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Rapidly Progressive Glomerulonephritis (Crescentic Glomerulonephritis) in the Course of Type I Idiopathic Membranoproliferative Glomerulonephritis
CASE REPORTS
Rapidly Progressive Glomerulonephritis (Crescentic Glomerulonephritis) in the Course of Type I Idiopathic Membranoproliferative Glomerulonephritis Ze'ev Korzets, MB, BS, Joelle Bernheim, MD, and Jacques Bernheim, MD • Membranoproliferative glomerulonephritis is a chronic glomerulopathy with a generally progressive course toward end-stage renal disease and a high recurrence rate in renal allografts. Described herein is the appearance of rapidly progressive glomerulonephritis (crescentic glomerulonephritis) in the course of type I membranoproliferative glomerulonephritis. This transition occurred within 6 weeks, documented histologically by an initial and subsequent renal biopsy. No recurrence of the disease was noted in a living donor graft 18 months posttransplantation. © 1987 by the National Kidney Foundation, Inc. INDEX WORDS: Crescentic glomerulonephritis; membranoproliferative glomerulonephritis.
M
EMBRANOPROLIFERATIVE glomerulonephritis (MPGN) is a well-defined form of chronic glomerulonephritis (GN) characterized by distinctive glomerular pathology. I 3 Two main types of MPGN have been distinguished: type I (subendothelial deposit variety) and type II (linear dense deposit disease). 3-6 Each of these types are considered to be distinct, with no change from one form of the disease to the other. Although the presence of crescents in either type has been documented, the appearance of rapidly progressive glomerulonephritis (RPGN), defined as greater than 60% of glomeruli affected by crescents, is a rare occurrence. 3 MPGN has a generally bad prognosis with more than 50 % of those affected progressing to death, dialysis, or transplantation within 10 years of the onset of the disease. 3.5 Only two patients have been described in which type I MPGN has progressed from the pure form to RPGN. 3.7 This transition occurred within 0.6 years in the one patient 3 to 3 years in the second patient. 7 We describe a patient who showed such a transition within a period of 6 weeks. After 6 months on dialysis (continuous ambulatory peritoneal dialysis [CAPD]), the patient was transplanted with a living donor graft donated by his father. Currently,
From the Departments of Nephrology and Pathology, Meir General Hospital; and the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Address reprint requests to Jacques Bernheim, MD, Department of Nephrology, Meir General Hospital, 44281 Kfar Saba, Israel. © 1987 by the National Kidney Foundation, Inc. 0272-6386/87/1001-0010$3.00/0 56
1 liz years posttransplantation, his renal function is normal, with no clinical or laboratory evidence of recurrence of the original disease. CASE REPORT A 16-year-old boy was admitted on May 25, 1983, because of nausea and vomiting. A month previously, he was hospitalized for five days at another hospital with a right epididymoorchitis clinically diagnosed as being secondary to mumps. He was treated witb analgesics, sulphametboxazole-trimethoprim, and ampicillin. His condition improved and he was discharged on April 29. On May 20, he was readmitted to the same hospital, complaining of nausea. On examination he was edematous with a BP reading of 165/105 mm Hg. Urinary output ranged between 600 and 1000 mUd. Proteinuria was 10 g/d. The urinary sediment contained many leukocytes, 15 to 20 erythrocytes (RBC) per high power field, and granular casts. No RBC casts were seen. Serum creatinine was 6.6 mg/dL, and serum albumin 2.0 g/dL. Treatment with prednisone, 60 mg/d, was begun on May 22. Three days later he was transferred to Meir General Hospital for further evaluation. On admission, periorbital with dependent ankle edema and ascites were evident. His BP was 1501100 mm Hg. Neither asterixis or a pericardial friction rub were present. Laboratory data were as follows: serum hemoglobin 9 g/dL, hematocrit 28.8%, sodium 135 mEq/L, potassium 4.8 mEq/L, urea 306 mg/dL, creatinine 4.2 mg/dL, calcium 7.2 mg/dL, phosphorus 8.7 mg/dL, uric acid 9.9 mg/dL, total protein 5.6 g/dL, with an albumin of2.3 g/dL, and cholesterol 185 mg/dL. Urinary output was 1,000 mUd with a proteinuria of 4.4 g/d. Urinalysis was unchanged. Serologic survey, including Rose-Waaler, latex, lupus erythematosus (LE) latex, antinuclear factor and dsDNA, Australian antigen, and cryoglobulins, was negative. C3 and C4 were 100 mg/dL and 26 mg/dL, respectively, (normal values 100 mg/dL and 16 mg/dL, respectively, measured by the radial immunodiffusion method). Serum level of IgG was 1,683 mg/dL, IgA 240 mg/dL, and IgM 168 mg/dL. Chest xray was normal. A plain film of the abdomen showed two kidneys of normal size. Hemodialysis was begun via an external
American Journal of Kidney Diseases, Vol X, No 1 (July), 1987: pp 56-61
57
RPGN IN TYPE I MPGN
shunt. With the patient already undergoing steroid treatment, it was decided to continue prednisone with the addition of azathioprine, 100 mg/d; dipyridamole , 75 mg thrice daily; and miniheparinization. On May 29, an open renal biopsy was performed. The following day, the patient experienced grand mal convulsions. His BP was 150/90 mm Hg. Funduscopic examination showed no papilloedema. Serum urea was 248 mg/ dL and creatinine concentration was 2.8 mg/dL. Serum electrolytes were all within the normal range. Cerebrospinal fluid revealed no abnormality. An electroencephalogram showed changes consistent with a metabolic encephalopathy. The seizures abated on treatment with intravenous (IV) diazepam and phenytoin. On the strength of the renal biopsy, therapy with steroids and azathioprine was stopped. Serum creatinine concentration continued to decrease, reaching 1.8 mg/dL on June 2. A day later, the patient's temperature spiked. Lobar pneumonia involving the left lower lobe was diagnosed. Treatment with crystalline penicillin, 4 million U/d, was instituted, resulting in a prompt response. Penicillin was continued for a period of nine days. Hemodynamically, the patient was stable throughout this period. From June 3 to 16, in parallel to the development of the lobar pneumonia and its treatment, the patient's renal function deteriorated. Serum creatinine increased from 1.8 mg/dL to a peak of 9.3 mg/dL. At no stage was oliguria evident. The patient's BP, which up to this time had been well controlled on hydralazine, increased to 170/ 120 mm Hg, necessitating the addition of clonidine. A second renal biopsy was performed percutaneously on July 18. With an established diagnosis of RPGN , treatment with steroids and azathioprine was recommenced. Hemodialysis was resumed. Due to continuous vascular access problems , the patient was transferred to CAPD. His renal function failed to improve, and after a month , therapy was stopped. On January 29, 1984, the patient was transplanted with a living donor graft from his father. At 18 months posttransplant, his renal function was normal , with no clinical or laboratory parameters suggesting a recurrence of the original disease.
Fig 1. First biopsy. Glomeruli showing accentuated lobular pattern, diffuse proliferative changes, and an increase in mesanglal matrix (PAMS stain, original magnification x 250). Inset: Glomerular segment showing .. reduplication" of the basement membrane (PAMS stain, original magnification x 1,000).
PATHOLOGIC FINDINGS
First Renal Biopsy
By light microscopy, the biopsy sample contained 14 glomeruli. All glomeruli showed an accentuated lobular pattern, diffuse proliferative and exudative changes, and an increase in mesangial matrix. There was a marked thickening of the glomerular basement membrane (Fig 1). In only one glomerulus, a large cellular crescent was present. The tubules, interstitium, and blood vessels were without any pathology. On immunofluorescent study, there was prominent granular deposition of C3 along the glomerular capillary wall as well as in the mesangium (Fig 2). With electron microscopy, electron-dense deposits were present in both subendothelial and subepithelial positions (Fig 3). Type I MPGN was diagnosed. Second Renal Biopsy
By light microscopy, the biopsy sample contained 25 glomeruli; in 23 exuberant cellular and, at times, fibrotic crescents were present (Fig 4). There was moderate diffuse tubular atrophy, an interstitial cellular infiltrate of lymphocytes, and interstitial fibrosis. With immunofluorescence, the findings were similar to the first biopsy (immunofluorescence for fibrinogen was not performed). By electron microscopy, total collapse of the glomerular tuft was noted. The pathologic diagnosis was crescentic GN.
58
KORZETS, BERNHEIM, AND BERNHEIM
Fig 2. First biopsy. Immunofluorescent study showing prominent granular deposition of C3 along glomerular basement membrane and in the mesangium.
DISCUSSION
MPGN (also called mesangiocapillary GN) is a chronic glomerulopathy divided by ultrastructural morphology into two main types. 3 -6 It may be found in a variety of clinical situations, reviewed extensively by several authors,1.5,6 but in the majority, it is usually classified as idiopathic. Type I MPGN is characterized by the presence of subendothelial deposits and type II by intramembranous dense deposits. Strife et a1 8 and Anders et a1 9 ,IO defined a third type of MPGN (type III), consisting of both subendothelial and subepithelial deposits. However, others have been reluctant to accept this type as a distinct subgroup, because there are, as yet, no distinguishing features between patients having type III MPGN and those classified as type I. In addition, scattered subepithelial deposits may be seen in otherwise typical type I disease. In fact, the patient presented herein demonstrated just such an association, ie, the presence of "humps" with subendothelial deposits. In this context, although the pathogenesis of type I MPGN is unknown, the morphologic similarity to immune complex GN secondary to certain infections, 1113 the frequent association of humps in poststreptococcal GN, the onset of the disease after a preceding upper respiratory tract infection or influenzal illness in up to 40% of cases, all suggest an infectious etiology.5 It may be speculated whether the preceding illness diagnosed as mumps in the patient reported played any pathogenetic role. Our patient with documented type I MPGN pre-
sented with an acute nephritic-nephrotic syndrome. Although an acute nephritic episode is said to be rather uncommon in type I MPGN,5,14 Cameron et al,3 in a 1983 review of 104 patients, found no such difference in the clinical presentation between types I and II. The course of MPGN may be quite variable, but in general it is slowly progressive toward end-stage renal disease (50% within 10 years of the onset of the disease).2 At times, patients presenting with an acute nephrotic syndrome and advanced renal failure may temporarily improve their renal function. 15 Such was the clinical course in the patient presented herein. Factors that may adversely affect the prognosis in type I MPGN are the presence of a nephrotic syndrome, an initial reduction in glomerular filtration rate, and the existence of hypertension. Histologically, the presence of even a single sclerosed glomerulus or a single large crescent may predict a poorer prognosis. 3 The initial renal biopsy of our patient showed type I MPGN with no evidence of sclerosed glomeruli and only one crescentic glomerulus. The second biopsy performed 6 weeks after the first, showed the typical appearance of RPGN with 92 % of glomeruli affected by crescents. Aggressive immunosuppressive therapy, combined with anticoagulants and antiplatelet drugs, has been advocated as treatment for RPGN .16 Such a trial was attempted in our patient, but to no avail. Only five of the 69 patients with type I MPGN reported by Cameron et a1 3 have had RPGN defined as greater than 60% crescents. The transition
RPGN IN TYPE I MPGN
59
Fig 3. (A and B) First biopsy. Segments of glomerular capillary showing electron-dense deposits in the subendothelial space (arrows) and subepithelial humps (arrowheads). Mesangial interposition (M) is clearly seen between endothelial cell (E) and glomerular basement membrane (A, original magnification x 3,000; B, original magnification x 8,000).
60
KORZETS, BERNHEIM , AND BERNHEIM
Fig 4. Second biopsy. Fi· broepithellal crescents as demonstrated here were present in 23 of the 25 glomeruli present (H&E stain, original magnification x 100).
from pure type I MPGN to RPGN is an extremely rare and unusual course of type I MPGN. Of these five patients, only one showed such a transition occurring within 6 months. This patient was transplanted and the graft was destroyed with extensive crescents after 3 weeks. One further patient was described by McCoy et aF in which the transition occurred within 3 years . This patient is remarkable in that the transition repeated itself in a living donor graft from an identical sibling. Pure type I MPGN recurred in the graft within I month of transplantation and subsequently developed into the crescentic form in 21/2 months. In light of these two reports of rapid recurrence of RPGN in renal allografts in such circumstances, we were reluctant to transplant our patient. However, due to repeated vascular access problems and
repeated episodes of peritonitis on CAPD, the patient was nevertheless transplanted with a living donor graft from his father. At 18 months posttransplantation, his renal function was normal with no clinical or laboratory evidence of recurrence of the original renal disease. In conclusion, to the best of our knowledge, our patient is only the third with such a unique course of type I MPGN. After 6 months of dialysis, the patient was transplanted. Contrary to the previously cited reports,3.7 his renal graft is functioning well. Thus, the extremely poor outlook regarding transplantation in such patients should not be accepted as universal. Instead, each patient should be evaluated individually and a renal allograft considered despite the high risk of recurrence of the original disease.
REFERENCES I. Herdman RC , Pickering RJ , Michael AF, et al : Chronic glomerulonephritis associated with low serum complement activity (chronic hypocomplementemic glomerulonephritis) . Medicine (Baltimore) 49:207-226, 1970 2. Habib R, Kleinknecht C , Gubler MC, et al: Idiopathic membranoproliferative glomerulonephritis in children. Report of 105 cases. Clin Nephrol 1:194-214, 1973 3. Cameron JS, Thrner DR, Heaton J, et al: Idiopathic mesangiocapillary glomerulonephritis. Comparison of types I and II in children and adults and long term prognosis. Am J Med 74:175-192, 1983 4 . Bohle A , Gartner HB , Fischbach H , et al: The morphological aDd clinical features of membranoproliferative glomerulonephritis in adults . Virchows Arch (Pathol Anat) 363:213224, 1974 5. Kim y, Michael AF: Idiopathic membranoproliferative glomerulonephritis. Annu Rev Med 31 :273-288, 1980
6. Zamurovic 0 , Churg J: Idiopathic and secondary mesangiocapillary glomerulonephritis. Nephron 38 : 145-153, 1984 7. McCoy RC, Clapp J, Seigler HF: Membranoproliferative glomerulonephritis: Progression from the pure form to the crescentic form with recurrence after transplantation. Am J Med 59:288-292, 1975 8. Strife CF, McEnery PT, McAdams AJ , et al: Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane . Clin Nephrol 7:65-72, 1976 9 . Anders 0 , Thoenes W: Basement membrane changes in membranoproliferative glomerulonephritis. A light and electron microscopic study. Virchows Arch (Pathol Anat) 369:87109, 1975 10. Anders 0, Agricola B, Sippel M, et al: Basement membrane changes in membranoproliferative glomerulonephritis. II. Characterisation of a third type of silver impregnation of
61
RPGN IN TYPE I MPGN
ultra-thin sections. Virchows Arch (Pathol Anat) 376:1-19, 1977 11. Hendrickse RG: The quartan malarial nephrotic syndrome. Adv Nephrol 6:229-347 , 1976 12. Andrade ZA, Rocha H: Schistosoma! glomerulopathy. Kidney Int 16:23-29, 1979 13 . Gutman RA, Striker GE, Gilliland BC, et al : The immune complex glomerulonephritis of bacterial endocarditis. Medicine 51:1 -25, 1972
14. Antoine B, Faye C: The clinical course associated with dense deposits in the kidney basement membranes. Kidney Int 1:420-427, 1972 15. Habib R: Glomerulonephrite membranoproliferative, in Royer P, Habib R, Mathieu H, et a! (eds): Nephrologie Pediatrique. Paris, F1ammarion, 1983, p 318 16. Niaudet P, Levy M: Glomerulonephrite croissants diffu s, in Royer P, Habib R, Mathieu H et al (eds): Nephrologie Pediatrique. Paris, Flammarion, 1983, pp 390-391
a
Rapidly Progressive Glomerulonephritis (Crescentic Glomerulonephritis) in the Course of Type I Idiopathic Membranoproliferative Glomerulonephritis Ze'ev Korzets, MB, BS, Joelle Bernheim, MD, and Jacques Bernheim, MD • Membranoproliferative glomerulonephritis is a chronic glomerulopathy with a generally progressive course toward end-stage renal disease and a high recurrence rate in renal allografts. Described herein is the appearance of rapidly progressive glomerulonephritis (crescentic glomerulonephritis) in the course of type I membranoproliferative glomerulonephritis. This transition occurred within 6 weeks, documented histologically by an initial and subsequent renal biopsy. No recurrence of the disease was noted in a living donor graft 18 months posttransplantation. © 1987 by the National Kidney Foundation, Inc. INDEX WORDS: Crescentic glomerulonephritis; membranoproliferative glomerulonephritis.
M
EMBRANOPROLIFERATIVE glomerulonephritis (MPGN) is a well-defined form of chronic glomerulonephritis (GN) characterized by distinctive glomerular pathology. I 3 Two main types of MPGN have been distinguished: type I (subendothelial deposit variety) and type II (linear dense deposit disease). 3-6 Each of these types are considered to be distinct, with no change from one form of the disease to the other. Although the presence of crescents in either type has been documented, the appearance of rapidly progressive glomerulonephritis (RPGN), defined as greater than 60% of glomeruli affected by crescents, is a rare occurrence. 3 MPGN has a generally bad prognosis with more than 50 % of those affected progressing to death, dialysis, or transplantation within 10 years of the onset of the disease. 3.5 Only two patients have been described in which type I MPGN has progressed from the pure form to RPGN. 3.7 This transition occurred within 0.6 years in the one patient 3 to 3 years in the second patient. 7 We describe a patient who showed such a transition within a period of 6 weeks. After 6 months on dialysis (continuous ambulatory peritoneal dialysis [CAPD]), the patient was transplanted with a living donor graft donated by his father. Currently,
From the Departments of Nephrology and Pathology, Meir General Hospital; and the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Address reprint requests to Jacques Bernheim, MD, Department of Nephrology, Meir General Hospital, 44281 Kfar Saba, Israel. © 1987 by the National Kidney Foundation, Inc. 0272-6386/87/1001-0010$3.00/0 56
1 liz years posttransplantation, his renal function is normal, with no clinical or laboratory evidence of recurrence of the original disease. CASE REPORT A 16-year-old boy was admitted on May 25, 1983, because of nausea and vomiting. A month previously, he was hospitalized for five days at another hospital with a right epididymoorchitis clinically diagnosed as being secondary to mumps. He was treated witb analgesics, sulphametboxazole-trimethoprim, and ampicillin. His condition improved and he was discharged on April 29. On May 20, he was readmitted to the same hospital, complaining of nausea. On examination he was edematous with a BP reading of 165/105 mm Hg. Urinary output ranged between 600 and 1000 mUd. Proteinuria was 10 g/d. The urinary sediment contained many leukocytes, 15 to 20 erythrocytes (RBC) per high power field, and granular casts. No RBC casts were seen. Serum creatinine was 6.6 mg/dL, and serum albumin 2.0 g/dL. Treatment with prednisone, 60 mg/d, was begun on May 22. Three days later he was transferred to Meir General Hospital for further evaluation. On admission, periorbital with dependent ankle edema and ascites were evident. His BP was 1501100 mm Hg. Neither asterixis or a pericardial friction rub were present. Laboratory data were as follows: serum hemoglobin 9 g/dL, hematocrit 28.8%, sodium 135 mEq/L, potassium 4.8 mEq/L, urea 306 mg/dL, creatinine 4.2 mg/dL, calcium 7.2 mg/dL, phosphorus 8.7 mg/dL, uric acid 9.9 mg/dL, total protein 5.6 g/dL, with an albumin of2.3 g/dL, and cholesterol 185 mg/dL. Urinary output was 1,000 mUd with a proteinuria of 4.4 g/d. Urinalysis was unchanged. Serologic survey, including Rose-Waaler, latex, lupus erythematosus (LE) latex, antinuclear factor and dsDNA, Australian antigen, and cryoglobulins, was negative. C3 and C4 were 100 mg/dL and 26 mg/dL, respectively, (normal values 100 mg/dL and 16 mg/dL, respectively, measured by the radial immunodiffusion method). Serum level of IgG was 1,683 mg/dL, IgA 240 mg/dL, and IgM 168 mg/dL. Chest xray was normal. A plain film of the abdomen showed two kidneys of normal size. Hemodialysis was begun via an external
American Journal of Kidney Diseases, Vol X, No 1 (July), 1987: pp 56-61
57
RPGN IN TYPE I MPGN
shunt. With the patient already undergoing steroid treatment, it was decided to continue prednisone with the addition of azathioprine, 100 mg/d; dipyridamole , 75 mg thrice daily; and miniheparinization. On May 29, an open renal biopsy was performed. The following day, the patient experienced grand mal convulsions. His BP was 150/90 mm Hg. Funduscopic examination showed no papilloedema. Serum urea was 248 mg/ dL and creatinine concentration was 2.8 mg/dL. Serum electrolytes were all within the normal range. Cerebrospinal fluid revealed no abnormality. An electroencephalogram showed changes consistent with a metabolic encephalopathy. The seizures abated on treatment with intravenous (IV) diazepam and phenytoin. On the strength of the renal biopsy, therapy with steroids and azathioprine was stopped. Serum creatinine concentration continued to decrease, reaching 1.8 mg/dL on June 2. A day later, the patient's temperature spiked. Lobar pneumonia involving the left lower lobe was diagnosed. Treatment with crystalline penicillin, 4 million U/d, was instituted, resulting in a prompt response. Penicillin was continued for a period of nine days. Hemodynamically, the patient was stable throughout this period. From June 3 to 16, in parallel to the development of the lobar pneumonia and its treatment, the patient's renal function deteriorated. Serum creatinine increased from 1.8 mg/dL to a peak of 9.3 mg/dL. At no stage was oliguria evident. The patient's BP, which up to this time had been well controlled on hydralazine, increased to 170/ 120 mm Hg, necessitating the addition of clonidine. A second renal biopsy was performed percutaneously on July 18. With an established diagnosis of RPGN , treatment with steroids and azathioprine was recommenced. Hemodialysis was resumed. Due to continuous vascular access problems , the patient was transferred to CAPD. His renal function failed to improve, and after a month , therapy was stopped. On January 29, 1984, the patient was transplanted with a living donor graft from his father. At 18 months posttransplant, his renal function was normal , with no clinical or laboratory parameters suggesting a recurrence of the original disease.
Fig 1. First biopsy. Glomeruli showing accentuated lobular pattern, diffuse proliferative changes, and an increase in mesanglal matrix (PAMS stain, original magnification x 250). Inset: Glomerular segment showing .. reduplication" of the basement membrane (PAMS stain, original magnification x 1,000).
PATHOLOGIC FINDINGS
First Renal Biopsy
By light microscopy, the biopsy sample contained 14 glomeruli. All glomeruli showed an accentuated lobular pattern, diffuse proliferative and exudative changes, and an increase in mesangial matrix. There was a marked thickening of the glomerular basement membrane (Fig 1). In only one glomerulus, a large cellular crescent was present. The tubules, interstitium, and blood vessels were without any pathology. On immunofluorescent study, there was prominent granular deposition of C3 along the glomerular capillary wall as well as in the mesangium (Fig 2). With electron microscopy, electron-dense deposits were present in both subendothelial and subepithelial positions (Fig 3). Type I MPGN was diagnosed. Second Renal Biopsy
By light microscopy, the biopsy sample contained 25 glomeruli; in 23 exuberant cellular and, at times, fibrotic crescents were present (Fig 4). There was moderate diffuse tubular atrophy, an interstitial cellular infiltrate of lymphocytes, and interstitial fibrosis. With immunofluorescence, the findings were similar to the first biopsy (immunofluorescence for fibrinogen was not performed). By electron microscopy, total collapse of the glomerular tuft was noted. The pathologic diagnosis was crescentic GN.
58
KORZETS, BERNHEIM, AND BERNHEIM
Fig 2. First biopsy. Immunofluorescent study showing prominent granular deposition of C3 along glomerular basement membrane and in the mesangium.
DISCUSSION
MPGN (also called mesangiocapillary GN) is a chronic glomerulopathy divided by ultrastructural morphology into two main types. 3 -6 It may be found in a variety of clinical situations, reviewed extensively by several authors,1.5,6 but in the majority, it is usually classified as idiopathic. Type I MPGN is characterized by the presence of subendothelial deposits and type II by intramembranous dense deposits. Strife et a1 8 and Anders et a1 9 ,IO defined a third type of MPGN (type III), consisting of both subendothelial and subepithelial deposits. However, others have been reluctant to accept this type as a distinct subgroup, because there are, as yet, no distinguishing features between patients having type III MPGN and those classified as type I. In addition, scattered subepithelial deposits may be seen in otherwise typical type I disease. In fact, the patient presented herein demonstrated just such an association, ie, the presence of "humps" with subendothelial deposits. In this context, although the pathogenesis of type I MPGN is unknown, the morphologic similarity to immune complex GN secondary to certain infections, 1113 the frequent association of humps in poststreptococcal GN, the onset of the disease after a preceding upper respiratory tract infection or influenzal illness in up to 40% of cases, all suggest an infectious etiology.5 It may be speculated whether the preceding illness diagnosed as mumps in the patient reported played any pathogenetic role. Our patient with documented type I MPGN pre-
sented with an acute nephritic-nephrotic syndrome. Although an acute nephritic episode is said to be rather uncommon in type I MPGN,5,14 Cameron et al,3 in a 1983 review of 104 patients, found no such difference in the clinical presentation between types I and II. The course of MPGN may be quite variable, but in general it is slowly progressive toward end-stage renal disease (50% within 10 years of the onset of the disease).2 At times, patients presenting with an acute nephrotic syndrome and advanced renal failure may temporarily improve their renal function. 15 Such was the clinical course in the patient presented herein. Factors that may adversely affect the prognosis in type I MPGN are the presence of a nephrotic syndrome, an initial reduction in glomerular filtration rate, and the existence of hypertension. Histologically, the presence of even a single sclerosed glomerulus or a single large crescent may predict a poorer prognosis. 3 The initial renal biopsy of our patient showed type I MPGN with no evidence of sclerosed glomeruli and only one crescentic glomerulus. The second biopsy performed 6 weeks after the first, showed the typical appearance of RPGN with 92 % of glomeruli affected by crescents. Aggressive immunosuppressive therapy, combined with anticoagulants and antiplatelet drugs, has been advocated as treatment for RPGN .16 Such a trial was attempted in our patient, but to no avail. Only five of the 69 patients with type I MPGN reported by Cameron et a1 3 have had RPGN defined as greater than 60% crescents. The transition
RPGN IN TYPE I MPGN
59
Fig 3. (A and B) First biopsy. Segments of glomerular capillary showing electron-dense deposits in the subendothelial space (arrows) and subepithelial humps (arrowheads). Mesangial interposition (M) is clearly seen between endothelial cell (E) and glomerular basement membrane (A, original magnification x 3,000; B, original magnification x 8,000).
60
KORZETS, BERNHEIM , AND BERNHEIM
Fig 4. Second biopsy. Fi· broepithellal crescents as demonstrated here were present in 23 of the 25 glomeruli present (H&E stain, original magnification x 100).
from pure type I MPGN to RPGN is an extremely rare and unusual course of type I MPGN. Of these five patients, only one showed such a transition occurring within 6 months. This patient was transplanted and the graft was destroyed with extensive crescents after 3 weeks. One further patient was described by McCoy et aF in which the transition occurred within 3 years . This patient is remarkable in that the transition repeated itself in a living donor graft from an identical sibling. Pure type I MPGN recurred in the graft within I month of transplantation and subsequently developed into the crescentic form in 21/2 months. In light of these two reports of rapid recurrence of RPGN in renal allografts in such circumstances, we were reluctant to transplant our patient. However, due to repeated vascular access problems and
repeated episodes of peritonitis on CAPD, the patient was nevertheless transplanted with a living donor graft from his father. At 18 months posttransplantation, his renal function was normal with no clinical or laboratory evidence of recurrence of the original renal disease. In conclusion, to the best of our knowledge, our patient is only the third with such a unique course of type I MPGN. After 6 months of dialysis, the patient was transplanted. Contrary to the previously cited reports,3.7 his renal graft is functioning well. Thus, the extremely poor outlook regarding transplantation in such patients should not be accepted as universal. Instead, each patient should be evaluated individually and a renal allograft considered despite the high risk of recurrence of the original disease.
REFERENCES I. Herdman RC , Pickering RJ , Michael AF, et al : Chronic glomerulonephritis associated with low serum complement activity (chronic hypocomplementemic glomerulonephritis) . Medicine (Baltimore) 49:207-226, 1970 2. Habib R, Kleinknecht C , Gubler MC, et al: Idiopathic membranoproliferative glomerulonephritis in children. Report of 105 cases. Clin Nephrol 1:194-214, 1973 3. Cameron JS, Thrner DR, Heaton J, et al: Idiopathic mesangiocapillary glomerulonephritis. Comparison of types I and II in children and adults and long term prognosis. Am J Med 74:175-192, 1983 4 . Bohle A , Gartner HB , Fischbach H , et al: The morphological aDd clinical features of membranoproliferative glomerulonephritis in adults . Virchows Arch (Pathol Anat) 363:213224, 1974 5. Kim y, Michael AF: Idiopathic membranoproliferative glomerulonephritis. Annu Rev Med 31 :273-288, 1980
6. Zamurovic 0 , Churg J: Idiopathic and secondary mesangiocapillary glomerulonephritis. Nephron 38 : 145-153, 1984 7. McCoy RC, Clapp J, Seigler HF: Membranoproliferative glomerulonephritis: Progression from the pure form to the crescentic form with recurrence after transplantation. Am J Med 59:288-292, 1975 8. Strife CF, McEnery PT, McAdams AJ , et al: Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane . Clin Nephrol 7:65-72, 1976 9 . Anders 0 , Thoenes W: Basement membrane changes in membranoproliferative glomerulonephritis. A light and electron microscopic study. Virchows Arch (Pathol Anat) 369:87109, 1975 10. Anders 0, Agricola B, Sippel M, et al: Basement membrane changes in membranoproliferative glomerulonephritis. II. Characterisation of a third type of silver impregnation of
61
RPGN IN TYPE I MPGN
ultra-thin sections. Virchows Arch (Pathol Anat) 376:1-19, 1977 11. Hendrickse RG: The quartan malarial nephrotic syndrome. Adv Nephrol 6:229-347 , 1976 12. Andrade ZA, Rocha H: Schistosoma! glomerulopathy. Kidney Int 16:23-29, 1979 13 . Gutman RA, Striker GE, Gilliland BC, et al : The immune complex glomerulonephritis of bacterial endocarditis. Medicine 51:1 -25, 1972
14. Antoine B, Faye C: The clinical course associated with dense deposits in the kidney basement membranes. Kidney Int 1:420-427, 1972 15. Habib R: Glomerulonephrite membranoproliferative, in Royer P, Habib R, Mathieu H, et a! (eds): Nephrologie Pediatrique. Paris, F1ammarion, 1983, p 318 16. Niaudet P, Levy M: Glomerulonephrite croissants diffu s, in Royer P, Habib R, Mathieu H et al (eds): Nephrologie Pediatrique. Paris, Flammarion, 1983, pp 390-391
a