|Year : 2012 | Volume
| Issue : 1 | Page : 1-5
Hydronephrosis due to pelviureteric junction narrowing: Utility of urinary enzymes to predict the need for surgical management and follow-up
Kirtikumar J Rathod1, Ram Samujh1, Sumeet Agarwal1, Ravi Prakash Kanojia1, Ujjawal Sharma2, Rajendra Prasad2
1 Department of Paediatric Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||22-Dec-2011|
Department of Paediatric Surgery, APC, Block 3-A, PGIMER, Sect 12, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aim: To study the role of urinary enzymes N-acetyl-b-glucosaminidase (NAG), alkaline phosphatase (AKP) and gamma glutamyl transferase (GGT) in the diagnosis and follow-up of patients with suspected pelviureteric junction obstruction (PUJO). Materials and Methods: A total of 70 patients, 29 managed conservatively (group A) and 41 managed by pyeloplasty (group B), were studied prospectively. A serial measurement of urinary enzymes NAG, AKP and GGT level was performed in both the groups. The mean levels of these urinary enzymes were compared between the two groups and among the patients of the same group at presentation as well as during follow-up. Results: There was a significant fall in the mean AKP level in patients managed conservatively at 8 months of follow-up. Similarly, in the operated group, there was a significant fall in the AKP levels at both 3 months and 8 months of follow-up. The mean level of GGT also showed a significant fall after 3 months of surgery but did not show further significant change at 8 months after surgery. The mean levels of NAG and GGT in the conservatively managed group were significantly low compared with that of patients requiring pyeloplasty at presentation as well as in the follow-up. The mean level of AKP was significantly low in the conservatively managed group when compared with the patients requiring surgery, but did not differ significantly in both the follow-ups after surgery. Conclusions: The level of urinary enzymes NAG, AKP and GGT are significantly high in the patients with hydronephrosis (HDN) requiring pyeloplasty when compared with the patients managed conservatively. The level of AKP significantly falls after pyeloplasty in the patients of HDN due to PUJO. There is a negative correlation with the preoperative level of enzyme NAG with split renal function in the patients of HDN requiring pyeloplasty.
Keywords: Alkaline phosphatase, gamma glutamyl transferase, N-acetyl-b-glucosaminidase, pelviureteric junction obstruction, urinary biomarkers, urinary enzymes
|How to cite this article:|
Rathod KJ, Samujh R, Agarwal S, Kanojia RP, Sharma U, Prasad R. Hydronephrosis due to pelviureteric junction narrowing: Utility of urinary enzymes to predict the need for surgical management and follow-up. J Indian Assoc Pediatr Surg 2012;17:1-5
|How to cite this URL:|
Rathod KJ, Samujh R, Agarwal S, Kanojia RP, Sharma U, Prasad R. Hydronephrosis due to pelviureteric junction narrowing: Utility of urinary enzymes to predict the need for surgical management and follow-up. J Indian Assoc Pediatr Surg [serial online] 2012 [cited 2018 May 28];17:1-5. Available from: http://www.jiaps.com/text.asp?2012/17/1/1/91077
| Introduction|| |
Pelviureteric junction obstruction (PUJO) is one of the most common causes of hydronephrosis (HDN) and renal insufficiency in children. ,, It is important to predict which cases of HDN will resolve spontaneously and which will require surgical treatment. ,, Investigations like dynamic radioisotope scan, ultrasonography and, infrequently, intravenous pyelography are utilized for investigating these patients.  Certain urinary biomarkers have been used as indicators of renal damage in HDN patients.  Measurement of urinary enzymes can be used as biomarkers for various renal diseases.  We evaluated the role of lysosomal enzyme N-acetyl-b-glucosaminidase (NAG) and brush border enzymes alkaline phosphatase (AKP) and gamma glutamyl transferase (GGT) in the diagnosis and follow-up of patients with HDN.
| Materials and Methods|| |
This is a prospective observational study from July 2009 to December 2010. All consecutive children with HDN due to suspected PUJO were included in the study. The patients managed by percutaneous nephrostomy, patients with urolithiasis and urine samples with positive bacterial cultures were excluded from the study.
All the patients underwent blood urea and creatinine levels estimation, ultrasonography of abdomen, dynamic renal scan using ethylene dicysteine (EC) renography and urinary levels of NAG, AKP, GGT and creatinine (Cr). The levels of urinary enzymes were expressed as enzyme to Cr ratios as urinary NAG-to-Cr, urinary AKP-to-Cr and urinary GGT-to-Cr ratios, expressed as mU/mg, μmol/mg/min and IU/gm, respectively.
Based on the EC scintigraphy, the patients were divided into two groups. Group A included patients with nonobstructed (t½ of less than 10 min) and equivocal (t½ of 10-20 min) renogram curve on the scan and the corresponding split renal function (SRF) of more than 40%. These patients were managed conservatively. Group B included patients with obstructed renogram curve on the scan, i.e. t½ of more than 20 min and corresponding SRF of less than 40%. These patients underwent pyeloplasty.
N-Acetyl-b-D-glucosaminidase (NAG) was measured by a modification of the method of Maruhn.  Activity of AKP was assayed by the method of Bergmeyer using 4-nitro phenyl phosphate as a substrate. , Gama GGT was measured by a modification of the method of Szasz.  Statistical analysis was performed using statistical software SPSS V17.
| Results|| |
A total of 70 patients were included in the study, of which 29 patients were in group A and 41 patients were in group B. The mean age of group A patients was 20.6 months (range: 1-144 months) while in group B was 26.2 months (range: 2-120 months). There were seven females in group A while group B had three females. The gender difference was statistically comparable (P = 0.0803).
Of the 29 patients in group A, 10 patients had left-sided HDN. Two patients in this group had bilateral renal involvement. On the other hand, in group B, 28 of 41 patients had left-sided PUJO. This difference in the side of renal involvement among the groups was significant (P = 0.0139).
The mean ± standard deviation baseline SRF in group A was 50.6 ± 4.4, which remained unchanged at
3 and 8 months of follow-up (50.1 ± 2.1 and 50.6 ± 1.8, respectively). In group B, the mean preoperative SRF of 33.5 ± 14.5 significantly improved to 37.5 ± 12.7 at 3 months after surgery (P < 0.001). However, on further follow-up at 8 months, the mean SRF remained the same (37.8 ± 12.4, P = 0.6626).
[Table 1] demonstrates the drainage patterns of kidneys as reported by EC scan in group A patients. More than 50% of the patients showed improvement on the drainage within the observation period of 8 months from diagnosis, P < 0.001. Similarly, in group B, the renogram curves showed significant improvement in the drainage pattern after surgery.
|Table 1: Comparison of drainage patterns in both the groups as reported by EC scan |
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The simple linear regression of baseline enzyme levels of NAG, AKP and GGT with the SRF in group A showed that there was no correlation between the enzyme levels and SRF in this group. However, the linear regression graph of NAG levels with SRF in group B [Figure 1] showed a significant negative correlation (r 2 = 0.198, P = 0.0035). The linear regression graph of AKP and GGT with SRF did not show any significant correlation in group B.
There was no change in the level of NAG on follow-up assays in group A patients. Although there was no significant change in the mean AKP level at the first follow-up (P = 0.2702), there was a significant fall in the mean AKP level on the second follow-up (P < 0.0001) in this group. This fall in the levels of AKP correlated with improvement in the drainage patterns during that follow-up. GGT levels in group A on follow-up did not show any significant change from baseline to follow-up values, P = 0.2344.
Similarly, in group B, there was no significant change in NAG level during both the follow-ups, but there was a significant decrease in the mean level of AKP from the baseline level of 0.02287 μmol/mg cr/min to 0.00423 μmol/mg cr/min at 3 months, which further decreased to 0.00172 μmol/mg cr/min on second-follow up at 8 months, P < 0.0001 [Figure 2]. The mean GGT level in group B also decreased significantly from a baseline value of 15.13 IU/gm cr to 13.39 IU/gm cr on first follow-up (P = 0.0178), but did not change on second follow-up (P = 0.166).
|Figure 2: Comparison of change in alkaline phosphatase levels in Group B|
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[Figure 3] shows a comparison of enzyme levels between the two groups. On comparison of mean NAG levels between group A and group B, it was observed that the baseline and both the follow-up mean NAG levels were significantly low in group A as compared with that of group B, P < 0.0001. The baseline mean AKP level in group A was significantly lower in comparison with that of group B, P = 0.005. However, there was no significant difference in the levels of mean AKP between groups A and B at the time of first and second follow-up, P = 0.452 and 0.1128, respectively. Similarly, the baseline and the follow-up mean levels of GGT in group A were significantly low as compared with that of group B, P = 0.008, 0.003 and 0.002, respectively.
An receiver operating characteristic (ROC) curve was constructed to identify the cut-off value of the urinary enzymes that provided the best diagnostic accuracy. A cut-off value of 5.73 mU/mg cr of NAG yielded a sensitivity of 82.5% and a specificity of 82.1% to identify the patients who were included in group B and underwent operative management. Similarly, the ROC of NAG level with the patients divided in the groups as split renal of less than 40% and more than 40% yielded a cut-off value of 8.27 mU/mg cr of NAG to be 88.9% sensitive and 86.3% specific in predicting split renal of less than 40% in the studied children. The ROC curves of AKP and GGT did not show any significant value.
| Discussion|| |
The use of biomarkers as a noninvasive tool in the diagnosis and management of various diseases is increasingly reported in the literature. , The use of these biomarkers is especially important in the pediatric age group as the use of invasive investigation is a matter of concern in children.
Lee et al. in their review article have described the role of various biomarkers in pediatric urological diseases like vesicoureteral reflux  and PUJO.  The diagnosis of PUJO is nowadays commonly made by antenatal ultrasonography (USG).  The postnatal diagnosis of the disease is confirmed by various investigations like USG, intravenous urography and renal scintigraphy.  Most of these investigations are confusing, time-consuming and invasive and involve radiation exposure of the neonate. Thus, the role of noninvasive markers in the diagnosis and follow-up of PUJO patients is important.
The present study demonstrated the role of urinary enzymes NAG, AKP and GGT in the diagnosis and follow-up of 70 children with PUJO as compared with EC scan. Our study clearly shows that mean levels of urinary enzymes NAG, AKP and GGT were significantly lower in the patients not requiring surgery in comparison with that of patients who required pyeloplasty. It can be derived from the observations in the study that the increased levels of these enzymes can be used to identify the patients who will require surgical management of congenital pelviureteric junction narrowing.
Taha et al. have compared the urinary levels of enzymes NAG, AKP and GGT in 35 patients of PUJO managed by pyeloplasty, with 15 patients of PUJO treated conservatively.  Their study showed that preoperative levels of urinary NAG, AKP and GGT were significantly higher in the group treated by pyeloplasty in comparison with the patients managed conservatively. They also demonstrated that there is a significant fall in the levels of the three urinary enzymes 12 months after pyeloplasty. Our study also showed that the mean baseline levels of urinary enzymes NAG, AKP and GGT were significantly higher (7.94 mU/mg cr, 0.0227 μmol/mg cr and 15.13 IU/gm cr, respectively) in the patients managed by pyeloplasty than in the patients managed conservatively (3.93 mU/mg cr, 0.0101 μmol/mg cr and 11.36 IU/gm cr, respectively, P < 0.05). Although the study described similar results, the baseline levels of NAG and GGT (12.6 mU/mg cr and 63.9 IU/gm cr, respectively) in their study were much higher than the baseline levels of these enzymes in our study (7.94 mU/mg cr and 15.13 IU/gm cr, respectively). We are not comparing the baseline levels of AKP, as the method used for estimating AKP activity in their study was different from the one used in the present study. The present study demonstrated significant decrease in the mean level of AKP at 3 and 8 months of pyeloplasty. However, the mean level of NAG in urine remains the same in our study at 3 and 8 months of follow-up after pyeloplasty. The mean level of GGT falls significantly at 3 months after pyeloplasty, but remains at the same level at 8 months after surgery in our study. These observations of fall in mean enzyme levels are different from the study by Taha et al., in which they had shown a significant decrease in the mean NAG level at 3 and 9 months after surgery; however, the mean levels of AKP and GGT remained the same at 3 months of follow-up in their report, and the levels of these enzymes decreased significantly only after 9 months of surgery.
The simple linear regression analysis of enzyme levels with SRF in our study showed that there was a significant (P = 0.0035) negative correlation between NAG levels and SRF in the patients in whom pyeloplasty was performed (r 2 = 0.198). However, the simple linear regression performed between AKP and GGT levels with SRF in operated patients did not show any significant correlation. The same was true for the linear regression analysis of enzymes levels with SRF in conservatively managed patients, which also did not show any significant correlation.
Shokeir et al. had studied the change in the level of urinary enzymes NAG, AKP and GGT in the patients with PUJO managed conservatively at 3, 9 and 15 months of presentation.  They showed that the levels of urinary enzymes remained the same in the patients in whom the renal function was stable and the dynamic renal scintigraphy showed unobstructed drainage. However, the level of all the three urinary enzymes increased significantly in the patients in whom the renal function deteriorated and the dynamic renal scintigraphy showed obstructed drainage. In 28/29 of our patients who had stable renal function and unobstructed drainage, the mean level of NAG and GGT did not change significantly at 3 and 8 months of follow-up. In conservatively managed patients, the mean level of AKP although at 3 months of follow-up did not change significantly compared with the mean baseline level (0.0101 μmol/mg/min cr), but decreased significantly to a mean level of 0.00266 μmol/mg/min cr at 8 months of follow-up, P < 0.0001. This corresponds to the significant improvement in drainage pattern as per EC scan in these kidneys.
Decramer et al. performed a urinary proteome analysis to predict the clinical outcome of the patients with PUJO.  An interesting observation that came out of our study was that right-sided HDN was more common in the patients managed conservatively (17/29), while it was the left-sided HDN that was common in the patients requiring pyeloplasty (28/41, P = 0.014). However, at this moment, we are unable to give a clinical explanation for this finding.
Our study had the following limitations. Although the sample size was adequate for the study, we had only a limited number of patients in each group. We had only two follow-up examinations: one at 3 months and another at 8 months of presentation or surgery. In the operated group, the second follow-up was available for only 45% of the patients at the time of data analysis because the second follow-up EC scan is done only after 1 year of surgery as per the departmental protocol. The nomograms for the normal values for the enzymes estimated in the age-matched groups are yet to be established. Once this is done in future studies, the data can be further validated.
| Conclusions|| |
The level of urinary enzymes NAG, AKP and GGT are significantly high in the patients with HDN requiring pyeloplasty when compared with the patients managed conservatively. Therefore, the levels of these enzymes can be used to identify patients requiring pyeloplasty. The baseline level of AKP significantly falls after pyeloplasty in the patients of HDN due to PUJO managed by surgery. This enzyme can be used as a marker of improvement in drainage after pyeloplasty. There is a negative correlation of preoperative level of NAG with SRF in the patients requiring pyeloplasty. The level of NAG may be used to predict preoperative renal function in these patients.
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[Figure 1], [Figure 2], [Figure 3]
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