thoracic aortic dissection in a patient with autosomal dominant ...

THORACIC AORTIC DISSECTION IN APATIENT WITH AUTOSOMAL DOMINANT

POLYCYSTIC KIDNEY DISEASETolulola Adeola, MD, Olufemi Adeleye, MD, James L. Potts, MD, Marquetta Faulkner, MD,

and Ayodeii Oso, MDNashville, Tennessee

Autosomal dominant polycystic kidney disease is one of the most common hereditary dis-eases, and frequently has well defined extrarenal manifestations. Very few cases of aorticaneurysms associated with this disorder are described in literature. We report a 42-year-oldmale with autosomal dominant polycystic kidney disease presenting with dissecting aneurysm ofthe thoracic aorta. J Natl Med Assoc. 2001;93:282-287.)

Key words: aortic aneurysm, thoracic *complications, etiology, diagnosis * kidney,

polycystic, autosomal dominant *physiopathology, genetics, epidemiology,

complications

Autosomal dominant polycystic kidney disease(PKD) is a systemic disorder primarily affecting thekidneys that develops multiple bilateral cysts thatare characteristic of this condition. Extrarenal man-ifestations of PKD include hepatic cysts,' colonicdiverticula,2 intracranial berry aneurysms,3 cardiacvalvular anomalies, particularly mitral valve pro-lapse,4 pancreatic,5 and splenic cysts.i Associationwith aortic aneurysm is uncommon, and the major-ity of reported cases involve abdominal aortic aneu-rysms.7'8 Descriptions of thoracic aortic dissectioncomplicating PKD are rare.9''2 We present one suchcase.

© 2001. From the Department of Internal Medicine, Meharry MedicalCollege, Nashville, Tennessee. Request for reprints should be ad-dressed to Dr. Olufemi Adeleye, Department of Internal Medicine,Meharry Medical College, 1005 D. B. Todd Boulevard, Nashville, TN37208.

CASE REPORTA 42-year-old African-American male presented

to the emergency room with complaints of constant,nonradiating substernal chest tightness occurring atrest, of about 24 hours' duration. There were noassociated symptoms. Past medical history is signifi-cant for hypertension since age 22.On physical examination, the patient was not in

apparent distress and had normal habitus. He wasafebrile, blood pressure was 214/148, pulse rate of104/min, and respiratory rate of 16/min. He had aheaving apical impulse, S4 gallop rhythm, grade 2/6holosystolic murmur at the left lower sternal border,and equal carotid and peripheral arterial pulsationsbilaterally.

Relevant laboratory test results were: creatininekinase 95 U/L, troponin I 0.12 ng/mL, blood ureanitrogen 28 mg/dL, serum creatinine 3.1 mg/dL,serum potassium 4.2 mEq/L, hemoglobin 9.9 g/dL,hematocrit 30.1%, and MCV 84.8 fl. There were nobaseline laboratory test results for comparison asthis was the patient's first visit to our facility. Urinal-ysis showed 3 + protein, no red blood cells or casts,and urine drug screen was positive for benzodiaz-epines. Electrocardiogram showed normal sinusrhythm with T wave inversion in leads V4 through

282 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 93, NO. 7/8, JULY/AUGUST 2001

THORACIC AORTIC DISSECTION IN POLYCYSTIC KIDNEY DISEASE

Figure 1. Posterior-anterior chest radiograph showingprominent aortic knob.

V6. Chest x-ray revealed prominence of the aorticknob, and blunting of the left costophrenic angleposteriorly (see Figs. 1 and 2).

The patient was admitted to the coronary careunit and intravenous nitroprusside and labetalol ad-ministered for blood pressure control. Magnetic res-onance imaging of the thorax was done, becausepatient's renal function precluded contrast-en-hanced computed tomography, and it revealed a4-cm aneurysm of the thoracic aortic arch with Stan-ford Type B dissection (Figs. 3 and 4) and fluid inthe left pleural space presumed to be blood. Subse-quent transesophageal echocardiography con-firmed the above finding and did not show evidenceof mitral valve prolapse. Myocardial infarction wasruled out and blood pressure controlled. Renal ul-trasound was done as part of work-up for renalfailure and it showed multiple cysts bilaterally con-sistent with PKD (Fig. 5). Left and right kidney sizeswere 19.1 cm and 20.7 cm, respectively. Three smallhepatic cysts were also noted on ultrasonography.

Surgical opinion was sought, and surgical inter-

Figure 2. Lateral chest radiograph showing posterior blunt-ing of the left costophrenic angle.

vention was recommended based on an increase insize of pleural fluid on subsequent imaging. How-ever, surgery was not done as patient declined peri-operative blood transfusion based on religious be-liefs. He was thus managed medically. Serialhemoglobin and hematocrit monitoring showed noappreciable change. The remainder of his hospitalstay was uneventful, and hemoglobin and hemato-crit were 9.6 and 29.9, respectively, on discharge.

Incidentally, a left popliteal Baker's cyst was de-tected on duplex sonography performed to rule outdeep venous thrombosis. At last follow-up, he wasasymptomatic, blood pressure was controlled, andthere had been no deterioration in his renal func-tion.

DISCUSSIONAutosomal dominant polycystic kidney disease

has a prevalence of 1:400 to 1:1000 in live births.13Approximately 90% of cases are inherited in an

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 93, NO. 7/8, JULY/AUGUST 2001 283


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THORACIC AORTIC DISSECTION IN POlYCYSTIC KIDNEY DISEASE

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Fiur 5 Ultasun of righ kine shwn mutil cysts.

autosomal dominant fashion whereas the remain-der result from genetic mutations. The genes in-volved have been identified. Eighty-five to ninetypercent of patients have the PKD1 gene on theshort arm of chromosome 16,14 whereas 10% to15% have the PKD2 on the long arm of chromo-some 4.15 The mechanisms involved in cyst forma-tion are still poorly understood. The PKD1 genecodes for a membrane glycoprotein called polycys-tin, which appears to function as a receptor forcell-cell or cell-matrix interactions, whereas thePKD2 gene product has significant homology to afamily of voltage-activated calcium channels. It isthought that polycystin has an essential role in epi-thelial cell differentiation. When defective, there isimpaired cell maturation, abnormal cell prolifera-tion, and expression of altered amounts of other-wise normal electrolyte transport proteins, culmi-nating in cyst formation.'167 Abnormalities inextracellular matrix components have been demon-strated,'8 which may be related to defective polycys-tin and are likely contributory to cyst formation.

Ultrasonography is the diagnostic procedure ofchoice because of its high sensitivity and safety. Sen-sitivity increases with patient's age and almost all

individual over the age of 30 have cysts. Detection ofat least three cysts in each kidney in an individualwith a family history of PKD is generally consideredas diagnostic.13 A positive family history was notelicited in our patient. One explanation for this isthat the disease could have resulted from geneticmutation. The other is the inability to rule out au-tosomal dominant inheritance based on family his-tory alone. Only 60% of patients will report a familyhistory of the disease, whereas renal imaging ofpatient's parents reveals the disease and autosomaldominant inheritance in another 30%.13

Currently, association of thoracic aortic dissec-tion with PKD is not well recognized. To our knowl-edge, there are only four previously reported casesof this association in the absence of Marfan's syn-drome.710 Incidence of thoracic aortic dissectionhas been reported to be seven times more commonin patients with PKD than in the general populationat autopsy.'9 There are two reported cases of pa-tients with both Marfan's syndrome and PKD whodeveloped thoracic aortic dissection.20'2' Marfan'ssyndrome is a well-recognized predisposing factor toaortic dissection and accounts for 6% to 9% of allthoracic dissections.22'23 Other predisposing factors



include Ehlers-Danlos syndrome, hypertension, age,bicuspid, aortic valve, iatrogenic trauma, and preg-nancy.24'25

Apart from hypertension, none of the above-mentioned factors was present in our patient. Hy-pertension is frequently present in patients withaortic dissection and one study reports a history ofhypertension in almost 80% of 236 cases of aorticdissection.22 The opinion that polycystin and extra-cellular matrix abnormalities may primarily predis-pose individuals with PKD to thoracic aortic dissec-tion is supported by a recent study. In that study,immunohistochemistry was used to demonstrate ex-pression of polycystin in normal arterial smoothmuscle cells, and an altered pattern of expression inspecimens of intracranial aneurysms, thoracic aorticdissection, and dolichoectatic arteries of ten pa-tients with PKD.26 In our patient, it is more likelythat the marked hypertension was the major predis-posing factor, with vascular anomalies secondary toPKD being contributory.

Management of thoracic aortic dissection de-pends on the site. Proximal dissections involve theascending aorta (Stanford type A or DeBakey typesI and II), and are managed surgically. In-hospitalmortality rate after surgery is 15% to 20%. Distaldissections involve the descending aorta (Stanfordtype B or DeBakey type III) and are managed med-ically with certain exceptions. The in-hospital mor-tality rate of medically managed treated patient withdistal dissection is 15% to 20%. Indications for sur-gery in distal dissection include clinical evidence ofpropagation, compromise of major branches of theaorta, rupture or impending rupture, and contin-ued pain.27

This case further emphasizes the systemic natureof PKD, and clinicians should bear this in mindwhen evaluating these patients. A high index ofsuspicion for thoracic aortic dissection should beentertained when these patients present with chestpain and appropriate work-up initiated. In the eventof misdiagnosis when chest pain is the presentingsymptom, use of anticoagulation to treat presumedmyocardial ischemia could be catastrophic.

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9. Paynter HE, Parnham A, Feest T.G, et al. Thoracic aorticdissection complicating autosomal dominant polycystic kidneydisease. Nephrol Dial Transplant. 1997;12:1711-1713.

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14. Reeders ST, Bretuning MH, Davies KE, et al. A highlypoly!morphic DNA marker linked to adult polycystic kidney dis-ease oIn chromosome 16. Natur-e (Loand). 1985;317:524-544.

15. Kimberling X\J, KuLmar S, Gabow P, et al. Auitosomaldominant polvcvstic kidnev disease: Localization of the secondgene to chromosome 4ql3-q23. Genomics. 1993;18:467-472.

16. WNatnick T, Germino GG. Molecular basis of auitosomaldominanit polycvstic kidney disease. Senin Nep)hrol. 1999;19:327-343.

17. Grantham,tJ. The etiology, pathogenesis, and treatmiientof autosomal dominant polycystic kidney disease: recent ad-vances. An JKidney Dis. 1996;28:788-803.

18. Wilson P, Schrier RWN, Breckoin RD, et al. A newv methodof studying huLmain kidney disease epithelia in cuLltuLre. Kidney Int.1986;30:371-378.

19. Torres YE. Systemic mainifestations of renal cystic dis-ease. In: Gaidner KD, Berniestein J, eds. The Cystic Kidniey. Dor-drecht, The Netherlands: Kluwer; 1990:295-326.

20. Somiilo S. Rutecki G, Giuffia IA, et al. A kindred exhib-itinlg cosegregation of an overlap connective tisstlCdisordel- anldthe chromosomie 16-linked form of an atitosomal dominant poly-cvstic kidney disease.J Ami Soc Nephrol. 1993;4:1371-1378.

21. Biermann CXV, Rutishlatuser G. Polycystic kidneys associ-ated with Marf:an's syndrome in an aduLlt. Scand./ Urcl ANphcol.1994;28:295-296.



22. Spitell PC, SpitellJAJr,JoyceJW, et al. Clinical featuresand differential diagnoses of aortic dissection: experience with236 cases (1980 through 1990). Mayo Clin Proc. 1993; 68:642.

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