Retroperitoneal fibrosis presenting as acute renal failure
Robert F Reilly Jr About the author
Correspondence Dallas Veterans Affairs Medical Center, 111G1/ Room 3A-308, 4500 South Lancaster Road, Dallas, TX 75216-7167, USA
Email robert.reilly2@med.va.gov
Summary
Background A 60-year-old man with a history of atherosclerotic disease of the carotid and coronary vasculature presented with lower back pain and acute renal failure. Imaging studies revealed bilateral ureteral obstruction by a large retroperitoneal mass.
Investigations Physical examination, urine and blood analysis, catheterization, radiography of the chest, abdominal and pelvic CT, magnetic resonance angiography, renal ultrasound and biopsy of mass.
Diagnosis Retroperitoneal fibrosis.
Management Ureteral stenting, laparoscopic ureterolysis, and immunosuppressive therapy with prednisone and mycophenolate mofetil.
The case
A 60-year-old white man presented to the emergency department with a 10-day history of lower back pain radiating to the lower abdomen and suprapubic region. He also noted fatigue and mild nausea, and as a result had been unable to take his blood pressure medication over the preceding several days. There was no history of fever or weight loss. His past medical history was remarkable for coronary artery bypass surgery, severe right carotid artery stenosis, hypertension diagnosed 5–7 years previously, gout, and an elevated serum cholesterol concentration. The patient had stopped smoking 20 years previously. Current medications included simvastatin 40 mg per day, omeprazole 20 mg per day, metoprolol 100 mg twice per day, lisinopril 40 mg per day, furosemide 20 mg twice per day, clopidogrel 75 mg per day, and aspirin 325 mg per day. There was no known history of methysergide ingestion or asbestos exposure. Blood pressure was 213/113 mmHg upon admission. Physical examination revealed a right carotid BRUIT, midline sternotomy scar, II/VI systolic murmur, and a scar on the right leg from venous harvesting for bypass surgery. Abdominal examination was unremarkable. Rectal examination showed that the prostate was not enlarged; no nodules were palpated.
Laboratory evaluation revealed a serum sodium concentration of 138 mmol/l, serum chloride of 98 mmol/l, serum potassium of 5.9 mmol/l, and serum bicarbonate of 14.8 mmol/l. Blood urea nitrogen and serum creatinine concentrations were 35.3 mmol/l and 1158 
mol/l, respectively. The hematocrit was 31.1% and the hemoglobin concentration 98 g/l. The serum total and LDL cholesterol concentrations were 5.1 mmol/l and 2.3 mmol/l, respectively. C-reactive protein concentration was 5.28 mg/dl and the sedimentation rate was 56 mm/h. Urinalysis was unremarkable. Insertion of a Foley catheter revealed that 100 ml of urine was present in the bladder. Rate of subsequent urine flow remained low.
Radiography of the chest detected a moderate left pleural effusion. A CT scan of the abdomen and pelvis without contrast showed bilateral pleural effusions, greater in the left pleural space than the right pleural space, and a retroperitoneal soft tissue mass extending from the renal arteries to the presacral space that completely and circumferentially surrounded the aorta and inferior vena cava (Figure 1). The CT scan also revealed mild to moderate bilateral hydronephrosis, and that the ureters were relatively nondilated in the pelvis. Calcification was noted in the aorta, and in the iliac and femoral arteries. Magnetic resonance angiography (MRA) showed a SACCULAR aneurysm in the distal abdominal aorta that was 2.7 cm in diameter, with a penetrating ulcer. Subsequent CT scans with and without contrast detected a 2.2 cm 
2.8 cm infrarenal aneurysm. Abdominal ultrasound did not detect an aneurysm. Measurement of the CT scans indicated that the retroperitoneal mass was 5.5 cm in the anteroposterior dimension and 10.1 cm in the transverse dimension. Stents were placed in both ureters. The serum creatinine concentration subsequently dropped to 106.1 mol/l. Laparoscopic URETEROLYSIS was performed on both ureters. A biopsy of the retroperitoneal mass showed fibrosis and chronic inflammation, with no evidence of malignancy. Foci of cellular infiltrates within the fibrous tissue were rare (Figure 2). The patient was subsequently started on prednisone 20 mg per day and mycophenolate mofetil 1,000 mg twice per day. A CT scan performed 6 months after therapy began was unchanged. The prednisone dose has been tapered to 10 mg per day. The patient has remained on mycophenolate mofetil at the same dose for 6 months. The serum creatinine concentration has remained in the 132–141 mol/l range.
Figure 1 Non-contrast transverse CT scan showing a retroperitoneal mass surrounding the aorta (arrow).
The aorta is denoted by a rim of calcification.
Full figure and legend (106K)Figures & Tables indexDownload Power Point slide (178K)Figure 2 Retroperitoneal biopsy specimen.
Full figure and legend (132K)Figures & Tables indexDownload Power Point slide (178K)
Discussion of diagnosis
Initial diagnosis
Urinary tract obstruction is a common cause of acute renal failure.1 The differential diagnosis varies depending on the patient's age and sex. In adult men, prostatic hyperplasia and carcinoma are the most common etiologies. In women, pelvic or retroperitoneal neoplasms are often responsible. In a patient with a solitary functioning kidney, such as a renal transplant recipient, a calculus can cause ureteral obstruction and acute renal failure.
Retroperitoneal fibrosis is a well described but uncommon cause of urinary tract obstruction and acute renal failure. First described in the English literature by Ormond in 1948, this entity is often known as Ormond's disease.2 It has an estimated prevalence of 1–2 per 100,000 and most commonly presents in men (male to female ratio, 3:1) between the ages of 40 and 60 years. As a 60-year-old man, the patient under discussion is a typical example of an individual presenting with retroperitoneal fibrosis. Early symptoms are often nonspecific and can include back pain and fatigue—as in the present case—in addition to fever, weight loss and malaise.3
In this patient, proliferation of fibrous tissue in the retroperitoneum caused ureteral occlusion and acute renal failure. The fibrotic process can compress other structures, including the inferior vena cava (leading to peripheral edema and thrombophlebitis) and the duodenum (resulting in intestinal obstruction). The elevated blood pressure observed in this patient is a frequent finding in cases of retroperitoneal fibrosis.3 Biochemical abnormalities of the disease can include anemia, an elevated blood sedimentation rate, and elevated levels of the inflammatory marker C-reactive protein as observed in this patient.
In this case, renal ultrasound detected hydronephrosis. Relative nondilation of the pelvic ureters, revealed by CT scans in this case, is often thought to be a classic feature of retroperitoneal fibrosis; however, in practice, the upper ureters and renal pelvis are usually dilated. Hydronephrosis is not reported in all cases of retroperitoneal fibrosis. In the case presented here, the diagnosis of retroperitoneal fibrosis was confirmed noninvasively by an abdominal CT scan and MRA, and subsequently by biopsy of the inflammatory mass. The abdominal CT did not show anterior displacement of the aorta, as is commonly seen with retroperitoneal fibrosis secondary to malignancy.4 Contrast-enhanced CT or gadolinium-enhanced MRA are the diagnostic tests of choice for retroperitoneal fibrosis.5 More recently, POSITRON EMISSION TOMOGRAPHY has been used in a small number of patients to assess the degree of retroperitoneal inflammation, and might be helpful in tracking the patient's response to therapy.6 The patient discussed here underwent a biopsy, which is advocated by most clinicians to rule out a malignant process. Imaging studies in this case detected atherosclerotic disease in the distal aorta, but the aortic diameter did not fit the criteria for diagnosis of an aneurysm.
Risk factors
Retroperitoneal fibrosis can be subdivided into primary and secondary subtypes (Box 1). Primary retroperitoneal fibrosis is often associated with abdominal aortic aneurysms,7, 8, 9 as in the present case. Secondary forms of the disease occur as a result of factors including pelvic malignancy, abdominal surgery, radiation therapy, pancreatitis, diverticulitis, ureteral rupture and certain drugs, including methysergide.10 Although—as in the current case—patients presenting with the condition are often receiving antihypertensive agents, it is unlikely that these drugs cause retroperitoneal fibrosis.11
Box 1 Causes of primary and secondary retroperitoneal fibrosis.
Primary
- Association with an aortic aneurysm
- Idiopathic
Secondary
- Asbestos exposure
- Pelvic malignancies
- Abdominal surgery
- Radiation therapy
- Pancreatitis
- Diverticulitis
- Ureteral rupture
- Drugs
Recently, a case–control study of 43 patients in Finland identified asbestos exposure as a risk factor for retroperitoneal fibrosis.12 Exposure to methysergide and ergot, smoking, and the presence of an abdominal aortic aneurysm, have also been identified as risk factors for retroperitoneal fibrosis.
Although no features of the present case indicated an association with autoimmunity, there is evidence that, in some instances, retroperitoneal fibrosis occurs as part of a systemic inflammatory process triggered by autoimmunity.13 In many of these cases, an abdominal aortic aneurysm or atherosclerosis of the distal aorta is present. Some investigators have proposed that an immune response to atherosclerotic plaque antigens, such as oxidized LDL and CEROID, results in periaortic inflammation and fibrosis. Others argue that the disease originates as a vasculitis that involves the vasa vasorum in the adventitia of the aorta. This hypothesis is supported by the presence of anemia, an elevated sedimentation rate, increased levels of C-reactive protein, constitutional symptoms, and the association with autoimmune diseases and systemic vasculitides. Autoimmune disorders associated with retroperitoneal fibrosis include autoimmune thyroiditis, small vessel vasculitis, autoimmune pancreatitis, sclerosing cholangitis and primary biliary cirrhosis.
Discussion of treatment
Initial management of ureteral obstruction and renal failure caused by retroperitoneal fibrosis involves placement of ureteral stents to temporarily relieve obstruction and restore renal function. This can be followed by either open or laparoscopic ureterolysis. Both techniques are effective, but open surgery is associated with higher morbidity and mortality.14 Although ureterolysis removes the ureters from the retroperitoneal space and relieves urinary obstruction, compression of other retroperitoneal structures can still occur. There is no conclusive evidence to indicate whether the ureters should be wrapped in omentum within the abdomen during this procedure. Some authors have used a combination of ureteral stenting and medical therapy to treat retroperitoneal fibrosis in the absence of an open or laparoscopic surgical approach.
Abdominal aortic aneurysms associated with retroperitoneal fibrosis should be treated surgically if they are greater than 5 cm in diameter; however, the optimal surgical approach remains controversial. Some investigators argue that these aneurysms have a lower rate of rupture and are associated with higher perioperative mortality than noninflammatory aneurysms. Others suggest that elective or emergency open repair can be accomplished with morbidity and mortality rates similar to those of noninflammatory aneurysms.15 Transfemoral endoluminal prostheses have been used successfully in a small number of patients.
There are no prospective trials of medical treatment for retroperitoneal fibrosis, so the optimal approach to medical management of the condition is unknown.16 Because the retroperitoneal infiltrate comprises inflammatory cells such as lymphocytes, plasma cells and macrophages, steroids and other immunosuppressive agents have been advocated. In one study in 12 patients treated with prednisolone and ureteral stenting, but not ureterolysis, the masses regressed in 9 cases. In another trial, 26 patients were treated with azathioprine and prednisone for 12 months, or cyclophosphamide and prednisone for 6 months. Periodic ureteral stenting was performed in both groups.17 Urinary obstruction was resolved in 25 patients and 7 required a second course of therapy. The adverse-effect rate in the azathioprine plus prednisone group was lower than in the cyclophosphamide plus prednisone group. A small number of case reports have described the efficacy of tamoxifen in this condition, as either monotherapy or in combination with prednisone. One case report describes successful use of mycophenolate to treat idiopathic retroperitoneal fibrosis.18
Conclusion
This case illustrates several teaching points in the patient with retroperitoneal fibrosis. The physician must have a high index of suspicion for diagnosis of retroperitoneal fibrosis, because the presenting symptoms, such as back pain and fatigue, can be nonspecific. Hypertension and anemia are often present. Retroperitoneal fibrosis can be of idiopathic origin, or occur in association with an aortic aneurysm, or secondary to factors such as malignancy or abdominal surgery. Recent studies have identified asbestos exposure and smoking as risk factors. Although retroperitoneal fibrosis often occurs in patients receiving beta blockers or other antihypertensive medications, it is unlikely that such agents cause the condition, although this issue remains controversial. Contrary to what is most commonly taught, the proximal ureters and renal pelvis often appear dilated on ultrasound examination. CT scan or MRI are the diagnostic tests of choice for retroperitoneal fibrosis, and biopsy should be performed to exclude the presence of malignancy. Treatment of ureteral obstruction resulting from retroperitoneal fibrosis involves ureteral stenting and ureterolysis, but the optimal medical approach to the condition itself, and the optimal surgical management of associated aneurysms, remain controversial. Inflammatory cell infiltration of retroperitoneal fibrotic masses provides a rationale for the therapeutic use of steroids and other immunosuppressive agents in this condition.
References
- Hou SH et al. (1983) Hospital-acquired renal insufficiency: a prospective study. Am J Med 74: 243–248 | Article | PubMed | ISI | ChemPort |
- Ormond JK et al. (1948) Bilateral ureteral obstruction due to envelopment and compression by an inflammatory retroperitoneal process. J Urol 59: 1072–1079 | ISI |
- Baker LR et al. (1987) Idiopathic retroperitoneal fibrosis. A retrospective analysis of 60 cases. Br J Urol 60: 497–503 | PubMed | ISI | ChemPort |
- Kottra JJ and Dunnick NR (1996) Retroperitoneal fibrosis. Radiol Clin North Am 34: 1259–1275 | PubMed | ISI | ChemPort |
- Mitnick H et al. (2004) Periaortitis: gadolinium-enhanced magnetic resonance imaging and response to therapy in four patients. Ann Vasc Surg 18: 100–107 | Article | PubMed | ISI |
- Salvarani C et al. (2005) Positron emission tomography (PET): evaluation of chronic periaortitis. Arthritis Rheum 53: 298–303 | Article | PubMed | ISI |
- Katz R et al. (2002) Primary and postoperative retroperitoneal fibrosis—experience with 18 cases. Urology 60: 780–783 | Article | PubMed | ISI |
- Walker DI et al. (1972) Inflammatory aneurysms of the abdominal aorta. Br J Surg 59: 609–614 | PubMed | ISI | ChemPort |
- Leseche G et al. (1992) Diagnosis and management of 17 consecutive patients with inflammatory abdominal aortic aneurysm. Am J Surg 164: 39–44 | PubMed | ISI | ChemPort |
- Thomas A et al. (2003) Urologic complications of nonurologic medications. Urol Clin North Am 30: 123–131 | Article | PubMed | ISI |
- Pryor JP et al. (1983) Do beta-adrenoceptor blocking drugs cause retroperitoneal fibrosis? Br Med J (Clin Res Ed) 287: 639–641 | PubMed | ChemPort |
- Uibu T et al. (2004) Asbestos exposure as a risk factor for retroperitoneal fibrosis. Lancet 363: 1422–1426 | Article | PubMed | ISI | ChemPort |
- Vaglio A et al. (2003) Evidence of autoimmunity in chronic periaortitis: a prospective study. Am J Med 114: 454–462 | Article | PubMed | ISI |
- Fugita OE et al. (2002) Laparoscopic treatment of retroperitoneal fibrosis. J Endourol 16: 571–574 | Article | PubMed | ISI |
- Tambyraja AL et al. (2004) Ruptured inflammatory abdominal aortic aneurysm: insights in clinical management and outcome. J Vasc Surg 39: 400–403 | Article | PubMed | ISI |
- Kardar AH et al. (2002) Steroid therapy for idiopathic retroperitoneal fibrosis: dose and duration. J Urol 168: 550–555 | PubMed | ISI | ChemPort |
- Marcolongo R et al. (2004) Immunosuppressive therapy for idiopathic retroperitoneal fibrosis: a retrospective analysis of 26 cases. Am J Med 116: 194–197 | Article | PubMed | ISI |
- Grotz W et al. (1998) Treatment of retroperitoneal fibrosis by mycophenolate mofetil and corticosteroids. Lancet 352: 1195 | Article | PubMed | ISI | ChemPort |
Competing interests
The author declared no competing interests.
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Subject areas under which this article appears: Acute renal failure
