Excretion Of Epidermal Growth Factor Research Articles

Changes in cytokines and urothelial factors of urine in interstitial cystitis/painful bladder syndrome

Interstitial cystitis/bladder pain syndrome (IC/BPS) is thought to have an autoimmune component due to increased prevalence of certain autoimmune conditions in the patients. Recent studies have revealed abnormalities in cytokine signaling in cultured urothelial cells of the urinary bladder. However, there is only scarce information on concentration of cytokines and some biomarkers, e.g., heparin-binding growth factor (HB-EGF) and epidermal growth factor (EGF), in the patients with IC/BPS. The purpose of present study was to determine concentrations of cytokines, HB-EGF and EGF in urine and their interrelations in patients with IC/BPS. 68 women with IC/BPS and 20 women without this disease (control group) were examined. The average age of women with IC/BPS was 54.2±12.4 years, the control group was 35.3±9.7 years. The morning urine samples were tested for interleukin contents (IL-1β, IL-6, IL-8), tumor necrosis factor-α (TNFα), as well as HB-EGF and EGF concentrations measured by ELISA technique. Statistical analysis of the obtained results was performed using Statistica software in Microsoft Excel. A relationship between the indexes was calculated with Pearson correlation quotient. The ratios for Th1/Th2 cytokines were calculated. Urination frequency, clinical symptoms including pollakiuria, nocturia and its urgency, were significantly more often in patients with IC/BPS compared to the control group (p 0.05-0.001). In patients with IC/BPS, the average levels of IL-1β, IL-8, IL-6 and TNFα exhibited, respectively, 2.4-, 2.3- and 2.0-fold increase over control values (p 0.05). The HB-EGF and EGF excretion in the urine was 2.3 times (p 0.05) over control levels. The IL-1β/IL-6 ratio averaged 1.16 in the group of patients with IC/BPS versus 0.95 in the control group, and the TNFα/IL-6 ratio was 1.0, respectively. There was a positive correlation between the levels of IL-1β and IL-6, TNFα (p 0.05), HB-EGF and EGF, and a negative correlation with IL-8 (p 0.01). In women with IC/BPS, there was a weak multidirectional correlation between IL-6 and other cytokines, as well as with HB-EGF and EGF contents. IL-8 levels in both groups showed weak correlation with other indexes. The TNFα amount weakly correlated with HB-EGF and EGF in IC/BPS. Based on the results obtained, one may state that, in IC/BPS, the excretion of pro-inflammatory cytokines was significantly increased, the balance of Th1/Th2 cytokines and contents of growth factors are disturbed. Expression of cytokines in combination with growth factors (HB-EGF and EGF) can be used to explain the pathophysiology of the clinical features in IC/BPS. Analysis of cytokine profiles may be used for differential diagnosis of IC/BPS and other disorders of urinary bladder.

Urinary excretion of epidermal growth factor and rapid loss of kidney function.

Lower urinary excretion of the kidney tubule-specific biomarker epidermal growth factor (uEGF) is associated with increased risk of renal function [glomerular filtration rate (GFR)] loss in diabetes and in patients with established chronic kidney disease (CKD). We investigated whether uEGF is associated with rapid GFR decline or incident CKD in the general population. Subjects without CKD or diabetes were recruited from the general population in Tromso, Norway [Renal Iohexol Clearance Survey (RENIS); N = 1249] and Groningen, the Netherlands [Prevention of REnal and Vascular END-stage disease (PREVEND); N = 4534], with a median follow-up of 5.6 and 7.4 years, respectively. GFR was measured by iohexol clearance in the RENIS and estimated using the CKD Epidemiology Collaboration creatinine-cystatin C equation in the PREVEND study. Rapid GFR decline was defined as an annual GFR loss >3.0 mL/min/1.73 m2 and in sensitivity analyses as subjects with the 10% steepest GFR slope within each cohort. Lower baseline uEGF excretion was associated with rapid GFR loss in both cohorts {RENIS, odds ratio [OR] per 1 μg/mmol lower uEGF 1.42 [95% confidence interval (CI) 1.06-1.91], P = 0.02; PREVEND, OR 1.29 [95% CI 1.10-1.53], P < 0.01}, adjusted for baseline GFR, albumin:creatinine ratio and conventional CKD risk factors. Similar results were obtained using the outcome of the 10% steepest GFR slope in each cohort. Lower uEGF levels were associated with incident CKD in the combined analysis of both cohorts. Lower uEGF levels are associated with increased risk of rapid GFR loss and incident CKD in the general population. This finding, together with previous findings in CKD and high-risk populations, supports that uEGF may serve as a broadly applicable biomarker representing the tubular component of the current glomerulus-centric clinical risk assessment system.

Urinary excretion of EGF and MCP-1 in children with vesicoureteral reflux.

ABSTRACTPurpose The aim of this study was to investigate the urinary concentration of epidermal growth factor (EGF) and monocyte chemotactic protein-1 (MCP-1) as reflux nephropathy (RN) biomarkers before and after endoscopic treatment of moderate to severe vesico-ureteral reflux (VUR).Materials and methods A prospective study was carried out on 72 children with moderate to severe VUR. All patients underwent endoscopic treatment using Macroplastique® or Deflux®. Vesico-ureteral reflux resolution was tested by post-operative voiding cystourethrography after 3 months and 2 years. Follow-up urinary samples were collected at that time. Control samples were taken from healthy children with no clinical evidence of renal and bladder disease and no history of UTI.Results In VUR patients, pre-operative urinary EGF levels had a down-regulation when compared to controls. Following successful VUR repair, urinary EGF levels of VUR children progressively increased only at long term follow-up but without returning to normal levels. Urinary MCP-1 levels were highly expressed in pre-operative samples and decreased markedly during early post-operative measurements. Urinary MCP-1 levels did not further decreased in late post-operative follow-up. In fact, these levels remained significantly higher when compared to controls.Conclusions Urinary levels of EGF and MCP-1 may become useful markers for monitoring the response to surgical treatment in VUR patients. Although endoscopic VUR treatment is effective in reducing the inflammatory response, the persistence of significant abnormal levels of inflammatory cytokines (such as urinary MCP-1) at long term follow-up suggests that surgery alone may not completely treat the chronic renal inflammation evidenced in these children.

Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation

Cyclosporine (CsA) treatment is associated with hypomagnesaemia due to a renal Mg(2+) leak. In animal studies a role for the Mg(2+) channel TRPM6 localized in the distal convoluted tubule and stimulated by epidermal growth factor (EGF) is suggested. We hypothesize that CsA-induced hypomagnesaemia is due to a renal magnesium leak, also in patients, resulting from a downregulation of the renal EGF production, thereby inhibiting the activation of TRPM6. Renal transplant patients treated with CsA (n = 55) and 35 chronic kidney disease (CKD) patients were included. At three time points, with an interval of at least 1 month, blood and urine samples were taken to determine creatinine, Mg(2+), sodium and EGF. Serum Mg(2+) was significantly lower in the CsA group versus the CKD group with significantly more CsA-treated patients developing hypomagnesaemia. Although the fractional excretion (FE) Mg(2+) did not differ significantly between the two groups, subanalysis of the patients with hypomagnesaemia showed a significantly higher FE Mg(2+) in CsA-treated patients compared with CKD patients (P = 0.05). The urinary EGF excretion was significantly decreased in the CsA group and was a predictor of the FE Mg(2+) in the two groups. Serum sodium was significantly decreased in the CsA group simultaneously with an increased FE Na(+). In CsA-treated patients, the association of a low urinary EGF excretion and a decreased renal Mg(2+) reabsorption is in accordance with in vitro and animal studies. In the whole study population, log urinary EGF excretion is an independent predictor of the FE Mg(2+), supporting the role of EGF in magnesium reabsorption.

The Ratio of Epidermal Growth Factor (EGF) to Monocyte Chemotactic Peptide-1 (MCP1) in the Urine May Predict Renal Prognosis in HTx

Purpose Heart transplant recipients (HTx) have increased mortality rates when they advance toward renal insufficiency. Being able to predict whether renal failure will progress should be a major target to improve outcomes after HTx. Kidneys with tubulointerstitial damage exhibit a decreased urinary excretion of EGF. Conversely, MCP1 plays a major role in the progression of renal disease. Thus, EGF/MCP-1 ratio measurement might help to predict the progressive deterioration of renal function. Methods and Materials Preliminarly, we measured EGF/MCP1 in 517 urinary samples to assess whether this ratio had any relationship with creatinine, estimated glomerular filtration rate measured as MDRD, albuminuria or proteinuria. Then we conducted a retrospective case-control study in 24 HTx patients with mild renal dysfunction. Patients whose renal function has deteriorated (cases) were matched for age, gender, f-up, creatinine and MDRD with patients with stable renal function (controls). Results In all samples there were significant negative linear relationship between EGF/MCP1 and creatinine (p Conclusions The degree of urinary EGF/MCP1 excretion has a linear relationship with creatinine, proteinuria and estimated glomerular filtration rate. EGF/MCP1 excretion predicts renal outcomes and may be useful to identify HtTx patients at higher risk for progression of renal failure.

Histone deacetylase inhibition attenuates diabetes-associated kidney growth: potential role for epigenetic modification of the epidermal growth factor receptor

Clinical trials and experimental studies have highlighted the importance of epigenetic processes in the development of diabetic complications. One of the earliest features of diabetic nephropathy is renal enlargement. The epidermal growth factor (EGF) has a pivotal role in the development of diabetic nephromegaly and transactivation of its receptor has been implicated in the pathogenesis of later-stage disease. As EGF signaling is altered by the acetylation status of histone proteins, we measured the effects of the histone deacetylase (HDAC) inhibitor, vorinostat, in mediating renal enlargement in diabetes focusing on the EGF-EGF receptor (EGFR) axis. In cultured proximal tubule (normal rat kidney) cells, vorinostat treatment reduced EGFR protein and mRNA, and attenuated cellular proliferation. Within 72 h of diabetes induction with streptozotocin, urinary EGF excretion was increased approximately threefold and was unaffected by vorinostat, even though the kidneys of vorinostat-treated diabetic rats had reduced tubular epithelial cell proliferation. Daily treatment of diabetic rats with vorinostat for 4 weeks blunted renal growth and glomerular hypertrophy. Thus, early renal changes in diabetes are amenable to epigenetic intervention. Attenuating effects of HDAC inhibition, although multifactorial, are likely to be mediated in part through downregulation of the EGFR.

Urinary epidermal growth factor, monocyte chemotactic protein-1, and β2-microglobulin in children with ureteropelvic junction obstruction

Background/PurposeWe demonstrated down-regulation of epidermal growth factor (EGF) and up-regulation of monocyte chemotactic protein-1 (MCP-1) in the renal parenchyma in children who underwent pyeloplasty for ureteropelvic junction obstruction (UPJO). These findings were paralleled by urinary levels of EGF and MCP-1 before and after surgery. The aim of this study is to evaluate the urinary excretion of these cytokines and β2-microglobulin (β2M) in children with urine flow impairment at the ureteropelvic junction or who underwent pyeloplasty. MethodsSeventy-six patients with UPJO and 30 normal children (CTRL) were enrolled in the study. The UPJO patients were divided into obstructive (12), functional (36), and operated (28). Epidermal growth factor, MCP-1, and β2M urinary levels were measured by enzyme-linked immunosorbent assay and normalized to urine creatinine. ResultsUrinary β2M and MCP-1 increased significantly in the UPJO groups compared with the CTRL and significantly improved in the operated group. The obstructive group displayed reduced EGF excretion compared with the CTRL group. The urinary (u)EGF/uMCP-1, and uEGF/uβ2M ratios significantly decreased in both untreated groups. In the operated group, these ratios improved significantly. ConclusionsThe present study substantiates the role of urinary EGF, MCP-1, and β2M as markers of tubulointerstitial damage in human obstructive nephropathy. Furthermore, it suggests that surgical intervention is effective in the management of children with UPJO.

Urinary levels of epidermal growth factor, interleukin‐6 and monocyte chemoattractant protein‐1 may act as predictor markers of renal function outcome in immunoglobulin A nephropathy

Urinary cytokine excretion may reflect histological changes in immunoglobulin A nephropathy (IgAN), and their measurement can give information about disease outcome. Thirty-three IgAN patients were prospectively followed for 5.6 +/- 3.1 years. Urinary levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6 and epidermal growth factor (EGF) were measured at diagnosis and repeated 1 year later for IL-6 and EGF. Urinary MCP-1 and IL-6 levels were increased significantly, while EGF excretion reduced in IgAN patients, compared to controls. IL-6 urinary levels showed significant positive correlation with chronic histological lesions. Patients were classified into five groups, according to the Haas classification system. MCP-1 and IL-6 urinary levels were increased, whereas EGF levels were reduced in the progression of staging. EGF urinary excretion was a strong predictor factor of disease outcome, significantly correlated with creatinine clearance at time of diagnosis (r = 0.5, P = 0.005), and at the end of follow up (r = 0.6, P = 0.001). Urinary EGF levels measured a year later could predict long-term outcome better, and a cut of 0.05 pg/mg urine creatinine levels could distinguish between progressors and non-progressors. Urinary MCP-1, IL-6 and EGF levels may represent histology in IgAN. EGF excretion can be a predictive marker and its serial measurements may give information about disease outcome and the effect of treatment.

Intravenously Administered Human Epidermal Growth Factor in the Rat

Background/Aim: Epidermal growth factor (EGF) is known to exert mitogenic effects in different tissues, including the digestive tract and pancreas. EGF is also found in high concentrations in pancreas. Infusion of human EGF has been shown to induce proliferation of cells in exocrine pancreas, and to increase the thickness of the small intestine. The aim of this study was to investigate the influence of intravenously administered human EGF on pancreatic and biliary secretions in the rat. Materials and Methods: Rats were fasted overnight and were given human EGF intravenously, either as a bolus dose of 5 µg or as a continuous infusion in increasing doses from 0.5 to 10 µg/h. Bile and pancreatic juice were either collected together or separately. The concentration of human EGF in bile and pancreatic juice was measured. Results: After a bolus dose of EGF increased bile/pancreatic secretion was seen after 60 and 90 min when the bile and pancreatic secretions were not separated. Continuous infusion of EGF increased the joint secretion rate of bile and pancreatic juice in a dose-dependent manner. No effect on secretion rate was seen when bile and pancreatic juice were collected separately. After intravenous infusion of human EGF a 1,000-fold increase of human EGF excretion was found in bile but not in pancreatic juice. Conclusion: Intravenously administered human EGF was excreted in high concentrations in bile and increased the secretion rate of pancreatic juice when collected together with bile. The results suggest that EGF, at least partly, exerts its effect on the pancreas and the proximal gastrointestinal tract after excretion with bile and stimulates pancreatic secretion via this route.

Early urinary changes in Tamm-Horsfall protein and epidermal growth factor in diabetic children.

Both glomerular and tubular markers have been used to follow diabetic nephropathy. However, neither albumin nor proximal tubular markers have proven useful in prepubertal diabetes. Hence we studied two markers derived from the distal tubular cells, Tamm-Horsfall protein (THP) and epidermal growth factor (EGF). The urinary excretion of THP and EGF was examined in samples obtained during the first 20 days and 1 year after diagnosis of diabetes in children aged 4-15 years. Fourteen children without and 18 with ketonuria were examined, and 17 age-matched healthy children participated as controls. The excretion rate of EGF was increased at diagnosis, while that of THP was not. After 20 days of treatment the excretion of EGF had normalized, while the excretion of THP was decreased. Similar results were obtained after 1 year. In conclusion, in spite of good metabolic control a reduced excretion of THP persisted for at least 1 year after the diagnosis of diabetes. Whether the finding of reduced excretion of THP has any biological significance awaits further study.

A review on urinary proteins in outflow disease of the upper urinary tract

Introduction: No review articles on outflow disease of the upper urinary tract discuss urinary protein excretion. Discussion: Following acute partial and/or complete ureteral obstruction (UO) or chronic partial UO, α-1-microglobulin excretion is significantly higher than in the reference population or patients with proven renal dilatation without obstruction, but is not found to be diagnostic for these conditions as such. Chronic partial UO is followed first by a destructive and then by a steady-state phase in renal damage. The observed increase in tubular proteinuria during the destructive phase correlates with the decrease in absolute dimercaptosuccinic acid (DMSA) uptake. If the destructive phase is not followed by a stable phase, a mixed tubular and glomerular proteinuria is seen. Urinary α-1-microglobulin excretion is found to be diagnostically useful in vesico-ureteral reflux (VUR) patients, increases with higher intravesical–intrapyelic pressure, correlates with the decrease in absolute DMSA uptake or with urinary epidermal growth factor excretion (both markers of the number of functioning nephrons) and predicts the outcome after treatment. Conclusion: α-1-Microglobulin is useful in the detection of renal tubular damage in patients with outflow disease of the upper tract, is diagnostic for VUR but is not so for ureteral obstruction.

Renal content and output of epidermal growth factor in long-term adrenergic agonist-treated rats

This study investigates the renal and urinary levels of epidermal growth factor (EGF) in rats under long-term treatment with α- or β-adrenergic agonists. Urine samples were obtained on days 7, 14 and 21, and renal tissue samples on day 21. EGF was quantified by ELISA and tissue sections were used for immunohistochemistry and in situ hybridization. Fractional kidney weight was increased in the α-adrenergic agonist-treated group by 35% when compared with controls. Histological examination of the kidney revealed well-defined wedge-shaped areas of tubular dilatations and luminal amorphous material in the distal tubules. Concomitantly, reduced levels of EGF and EGF mRNA were observed, and also the urinary levels of EGF were reduced. Together, these observations indicate α-adrenergic treatment to affect the distal tubules. Treatment with the β-adrenergic agonist did not change fractional kidney weight, but initially the urinary excretion of EGF was reduced. The data add further evidence to the suggestion that activity of the sympathetic nervous system influences renal homeostasis of EGF, either directly or indirectly through renal histopathological changes.

Urinary Epidermal Growth Factor Excretion in Children with Chronic Renal Failure

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.

Adrenergic Blockade in Diabetic and Uninephrectomized Rats: Effects on Renal Size and on Renal and Urinary Contents of Epidermal Growth Factor

The present study reports on the effects of adrenergic blocking agents on the renal growth and on the renal content and urinary excretion of epidermal growth factor (EGF) in streptozotocin-induced diabetic or uninephrectomized rats. Diabetic and uninephrectomized rats were allocated to groups treated with either saline or adrenergic antagonists and compared to controls and sham-operated controls, respectively. 24-hour urine samples were obtained on days 7, 14, and 21 and renal tissue samples on day 21. The 24-hour urinary excretion of EGF from controls and saline-treated diabetic rats was comparable. In adrenergic antagonist treated diabetic rats, it was reduced by at least 40% throughout the study period. Uninephrectomy caused a 50% reduction in the urinary excretion of EGF. This was not influenced by treatment with an adrenergic antagonist. After 3 weeks, saline-treated diabetic rats had an increase of 33% in kidney weight when compared to controls. The adrenergic antagonist treated diabetic groups had a significantly lower increase of 15%. Postnephrectomized renal growth was not affected by adrenergic antagonists. The total renal content of EGF was comparable in the saline-treated diabetic group and the control group, but was reduced by approximately 50% in the kidneys from the adrenergic antagonist treated diabetic groups. Renal EGF mRNA levels were also reduced in adrenergic antagonist treated diabetic rats. In contrast to diabetes, the renal growth following nephrectomy was not affected by adrenergic blocking agents. These results provide evidence for fundamental differences between diabetes-related renal growth and that observed in compensation to nephrectomy and suggest a connection between adrenergic activity, renal growth, and EGF in diabetes.

Correlation between Urinary Epidermal Growth Factor Excretion and Serum Thyroid Hormone in Premature and Term Neonates

Eighty neonates, including 14 full-term, 31 premature, 27 twin or triplet, 6 small-for-gestational-age, and 2 infants with hyperthyroidism, were evaluated. The urinary epidermal growth factor/creatinine ratio (EGF/Cr) on the 1st postnatal day was not statistically different among full-term, premature, multiple-pregnancy, and small-for-gestational-age infants (F = 1.06, p = 0.6). There was no difference in urinary EGF/Cr between the 1st postnatal day and the 7th day (p = 0.4 by paired t test). The urinary EGF/Cr was not correlated with the serum thyroid-stimulating hormone level (r = –0.162, n = 60, p = 0.21), but showed a positive correlation with serum total T₃ (r = 0.526, n = 60, p < 0.001) and with serum total T₄ (r = 0.460, n = 60, p < 0.001). The correlation between urinary EGF/Cr and serum free T₄ was even much better (r = 0.727, n = 25, p < 0.001). These results implicate that thyroid hormone may play a role in regulating urinary EGF excretion.

Urinary excretion of epidermal growth factor and Tamm–Horsfall protein in three rat models with increased renal excretion of urine

Epidermal growth factor (EGF) and Tamm–Horsfall protein (THP) are synthesized in the kidneys by the distal tubular cells and excreted into urine. The urinary excretion of these peptides has been suggested as a potential index for distal tubular function. The urinary excretion rates of EGF and THP were examined in three groups of rats with increased renal excretion of urine: uninephrectomy, non-osmotic polyuria and diabetic osmotic polyuria. Twenty-four hour urine samples were obtained after 7, 14 and 21 days. The urinary volume per kidney was doubled in uninephrectomy when compared to controls. There was a seven-fold increase in urinary volume in rats with non-osmotic polyuria and diabetic osmotic polyuria, as compared to controls. Uninephrectomy, non-osmotic polyuria and diabetes all affected the urinary excretion of EGF and THP differently. The EGF excretion in uninephrectomized rats was 60–80% of that of the controls, whereas THP excretion was unchanged, indicating that EGF excretion varied with renal tissue mass. Non-osmotic polyuria caused a five-fold increase in THP excretion but no change in EGF excretion. THP excretion in the diabetic rats was increased three-fold after 21 days when compared to controls, whereas EGF excretion was decreased when expressed per kidney weight. Immunohistochemistry demonstrated that EGF and THP were colocalized in the thick ascending limbs of Henle's loops and distal tubules in all five groups of rats. In conclusion, the EGF excretion appears to follow renal tissue mass and seems independent of urinary volume, whereas THP excretion is dependent mainly on urinary volume. This has implications for the use of EGF and/or THP excretion rates as an indicator for distal tubular function.

Effect of asphyxia on urinary epidermal growth factor levels in newborns.

Urinary epidermal growth factor (EGF) excretion in normal newborn as well as neonates with asphyxia was investigated by using radioimmunoassay, and serum creatinine (Scr) levels determined at the same time. The results showed that in severe asphyxia group the ratio of urinary EGF to urinary creatinine (Cr) (EGF/Cr), an index reflecting EGF excretion, was decreased on the first day (P < 0.05) and reached the lowest level on the third day (P < 0.01). However, EGF/Cr values were decreased only on the third day in neonates with mild asphyxia (P < 0.05). On the seventh day, EGF/Cr values of neonates with asphyxia rose to normal. There were a negative correlation between urinary EGF/Cr and Scr. It is suggested that EGF may play a role in the repair of acute renal injury after asphyxia and the detection of urinary EGF concentration is useful in the judgment of severity of renal injury and in the evaluation of the recovery of renal tubule after injury.

Increased epidermal growth factor in experimental diabetes related kidney growth in rats.

Renal enlargement is a characteristic feature of human and experimental diabetes mellitus that may be predictive of subsequent nephropathy. In the streptozotocin diabetic rat kidney growth rapidly follows the induction of experimental diabetes but the mechanisms responsible for this growth are poorly understood. Epidermal growth factor (EGF) is a potent mitogen for renal tubular cells. Thirty one male Sprague-Dawley rats aged 13 weeks were randomised to receive either streptozotocin (diabetic, n = 20) or buffer (control, n = 11). Animals were studied on days 1, 3, 5 and 7 following streptozotocin. Diabetes was associated with a 3-fold increase in urinary EGF excretion (223 +/- 15 vs 59 +/- 5 ng/day, mean +/- SEM, diabetic vs control, p < 0.0001) and 3-6 fold increase in renal EGF mRNA relative to controls (p < 0.001). A transient rise in kidney EGF protein was noted on day 1. There was no difference between diabetic and control animals with regard to intrarenal sites of EGF expression or in plasma EGF. These data suggest that the increased urinary EGF excretion in diabetic animals is the result of enhanced local production and that EGF is not stored for a prolonged period within renal tubular cells but is released following its synthesis. In the context of the known intrarenal actions of EGF this growth factor may play a role in the pathogenesis of diabetes related kidney growth.

Urinary Excretion of Epidermal Growth Factor in Children with Reflux Nephropathy

Purpose We determined urinary levels of epidermal growth factor in children with reflux nephropathy to evaluate the clinical significance of urinary epidermal growth factor. Materials and Methods We studied 59 boys and 41 girls 3 to 15 years old with reflux nephropathy, and 64 boys and 36 girls 3 to 15 years old who were healthy. Levels of urinary epidermal growth factor were determined by sandwich enzyme immunoassay using spot urine samples. We also determined the levels of serum creatinine, urinary alpha 1-microglobulin and urinary microalbumin. Absolute values of function of the left and right kidneys were assessed by 99mtechnetium dimercapto-succinic acid (DMSA) uptake. Results Levels of urinary epidermal growth factor gradually decreased with age in healthy children. There were low levels of urinary epidermal growth factor in 20 of the 44 patients (45%) with unilateral low DMSA uptake and 18 of the 19 (95%) with low total DMSA uptake (right and left uptakes). Urinary epidermal growth factor significantly correlated with serum creatinine (R = -0.702, p <0.0001), urinary alpha 1-microglobulin (R = -0.606, p <0.0001), urinary microalbumin (R = -0.708, p <0.0001) and total DMSA uptake (R = 0.744, p <0.0001). Conclusions These results suggest that urinary epidermal growth factor may be a useful clinical tool to monitor functional nephron mass in children with reflux nephropathy.

Urinary Excretion of Epidermal Growth Factor in Children with Reflux Nephropathy

Urinary Excretion of Epidermal Growth Factor in Children with Reflux Nephropathy