- Email: [email protected]
Atheromatous Embolism as a Cause of Renal Failure
THJ:
VoL 83, No. 3. March 1960 Printed in U.S.A.
ATHER.O:'vlATOUS EMBOLISM AS A CAUSE OF RE.:'\AL FAILURE ROBERT M. GREENDYKE
AND
The anatomical demonstration of embolism from eroded atheromatous arterial plaques appears first to have been described in the American literature by Flory m 1945. 1 Athcromatous embolism, however, is mentioned in certain of the older German textbooks of pathology2 • 3 :md also is noted by a number of earl)' authors as quoted by Denson 4 and by Zak and Elias. 5 Since the publication of Flory's work, a small number of additional studies of this phenomenon have appeared. lVIeyer reported 2 cases 6 and Zak and Elias three additional cases 5 characterized by arterial embolization of various organs by athcromatous material. Zak and Elias pointed out that the embolic material need not necessarily come from aortic atheromata but may arise from a systemic artery or cardiac valve . Hancller 7 has reported a series of patients with atheromatous embolization, discussing the possible connection between renal involvement and systemic hypertension. Thurlbeck and Castleman 8 have described a grnup of cases demonstrating acute atheromatous (,mbolization of remd arteries following grafting operations for aortic aneurysms. The renal shutdow11 and/or uremia exhibited in many of their fatal cases was ascribed to this process. Accepted for publication September 24, 1959. This investigation was supported in part by Trnineeship No. 2G-1:33 (Cl) from the Research Trnining Branch, U. S. Pttblic Health Service. * Rockefeller Foundation Fellmv. 1 Flory, C. M.: Art1,rial occlusions produced by emboli from eroded aortic atheromatous plaques. Am. J.Path. 21: 549-565, HJ45. 2 Aschoff, L.: Pathologische Anatomie, ed. 5. Jenn: C. Fischer, 1921, p. 71. '1 Kaufman, E.: Pathologischen Anatomie, ed. 7 and 8. Berlin & Leipzig: Walter de Uruyter & Co., HJ22, vol. 1, p. 87. 4- Benson, R. L.: The present status of coronary arterinl disease. Arch. Path., 2: 876-916, 1926. 5 Zak, F. G. and Elias, K.: Embolization with nmterial frnm atheronrnta. Am. J. J\Ied. Sc., 218:
YASUYUKI AKAMATSU*
Atheromatous embolization manifested elini Winter" as cally has recently been described cause of cerebral infarction, by Probstein and associates 10 as a cause of acute pancreatitis, and by Witmer 11 in a case of retinal t1rterial emboliza tion. Little mention, however, is made in tl1t•, literature of atheromatous embolimn. as a cause of Ghronic, progressive renal failure. The purposr: of this communication is to report the cliniral and pathological findings in three such cases m which renal failure was either clinically un explained or attributed to other ca.uses. CASE REPORTS
Case 1. A 66-year-old white man was fir~t. admitted to the hospital on December 11, i 9/S8. He had been generally well until ,i montl,s previously when feelings of unexplairwd prompted him to consult his physician. Hr told that he had "heart failure" and waR italized at this time. Over the Pnsuing 3 mm1.ths the patient complained of mild dyspnea 011 exertion and anorexia, losing 25 pounds in An acute episode of short1wss of breath the of admission prompted him to seek tion. On admission, the patient had acute pulmonary edema and showed additional cviclenGe of congestive circulatory failure. His blood pressure was 150/90. A poorly felt, mid-abdominal mass was also thought to present. Urinalysis showed a specific l.014, 2 plus albumin, and occasional casts. Blood urea nitrogen at this time mw l 0 mg. per cent. A chest x-rny revealed n pleural effusion and an infiltrative dcnsit:\' in the lower lobe of the right lung. An electro cardiogram showed left ventricular sinus tachycardia, and evidence of old anterior and posterior myocardial infarcts. Initially, the patient improved with
510-,515, 1949. 6 Meyer, W. W. · Cholestrinkrystallembolie kleiner Organarterien. Virchow's Arch. f. path. Anat., 314: 616-638, Hl47. 7 Handler, F. P.: Clinical and pathologic sig nificance of atheromatous ernbolization, with emphasis on an etiology of renal hypertension.
Am. J. Med., 20: :36()-:373, HJ56.
"'Winter, W. J., Jr.· Atheromato11s emboli · cause of cerebral infarct.ion. Arch. Path., 137-142, 1957. 10 Probstein, J. G., ,Joshi, R. A. and Blume1t,, thal, H. T.: Atherornatous ernboli½ation, an etiol ogy of ncute pa.ncreatitis. Arch. Surg., 75: 5GG-fi7.t,
Hl57.
Thurlbeck, W. M. and Castlenrnn, B.: Atheromatous emboli to the kidneys after aortic surgery. Xew Eng. J. Med., 257: H2-447, 1957.
11 Witmer, R. and Schmiel, A.· Cholesturin · kristall als Retinaler arterieller Embolus.(lph thalmologic,1, 135: 4:32-4:3:3, Hl58.
8
2:31
232
R. M. GREENDYKE AND Y. AKAMATSU
therapy. His condition, however, deteriorated over the ensuing week so that by the eighth hospital day he had become semicomatose. Significant congestive circulatory failure was not present. Serial determinations of the blood urea nitrogen over this time showed a steady rise to levels of 100 mg. per cent. Over the ne:ld; 5 days the patient experienced a modest diuresis with fall in blood urea nitrogen to a low of 34 mg. per cent on December 23 and associated clinical improvement. Repeated urine examinations showed a specific gravity fixed at 1.013 and 2 plus to 4 plus albumin. The patient again began to fail
clinically, and again elevation of the blood urea nitrogen was noted. On December 30 a definite pulsating abdominal mass could be outlined for the first time. Blood urea nitrogen values rose to 90 mg. per cent, and the patient expired on January 3, 1959. The final clinical impression was abdominal aortic aneurysm with probable encroachment on the renal arteries and secondary uremia. At postmortem examination, the heart was enlarged to 500 gm. and exhibited diffuse, patchy myocardial scarring. The coronary arteries exhibited severe sclerosis, and the right coronary
Fm. l. Case l. Section of kidney. A, one of numerous areas of cortical scarring, with relatively normal parenchyma adjacent. Old atheromatous embolus occluded large artery at apex of this scar below photographed field. Hematoxylin and eosin, X20. B, note several small arteries occluded by atheromatous emboli and proliferated intimal tissue. Verhoff-van Gieson, X 16.
ATHEROMA'I'OUS EMBOLISM AS A CAUSE OF RENAL FAILURE
artery was ocdudecl a thrombus several days old. The tip of the right atrial appendage exhibited an infarct of approximately the same age as the coronary thrombus and in addition contained a recent mural thrombus. A single embolus in the lower lobe of the right lung was associated with a recent pulmonary infarct approximately 3 cm. in greatest dimension. Patchy ulcerating inflammation was present in the distal portions of the esophagus and colon. The entire aorta exhibited severe artcriosclerotic changes, more marked in the abdominal portion, with many ulcerations of plaques. A 4 by 10 by 13 cm. intact aneurysm partially filled with laminated blood clot was found distal to the renal artery orifices. Both renal arteries were widely patent. The kidneys each weighed 130 gm. and presented granular surfaces marked by small depressed scars. Irregular narrowing of both cortices was present. :\Iicroscopic examination of the kidneys disclosed numerous V-shapecl cortical areas of atrophy and scarring in which many of the glomeruli were hyalinized, with associated tubular atrophy, increase in interstitial tissue, and scant mononuclear cell infiltration (fig. 1, A). At the apex of many of these abnormal areas was found a. medium sized artery occluded by a mass of proliferated intimal tissue containing one to several acicular clefts (fig. 1, B). In most instances the internal elastic lamina and media of these arteries showed no change, although in a few instances these clefts extended into or through the wall of the vessel and were associated with reactive fibrosis in the adventitia. In some instances, multinuclcated, foreign-body giant cells were found about these clefts. In a few vessels, brown, iron-containing pigment was seen in the proliferated intimal tissue. Recanalization of one artery was seen. In addition to older, more chronic changes of the above type, a fe11· arterial lumina were seen to contain acicular clefts surrounded either by fresh thrombus or unagglutina.tcd erythrocytes. The changes described were not confined solely to arcuate arteries, but were found in smaller vessels ranging in size down to afferent arterioles. Scattered glomeruli outside of the larger zones of atrophy also exhibited hyalinization. No areas of recent infarction were seen in either kidney, nor was significant inflammation present. Appreciable arteriolar sclerosis was not demonstrated. Marked
intimal thickening of interlobular and intrn lobular arteries was seen in some areas, hut step-sections taken through the blocks of tissuP frequently revealed atheromatous cmboli occluding these vessels at other levds. Scl) and 3. Frozen sections of forrnalin-fix<~d renal tis~ue when viewed by polarized light disdosc,cl refractile crystals occupying the cleft--like spacer, noted in arterial lumirni, in the paraffin sections (fig. 4). Treatment of such sect.ions to dermmstrate the Liebermann-Burchard reaction gave a positive result for cholesterol in these area,,;. Frozen sections stained with oil red O to derno11strate neutral fats were negative. Atheromatous emboli of the type described the kidneys were also fournl in rontiuc scd.imrn of pancreas, gallbladder, colon, and prostate. No associated changes iri these organs \HTe found Case .!/!. A 52-year-old white man was first admitted to the hospital on August :3, 1958. He had been known to be hypertensfre for a.t Jem,ttwo years. An asymptomatic abdominal aortic; aneurysm had been discovered 7 months to admission. He had suffered intermitte11t claudication of progressively for the past 6 months and had "'"'""r'""' episode of retinal arterial embolism 2 week8 prior to admission. Severe occipital headacbH, and emotional instability prompted tion for control of his hypertension. On the patient appeared robust and healthy. The bJood pressure was 230/13ll Hypertensiw. n,tinopathy, cardiomegaly, and a pulsatile 8 cm. 8bdominal mass were noted. Urinalysis showed specific gravity of 1.008, 1 plus ;dbumin. and small numbers of leukocytes and hyaline ea8t~ in the centrifuged sediment. Blood 1.1rea at this time was 29 mg. per cent. Phenolsul-· fonphthalcin excretion was 20 per cent in hours. The patient was discharged on medications on August la days later (August 22) ir1 of complaining of nausea and unrelenting headache. Blood pressure at this time waR 140,. awl papilledema present. Gradual diuical ment occurred over the next sen,ral blood urea nitrogen wm; 64- mg. per cent on admission (August 22), rising to s::i on falling to 36 on s~ptember 5, and climbinµ; to .rn on the clay of discharge (Sept.ember lO). Per
i
i
J
i
•.• -_l
,.
~
Ci:)
~
~
~
I zlj ~t,j
p,-
zlj ~
; q
FIG. 3 Fm. 2 Frns. 2 and 3. Interlobular renal artery sectioned at four levels in a single paraffin block. Marked endarteritis seen in A is noted to be associated with atheromatous occlusion of vessel at deeper levels. Hematoxylin and eosin, XlOO.
.\THJ~ROMA'rous EMBOLISM .-\S .-\ CAUSE OF REXAL FAILURJ,J
sistent hiccoughs and guaiac positive stools were features of this admission. Albuminuria and in. ability to produce concentrated urine \n,re again noted. The patient's final admission on September 26 was prompted by increasing nwntal confusion and irritability. No change in the aneurysm was noted. Blood urea nitrogen was 49 mg. per cent, rising to 93 mg. per cent ovn the ensuing 10 days. On October 10 the patic'nt suddenly went into shock and expin·cl. The clinical impression was hypertensive cardiovascular disease in an accelerated phase, nephrosc.lerosis, and artcri· osclerotic aneurysm of the aorta with possible involvement of the rerml arteries and terminal rupture. At postmortem examination, the heart was enlarged to 700 gm. with marked left ventricular hypertrophy and pakhy sulwndocardial scarring. The aorta revealed sewrc artcriosdcrotic changes with extensive areas of ulceration over its entire length. An aneurysm 8 cm. in length ancl 5 to 7 cm. in width was situated distal to the origin of the renal arteries, not encrnaching upon their orifices. A posterior rupture was present in the aneurysm, associated with an extensive: fresh retro. peritoneal hematoma. The kidneys weighed 180 and 150 gm. and exhibited granular surfaces free from major scars. Tbe cortires were irregularly narrowed,
:\Ticroscopically, the appem·am:c of the tions of kidney was very similar to that described in the previous case, with large numlwrn of old atheromatous emboli occluding arterial vess<'ls or all sizes. Cholesterol crystals lying frer in artcria l lumina were present in small numbcrn. of atrophic parenchyrna were found in assocJ:1· tion with the older vascular lesions, No degree of arteriolar sclerosis or inflammation was present. Atlwromatous emboli were also found in one to six :n'teries per section of spleen, esophagus, liver, and adrenals. Case 3. A 7l·year·olcl white man was admittrnJ to the hospital on August 22, J 956. He had bec·11 well until 5 months previously when he had IJCPH briefly hospitalized for symptoms of circulatory failure which n'spcmdccl well to ther· apy. He had been anorctie sine(; this time, hmr· ever, and a semi.invalid. On the day of admissim1 he had fallen and sustained a fracture of the femoral neck. On admission to the he appeared chronically ill and showed elinic:ll. and radiological evidence of the fracture. The blood pressure was 180 /90. Pulmonary scma, cardiomegaly with atrial fibrillation, of mild rongestive circulatory failure, and monary ostcoarthropathy \\·ere present. l:rinaJ ysis showed 2 phrn albumin and :small mmiberc of leukocytes in the crntrifuged scdinwnt, Tlw blood urea nitrogen was 05 mg. per eent. The pa-
Fm. 4. Case 1. Fresh frozen section of renal tissue viewed under polarized light. Intedobi1la1 artery is seen to contain numerons doubly-refractik crystals within its lumen, presumably ehol(•sterril, Unstained, X 100.
236
R. M. GREENDYKE AND Y. AKAMATSU
tient became confused and began to vomit. Three days after admission, the blood urea nitrogen had risen to 120 mg. per cent. The patient expired on August 31. The clinical impression was: uremia, cause undetermined, probably due to nephrosclerosis. At postmortem examination, the body was poorly nourished and disclosed evidence of fracture of the femoral neck. The heart was enlarged to 540 gm. and showed focal scarring of the left ventricular myocardium. Emphysema, marked edema, and evidence of chronic passive hyperemia were present in the lungs. The aorta, especially in its abdominal portion, evidenced severe arteriosclerosis with erosion of numerous plaques. The kidneys weighed 150 gm. each and exhibited granular surfaces and narrow cortices. Microscopically, the kidneys showed numerous old and recent atheromatous arterial emboli with associated cortical atrophy. No other significant alterations were present in the kidneys. Arteriolar sclerosis unassociated with cholesterol emboli was not seen. Old atheromatous emboli numbering 1 to 5 per section were also present in spleen, stomach, jejunum, pancreas, liver, adrenals, testes, and thyroid without discernible parenchymatous change. No fat embolism could be demonstrated. DISCUSSION
Despite several recent articles in the literature, the phenomenon of atberomatous embolization appears to have attracted little attention. Little or no mention of the process is made in the standard English language texts of pathology, medicine, or surgery, although the concept of atheromatous embolization is not a new one, having been suggested by Panum12 in 1862. As Benson observed in 1926, atheromatous embolization probably occurs with considerably greater frequency than is generally appreciated. In a group of 57 cases showing aortic arteriosclerosis with marked erosion of plaques, Flory found the incidence of atheromatous embolization to be 12.3 per cent. In 147 cases exhibiting erosions of only slight or moderate degree, this incidence was only 1.3 per cent. Handler found an incidence of atheromatous embolization of 8.6 per cent in 70 consecutive routine autopsies. 12 Panum, L. P.: Experimentelle Beitrage zur Lehre von der Embolie. Virchow's Arch. f. path. Anat., 26: 308-338, 1862.
In a study conducted by the present authors, 13 atheromatous embolism to the kidneys was found in 7 per cent of an autopsied group of 172 patients with arteriosclerotic aortic aneurysms on whom no vascular surgery bad been performed. The degree of erosion of aortic atheromata in these cases, unfortunately, could not be assessed accurately from most of the protocols. The clinical significance of atheromatous embolism is not fully appreciated. The possible consequences of coronary artery embolization, such as occurred in one of the cases of Zak and Elias, are obvious. Only more recently, however, has atheromatous embolization been recognized as an etiological factor in cases of pancreatitis and cerebral infarction. Thurlbeck and Castleman showed that acute renal shutdown and uremia occurring in patients subjected to surgical aortic grafting frequently were explainable on this basis, and also quite conclusively proved that the vascular lesions under discussion are indeed embolic in nature and not unusual forms of localized arteriosclerosis. The correlation between the renal failure observed clinically in the patients reported in this study and the indictment of atheromatous emboli as the underlying anatomical cause of this failure is based on the following observations: 1) Extensive atrophy and scarring of renal parenchyma was present in each case. This change, however, was not diffuse in character, but present in wedge shaped zones separated by relatively unaffected tissue. This is the type of alteration characteristically associated with irregular involvment of vascular supply to an organ and is consistent with embolization. 2) At the apex of most of the affected wedges of renal tissue was found a large artery occluded by an atheromatous embolus. Similarly occluded smaller cortical vessels frequently were found near small foci of scarring. 3) Step-sections taken through blocks of tissue showing arteries exhibiting only severe sclerotic changes in the initial sections frequently revealed occlusion by atheromatous emboli at another level. 4) Features of other renal diseases which might account for the observed parenchymal atrophy and scarring were absent. Specifically, pyelonephritis and arteriolar sclerosis of the usual type were not present. 13 Greendyke, R. M. and Akamatsu, Y.: Unpublished data.
ATHEl:WMATOUS EMBOLISM AS :\_ CAUSE OF RENAL FAILU8.E
The anatomieal changes seen in the kidneys of the patients discussed suggest a chronic, continuing eourse of rPpeatecl atheromatous embolization. Acute infarcts of the type reported by Thurlheck and Castleman were not seen. Rather, the process appeared to be one of gradual vascular occlusion, the cumulative effect of which finally may reduce the amount of functioning parenchyma to the point where renal failure occasionally becomes clinically apparent. In this regard, the im:ompleteness of our present knowledge regarding the correlation between the histologic appearance and functional capacity of the kidney is only re-emphasized. It is felt that atheromatous embolization of thn renal arteries should be considered clinically in the differential diagnosis of patients in older age groups suffering from unexplained renal failure.
Even in cases where an adequate appears to be present, this possibility de~erv(:c; consideration. The first two cases in this report, where aneurysmal encroachment on renal Yascul:tr supply was felt clinically to bco tbe rau~e of rcn:JJ failure, illustrate the reason for tbi8 SUMMARY
Three cases of chronic renal failure due to athcromatous embolism from eroded arterial plaques are presented. The literature atheromatous embolism is brief-iy reviewed. It is suggested that this phenomenon is more common than is generally appreciated. Atl1eroma.tom, embolism deserves consideration in the clinical differential diagnosis of any t:ase of renal failure of unexplained etiology occurring in older patirnts,
VoL 83, No. 3. March 1960 Printed in U.S.A.
ATHER.O:'vlATOUS EMBOLISM AS A CAUSE OF RE.:'\AL FAILURE ROBERT M. GREENDYKE
AND
The anatomical demonstration of embolism from eroded atheromatous arterial plaques appears first to have been described in the American literature by Flory m 1945. 1 Athcromatous embolism, however, is mentioned in certain of the older German textbooks of pathology2 • 3 :md also is noted by a number of earl)' authors as quoted by Denson 4 and by Zak and Elias. 5 Since the publication of Flory's work, a small number of additional studies of this phenomenon have appeared. lVIeyer reported 2 cases 6 and Zak and Elias three additional cases 5 characterized by arterial embolization of various organs by athcromatous material. Zak and Elias pointed out that the embolic material need not necessarily come from aortic atheromata but may arise from a systemic artery or cardiac valve . Hancller 7 has reported a series of patients with atheromatous embolization, discussing the possible connection between renal involvement and systemic hypertension. Thurlbeck and Castleman 8 have described a grnup of cases demonstrating acute atheromatous (,mbolization of remd arteries following grafting operations for aortic aneurysms. The renal shutdow11 and/or uremia exhibited in many of their fatal cases was ascribed to this process. Accepted for publication September 24, 1959. This investigation was supported in part by Trnineeship No. 2G-1:33 (Cl) from the Research Trnining Branch, U. S. Pttblic Health Service. * Rockefeller Foundation Fellmv. 1 Flory, C. M.: Art1,rial occlusions produced by emboli from eroded aortic atheromatous plaques. Am. J.Path. 21: 549-565, HJ45. 2 Aschoff, L.: Pathologische Anatomie, ed. 5. Jenn: C. Fischer, 1921, p. 71. '1 Kaufman, E.: Pathologischen Anatomie, ed. 7 and 8. Berlin & Leipzig: Walter de Uruyter & Co., HJ22, vol. 1, p. 87. 4- Benson, R. L.: The present status of coronary arterinl disease. Arch. Path., 2: 876-916, 1926. 5 Zak, F. G. and Elias, K.: Embolization with nmterial frnm atheronrnta. Am. J. J\Ied. Sc., 218:
YASUYUKI AKAMATSU*
Atheromatous embolization manifested elini Winter" as cally has recently been described cause of cerebral infarction, by Probstein and associates 10 as a cause of acute pancreatitis, and by Witmer 11 in a case of retinal t1rterial emboliza tion. Little mention, however, is made in tl1t•, literature of atheromatous embolimn. as a cause of Ghronic, progressive renal failure. The purposr: of this communication is to report the cliniral and pathological findings in three such cases m which renal failure was either clinically un explained or attributed to other ca.uses. CASE REPORTS
Case 1. A 66-year-old white man was fir~t. admitted to the hospital on December 11, i 9/S8. He had been generally well until ,i montl,s previously when feelings of unexplairwd prompted him to consult his physician. Hr told that he had "heart failure" and waR italized at this time. Over the Pnsuing 3 mm1.ths the patient complained of mild dyspnea 011 exertion and anorexia, losing 25 pounds in An acute episode of short1wss of breath the of admission prompted him to seek tion. On admission, the patient had acute pulmonary edema and showed additional cviclenGe of congestive circulatory failure. His blood pressure was 150/90. A poorly felt, mid-abdominal mass was also thought to present. Urinalysis showed a specific l.014, 2 plus albumin, and occasional casts. Blood urea nitrogen at this time mw l 0 mg. per cent. A chest x-rny revealed n pleural effusion and an infiltrative dcnsit:\' in the lower lobe of the right lung. An electro cardiogram showed left ventricular sinus tachycardia, and evidence of old anterior and posterior myocardial infarcts. Initially, the patient improved with
510-,515, 1949. 6 Meyer, W. W. · Cholestrinkrystallembolie kleiner Organarterien. Virchow's Arch. f. path. Anat., 314: 616-638, Hl47. 7 Handler, F. P.: Clinical and pathologic sig nificance of atheromatous ernbolization, with emphasis on an etiology of renal hypertension.
Am. J. Med., 20: :36()-:373, HJ56.
"'Winter, W. J., Jr.· Atheromato11s emboli · cause of cerebral infarct.ion. Arch. Path., 137-142, 1957. 10 Probstein, J. G., ,Joshi, R. A. and Blume1t,, thal, H. T.: Atherornatous ernboli½ation, an etiol ogy of ncute pa.ncreatitis. Arch. Surg., 75: 5GG-fi7.t,
Hl57.
Thurlbeck, W. M. and Castlenrnn, B.: Atheromatous emboli to the kidneys after aortic surgery. Xew Eng. J. Med., 257: H2-447, 1957.
11 Witmer, R. and Schmiel, A.· Cholesturin · kristall als Retinaler arterieller Embolus.(lph thalmologic,1, 135: 4:32-4:3:3, Hl58.
8
2:31
232
R. M. GREENDYKE AND Y. AKAMATSU
therapy. His condition, however, deteriorated over the ensuing week so that by the eighth hospital day he had become semicomatose. Significant congestive circulatory failure was not present. Serial determinations of the blood urea nitrogen over this time showed a steady rise to levels of 100 mg. per cent. Over the ne:ld; 5 days the patient experienced a modest diuresis with fall in blood urea nitrogen to a low of 34 mg. per cent on December 23 and associated clinical improvement. Repeated urine examinations showed a specific gravity fixed at 1.013 and 2 plus to 4 plus albumin. The patient again began to fail
clinically, and again elevation of the blood urea nitrogen was noted. On December 30 a definite pulsating abdominal mass could be outlined for the first time. Blood urea nitrogen values rose to 90 mg. per cent, and the patient expired on January 3, 1959. The final clinical impression was abdominal aortic aneurysm with probable encroachment on the renal arteries and secondary uremia. At postmortem examination, the heart was enlarged to 500 gm. and exhibited diffuse, patchy myocardial scarring. The coronary arteries exhibited severe sclerosis, and the right coronary
Fm. l. Case l. Section of kidney. A, one of numerous areas of cortical scarring, with relatively normal parenchyma adjacent. Old atheromatous embolus occluded large artery at apex of this scar below photographed field. Hematoxylin and eosin, X20. B, note several small arteries occluded by atheromatous emboli and proliferated intimal tissue. Verhoff-van Gieson, X 16.
ATHEROMA'I'OUS EMBOLISM AS A CAUSE OF RENAL FAILURE
artery was ocdudecl a thrombus several days old. The tip of the right atrial appendage exhibited an infarct of approximately the same age as the coronary thrombus and in addition contained a recent mural thrombus. A single embolus in the lower lobe of the right lung was associated with a recent pulmonary infarct approximately 3 cm. in greatest dimension. Patchy ulcerating inflammation was present in the distal portions of the esophagus and colon. The entire aorta exhibited severe artcriosclerotic changes, more marked in the abdominal portion, with many ulcerations of plaques. A 4 by 10 by 13 cm. intact aneurysm partially filled with laminated blood clot was found distal to the renal artery orifices. Both renal arteries were widely patent. The kidneys each weighed 130 gm. and presented granular surfaces marked by small depressed scars. Irregular narrowing of both cortices was present. :\Iicroscopic examination of the kidneys disclosed numerous V-shapecl cortical areas of atrophy and scarring in which many of the glomeruli were hyalinized, with associated tubular atrophy, increase in interstitial tissue, and scant mononuclear cell infiltration (fig. 1, A). At the apex of many of these abnormal areas was found a. medium sized artery occluded by a mass of proliferated intimal tissue containing one to several acicular clefts (fig. 1, B). In most instances the internal elastic lamina and media of these arteries showed no change, although in a few instances these clefts extended into or through the wall of the vessel and were associated with reactive fibrosis in the adventitia. In some instances, multinuclcated, foreign-body giant cells were found about these clefts. In a few vessels, brown, iron-containing pigment was seen in the proliferated intimal tissue. Recanalization of one artery was seen. In addition to older, more chronic changes of the above type, a fe11· arterial lumina were seen to contain acicular clefts surrounded either by fresh thrombus or unagglutina.tcd erythrocytes. The changes described were not confined solely to arcuate arteries, but were found in smaller vessels ranging in size down to afferent arterioles. Scattered glomeruli outside of the larger zones of atrophy also exhibited hyalinization. No areas of recent infarction were seen in either kidney, nor was significant inflammation present. Appreciable arteriolar sclerosis was not demonstrated. Marked
intimal thickening of interlobular and intrn lobular arteries was seen in some areas, hut step-sections taken through the blocks of tissuP frequently revealed atheromatous cmboli occluding these vessels at other levds. Scl) and 3. Frozen sections of forrnalin-fix<~d renal tis~ue when viewed by polarized light disdosc,cl refractile crystals occupying the cleft--like spacer, noted in arterial lumirni, in the paraffin sections (fig. 4). Treatment of such sect.ions to dermmstrate the Liebermann-Burchard reaction gave a positive result for cholesterol in these area,,;. Frozen sections stained with oil red O to derno11strate neutral fats were negative. Atheromatous emboli of the type described the kidneys were also fournl in rontiuc scd.imrn of pancreas, gallbladder, colon, and prostate. No associated changes iri these organs \HTe found Case .!/!. A 52-year-old white man was first admitted to the hospital on August :3, 1958. He had been known to be hypertensfre for a.t Jem,ttwo years. An asymptomatic abdominal aortic; aneurysm had been discovered 7 months to admission. He had suffered intermitte11t claudication of progressively for the past 6 months and had "'"'""r'""' episode of retinal arterial embolism 2 week8 prior to admission. Severe occipital headacbH, and emotional instability prompted tion for control of his hypertension. On the patient appeared robust and healthy. The bJood pressure was 230/13ll Hypertensiw. n,tinopathy, cardiomegaly, and a pulsatile 8 cm. 8bdominal mass were noted. Urinalysis showed specific gravity of 1.008, 1 plus ;dbumin. and small numbers of leukocytes and hyaline ea8t~ in the centrifuged sediment. Blood 1.1rea at this time was 29 mg. per cent. Phenolsul-· fonphthalcin excretion was 20 per cent in hours. The patient was discharged on medications on August la days later (August 22) ir1 of complaining of nausea and unrelenting headache. Blood pressure at this time waR 140,. awl papilledema present. Gradual diuical ment occurred over the next sen,ral blood urea nitrogen wm; 64- mg. per cent on admission (August 22), rising to s::i on falling to 36 on s~ptember 5, and climbinµ; to .rn on the clay of discharge (Sept.ember lO). Per
i
i
J
i
•.• -_l
,.
~
Ci:)
~
~
~
I zlj ~t,j
p,-
zlj ~
; q
FIG. 3 Fm. 2 Frns. 2 and 3. Interlobular renal artery sectioned at four levels in a single paraffin block. Marked endarteritis seen in A is noted to be associated with atheromatous occlusion of vessel at deeper levels. Hematoxylin and eosin, XlOO.
.\THJ~ROMA'rous EMBOLISM .-\S .-\ CAUSE OF REXAL FAILURJ,J
sistent hiccoughs and guaiac positive stools were features of this admission. Albuminuria and in. ability to produce concentrated urine \n,re again noted. The patient's final admission on September 26 was prompted by increasing nwntal confusion and irritability. No change in the aneurysm was noted. Blood urea nitrogen was 49 mg. per cent, rising to 93 mg. per cent ovn the ensuing 10 days. On October 10 the patic'nt suddenly went into shock and expin·cl. The clinical impression was hypertensive cardiovascular disease in an accelerated phase, nephrosc.lerosis, and artcri· osclerotic aneurysm of the aorta with possible involvement of the rerml arteries and terminal rupture. At postmortem examination, the heart was enlarged to 700 gm. with marked left ventricular hypertrophy and pakhy sulwndocardial scarring. The aorta revealed sewrc artcriosdcrotic changes with extensive areas of ulceration over its entire length. An aneurysm 8 cm. in length ancl 5 to 7 cm. in width was situated distal to the origin of the renal arteries, not encrnaching upon their orifices. A posterior rupture was present in the aneurysm, associated with an extensive: fresh retro. peritoneal hematoma. The kidneys weighed 180 and 150 gm. and exhibited granular surfaces free from major scars. Tbe cortires were irregularly narrowed,
:\Ticroscopically, the appem·am:c of the tions of kidney was very similar to that described in the previous case, with large numlwrn of old atheromatous emboli occluding arterial vess<'ls or all sizes. Cholesterol crystals lying frer in artcria l lumina were present in small numbcrn. of atrophic parenchyrna were found in assocJ:1· tion with the older vascular lesions, No degree of arteriolar sclerosis or inflammation was present. Atlwromatous emboli were also found in one to six :n'teries per section of spleen, esophagus, liver, and adrenals. Case 3. A 7l·year·olcl white man was admittrnJ to the hospital on August 22, J 956. He had bec·11 well until 5 months previously when he had IJCPH briefly hospitalized for symptoms of circulatory failure which n'spcmdccl well to ther· apy. He had been anorctie sine(; this time, hmr· ever, and a semi.invalid. On the day of admissim1 he had fallen and sustained a fracture of the femoral neck. On admission to the he appeared chronically ill and showed elinic:ll. and radiological evidence of the fracture. The blood pressure was 180 /90. Pulmonary scma, cardiomegaly with atrial fibrillation, of mild rongestive circulatory failure, and monary ostcoarthropathy \\·ere present. l:rinaJ ysis showed 2 phrn albumin and :small mmiberc of leukocytes in the crntrifuged scdinwnt, Tlw blood urea nitrogen was 05 mg. per eent. The pa-
Fm. 4. Case 1. Fresh frozen section of renal tissue viewed under polarized light. Intedobi1la1 artery is seen to contain numerons doubly-refractik crystals within its lumen, presumably ehol(•sterril, Unstained, X 100.
236
R. M. GREENDYKE AND Y. AKAMATSU
tient became confused and began to vomit. Three days after admission, the blood urea nitrogen had risen to 120 mg. per cent. The patient expired on August 31. The clinical impression was: uremia, cause undetermined, probably due to nephrosclerosis. At postmortem examination, the body was poorly nourished and disclosed evidence of fracture of the femoral neck. The heart was enlarged to 540 gm. and showed focal scarring of the left ventricular myocardium. Emphysema, marked edema, and evidence of chronic passive hyperemia were present in the lungs. The aorta, especially in its abdominal portion, evidenced severe arteriosclerosis with erosion of numerous plaques. The kidneys weighed 150 gm. each and exhibited granular surfaces and narrow cortices. Microscopically, the kidneys showed numerous old and recent atheromatous arterial emboli with associated cortical atrophy. No other significant alterations were present in the kidneys. Arteriolar sclerosis unassociated with cholesterol emboli was not seen. Old atheromatous emboli numbering 1 to 5 per section were also present in spleen, stomach, jejunum, pancreas, liver, adrenals, testes, and thyroid without discernible parenchymatous change. No fat embolism could be demonstrated. DISCUSSION
Despite several recent articles in the literature, the phenomenon of atberomatous embolization appears to have attracted little attention. Little or no mention of the process is made in the standard English language texts of pathology, medicine, or surgery, although the concept of atheromatous embolization is not a new one, having been suggested by Panum12 in 1862. As Benson observed in 1926, atheromatous embolization probably occurs with considerably greater frequency than is generally appreciated. In a group of 57 cases showing aortic arteriosclerosis with marked erosion of plaques, Flory found the incidence of atheromatous embolization to be 12.3 per cent. In 147 cases exhibiting erosions of only slight or moderate degree, this incidence was only 1.3 per cent. Handler found an incidence of atheromatous embolization of 8.6 per cent in 70 consecutive routine autopsies. 12 Panum, L. P.: Experimentelle Beitrage zur Lehre von der Embolie. Virchow's Arch. f. path. Anat., 26: 308-338, 1862.
In a study conducted by the present authors, 13 atheromatous embolism to the kidneys was found in 7 per cent of an autopsied group of 172 patients with arteriosclerotic aortic aneurysms on whom no vascular surgery bad been performed. The degree of erosion of aortic atheromata in these cases, unfortunately, could not be assessed accurately from most of the protocols. The clinical significance of atheromatous embolism is not fully appreciated. The possible consequences of coronary artery embolization, such as occurred in one of the cases of Zak and Elias, are obvious. Only more recently, however, has atheromatous embolization been recognized as an etiological factor in cases of pancreatitis and cerebral infarction. Thurlbeck and Castleman showed that acute renal shutdown and uremia occurring in patients subjected to surgical aortic grafting frequently were explainable on this basis, and also quite conclusively proved that the vascular lesions under discussion are indeed embolic in nature and not unusual forms of localized arteriosclerosis. The correlation between the renal failure observed clinically in the patients reported in this study and the indictment of atheromatous emboli as the underlying anatomical cause of this failure is based on the following observations: 1) Extensive atrophy and scarring of renal parenchyma was present in each case. This change, however, was not diffuse in character, but present in wedge shaped zones separated by relatively unaffected tissue. This is the type of alteration characteristically associated with irregular involvment of vascular supply to an organ and is consistent with embolization. 2) At the apex of most of the affected wedges of renal tissue was found a large artery occluded by an atheromatous embolus. Similarly occluded smaller cortical vessels frequently were found near small foci of scarring. 3) Step-sections taken through blocks of tissue showing arteries exhibiting only severe sclerotic changes in the initial sections frequently revealed occlusion by atheromatous emboli at another level. 4) Features of other renal diseases which might account for the observed parenchymal atrophy and scarring were absent. Specifically, pyelonephritis and arteriolar sclerosis of the usual type were not present. 13 Greendyke, R. M. and Akamatsu, Y.: Unpublished data.
ATHEl:WMATOUS EMBOLISM AS :\_ CAUSE OF RENAL FAILU8.E
The anatomieal changes seen in the kidneys of the patients discussed suggest a chronic, continuing eourse of rPpeatecl atheromatous embolization. Acute infarcts of the type reported by Thurlheck and Castleman were not seen. Rather, the process appeared to be one of gradual vascular occlusion, the cumulative effect of which finally may reduce the amount of functioning parenchyma to the point where renal failure occasionally becomes clinically apparent. In this regard, the im:ompleteness of our present knowledge regarding the correlation between the histologic appearance and functional capacity of the kidney is only re-emphasized. It is felt that atheromatous embolization of thn renal arteries should be considered clinically in the differential diagnosis of patients in older age groups suffering from unexplained renal failure.
Even in cases where an adequate appears to be present, this possibility de~erv(:c; consideration. The first two cases in this report, where aneurysmal encroachment on renal Yascul:tr supply was felt clinically to bco tbe rau~e of rcn:JJ failure, illustrate the reason for tbi8 SUMMARY
Three cases of chronic renal failure due to athcromatous embolism from eroded arterial plaques are presented. The literature atheromatous embolism is brief-iy reviewed. It is suggested that this phenomenon is more common than is generally appreciated. Atl1eroma.tom, embolism deserves consideration in the clinical differential diagnosis of any t:ase of renal failure of unexplained etiology occurring in older patirnts,