11Archivio Italiano di Urologia e Andrologia 2019; 91, 1 ORIGINAL PAPER Factors associated with urinoma accompanied by ureteral calculi Ercan Öğreden 1, Ural Oğuz 1, Mehmet Karadayı 1, Erhan Demirelli 1, Alptekin Tosun 2, Mücahit Günaydın 3 1 Giresun University, Faculty of Medicine, Department of Urology, Giresun, Turkey; 2 Giresun University, Faculty of Medicine, Department of Radiology, Giresun, Turkey; 3 Giresun University, Faculty of Medicine, Department of Emergency Medicine, Giresun, Turkey. Objective: Urinoma is a rare entity and mainly occurs due to acute obstruction such as ureteral stone. We aimed to demonstrate factors associated with urinoma accompanied by ureteral calculi. Material and methods: Data of 550 patients who were diag- nosed with ureteral stone by computed tomography (CT) were analyzed retrospectively. In 20 patients perirenal urinoma was associated with ureteral calculi (group I), whereas in other 530 patients no urinoma was detected (group II). Gender, age, size, side and localization of the stone, hydronephrosis, fever, sepsis, urinary tract infections (UTIs), hematuria, serum creatinine, blood urea nitrogen (BUN), white blood cell (WBC), C-reactive protein (CRP), presence of diabetes mellitus (DM), hyperten- sion (HT) and cronic kidney disease (CKD) of the two groups were compared. Results: The average age of the patients were 46.2 (20-71) and 44.9 (10-82) years in group I and group II, respectively (p > 0.05). According to our results leukocytosis, microscopic and macroscopic hematuria, UTIs, increase of serum creatinine, BUN and CRP, diagnosis of DM and HT were significantly associated with urinoma (p < 0.05). In addition, patients with distal ureteral stones are more prone to urinoma (p = 0.001). An interesting finding of the study was that the stone size in group I (median 5 mm [range 3-8]) was significantly smaller than in group II (9.3 mm [4-25]; p = 0.001). Conclusions: Small stone size, distal localisation of the stone in ureter, leukocytosis, hematuria, UTIs, increase of serum creati- nine, BUN and CRP, presence of DM and HT are associated with perirenal urinoma. KEY WORDS: Computerized tomography; Factors associated with urinoma; Prevalence; Ureteral calculi; Urinoma. Submitted 26 August 2018; Accepted 11 October 2018 Summary No conflict of interest declared. noma (2). When the intraluminal pressure exceeds 35 cm/H2O, rupture develops from the fornix, which is the weakest part of the collecting system, resulting in urino- ma. In this case, the urine is first spread to the subcap- sular area, then to the perirenal region and the retroperi- toneal area (3). Urinoma leads to local irritation, inflam- matory side effects, fever, malaise, sepsis, acute abdomen and deterioration of general condition (4). Computed Tomography (CT) is adequate for definitive diagnosis of urinoma. At CT, fluid collection around the kidney and imaging of the stone within the ureter is sufficient for the diagnosis of spontaneous urinoma. It may also document the contrast extravasation from the collecting system and determine the location of the rupture (5, 6). Ureterorenoscopic stone surgery and ureteral stent place- ment are recommended in the current treatment of spon- taneous urinoma (7). There is no specific finding of uri- noma and this may lead to delayed diagnosis and treat- ment causing increased morbidity and mortality in patients who have admitted to emergency clinics with colic pain. In this study, it was aimed to identify the risk factors for urinoma, to define parameters that would facilitate the diagnosis and help in choosing appropriate treatment, and to discuss the topic under light of current literature. MATERIAL AND METHODS Between May 2010 and March 2018, 11,000 patients were diagnosed with ureteral stone at our center. The diagnosis of stone was made by direct X-ray, intra- venous pyelogram (IVP), ultrasonography (USG), unen- hanced CT and contrast-enhanced CT. The data of 2100 patients who underwent ureterorenoscopy (URS) due to ureteral stone were retrospectively reviewed. Electronic and conventional medical records, including demo- graphic information, laboratory data, electronic notes, operative reports and radiological reports, were reviewed for each patient. A total of 550 patients who were diag- nosed with ureteral stone by CT and whose data were complete were included in the study. Patients with kidney trauma and patients with a history of kidney surgery were excluded from the study. Vital findings were also queried from the medical records and DOI: 10.4081/aiua.2019.1.11 INTRODUCTION Urinoma is defined as an extravasated urine collection with surrounded fibrous capsule. Urinary stones, surgi- cal ligation of ureters, tumors, posterior urethral valve (PUV) and blunt or penetrating traumas are involved in the etiology of urinoma (1). Spontaneous urinoma is rare and ureteral stones are among the most common causes of spontaneous urinoma. High hydrostatic pressure applied on the ureter wall by the impacted ureteral stone and formation of micro-tears in the mucosa during stone passage play an important role in the mechanism of uri- Ogreden_Stesura Seveso 25/03/19 17:13 Pagina 11 Archivio Italiano di Urologia e Andrologia 2019; 91, 1 E. Öğreden, U. Oğuz, M. Karadayı, E. Demirelli, A. Tosun, M. Günaydın 12 presence of UTIs, fever and urosepsis were recorded. Patients' age, gender, stone localization, presence of hydronephrosis, fever, sepsis, UTIs, microscopic and macroscopic hematuria, serum creatinine, BUN, WBC and CRP values were evaluated. Chronic diseases such as diabetes mellitus (DM), hypertension (HT) and chronic kid- ney disease (CKD) were recorded. Urine cultures were obtained from patients with asymptomatic bacteriuria and appropriate empirical treatment was initiated. Symptomatic UTIs criteria included fever, costovertebral angle sensitivity, pyuria (≥ 10 white blood cells per high- power field), and positive urine culture [≥ 105 colony- forming units (CFU) of uropathogen/mL]. Findings of urosepsis included at least 2 signs of SIRS (Systemic Inflammatory Response Syndrome) in the presence of infection (Fever > 38°C or < 36°C, heart rate > 90 beats/min, respiratory rate > 20/min or PaCO2 < 32 mm/Hg, WBC > 12,000/mm3 or < 4.000/mm3). Appropriate antibiotic therapy was started according to results of antibiotic susceptibility testing in patients who were diagnosed with urosepsis. Patients were classified as group I (n = 20; 3,6%) if were diagnosed with spontaneous urinoma secondary to ureteral stone and group II (n = 530; 96,4%), if without urinoma (Figure 1). Patients diagnosed with urinoma and ureteral stone were treated with ureteroscopy (URS) and lithotripsy and ureteral double J stent placement. The stents were removed after 4 weeks as treatment was completed. Both groups were compared in terms of gender, age, stone size and stone localization, fever, sepsis, UTIs, hematuria, serum cratinine, BUN, WBC, CKD values as well as pres- ence of DM, HT and CKD. All procedures performed in studies involving human participants were in accordance with the ethical stan- dards of the institutional and/or national research com- mittee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Statistical Analysis The data obtained in this study were analyzed with the SPSS 20 (IBM SPSS Statistics; Armonk, NY, USA) package program. Results are presented as frequency and percent- age (%). The abnormal distribution of data from each group was confirmed with the Kolmogorov-Smirnov test, thus statistical comparisons were performed using Mann Whitney-U Test. Chi-square test was used to examine the dependency between the groups. A P value less than 0.05 was considered statistically significant. RESULTS In this study, we found urinoma in 20 (0.2%) of 11000 patients diagnosed with ureteral stones in our clinic. The mean age of the patients was 46.2 (20-71) years in group I and 44.91 (10-82) years in group II (p > 0.005). Gender distributions of the patients were 16 (80%) male, 4 (20%) female in group I and 339 (63.96%) male and 191 (36.04%) women in group II (p > 0.005). Gender distributions of the patients were similar in both groups. Upper ureter was considered as the segment from renal pelvis to the upper border of the sacrum, middle ureter is as the segment from the upper to the lower border of the sacrum, and lower ureter as the segment which extends from lower border of the sacrum to the bladder. Proximal ureteral stones were not observed in group I, while they were present in 345 (65.1%) patients in group II. Middle ureteral stones were found in 5 (25%) patients in group I and 126 (23.8%) patients in group II. Distal ureteral stone distributions in group I and group II were 15 (75%) and 59 (11.1%), respectively (p = 0.001). The difference of distribution of stone localizations between the groups was statistically signifi- cant. Pyuria was found in 5 (25%) patients in group I and in 47 (8.9%) patients in group II (p = 0.032). Microscopic hematuria was detected in 16 patients (80%) in group I and in 42 (7.9%) patients in group II (p = 0.001). Macroscopic hematuria was posi- tive in 9 (45%) and 42 (7.9%) patients, respectively (p = 0.001). Fever was found in 12 (60%) patients in group I and in 30 (5.7%) patients in group II (p = 0.001) and UTIs were detected in Figure 1. The image of spontaneous urinoma. A: Perirenal urinary leak; B: Retroperitoneal urinary leakage; C: Stones of millimetric size in the distal ureter; D: Sagittal section view of urinoma and distal ureteral stone. A. B. C. D. Ogreden_Stesura Seveso 25/03/19 17:13 Pagina 12 5 (25%) and 24 (4.5%), respectively (p = 0.003). The difference between the two groups was statistically significant in terms of pyuria, hematuria, fever and UTIs. Urosepsis was observed in 2 (10%) patients in group I and in 10 (1.9%) patients group II, however the difference was not statistically significant (p > 0.05). CRP was higher in 14 (70%) patients in group I and in 22 (4.1%) patients in group II (p = 0.001). WBC was high in 10 (50%) patients in group I and in 24 patients (4.53%) in group II (p = 0.001). BUN was high in 7 (35%) patients in group I and in 38 (7.2%) patients in group II (p = 0.001). Creatinine was high in 10 (50%) patients in group I than and in 25 (4.7%) patients in group II (p = 0.001). DM was detected in 7 (35%) and 23 (4.3%) patients in group I and group II, respectively (p = 0.001). CKD was not seen in any patients in group I, where- as 7 (1.3%) patients had CKD in group II (p > 0.05). However, this difference was not statistically significant. HT was found in 10 (50%) patients in group I and in 24 (4.5%) patients in group II (p = 0.001). The difference between the two groups in terms of CRP, WBC, BUN and high serum creatinine values and presence of chronic dis- eases such as DM and HT was statistically significant. There was no statistically significant difference between the patient groups in term of presence of CKD (Table 1). The mean stone size was 5 (3- 8) mm in group I and 9.3 (4- 25) mm in group II (p = 0.001). The difference in stone size between the two groups was statistically significant (Table 2). According to logistic regression analysis results, 1 mm increase in stone length reduced the risk for urinoma 2.022-fold. The presence of microscopic hematuria and high serum CRP 13Archivio Italiano di Urologia e Andrologia 2019; 91, 1 Urinoma and ureteral calculi Table 1. Factors associated with urinoma accompanied by ureteral calculi. Mann Whitney U Test n Mean Median Min Max SD Rank Avarage z p Age Group I 20 46.2 45 20 71 13.88 274.89 -0.465 0.642 Group II 530 44.9 44 10 82 13.95 291.73 Total 550 45 44 10 82 13.94 Stone size/mm Group I 20 5 4 3 8 1.78 283.07 -5.785 0.001 Group II 530 9.3 9 4 25 3.56 74.9 Total 550 9.1 8 3 25 3.6 Table 2. The differences between groups with/without urinoma in terms of age and stone size. Group I Group II Total Chi Square Test n % n % n % Chi Square p Gender Male 16 80 339 64.0 355 64.6 1.522 0.217 Female 4 20 191 36.0 195 35.4 Total 20 100 530 100 550 100 Localization Proximal 0 0 345 65.1 345 62.7 * 0.001 Middle 5 25 126 23.8 131 23.8 Distal 15 75 59 11.1 74 13.5 Total 20 100 530 100 550 100 Pyuria Absent 15 75 483 91.1 498 90.5 Fisher's exact 0.032 Exist 5 25 47 8.9 52 9.5 Total 20 100 530 100 550 100 Microscopik hematuria Absent 4 20 488 92.1 492 89.5 Fisher's exact 0.001 Exist 16 80 42 7.9 58 10.5 Total 20 100 530 100 550 100 Gross hematuria Absent 11 55 488 92.1 499 90.7 Fisher's exact 0.001 Exist 9 45 42 7.9 51 9.3 Total 20 100 530 100 550 100 Fever Absent 8 40 500 94.3 508 92.4 Fisher's exact 0.001 Exist 12 60 30 5.7 42 7.6 Total 20 100 530 100 550 100 UTI Absent 15 75 506 95.5 521 94.7 Fisher's exact 0.003 Exist 5 25 24 4.5 29 5.3 Total 20 100 530 100 550 100 Urosepsis Absent 18 90 520 98.1 538 97.8 Fisher's exact 0.067 Exist 2 10 10 1.9 12 2.2 Total 20 100 530 100 550 100 CRP Normal 6 30 508 95.9 514 93.5 Fisher's exact 0.001 High 14 70 22 4.1 36 6.5 WBC Normal 10 50 506 95.5 516 93.8 Fisher's exact 0.001 High 10 50 24 4.5 34 6.2 Total 20 100 530 100 550 100 BUN Normal 13 65 492 92.8 505 91.8 Fisher's exact 0.001 High 7 35 38 7.2 45 8.2 Total 20 100 530 100 550 100 Creatinin Normal 10 50 505 95.3 515 93.6 Fisher's exact 0.001 High 10 50 25 4.7 35 6.5 Total 20 100 530 100 550 100 DM Absent 13 65 507 95.7 520 94.6 Fisher's exact 0.001 Exist 7 35 23 4.3 30 5.5 Total 20 100 530 100 550 100 CKD Absent 20 100 523 98.7 543 98.7 Fisher's exact 1 Exist 0 0 7 1.3 7 1.3 Total 20 100 530 100 550 100 HT Absent 10 50 506 95.5 516 93.8 Fisher's exact 0.001 Exist 10 50 24 4.5 34 6.2 Total 20 100 530 100 550 100 UTI: Urinary tract infection; CRP: C-reactive protein; WBC: White blood cell; BUN: Blood urea nitrogen, DM: Diyabetes Mellitus; CKD: Chronic kidney disease; HT: Hypertension. Ogreden_Stesura Seveso 25/03/19 17:13 Pagina 13 Archivio Italiano di Urologia e Andrologia 2019; 91, 1 E. Öğreden, U. Oğuz, M. Karadayı, E. Demirelli, A. Tosun, M. Günaydın 14 level were both detected high in patients with urinoma. Logistic regression analysis revealed that distal localiza- tion of the stones also increased the risk for urinoma 3.806-fold. DISCUSSION As a result of the collecting system disruption at any level from calyces to urethra, the urine that extravasates the urinary system is called urinoma. Urinomas may some- times, although rare, occur spontaneously. The most common etiological cause of spontaneous urinomas is the ureteral stones (8). Hydronephrosis, UTIs, and increased pressure due to obstruction, provide a basis for rupture. The intraluminal pressure increases on the col- lecting system as a result of obstruction elsewhere in the system due to a stone and extravasation occurs at the calyceal fornix, the weakest part of the collecting system. The kidneys have mechanisms to protect themselves against increasing pressure in the collecting system. These mechanisms include pyelo-sinus, pyelo-venous, and pyelo-lymphatic backflow. An increase of more than 35 cmH2O in intrapelvic pressure results in the failure of these mechanisms and leads to forniceal rupture (9). Furthermore, small-sized ureteral stones cause micro- tears during spontaneous passage; this in turn plays a facilitating role in the rupture of collecting system mucosa, resulting in extravasation of urine (10, 11). In their latest study, Gershman et al. (12) reported that 75.7% of distal ureteral stones cause primary urinoma. In the same study, the mean stone size was 4.09 mm with stone size decreasing significantly from proximal ureter- al to distal ureteral locations, and urinoma incidence was found to be more frequent in distal ureteral stones. In our present study, 75% of the patients with urinoma had distal ureteral stones and this finding was consistent with the literature. We found that the mean stone size was 5 mm and a 1 mm increase in stone length reduced the uri- noma risk of 2.022 fold, whereas the distal localization of stones increased the urinoma risk of 3.806 fold. Apart from obstruction and stasis caused by the stone in the ureteral lumen, in addition UTIs constitute a facili- tating factor for development of the urinoma. Spontaneous urinomas that develop due to an ureteral stone may cause side-pain, reno-ureteral pain, reno- abdominal pain, as well as vasovagal nausea and vomit- ing. Ureterovesical junction (UVJ) stones and UTIs can cause urinary urgency, fever, abdominal pain and pain in genital organs. Besides these symptoms, urinomas can result in serious complications. Possible complications include hydronephrosis, paralytic ileus and acute abdomen, electrolyte imbalances, abscess formation, sepsis, and chronic renal failure in delayed cases (11). Gershman et al. (12) reported a UTIs ratio of 5.2% in a retrospective study. The rate of UTIs in our study was 5.3% in accordance with previous reports. UTIs trigger the collecting system rupture and result in the accumu- lation of infected urine in the retroperitoneal space. This picture sets a ground for urosepsis and retroperi- toneal abscess formation in delayed cases (13). In our study, we found that the rate of patients diagnosed with urosepsis was 2.2%, a rate not statistically different from that observed in absence of urinoma. Furthermore, retroperitoneal abscess was not observed in any of the patients who were diagnosed with urosepsis. We think that early diagnosis of urinoma along with early surgical and medical treatment were effective in this respect. Sterile urine in contact with the retroperitoneum can trigger an inflammatory response, whereas infected urine may lead to acute abdomen, retroperitoneal abscess for- mation and retroperitoneal fibrosis in later stages. In patients with urinary infection and pyuria, these com- plications may be more aggressive and may result in a clinical picture with progression to sepsis by disturbing the general condition in the patients. In many case reports published to this time, it has been reported that urinary infection, pyuria, hematuria and sepsis were present in patients who had diagnosis of urinoma in the emergency room. Blood tests of these cases revealed high WBC, BUN and elevated serum creatinine levels (14). In our study pyuria, hematuria, fever, UTIs and urosep- sis were significantly common in the patients with uri- noma and CRP and WBC values were also high in these patients. Although urinoma has been reported to play a protective role in renal function, it has been shown an impaired kidney function in several recent case reports. Heikkila et al. (15) demonstrated that urinoma affects renal function and leads to progressive renal damage in 25% of patients. In our study, BUN and plasma creatinine values were sig- nificantly higher in the cases with urinoma but CKD did not develop in our patients, probably because of early treatment and early surgical intervention. HT, DM and CKD are common comorbid diseases. Comorbidities are important for the patient in terms of bearing an additional disease to the existing disease and facing an increased morbidity. Especially, the suppression of the current clinical picture by these comorbid diseases may delay the diagnosis and increase the complication rates. Many case reports published in the literature have reported that diagnosis of urinoma might be delayed with accompanied CKD and DM and as a result, the complication rates were increased (11, 15). In our pres- ent study, the DM rate was 35% vs 4.3% and the HT rate was 50% vs 4.5% in patients with and without urinoma (p < 0.05). CKD was not seen in any of the patients who had been diagnosed with urinoma. Spontaneous urinoma is a rare disease and most com- monly caused by ureteral stones. Until recently, literature about urinoma mainly consisted of case reports only and there was no study on prevalence of urinoma. However, the development of imaging modalities, availability of spiral CT and the widespread use of contrast agents in the clinical settings have led to a relative increase in the number of diagnosed spontaneous urinomas (16, 17). In fact, in the present study, we found urinoma in 0.2% of patients diagnosed with ureteral stones. CONCLUSIONS Infection related parameters such as CRP and WBC ele- vation, pyuria, hematuria, fever, and high creatinine lev- els were found to be higher in patients with ureteral stones and urinoma. Interestingly, urinomas were more Ogreden_Stesura Seveso 25/03/19 17:13 Pagina 14 common in the smaller-sized and distally ureter-located stones. In addition, chronic diseases such as HT and DM have attracted attention as factors that increase urinoma risk in patients with ureteral stones. REFERENCES 1. Nouira Y, Ben Younes A, Rekik H, et al. Spontaneous perirenal urinoma during nephritic colic. Ann Urol (Paris) 2000; 34:156-7. 2. Ay D, Yencilek E, Celikmen MF, et al. Spontaneous rupture of ureter: an unusual cause of acute abdominal pain. Am J Emerg Med. 2012, 30:1-2. 3. Miller NL, Lingeman JE. Management of kidney stones. BMJ. 2007; 334: 468-72. 4. Patil KK, Wilcox DT, Samuel M, et al. Management of urinary extravasation in 18 boys with posterior urethral valves. J Urol. 2003; 169:1508-11. 5. Chen GH, Hsiao PJ, Chang YH, et al. Spontaneous ureteral rup- ture and review of the literature. Am J Emerg Med. 2014; 32:772-4. 6. Pampana E, Altobelli S, Morini M, et al. Spontaneous ureteral rupture diagnosis and treatment. Case Rep Radiol. 2013; 2013:851859. 7. Stravodimos K, Adamakis I, Koutalellis G, et al. Spontaneous perforation of the ureter: clinical presentation and endourologic management. J Endourol. 2008; 22:479-84. 8. Jeon CH, Kang JH, Min JH, et al. Spontaneous Ureteropelvic Junction Rupture Caused by a Small Distal Ureteral Calculus. Chin Med J (Engl) 2015; 128:3118-19. 9. Georgieva M, Thieme M, Pernice W, et al. Urinary ascites and perirenal urinoma-a renoprotective "Complication" of posterior ure- thral valves. Aktuelle Urol. 2003; 34:410-12. 10. Ferri E, Casoni GL, Morabito G, et al. Rupture of the renal pelvis complicating a renal colic: report of a case. Am J Emerg Med. 2006; 24:383-5. 11. Gayer G, Zissin R, Apter S, et al. Urinomas caused by ureteral injuries: CT appearance. Abdom Imaging. 2002; 27:88-92. 12. Gershman B, Kulkarni N, Sahani DV, et al. Causes of renal for- niceal rupture. BJU Int. 2011; 108:1909-12. 13. Titton RL, Gervais DA, Hahn PF, et al. Urine leaks and urino- mas: diagnosis and imaging-guided intervention. Radiographics. 2003; 23:1133-47. 14. Pace K, Spiteri K, German K. Spontaneous proximal ureteric rupture secondary to ureterolithiasis. J Surg Case Rep. 2017, 2016. 15. Heikkilä J, Taskinen S, Rintala R. Urinomas associated with pos- terior urethral valves. J Urol. 2008; 180:1476-78. 16. Murawski M, Gołebiewski A, Komasara L, et al. Rupture of the normal renal pelvis after blunt abdominal trauma. J Pediatr Surg. 2008; 43:e31-33. 17. Ashebu SD, Elshebiny YH, Dahniya MH. Spontaneous rupture of the renal pelvis. Australas Radiol. 2000; 44:125-27. 15Archivio Italiano di Urologia e Andrologia 2019; 91, 1 Urinoma and ureteral calculi Correspondence Ercan Öğreden, MD (Corresponding Author) ercanogreden@gmail.com Ural Oğuz, MD Mehmet Karadayı, MD Erhan Demirelli, MD Giresun University, Faculty of Medicine, Department of Urology, Giresun (Turkey) Alptekin Tosun, MD Giresun University, Faculty of Medicine, Department of Radiology, Giresun (Turkey) Mücahit Günaydın, MD Giresun University, Faculty of Medicine, Department of Emergency Medicine, Giresun (Turkey) Ogreden_Stesura Seveso 25/03/19 17:13 Pagina 15