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Resolution of renal amyloidosis
CASE REPORTS
Resolution of Renal Amyloidosis
STEVEN H. DIKMAN,
A patient with renal amyloidosis and the nephrotic syndrome consequent to extensive infected burns demonstrated both clinical resolution of the nephrotic syndrome and morphologic regression of the renal amyloid deposits over a six year period. The regression of the amyloid deposits was associated with several changes in the glomerular capillary wall resulting in a double capillary wall contour. This case indicates that deposits of amyloid in the kidney may regress and suggests a sequence of events in this resolution.
M.D.
THOMAS KAHN, M.D. DONALD GRIBETZ, M.D. JACOB CHURG, M.D. New York, New York
The regression of the nephrotic syndrome consequent to renal amyloidosis has occasionally been recorded following improvement of the underlying disease [l-5]. Despite clinical improvement, however, only one previous report, to our knowledge, indicated that amyloid deposits may decrease in the kidney [5]. The present report documents the clinical and morphologic regression of renal amyloid as seen with four renal biopsy specimens in a child with amyloidosis following extensive infected burns.
CASE REPORT A 10 year old boy was admitted to the Mount Sinai Hospital 11 months after
From the Departments of Pathology, Medicine and Pediatrics, Mount Sinai School of Medicine of the City University of New York, New York, New York. This study was supported by U.S. Public Health Service Research Grant AM-00918 from the National institute of Arthritis, Metabolism, and Digestive Diseases, and a grant from the New York State Department of Health. Requests for reprints should be addressed to Dr. Steven H. Dikman, Department of Pathology, Mount Sinai Hospital, Fifth Avenue and 100th Street, New York, New York 10029. Manuscript accepted August 18, 1976.
430
September 1977
incurring burns of 30 to 40 per cent of the skin. Details of the original admission and hospital course were given in a previous publication [ 11. On admission, there were extensive infected burns, contractures and generalized edema which developed.during the prior two weeks. The liver was not palpable and the blood pressure was 1 lo/70 mm Hg. Urinalysis revealed only granular hyaline casts and protein. Other pertinent data are given in Table I. The patient received antibiotics, multiple skin grafts and treatment for his contractures. A liver and renal biopsy specimen both showed amyloidosis. After five and a half months he was discharged with no edema but 3-F proteinuria. A second kidney biopsy was performed eight months after the first biopsy when the urine showed 2+ protein; subsequent biopsies were performed three and six years after the burn when the urine was protein free (Table I). At his most recent follow-up, approximately 14 years after the burn, he is a fully active young man with no abnormal physical findings other than scars, and he remains normotensive. Urinalysis, hemoglobin, white blood cell count, liver function tests and electrolytes are all within normal limits. Urine and serum immunoelectrophoresis disclosed no abnormalities. Serum creatinine is 1.2 mg/iOO ml, and creatinine clearance is 85 ml/min.
PATHOLOGY Four renal biopsies were performed. Amyloid was demonstrated by Congo red stain with polarization, crystal violet and thioflavin T stains. The extent of glomerular amyloid was determined by estimating
The American Journalof Medicine Volume 63
RESOLUTION OF RENAL AMYLOIDOSIS-DIKMAN
TABLE I
ET AL.
Clinical Summary
Time (mo)
Edema
0 10 11 13 16 19 24 34 38 73 109 166
13 2i ‘li 4+ 2+ ‘3 3 ,3 0 3 3 D
Blood Urea Nitrogen (ms/ 100 ml)
Urine Protein
Serum Total Protein (g/100 ml)
4t 4+ 4+
5.1 6.1 6.5
;:i 1.6 2.3
11 11
‘3k.
6:i
ii
17 10 16 15 11 20 19
2+ 0 0 TWX 0 0
Serum Albumin (g/l00 ml)
7.7
45
;:2 7.3 77
47 4.8 4.8
the percentage of the area of each glomerular tuft containing stainable amyloid deposits. The first biopsy specimen (obtained 16 months after the burn and 10 months after the onset of the nephrotic syndrome) contained 8 glomeruli, all with prominent segmental amyloid deposits replacing an average of over one half of the glomerular tuft (range, 25 to 80 per cent) (Figure 1). There was pronounced segmental deposition of amyloid in the glomerular capillary walls with focal spike-like projections on the subepithelial aspect of the basement membrane best visualized with silver stains. A few arterioles showed mild to moderate focal amyloid deposits. A few tubules were atrophic; others contained hyaline droplets. Amyloid was not found in the interstitium. The second biopsy specimen (obtained two years after the burn) contained 29 nonobsolete glomeruli with amyloid deposits quantitatively similar to those in the first biopsy specimen (average 52 per cent replacement of the glomerular area, range, 5 to 90 per cent). No spike-like projections of amyloid were found,
Fig& 1. First renal biopsy specimen (obtained 16 months following the burn) showing extensive glomerular amyloid deposits. Periodic acid-Schiff stain; original magnification X 150, reduced by 34 per cent.
September
Creatinine (msi 100 ml)
Creatinine Clearance (mliminl
Cholesterol (mgi 100 ml)
Remarks
335 425 430
59
230 21 0 24 0
txopsy I I I Hpnalhopsy IV
Renal
and rare, scattered glomerular capillary walls had a double contour. Two obsolete glomeruli were present. The third biopsy specimen (obtained approximately three years after the burn) containecl only 4 glomeruli all of which had pronounced amyloid deposits, but the number of glomeruli was insufficient for proper evaluation. Double capillary wall outlines were present. The fourth biopsy specimen (obtained six years after the burn) contained 12 glomeruli of which 4 were small and obsolete, replaced by amyloid. Seven glomeruli had small segmental amyloid deposits and in 1 glomerulus no amyloid was found (average of 5 per cent over-all amyloid deposition in the nonobsolete glomeruli (range, 0 to 10 per cent) (Figure 2). The surviving glomeruli had segmental, irregularly thickened basement membranes, and a few double capillary wall contours were present. There was mild focal tubular atrophy. No amyloid was found in the interstitium, and only minute deposits were located in a few arterioles. No giant cells were found in any of the biopsy
specimens.
Figure 2. Fourth renal biopsy specimen (obtained six years following the burn) showing marked resolution of amyloid deposits. Periodic acid-Schiff stain; original magnification X 150, reduced by 34 per cent.
1977
The American
Journal of Medicine
Volume
63
431
RESOLUTION OF RENAL AMYLOIDOSIS-DIKMAN
ET AL.
,.. _ micrograph of second renal biopsy Figure 3. specimen showing amyloid fibrils in mesangial region. A = amyloid fib&; MC = mesangia, CM. Original magnification X 27,750, reduced by 34 per cent.
Figure 4. Electron micrograph of fourth renal biopsy specimen showing thick glomerular capillary wall with a double tayer of basement membrane-like material (arrow) enclosing amyloid fibrils. A = amyloid fibrils; Ep = epithelial cells (podocyte); En = endothelial ceil. Original magnification X 10,250, reduced by 34 per cent.
Electron microscopy disclosed glomerular amyloid fibrils in the mesangium, basement membrane and subendothelial areas in all four specimens (Figure 3). In the fourth renal biopsy specimen there were only small segmental glomerular areas with amyloid fibrils. There was focal podocyte foot process loss in all the specimens, but this was most extensive in the first. The epithelial aspect of the basement membrane markedly differed in sequential biopsy specimens. In the first, subepithelial amyloid fibrils were occasionally arranged in spike-like projections radiating perpendicular to the basement membrane. In rare areas, a thin layer of basement membrane-like material partially covered subepithelial amyloid fibrils. The glomerular basement membranes were generally of normal thickness in areas without amyloid fibrils. The subsequent specimens showed progressively more extensive subepithelial basement membrane-like material and smaller amounts of similar material on the subendothelial aspect forming a prominent double capillary wall contour corresponding to that seen by light microscopy (Figure 4). There were no subepithelial amyloid fibrils or spikes. Several capillary loops had irregular laminated thick basement membranes first noticeable in the second biopsy specimen but most prominent in the fourth. The appearance and measurements of the amyloid fibrils were similar in all four specimens, and intracellular amyloid fibrils were not found. A liver biopsy specimen (obtained 13 months after the burn) contained minute sinusoidal amyloid deposits found by electron microscopy.
of the underlying disease [3,4,6]. With remission of the nephrotic syndrome, however, repeated renal biopsy has not demonstrated a quantitative decrease in amyloid deposits [3,7] with the exception of a single report [ 51. The apparent irreversibility of renal amyloid deposits was also suggested in several studies of experimentally-induced amyloidosis in which, when the inciting stimulus was removed, renal deposits of amyloid remained stable or progressed whereas amyloid deposits in other organs decreased [8,9]. The long-term value of medical treatment and major surgical procedures solely to prevent or reverse the consequences of renal amyloidosis therefore remained unclear [4]. The present report together with that of Triger and Joekes [5] indicate that renal amyloid deposits may actually regress and thereby provide a more rational basis for aggressive treatment of these patients directed to the underlying disease. In addition to the quantitative decrease of renal amyloid deposits in this patient, certain qualitative glomerular changes are of note. Obsolete glomeruli contained extensive amyloid whereas the surviving glomeruli showed only very small segmental amyloid depostts. A variety of mechanisms have been suggested for the disappearance of amyloid, such as phagocytosis [ 9, lo] and degrading substances found in serum [ 111. These mechanisms all presumably require an adequate blood flow to the involved area. The pattern in the last biopsy specimen suggests that in glomeruli with an overwhelming deposition of amyloid sufficient to reduce the blood supply to that glomerulus, mechanisms for removing amyloid may be incapable of functioning, but that in less severely affected glomeruli these mechanisms are operative. Other forms of glomerular damage in the three later biopsy specimens consisted of irregularly thickened
COMMENTS In “secondary” amyloidosis, it has been demonstrated that amyloid deposits in the liver regress with remission
432
September1977 The American Journal of Medicine Volume63
RESOLUTION OF RENAL AMYLOIDOSIS-DIKMAN
basement membranes and double outlines of the capillary walls. Amyloid fibrils in the subepithelial or, rarely, the subendothelial aspect of the capillary wall are frequently covered by a thin layer of basement membrane-like material [ 121. Sufficient deposition of basement membrane-like material to give the appearante of a double capillary wall contour was noted by us in one other patient with renal amyloidosis and has been recently reported on light microscopy by others [lo]. The deposition of basement membrane-like material over subepithelial amyloid deposits appears to repre-
ET AL.
sent a reaction predominantly by the podocytes and has some features analogous to the alterations of the basement membrane in response to the subepithelial deposits in membranous nephropathy [ 131. Basement membrane thickening and double capillary wall contours, therefore, may represent a form of scarring similar to that found with other processes that affect the glomerular capillary wall. The presence of obsolete glomeruli coupled with alterations of the basement membrane may help to explain the modestly diminished creatinine clearance in this patient.
REFERENCES 1. Hoffman S, Simon BE, Fischel RA, et al.: Renal amyloidosis resulting from a chronically infected burn. Pediatrics 32: 888, 1963. 2. Parkins RA. Bywaters EGL: Regression of amyloidosis secondary to rheumatoid arthritis. Br Med J 50: 536, 1959. 3. Lowenstein J, Gallo G: Remission of the nephrotic syndrome in renal amyloidosis. N Engl J Med 262: 126, 1970. 4. Fitchen JH: Amyloidosis and granulomatous ileocolitis. Regression after surgical removal of the involved bowel. N Engl J Med 292: 352, 1975. 5. Triger DR, Joekes AM: Renal amyloidosis-a fourteen year follow-up. 0 J Med 42: 15, 1973. 6. Waldenstrom H: Formation and disappearance of amyloid in man. Acta Chir Stand 63: 479, 1926. 7. Lindeman RD, Scheer RL, Raisz LG: Renal amyloidosis. Ann Intern Med 54: 683. 1961.
September
6. DeLellis RA, Sri Ram J, Gfenner GG: Amyloid. IX. Further kinetic studies on experimental murine amyloidosis. Int Arch Allergy Appl lmmunol 37: 175, 1970. 9. Richter GW: The resorption of amyloid under experimental conditions. Am J Pathol 30: 239, 1954. 10. Watanabe T, Saniter T: Morphological and clinical features of renal amyloidosis. Virchows Arch (Pathot Anat) 366: 125, 1975. 11. Kedar (Keizman) I, Sohar E, Gafni J: Demonstration of amyloid-degrading activity in normal human serum. Proc Sot EXQ Biol Med 145: 343, 1974. 12. Dikman SH, Kahn T, Churg J: Renal amyloidosis (in preparation). 13. Ehrenreich T. Churg J: Pathology of membranous nephropathy. Pathology Annual, vol 3 (Sommers SC. ed), New York, Appleton-Century-Crofts, 1968, p 145.
1977
The American
Journal of Medicine
Volume 63
433
Resolution of Renal Amyloidosis
STEVEN H. DIKMAN,
A patient with renal amyloidosis and the nephrotic syndrome consequent to extensive infected burns demonstrated both clinical resolution of the nephrotic syndrome and morphologic regression of the renal amyloid deposits over a six year period. The regression of the amyloid deposits was associated with several changes in the glomerular capillary wall resulting in a double capillary wall contour. This case indicates that deposits of amyloid in the kidney may regress and suggests a sequence of events in this resolution.
M.D.
THOMAS KAHN, M.D. DONALD GRIBETZ, M.D. JACOB CHURG, M.D. New York, New York
The regression of the nephrotic syndrome consequent to renal amyloidosis has occasionally been recorded following improvement of the underlying disease [l-5]. Despite clinical improvement, however, only one previous report, to our knowledge, indicated that amyloid deposits may decrease in the kidney [5]. The present report documents the clinical and morphologic regression of renal amyloid as seen with four renal biopsy specimens in a child with amyloidosis following extensive infected burns.
CASE REPORT A 10 year old boy was admitted to the Mount Sinai Hospital 11 months after
From the Departments of Pathology, Medicine and Pediatrics, Mount Sinai School of Medicine of the City University of New York, New York, New York. This study was supported by U.S. Public Health Service Research Grant AM-00918 from the National institute of Arthritis, Metabolism, and Digestive Diseases, and a grant from the New York State Department of Health. Requests for reprints should be addressed to Dr. Steven H. Dikman, Department of Pathology, Mount Sinai Hospital, Fifth Avenue and 100th Street, New York, New York 10029. Manuscript accepted August 18, 1976.
430
September 1977
incurring burns of 30 to 40 per cent of the skin. Details of the original admission and hospital course were given in a previous publication [ 11. On admission, there were extensive infected burns, contractures and generalized edema which developed.during the prior two weeks. The liver was not palpable and the blood pressure was 1 lo/70 mm Hg. Urinalysis revealed only granular hyaline casts and protein. Other pertinent data are given in Table I. The patient received antibiotics, multiple skin grafts and treatment for his contractures. A liver and renal biopsy specimen both showed amyloidosis. After five and a half months he was discharged with no edema but 3-F proteinuria. A second kidney biopsy was performed eight months after the first biopsy when the urine showed 2+ protein; subsequent biopsies were performed three and six years after the burn when the urine was protein free (Table I). At his most recent follow-up, approximately 14 years after the burn, he is a fully active young man with no abnormal physical findings other than scars, and he remains normotensive. Urinalysis, hemoglobin, white blood cell count, liver function tests and electrolytes are all within normal limits. Urine and serum immunoelectrophoresis disclosed no abnormalities. Serum creatinine is 1.2 mg/iOO ml, and creatinine clearance is 85 ml/min.
PATHOLOGY Four renal biopsies were performed. Amyloid was demonstrated by Congo red stain with polarization, crystal violet and thioflavin T stains. The extent of glomerular amyloid was determined by estimating
The American Journalof Medicine Volume 63
RESOLUTION OF RENAL AMYLOIDOSIS-DIKMAN
TABLE I
ET AL.
Clinical Summary
Time (mo)
Edema
0 10 11 13 16 19 24 34 38 73 109 166
13 2i ‘li 4+ 2+ ‘3 3 ,3 0 3 3 D
Blood Urea Nitrogen (ms/ 100 ml)
Urine Protein
Serum Total Protein (g/100 ml)
4t 4+ 4+
5.1 6.1 6.5
;:i 1.6 2.3
11 11
‘3k.
6:i
ii
17 10 16 15 11 20 19
2+ 0 0 TWX 0 0
Serum Albumin (g/l00 ml)
7.7
45
;:2 7.3 77
47 4.8 4.8
the percentage of the area of each glomerular tuft containing stainable amyloid deposits. The first biopsy specimen (obtained 16 months after the burn and 10 months after the onset of the nephrotic syndrome) contained 8 glomeruli, all with prominent segmental amyloid deposits replacing an average of over one half of the glomerular tuft (range, 25 to 80 per cent) (Figure 1). There was pronounced segmental deposition of amyloid in the glomerular capillary walls with focal spike-like projections on the subepithelial aspect of the basement membrane best visualized with silver stains. A few arterioles showed mild to moderate focal amyloid deposits. A few tubules were atrophic; others contained hyaline droplets. Amyloid was not found in the interstitium. The second biopsy specimen (obtained two years after the burn) contained 29 nonobsolete glomeruli with amyloid deposits quantitatively similar to those in the first biopsy specimen (average 52 per cent replacement of the glomerular area, range, 5 to 90 per cent). No spike-like projections of amyloid were found,
Fig& 1. First renal biopsy specimen (obtained 16 months following the burn) showing extensive glomerular amyloid deposits. Periodic acid-Schiff stain; original magnification X 150, reduced by 34 per cent.
September
Creatinine (msi 100 ml)
Creatinine Clearance (mliminl
Cholesterol (mgi 100 ml)
Remarks
335 425 430
59
230 21 0 24 0
txopsy I I I Hpnalhopsy IV
Renal
and rare, scattered glomerular capillary walls had a double contour. Two obsolete glomeruli were present. The third biopsy specimen (obtained approximately three years after the burn) containecl only 4 glomeruli all of which had pronounced amyloid deposits, but the number of glomeruli was insufficient for proper evaluation. Double capillary wall outlines were present. The fourth biopsy specimen (obtained six years after the burn) contained 12 glomeruli of which 4 were small and obsolete, replaced by amyloid. Seven glomeruli had small segmental amyloid deposits and in 1 glomerulus no amyloid was found (average of 5 per cent over-all amyloid deposition in the nonobsolete glomeruli (range, 0 to 10 per cent) (Figure 2). The surviving glomeruli had segmental, irregularly thickened basement membranes, and a few double capillary wall contours were present. There was mild focal tubular atrophy. No amyloid was found in the interstitium, and only minute deposits were located in a few arterioles. No giant cells were found in any of the biopsy
specimens.
Figure 2. Fourth renal biopsy specimen (obtained six years following the burn) showing marked resolution of amyloid deposits. Periodic acid-Schiff stain; original magnification X 150, reduced by 34 per cent.
1977
The American
Journal of Medicine
Volume
63
431
RESOLUTION OF RENAL AMYLOIDOSIS-DIKMAN
ET AL.
,.. _ micrograph of second renal biopsy Figure 3. specimen showing amyloid fibrils in mesangial region. A = amyloid fib&; MC = mesangia, CM. Original magnification X 27,750, reduced by 34 per cent.
Figure 4. Electron micrograph of fourth renal biopsy specimen showing thick glomerular capillary wall with a double tayer of basement membrane-like material (arrow) enclosing amyloid fibrils. A = amyloid fibrils; Ep = epithelial cells (podocyte); En = endothelial ceil. Original magnification X 10,250, reduced by 34 per cent.
Electron microscopy disclosed glomerular amyloid fibrils in the mesangium, basement membrane and subendothelial areas in all four specimens (Figure 3). In the fourth renal biopsy specimen there were only small segmental glomerular areas with amyloid fibrils. There was focal podocyte foot process loss in all the specimens, but this was most extensive in the first. The epithelial aspect of the basement membrane markedly differed in sequential biopsy specimens. In the first, subepithelial amyloid fibrils were occasionally arranged in spike-like projections radiating perpendicular to the basement membrane. In rare areas, a thin layer of basement membrane-like material partially covered subepithelial amyloid fibrils. The glomerular basement membranes were generally of normal thickness in areas without amyloid fibrils. The subsequent specimens showed progressively more extensive subepithelial basement membrane-like material and smaller amounts of similar material on the subendothelial aspect forming a prominent double capillary wall contour corresponding to that seen by light microscopy (Figure 4). There were no subepithelial amyloid fibrils or spikes. Several capillary loops had irregular laminated thick basement membranes first noticeable in the second biopsy specimen but most prominent in the fourth. The appearance and measurements of the amyloid fibrils were similar in all four specimens, and intracellular amyloid fibrils were not found. A liver biopsy specimen (obtained 13 months after the burn) contained minute sinusoidal amyloid deposits found by electron microscopy.
of the underlying disease [3,4,6]. With remission of the nephrotic syndrome, however, repeated renal biopsy has not demonstrated a quantitative decrease in amyloid deposits [3,7] with the exception of a single report [ 51. The apparent irreversibility of renal amyloid deposits was also suggested in several studies of experimentally-induced amyloidosis in which, when the inciting stimulus was removed, renal deposits of amyloid remained stable or progressed whereas amyloid deposits in other organs decreased [8,9]. The long-term value of medical treatment and major surgical procedures solely to prevent or reverse the consequences of renal amyloidosis therefore remained unclear [4]. The present report together with that of Triger and Joekes [5] indicate that renal amyloid deposits may actually regress and thereby provide a more rational basis for aggressive treatment of these patients directed to the underlying disease. In addition to the quantitative decrease of renal amyloid deposits in this patient, certain qualitative glomerular changes are of note. Obsolete glomeruli contained extensive amyloid whereas the surviving glomeruli showed only very small segmental amyloid depostts. A variety of mechanisms have been suggested for the disappearance of amyloid, such as phagocytosis [ 9, lo] and degrading substances found in serum [ 111. These mechanisms all presumably require an adequate blood flow to the involved area. The pattern in the last biopsy specimen suggests that in glomeruli with an overwhelming deposition of amyloid sufficient to reduce the blood supply to that glomerulus, mechanisms for removing amyloid may be incapable of functioning, but that in less severely affected glomeruli these mechanisms are operative. Other forms of glomerular damage in the three later biopsy specimens consisted of irregularly thickened
COMMENTS In “secondary” amyloidosis, it has been demonstrated that amyloid deposits in the liver regress with remission
432
September1977 The American Journal of Medicine Volume63
RESOLUTION OF RENAL AMYLOIDOSIS-DIKMAN
basement membranes and double outlines of the capillary walls. Amyloid fibrils in the subepithelial or, rarely, the subendothelial aspect of the capillary wall are frequently covered by a thin layer of basement membrane-like material [ 121. Sufficient deposition of basement membrane-like material to give the appearante of a double capillary wall contour was noted by us in one other patient with renal amyloidosis and has been recently reported on light microscopy by others [lo]. The deposition of basement membrane-like material over subepithelial amyloid deposits appears to repre-
ET AL.
sent a reaction predominantly by the podocytes and has some features analogous to the alterations of the basement membrane in response to the subepithelial deposits in membranous nephropathy [ 131. Basement membrane thickening and double capillary wall contours, therefore, may represent a form of scarring similar to that found with other processes that affect the glomerular capillary wall. The presence of obsolete glomeruli coupled with alterations of the basement membrane may help to explain the modestly diminished creatinine clearance in this patient.
REFERENCES 1. Hoffman S, Simon BE, Fischel RA, et al.: Renal amyloidosis resulting from a chronically infected burn. Pediatrics 32: 888, 1963. 2. Parkins RA. Bywaters EGL: Regression of amyloidosis secondary to rheumatoid arthritis. Br Med J 50: 536, 1959. 3. Lowenstein J, Gallo G: Remission of the nephrotic syndrome in renal amyloidosis. N Engl J Med 262: 126, 1970. 4. Fitchen JH: Amyloidosis and granulomatous ileocolitis. Regression after surgical removal of the involved bowel. N Engl J Med 292: 352, 1975. 5. Triger DR, Joekes AM: Renal amyloidosis-a fourteen year follow-up. 0 J Med 42: 15, 1973. 6. Waldenstrom H: Formation and disappearance of amyloid in man. Acta Chir Stand 63: 479, 1926. 7. Lindeman RD, Scheer RL, Raisz LG: Renal amyloidosis. Ann Intern Med 54: 683. 1961.
September
6. DeLellis RA, Sri Ram J, Gfenner GG: Amyloid. IX. Further kinetic studies on experimental murine amyloidosis. Int Arch Allergy Appl lmmunol 37: 175, 1970. 9. Richter GW: The resorption of amyloid under experimental conditions. Am J Pathol 30: 239, 1954. 10. Watanabe T, Saniter T: Morphological and clinical features of renal amyloidosis. Virchows Arch (Pathot Anat) 366: 125, 1975. 11. Kedar (Keizman) I, Sohar E, Gafni J: Demonstration of amyloid-degrading activity in normal human serum. Proc Sot EXQ Biol Med 145: 343, 1974. 12. Dikman SH, Kahn T, Churg J: Renal amyloidosis (in preparation). 13. Ehrenreich T. Churg J: Pathology of membranous nephropathy. Pathology Annual, vol 3 (Sommers SC. ed), New York, Appleton-Century-Crofts, 1968, p 145.
1977
The American
Journal of Medicine
Volume 63
433