Pattern of Renal Function Deterioration as a Predictive Factor of Unilateral Ureteropelvic Junction Obstruction Treatment

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european urology 51 (2007) 551 555 available at www.sciencedirect.com journal homepage: www.europeanurology.com Pediatric Urology Pattern of Renal Function Deterioration as a Predictive Factor of Unilateral Ureteropelvic Junction Obstruction Treatment Christos Kaselas *, Georgios Papouis, Georgios Grigoriadis, Aris Klokkaris, Vasilios Kaselas Pediatric Surgery Department, Hippokration General Hospital, Thessaloniki, Greece Article info Article history: Accepted May 31, 2006 Published online ahead of print on June 15, 2006 Keywords: Pyeloplasty Renal function deterioration Ureteropelvic junction obstruction Abstract Objectives: To assess the process of renal function deterioration in patients with unilateral ureteropelvic junction (UPJ) obstruction and its impact on their treatment course. Material and methods: The files of patients treated for unilateral UPJ obstruction at our department from 1996 to 2003 were retrospectively reviewed. All patients were initially treated conservatively and followed up regularly. Criteria for conversion to surgical treatment were increase in anteroposterial renal pelvis diameter, increase in T washout pattern, and drop of relative renal function (RRF) below 40% in diuretic renogram. Patients operated on because of multiple urinary infections, pelvic stones, or solitary kidneys were excluded. Patients were divided into group A, which included those whose treatment was converted from conservative to surgical, and group B in which patients were treated conservatively. All patients operated on underwent dismembered pyeloplasty. Results: Sixty-four patients with grade three or four hydronephrosis in postnatal ultrasound examination and an obstructive pattern in diuretic renogram were studied. All group A patients (n = 47) reached an RRF below 40%; in 41 (87.2%) deterioration of RRF was detected in at least two sequential follow-up studies. In group B patients (n = 17), deterioration was also detected in seven (41.1%) patients in two sequential studies ( p < 0.0005), although the RRF never dropped below 40%. No differences in gender, side of obstruction, or frequency of follow-up were detected between the two groups. Conclusions: RRF deterioration and its progression for at least two sequential follow-ups could serve as a predictive factor for surgical treatment. # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. 4, I. Dragoumi str, Panorama, 55236, Thessaloniki, Greece. Tel. +306944413788/+302310321007; Fax: +302310892338. E-mail address: xkaselas@otenet.gr (C. Kaselas). 0302-2838/$ see back matter # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2006.05.053

552 european urology 51 (2007) 551 555 1. Introduction The management of unilateral hydronephrosis caused by ureteropelvic junction (UPJ) obstruction still remains a controversial issue. Congenital anomalies of the urinary tract can be diagnosed from the 14th week of gestation by ultrasound examination (US). However, for a more accurate diagnosis, a prenatal US study around the 20th week of gestation is recommended, followed by another US study on the 28th week of gestation. Postnatal evaluation traditionally involves US examination, voiding cystography, and diuretic renogram. The need and timing of surgical intervention for such patients is still debated. There are supporters of early surgical intervention to give the kidney the opportunity to preserve its healthy parenchyma and its function as early as possible [1]. Proponents of conservative initial management strongly support prolonged observation and delayed pyeloplasty on the basis of findings of spontaneous resolution of UPJ obstruction in some patients [1]. They reserve pyeloplasty for cases in which RRF deteriorates <40%, or if other clinical findings such as urinary tract infection, kidney stones, and so forth exist [2]. Despite he differing opinions, the current trend in the treatment of patients with unilateral UPJ obstruction is a nonoperative one. However, the existing controversy has encouraged us to investigate the natural history of such patients in an attempt to establish a new approach to the criteria that suggest the conversion of nonoperative management to surgical intervention. 2. Material and methods We retrospectively reviewed all the files of patients treated for unilateral UPJ obstruction from 1996 to 2003 at our department. For patients with prenatally diagnosed hydronephrosis, confirmation of the diagnosis was based on renal US scan performed on the first week of life followed immediately by voiding cystography and radionuclide studies at the age of 6 wk. The rest of the patients who presented after the onset of symptoms such as flank pain, palpable mass, or urinary tract infection were diagnosed on the basis of the same screening program immediately after presentation. The protocol that we followed for the management of all patients was observation with regular follow-ups with renal US every 6 mo and diuretic renogram every 6 mo until the age of 12 mo and every year thereafter. Criteria for the change to surgical intervention were increase of anteroposterial renal pelvis diameter leading to increase of Society for Fetal Urology (SFU) grade, increase of drainage T with worsening of the obstructive curve in the diuretic renogram, and drop of RRF below 40%. Patients whose operation was justified by other clinical presentations such as urinary tract infections, pelvic stones, and solitary kidney were excluded from our study. Our study group included 64 patients: 42 males and 22 females. In 46 of them, a prenatal US indicative of unilateral hydronephrosis associated was available. All patients had an SFU grade 3 or 4 hydronephrosis in postnatal US examination and an obstructive pattern in diuretic renogram with T 20 min. We observed that, in most patients, RRF deterioration was detected in at least two successive follow-up studies; the natural history was for RRF to finally drop below 40%. Wanting to investigate this observation even more, we divided our patients into two groups: group A, which included patients whose treatment was converted from conservative to surgical and Group B in which patients were treated nonoperatively and were followed up regularly. All patients were maintained on prophylactic antibiotics. The technique that we used for operated patients was dismembered pyeloplasty. 2.1. Statistical analysis Statistical evaluation of differences in proportions of recurrences in different groups of patients and calculation of odds ratio (OR) and 95% confidence intervals (CIs) were performed by the Fisher exact test. A two-sided p value of 0.05 indicated statistical significance. Statistical analysis was performed by using the Instat statistical program (Graphpad Inc, San Diego, CA, USA). 3. Results Group A included 47 patients, 31 males and 16 females, and Group B included 17 patients, 11 males and 6 females. The natural history of all group A patients was deterioration and a drop of RRF below 40%, which evidently resulted in conversion of nonoperative to surgical treatment (47 of 64 [73.4%] patients). On the other hand, the RRF of all group B patients never dropped below 40%, their follow-up studies are satisfactory and they are still under observation (17 of 64 [26.6%] patients). It was worth noticing that, in 41 of 47 (87.2%) group A patients, when deterioration of RRF begun, a drop was detected in at least two sequential followup studies (Table 1). In contrast, a drop of RRF was detected in two sequential studies in only 7 of 17 Table 1 Natural history of study patients No. of pts No. of pts with RFD on two sequential follow-up studies (%) Surgical treatment 47 41 (87.2) Conservative treatment 17 7 (41.1) Total 64 48 (75) Pts: patients, RFD: renal function deterioration.

european urology 51 (2007) 551 555 553 (41.1%) group B patients ( p = 0.0005; odds ratio [OR]: 9.762; 95%CI, 2.683 55.512; Table 1). There were no differences in gender ( p = 1; OR: 1.057; 95%CI, 0.330 3.384), side of UPJ obstruction ( p = 1; OR: 1.128; 95%CI, 0.364 3.495), and frequency of conservative follow-ups between the two groups. In an attempt to explore the meaning of detection of RRF deterioration in two sequential studies, we focused on the course of treatment of these patients. In the 64 patients that comprised our study group, a drop of RRF in two sequential follow-up studies was detected in 48 (75%) patients. In 41 of these 48 (85.4%) patients, RRF finally dropped below 40%, and they were finally operated on, indicating that RRF deterioration on two consecutive follow-ups served as a predictive factor in 85.4% of those patients. The remaining seven (14.6%) patients are doing well, their hydronephrosis is not worsening, and their RRF never dropped below the critical value of 40%. However, they are still under observation. All patients who were operated on were followed up postoperatively. Data for a 3-yr follow-up exist for all patients, whereas some of them were followed up as far as 5 yr after operation. No patient needed reoperation. In the 3-yr follow-up studies, 43 of 47 (91.4%) patients showed no signs of worsening of their anteroposterial renal pelvis diameter, whereas their diuretic renogram washout pattern reached values not indicative of UPJ obstruction. In none of these 43 patients did the RRF deteriorate further. The remaining four (8.5%) patients showed partial recovery of their diuretic renogram washout pattern and were under observation for 2 more years. They belonged to the group of the 41 patients in whom a drop of RRF was detected in two sequential follow-up studies. During this 2-yr period, no further deterioration of RRF was diagnosed. After that time they also had satisfying results. No patient in group B suffered from any urinary infections, and hydronephrosis in these patients is improving. Complete recovery of their diuretic renogram washout pattern to nonobstructive values was detected in four (23.5%) patients, partial recovery in eight (47%), no change in three (17.6%), and further deterioration in two (11.7%). However, in none of these patients did RRF ever drop below 40%. In addition, RRF seems to be rising in 12 (70.5%) patients who showed full or partial recovery of their diuretic renogram. 4. Discussion In UPJ obstruction treatment, the two debatable facts are first the initial management of patients and second the appropriate time of surgical intervention. In the last 10 15 yr, because of the important work of many investigators, the initial nonoperative approach for patients with unilateral UPJ obstruction has gained lots of ground compared with surgical treatment. This result was based on the fact that, in long-term studies of nonoperative management of such patients with prenatally diagnosed hydronephrosis, loss of RRF was not usual and that only a small percentage of them finally required pyeloplasty [3 5]. Others propose early pyeloplasty on the basis of the need to preserve maximum healthy renal parenchyma and normal renal function [6,7]. Conversion from nonoperative to operative treatment is proposed when the washout pattern in the renogram is obstructive and RRF is 40% [8,9]. The results of the observation series that convert treatment to delayed pyeloplasty vary. Many series report that as many as 50% of patients did not regain lost RRF [3,10,11]. Others report percentages of recovery of RRF as high as 100% [12,13]. Early pyeloplasty is suggested after obstructive patterns in diuretic renogram and US examination are diagnosed, to preserve the detected RRF because there is little or no chance of RRF improvement after surgery [1,2]. The protocol that we follow regarding the management of patients with unilateral UPJ obstruction is initial observation with regular follow-ups and conversion to surgical treatment when RRF deterioration below 40% is detected or if other reasons such as multiple urinary tract infections, pelvic stones, solitary kidney require the use of pyeloplasty. The crucial problem in the management of patients with unilateral UPJ obstruction is to decide between nonoperative or surgical treatment for those children in whom RRF will deteriorate. Hafez et al. [12], wanting to provide a possible solution to this question, stated that progression of hydronephrosis in two consecutive US studies could serve as an indication for surgery. In a recent study, Chertin et al. [13] evaluated the course of treatment of 343 children with an antenatal diagnosis of hydronephrosis and a postnatal diagnosis of UPJ obstruction over a 16-yr period. The authors used as indication for surgery the combination of >5% renal function deterioration of the hydronephrotic kidney and worsening of hydronephrosis. They found that 52.2% of patients initially managed conservatively will finally need pyeloplasty. They also found that 88.3% of patients with SFU grades 3-4 and 88.9% of patients with renal

554 european urology 51 (2007) 551 555 function <40% required surgery, whereas only 11.7% and 11.1% of patients, respectively, did well on conservative treatment. In our study we found that, in 75% of patients with diagnosed UPJ obstruction who were managed nonoperatively, when deterioration of RRF began, it was detected in at least two consecutive follow-up studies. In 85.4% of these patients, RRF finally dropped below 40%, and they underwent dismembered pyeloplasty. In other words this finding means that more than three fourths of patients with RRF deterioration on two consecutive followup studies will be candidates for surgery or will require surgery. These results are similar to those published by Chertin et al. [13] when patients with SFU grades 3-4 are discussed. However the advantage of our finding is that these patients will be operated on even before their RRF drops below 40% to preserve as much healthy renal parenchyma and its normal function as possible. In the remaining 14.6% of these patients, RRF never dropped below 40%, and they are still under observation. One may argue that, if our new proposition was followed, these patients would undergo a needless operation. However, these patients are still under observation, and their course remains to be seen. At present, we consider the preservation of healthy parenchyma in 86.4% of patients as the great advantage of our finding. Our postoperative results regarding the course of hydronephrosis and RRF and also the recurrence of UPJ obstruction are extremely satisfactory, and reach those published by Koff [14] and Cartwright [15]. The results that we present are not the conclusions of any new protocol but purely indications after statistical analysis of specific data. A prospective study is definitely needed and is already under preparation. However, it has been shown clearly that there is a statistically significant relationship between the detection of two subsequent drops of RRF and the critical value of 40% of RRF, which the patient will finally reach and will lead us to conversion of the nonoperative management to a surgical treatment. The time between the two critical moments of diagnosis of unilateral UPJ obstruction and possible conversion of nonsurgical to surgical treatment may vary significantly and should not be underestimated, because it may prove harmful for the renal parenchyma. Because many studies report a low percentage of recovery after delayed pyeloplasty, signs that could lead us to earlier surgical intervention are investigated. We consider that, in patients with unilateral UPJ obstruction, our finding that detection of renal function deterioration in two consecutive follow up studies will finally lead to a drop of renal function below the critical value of 40% may prove to be of great predictive value. Our findings do not support routine or immediate surgery in every patient with renal function deterioration in two consecutive follow-up studies. However, in these patients earlier conversion of their treatment from nonoperative to surgical should be considered to increase the possibilities of renal function preservation and recovery. The importance of this new approach to the criteria that suggest conversion from nonoperative management to surgery needs further investigation. References [1] McAleer IM, Kaplan GW. Renal function before and after pyeloplasty: does it improve? J Urol 1999;162: 1041 4. [2] Chertin B, Fridmans A, Knizhnik M, Hadas-Halperin I, Hain D, Farkas A. Does early detection of ureteropelvic junction obstruction improve surgical outcome in terms of renal function? J Urol 1999;162:1037 40. [3] Ransley PG, Dhillon HK, Gordon I, Duffy PG, Dillon MJ, Barratt TM. The postnatal management of hydronephrosis diagnosed by prenatal ultrasound. J Urol 1990;144: 584. [4] Chung YK, Chang PY, Lin CJ, Wang NL, Sheu JC, Shih BF. Conservative treatment of neonatal hydronephrosis. J Formosan Med Assoc 1992;91:75. [5] Koff SA, Campbell K. Nonoperative management of unilateral neonatal hydronephrosis. J Urol 1992;148: 525. [6] DiSandro MJ, Kogan BA. Neonatal management: role for early intervention. Urol Clin N Amer 1998;25:187. [7] Reddy PP, Mandell J. Prenatal diagnosis: therapeutic implications. Urol Clin North Am 1998;25:171. [8] Blyth B, Snyder HM, Duckett JW. Antenatal diagnosis and subsequent management of hydronephrosis. J Urol 1993;149:693. [9] Maizels M, Mitchell B, Kass E, Fernbach SK, Conway JJ. Outcome of nonspecific hydronephrosis in the infant: a report from the registry of the Society for Fetal Urology. J Urol 1994;152:2324. [10] Dejter Jr SW, Eggli DF, Gibbons MD. Delayed management of neonatal hydronephrosis. J Urol 1988;140:1305. [11] Palmer L, Cartwright P, Fernbach S. Surgery versus observation in managing obstructive SFU grade 3-4 unilateral hydronephrosis: a report from the Society of Fetal Urology. Annual Meeting of American Academy of Pediatrics; 1997 Oct 31 Nov 4; New Orleans, Louisiana; 1997.

european urology 51 (2007) 551 555 555 [12] Hafez AT, McLorie G, Bägli D, Khouri A. Analysis of trends on serial ultrasound for high grade neonatal hydronephrosis. J Urol 2002;168:1518 21. [13] Chertin B, Pollack A, Koulikov D, Rabinowitz R, Hain D, Hadas-Halpren I, Farkas A. Conservative treatment of ureteropelvic junction obstruction in children with antenatal diagnosis of hydronephrosis: lessons learned after 16 years of follow-up. Eur Urol 2006;49: 734 9. [14] Koff SA. Neonatal management of unilateral hydronephrosis. Role for delayed intervention. Urol Clin North Am 1998;25:181. [15] Cartwright P, Duckett J. The case for functional assessment of apparent UPJ obstruction. Dialog Pediatr 1991;14:4.