Nephrotic range proteinuria associated with unilateral renal artery stenosis

Abstract

Sir, Mild proteinuria is often present in patients with renal artery stenosis (RAS) [1]. However, heavy proteinuria is an uncommon finding in this setting, and many of the reported cases are due to bilateral RAS [2]. A 62-year-old Caucasian male was referred to our nephrology service for worsening kidney function. He had a history of coronary artery disease, chronic kidney disease (baseline serum creatinine level of 2–3 mg/dl), and hypertension. For the past few months prior to admission, he had presented with progressive deterioration in kidney function associated with refractory hypertension. At the time of admission, he had bilateral lower extremity edema with a creatinine of 4.4 mg/dl, proteinuria of 15 g/24 h, and was treated with six antihypertensive medications. Further investigations including immunologic studies and renal ultrasound were normal, except for a plasma renin activity of 11 ng/ml/h (normal: 1–3.8) and an aldosterone level of 35 ng/dl (normal: 1–14). A carbon dioxide angiogram revealed severe ostial right RAS with normal left renal artery. A stent was placed at the site of stenosis with subsequent improvement in renal perfusion. Over the next 2 weeks, the kidney function returned to its baseline (creatinine 3.1 mg/dl), blood pressure was better controlled (needing only one antihypertensive agent), and proteinuria decreased to 2.3 g/24 h. Although mild-to-moderate proteinuria is commonly seen in patients with RAS, massive proteinuria or nephrotic syndrome is considered a rare presentation in this setting. The pathophysiology of this phenomenon is poorly understood, and the main suggested mechanisms are thought to be hormonal and hemodynamic disturbances. The ischemia induced by renal hypoperfusion can result in an increased secretion of renin from the affected kidney. Activation of the renin-angiotensin-aldosterone system (RAAS) is associated with a number of physiologic and pathophysiologic consequences [3]. The role of RAAS in the development of proteinuria was first observed in experimental animals [4] and was then confirmed in human studies. In a study on 96 patients with renal artery occlusion, Rossignol et al. found that the degree of proteinuria was independently related to the active renin level, which reflects plasma angiotensin II concentration. Angiotensin II constricts the efferent arterioles in the unaffected kidney leading to increased intraglomerular pressure [5]. It also acts directly on the endothelial cells resulting in widening of the intra-endothelial gaps and an increase in glomerular capillary permeability [5]. Our patient also showed a high plasma renin activity, likely secondary to RAS. Although biopsy was not done, the significant reduction in the amount of proteinuria over a short period of time supports the hypothesis that the renal hypoperfusion, with A. Wadhwa A. Kazory (&) Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0224, USA e-mail: amir.kazory@medicine.ufl.edu