Sep 18, 1974 - Address reprint requests to Dr. David B. Jones, Department of ..... Oestreich R: Pl6tzlicher Tod durch Verstopfung beider Kranzarterien [Sud-.
Atheromatous Emboli in Renal Biopsies An Ultrastructural Study David B. Jones, MD and Philip M. lannaccone, MD
In a series of 755 renal biopsies atheromatous emboli were found in biopsies of 8 men from 49 to 72 years of age. Unexplained recent deterioration of renal function was present in each. This previously unreported incidence of 8 755 biopsies is ascribed to the selection for biopsy of patients with unexplained decrease in renal function. Hypertension was a major feature in 6, hyperlipidemia in 2, a leaking aortic aneurysm in 1, carcinoma of the pancreas in 1, and chronic glomerulonephritis in 1 patient. Toluidine-blue-stained epoxy sections proved to be more effective in recognizing small emboli than paraffin sections. Ultrastructural observation concerned a) early lesions (eg, fresh emboli with endothelial distortion or injury), b) intermediate lesions (eg, histiocytic or giant cell reaction and intimal proliferation), and c) later lesions (eg, extraluminalization of the crystals eventually resulting in inert location in intimal stroma). Osmiophilic deposits on the crystal surfaces were myelin-form in structure and were felt to result from lysosomal action. (Am J Pathol 78:261-276, 1975)
ATHEROMATOUS ENMBOL were described in various early rein German literature 1- and in the English literature in 1926 the ports by Benson.4 The first systematic studv of the pathologic changes consequent to atheromatous embolization, based on 267 autopsies, was presented in 1945 by Flory.5 Since that time there have been several reports of renal failure following embolization to the kidneys.--' Thurlbeck and Castleman studied postoperative patients after surgical repair of abdominal aortic aneurvsm and found that 77% of these patients suffered atheromatous embolization to the kidneys as a complication. In many of these patients the embolization resulted in a syndrome of chronic renal failure and hvpertension.6 These cases and other similar reports were of nonspontaneous embolization,9 that is following surgerv or trauma. With the exception of two isolated case reports,7-10 all of these studies dealt with autopsv material, and it was suggested that the diagnosis cannot be From the Department of Pathology, State University of New York, Upstate Medical Center, Syracuse, NY. Supported in part by Grant HL-04300 from the Heart and Lung Institute, US Public Health Service. Accepted for publication September 18, 1974. Address reprint requests to Dr. David B. Jones, Department of Pathologp, State University of New York, Upstate Medical Center, 766 Irning Ave, Syracuse, NY 13210. 261
262
JONES AND IANNACCONE
American Journal of Pathology
made during life because of the sampling error of percutaneous biopsy and the absence of diagnostic roentgenologic signs.'0 There have been no ultrastructural studies of atheromatous emboli in human biopsies of which the authors are aware. The purpose of this report is to describe light and electron microscopic findings of renal biopsies in 8 patients with spontaneous atheromatous embolization to the kidneys associated with deterioration of renal function in 7. These ultrastructural findings provide useful correlates to recent studies in experimental animals." Materials and Methods From 755 consecutive renal biopsies, 8 cases of atheromatous embolization to the kidney were found. Material in 7 cases from percutaneous renal biopsy was received, fixed in 2% buffered isotonic gluteraldehyde and divided longitudinally. Half of the material was embedded in paraffin, sectioned at 2 t and stained with hematoxylin and eosin and periodic acid-Schiff (PAS). The other half was postfixed with osmium, embedded in Epon 812 (R), sectioned with an LKB ultramicrotome, and stained with lead citrate and uranyl acetate. One case was an open renal biopsy taken at the time of an abdominal aorta aneurysm repair. This had been embedded in paraffin, but part was rehydrated, treated with osmic acid, embedded in epoxy resin and cut for electron microscopy. Thick plastic sections (1 [i) were prepared by staining with borax toluidine blue and studied by light microscopy. These sections proved to be much more efficient than the hematoxylin and eosin-stained sections in visualizing small crystals of cholesterol. Electron microscopy was carried out with a Phillips EM 300 or an RCA EMU3G electron microscope.
Results Clinical Findings
The 8 patients ranged in age from 49 to 72 years, and all were male (Table 1). The patients could be divided into three clinical groups: those with severe or malignant hypertension (4 cases) ranging in duration from several months to 28 years; those with serum lipid disorders (2 cases); and a miscellaneous group (2 cases). Each of these patients had recent clinical evidence of decreased renal function which prompted the renal biopsy. Text-figure 1 illustrates the evidence of failing renal function in 2 cases. Five of the 7 patients suffered from some form of hypertension for varying periods of time prior to the renal biopsy. Of the 4 patients in the hypertensive group, 3 had frank malignant hypertension of recent onset at the time of biopsy. Patient JH was a long-term hypertensive with recent accelerated hypertension and hydralazine-induced lupus syndrome. Progressive deterioration of renal function developed fol-
RENAL EMBOLI
Vol. 78, No. 2 February 1975
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