| | Quiz Page September 2009: Long-standing High-Renin Hypertension and HypokalemiaClinical Presentation  A 43-year-old white woman was evaluated for uncontrolled hypertension, progressive weakness, and fatigue. High blood pressure (BP) was diagnosed at the age of 28 years during the first trimester of pregnancy. A caesarean section was performed at week 37 for intrauterine growth retardation and preeclampsia. From 1993 through 2007, her BP was poorly controlled, first on atenolol and indapamide therapy, and then on candesartan and nebivolol therapy. Canrenoate was not tolerated because of nausea and abdominal pain. Her course also has been notable for persistent hypokalemia, with potassium values ranging from 2.8 to 3.2 mEq/L (2.8 to 3.2 mmol/L). On physical examination, the patient's BP was 150/105 mm Hg and pulse rate was 88 beats/min. Grade II retinopathy was present. Serum laboratory data included the following values: potassium ion, 2.9 mEq/L (2.9 mmol/L); bicarbonate, 33 mEq/L (33 mmol/L); serum creatinine, 0.7 mg/dL (61.9 μmol/L); estimated glomerular filtration rate, 97 mL/min/1.73 m2 (1.62 mL/s/1.73 m2); and magnesium ion, 1.64 mEq/L (0.82 mmol/L). Urinalysis showed pH 6.0; specific gravity, 1,019; negative glucose, ketone, and nitrite; and 2+ protein; urinary sediment was unremarkable. Twenty-four–hour urinary protein excretion ranged between 518 and 1,409 mg. Echocardiography showed mild concentric left ventricular hypertrophy. Twenty-four–hour urinary excretion of free cortisol and metanephrines was normal. After felodipine and doxazosin were substituted for nebivolol and candesartan, plasma renin activity (PRA) was increased at 39.94 ng/mL/h (reference range, 1.50 to 5.70 ng/mL/h [11.09 ng/L/s; reference range, 0.42 to 1.58 ng/L/s]) and aldosterone level in the upright position was very high at 92.9 ng/dL (reference range, 3.8 to 31.3 ng/dL [2.58 nmol/L; reference range, 0.11 to 0.87 nmol/L]). Abdominal computed tomography (CT) with contrast injection was performed (Fig 1A and B). ■ What is the differential diagnosis of hypertension with increased PRA and aldosterone level? ■ What is the appropriate diagnostic workup in this situation? ■ What does the abdominal CT reveal? ■ What is your diagnosis? Discussion What is the differential diagnosis of hypertension with increased PRA and aldosterone level? Between 12% and 20% of patients with essential hypertension have PRA greater than the upper limit of the renin-sodium profile of normotensive control patients1; however, less than 30% of these patients with high-renin essential hypertension have PRA exceeding 11 ng/mL/h (3.06 ng/L/s), independent of daily sodium excretion. Therefore, one would anticipate encountering no more than 3.5% to 6% of all patients with PRA greater than this value. The persistence of unusually high PRA despite treatment with a β-blocker rendered the hypothesis of high-renin essential hypertension less likely in this case. High PRA also may suggest renovascular or malignant hypertension. In a recently published series of malignant hypertension, 76% of patients had PRA greater than 4.9 ng/mL/h (>1.36 ng/L/s), with 25% greater than 20 ng/mL/h (>5.56 ng/L/s).2 However, patients with malignant hypertension usually present with a dramatic clinical picture and significant target-organ damage, including kidney damage and advanced retinopathy,2 neither of which was observed in our patient. Finally, the hypothesis of a renin-secreting tumor of the juxtaglomerular apparatus (TJGA) should be considered despite the rarity of this disease.3 In the largest (38 cases) published series,4 mean PRA was 36.86 ng/mL/h (range, 2.80 to 151.00 ng/mL/h [10.29 ng/L/s; range, 0.78 to 41.95 ng/L/s]) with a median value of 22.00 ng/mL/h (6.11 ng/L/s) (25th to 75th percentile, 9.65 to 58.50 ng/mL/h [2.68 to 16.25 ng/L/s]). Hypokalemia, attributable to secondary hyperaldosteronism, was highly prevalent (84%) in these patients, with mean serum potassium ion of 2.9 ± 0.4 (SD) mEq/L (2.9 ± 0.4 mmol/L). What is the appropriate diagnostic workup in this situation? The captopril test has been used as a screening test for renovascular hypertension; however, remarkable variability exists in the diagnostic PRA cutoff values. Renal Doppler ultrasonography, CT, and magnetic resonance renal angiography have greater diagnostic accuracy for renovascular hypertension compared with the captopril test.5 Renal Doppler ultrasonography and CT renal angiography were performed in our patient and excluded renovascular disease. Abdominal CT with contrast injection also was performed for suspected TJGA. What does the abdominal CT reveal? Abdominal CT identified a 2.2 × 2.2-cm mass at the level of the corticomedullary junction between the middle and lower third of the left kidney (Fig 1A), with very weak contrast enhancement in the late parenchymal phase (Fig 1B). This location and these features are consistent with TJGA. Renal CT with contrast injection has almost 100% sensitivity for the detection of TJGA.3, 4 Selective renal arteriography failed to identify these tumors, which usually appear as small hypovascular areas within the renal parenchyma in approximately 60% of patients, when this procedure was performed systematically.4 Renal vein sampling has at best 50% to 60% sensitivity in detecting renin lateralization,3, 4 possibly due to the superficial location of these tumors draining through pericapsular veins rather than the main renal veins, variable blood dilution by extrarenal veins, or secretory intermittence. What is your diagnosis? The diagnosis was TJGA, and conservative surgery with tumor enucleation was performed. Histological examination showed a uniform population of polygonal cells arranged in an organoid pattern, but also hemangiopericytoma-like aspects with gaping vascular lacunae (Fig 2). The cells had round nuclei and eosinophilic cytoplasmic granules (Fig 3). Immunostaining was positive for vimentin and CD 34 (Fig 4A and B).3 Electron microscopy (Fig 5A and B) showed characteristic electron-dense secretory granules in the cytoplasm. Serum potassium ion and office BP values normalized within 7 days after surgery. At the 6-month follow-up, the patient remained normotensive (24-hour mean BP, 115/76 mm Hg). Serum potassium ion level was 4.6 mEq/L (4.6 mmol/L), upright PRA was 0.67 ng/mL/h (0.19 ng/L/s), aldosterone level was 9.0 ng/dL (0.25 nmol/L), and 24-hour proteinuria decreased to 60 mg of protein. Final Diagnosis Renin-secreting tumor of the juxtaglomerular apparatus. References 1. 1Brunner HR, Laragh JH, Baer L, et al. Essential hypertension: Renin and aldosterone, heart attack and stroke. N Engl J Med. 1972;286:441–449. MEDLINE 2. 2van den Born B-JH, Koopmans RP, van Montfrans GA. The renin-angiotensin system in malignant hypertension revisited: Plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension. Am J Hypertens. 2007;20:900–906.
CrossRef
3. 3Wong L, Hsu THS, Perlroth MG, Hofmann LV, Haynes CM, Katzelson L. Reninoma: Case report and literature review. J Hypertens. 2008;26:368–373.
CrossRef
4. 4McVicar M, Carman C, Chandra M, Abbi RJ, Teichberg S, Kahn E. Hypertension secondary to renin-secreting juxtaglomerular cell tumor: Case report and review of 38 cases. Pediatr Nephrol. 1993;7:404–412.
CrossRef
5. 5Vasbinder GBC, Nelemans PJ, Kessels AGH, Kroon AA, de Leeuw PW, van Engelshoven JMA. Diagnostic tests for renal artery stenosis in patients suspected of having renovascular hypertension: A meta-analysis. Ann Intern Med. 2001;135:401–411. MEDLINE Case provided and authored by Giuseppe Regolisti, MD,1 Aderville Cabassi, MD,1 Elisabetta Parenti, MD,1 Paolo Greco, MD,1 Caterina Maccari, MD,1 Letizia Gnetti, MD,2 Massimo Melissari, MD, PhD,2 Domenico Potenzoni, MD,3 and Enrico Fiaccadori, MD, PhD,1 1Dipartimento di Clinica Medica, Nefrologia e Scienze della Prevenzione, and 2Sezione di Anatomia Patologica, Dipartimento di Medicina di Laboratorio, Università di Parma; and 3Divisione di Urologia, Ospedale di Vaio, AUSL di Parma, Parma, Italy. Address correspondence to Giuseppe Regolisti, MD, Terapia Intensiva, Dipartimento di Clinica Medica, Nefrologia e Scienze della Prevenzione, Università di Parma, Via Gramsci, 14 - 43100 Parma, Italy. E-mail: gregolisti@ao.pr.it Financial Disclosure: None. PII: S0272-6386(09)00765-3 doi:10.1053/j.ajkd.2009.04.030 © 2009 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved. | 
 39 of 39
|
| |
|
FULL TEXT00765-3/journalimage?img=PIIS0272638609007653.gr1.lrg.gif&fig=fig1&kwhquery=&issn=0272-6386&ishighres=false&allhighres=false&free=yes','journalimage');)
00765-3/journalimage?img=PIIS0272638609007653.gr2.lrg.gif&fig=fig2&kwhquery=&issn=0272-6386&ishighres=false&allhighres=false&free=yes','journalimage');)
00765-3/journalimage?img=PIIS0272638609007653.gr3.lrg.gif&fig=fig3&kwhquery=&issn=0272-6386&ishighres=false&allhighres=false&free=yes','journalimage');)
00765-3/journalimage?img=PIIS0272638609007653.gr4.lrg.gif&fig=fig4&kwhquery=&issn=0272-6386&ishighres=false&allhighres=false&free=yes','journalimage');)
00765-3/journalimage?img=PIIS0272638609007653.gr5.lrg.gif&fig=fig5&kwhquery=&issn=0272-6386&ishighres=false&allhighres=false&free=yes','journalimage');)