ABSTRACT
OBJECTIVE: To assess the role of transforming growth factor-β1 (TGF-β1) in congenital ureteropelvic junction obstruction at diagnosis and during postoperative follow-up. MATERIAL AND METHODS: We conducted a case-control study including 19 patients with a mean age of 6.7 years and 19 matched controls. All patients presented negative voiding cystourethrography, obstructive diuretic renogram and underwent dismembered pyeloplasty. Urinary TGF-β1 and other markers were measured pre-, intra- and postoperatively. RESULTS: The mean bladder urine TGF-β1 concentration in obstructed patients prior to pyeloplasty was higher than in controls (92.5 pg/mL ± 16.8 vs. 35.8 pg/mL ± 16.2; p = 0.0001). The mean renal pelvic urine TGF-β1 concentration in the hydronephrotic kidney was higher than in the preoperative bladder urine sample (122.3 pg/mL ± 43.9 vs. 92.5 pg/mL ± 16.8; p = 0.036). Postoperative mean TGF-β1 concentration was significantly lower than preoperative TGF-β1 (48.7 pg/mL ± 13.1 vs. 92.5 pg/mL ± 16.8; p = 0.0001). CONCLUSION: TGF-β1 is a cytokine leading to renal fibrosis. The measurement of urinary TGF-β1 could become a useful tool for the diagnosis of obstructive hydronephrosis and the evaluation of the parenchyma function status, pre and postoperatively.
Subject(s)
Child , Female , Humans , Male , Hydronephrosis/diagnosis , Transforming Growth Factor beta1/urine , Ureteral Obstruction/diagnosis , Biomarkers/urine , Case-Control Studies , Follow-Up Studies , Hydronephrosis/urine , Kidney Pelvis , Perioperative Period , Sensitivity and Specificity , Treatment Outcome , Ureteral Obstruction/congenital , Ureteral Obstruction/surgery , Ureteral Obstruction/urine , Urinary Bladder/metabolism , Vesico-Ureteral Reflux/diagnosisABSTRACT
Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-¦Â1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (~260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg¡¤kg-1¡¤day-1 (D0.01, N = 14), 1 mg¡¤kg-1¡¤day-1 (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-¦Â1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40 percent), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28 percent (P < 0.0001) and GLUT2 by 76 percent (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P ¡Ü 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-¦Â1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.
Subject(s)
Animals , Male , Rats , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Glucose Transporter Type 1/metabolism , /metabolism , Kidney Cortex/chemistry , Ramipril/pharmacology , Albuminuria , Diabetes Mellitus, Experimental , Glucose/analysis , Kidney Cortex/drug effects , Rats, Inbred SHR , Transforming Growth Factor beta1/urineABSTRACT
Systemic lupus erythematosus [SLE] is a disease characterized by loss of immunologic tolerance to self-antigens. About two thirds of children with SLE develop renal involvement during the course of their disease. Transforming growth factor beta 1 [TGF-beta 1] has an inhibitory effect on the immune system and it plays a central role in the pathogenesis of renal diseases. To assess plasma and urinaly TGF beta1 levels in children with active SLE and its possible role in the pathogenesis of the disease. Plasma and urinary [latent and active] TGF-beta 1 levels were assessed-by ELISA-in 32 children with active SLE and compared to 15 healthy controls of matched age and sex. Plasma latent and active TGF-beta 1 levels in children with active SLE were significantly lower than controls [median [IQR]=9.75 [9-27.6] Vs 18.9 [16-30] ng/mI,=0.004 and 0.38 [0.3-0.4] Vs 0.9 [0.8-1] ng/ml, p<0.001; respectively]. Plasma active TGF-beta 1 correlated negatively with Systemic Lupus Erythematosus Disease Activity Index [r=-0.38, P=0.03]. On the contrary; urinary latent and active TGF-beta 1 levels in children with active SLE were significantly higher than controls [median [IQR]=2.1[1.9-6.4] Vs 1.1[0.9-1.9] ng/mg creatinine, p<0.001 and 1.2 [1.07-1.53] Vs 0.7 [05-1] ng/mg creatinine, p=0.003; respectively]. Urinary active TGF-beta 1 levels correlated positively with Anti-ds DNA titer [r=0.42, p=0.015] and negatively with serum C3 levels [r=-0.48, p=0.005]. Patients with symptomatic nephritis had significantly elevated active urinary TGF-beta 1 levels in comparison to children with silent nephritis [P=0,008].In children with active SLE, lowered plasma TGF-beta 1 levels may be a feature of systemic immune dysfunction, which may have a role in the pathogenesis of the disease. On the other hand; increased renal production of TGF-beta 1 plays an important role in the pathogenesis and clinical presentation of lupus nephritis