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Ureteral stents versus percutaneous nephrostomy for initial urinary drainage in children with obstructive anuria and acute renal failure due to ureteral calculi: a prospective, randomized study1

Mohammed S Elsheemy*, Ahmed M Shouman, Ahmed I Shoukry, Ahmed ElShenoufy, Waseem Aboulela, Kareem Daw, Ahmed Ali Hussein, Hany A Morsi, Hesham Badawy Division of Pediatric Urology, Aboul-Riche Children’s Hospital, Cairo University, Cairo, Egypt

*Corresponding author. Urology department, Division of Pediatric Urology, AboulRiche Children’s Hospital, Kasr Al-Ainy hospitals, Cairo University, Cairo, Egypt. Tel.:00201006117755. Fax: 00237809663. E-mail address: [email protected]

Word count for the Abstract: 474 Word count for the manuscript text: 3297

Conflict of interest: None. The trial is registered at ClinicalTrials.gov, number NCT02055430 Kay words: anuria; children; nephrostomy; stents; urinary calculi

Abstract Objectives:  To compare percutaneous nephrostomy (PCN) versus double J ureteric stent (JJ) as an initial urinary drainage in children with obstructive calcular

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bju.12768 This article is protected by copyright. All rights reserved.

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anuria (OCA) and post-renal acute renal failure (ARF) due to bilateral ureteric calculi to identify the selection criteria for the initial urinary drainage method that will improve the urinary drainage, decrease the complications and facilitate the subsequent definitive clearance of stones.

 As this comparison is lacking in literature. Patients and methods:  A series of 90 children ≤12 years old presenting with OCA and ARF due to bilateral ureteric calculi were included from March 2011 to September 2013 at Cairo University Pediatric hospital in this randomized comparative study.

 Patients with grade 0-1 hydronephrosis, fever or pyonephrosis were excluded. No patient had any contraindication to both methods of drainage.

 Stable patients (or patients stabilized by dialysis) were randomized (nonblinded, block randomization, closed envelope method) into PCN or bilateral JJ (45 patients for each group).

 Initial urinary drainage was performed under general anesthesia and fluoroscopic guidance. We used 4.8-6Fr JJ or 6-8Fr PCN.

 Primary outcome was the safety and efficacy of both groups in the recovery of renal functions. Both groups were compared in the operative and imaging times, complications, and period for return to normal serum creatinine. Secondary outcome included the number of subsequent interventions needed for clearance of stones. Additional analysis was done for factors affecting outcome inside each group.

Results:

 All presented patients completed the study with intention-to-treat analysis.

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 There was no significant difference between PCN and JJ in the operative and imaging times, period to return to normal creatinine and failure of insertion. The complications were significantly more with PCN group.

 The stone size (> 2cm) was the only factor affecting the rates of mucosal complications, operative time and failure of insertion in JJ group.

 The degree of hydronephrosis affected significantly the operative time for PCN insertion. Grade two hydronephrosis was associated with all cases of insertion failure in PCN group.

 The total number of the needed subsequent interventions to clear stones was significantly higher with PCN group especially in patients with bilateral stones prepared for chemolytic dissolution (alkalinization) or shockwave

lithotripsy (ESWL).

Conclusion:  We recommend the use of JJ as an initial urinary drainage in stones prepared for chemolytic dissolution or ESWL as this will lower the total number of the needed subsequent interventions to clear stones. This is also true for stones prepared for ureteroscopy, as JJ insertion will facilitate subsequent ureteroscopy due to previous ureteric stenting.

 Mild hydronephrosis will prolong the operative time for PCN insertion and may increase the incidence of insertion failure.

 We recommend the use of PCN if the stone size is > 2 cm as there was a more risk of possible iatrogenic ureteric injury during stenting alongside these large ureteric stones in addition to prolongation of operative time with increased incidence of failure.

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Introduction Urgent urinary drainage is the standard of care in patients with

obstructive calcular anuria (OCA) and post-renal acute renal failure (ARF). This is done with retrograde ureteric stenting or a percutaneous nephrostomy tube (PCN); however, the indications for use have not been studied. Although few studies compared ureteric stenting with PCN in obstructive urolithiasis associated with infection [1-2] or pain [3], but this comparison is lacking in literature as regard obstructive urolithiasis associated with anuria and ARF particularly in children. In this study, we compared PCN versus double J ureteric stent (JJ) as

an initial urinary drainage in children with OCA and ARF due to ureteric calculi to determine the selection criteria for the initial urinary drainage method that will improve the urinary drainage, decrease the complications and facilitate the subsequent definitive clearance of stones. Patients and methods A series of 90 children ≤ 12 years old presenting with OCA and ARF

due to bilateral ureteric stones were included in this non-blinded, randomized comparative study of two different techniques of initial urinary drainage. They were managed at Pediatric Urology Department, Cairo University from March 2011 to September 2013. Pediatric patients all over the country are referred to

our center which is the largest pediatric hospital in Egypt. Informed consent was obtained from parents of all presented children. Examination was done to detect signs of acidosis, sepsis or fluid retention in addition to evaluation of serum creatinine, electrolytes, blood urea and arterial blood gases. Abdominal ultrasound and plain urinary tract imaging were done to determine the degree

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of obstruction and the size and level of obstructing stones. Plain CT scan was used to detect radiolucent stones. The Society for Fetal Urology grading system for hydronephrosis was used to classify patients into five grades [4].

Patients with grade 0-1 hydronephrosis, fever or pyonephrosis were excluded. Critically ill patients, who had signs of overload, had elevated serum

potassium > 7 meq/l and/or blood pH < 7.1, were stabilized by peritoneal dialysis. Stable patients (or patients stabilized by dialysis) were randomized (non-blinded, block randomization, closed envelope method) into PCN or bilateral JJ (45 patients for each group). No patient had any contraindication

to both methods of drainage (urinary diversion, urethral stricture or uncontrolled coagulopathy). If ureteric stenting failed on both sides, PCN was inserted. If PCN insertion failed on one side, it was tried on the contralateral side. If failed on both sides, retrograde ureteric stents were inserted. Initial urinary drainage was done under general anesthesia and

fluoroscopic guidance. We used 6-8 Fr PCN or 4.8-6 Fr JJ. Insertion of JJ was done using 9-13 Fr cystoscopes. Definitive stone management was performed after normalization of

renal functions. Patients with radiolucent stones were treated by chemolytic dissolution therapy (alkalinization). Upper ureteric radiopaque stones less than 10 mm in size were treated with ESWL. Open surgery was reserved for cases with bilateral stones more than 20 mm in size. Ureteroscopy was done for the remaining sizes and sites of stones. Success was defined as no evidence of residual stones more than two mm in diameter. Ureteroscopies were done under general anesthesia using 7.5 or 9 Fr

semirigid ureteroscopes (Karl Storz, Germany). Stones were completely

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fragmented under direct vision with laser lithotripsy (SphinX 30W, holmiumYAG laser, LISA Laser Products–OHG, Germany). ESWL was performed using Dornier electromagnetic Do Li S lithotripter

(upgraded to Dornier Lithotripter S EMSE 220F-XXP) with fluoroscopic localization and gradual energy increase up to the third power level. All procedures were performed under general anesthesia using ketamine 1.5mg/kg and midazolam 0.05mg/kg. Intravenous sedation was adequate for some old children. Chemolytic dissolution therapy was done using Oral granules of

potassium sodium hydrogen citrate at a dose of half measured spoonful three times daily dissolved in a glass of water (one spoonful contain 2.4 g) to achieve a pH around 6.5. This was associated with maintenance of a high urine volume. Urinary pH was monitored and adjusted using pH papers to avoid higher pH values (higher than seven) that can result in calcium phosphate stone formation. Primary outcome was the safety and efficacy of both groups in

recovery of renal functions. Consequently, both groups were compared in the operative and imaging times, complications, and period for return to the normal serum creatinine. Additional analysis was done for factors affecting the outcome inside each group. Secondary outcome included the number of subsequent interventions needed for clearance of stones after normalization of renal functions. All statistical calculations were done using computer program SPSS

version 15. Comparison of numerical variables between the study groups was done using Student t test for independent samples in comparing two groups

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when normally distributed and Mann Whitney U test for independent samples when not normally distributed. For comparing categorical data, Chi square (2)

test was performed. Exact test was used instead when the expected frequency was less than 5. P values < 0.05 were considered statistically

significant. Sample size calculation was done based on the time to reach normal

creatinine. Student's t test for independent samples was chosen to perform the analysis. α-error level was fixed at 0.05 and the power was entered to be 80% and the groups were assumed to be of equal size. There was no previous data in the literature concerning the comparison between JJ and PCN in the time to reach normal creatinine, so we assumed that a difference of one day would represent a clinically significant difference between both groups. Accordingly, the minimum sample size to achieve the determined statistical power was 17 patients per group assuming a total period to reach normal creatinine of 3±1 days in one group and 4±1 days in the other group.

Results This study has included 64 boys and 26 girls presented with OCA for 1-

2 days due to bilateral ureteric stones. All presented patients were free of fever, pyonephrosis or sepsis. They had no contraindication to both methods of drainage and they had at least grade two or more hydronephrosis. All patients completed the study and the analysis was intention-to-treat and involved all patients. Peritoneal dialysis was done in 19 patients. All children

regained normal serum creatinine level within 72 hours after initial urinary drainage. Postoperative polyuria was observed in all patients. This decreased

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gradually to normal within six days. The perioperative data are presented in

table 1.

There was no significant difference between PCN and JJ groups of

patients as regard age, gender, degree of hydronephrosis, stone size, site and radiolucency (table 2). There was also no significant difference between both groups in the operative and imaging times, the period to return to the normal creatinine level and the number of cases with unilateral or bilateral failure of insertion. The complications were described according to modified Clavien classification system. They were significantly more in PCN group (p value = 0.044), but they were mild (table 3). Only one case in PCN group (2%) and another one case in JJ group (2%) were converted to the other method of initial urinary drainage due to bilateral failure of insertion. This was associated with no significant difference between both groups (p value = 0.475).

Factors that affect the operative time, complications and failure rate

were analyzed inside each group (table 4-5). The stone size (> 2 cm) was the only factor affecting the rates of mucosal complications (p value = 0.036), operative time (p value < 0.001) and failure of insertion (p value < 0.001) in JJ group (table 4). It was associated with 37% mucosal complications and 50%

failure. These mucosal complications included abrasions, false passage, perforation or extravasation. The degree of hydronephrosis affected significantly the operative time

for PCN insertion with prolongation in patients with grade two hydronephrosis (p value < 0.001). Furthermore, all cases of failure of PCN insertion occurred only in patients with grade two hydronephrosis (5/27) (18%) (table 5).

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The stone free rate was 93% after all secondary procedures and

treatment conversions. Treatment was converted to ureteroscopy in 11 ureterorenal units (six units in PCN group and five units in JJ group) after failure of chemolytic dissolution of stones while it was converted to ureteroscopy after failure of ESWL in two ureterorenal units (one unit in each group) (table 6). As regard the definitive stone management including all secondary

procedures and treatment conversions, 82 (91%) procedures were performed endourologically while only eight (8%) procedures were performed surgically. These procedures were performed either for one side only or for both sides simultaneously (table 6). Five (50%) patients with stones prepared for bilateral

URS were treated bilaterally in the same session while the remaining five (50%) patients were staged while the open ureterolithotomy was done bilaterally in the same session for the eight patients with bilateral large stones (table 6). In JJ group, 27 (60%) patients required a single subsequent

intervention to clear stones while only four (8%) patients required two subsequent intervention. No subsequent interventions to clear stones were needed in 14 patients (31%) after the initial urinary drainage. These 14 patients were treated with chemolytic dissolution therapy for the bilateral stones without any procedure except the initial urinary drainage using JJ. When this was compared with PCN group, a statistically significant difference was found (p value < 0.001) as all patients required subsequent intervention(s) to clear stones. This was in the form of one subsequent intervention in 35 (77%) patients or two interventions in 10 (22%) patients.

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The number of subsequent interventions to clear stones after initial

urinary drainage was analyzed for each type of definitive stone management (table 6). There was no significant difference in the type of subsequent definitive stone management between both groups, but the total number of the needed subsequent interventions to clear stones was significantly more with PCN group (p value=0.003) especially in patients with oral chemolytic

dissolution therapy or ESWL for bilateral stones (p value 2 cm) was the only factor affecting the rates of mucosal complications, operative time and failure of insertion in JJ group. Thus, we recommend to use PCN if the stone size is > 2cm as there is a more risk of possible iatrogenic ureteric injury (37%) during stenting alongside these large ureteric stones in addition to prolongation of operative time with increased incidence of failure (50%). Although there was no significant difference in the type of subsequent

definitive stone management between both groups, the total number of the needed subsequent interventions to clear stones was significantly higher with PCN group especially in patients with chemolytic dissolution therapy or ESWL. Our study showed that JJ has an advantage over PCN in this point. JJ insertion forms a part of definitive management of stones prepared for chemolytic dissolution or ESWL, lowering the number of subsequent

interventions needed to clear stones. Furthermore, it will facilitate subsequent ureteroscopy due to previous ureteric stenting. Goldsmith et al reported that the likely method of definitive stone management is considered when selecting the initial urinary drainage method. Patients treated with PCN were more likely to be treated definitively with a percutaneous nephrolithotripsy (22/58) (38%), while patients treated with JJ were more likely to be treated ureteroscopically (45/69) (65%) [1]. In the previously mentioned study which

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was done on 93 children in our center, JJ and PCN formed a part of the definitive stone management in 18/40 ureterorenal units (45%) and 19/26 ureterorenal units (73%), respectively [11]. In the other study done in our

center on 24 infants, JJ insertion was a part of definitive stone management in 29/31 ureterorenal units (93%) while PCN was not a part of definitive stone management in any patient [10]. Our study may be the 1st one discussing the method of the initial

urinary drainage in children with OCA associated with ARF due to ureteric stones. The prospective randomized design adds to the strength of this study. The multiple surgeons involved in this study with different levels of experience is a limiting factor. Another limiting factor is the exclusion of ultrasound guided PCN from the comparison as this method of initial urinary drainage is not available as an emergency method in our center. Moreover, we use it mainly in patients with lower grades of hydronephrosis. Conclusion: JJ and PCN have equivalent operative and imaging times with success

in insertion and drainage in children with OCA and ARF due to bilateral ureteric stones. Although complications were higher with PCN, they were mild and did not affect the drainage or recovery of renal functions. Mild hydronephrosis (grade two or less) will prolong the operative time

for PCN insertion and may increase the incidence of insertion failure. We recommend the use of PCN if the stone size is more than 2 cm as there was a more risk of possible iatrogenic ureteric injury during stenting alongside these large ureteric stones in addition to prolongation of operative time with increased incidence of failure. We recommend the use of JJ in stones

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prepared for chemolytic dissolution (alkalinization) or ESWL as this will lower

the total number of the needed subsequent interventions to clear stones. This is also true for stones prepared for ureteroscopy, as JJ insertion will facilitate the subsequent ureteroscopy due to previous ureteric stenting. Conflict of interest None.

Funding Source: None.

This study was approved by the local ethical committee. The trial is registered at ClinicalTrials.gov, number NCT02055430 References:

1.

Goldsmith ZG, Oredein-McCoy O, Gerber L, et al. Emergent ureteric stent vs percutaneous nephrostomy for obstructive urolithiasis with sepsis: patterns of use and outcomes from a 15-year experience. BJU Int. 2013 Jul;112(2):E122-8.

2.

Pearle MS, Pierce HL, Miller GL, et al. Optimal method of urgent decompression of the collecting system for obstruction and infection due to ureteral calculi. J Urol. 1998 Oct;160(4):1260-4.

3.

Mokhmalji H, Braun PM, Martinez Portillo FJ, Siegsmund M, Alken P, Köhrmann KU. Percutaneous nephrostomy versus ureteral stents for diversion of hydronephrosis caused by stones: a prospective, randomized clinical trial. J Urol. 2001 Apr;165(4):1088-92.

4.

Fernbach SK, Maizels M, Conway JJ. Ultrasound grading of hydronephrosis: introduction to the system used by the Society for Fetal Urology. Pediatr Radiol 1993;23:478-80.

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Agrawal MS, Aron M, Asopa HS. Endourological renal salvage in patients

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5.

with calculus nephropathy and advanced uraemia. BJU Int. 1999 Aug;84(3):252-6.

6.

Darabi M, Keshvari M. Bilateral same-session ureteroscopy: its efficacy and safety for diagnosis and treatment. Urol J. 2005 Winter;2(1):8-12.

7.

Jiang H, Wu Z, Ding Q. Ureteroscopy and holmium: YAG laser lithotripsy as

emergency treatment for acute renal failure caused by impacted ureteral calculi. Urology. 2008 Sep;72(3):504-7.

8.

Hollenbeck BK, Schuster TG, Faerber GJ, Wolf JS. Safety and efficacy of same-session bilateral ureteroscopy. J Endourol 2003; 17: 881–885.

9.

Elgammal AM, Abdelkhader MS, Kurkar A, Mohammed OA, Hammouda HM. Management of calculus anuria in children: experience in 54 children. J Pediatr Urol 2009;5:462-5

10. Kotb S, Elsheemy MS, Morsi HA, Zakaria T, Salah M, Eissa MA. Renal recoverability in infants with obstructive calcular anuria: Is it better than in older children? J Pediatr Urol. 2013;9:1178-1182

11. Ziada AM, Sarhan OM, Habib EI, et al. Assessment of recoverability of kidney function in children with obstructive calcular anuria: multicenter study. J Pediatr Urol. 2011 Jun;7(3):252-6.

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Table1. Perioperative data* Age 4.42 ± 2.213 yrs (1-9) Symptoms and signs: Vomiting 16 (17%) patients Volume overload 19 (21%) patients Loin pain 20 (22%) patients Cr on presentation 4.59 ± 1.90 mg% (2-9) Stones: Size 14.1 ± 5.2 mm (6-30) Patients with radiolucent stones 55/90 (61%) Site: Proximal ureter 74/180 (41%) stones Middle ureter 31/180 (17%) stones Distal ureter 75/180 (41%) stones Postoperative serum Creatinine 0.44 ± 0.13 mg% (0.3-0.7) Period to normal serum Creatinine 2.2 ± 0.76 days (1-3) *Data are presented as mean ± SD (range) or number (%)

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Table 2. Preoperative characteristics of patients in both groups of initial urinary drainage* PCN JJ

Age (yr)

45 patients

45 patients

(45 URU)

(90 URU)

4.78 ± 2.295 (1-9)

4.07 ± 2.093 (1-9)

Male patients 30 (66%) 34 (75%) Female patients 15 (33%) 11 (24%) Degree of hydronephrosis: Grade 2 27/45 (60%) 60/90 (66%) Grade 3-4 18/45 (40%) 30/90 (33%) Stone size (mm) 15.011 ± 4.22 (8-27) 13.25 ± 5.37 (8-30) Stone site: Upper ureter 37/90 (41.1%) 37/90 (41.1%) Middle ureter 16/90 (17.8%) 15/90 (16.7%) Lower ureter 37/90 (41.1%) 38/90 (42.2%) Patients with radiolucent stones 27 (60%) 82 (62.22%) *Data are presented as mean ± SD (range) or number (%) JJ: double J ureteric stent; PCN: percutaneous nephrostomy tube; URU: ureterorenal units.

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P value

0.128 0.352 0.446

0.088 0.977

0.613

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Table 3. Comparison of the results of both methods of the initial urinary drainage. PCN JJ

Operative time (min) Imaging time (min) Period to normal Cr (d) Failure of insertion (URU) Complications: (URU) Grade 1: Hematuria Leakage around PCN Grade 2: Febrile UTI Grade 3b: Mucosal complications Stent or PCN Slippage

45 patients

45 patients

(45 URU)

(90 URU)

01.44 ± 3.54 (6-80) 1.42 ± 0.904 (1-4) 2.22 ± 0.765 (1-3) 5/45 (11%)

9.93 ± 3.55 (5-88) 1.1 ± 0.751 (1-3) 2.18 ± 0.777 (1-3) 9/90 (10%)

2/45 (4%) 3/45 (6%)

0 NA

2/45 (4%)

1/90 (1%)

NA 4/45 (8%)

9/90 (10%) 0

P value 0.497 0.069 0.785 0.92

Total 11/45 (24%) 10/90 (11%) 0.044* Data are presented as mean ± SD (range) or number (%) * Significant Cr: serum creatinine; JJ: double J ureteric stent; NA: not applicable; PCN: percutaneous nephrostomy tube; URU: ureterorenal units.

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Table 4. Analysis of factors affecting the results in the double J group.

Stone size: 2cm

Stone site: Upper ureter Middle ureter Lower ureter

Age: 2 yrs

Gender: Male Female

Mucosal

Failure of

Operative time

complications

insertion

(min)

6/82 (7%) 3/8 (37%)

5/82 (6%) 4/8 (50%)

9.08 ± 4.44 18.67 ± 5.02

P = 0.036 *

P = 0.001 *

4/37 (10%) 1/15 (6%) 4/38 (10%)

4/37 (10%) 1/15 (6%) 4/38 (10%)

9.94 ± 2.388 11.42 ± 5.564 9.4 ± 3.648

P = 0.952

P = 0.894

P = 0.44

5/30 (16%) 4/60 (6%)

4/30 (13%) 5/60 (8%)

10.2 ± 2.883 9.8 ± 3.889

P = 0.264

P = 0.709

P = 0.727

6/60 (10%) 3/30 (10%)

5/60 (8%) 3/30 (10%)

10.13 ± 3.76 9.53 ± 3.18

P = 0.79 P = 0.821 Data are presented as mean ± SD or number of ureterorenal units (%) * Significant; P: p value.

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P < 0.001 ⃰

P = 0.6

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Table 5. Analysis of factors affecting the results in the percutaneous nephrostomy group.

Age: 2 yrs

HN: Grade 2 Grade 3-4

Failure of

Operative time

insertion

(min)

2/10 (20%) 3/35 (8%)

12.1 ± 4.012 9.971 ± 3.31

P = 0.657

P = 0.094

5/27 (18%) 0/18

12.06 ± 7.26 8.12 ± 2.74

P = 0.146 P < 0.001* Data are presented as mean ± SD or number of ureterorenal units (%) * Significant; HN: hydronephrosis; P: p value

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Table 6. Subsequent interventions to clear stones for both groups of the initial urinary

Definitive stone management

drainage. No of patients subjected to definitive stone management All patients

after PCN

after JJ

P Value

No of SICS after initial urinary drainage All SICS

after after PCN JJ

P Value

Bilateral CD or ESWL 33(36%) 15(33%) 18(40%) 0.511 23 19∞ 4∞

Ureteric stents vs percutaneous nephrostomy for initial urinary drainage in children with obstructive anuria and acute renal failure due to ureteric calculi: a prospective, randomised study.

To compare percutaneous nephrostomy (PCN) tube vs JJ ureteric stenting as the initial urinary drainage method in children with obstructive calcular an...
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