epidermal-growth-factor and Proteinuria

This study investigated the association between urinary epidermal growth factor (EGF) and complete remission (CR) of proteinuria in children with IgA nephropathy (IgAN).. We included 108 patients from the Registry of IgA Nephropathy in Chinese Children. The urinary EGF at the baseline and follow-up were measured and normalized by urine creatinine (expressed as uEGF/Cr). The person-specific uEGF/Cr slopes were estimated using linear mixed-effects models for the subset of patients with longitudinal data of uEGF/Cr. Cox models were used to analyze the associations of baseline uEGF/Cr and uEGF/Cr slope with CR of proteinuria.. Patients with high baseline uEGF/Cr were more likely to achieve CR of proteinuria (adjusted HR 2.24, 95% CI: 1.05-4.79). The addition of high baseline uEGF/Cr on the traditional parameters significantly improved the model fit for predicting CR of proteinuria. In the subset of patients with longitudinal data of uEGF/Cr, high uEGF/Cr slope was associated with a higher likelihood of CR of proteinuria (adjusted HR 4.03, 95% CI: 1.02-15.88).. Urinary EGF may be a useful noninvasive biomarker for predicting and monitoring CR of proteinuria in children with IgAN.. High levels of baseline uEGF/Cr (>21.45 ng/mg) could serve as an independent predictor for CR of proteinuria. The addition of baseline uEGF/Cr on the traditional clinical pathological parameters significantly improved the fitting ability for the prediction of CR of proteinuria. Longitudinal data of uEGF/Cr were also independently associated with CR of proteinuria. Our study provides evidence that urinary EGF may be a useful noninvasive biomarker in the prediction of CR of proteinuria as well as monitoring therapeutic response, thus guiding treatment strategies in clinical practice for children with IgAN.

Topics: Biomarkers; Child; Creatinine; East Asian People; Epidermal Growth Factor; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Proteinuria

There is a need for sensitive and specific biomarkers to predict kidney damage and therapeutic response in lupus nephritis (LN). Monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF) are cytokines with divergent roles. EGF or EGF/MCP1 ratio have been shown to correlate with prognosis in primary glomerulonephritis, but there is limited information in lupus nephritis (LN). This study evaluated the roles of MCP-1, EGF or their ratio as biomarkers of histopathology and response to treatment in LN.. This was a cross-sectional and observational study. Baseline urine MCP-1 and EGF levels in systemic lupus erythematosus (SLE) patients and controls (total n = 101) were compared, and levels were correlated with clinicopathological findings and subsequent response to treatment.. MCP-1 was higher in active LN (n = 69) compared to other SLE groups and controls, whereas EGF was not different. MCP-1 correlated with disease activity (proteinuria, renal SLEDAI, classes III/IV/V, and high activity index.) By contrast, EGF correlated with eGFR, but not with proteinuria, activity index, or class III/IV/V. MCP-1 was higher, and EGF was lower in high chronicity index. EGF/MCP-1 decreased with greater clinicopathological severity. In a subgroup with proliferative LN who completed six months of induction therapy (n = 41), EGF at baseline was lower in non-responders compared to responders, whereas MCP-1 was similar. By multivariable analysis, baseline EGF was independently associated with subsequent treatment response. Area under the curve for EGF to predict response was 0.80 (0.66-0.95). EGF ≥ 65.6 ng/ mgCr demonstrated 85% sensitivity and 71% specificity for response. EGF/MCP-1 did not improve the prediction for response compared to EGF alone.. MCP-1 increased with disease activity, whereas EGF decreased with low GFR and chronic damage. Urine EGF may be a promising biomarker to predict therapeutic response in LN. EGF/MCP-1 did not improve the prediction of response.

Topics: Biomarkers; Chemokine CCL2; Cross-Sectional Studies; Epidermal Growth Factor; Female; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Proteinuria

Kidney biopsies of patients with diabetic nephropathy (DN) and normal kidney function may exhibit interstitial fibrosis (IF) without reduction of glomerular filtration rate (GFR) because of hyperfiltration. The aim of our study was to analyse the performance of a set of biomarkers of tubular injury to estimate the extent of IF in patients with DN and normal kidney function.. This cross-sectional study included 118 adults with DN diagnosed by kidney biopsy and GFR ≥90 mL/min/1.73 m2 and a control group of healthy subjects. We measured the urinary excretion of monocyte chemoattractant protein-1 (MCP-1) neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), β2-microglobulin and dickkopf-3 protein (DKK-3) at the time of kidney biopsy. GFR was measured by chromium-51 labeled ethylenediamine tetraacetic acid (Cr-EDTA) (measured GFR). IF was quantified using a quantitative morphometric procedure. Predictive multivariate models were developed to estimate the IF surface.. Patients with DN showed significantly higher levels of DKK-3, MCP-1 and L-FABP and significantly lower levels of epidermal growth factor (EGF) than healthy controls. There were no significant between-group differences in the levels of β2-microglobulin, KIM-1 or NGAL. IF was negatively associated with EGF and positively with age, proteinuria, MCP-1, DKK-3 and L-FABP, but not with β2-microglobulin, KIM-1, NGAL or GFR. The best model to predict IF surface accounted for 59% of its variability and included age, proteinuria, EGF, DKK-3 and MCP-1.. Our study provides a model to estimate the IF in DN that can be useful to assess the progression of IF in patients with normal kidney function.

Topics: Adult; Biomarkers; Chemokine CCL2; Cross-Sectional Studies; Diabetes Mellitus; Diabetic Nephropathies; Edetic Acid; Epidermal Growth Factor; Fatty Acid-Binding Proteins; Fibrosis; Glomerular Filtration Rate; Humans; Kidney; Lipocalin-2; Proteinuria

Rho GTPases are regulators of the actin cytoskeleton and their activity is modulated by GTPase-activating proteins (GAPs) and guanine nucleotide exchanging factors (GEFs). Glomerular podocytes have numerous actin-based projections called foot processes and their alteration is characteristic of proteinuric kidney diseases. We reported previously that Rac1 hyperactivation in podocytes causes proteinuria and glomerulosclerosis in mice. However, which GAP and GEF modulate Rac1 activity in podocytes remains unknown. Here, using a proximity-based ligation assay, we identified CdGAP (ARHGAP31) and β-PIX (ARHGEF7) as the major regulatory proteins interacting with Rac1 in human podocytes. CdGAP interacted with β-PIX through its basic region, and upon EGF stimulation, they both translocated to the plasma membrane in podocytes. CdGAP-depleted podocytes had altered cell motility and increased basal Rac1 and Cdc42 activities. When stimulated with EGF, CdGAP-depleted podocytes showed impaired β-PIX membrane-translocation and tyrosine phosphorylation, and reduced activities of Src kinase, focal adhesion kinase, and paxillin. Systemic and podocyte-specific CdGAP-knockout mice developed mild but significant proteinuria, which was exacerbated by Adriamycin. Collectively, these findings show that CdGAP contributes to maintain podocyte function and protect them from injury.

Topics: Animals; Epidermal Growth Factor; Focal Adhesions; Humans; Mice; Mice, Knockout; Podocytes; Proteinuria; Rho Guanine Nucleotide Exchange Factors; src-Family Kinases

The balance of several cytokines likely influences the resolution of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1) is a chemokine that promotes renal inflammation whereas epidermal growth factor (EGF) stimulates protective responses. Previously, high urine MCP-1(MCP-1) and low urine EGF (EGF) levels were found to be associated with tubulointerstitial fibrosis, but there is limited information on the value of these mediators as predictors of therapeutic responses or long term outcome in primary glomerulonephritis.. To determine the performance of urine EGF, MCP-1 or their ratio at baseline as biomarkers to predict complete remission, and the relationship of these mediators with subsequent renal function 24 months later in primary glomerulonephritis.. This is a prospective study of patients with biopsy-proven primary glomerulonephritis. Baseline urine samples were collected at biopsy before therapy. MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assays and expressed as a ratio to urine creatinine (ng/mgCr) or as EGF/MCP-1 ratio (ng/ng). Proteinuria and estimated glomerular filtration rate (eGRF) were monitored after therapy. Complete remission (CR) was defined as proteinuria ≤ 0.3 g/gCr.. Median follow-up was 20 months. Of all patients (n = 74), 38 patients (51.4%) subsequently achieved CR. Baseline urine EGF and EGF/MCP-1 levels were significantly higher in CR compared to Not CR. By contrast, MCP-1 was not different. High EGF (EGF > 75 ng/mgCr) was a significant predictor (OR 2.28) for CR by multivariate analysis after adjusting for proteinuria, blood pressure, baseline eGFR. In patients who completed 24 months follow-up (n = 43), baseline EGF correlated inversely with proteinuria and positively with eGFR at 24 months.. High urine EGF level is a promising biomarker of CR. Baseline EGF levels correlated with kidney function at 2 years. EGF/MCP-1 was not superior to EGF alone. Further studies are necessary to determine the role of urine EGF as a guide to therapy in primary GN.

Topics: Biomarkers; Chemokine CCL2; Cytokines; Epidermal Growth Factor; Female; Follow-Up Studies; Glomerular Filtration Rate; Glomerulonephritis; Humans; Male; Middle Aged; Multivariate Analysis; Proteinuria; Remission Induction; ROC Curve

In experimental membranous nephropathy, complement C5b-9-induces glomerular epithelial cell (GEC) injury and proteinuria. The effects of C5b-9 are mediated via signaling pathways, including calcium-independent phospholipase A(2)γ (iPLA(2)γ), and mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. The iPLA(2)γ pathway is cytoprotective. This study addresses the mechanisms of iPLA(2)γ activation. iPLA(2)γ activity was monitored by quantifying prostaglandin E(2) (PGE(2)) production. In GECs, iPLA(2)γ localized at the endoplasmic reticulum and mitochondria. Complement-mediated production of PGE(2) was amplified in GECs that overexpress iPLA(2)γ, compared with control cells, and was blocked by the iPLA(2)γ inhibitor bromoenol lactone in both iPLA(2)γ-overexpressing and control GECs. In GECs that overexpress iPLA(2)γ, complement-mediated PGE(2) production was reduced by inhibitors of MAP/ERK kinase 1 (MEK1) and p38 but not JNK. In COS-1 cells that overexpress iPLA(2)γ and cyclooxygenase-1, PGE(2) production was induced by co-expression of constitutively active MEK1 or MAPK-interacting kinase 1 (MNK1) as well as by stimulation with epidermal growth factor (EGF) + ionomycin. Complement- and EGF + ionomycin-stimulated iPLA(2)γ activity was attenuated by the S511A/S515A double mutation. Moreover, complement and EGF + ionomycin enhanced phosphorylation of Ser-511. Thus, complement-mediated activation of iPLA(2)γ is mediated via ERK and p38 pathways, and phosphorylation of Ser-511 and/or Ser-515 plays a key role in the catalytic activity and signaling of iPLA(2)γ. Defining the mechanisms by which complement activates iPLA(2)γ provides opportunities for development of novel therapeutic approaches to GEC injury and proteinuria.

Topics: Amino Acid Substitution; Animals; Calcium Ionophores; Cell Line; Chlorocebus aethiops; Complement Membrane Attack Complex; COS Cells; Cyclooxygenase 1; Dinoprostone; Endoplasmic Reticulum; Epidermal Growth Factor; Glomerulonephritis, Membranous; Group VI Phospholipases A2; Humans; Immunologic Factors; Intracellular Signaling Peptides and Proteins; Ionomycin; Kidney Glomerulus; MAP Kinase Kinase 1; Mutation, Missense; Phosphorylation; Protein Serine-Threonine Kinases; Proteinuria; Rats

Chronic renal disease is characterized by declining renal function, loss of intrinsic renal cells, and their replacement with fibrotic tissue. This study investigates apoptosis and its regulation in the context of chronic renal disease. RNA was extracted from renal biopsies from patients with various forms of chronic renal disease. Expression of genes of the Bcl-2 family, death receptor pathway, and growth factors were measured by reverse-transcription real-time polymerase chain reaction. Apoptosis was detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling technique. Tubulointerstitial apoptosis was positively associated with tubulointerstitial injury and renal dysfunction and increased 2.3-fold per unit (U) increase in transforming growth factor beta(1) (TGFbeta(1)) mRNA (P<0.05). Conversely, a 1 U increase in epidermal growth factor (EGF) mRNA was associated with a 47% decrease in tubulointerstitial apoptosis (P<0.05). Tubulointerstitial injury was correlated with increased TGFbeta(1) and tumour necrosis factor alpha (TNFalpha) mRNA (P<0.005) and decreased EGF mRNA (P<0.05). Additionally, for a 10 U decrease in the glomerular filtration rate there was an estimated increase of 5 and 10% in TGFbeta(1) and TNFalpha mRNA, respectively (P<0.05), whereas EGF mRNA decreased by an estimated 15% (P<0.005). Therefore dysregulation of cytokine/growth factor expression plays a central role in the progression of chronic renal disease through contribution to renal cell loss, tubulointerstitial injury, and renal dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Biomarkers; Biopsy; Chronic Disease; Epidermal Growth Factor; Female; Gene Expression; Gene Expression Regulation; Glomerular Filtration Rate; Humans; Intercellular Signaling Peptides and Proteins; Kidney; Kidney Diseases; Kidney Tubules; Male; Middle Aged; Proteinuria; RNA, Messenger; Transforming Growth Factor beta1; Treatment Outcome; Tumor Necrosis Factor-alpha

Diabetic nephropathy (DN) is a frequent complication in patients with diabetes. Although the majority of DN models and human studies have focused on glomeruli, tubulointerstitial damage is a major feature of DN and an important predictor of renal dysfunction. This study sought to investigate molecular markers of pathogenic pathways in the renal interstitium of patients with DN. Microdissected tubulointerstitial compartments from biopsies with established DN and control kidneys were subjected to expression profiling. Analysis of candidate genes, potentially involved in DN on the basis of common hypotheses, identified 49 genes with significantly altered expression levels in established DN in comparison with controls. In contrast to some rodent models, the growth factors vascular endothelial growth factor A (VEGF-A) and epidermal growth factor (EGF) showed a decrease in mRNA expression in DN. This was validated on an independent cohort of patients with DN by real-time reverse transcriptase-PCR. Immunohistochemical staining for VEGF-A and EGF also showed a reduced expression in DN. The decrease of renal VEGF-A expression was associated with a reduction in peritubular capillary densities shown by platelet-endothelial cell adhesion molecule-1/CD31 staining. Furthermore, a significant inverse correlation between VEGF-A and proteinuria, as well as EGF and proteinuria, and a positive correlation between VEGF-A and hypoxia-inducible factor-1alpha mRNA was found. Thus, in human DN, a decrease of VEGF-A, rather than the reported increase as described in some rodent models, may contribute to the progressive disease. These findings and the questions about rodent models in DN raise a note of caution regarding the proposal to inhibit VEGF-A to prevent progression of DN.

Topics: Adolescent; Adult; Aged; Biomarkers; Biopsy; Capillaries; Diabetic Nephropathies; Epidermal Growth Factor; Female; Humans; Immunohistochemistry; Kidney Tubules; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Platelet Endothelial Cell Adhesion Molecule-1; Proteinuria; RNA, Messenger; Species Specificity; Vascular Endothelial Growth Factor A

In this study, we attempted to determine whether heparin-binding epidermal growth factor-like growth factor (HB-EGF) was up-regulated in two chronic models of proteinuria.. Chronic passive Heymann nephritis (PHN) and puromycin aminonucleoside (PAN) models were induced in Sprague-Dawley rats. HB-EGF expression was studied by Northern blotting, in situ hybridization, and immunohistochemistry.. The chronic PAN model was associated with the development of glomerular lesions of focal glomerular sclerosis (FGS), severe interstitial fibrosis, and renal failure. Lesions of FGS were seen in approximately 80% of glomeruli at all time points, with a slight increase in the number of glomeruli showing extensive adhesion between 40 and 90 days. Northern blots of whole kidney tissue showed a 3- to 5.8-fold increased expression of HB-EGF mRNA in the chronic PAN group. Increased mRNA and protein were localized by in situ hybridization and immunohistochemistry to tubules, glomerular epithelial cells (GECs), and cells of Bowman's capsule. HB-EGF mRNA and protein were strongly expressed by epithelial cells involved in the formation of the lesions of FGS. By contrast, in chronic PHN, there was a small increase in HB-EGF, and the extensive lesions of FGS did not develop despite continued, heavy proteinuria.. These data suggest that HB-EGF may contribute to formation of the lesions of FGS, perhaps through stimulation of abortive mitogenesis in GECs or an adhesive interaction between transmembrane HB-EGF and the exposed glomerular basement membrane.

Topics: Actins; Animals; Creatinine; Disease Models, Animal; Epidermal Growth Factor; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Heparin-binding EGF-like Growth Factor; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Macrophages; Male; Proteinuria; Puromycin Aminonucleoside; Rats; Rats, Sprague-Dawley; RNA, Messenger; Up-Regulation

Topics: Biopsy; Blood Pressure; Chronic Disease; Drug Therapy, Combination; Epidermal Growth Factor; Fibroblast Growth Factor 2; Graft Rejection; Growth Substances; Humans; Immunosuppressive Agents; Interleukin-1; Kidney Transplantation; Platelet-Derived Growth Factor; Polymerase Chain Reaction; Proteinuria; RNA, Messenger; Transcription, Genetic; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Epidermal growth factor (EGF) is mainly produced in the submandibular glands (SMG) and in the kidneys. It has recently been reported that EGF-related ligands may induce their own biosynthesis (autoinduction) in vitro. In the present paper, we investigated whether chronic systemic treatment with EGF influenced the amount of endogenous EGF in the SMG and kidneys. Eight-week-old female Wistar rats were treated with subcutaneous injections of placebo (n = 16) or human recombinant EGF (150 micrograms/kg per day, n = 8) for 4 weeks. Urine was sampled the last 24 h of the study period. At the time of killing, the SMG and the kidneys were removed. The SMG was larger in the EGF-treated animals, 229.8 +/- 35.5 (mean +/- SD) mg than in the control animals, 181.7 +/- 18.1 mg (P < 0.01). The total EGF content was smaller (0.51 +/- 0.15 vs. 1.12 +/- 0.40 nmol EGF/SMG, P < 0.001). The kidneys were larger in the EGF-treated animals (1.38 +/- 0.08 vs. 1.28 +/- 0.08 g, P < 0.05), but the EGF content and urinary excretions were not changed. In conclusion, chronic systemic treatment with EGF causes growth of the SMG with concomitantly reduced contents of EGF, and growth of the kidneys with unchanged content and excretion of EGF. These findings suggest that EGF may play a part in the regulation of the growth of the SMG and in EGF biosynthesis.

Topics: Animals; Creatinine; Epidermal Growth Factor; Female; Humans; Immunohistochemistry; Kidney; Organ Size; Proteinuria; Rats; Rats, Wistar; Recombinant Proteins; Submandibular Gland

Focal glomerular sclerosis was induced in rats by chronic injections of puromycin aminonucleoside (PAN) on Days 0, 27, 34, and 41 and by unilateral nephrectomy on Day 22. Rats were sacrificed on Days 0, 8, and 20 (acute phase) and on Days 48, 60, and 80 (sclerotic phase). The percentage of sclerosing glomeruli was 16.6% on Day 48 and increased significantly to 72.8% on Day 80. We examined glomerular mRNA levels for proliferating cell nuclear antigen (PCNA), platelet-derived growth factor (PDGF)-A and B chains, transforming growth factor (TGF)-beta, epidermal growth factor (EGF), insulin-like growth factor (IGF)-I, and basic fibroblast growth factor (bFGF) on Days 0, 8, 20, 48, 60, and 80. Although these growth factor mRNA levels showed little change in glomeruli until Day 20, all growth factor mRNA levels increased in glomeruli during the sclerotic phase of PAN nephrosis as glomerular sclerosis progressed. On Day 80, mRNA levels for PCNA, PDGF-A and B chains, TGF-beta, EGF, IGF-I, and bFGF increased 12-, 10-, 12-, 15-, 2-, 2-, and 8-fold, respectively, in the glomeruli of PAN-treated rats with marked glomerular sclerosis when compared with control rats. Unilateral nephrectomy without PAN administration did not cause glomerular sclerosis up to Day 80 and mRNA levels for PCNA, PDGF-A and -B chains, TGF-beta, EGF, IGF-I, and bFGF in this group were almost the same as those in the normal sham-operated group. These data suggest that changes in growth factor mRNA levels in glomeruli may contribute to the development of PAN-induced glomerular sclerosis.

Topics: Animals; Blotting, Northern; Epidermal Growth Factor; Fibroblast Growth Factor 2; Gene Expression; Glomerulosclerosis, Focal Segmental; Growth Substances; Insulin-Like Growth Factor I; Kidney Glomerulus; Male; Nuclear Proteins; Platelet-Derived Growth Factor; Proliferating Cell Nuclear Antigen; Proteinuria; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transforming Growth Factor beta

Normal Sprague Dawley (SPRD) rats of both sexes secrete an 165 kDa EGF prohormone in urine. Sexually mature Hannover-Sprague Dawley rats (Han:SPRD) heterozygous males and females with autosomal dominant polycystic kidney disease (ADPKD) secrete a prohormone of similar molecular mass in urine. The male, but not the female, also secretes two variant prohormone isoforms with molecular masses close to 200 kDa. Both the 165 and 200 kDa EGF prohormone isoforms are totally absent, in urine, at 11 months of age in male but not in female heterozygous Han:SPRD rats. At this age, the male kidneys exhibit numerous cysts filled with colorless fluids and these fluids contain abundant quantities of a 66 kDa EGF prohormone metabolite. Homozygous Han:SPRD rats which are born with cystic disease secrete only trace amounts of 165 kDa EGF prohormone in their urine while their normal looking littermates secrete the 165 kDa EGF prohormone in abundant quantities. The cyst fluids of homozygous rats contain trace amounts of 165 and 154 kDa EGF prohormone isoforms while the 66 kDa EGF prohormone metabolites present in abundant quantities. The massive amounts of 66 kDa EGF prohormone metabolite in cyst fluids of PKD rats suggests that EGF prohormone and its isoforms undergo aberrant proteolysis in association with cyst pathogenesis both in heterozygous and homozygous kidneys. The specific retention of the 66 kDa EGF prohormone metabolite within the cyst suggests that this molecule may function as a cystogen.

Topics: Animals; Disease Models, Animal; Epidermal Growth Factor; Female; Genes, Dominant; Glycopeptides; Heterozygote; Homozygote; Humans; Immunoblotting; Kidney; Male; Mice; Oligosaccharides; Polycystic Kidney Diseases; Protein Precursors; Proteinuria; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Sex Factors

Acute administration of epidermal growth factor (EGF) has been shown to promote recovery from ischemic and nephrotoxic acute renal failure in vivo. The question of whether chronic subcutaneous administration of EGF (19.1 micrograms/day for 3 or 6 wk) could alter the course of chronic renal failure in rats subjected to 5/6 nephrectomy was studied. By week 6, there was no difference in renal function, as assessed by animal survival, BUN, urea and inulin clearances, proteinuria, renal morphometry, or renal size, between EGF- and vehicle-treated rats. This suggests that chronic renal insufficiency differs from acute tubular injury in its sensitivity to exogenous EGF. Unexpectedly, EGF significantly attenuated the rise in systolic blood pressure that occurred by the fourth week after 5/6 nephrectomy. The antihypertensive effect of EGF was still evident at week 5. Urinary flow rate, free water clearance, and excretion of total solutes, Na+, and K+, however, were not significantly altered by EGF at weeks 2, 4, 5, or 6, suggesting a mechanism other than increased natriuresis or diuresis for this antihypertensive effect.

Topics: Acute Kidney Injury; Animals; Blood Pressure; Blood Urea Nitrogen; Disease Models, Animal; Diuresis; Epidermal Growth Factor; Kidney; Male; Natriuresis; Nephrectomy; Organ Size; Postoperative Period; Potassium; Proteinuria; Rats; Rats, Sprague-Dawley; Urea

We surveyed the tumor-related proteins present in the urine specimens of 118 bladder cancer patients to seek a possible marker enabling future diagnosis and prognosis of this disease. We identified a protein of 180 kDa. by sodium dodecyl sulfate polyacrylamide gel electrophoresis in urine samples subjected to prior adsorption by protein-A conjugated to a sepharose bead. This protein appears to be a glycoprotein because it binds to concanavalin A-conjugated sepharose and can be eluted by alpha-methyl D-mannoside. It does not react immunochemically with antibodies prepared against either carcinoembryonic antigen or epidermal growth factor receptor, both of which have an apparent molecular weight close to 180 kDa. We found this protein in the urine of 74.3% of the patients with transitional cell carcinoma. It was not present in age-matched controls, patients with benign prostatic hyperplasia or patients with 10 other cancers. There was 1 false positive result in a patient with prostate cancer. It does not appear to be associated with urinary tract infection, blood contamination, premedication or anesthesia.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Electrophoresis, Polyacrylamide Gel; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Molecular Weight; Proteinuria; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Urinary Tract Infections