Obstructed versus dilated nonobstructed kidneys in children with congenital ureteropelvic junction narrowing: role of urinary tubular enzymes.

PURPOSE: We evaluated the role of voided urine lysosomal enzyme N-acetyl-beta-D-glucosaminidase and brush border enzymes alkaline phosphatase and gamma-glutamyl transferase in differentiating between children with ureteropelvic junction obstruction in need of pyeloplasty and those with dilated nonobstructed kidneys suitable for conservative treatment. MATERIALS AND METHODS: The study included 35 children with unilateral ureteropelvic junction obstruction treated with pyeloplasty (study group) and 15 children with dilated nonobstructed kidneys who were treated conservatively and followed for 15 months (control group). Voided urine samples were obtained before treatment from both groups, and from the study group at 1, 2, 3, 6, 9 and 12 months postoperatively and the control group at 3, 9 and 15 months of followup. N-acetyl-beta-D-glucosaminidase, alkaline phosphatase and gamma-glutamyl transferase were measured in urine samples collected from both groups. RESULTS: In the study group the activities of preoperative urinary N-acetyl-beta-D-glucosaminidase, alkaline phosphatase and gamma-glutamyl transferase were significantly higher than in the control group. A cutoff value of 7.8 mU/mg creatinine N-acetyl-beta-D-glucosaminidase yielded a sensitivity of 97.1%, a specificity of 80% and an overall accuracy of 92%. A cutoff value of 34.5 IU/gm creatinine alkaline phosphatase resulted in a sensitivity of 91.4%, a specificity of 100% and an overall accuracy of 94%. A cutoff value of 54 IU/gm creatinine gamma-glutamyl transferase yielded a sensitivity of 62.9%, a specificity of 100% and an overall accuracy of 74%. The combination of urinary N-acetyl-beta-D-glucosaminidase and alkaline phosphatase resulted in a sensitivity of 100%, a specificity of 80% and an overall accuracy of 94%. Compared to preoperative activities, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase and gamma-glutamyl transferase decreased significantly at 12 months after pyeloplasty in the study group. CONCLUSIONS: Voided urinary N-acetyl-beta-D-glucosaminidase, alkaline phosphatase and gamma-glutamyl transferase are accurate markers for differentiating between children with ureteropelvic junction obstruction requiring pyeloplasty and those with dilated nonobstructed kidneys suitable for conservative treatment. Measurement of these enzymes in voided urine could be used as a noninvasive tool for long-term followup of children with ureteropelvic junction obstruction after pyeloplasty and those receiving conservative treatment.

Diagnosis of ureteropelvic junction obstruction in children: role of endothelin-1 in voided urine.

OBJECTIVES: To examine the role of voided urine endothelin-1 (ET-1) in the diagnosis and follow-up of children with ureteropelvic junction obstruction. METHODS: The study included 35 children with unilateral ureteropelvic junction obstruction who underwent pyeloplasty and 30 control children, including 10 healthy children, 10 with vesicoureteral reflux, and 10 with renal stones. Voided urine samples were obtained from the children in the study group before surgery and from the renal pelvis by needle aspiration during pyeloplasty. Bladder urine samples were also collected from the study group 1, 2, 3, 6, 9, and 12 months postoperatively. Bladder urine samples were also collected from all 30 control children. ET-1 was measured in the urine samples collected from the study and control groups. RESULTS: The preoperative ET-1 level in the voided urine of the study group was significantly greater than its level in each of the three control groups. For the whole study group, a cutoff value of 3 fmol/mg creatinine gave a sensitivity of 74.3%, a specificity of 90%, and an overall accuracy of 81.5%. In 8 children (1 year old or younger), a cutoff value of 4 fmol/mg creatinine gave a sensitivity and specificity of 100%. Compared with the preoperative value, ET-1 had decreased significantly at 12 months after pyeloplasty. CONCLUSIONS: The ET-1 level in voided urine is a useful marker that could be used as a noninvasive tool for the diagnosis and long-term follow-up of children with ureteropelvic junction obstruction.

Pelvi-ureteric junction obstruction in children: the role of urinary transforming growth factor-beta and epidermal growth factor.

OBJECTIVES: To investigate the role of transforming growth factor beta(1) (TGF-beta(1)) and epidermal growth factor (EGF) in voided urine for the diagnosis and follow-up of children with pelvi-ureteric junction obstruction (PUJO). PATIENTS, SUBJECTS AND METHODS: The study included 35 children with unilateral PUJO who had a pyeloplasty, and 30 healthy control children. Urine samples were obtained from the bladders of patients before surgery, and as voided samples at 1, 2, 3, 6, 9 and 12 months after surgery. Bladder urine samples were also collected from all 30 children in the control group. TGF-beta(1) and EGF were then measured in all the urine samples. RESULTS: The level of bladder TGF-beta(1) before surgery in the patients was significantly higher than that in the healthy control group. A threshold of 190 pg/mg creatinine gave a sensitivity of 100%, a specificity of 80%, a positive predictive value of 85.4%, negative predictive value of 100% and an overall accuracy of 90.8%. Compared with the value before surgery, urinary TGF-beta(1) was significantly lower at 1 year after pyeloplasty. There was no significant difference between the level of EGF before surgery in the patients and that in the control group, and no significant difference in the level of EGF before and after surgery over the follow-up. CONCLUSION: We do not recommend using EGF levels in voided urine in the routine diagnosis of children with hydronephrosis. The urinary level of TGF-beta(1) is a useful noninvasive tool for the long-term follow-up of children with PUJO treated by pyeloplasty. Further studies with various controls are required to confirm the diagnostic accuracy of TGF-beta(1) in children with PUJO.

P-glycoprotein (P-170) expression in acute leukemias.

Multidrug resistance (MDR) is still a major obstacle to chemotherapy success in acute myeloid leukemia (AML) and to a less extent acute lymphoblastic leukemia (ALL). Recent studies have shown that the expression of certain gene products mediate the development of resistance to chemotherapeutic agents. The most well characterized of these genes is the multidrug resistance gene MDR-1. This study was planned to study the expression of P-glycoprotein/170 in patients with acute leukemia and the effect of Cyclosporin A (CSA) as a modulator of P-glycoprotein functional activity. The study was carried out on 20 patients with acute leukemia (14 AML cases and 6 ALL cases). In addition, 6 normal individuals served as a reference group. Flow cytometric analysis of P-gp/170 surface expression was performed using UIC-2 MoAb together with the functional assay using Rhodamine 123 (Rh 123) and Cyclosporin A as a modulator.P-gp/170 was expressed on the leukemic cells of 37.5% of relapsed patients (40.0% of AML and 33.3% of ALL cases), whereas 27.2% of de novo patients expressed P-gp/170 (33.3% of AML cases and 0% of ALL cases). The functional activity of MDR-1 gp was 71.4% in AML and 33.3% in ALL patients compared with16.6% in normal lymphocytes. From this study, it is clear that P-gp/170 is expressed to a higher degree in leukemic cells and this is greater in relapsed compared to de novo cases and more in AML than ALL blasts. Functional activity is a more sensitive predictor of chemoresistance than P-gp/170 surface expression.

Glutathione peroxidase activity in patients with renal disorders.

BACKGROUND: Glutathione peroxidase (GPx) protects cells from oxidative damage by catalyzing the reduction of both organic and hydrogen peroxides, using glutathione as a reducing agent. Both plasma GPx (P-GPx) and erythrocyte GPx (E-GPx) have been identified in human blood. Kidney proximal tubular cells are the main source of GPx activity in the plasma. Oxidative damage has been reported to participate in the progression and complications of renal diseases. METHODS: The activities of both E-GPx and P-GPx were determined, using Randox commercial kits, in 12 patients with nephrotic syndrome (NS), 48 patients with renal impairment (RI), and 50 patients with chronic renal failure on maintenance hemodialysis (HD; before as well as immediately after dialysis), and in 50 healthy volunteers who served as controls. RESULTS: Compared to the results in healthy controls, P-GPx activity was reduced in the HD group and the RI group, whereas the NS group showed no significant difference from the control. The HD group showed a higher drop in P-GPx (reduced to 36.6% of the mean control value) than the RI group (reduced to 61.8% of the mean control value). Further analysis of the RI group showed a highly significant negative correlation between P-GPx activity and serum creatinine level (r = -0.691; P < 0.001). Also, a highly significant negative correlation was found between P-GPx and blood urea nitrogen (r = -0.792; P < 0.001). However, E-GPx activity showed no significant correlation with either serum creatinine or blood urea nitrogen. E-GPx was reduced to 55.2% and 68.9% of the mean control 1 value in the NS group and the RI group respectively, while the HD group showed no significant change. Further analysis of the RI group found that E-GPx activity showed no significant correlation with either serum creatinine or blood urea nitrogen. In HD patients, GPx activity was measured before and immediately after hemodialysis. E-GPx activity was similar before and after dialysis, without a significant difference (pre-dialysis, 37.7 +/- 13.5 U/g hemoglobin [Hb]; post-dialysis, 38.72 +/- 12.31 U/g Hb). However, P-GPx activity was significantly increased (pre-dialysis, 254.4 +/- 62.6 U/ml; post-dialysis, 296.98 +/- 74.04 U/ml; P < 0.001), but it was still significantly lower when compared to that in the healthy controls. CONCLUSIONS: P-GPx activity is an important test to assess the oxidative damage in patients with kidney diseases. The progression of renal disorders is accompanied by a decrease in P-GPx activity, but not by a decrease in E-GPx activity. Thus, we conclude that P-GPx activity largely depends on physiological renal function, whereas E-GPx activity does not.

Reference intervals of cadmium, lead, and mercury in blood, urine, hair, and nails among residents in Mansoura city, Nile delta, Egypt.

A random sample of 68 males and 25 females who reside in Mansoura city, Egypt, was examined for concentrations of cadmium, lead, and mercury in blood, urine, hair, and nails. The effect of gender and smoking on such levels was studied. The influence of dental amalgam on the levels of mercury in these biological samples was also examined. The results obtained show that only blood lead, which increased among males, was affected by gender. Blood levels of cadmium and lead as well as hair lead appeared to increase with smoking habit. Mercury levels in blood and urine were related to the presence of dental amalgam fillings. International comparisons between our results and the corresponding levels in other localities in the world showed that there were environmentally related variations in terms of cadmium levels in hair, lead levels in blood, urine, hair, and nails, and mercury levels in blood, hair, and nails. In conclusion, reference intervals of cadmium, lead, and mercury in the biological samples are environmentally related parameters. Some factors, such as gender, smoking habit, and the presence of dental amalgam fillings, may affect such levels and therefore should be considered.

Mercury in dental restoration: is there a risk of nephrotoxicity?

BACKGROUND: Concern has been voiced about exposure to mercury (Hg) from dental amalgam fillings, and there is a need to assess whether this leads to signs of nephrotoxicity. METHODS: A total of 101 healthy adults (80 males and 21 females) were included in this study. The population as grouped into those having amalgam fillings (39 males and 10 females) and those without (41 males and 11 females). Hg was determined in blood, urine, hair and nails to assess exposure. Urinary excretion of beta2-microglobulin (beta2M), N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyltransferase (gammaGT) and alkaline phosphatase (ALP) were determined as markers of tubular damage. Albuminuria was assayed as an early indicator of glomerular dysfunction. Serum creatinine, beta2M and blood urea nitrogen (BUN) were determined to assess glomerular filtration. RESULTS: Hg levels in blood and urine were significantly higher in persons with dental amalgam than those without; in the dental amalgam group, blood and urine levels of Hg significantly correlated with the number of amalgams. Urinary excretion of NAG, gammaGT and albumin was significantly higher in persons with dental amalgam than those without. In the amalgam group, urinary excretion of NAG and albumin significantly correlated with the number of fillings. Albuminuria significantly correlated with blood and urine Hg. CONCLUSION: From the nephrotoxicity point of view, dental amalgam is an unsuitable filling material, as it may give rise to Hg toxicity. Hg levels in blood and urine are good markers of such toxicity. In these exposure conditions, renal damage is possible and may be assessed by urinary excretions of albumin, NAG, and gamma-GT.