epidermal-growth-factor and Kidney-Failure--Chronic

An understanding of the mechanisms underlying the formation of renal lesions is necessary for the development of strategies aiming to delay the progression of chronic renal failure. The generation of transgenic mice in the past 20 years has contributed significantly to the study of this phenomenon. Overexpression and/or inactivation of single factors in renal tissue demonstrated that molecules such as growth factors, proto-oncogenes, and renin-angiotensin system elements play major roles in renal deterioration. Several mouse models of renal injury have been developed in the past 10 yr. Transgenic mice that exhibit a normal phenotype under physiologic conditions allow analysis of the roles of single factors in the progression of chronic renal failure when renal injury models are used. Using this strategy, it was demonstrated that vascular adaptation, which is a process that involves the endothelin/nitric oxide balance, is essential for the survival of mice after nephron reduction and that the epidermal growth factor/activator protein-1/Bcl-2 pathway is involved in the development of renal lesions after renal injury, possibly via adjustment of the proliferation/apoptosis balance. Moreover, it was demonstrated that selective inhibition of epidermal growth factor signaling in the kidney successfully prevents the progression of chronic renal failure. These results indicate the power of transgenesis for elucidation of the pathogenesis of renal disease.

Topics: Adaptation, Physiological; Animals; Disease Progression; Epidermal Growth Factor; Hemodynamics; Kidney; Kidney Failure, Chronic; Mice; Mice, Knockout; Mice, Transgenic; Nephrectomy; Vimentin

Polypeptide growth factors regulate kidney development, growth, and function and participate in processes of repair after renal injury. The use of one or more growth factors as therapeutic agents has been proposed in the settings of acute and chronic renal failure. In animal models of acute renal injury, the administration of epidermal growth factor, insulin-like growth factor I (IGF-I), or hepatocyte growth factor accelerates the restoration of kidney function and the normalization of histology post-acute renal injury and reduces mortality. The mechanisms by which the growth factors act in acute renal failure include the stimulation of anabolism, the maintenance of glomerular filtration, and the enhancement of tubular regeneration. IGF-I has been safely administered to humans with chronic renal failure. The growth factor enhances GFR and RPF in these individuals. Further studies will be required to establish a role for IGF-I or other growth factors as therapeutic agents for acute renal failure in humans and to define the utility of IGF-I as a medical therapy for chronic renal insufficiency.

Topics: Acute Kidney Injury; Animals; Epidermal Growth Factor; Glomerular Filtration Rate; Growth Substances; Hepatocyte Growth Factor; Insulin-Like Growth Factor I; Ischemia; Kidney; Kidney Failure, Chronic; Rats; Regeneration

Topics: Adolescent; Adult; Aged; Child; Epidermal Growth Factor; ErbB Receptors; Female; Genetic Predisposition to Disease; Graft Rejection; Humans; Kidney Failure, Chronic; Kidney Transplantation; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Single Nucleotide; Republic of Korea; Transplantation, Homologous; Young Adult

In diabetic kidney disease (DKD), it is important to find biomarkers for predicting initiation and progression of the disease. Besides glomerular damage, kidney tubular injury and inflammation are also involved in the development of DKD. The current study investigated the associations of urinary epidermal growth factor (uEGF), monocyte chemotactic protein-1 (MCP-1) and the uEGF:MCP-1 ratio with kidney involvement in patients at early and advanced stages of DKD.. The concentration of uEGF and uMCP-1 was measured in two Chinese population-based studies. The associations of uEGF, uMCP-1 and uEGF/MCP-1 with occurrence of DKD were studied in a cross-sectional study (n = 1811) of early stage DKD. Associations of baseline uEGF, uMCP-1 and uEGF/MCP-1 with kidney outcome were assessed in a longitudinal cohort (n = 208) of advanced-stage DKD.. In both studies, positive correlations were found between uEGF/urine creatinine (Cr) and estimated glomerular filtration rate (eGFR) at sampling and between uMCP-1/Cr and urinary albumin:creatinine ratio (uACR). In the cross-sectional study, uEGF/Cr and uEGF/MCP-1 were negatively associated with the occurrence of DKD {odds ratio (OR) 0.65 [95% confidence interval (CI) 0.54-0.79], P < 0.001; 0.82 (0.71-0.94), P = 0.005, respectively}. In the longitudinal cohort, the uEGF:MCP-1 ratio correlated more closely with the percentage change of eGFR slope (r = 0.33, P < 0.001) as compared with uEGF/Cr or uMCP-1/Cr alone. The composite endpoint was defined as end-stage renal disease or 30% reduction of eGFR. These three markers were independently associated with composite endpoint after adjusting for potential confounders [hazard ratio 0.76 (0.59-1.00), P = 0.047 for uEGF/Cr; 1.18 (1.02-1.38), P = 0.028 for uMCP-1/Cr; 0.79 (0.68-0.91), P = 0.001 for uEGF/MCP-1].. In Chinese patients, urinary EGF/MCP-1 was negatively associated with the occurrence of DKD. Moreover, uEGF/MCP-1 had a better ability to predict the composite endpoint and correlated more closely with kidney function decline in advanced DKD as compared with uEGF/Cr or uMCP-1/Cr alone.

Topics: Biomarkers; Chemokine CCL2; Creatinine; Cross-Sectional Studies; Diabetic Nephropathies; Disease Progression; Epidermal Growth Factor; Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged

Alport syndrome is a rare hereditary kidney disease manifested with progressive renal failure. Considerable variation exists in terms of disease progression among patients with Alport syndrome. Identification of patients at high risk of rapid progression remains an unmet need. Urinary epidermal growth factor (uEGF) has been shown to be independently associated with risk of progression to adverse kidney outcome in multiple independent adult chronic kidney disease (CKD) cohorts. In this study, we aim to assess if uEGF is associated with kidney impairment and its prognostic value for children with Alport syndrome.. One hundred and seventeen pediatric patients with Alport syndrome and 146 healthy children (3-18 years old) were included in this study. uEGF was measured in duplicates in baseline urine samples using ELISA (R&D) and concentration was normalized by urine creatinine (uEGF/Cr). In patients with longitudinal follow-up data (n = 38), progression was defined as deteriorated kidney function (CKD stage increase) during follow-up period (follow-up length is about 31 months in average). The association of baseline uEGF/Cr level with estimated glomerular filtration rate (eGFR) slope and Alport syndrome patients' progression to a more advanced CKD stage during the follow-up period was used to evaluate the prognostic value of the marker.. We found that uEGF/creatinine (uEGF/Cr) decreases with age in pediatric patients with Alport syndrome with a significantly faster rate than in healthy children of the same age group. uEGF/Cr is significantly correlated with eGFR (r = 0.75, p < 0.001), after adjustment for age. In 38 patients with longitudinal follow-up, we observed a significant correlation between uEGF/Cr and eGFR slope (r = 0.58, p < 0.001). Patients with lower uEGF/Cr level were at increased risk of progression to a higher CKD stage. uEGF/Cr was able to distinguish progressors from non-progressors with an AUC of 0.88, versus 0.77 by eGFR and 0.81 by 24-h urinary protein (24-h UP).. Our study suggests that uEGF/Cr is a promising biomarker for accelerated kidney function decline in pediatric patients with Alport syndrome. It may help to identify patients at high risk of progression for targeted clinical care and improve the patients' stratification in interventional trials.

Topics: Adolescent; Age Factors; Biomarkers; Case-Control Studies; Child; Child, Preschool; Creatinine; Disease Progression; Epidermal Growth Factor; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Nephritis, Hereditary; Prognosis; Risk Assessment; Severity of Illness Index

Chronic renal failure (CRF) is a progressive, life-threatening condition with limited treatment options. Cordyceps sinensis is a fungus that has nephroprotective effects, and Isaria felina (IF) is a fungus isolated from C. sinensis fruiting bodies. We evaluated IF efficacy using an adenine-induced CRF animal model.. Forty male Sprague-Dawley rats were divided into normal control (n = 8) and adenine groups (n = 32; 100 mg/kg for 30 days). The adenine group was subdivided into a model control group (n = 7), a positive control group (200 mg/kg Jinshuibao capsule (JSB; n = 8), and two IF groups (200 mg/kg, n = 8; 100 mg/kg, n = 8). After treatment for 30 days, animals were narcotized and abdominal aortic blood was analysed. Kidney functions were evaluated.. Higher serum creatinine, blood urea nitrogen and uric acid levels, and lower creatinine clearance was observed in the model control group compared with JSB and IF groups (P < 0.05). Red blood cell count, haemoglobin and haematocrit levels in the 200 mg/kg IF group were higher than in the model control group (P < 0.05). Transforming growth factor-β1 mRNA expression in the model control group was higher than the normal control and 200 mg/kg IF groups (P < 0.05). Epidermal growth factor mRNA in the model control group was lower than in the normal control and both IF-treated groups (P < 0.05). Structural renal damage was observed in all adenine-treated rats, but was less severe in the JSB and IF groups.. IF may reverse the damaged kidney functions-induced with adenine in rats.

Topics: Adenine; Animals; Ascomycota; Biological Products; Blood Urea Nitrogen; Cordyceps; Creatinine; Disease Models, Animal; Epidermal Growth Factor; Erythrocyte Count; Fruiting Bodies, Fungal; Hematocrit; Hemoglobins; Kidney; Kidney Failure, Chronic; Male; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transforming Growth Factor beta1; Uric Acid

Proteinuria, inflammation, chronic hypoxia, and rarefaction of peritubular capillaries contribute to the progression of renal disease by affecting proximal tubular epithelial cells (PTECs). To study the transcriptional response that separates patients with a stable course from those with a progressive course of disease, we isolated PTECs by laser capture microdissection from cryocut tissue sections of patients with proteinuric glomerulopathies (stable n=20, progressive n=11) with a median clinical follow-up of 26 months. Gene-expression profiling and a systems biology analysis identified activation of intracellular vascular endothelial growth factor (VEGF) signaling and hypoxia response pathways in progressive patients, which was associated with upregulation of hypoxia-inducible-factor (HIF)-1alpha and several HIF target genes, such as transferrin, transferrin-receptor, p21, and VEGF-receptor 1, but downregulation of VEGF-A. The inverse expression levels of HIF-1alpha and VEGF-A were significantly superior in predicting clinical outcome as compared with proteinuria, renal function, and degree of tubular atrophy and interstitial fibrosis at the time of biopsy. Interactome analysis showed the association of attenuated VEGF-A expression with the downregulation of genes that usually stimulate VEGF-A expression, such as epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and HIF-2alpha. In vitro experiments confirmed the positive regulatory effect of EGF and IGF-1 on VEGF-A transcription in human proximal tubular cells. Thus, in progressive but not in stable proteinuric kidney disease, human PTECs show an attenuated VEGF-A expression despite an activation of intracellular hypoxia response and VEGF signaling pathways, which might be due to a reduced expression of positive coregulators, such as EGF and IGF-1.

Topics: Basic Helix-Loop-Helix Transcription Factors; Cell Hypoxia; Cohort Studies; Epidermal Growth Factor; Epithelial Cells; Gene Expression Profiling; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Insulin-Like Growth Factor I; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Tubules, Proximal; Microdissection; Oligonucleotide Array Sequence Analysis; p21-Activated Kinases; Signal Transduction; Vascular Endothelial Growth Factor A

During progression of chronic renal disease, qualitative and quantitative changes in the composition of tubular basement membranes (TBMs) and interstitial matrix occur. Transforming growth factor (TGF)-beta(1)-mediated activation of tubular epithelial cells (TECs) is speculated to be a key contributor to the progression of tubulointerstitial fibrosis. To further understand the pathogenesis associated with renal fibrosis, we developed an in vitro Boyden chamber system using renal basement membranes that partially mimics in vivo conditions of TECs during health and disease. Direct stimulation of TECs with TGF-beta(1)/epithelial growth factor results in an increased migratory capacity across bovine TBM preparations. This is associated with increased matrix metalloproteinase (MMP) production, namely MMP-2 and MMP-9. Indirect chemotactic stimulation by TGF-beta(1)/EGF or collagen type I was insufficient in inducing migration of untreated TECs across bovine TBM preparation, suggesting that basement membrane integrity and composition play an important role in protecting TECs from interstitial fibrotic stimuli. Additionally, neutralization of MMPs by COL-3 inhibitor dramatically decreases the capacity of TGF-beta(1)-stimulated TECs to migrate through bovine TBM preparation. Collectively, these results demonstrate that basement membrane structure, integrity, and composition play an important role in determining interstitial influences on TECs and subsequent impact on potential aberrant cell-matrix interactions.

Topics: Adult; Animals; Basement Membrane; Cattle; Cell Movement; Cells, Cultured; Chemotaxis; Electrophoresis, Polyacrylamide Gel; Epidermal Growth Factor; Epithelial Cells; Extracellular Matrix; Fibrosis; Humans; Kidney Failure, Chronic; Kidney Tubules; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Rabbits; Transforming Growth Factor beta; Transforming Growth Factor beta1

Obstructive nephropathy is a primary cause of renal insufficiency in infants and children. This study was designed to distinguish the reversible and irreversible cellular consequences of temporary unilateral ureteral obstruction (UUO) on the developing kidney.. Rats were subjected to UUO or sham operation in the first 48 hours of life, and the obstruction was removed five days later (or was left in place). Kidneys were removed for study 14 or 28 days later. In additional groups, kidneys were removed at the end of five days of obstruction. Immunoreactive distribution of renin was determined in arterioles, and the distribution of epidermal growth factor, transforming growth factor-beta1, clusterin, vimentin, and alpha-smooth muscle actin was determined in tubules and/or interstitium. The number of glomeruli, glomerular maturation, tubular atrophy, and interstitial collagen deposition was determined by morphometry. Renal cellular proliferation and apoptosis were measured by proliferating cell nuclear antigen and the TdT uridine-nick-end-label technique, respectively. The glomerular filtration rate was measured by inulin clearance.. Renal microvascular renin maintained a fetal distribution with persistent UUO; this was partially reversed by the relief of obstruction. Although glomerular maturation was also delayed and glomerular volume was reduced by UUO, the relief of obstruction prevented the reduction in glomerular volume. Although relief of obstruction did not reverse a 40% reduction in the number of nephrons, the glomerular filtration rate of the postobstructed kidney was normal. The relief of obstruction did not improve tubular cell proliferation and only partially reduced apoptosis induced by UUO. This was associated with a persistent reduction in the tubular epidermal growth factor. In addition, the relief of obstruction reduced but did not normalize tubular expression of transforming growth factor-beta1, clusterin, and vimentin, all of which are evidence of persistent tubular injury. The relief of obstruction significantly reduced interstitial fibrosis and expression of alpha-smooth muscle actin by interstitial fibroblasts, but not to normal levels.. The relief of obstruction in the neonatal rat attenuates, but does not reverse, renal vascular, glomerular, tubular, and interstitial injury resulting from five days of UUO. Hyperfiltration by remaining nephrons and residual tubulointerstitial injury in the postobstructed kidney are likely to lead to deterioration of renal function later in life.

Topics: Actins; Animals; Animals, Newborn; Child; Clusterin; Disease Models, Animal; Epidermal Growth Factor; Glomerular Filtration Rate; Glycoproteins; Humans; Infant; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Tubules; Molecular Chaperones; Rats; Rats, Sprague-Dawley; Renin; Time Factors; Transforming Growth Factor beta; Ureteral Obstruction; Vimentin

To investigate the excretion of urinary epidermal growth factor (EGF) in children with chronic renal failure (CRF), we have measured the urinary EGF/creatinine ratio (EGF/Cr) and the 24-hour urine EGF concentration in 19 children with CRF, 11 children with kidney disease and normal creatinine clearance, and 12 healthy children. Children with CRF had a significantly lower daily urine EGF concentration as well as urinary EGF/Cr. In contrast, children with kidney disease and normal renal function had normal daily urine EGF levels and urinary EGF/Cr. Accompanied by no difference in serum EGF between these two groups of patients, these data provide indirect evidence of the kidney as a source of human urinary EGF. There was a positive correlation of urinary EGF/Cr with creatinine clearance in all renal patients (r = 0.608, n = 30, p < 0.001). A much better correlation was found between daily urine EGF and creatinine clearance (r = 0.855, n = 30, p < 0.001). Our results implicate that there is a functional relationship between glomerular filtration and urinary EGF excretion, and that the urinary EGF/Cr may be a reliable indicator of urinary EGF excretion in children with CRF.

Topics: Case-Control Studies; Child; Creatinine; Epidermal Growth Factor; Humans; Kidney Failure, Chronic

Beta 2-microglobulin amyloidosis (A beta 2m) is a serious complication for patients undergoing long-term dialysis. beta 2-microglobulin modified with advanced glycation end products (beta 2m-AGE) is a major component of the amyloid in A beta 2m. It is not completely understood whether beta 2m-AGE plays an active role in the pathogenesis of A beta 2m, or if its presence is a secondary event of the disease. beta 2-microglobulin amyloid is mainly located in tendon and osteo-articular structures that are rich in collagen, and local fibroblasts constitute the principal cell population in the synthesis and metabolism of collagen. Recent identification of AGE binding proteins on human fibroblasts lead to the hypothesis that the fibroblast may be a target for the biological action of beta 2m-AGE. The present study demonstrated that two human fibroblast cell lines exhibited a decrease in procollagen type I mRNA and type I collagen synthesis after exposure to beta 2m-AGE for 72 hours. Similar results were observed using AGE-modified albumin. Antibody against the RAGE, the receptor for AGE, attenuated this decrease in synthesis, indicating that the response was partially mediated by RAGE. In addition, antibody against epidermal growth factor (EGF) attenuated the decrease in type I procollagen mRNA and type I collagen induced by beta 2m-AGE, suggesting that EGF acts as an intermediate factor. These findings support the hypothesis that beta 2m-AGE actively participates in connective tissue and bone remodeling via a pathway involving fibroblast RAGE, and at least one interposed mediator, the growth factor EGF.

Topics: Amyloidosis; Antibodies; beta 2-Microglobulin; Cell Line; Collagen; Epidermal Growth Factor; Fibroblasts; Glycation End Products, Advanced; Humans; Interleukin-1; Kidney Failure, Chronic; Procollagen; Receptor for Advanced Glycation End Products; Receptors, Immunologic; RNA, Messenger

Tamm-Horsfall protein (THP) and epidermal growth factor (EGF) are both synthesized by tubular cells in the distal part of the nephron and excreted with the urine. The present study examines the urinary excretion rates of the two peptides in relation to functional tubular markers in patients with chronic nephropathy. Four groups of patients with moderate to severely reduced renal function were studied: glomerulonephritis (n = 10), diabetic nephropathy (n = 11), tubulointerstitial nephropathy (n = 13), and polycystic kidney disease (n = 8). The renal function was evaluated by glomerular filtration rate (GFR) as an indicator for the general renal function, lithium clearance (C(Li)) as an indicator for proximal tubular function, and absolute distal reabsorption of sodium (ADR(Na)) as an indicator for distal tubular function. The excretion rate of EGF was rather closely correlated with GFR, C(Li) and ADR(Na) (Spearman coefficients of variation 0.88, 0.69, and 0.74, respectively). The correlations between the excretion rate of THP and GFR, C(Li) and ADR(Na) were weaker (Spearman coefficients of variation 0.68, 0.42, and 0.44). When the effect of GFR had been accounted for by multiple variance analyses, the excretion rates of the two peptides were still associated with ADR(Na) but not with C(Li). In conclusion, the urinary excretion rates of especially EGF but also those of THP were correlated with renal function and distal tubular reabsorption of sodium in patients with chronic nephropathy.

Topics: Adjuvants, Immunologic; Adult; Aged; Diabetic Nephropathies; Epidermal Growth Factor; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Kidney Failure, Chronic; Kidney Tubules, Distal; Kidney Tubules, Proximal; Loop of Henle; Male; Middle Aged; Mucoproteins; Polycystic Kidney Diseases; Uromodulin

In chronic renal failure, epidermal growth factor (EGF) excretion is decreased. In this study, asymptomatic adult polycystic kidney disease (APKD) patients with a relatively preserved glomerular filtration rate were examined. Excretion of EGF was studied in 6 patients with APKD (median age 42 years; serum creatinine [median] 95 [range-80-133] mumol/l) and compared with that of 28 healthy controls. EGF was determined in a spot morning urine by using a specific radioimmunoassay, and expressed in relation to creatinine excretion. Excretion of EGF in APKD was (median) 157 (range-13-359) and in the controls (median) 546 (range-238-1199) pmol/mmol creatinine (p < 0.001). Low excretion of EGF in APKD patients with preserved kidney function suggests a distal abnormality at an early stage of the disease, prior to the development of renal failure.

Topics: Adult; Aged; Case-Control Studies; Creatinine; Epidermal Growth Factor; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Kidney Tubules, Distal; Male; Middle Aged; Polycystic Kidney Diseases; Radioimmunoassay

Topics: Creatinine; Epidermal Growth Factor; Humans; Kidney Failure, Chronic; Polycystic Kidney, Autosomal Dominant

We studied urinary epidermal growth factor (uEGF) in kidney transplant patients with normal and elevated serum creatinine, in cardiac transplant patients with normal serum creatinine, and in patients with chronic renal failure. Patients with chronic renal failure had the lowest uEGF levels. uEGF was reduced in normally functioning kidney transplant patients. If the kidney graft was failing, this reduction was more marked. Cardiac transplant patients had normal uEGF. The type of immunosuppressive therapy did not influence the uEGF excretion. Kidney function and kidney tissue mass appeared to be the most important factors in uEGF excretion.

Topics: Adult; Aged; Aged, 80 and over; Creatinine; Epidermal Growth Factor; Female; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Radioimmunoassay

Urinary epidermal growth factor (EGF) excretion is seen as a marker of tubular function, and some studies conclude that EGF excretion can already be reduced early in the development of diabetic renal disease. It is even suggested that EGF could play a role in kidney and glomerular enlargement and hypertrophy in diabetic subjects. We have investigated various groups of subjects, namely healthy controls (n = 5), patients with non-diabetic chronic renal insufficiency (n = 10), and normoalbuminuric (n = 9), microalbuminuric (n = 13) and nephropathic (n = 9) insulin-dependent diabetic subjects. In all subjects glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured using a continuous infusion of 125I-iothalamate and 131I-hippuran, respectively. Diabetic subjects were tested during (near) normoglycaemic conditions. During the renal function test urine was collected for EGF measurement (in ng). With lower GFR values, EGF excretion/min was also lower. GFR correlated well with EGF/min (r = 0.63, p < 0.001). Fractional EGF clearance (EGF/GFR) was comparable in all groups. There was no correlation between urinary albumin excretion rate and EGF excretion in the diabetic subjects (r = -0.18, n.s.) and in all subjects (r = -0.12, n.s.). There was a significant correlation between UAER and GFR (r = -0.51, p < 0.005). No significant correlation could be found between urinary albumin excretion rate (UAER) and EGF/GFR (r = -0.07, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Albuminuria; Biomarkers; Blood Flow Velocity; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Epidermal Growth Factor; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Circulation

Epidermal growth factor (EGF) was measured in the saliva of 36 patients with chronic renal failure (CRF) and 29 matched control subjects. Salivary EGF in controls was 0.65 +/- 0.009 nmol/L compared with 0.99 +/- 0.24 nmol/L in nondialyzed CRF patients, 1.15 +/- 0.23 in hemodialyzed patients and 1.96 +/- 0.25 (p less than 0.01, Wilcoxon Rank Sum Test) in CAPD-treated patients. On Sephadex chromatography, the major peak of immunoreactive EGF from patient and control saliva samples coeluted with purified human EGF. We conclude that salivary concentrations of human EGF are significantly elevated in end-stage renal failure, particularly in patients treated by CAPD.

Topics: Adult; Epidermal Growth Factor; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Saliva

In 25 patients with chronic renal failure undergoing hemodialysis the level of epidermal growth factor (EGF) was significantly increased in plasma (61 +/- 10 vs. 36 +/- 12 pM in 23 aged-matched controls; p less than 0.0001) and serum (189 +/- 51 vs. 138 +/- 69 pM, p less than 0.006) and slightly increased in platelets (391 +/- 134 vs. 308 +/- 87 aM/10(6) platelets in controls; p less than 0.0582). In those 15 patients who produced urine, EGF was absent or close to the low limit of the sensitivity of the method (17 pM). Thus, kidneys are not delivering EGF to blood but their role in EGF removal is possible. Urinary EGF virtually disappears in severe chronic renal failure.

Topics: Aged; Blood Platelets; Epidermal Growth Factor; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Plasma; Renal Dialysis