- Email: [email protected]
Current approach to classification of membranoproliferative glomerulonephritis
IAP 2014 ABSTRACTS
membranous glomerulonephritis, depending on individual susceptibility, environmental triggers and the physic-chemical characteristics of the immune deposits. The clinical manifestations include varying degrees of proteinuria, hematuria, nephrotic syndrome, renal insufficiency and hypertension. The proliferative categories can be qualified by several additional features, such as the pattern of proliferative disease, crescents, wire loop lesions and hyaline thrombi, the latter two representing amount and location of immune deposits apparent by light microscopy. Classification of lupus nephritis has evolved from the first version in 1975 as the original WHO classification. Subsequent versions have incorporated additional prognostic features into the various classes/categories. The current ISN/RPS classification of lupus glomerulonephritis has gained wide acceptance and was published in 2004, following an international consensus with significant refinement of the definitions and classes. The advantages and problems associated with this classification are discussed, based on subsequent clinicopathologic validation studies in the last 10 years. Renal Pathology: SY23-1 CURRENT APPROACH TO CLASSIFICATION OF MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS Cynthia C. Nast Cedars-Sinai Medical Center, Los Angeles, CA, USA Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury, which historically has been classified using light and electron microscopic morphologic features. Primary (idiopathic) MPGN was divided into types I, II (dense deposit disease) and III, respectively defined by the presence of subendothelial deposits with capillary double contours, intramembranous electron dense material, or subepithelial and/or intramembranous deposits with or without basement membrane irregularities and subendothelial deposits. Secondary MPGN was associated with underlying diseases including infection, lymphoplasmacytic disorders, autoimmune disease, and malignancy. However, this classification encompasses entities with overlapping pathogenesis, clinical features, and treatment approaches. Therefore, classification of MPGN based on pathogenesis and associated immunofluorescence findings has been suggested. MPGN is divided into immune complex (IC)-mediated (immunoglobulin and complement deposition), complement (C)-mediated (C deposition) and non-IC, nonC-mediated forms. IC-mediated MPGN results from chronic antigenemia, including those previously designated type I, type III and secondary. C-mediated MPGN includes type II (dense deposit disease) and C3 glomerulonephritis, the latter with features of MPGN types I or III. Non-IC, non-C MPGN is secondary to few underlying causes, predominantly thrombotic microangiopathy of any cause. This classification allows for improved prognostic information and optimized approach to therapy. As pathogenesis is better understood, primary MPGN may cease to exist.
S41
A 41-year-old woman was discovered to have enteric infection of Aeromonas caviae and was treated with antibiotics. Subsequently she developed nephrotic syndrome. Renal biopsy showed a nonargentaffine hole in the glomerular basement membrane (GBM) in PAM stain with IgG and C3 deposition. This finding was similar to membranous glomerulonephritis. However, electron microscopy showed no electron dense deposits but microspheres or microtubular structures associated with podocytic infolding into the GBM. Corticosteroid treatment resulted in rapid remission.1 This case corresponds to a new disease entity of podocytic infolding glomerulopathy, which was proposed by a working group of The Japanese Society of Nephrology on the basis of 25 cases corrected from 17 institutions all over Japan.2 The question arises whether these morphological changes are specific for a new disease entity or they could reflect a nonspecific cellular response of the podocyte to an injury. References 1. Nagayama Y, Morita H, Kawashima E, et al. Light microscopic features of membranous nephropathy with unusual changes of the podocyte and glomerular basement membrane in a patient with sudden onset of nephrotic syndrome. Am J Kidney Dis 2010; 55: 962–6. 2. Joh K, Taguchi T, Shigematsu H, et al. Proposal of podocytic infolding glomerulopathy as a new disease entity: a review of 25 cases from nationwide research in Japan. Clin Exp Nephrol 2008; 12: 421–31.
Renal Pathology: SY23-2 A CASE OF PERSISTENT LOW C3 SERUM LEVEL WITH MPGN PATTERN: FIVE-YEAR FOLLOW UP Yong-Jin Kim1, Myoung-Uk Kim2 and Yong-Hoon Park2 1Department of Pathology, Yeungnam University College of Medicine, Daegu, and 2Department of Pediatrics, Yeungnam University College of Medicine, Daegu, Korea A 10-year-old girl visited for microscopic hematuria and proteinuria on school urine screening. She was asymptomatic with normal renal function. Persistent C3 hypocomplementemia led her to a kidney biopsy. First biopsy showed membranoproliferative glomerulonephritis (MPGN) pattern with only C3 deposition on IF and mesangial electron dense deposits. She was under supportive therapy including angiotensin-converting enzyme (ACE) inhibitor for over two years. During the period, she did not have renal symptoms nor proteinuria. But microscopic hematuria and C3 hypocomplementemia had persisted. After 33 months of treatment, the patient quit medication on her own. Over one year later, she revisited clinic with microscopic hematuria and normal renal function at the age of 15. She denied of any symptoms during the entire period. Kidney function was within normal range, without decline, and C3 hypocomplementemia persisted. A second kidney biopsy was taken for nephrotic-range proteinuria (53.37 mg/m2/hr). Points of interest: (1) Morphologic progression of this GN after five years with only supportive therapy, (2) pathogenesis and treatment strategies, so far. Renal Pathology: SY23-2
Renal Pathology: SY23-2 A CASE OF A NEW DISEASE ENTITY: PODOCYTIC INFOLDING GLOMERULOPATHY Kensuke Joh Department of Pathology, Tohoku University Graduate School of Medicine, Japan
HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS SYNDROME – A CASE REPORT Alenka Vizjak1, Jelka Lindicˇ2, Jerica Mraz1 and Dusˇ an Ferluga1 1Institute of Pathology Faculty of Medicine University of Ljubljana, and 2Department of Nephrology, University Medical Center Ljubljana, Slovenia
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
membranous glomerulonephritis, depending on individual susceptibility, environmental triggers and the physic-chemical characteristics of the immune deposits. The clinical manifestations include varying degrees of proteinuria, hematuria, nephrotic syndrome, renal insufficiency and hypertension. The proliferative categories can be qualified by several additional features, such as the pattern of proliferative disease, crescents, wire loop lesions and hyaline thrombi, the latter two representing amount and location of immune deposits apparent by light microscopy. Classification of lupus nephritis has evolved from the first version in 1975 as the original WHO classification. Subsequent versions have incorporated additional prognostic features into the various classes/categories. The current ISN/RPS classification of lupus glomerulonephritis has gained wide acceptance and was published in 2004, following an international consensus with significant refinement of the definitions and classes. The advantages and problems associated with this classification are discussed, based on subsequent clinicopathologic validation studies in the last 10 years. Renal Pathology: SY23-1 CURRENT APPROACH TO CLASSIFICATION OF MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS Cynthia C. Nast Cedars-Sinai Medical Center, Los Angeles, CA, USA Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury, which historically has been classified using light and electron microscopic morphologic features. Primary (idiopathic) MPGN was divided into types I, II (dense deposit disease) and III, respectively defined by the presence of subendothelial deposits with capillary double contours, intramembranous electron dense material, or subepithelial and/or intramembranous deposits with or without basement membrane irregularities and subendothelial deposits. Secondary MPGN was associated with underlying diseases including infection, lymphoplasmacytic disorders, autoimmune disease, and malignancy. However, this classification encompasses entities with overlapping pathogenesis, clinical features, and treatment approaches. Therefore, classification of MPGN based on pathogenesis and associated immunofluorescence findings has been suggested. MPGN is divided into immune complex (IC)-mediated (immunoglobulin and complement deposition), complement (C)-mediated (C deposition) and non-IC, nonC-mediated forms. IC-mediated MPGN results from chronic antigenemia, including those previously designated type I, type III and secondary. C-mediated MPGN includes type II (dense deposit disease) and C3 glomerulonephritis, the latter with features of MPGN types I or III. Non-IC, non-C MPGN is secondary to few underlying causes, predominantly thrombotic microangiopathy of any cause. This classification allows for improved prognostic information and optimized approach to therapy. As pathogenesis is better understood, primary MPGN may cease to exist.
S41
A 41-year-old woman was discovered to have enteric infection of Aeromonas caviae and was treated with antibiotics. Subsequently she developed nephrotic syndrome. Renal biopsy showed a nonargentaffine hole in the glomerular basement membrane (GBM) in PAM stain with IgG and C3 deposition. This finding was similar to membranous glomerulonephritis. However, electron microscopy showed no electron dense deposits but microspheres or microtubular structures associated with podocytic infolding into the GBM. Corticosteroid treatment resulted in rapid remission.1 This case corresponds to a new disease entity of podocytic infolding glomerulopathy, which was proposed by a working group of The Japanese Society of Nephrology on the basis of 25 cases corrected from 17 institutions all over Japan.2 The question arises whether these morphological changes are specific for a new disease entity or they could reflect a nonspecific cellular response of the podocyte to an injury. References 1. Nagayama Y, Morita H, Kawashima E, et al. Light microscopic features of membranous nephropathy with unusual changes of the podocyte and glomerular basement membrane in a patient with sudden onset of nephrotic syndrome. Am J Kidney Dis 2010; 55: 962–6. 2. Joh K, Taguchi T, Shigematsu H, et al. Proposal of podocytic infolding glomerulopathy as a new disease entity: a review of 25 cases from nationwide research in Japan. Clin Exp Nephrol 2008; 12: 421–31.
Renal Pathology: SY23-2 A CASE OF PERSISTENT LOW C3 SERUM LEVEL WITH MPGN PATTERN: FIVE-YEAR FOLLOW UP Yong-Jin Kim1, Myoung-Uk Kim2 and Yong-Hoon Park2 1Department of Pathology, Yeungnam University College of Medicine, Daegu, and 2Department of Pediatrics, Yeungnam University College of Medicine, Daegu, Korea A 10-year-old girl visited for microscopic hematuria and proteinuria on school urine screening. She was asymptomatic with normal renal function. Persistent C3 hypocomplementemia led her to a kidney biopsy. First biopsy showed membranoproliferative glomerulonephritis (MPGN) pattern with only C3 deposition on IF and mesangial electron dense deposits. She was under supportive therapy including angiotensin-converting enzyme (ACE) inhibitor for over two years. During the period, she did not have renal symptoms nor proteinuria. But microscopic hematuria and C3 hypocomplementemia had persisted. After 33 months of treatment, the patient quit medication on her own. Over one year later, she revisited clinic with microscopic hematuria and normal renal function at the age of 15. She denied of any symptoms during the entire period. Kidney function was within normal range, without decline, and C3 hypocomplementemia persisted. A second kidney biopsy was taken for nephrotic-range proteinuria (53.37 mg/m2/hr). Points of interest: (1) Morphologic progression of this GN after five years with only supportive therapy, (2) pathogenesis and treatment strategies, so far. Renal Pathology: SY23-2
Renal Pathology: SY23-2 A CASE OF A NEW DISEASE ENTITY: PODOCYTIC INFOLDING GLOMERULOPATHY Kensuke Joh Department of Pathology, Tohoku University Graduate School of Medicine, Japan
HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS SYNDROME – A CASE REPORT Alenka Vizjak1, Jelka Lindicˇ2, Jerica Mraz1 and Dusˇ an Ferluga1 1Institute of Pathology Faculty of Medicine University of Ljubljana, and 2Department of Nephrology, University Medical Center Ljubljana, Slovenia
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.