Obstructive uropathy caused by retroperitoneal fibrosis presents as a late manifestation of sarcoidosis

Abstract

Obstructive uropathy in sarcoidosis can result from retroperitoneal involvement, retroperitoneal fibrosis (RPF), renal stones, or ureteral involvement. We report acute kidney injury (AKI) from obstructive uropathy because of RPF in a female patient, 2 years following the resolution of pulmonary sarcoidosis. We propose that RPF may occur in sarcoidosis even when a lag of years separates the presentations of the illnesses.

Keywords:

• kidney injury
• obstruction
• retroperitoneal fibrosis
• sarcoidosis
• pulmonary

INTRODUCTION

Although two-thirds of the cases are idiopathic,¹ retroperitoneal fibrosis (RPF) may result from malignancies, medications, hemorrhage, surgery, infections, irradiation, inflammatory bowel diseases, periarteritis secondary to autoimmune diseases, arteriosclerosis, or abdominal aortic aneurysm.^2,3 Genetic and environmental factors may predispose to RPF, as well.³ We report acute kidney injury (AKI) resulting from obstructive uropathy because of RPF, presenting 2 years following the resolution of pulmonary sarcoidosis.

CASE REPORT

A 49-year-old woman presented with abdominal pain, nausea, and AKI. Before 2 years, she suffered from sarcoidosis manifested as pulmonary infiltrates, for which recovery, assessed both clinically and radiologically, was complete following 6 months of steroid therapy. Her current physical examination was unremarkable and vital signs were normal. A urinary catheter drained 100 mL of clear urine. Blood tests were abnormal for serum creatinine (7.2 mg/dL), blood urea nitrogen (BUN) (63 mg/dL), calcium (7.8 mg/dL), phosphorous (7.9 mg/dL), potassium (6.5 mEq/L), and hemoglobin (10.7 g%). Both ultrasonography and an abdominal CT scan without contrast media demonstrated severe bilateral hydroureteronephrosis with medial deviation of ureters, extrinsically compressed by a retroperitoneal mass at the level of L4 (Figure 1a,b). The serum creatinine normalized following an urgent decompression of the obstruction by the insertion of bilateral percutaneous nephrostomies. A contrast CT scan and an MRI revealed retroperitoneal soft tissue mass, enveloping the great vessels and ureters. No lymphadenopathy was noted. In addition, right pleural thickening that was minimal in a chest CT scan of 2 years earlier (Figure 1c) was now prominent. A pleural biopsy performed by thoracoscopy confirmed fibrosis, with no evidence of granulomatous process. Arterial blood gases, serum angiotensin-converting enzyme, and a gallium scan were normal. Chest CT and spirometry did not show lung abnormalities. Bone marrow aspiration and biopsy and purified protein derivative (PPD) skin test were negative. Once RPF was diagnosed and 60 mg of oral prednisone was administered, the patient was discharged. Within 4 months, prednisone was tapered to 5 mg. After 6 months of steroid treatment, poor blood glucose control led to its replacement with 2 mg/kg of daily azathioprine. The latter was later discontinued because of nonadherence, pruritus, and marked elevation of liver enzymes. Both intravenous pyelogram and CT continued to demonstrate the moderate bilateral hydroureteronephrosis and smoothly tapered ureters at the level of L4–L5, although the diameter of the fibrotic plaque decreased from 14 mm to 8 mm (Figure 2). A year after diagnosis, following medical therapy failure, open bilateral ureterolysis, and reposition of both ureters within the peritoneal cavity, while wrapped within a sleeve of omentum, were performed. Deep biopsies of the fibrotic mass revealed the foci of lymphocytes and fibrosis with no evidence of granulomas. The postoperative course was uneventful and nephrostomies were removed. Normal blood tests and renal DTPA scan confirmed intact kidney function.

Figure 1. CT scan on admission showed (a) severe bilateral hydronephrosis and ureteral obstruction caused by a retroperitoneal mass at the level of L4; (b) a retroperitoneal mass that appeared as fibrosis; and (c) prominent right pleural fibrosis.

Figure 2. CT scan performed 3 months following steroid treatment demonstrated a decrease of the diameter of the fibrotic plaque from 14 mm to 8 mm.

DISCUSSION

Patient medical history, imaging, laboratory, and histopathological findings did not indicate a cause of RPF. Because the patient suffered from sarcoidosis with pulmonary involvement that resolved before 2 years, we assume the association between the sarcoidosis and the RPF. Clinical evidence attests to renal involvement in 11% of sarcoidosis patients.⁴ Renal manifestations are usually consequent to hypercalcemia or hypercalciuria. Nephrolithiasis, nephrocalcinosis, and kidney insufficiency are prevalent, with granulomatous interstitial nephritis, glomerular disease, and obstructive uropathy also presenting. The latter may result from retroperitoneal involvement, RPF, renal stones, and ureteral involvement.⁴ Obstruction in sarcoidosis patients, without evidence of nephrolithiasis, as in the present case, is rarely documented. Ureteral sarcoidosis presented in a female patient treated with β-blockers, who had left flank pain, left hydronephrosis, and irregular soft tissue surrounding the ureter. Following ureterolysis and omental wrapping, noncaseating granulomas were detected in the resected portion of the ureter.⁵ In another female, fibrosis surrounding kidneys and proximal ureters caused obstruction and renal insufficiency 10 years following a primary diagnosis of tuberculous cervical lymphadenitis.⁶ Detection of noncaseating granulomas upon reevaluation of an earlier cervical lymph node biopsy led to the diagnosis of sarcoidosis.⁶

We suggest that the bilateral hydroureteronephrosis in our patient was a late manifestation of the sarcoidosis, diagnosed 2 years earlier. Perhaps the RPF progressed insidiously, parallel to the healing of pulmonary sarcoidosis with underlying retroperitoneal involvement, and to the progression of pleural fibrosis.⁷ Lack of abdominal CT scans at pulmonary sarcoidosis diagnosis and follow-up defers validation of this hypothesis. Alternatively, pleural fibrosis could have resulted from an extraperitoneal manifestation of idiopathic RPF,⁸ without any association to sarcoidosis. Albeit, it seems unlikely that two uncommon and unrelated conditions occurred consecutively in the same patient.

Ureteral obstruction occurs in 80–100% of patients with RPF.⁸ Although usually developing in the later stages of the disease, it sometimes parallels constitutional symptoms.^2,4 Ultrasonography, CT scanning, and MRI facilitate the diagnosis of RPF. Typically, fibrosis appears as a periaortic confluent mass and a low-intensity T1 signal in MRI. As in our case, imaging may demonstrate proximal hydroureteronephrosis, medial deviation of the ureters, mainly at the level of L3–L4, and extrinsic compression of the ureters.^1,9 Recently, fluorodeoxyglucose–positron emission tomography served as an additional, though not specific, modality for the assessment of extraperitoneal tissue involvement and response to therapy.³ A definitive tissue diagnosis is recommended when secondary RPF, because of malignancy, is suspected.^3,10 Furthermore, biopsies should be routinely performed when surgical intervention is required.³ Histopathological findings usually demonstrate the invasion of tissue by inflammatory cells and myofibroblasts, followed by fibrous scarring.¹¹

Well-controlled, prospective studies comparing treatments for RPF are lacking. Currently, the combination of steroids with either a ureteral stent or a nephrostomy is suggested. Administration of an immune-suppressive agent such as azathioprine or antiestrogen preparation is optional. Medical treatment demonstrates particular effectiveness for systemic complaints and for fibrosis involving multiple sites, although relapse may occur.¹² Ureterolysis with lateral or intraperitoneal displacement and omental wrapping is usually indicated when the above fails³ or are poorly tolerated, as with our patient.

In summary, a 49-year-old woman with a history of sarcoidosis presented with obstructive uropathy and AKI apparently because of RPF. We propose sarcoidosis as a possible cause of RPF even when a lag of years separates the presentations of the illnesses. Studies evaluating the extent and markers of retroperitoneal involvement in patients with active sarcoidosis, or up to several years subsequent to such, are needed to determine effective treatment.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.