Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory arterial disease, commonly involving the renal arteries. Here we report a case of a 16-year-old Chinese male who was found to have severe hypertension with proteinuria for 2 years. Computed tomography showed absence of the left kidney and enlargement of the right kidney. Subsequent angiography confirmed the above findings and revealed narrowing of both the upper and lower branches of the right renal artery caused by FMD. These combined lesions are very rare, and individuals affected are at increased risk of renal dysfunction if left untreated. Treatment with percutaneous balloon angioplasty is the first choice in such a patient and usually results in optimal outcomes.
Fibromuscular dysplasia (FMD), first observed and described in 1938, is a nonatherosclerotic, noninflammatory angiopathy found predominantly in young women of childbearing age.[1, 2] Involvement of medium-sized arteries, including the renal, carotid, intracranial, splanchnic, and lower limb arteries can be observed in FMD patients based on its higher than expected prevalence. However, it is extremely rare to encounter a patient with a solitary kidney and 2-branched renal arterial lesions caused by FMD. Timely diagnosis and treatment are crucial, because the patient's renal function is at high risk of deteriorating, and flash pulmonary edema may develop.[5, 6] Follow-up visits are mandatory to confirm therapeutic effects.
A 16-year-old Chinese male was admitted to our ward in December 2012 with a chief complaint of hypertension, which had been diagnosed 2 years previously. He denied polyuria, palpitations, sweating, headache, heat intolerance, nocturnal snoring, and other related symptoms. Both his creatinine and blood urea nitrogen level remained within normal range, whereas his urine protein was found to be elevated for 1 year. Abdominal ultrasound and computed tomography scan had been performed in 2011 and showed a solitary enlarged right kidney (12.1 × 5.4 cm) accompanied by stenotic lesions in the 2 branches of a bifurcated right renal artery (Figure 1). An antihypertensive regimen of felodipine (5 mg/day) and metoprolol sustained-release tablets (23.5 mg/day) had been prescribed for 2 years, which resulted in unsatisfactory blood pressure control. Past medical history was unremarkable. The patient's blood pressure on admission was 200/120 mm Hg, pulse was regular, and temperature was 36.5 °C. Physical examination revealed a grade III systolic murmur in the right periumbilical region.
Blood samples were drawn, and the patient's kidney function appeared normal with an estimated glomerular filtration rate (GFR) of 101.48 mL/min (Cockcroft-Gault equation), a moderate leukocytosis (10 700/mm), a slight elevation of C-reactive protein (1.9 mg/dL), and hypokalemia (3.25 mmol/L) (Table 1). Proteinuria was noted in his morning urine sample. Eighteen-lead electrocardiogram showed sinus rhythm with heart rate of 55 beats per minute. Chest x-ray and carotid ultrasound revealed normal findings, whereas echocardiography showed mild left ventricular wall thickening. Twenty-four hour blood pressure monitoring found his average blood pressure to be 176/98 mm Hg. Olmesartan 10 mg orally once daily and long-acting nifedipine 20 mg orally twice daily were prescribed, and his blood pressure was maintained around 160/90 mm Hg in the ward.
Table 1. Patient's Relevant Lab Results at His First Month and 3-Month Follow-up Visits
Interventional angiography was subsequently conducted in the catheter lab and showed the absence of a left kidney in addition to a right renal artery that was divided into upper and lower branches. Diffuse narrowing in the distal portion of the upper branch and local narrowing in the middle portion of the lower branch was observed, which follows the patterns of arterial lesions caused by FMD (Figures 2 and 3). Percutaneous balloon angioplasty was performed on the 2 branches, and the narrowing was corrected with no remaining stenosis (Figures 4-6, and 7). The patient's blood pressure was maintained at approximately 150/80 mm Hg prior to his discharge.
At both 1-month and 3-month follow-up visits, our patient remained normotensive while taking the above antihypertensive regimen. No proteinuria was detected, and his kidney function remained normal (Table 1). Renal arterial ultrasound was performed twice, and no stenosis was discovered.
Epidemiology and Possible Etiology
FMD, a well-described arterial disease that is now considered the second most common cause of renal artery stenosis, usually affects the middle or the distal segment of the renal arteries. Although its prevalence in the general population remains unknown, several studies estimate that in possible renal donors, FMD's prevalence is around 3.8% to 6.6%. It has been believed that FMD typically occurs in young women. However, a recent epidemiological study concluded that FMD is predominantly a disease of the middle-aged and could affect both sexes over an entire lifetime. In our case, the patient affected is an adolescent male. Various studies have been conducted to explore FMD's possible etiologies, but no single etiology is confirmed. Its vertical transmission might follow the rule of autosomal dominant inheritance, and several candidate genes, including type 1 and 3 collagen gene mutations, polymorphism of the α-1 antitrypsin gene, and human leukocyte antigen Drw6 have been postulated to play a role, but none have been confirmed.[9-12] A positive family history of cardiovascular disease might also play a role in the development of FMD. In our case, the patient's father had been diagnosed with essential hypertension in his early 30s. Environmental factors, such as smoking, oral contraceptive use, autoimmune responses, and renal morbidity, have been reported but are less convincing due to study design limitations in the current literature.[8, 10]
Clinical Manifestations and Possible Pathophysiology
The most common manifestation of renal artery FMD is treatment-resistant renovascular hypertension (RVHT), which depicts the causal relationship between confirmed renal arterial narrowing and elevated blood pressure.[1, 7, 13] In our case, the young individual initially presented with treatment-resistant uncontrolled hypertension. It is estimated that renal artery FMD accounts for nearly 10% of all RVHT causes. Discovered by Goldblatt in 1934, RVHT has been increasingly recognized as an important cause of nonessential hypertension and chronic kidney disease. Studies have reported 2 basic RVHT animal models: activation of the renin-angiotensin-aldosterone system (RAAS), and volume-dependence secondary to reduced renal mass. Although it is generally believed that individuals with a solitary kidney conform to the second model, the role of renin remains controversial because numerous studies support the view that RAAS is also activated in these patients.[16, 17] Patients with solitary kidneys and stenotic renal arteries are likewise at increased risk of worsened kidney function due to secondary hypertension, chronic kidney disease, and possible contrast media nephropathy, even if renal FMD-affected patients rarely develop high creatinine levels.[5, 8, 17] In the present case, the patient's GFR remained within normal range, whereas proteinuria was found for 1 year before admission. At 1-month and 3-month follow-up visits, the patient's urine protein remained negative, which allowed us to eliminate several possible causes, including primary glomerular diseases, and allowed us to link its presence with hypertensive nephrosclerosis and reduced nephron mass. Another important issue for these patients is that they might develop Pickering syndrome, in which patients with renal artery stenosis experience multiple episodes of acute pulmonary edema. First reported by Thomas G. Pickering, this conundrum has been well studied, and its main pathophysiologies are noted: increased hemodynamic burden, activation of RAAS, defective pressure natriuresis, cardiac diastolic dysfunction, and failure of the pulmonary capillary blood-gas barrier.[18-20] Not surprisingly, previous studies show that patients with a solitary kidney and renal artery stenosis, falling into the category of the 1-kidney 1-clip hypertension model, are at high risk of developing flash pulmonary edema.[6, 18, 20] In our case, the patient denies relevant history and remained free of dyspnea at follow-ups.
Diagnosis and Treatments
Although pathology has revealed FMD's nonatherosclerotic and noninflammatory nature, an intra-arterial angiogram still remains the gold standard for diagnosis.[21-23] In our case, angiography discovered the solitary right kidney as well as FMD-mediated focal and tubular narrowing affecting both upper and lower branches of the right renal artery. The prevalence of a solitary kidney in renal FMD patients is relatively low. Moreau et al. searched through 104 FMD individuals presenting with RVHT, and 10 were found to have a solitary kidney. However, this combination of a bifurcated renal artery FMD in the setting of a solitary kidney is much rarer, and its prevalence in renal FMD patients is unknown. Renal angioplasty has been proven a safe and durable modality for correcting FMD-related renal artery stenosis based on encouraging follow-up results and is highly recommended, especially when the patient is of young age and FMD-related RVHT is newly diagnosed.[25, 26] Surgery may also be considered if dysplastic lesions are more extensive. Relapses may occur as the result of inadequate dilation, and pressure gradient measurement before and after the angioplasty is crucial. In our present case, the patient's blood pressure has been maintained within normal range, and GFR remains normal during 3-month follow-up.
Xiongjing Jiang conducted the angioplasty and supervised the entire case report. Hui Dong, Yubao Zou, and Lei Song also contributed to the intervention procedure. Ting Guan, Xianliang Zhou, and Yuejin Yang supervised clinical care for the patient. Special thanks to Otto Thomas, first-year resident in anesthesiology in Cedars-Sinai Medical Center, Los Angeles, California, who performed the final editing of the manuscript. As first author, Xuanqi An is the first-year resident who took care of the patient and wrote the article.