301Archivio Italiano di Urologia e Andrologia 2017; 89, 4 ORIGINAL PAPER A rare cause of acute post renal failure: Retroperitoneal fibrosis Kamil Gokhan Seker, Mithat Eksi, Yunus Colakoglu, Mustafa Gürkan Yenice, Fatih Gokhan Akbay, Volkan Tugcu, Abdulmuttalip Simsek Bakirkoy Sadi Konuk Research and Training Hospital, Department of Urology, Istanbul, Turkey. Retroperitoneal fibrosis is an inflammatory process which may cause acute renal failure. In patients who admitted to emergency services with obstruc- tive uropathy, retroperitoneal fibrosis should be considered in the differential diagnosis. We present our ten cases who admit- ted to emergency department with obstructive acute renal fail- ure related to retroperitoneal fibrosis. KEY WORDS: Retroperitoneal fibrosis; Postrenal acute renal failure; Obstructive uropathy. Submitted 18 July 2017; Accepted 23 September 2017 Summary No conflict of interest declared. my tube (PNT). Further medical treatments were consult- ed with nephrology department. Demographic data, phys- ical examination findings, laboratory data, radiological examinations, treatments modalities and follow-up data were retrospectively analyzed. Patients were followed up with 3-monthly laboratory tests and radiological observations. At the end of the one-year follow-up period, the patients were evaluated by comparing their initial and recent CT. Statistical analysis was performed using SPSS (IBM Statistical Package for the Social Sciences, New York, USA) 17.0 program. RESULTS The mean age was 65.2 ± 20.2 years. Male/female ratio was 8/2. The demographic data of the patients were shown in Table 1. The side pain was the most frequent presenting symptom. CT scan revealed increase in retroperitoneal soft tissue density at the periaortic and periureteral area in 8 patients with addition perinephrit- ic area in 2 patients. Unilateral renal atrophy was observed in two patients as a result of fibrosis. After the initial intervention, medical therapy was applied. Corticostreoids (CS) were used as a first line ther- apy for all patients. The antihypertensive treatment of the patient who admitted with beta-blocker toxicity was changed to another antihypertensive drug. For mainte- nance therapy, additionally to corticosteroids; seven patients were treated with azathioprine (AZA) and one DOI: 10.4081/aiua.2017.4.301 INTRODUCTION Retroperitoneal fibrosis (RF) is a clinical entity that causes inflammatory and fibrotic reactions in retroperitoneal organs and produces obstruction in ureters. It was first described by Albarran in 1905 and in 1948, the idio- pathic form was described as Ormond's disease (1, 2). Recently, an international consensus has begun to use the term "IgG4-related disease (IgG4-RD)" which defines several organ-related disorders (3). The incidence is about 0.1-1.3/100.000. RF generally seen over 50 years of age and 3 times more often in men (4, 5). Two-thirds of RF cases are idiopathic. Other causes include such as drugs, malignancies, infectious processes, radiotherapy, trauma and previous abdominal surgery (6). RF may cause the symptoms of hydronephrosis and ure- mia resulting from the external pressure of the retroperi- toneum and the deterioration of the ureteral passage. In this study, we aimed to present the diagnosis and treat- ment management of ten patients who were admitted to the emergency department (ED) with postrenal acute renal failure (ARF). MATERIALS AND METHODS We retrospectively analyzed the records of patients diag- nosed with postrenal ARF caused by RF in our clinic between 2013 and 2016. The RF was diagnosed accord- ing to the computed tomography (CT) images taken at the ED. Biopsy was not performed due to absence of atypical appearance and no need of surgical intervention during follow-up. Urinary system decompression was made by placement of double J (DJ) stent or percutaneous nephrosto- Table 1. Demographic datas and serum creatinine levels during follow up. No. total patients 10 Male/female (n) 8/2 Age mean ± SD (year) 65.2 ± 20.2 Idiopathic/secondary 9/1 Serum creatinine levels (mg/dl) Mean ± SD Initial 5.7 ± 3.5 After urinary system decompression 1.1 ± 0.2 After medical therapy 0.9 ± 0.1 Simsek5_Stesura Seveso 03/01/18 12:24 Pagina 301 Archivio Italiano di Urologia e Andrologia 2017; 89, 4 K. Gokhan Seker, M. Eksi, Y. Colakoglu, M. Gürkan Yenice, F. Gokhan Akbay, V. Tugcu, A. Simsek 302 patient was treated with tamoxifen (TMX). Total regres- sion and regression were observed in two and five patients respectively. The mean initial serum creatinine level was 5.7 ± 3.5 mg/dl. After the first intervention by decompressing urinary system, mean serum creatinine level regressed to 1.1 ± 0.2 mg/dl. At the end of medical therapy, the mean serum creatinine level was 0.9 ± 0.1 mg/dl. Demographic data, presenting symptoms, lab- oratory and radiological findings, follow-up times and treatment data are summarized in Table 2. Patient's radiological images were shown in Figures 1-5. DISCUSSION Two-thirds of RF patients are idiopathic and the remaining are secondary to causes including infection, trauma, previ- ous surgery and malignancy. In the literature, presence of Figure 3. Significant regression of the hydronephrosis and soft tissue density after steroid therapy. Figure 5. Bilateral medial retraction due to periureteral fibrosis. Figure 1. A. Bilateral hydroureteronephrosis due to periureteral fibrosis. B. Soft tissue density that extends from paraaortic area to caudal. Figure 4. Left atrophic kidney. Grade 2 hydronephrosis on the right kidney. Soft tissue enlargement and calcification extending around the large vessels and extending from the periureteral area to the pelvic region. Figure 2. A. Right DJ stent and left percutaneous nephrostomy tube. B. Bilateral DJ stents. Table 2. Demographic datas and serum creatinine levels during follow up. Patient No. Gender Symptom Urinary system decompression Medical therapy Follow-up (month) Status 1 M Side pain, weakness PNT + D-J CS + AZA 42 Full regression 2 F Hypotension D-J CS + TMX 27 Regression 3 M Bilateral side pain D-J CS + AZA 12 Stable 4 M Bilateral side pain PNT + DJ CS + AZA 12 Regression 5 F Side pain, weakness PNT CS + AZA 18 Regression 6 M Bilateral side pain PNT + DJ CS + AZA 24 Stable 7 M Bilateral side pain PNT CS 18 Regression 8 M Fever, weakness PNT + DJ CS + AZA 30 Full regression 9 M Fever, side pain PNT CS + AZA 12 Stable 10 M Abdominal pain PNT + DJ CS 18 Regression Simsek5_Stesura Seveso 03/01/18 12:24 Pagina 302 retroperitoneal fibrosis following high doses of beta-block- ers usage have been reported (7). In this study, we found that in 9 patients RF was idiopathic (90%) and in one patient (10%) it was related to drug overdose. Diagnosis of idiopathic RF is generally delayed due to atypical symp- toms of the disease and patients may be diagnosed with postrenal ARF in ED. Urologically, the most frequent and most serious complication of the disease is ARF due to bilateral ureteral obstruction (8, 9). In two large studies in the literature, pain was the most common presenting symptom, and additionally undefined symptoms such as fatigue, weakness, myalgia were observed (4, 10). Renal failure due to bilateral ureteral obstruction is seen in 42- 95% of the cases. Patients may also be referred to the urol- ogy clinic with scrotal edema, hydrocele or varicocele due to the involvement of the gonadal vessels (11). Erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), which are non-specific inflammation markers, are laboratory parameters used for diagnosis and follow-up (12, 13). In our study, side pain and uremic symptoms due to bilat- eral ureteral involvement were observed in 8 patients. The other two patients had different symptoms: one patient had hypotension and the other had fever and weakness. Initial inflammation markers were found to be high in all patients. Non-contrast abdominal CT and magnetic resonance imaging (MRI) provide limited information in the diag- nosis of the disease (14). In non-contrast CT, RF usually appears as an increase in soft tissue density, surrounding the abdominal aorta and iliac vessels, and usually sur- rounding the ureter and inferior vena cava (15). Positron emission tomography (PET-CT) provides more compre- hensive clinical information as it includes whole-body metabolic studies. It shows active inflammation and post-treatment relapses, and reveals occult malignancies (16, 17). In our cases, we used non-contrast CT in con- sideration of the risk of contrast nephropathy due to the presence of ARF. During follow-up, if the creatinine level was in the normal range; contrast-enhanced MRI and CT examinations were performed. In patients with radiologically diagnosed RF, which typi- cally have mild symptoms and considered as a benign disease, medical treatment can be started without biopsy. Biopsy is usually preferred in cases of partial response or failure to the medical therapy (18). We did not perform biopsy because no progression was observed in any of our patients and CT had no atypical appearance. The aim of the treatment is to relieve the fibro-inflam- matory reaction, in order to reduce ureteral obstruction and prevent recurrence (19). After the urinary system decompression by PNT or DJ stent, there are two options as first line medical treatment (20). CS alone or CS with tamoxifen (TMX) can be used as first line therapy (21). The second step is the addition of drugs such as immunosuppressive azathioprine (AZA), mycophenol mofetil, rituximab, bortezomip, cyclophosphamide, cyclo spo - rine in the course of treatment or relapse (22). In the case of failure to respond to medical treatment, the treatment approach is adjuvant CS therapy after surgical obstruction is reduced by ureterolysis. Secondary RF is treated for the underlying cause (8). Urinary system decompression was achieved by DJ stent in two of our patients, by PNT in three patients and by both DJ stent and PNT placement in five other patients. In two of the 5 patients treated by both DJ and PNT, a DJ stent was inserted firstly but a PNT had to be inserted subsequent- ly because of the lack of adequate radiological and clini- cal regression. After initial treatment, CS was initially administered with additionally AZA and TMX. In a randomized controlled trial, after achieving remis- sion with high-dose prednisolone as an induction thera- py, patients were divided into 2 groups and followed up with CS (prednisone) or TMX mono therapy for 8 months. In this study, maintenance therapy with CS was associated with lower relapse rates, with a higher side effect profile than TMX group (21). Van der Bilt et al. reported that CSs were superior to TMX for induction therapy, but the rate of recurrence was lower in patients treated with TMX for the maintenance therapy (23). Surgical treatment may be applied in case of non response to medical treatment or interruption of medical treatment due to side effects. Open, laparoscopic and robotic ureterolysis can be performed as a salvage procedure in case of failure with medical therapy (24). In our manage- ment, all patients were treated by consecutive three line therapy, initial decompression and achieving of improved renal function, induction with corticosteroids and mainte- nance therapy with CS or addition of AZA or TMX. With the success of this third line therapy, surgical treatment was not performed during the follow-up period. Our study has some limitations such as the small sample size and as the retrospective design. In addition, there were no long-term follow-up results of patients. CONCLUSIONS Retroperitoneal fibrosis should be kept in mind in patients who admitted to the ED with hydroureteronephrosis and uremic symptoms. After the initial treatment with urinary system decompression, remission can be achieved with appropriate medical treatments. REFERENCES 1. Albarran J. Retention renale par periureterite: Liberation externe uretere. Ass Fr Urol. 1905; 9:511. 2. Ormond JK. 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Outcome in patients with idiopathic retroperitoneal fibrosis treated with corticosteroid or tamoxifen monotherapy. Clin Kidney J. 2016; 9:184-91. 24. Omer A, Esen T Retroperitoneal fibroziste cerrahi tedavi: nelere dikkat edilmeli? Endoüroloji Bülteni 2013; 6:10-15. Correspondence Kamil Gokhan Seker, MD Mithat Eksi, MD Yunus Colakoglu, MD Mustafa Gürkan Yenice, MD Fatih Gokhan Akbay, MD Volkan Tugcu, MD Abdulmuttalip Simsek, MD simsek76@yahoo.com Bakirkoy Sadi Konuk Research and Training Hospital, Department of Urology, Zuhuratbaba, Tevfik Saglam Cad. NO:11 Bakirkoy, Istanbul, Turkey Simsek5_Stesura Seveso 03/01/18 12:24 Pagina 304