Neurofibromatosis with Bilateral Renal Artery Stenosis and End Stage Renal Disease Case Report *Mohamed Al-Rawahi,1 Dawood Al-Riyami,1 Mahfooz A Farooqui,1 and Humoud Al-Duhli2 case report SQU Med J, August 2009, Vol. 9, Iss. 2, pp. 167-169, Epub 30th June 2009 Submitted - 4th Nov 2008 Revision Req. 21st Dec 08, Revision Recd. 18th Jan 09 Accepted - 3rd February 09 مرض الورام العصيب الليفي مع تضيق الشرايني الكلوية الثنائية وفشل ُكلِْويٌّ باملَْرَحلَِة النَِّهائِيَّة تقرير حالة محمد الرواحي، داوود الريامي، حمود الذهلي، محفوظ فاروقي امللخص: الورام العصبي الليفي - النوع األول هو مرض وراثي ذو صفة وراثية سائدة ، وهو عبارة عن متالزمة عصبية جلدية تصيب مختلف أعضاء أو أجهزة اجلسم بصفة أولية أو ثانوية ، ومن ضمنها اجلهاز القلبي الوعائي. وأكثر األوعية الدموية تأثرا باملرض هي الشرايني الكلوية التي تصاب بالتضيق مما يؤدي إلى ارتفاع ضغط الدم. هنا نعرض تقرير وصفي بحالة مريض في أواسط العمر راجع مستشفى جامعة السلطان قابوس وقد أصيب بفشل كلوي باملرحلة النهائية مصحوبا بارتفاع شديد في ضغط الدم ناجت عن ضيق الشريانني الكلويني جراء اإلصابة مبرض الورام العصبي الليفي. مفتاح الكلمات: مرض الورام العصبي الليفي ، تضيق الشريان الكلوي ، فشل ُكلِْويٌّ باملَرَْحلَِة النَِّهائِيَّة ، ارتفاع ضغط الدم كلوي املنشأ ، غسيل كلوي ، تقرير حالة ، عمان. abstract: Neurofibromatosis type 1 )NF-1( is an autosomal dominant, hereditary, neurocutaneous syndrome that may, primarily or secondarily, affect different organs or systems of the body including the cardiovascular system. The most common vascular abnormality in patients with NF-1 is renal artery stenosis. Here we report the case of a middle- aged gentleman who presented at Sultan Qaboos University Hospital, Oman, with end stage renal disease and severe hypertension and was diagnosed to have NF-1 with bilateral renal artery stenosis. He was started on renal replacement therapy. Keywords: Neurofibromatosis; Renal artery stenosis; End stage renal disease; Renal hypertension; Haemodialysis; Case report; Oman. Department of 1Medicine, 2Radiology & Molecular Imaging, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman *To whom correspondence should be addressed. Email: mohdrawahi@gmail.com Type 1 Neurofibromatosis (NF-1) is a common genetic disorder, with variable clinical manifestations, which affects at least one million persons throughout the world. Although rare, vascular abnormalities are a well- recognised manifestation of neurofibromatosis and may lead to renal artery stenosis and renovascular hypertension. Here, we present the case of a young Omani man who presented with end stage renal disease (ESRD) and severe hypertension, and was diagnosed to have NF-1 with bilateral renal artery stenosis. Case Report A 37 years old Omani man presented at Sultan Qaboos University Hospital, Oman, with a headache of two years duration and was found to be severely hypertensive. Upon presentation, his blood pressure was 190/105 mmHg. His past medical history was significant for decreasing hearing in the left ear since early childhood. His family history was significant for neurofibromatosis in one son. The patient was evaluated for the possibility of neurofibromatosis. He was noted to have decreased hearing in the left ear due to mastoid sinus disease and fundoscopy revealed Lisch nodules. Clinically, the patient had multiple café au lait spots and a neurofibroma in the cervical region. Laboratory investigations revealed: creatinine 1387umol/L; urea 71 mmol/L; bicarbonate 7mmol/L and potassium 5.4 mmol/L. The urine dipstick was positive for proteins (+2) and trace red blood cells (RBC). Urine microscopy showed few RBCs and numerous Neurofibromatosis with Bilateral Renal Artery Stenosis and end Stage Renal Disease Case report 168 | SQU Medical Journal, August 2009, Volume 9, Issue 2 granular casts. Haemoglobin was 10.1 g/dl; platelets 204 x 109l; serum catecholamines 1 pmol/l; serum calcium 1.89 mmol/l and serum phosphate was 3.81mmol/l. Tests for cytoplasmic antibodies (ANCA), anti-nuclear antibodies (ANA), hepatitis B, hepatitis C and HIV 1&2 were negative. An ultrasound of the abdomen demonstrated that both kidneys were small in size with significantly increased cortical echogenicity. The left kidney measured 8.1 cm in length and the right kidney 7.8 cm. A renal magnetic resonance angiography (MRA) showed severe proximal bilateral renal artery stenosis [Figure 1]. Magnetic resonance imaging (MRI) of the head showed chronic otitis media with mastoitidis and an intercostal neurofibroma in the cervical area. The patient was started on haemodialysis three times per week with a satisfactory outcome. His blood pressure was controlled on atenolol. An arteiovenous fistula was created for long term renal replacement therapy. He had no potential donor for a kidney transplant. Discussion Neurofibromatosis is an autosomal dominant neurocutaneous disorder with an incidence of approximately 1 in 3,000 individuals.1 Approximately half of the cases are familial and the remainder are due to new mutations.2 The diagnostic criteria developed by the National Institutes of Health are based upon the presence of specific clinical features, at least two of which must be present to make a diagnosis of NF-1:1 1. Six or more café au lait macules >5 mm in diameter in prepubertal and >15 mm in diameter in postpubertal individuals. 2. Two or more neurofibromas of any type or one plexiform neurofibroma. 3. Freckling in the axillary or inguinal regions. 4. Optic glioma. 5. Two or more Lisch nodules (iris hamartomas) 6. A distinctive bony lesion such as sphenoid dysplasia or thinning of the long bone cortex with or without pseudoarthrosis. 7. A first-degree relative with NF-1 based upon the above criteria. The cardinal features of NF-I in this patient were the presence of Lisch nodules and a positive family history. This patient illustrates the complete penetrance of the affected gene. The likelihood is that individuals carrying the mutation will be affected over several generations, but with a variable expression of the disease.3 Hypertension is a frequent finding in adults with NF-1 and may develop during childhood. It is found in most cases, but vascular lesions producing renovascular hypertension are more frequent in NF-1 patients.4 Renovascular lesions can be detected in patients who are still normotensive; the frequency with which such patients will develop hypertension is not known. Coarctation of the aorta is a known cause of hypertension that also tends to occur in NF-1. A much less common cause of hypertension in NF-1 is pheochromocytoma, which has been clinically identified in 0.1 to 5.7% of patients. The mean age at diagnosis was 42 years.5 Our patient had hypertension upon presentation and was found to have bilateral proximal renal artery Figure 1: Minimum Intensity Projection (MIP) of magnetic resonance angiography (MRA) of the renal arteries shows severe stenosis of the proximal segments of both renal arteries (arrows). Mohamed Al-Rawahi, Dawood Al-Riyami, Mahfooz A Farooqui, and Hamoud Al-Duhli Case Report | 169 stenosis. Serum catecholamine levels were normal hence pheochromocytoma was ruled out as a cause of secondary hypertension. Most patients with NF-I vascular abnormalities are asymptomatic, but have involvement of multiple vessels.6 The prevalence of vascular lesions is not well known, however, large clinical series estimate them to be around 0.4% to 6.4%.6 Symptoms usually occur in childhood or early adulthood. The renal artery is the most frequent site of involvement with a prevalence of 41% of all vascular abnormalities, of which 68% are unilateral. In addition, these lesions are more stenotic than aneurysmal.7 Renovascular hypertension is the most common presentation of these vascular abnormalities.8 Abdominal aortic coarctation, internal carotid artery aneurysms, and cervical vertebral arteriovenous malformations are other common manifestations.8 End stage renal disease (ESRD) has been reported in very few individual case series in the literature due to chronic ischaemia of the kidneys as a result of renal vascular abnormalities. This patient had ESRD which was due to bilateral renal artery stenosis and secondary hypertension. His ESRD was managed with renal replacement therapy as no suitable donor was found. His hypertension was managed with atenolol with good response. Percutaneous transluminal angioplasty (PTA) had a limited role for this patient as the blood pressure was well controlled with anti-hypertensive therapy. Renal failure would have not improved with PTA as both kidneys were small and indicated chronic renal insult. Moreover, the success due to the ostial localisation of renal arterial stenosis (RAS) and the tough fibrotic tissue involved is often refractory to dilatation.9, 10 Nephrectomy would have been a probable choice if blood pressure were difficult to manage medically. Conclusion In summary, neurofibromatosis is a disorder usually associated with unilateral RAS. We believe that this is the first case report of this condition to present as ESRD. All young patients (< 30 year) with hypertension should be clinically screened very early for secondary causes of hypertension including neurofibromatosis so that renal revascularization can be offered before permanent end organ damage has occurred as in this patient. References 1. National Institutes of Health consensus development conference: neurofibromatoses. Arch Neurol 1988; 45:575-8. 2. Riccardi VM. Neurofibromatosis: Phenotype, natural history, and pathogenesis. Baltimore: Johns Hopkins University Press, 1992. 3. Easton DF, Ponder MA, Huson SM, Ponder BA. An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet 1993; 53:305. 4. Fossali E, Signorini E, Intermite RC, Casalini E. Renovascular disease and hypertension in children with neurofibromatosis. Pediatr Nephrol 2000; 14:806. 5. Walther MM, Herring J, Enquist E, Keiser HR, Linehan WM. Von Recklinghausen’s disease and pheochromocytomas. J Urol 1999; 162:1582. 6. Lin AE, Birch P, Korf BR, Tenconi R, Niimura M, Poyhonen M, et al. Cardiovascular malformations and other cardiovascular abnormalities in Neurofibromatosis type I. Am J Med Genet 2000; 95:108-17. 7. Elias DL, Ricketts RR, Smith RB. Renovascular hypertension complicating neurofibromatosis. Am Surg 1985; 51:97-106. 8. Hamilton SJ, Friedman JM. Insights into the pathogenesis of neurofibromatosis 1 vasculopathy. Clin Genet 2000; 58:341-4. 9. Hughes RJ, Scoble JE, Reidy JF. Renal Angioplasty in Non-Atheromatous Renal Artery Stenosis: Technical Results and Clinical Outcome in 43 Patients. Cardiovasc Intervent Radiol 2004; 27:435-40. 10. Miller GA, Ford KK, Braun SD, Moore AV Jr, Malone R, Dunnick NR. Percutaneous Transluminal Angioplasty vs. Surgery for Renovascular Hypertension. AJR 1985; 144:447-50.