Hemolytic-uremic Syndrome in an Adult. Tomoko GOMI, M.D., Mikio YUHARA, M.D., and Takao IKEDA, M.D.

Transcription

1 Hemolytic-uremic Syndrome in an Adult Tomoko GOMI, M.D., Mikio YUHARA, M.D., and Takao IKEDA, M.D. SUMMARY This report describes a 45-year-old man who suffered from hemolytic-uremic syndrome. In his autopsy findings, kidney arteriolar walls showed marked hyaline degeneration and interlobular arteries were occluded by severe intimal proliferation. No vascular changes were found in other organs. There were no arteriosclerotic changes in either main branches from the aorta or the aorta. These vascular changes are correspond well with the early features of malignant nephrosclerosis without any clinical findings of malignant hypertension. This type is called primary malignant nephrosclerosis by Bohle et al.6) We would like to point out the significance of this case in the re-consideration of the pathogenesis of malignant nephrosclerosis. Additional Indexing Words: Primary malignant nephrosclerosis Secondary malignant nephrosclerosis ASSER et al1) first reported a disease occurring in infants and young children, characterized by severe hemolytic anemia, thrombocytopenia and renal failure. This disease was termed the hemolytic-uremic syndrome. Since then, over 1,000 cases of this syndrome have been reported in the world and 90% of them were observed in children under 4 years of age. This syndrome has also been reported in adults and the number of reports has increased in recent years. The present report concerns a patient who suffered from adult hemolytic-uremic syndrome. CASE REPORT The patient, a 45-year-old man, had apparently been in good health until September He had been receiving regular physical check-ups twice a year. He was told that he was in good health and his blood pressure was 120mmHg systolic and 80mmHg diastolic. His urinalysis revealed From the Department of Nephrology, Internal Medicine, the Kanto Teisin Hospital, 5-chome, Higashi-Gotanda, Shinagawa-ku, Tokyo 141, Japan. Received for publication June 15,

2 464 GOMI, YUHARA, AND IKEDA Jpn. Heart J. May 1983 Fig. 1. Glomerular tufts showed general ischemia and were collapsed and Bowman's capsules displayed cyst-like dilatation. Fig. 2. Arteriolar walls showed marked hyaline degeneration and these changes extended in to the glomerulus. proteinuria only in trace to one plus levels. On September 28th, 1976, he began to complain of anorexia and nausea and a puffiness of his face was noticed. Until that time, he did not show any change in urine volume, and had not suffered from any inflammatory diseases, except for otitis media when he was 20 years old. Thus, he was admitted to our hospital with complaints of anorexia, nausea, and edema on October 6th, Physical findings on admission were as follows: The patient was 170cm tall but thin, weighing only 49Kg and having an ill appearance. He had a swollen face but no pitting edema. There were scratches with bleeding and ecchymosis on his chest wall. The blood pressure was 176/94mmHg on both arms. The heart rate was 76/min. The chest was clear on percussion, and systolic functional murmurs were heard at the

3 Vol.24 No.3 HEMOLYTIC-UREMIC SYNDROME IN AN ADULT 465 Fig. 3. Interlobular arteries showed marked fibrin growth in the intima which narrowed their lumens. Fig. 4. Small arteries showed a fibrinous thickening of the intima with reduplication of the lamina elastica interna. cardiac apical region on auscultation. There were no abnormal findings in the abdomen. Laboratory examinations revealed proteinuria of 1,960mg/ 100ml. The RBC was 20-40/f in the urinary sediment. His urine volume on the first hospital day was only 70ml/day. The serum creatinine level was 11.2mg/100ml and BUN was 117mg/100ml. In peripheral blood, the red blood cell count was 274 ~104/mm3, the hemoglobin count was 8.9Gm/ 100ml, the platelet count was 39,000/mm3, reticulocytes were 55 ñ, and the white blood cell count was 8,000/mm3 with a normal differential cell count. Numerous red cells were irregular, fragmented and triangular in shape on the peripheral blood smears. Serum LDH was greater than 1,290 U, total bilirubin was 2.1mg/100ml, FDP in serum was 40ƒÊg/100ml, and ESR was 92mm/hour. Chest X-ray films and electrocardiograms on admission were

4 466 GOMI, YUHARA, AND IKEDA Jpn. Heart J. May 1983 interlobar Fig. 5. There were no arteriosclerotic changes in the main renal and arteries. normal. In a plain abdominal X-ray, kidney contours barely exceeded the normal size level. Retinal examination revealed one hemorrhaging spot and some white flakes, with neither vascular sclerotic changes nor papilloedema. In light of these findings, the patient was diagnosed as having uremia with microangiopathic hemolytic anemia. On the second hospital day, an operation for an external shunt was performed and the first hemodialysis was done immediately. After the first hemodialysis, his complaints were markedly reduced but the urine volume did not increase. Blood pressure was at the level of mmHg systolic and mmHg diastolic. On the 7th hospital day, an operation for an arteriovenous fistula was performed on the left hand with the intention of beginning permanent hemodialysis at 18 hours/week. The external shunt was removed. The blood pressure was maintained at the level of 110/ 80mmHg by regular hemodialysis without antihypertensive drugs. His general condition improved, but he did not show any increase in appetite. Feeding via a gastric tube was attempted, but malnutrition ensued and his body weight continued to decrease. Even under strict control of water balance, heart failure could not be prevented and disturbances in consciousness appeared. Generalized petechiaes followed. He died of congestive heart failure on January 6th, Autopsy findings: The body was extremely emaciated, with a height of 172cm and weight of 28Kg. The left kidney weighed 85Gm and right 130Gm. Marked cortical atrophy was seen grossly. Glomerular tufts showed general ischemia and were collapsed. The capillary lumen could not be recognized in collapsed glomeruli. There was no glomerular hypercellularity, no areas of

5 Vol.24 HEMOLYTIC-UREMIC SYNDROME IN AN ADULT 467 No.3 membranous thickening, and no wire loop formation. The dilated Bowmann's capsules looked like cysts (Fig. 1). Tortuous changes of basement membrane, due to collapse of tufts, were shown clearly with the PAS stain and by electron microscopy. Atrophic changes were dominant among tubules, but there was neither interstitial fibrosis nor inflammatory infiltration. Arteriolar walls showed marked hyaline degeneration and these changes sometimes extended to the glomerulus of the kidney (Fig. 2). The interlobular arteries were occluded by severe intimal proliferation, causing constriction of their lumens (Fig. 3). Small arteries showed fibrinous thickening of the intima, with reduplication of the lamina elastica interna (Fig. 4). There were no arteriosclerotic changes in the main renal and interlobular arteries (Fig. 5). Fibrinoid necrosis could be found in some parts of walls of arterioles and small arteries. Both lungs weighed 789Gm, with marked edema and congestion. They showed very severe fibrin exudation in some parts and hyaline membrane formation in other parts. The heart weighed 340Gm, with dilatation of both ventricles which was especially marked on the left. The aorta showed minimal atherosclerotic changes and small arteries and arterioles in other organs (except the kidney) were within normal limits. DISCUSSION Volhard and Fahr2) clarified the concepts of renal and arterial disease. In their classification, arteriosclerotic disease was clearly separable from the degenerative disease and inflammatory disease. Fahr3) pointed out that there were some characteristic changes in arterioles, termed malignant nephrosclerosis. These changes include splitting of nuclei, fibrinoid deposits, necrotic changes of arterial walls with occasional red cell exudation, and cellular thicking of the intima without reduplication of lamina elastica interna. He added that these changes are most marked in the kidney, but can also be present in organs such as the intestines, pancreas, and suprarenal glands. Heptinstall4) pointed out that the fibrinoid arteriolar lesions characterizing malignant nephrosclerosis result from severe hypertension, termed malignant hypertension. Until recently this view has been accepted as a general concept for malignant nephrosclerosis. In recent years, Bohle et al5)-7) have concluded a detailed review of cases diagnosed as malignant nephrosclerosis, comparing clinical pictures with hisopathological changes. They concluded that there are 2 types of malignant nephrosclerosis. The first type shows the clinical picture of malignant hypertension. Pathological findings in the kidney are characterized by glomerular hyalinoid degeneration, arteriosclerotic changes

6 468 GOMI, YUHARA, AND IKEDA Jp n. Heart J. May 1983 in arterioles, small arteries and interlobular arteries, interstitial fibrosis and tubular atrophy. These findings typify the chronic stage of malignant nephrosclerosis, and they have termed this "the secondary type". The second type presents pathological findings of the early features of malignant nephrosclerosis, characterized by glomerular collapse, arteriosclerotic changes shown in arterioles and small arteries and acute tubular damage in the interstitia. This type follows a course of severe anemia, resulting in rapid, progressive renal insufficiency. Furthermore, these changes occur in patients without malignant hypertension. This type is named "the primary type". This concept is currently being accepted by others.11) The present case was diagnosed as hemolytic-uremic syndrome from his clinical course, characterized by rapid, progressive renal failure with microangiopathic hemolytic anemia, thrombocytopenia, and reticulocytosis. The diagnosis was confirmed by pathological changes, post-mortum. An outstanding feature of this case is that reliable data from his check-ups assured that his blood pressure was within the normal range prior to hospitalization. Furthermore, after admission, his blood pressure was slightly elevated for a period of less than 1 month. Therefore, a period of malignant hypertension was not observed clinically during his life. Despite clinical observations about his blood pressure, pathological exploration revealed early features of malignant nephrosclerosis, which follows a course of rapid, progressive renal insufficiency. This case corresponds well to the primary type of malignant nephrosclerosis. In this case, arteriosclerotic changes were shown in arterioles and small arteries in the kidneys. But there were no these changes in the same sized vessels of the other organs. Moreover no atherosclerotic changes were shown in all main arteries and branches from the aorta. Given these findings, the pathogenesis of this primary nephrosclerosis remains unclear, for these changes seem to be caused by mechanisms other than malignant hypertension. Bohle et al6) and other authors8)-10) suggest that intervascular coagulation takes place in the kidney. In consideration of the concepts of primary malignant nephrosclerosis presented by Bohle et al,6) this case appears to be particularly relevant to the reevaluation of the pathogenesis of malignant nephrosclerosis. REFERENCES 1. Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R: Hemolytische-Uremische Syndrome. Bilaterale Nierenridennekrosen Bei Akuten Erworbenen Hemolytischen Anemien. Schwiez Med Wochenschr 85: 906, Volhard F, Fahr T: Die Brightsch Nieren Krankheit, Springer, Berlin, Fahr T: Uber Nephrosklerose. Virchows Arch [Pathol Anat] 226: 119, 1919

7 Vol.24 HEMOLYTIC-UREMIC SYNDROME IN AN ADULT 469 No.3 4. Heptinstall RH: Renal biopsies in hypertension. Br Heart J 16: 133, Bohle A, Helmchen U, Meyer D, Bock KD, Bruning L, Edel HH, Heimsoth V, Scheler F: Uber Die Primate and Sekundare Maligne Nephrosklerose. Klin Wsch 51: 841, Bohle A, Grund KE, Helmchen U, Meyer D: Primary malignant nephrosclerosis. Clin Sci Mol Med 51: 23s, Bohle A, Jannecke J, Meyer D, Schubert GE: Morphology of acute renal failure. Comparative data from biopsy and autopsy. Kid Inter 10: s9, Brown CB, Clarkson AR, Robson JS, Cameron JS, Thomson D, Ogg CS: Hemolytic uremic syndrome in women taking oral contraceptives. Lancet 1: 1479, George CRP, Slichter SJ, Quadracci LJ, Striker GE, Harker LA: A kinetic evaluation of hemostasis in renal disease. New Engl J Med 291: 1111, Harker LA, Slichter SJ: Platelet and fibrinogen consumption in man. New Engl J Med 287: 999, Churg J: Malignant nephrosclerosis. in Renal Disease, ed by Churg J, Sobin LH, Igaku- Shoin, Tokyo, New York, p 212, 1982