre-neoplastic lesions and tumors.. Our data indicates that de novo expression of KRT7 and KRT19 resulting in altered plasticity and stem cell characteristics of epithelial cells might be a crucial factor in increasing the risk of tumor development in end-stage kidneys.

Topics: Disease Progression; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Keratin-19; Keratin-7; Keratins; Kidney Failure, Chronic; Kidney Neoplasms; Male

Topics: Aged; Biomarkers, Tumor; Biopsy; Carcinosarcoma; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Peritoneal Neoplasms; Renal Dialysis

Congenital obstructive nephropathy (CON) is a leading cause of pediatric chronic kidney disease (CKD). Despite optimal surgical and medical care, there is a high rate of CKD progression. Better understanding of molecular and cellular changes is needed to facilitate development of improved biomarkers and novel therapeutic approaches in CON.. The megabladder (mgb) mouse is an animal model of CKD with impaired bladder emptying, hydronephrosis, and progressive renal injury. In this study, we characterize a particular microRNA, miR-205, whose expression changes with the degree of hydronephrosis in the mgb(-/-) kidney.. Expression of miR-205 is progressively increased in the adult mgb(-/-) mouse with worsening severity of hydronephrosis. miR-205 expression is correlated with altered expression of cytokeratins and uroplakins, which are markers of cellular differentiation in urothelium. We describe the spatial pattern of miR-205 expression, including increased expression in renal urothelium and novel miR-205 expression in medullary collecting duct epithelium in the congenitally obstructed kidney.. miR-205 is increased with severity of CON and CKD in the mgb(-/-) mouse and may regulate urothelial differentiation.

Topics: Animals; Biomarkers; Cell Differentiation; Disease Models, Animal; Disease Progression; Epithelium; Female; Gene Expression Regulation; Hydronephrosis; Keratins; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Tubules, Collecting; Male; Mice; Mice, Transgenic; MicroRNAs; Tight Junctions; Uroplakins; Urothelium

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a subtype of renal cell carcinoma (RCC) with unique morphologic features found exclusively in the background of end-stage renal disease. We analyzed the clinicopathologic features and immumoreactive profiles of 12 cases of ACD-RCC to further characterize this recently recognized entity. Review of histologic slides was performed in conjunction with immunohistochemical staining directed to the contemporary diagnostic antibodies and the putative target therapy-related markers. Histologically, the tumors showed characteristic inter-or intracellular microlumens and eosinophilic tumor cells. Intratumoral hemosiderin deposition and degenerating foamy tumor cells were consistent findings which were not previously described. Immunohistochemically, all the tumors were positive for alpha-methylacyl-CoA-racemase, CD10, pan-cytokeratin, PTEN (phosphatase and tensin homolog deleted on chromosome 10) and c-met, while negative for carbonic anhydrase-9, CD57, CD68, c-kit, pax-2, platelet-derived growth factor receptor (PDGFR)-α or vascular endothelial growth factor receptor (VEGFR)-2. Heterogenous staining was found for CK7 and kidney-specific cadherin. Positive reaction to c-met suggests its utility as a plausible therapeutic target in ACD-RCC. Thus, we present the unique morphologic and immunopathologic features of ACD-RCC, which may be helpful in both diagnostic and therapeutic aspects.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Humans; Keratins; Kidney Failure, Chronic; Kidney Neoplasms; Male; Middle Aged; Neprilysin; Proto-Oncogene Proteins c-met; Racemases and Epimerases

Topics: Adult; Biomarkers; Cell Dedifferentiation; Disease Progression; Glomerulonephritis; HIV Seronegativity; Humans; Intellectual Disability; Keratins; Ki-67 Antigen; Kidney Failure, Chronic; Kidney Glomerulus; Macrophages; Male; Podocytes; Renal Dialysis

OBJECTIVE. Tumour markers are widely used for monitoring cancer patients and for screening certain tumours. It has recently been shown that the concentrations of some tumour markers are higher in patients with chronic kidney disease (CKD) than in healthy subjects. We analysed the influence of renal function and hemodialysis treatment on the serum levels of CA19-9, CA125, alpha fetoprotein (AFP), CA15.3, CA72.4, CYFRA 21-1, neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC-Ag).. 232 non-dialysis patients with CKD and 37 uraemic patients treated with maintenance hemodialysis were enrolled in this study. The nondialysis patients were divided into three groups depending on their creatinine clearance (Ccr) levels: group 1 = Ccr < or =25 mL/min; group 2 = 25.1-49.9 mL/min; group 3 = Ccr > or =50 mL/min. For comparison, we chose 37 non-dialysis patients with similar Ccr, age and same gender as controls.. The serum concentrations of CA19-9, CA125 (male), CYFRA 21-1, NSE and SCC-Ag correlated negatively with Ccr, while there were no significant differences in the concentrations of CA125 (female), AFP, CA15.3, CA72.4. The serum levels of CA19-9, CA125, AFP, CA15.3, CA72.4, CYFRA 21-1, NSE and SCC-Ag showed no differences between hemodialysis patients and non-dialysis controls (p > 0.017).. The increase in the serum levels of CA19-9, CA125 (in males), CYFRA 21-1, NSE and SCC-Ag in patients with CKD affects the specificity of these markers in the diagnosis of cancer. Hemodialysis does not affect the serum levels of CA19-9, CA125, AFP, CA15.3, CA72.4, CYFRA 21-1, NSE and SCC-Ag.

Topics: Adult; Aged; alpha-Fetoproteins; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Female; Glomerular Filtration Rate; Humans; Keratin-19; Keratins; Kidney Failure, Chronic; Male; Middle Aged; Mucin-1; Renal Dialysis

During peritoneal dialysis (PD), the peritoneum is exposed to bioincompatible dialysis fluids that cause epithelial-to-mesenchymal transition of mesothelial cells, fibrosis, and angiogenesis. Ultrafiltration failure is associated with high transport rates and increased vascular surface, indicating the implication of vascular endothelial growth factor (VEGF). Sources of VEGF in vivo in PD patients remain unclear. We analyzed the correlation between epithelial-to-mesenchymal transition of mesothelial cells and both VEGF level and peritoneal functional decline.. Effluent mesothelial cells were isolated from 37 PD patients and analyzed for mesenchymal conversion. Mass transfer coefficient for creatinine (Cr-MTC) was used to evaluate peritoneal function. VEGF concentration was measured by using standard procedures. Peritoneal biopsy specimens from 12 PD patients and 6 controls were analyzed immunohistochemically for VEGF and cytokeratin expression.. Nonepithelioid mesothelial cells from effluent produced a greater amount of VEGF ex vivo than epithelial-like mesothelial cells (P < 0.001). Patients whose drainage contained nonepithelioid mesothelial cells had greater serum VEGF levels than those with epithelial-like mesothelial cells in their effluent (P < 0.01). VEGF production ex vivo by effluent mesothelial cells correlated with serum VEGF level (r = 0.6; P < 0.01). In addition, Cr-MTC correlated with VEGF levels in culture (r = 0.8; P < 0.001) and serum (r = 0.35; P < 0.05). Cr-MTC also was associated with mesothelial cell phenotype. VEGF expression in stromal cells, retaining mesothelial markers, was observed in peritoneal biopsy specimens from high-transporter patients.. These results suggest that mesothelial cells that have undergone epithelial-to-mesenchymal transition are the main source of VEGF in PD patients and therefore may be responsible for a high peritoneal transport rate.

Topics: Adult; Aged; Biopsy; Cell Differentiation; Cell Membrane Permeability; Cells, Cultured; Epithelial Cells; Epithelium; Female; Fibrosis; Glucose; Hemodialysis Solutions; Hemoperitoneum; Humans; Keratins; Kidney Failure, Chronic; Male; Mesoderm; Middle Aged; Neovascularization, Pathologic; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis; Stromal Cells; Vascular Endothelial Growth Factor A

We present a case of adenocarcinoma developing at the vesicocutaneous edge of a vesicostomy, 40 years after it was created, in a patient who underwent cadaveric kidney transplant. Although transitional and squamous cell carcinoma of a vesicostomy have been reported, to our knowledge, the presence of adenocarcinoma at the vesicostomy edge has not been reported previously.

Topics: Abnormalities, Multiple; Adenocarcinoma; Adult; Biomarkers, Tumor; Cell Transformation, Neoplastic; Cystostomy; Dermatologic Surgical Procedures; Female; Humans; Immunosuppression Therapy; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Failure, Chronic; Kidney Transplantation; Neoplasm Proteins; Postoperative Complications; Surgical Stomas; Time Factors; Urinary Bladder Neoplasms; Urinary Bladder, Neurogenic; Urogenital Abnormalities; Urothelium

It has been reported that cytokeratin 19 fragment (CYFRA 21-1) is superior to tissue polypeptide antigen (TPA) as a tumor marker, although there is a high correlation between CYFRA 21-1 and TPA levels in patients with lung cancer. We investigated correlations between these tumor markers in patients with non-malignant diseases. Marked correlations were found between CYFRA 21-1 and TPA levels in healthy subjects (n = 31), non-insulin-dependent diabetes mellitus (n = 160) and hemodialysis patients (n = 83) (range of r-value = 0.90-0.93, P < 0.0001). However in liver cirrhosis patients (n = 36), only a weak correlation was found (r = 0.39, P < 0.0001) and there were correlations between only TPA and both aspartate aminotransferase and alanine aminotransferase levels (r2 = 0.48 and 0.36, P < 0.0001). The elevated TPA levels in liver cirrhosis patients may be related to the decreased specificity of TPA as a tumor marker.

Topics: Alanine Transaminase; Antigens, Neoplasm; Aspartate Aminotransferases; Biomarkers, Tumor; Diabetes Mellitus, Type 2; Humans; Keratin-19; Keratins; Kidney Failure, Chronic; Liver Cirrhosis; Renal Dialysis; Tissue Polypeptide Antigen

Serum levels of CYFRA 21-1(cytokeratin-19 fragment) and ProGRP (pro-gastrin-releasing peptide), the new prognostic markers of lung cancer, were measured by ELISA (enzyme-linked immunoadsorbent assay) in 27 (for CYFRA 21-1; male 13, female 14; age 54+/-17 years) or 22 (for ProGRP; male 9, female 13; age 59+/-18 years) patients with various serum creatinine levels, 42 haemodialysis (HD) patients (male 24, female 18; age 59+/-14 years) and 30 continuous ambulatory peritoneal dialysis (CAPD) patients (male 18, female 12; age 48+/-9 years). All the patients were without clinical and radiological signs of lung cancer. Positive correlations were found between serum creatinine and serum CYFRA 21-1 and ProGRP levels. Serum levels of CYFRA 21-1 were above the cutoff limit (3.5 ng/mL) in 57% of HD patients (mean 4.07+/-1.56 ng/mL) and in 73% of CAPD patients (mean 4.87+/-1.56 ng/mL). Serum levels of ProGRP were above the cutoff limit (46.0 pg/mL) in 90% of HD patients (mean 107.0+/-59.4 pg/mL) and in 93% of CAPD patients (mean 112.4+/-44.5 pg/mL). Our data indicate that evaluation of renal function is essential when the measurement of these tumor markers is to be applied as one of the diagnostic tools of lung cancer.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Creatinine; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratin-19; Keratins; Kidney Failure, Chronic; Lung Neoplasms; Male; Middle Aged; Peptide Fragments; Peptides; Recombinant Proteins

We examined serum and urinary cytokeratin 19 fragment (CYFRA 21-1) levels in patients with diabetic nephropathy as a model of chronic renal failure, to investigate the mechanism of increased serum CYFRA 21-1 levels in chronic renal failure. Serum and urinary CYFRA 21-1 levels in non-insulin-dependent diabetes mellitus (NIDDM) patients with abnormal urinary immunoglobulin G (IgG) levels (>1.1 mg/g x Cr, n=126) were higher than those with normal urinary IgG levels. In NIDDM patients with normal urinary IgG levels (n=81); the urinary albumin or transferrin levels were not related to serum or urinary CYFRA 21-1 levels. We speculate that the increased serum CYFRA 21-1 levels contribute to metabolic abnormality in the kidney itself rather than the decreased urinary excretion per se, and that increased urinary CYFRA 21-1 levels are found in advanced cases of diabetic nephropathy with destruction of the size barrier.

Topics: Albuminuria; Antigens, Neoplasm; Biomarkers, Tumor; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Immunoglobulin G; Immunoradiometric Assay; Keratin-19; Keratins; Kidney Failure, Chronic; Male; Middle Aged; Prognosis; Severity of Illness Index; Transferrin

Visceral glomerular epithelial cells (vGECs) originate from a mesenchymal blastema and transiently express cytokeratin during embryogenesis. There are no reports of cytokeratin expression in vGECs of mature, normal or damaged, human or other mammalian kidneys in vivo, but in vitro studies have provided evidence of the synthesis of cytokeratin in cultured vGECs. Cytokeratin expression was observed in vGECs in the damaged kidneys of four dogs with spontaneous renal diseases and, by using monoclonal antibodies, type 18 cytokeratin was identified. vGECs are apparently able to (re-) activate in vivo a mechanism for switching on the synthesis of cytokeratin in damaged glomeruli.

Topics: Animals; Dogs; Epithelium; Glomerulonephritis; Keratins; Kidney Failure, Chronic; Kidney Glomerulus; Male

Serum levels of cytokeratin subunit 19 (CYFRA 21-1) were measured in 42 healthy volunteers, 104 cases of malignant diseases, 30 patients with chronic renal failure and 13 patients with nonmalignant and infectious diseases. The reliability of the method was demonstrated after dilution of serum samples and intra- and inter-assay reproducibility. Serum CYFRA-21-1 concentrations were less than 2.00 ng/ml in all healthy controls and 86% of the malignant cases had high serum CYFRA 21-1 levels. However slightly elevated values of CYFRA 21-1 were observed in most chronic renal failure patients. High correlation was observed between serum CYFRA 21-1 and Tissue Polypeptide Antigen (TPA) values (r = 0.90, n = 10) but not with serum alpha-feto protein (AFP) concentrations. Furthermore, cross binding tests with the CYFRA 21-1 tracer/CYFRA 21-1 antibody-coated beads and CYFRA 21-1 tracer/TPA antibody-coated beads also gave an almost linear graph. These results indicate that CYFRA 21-1 and TPA share similar type of antigens.

Topics: Biomarkers, Tumor; Communicable Diseases; Cross Reactions; Female; Humans; Immunoradiometric Assay; Keratins; Kidney Failure, Chronic; Macromolecular Substances; Metabolic Diseases; Neoplasms; Reference Values; Reproducibility of Results

Human polycystic kidney disease (PKD) epithelia were successfully grown in culture and expressed abnormal characteristics. Cysts lining epithelia of superficial and deep cysts were microdissected and compared to individual normal human proximal straight tubules (PST) and cortical collecting tubules (CCT) grown in defined media. PKD cyst epithelia differed from normal renal tubular epithelia in growth patterns and structural and functional properties. PKD epithelia grew more rapidly and showed cyst-like areas in otherwise confluent monolayers. Polygonal and elongate cells contained an epithelial-specific cytokeratin antigen and had polarized morphology. An extremely abnormal basement membrane morphology was seen and consisted of some banded collagen and numerous unique blebs or spheroids. These blebs were apparently extruded from intracellular vacuoles and stained with ruthenium red, suggesting a proteoglycan component. Cytochemistry of marker enzymes demonstrated the presence of NaK-ATPase and alkaline phosphatase, but a lack of gamma-glutamyl transpeptidase. The response of adenylate cyclase activity to vasopressin, parathyroid hormone, and forskolin was significantly diminished in PKD cells as compared to PST and CCT. These studies suggest a defect in cell growth and basement membrane synthesis in human PKD. Cultured PKD epithelia provide a new tool for the study of the pathogenesis of this disease.

Topics: Adolescent; Adult; Cells, Cultured; Cytological Techniques; Epithelium; Histocytochemistry; Humans; Keratins; Kidney; Kidney Failure, Chronic; Microscopy, Electron; Polycystic Kidney Diseases