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1
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Finn LS. Nephrotic Syndrome Throughout Childhood: Diagnosing Podocytopathies From the Womb to the Dorm. Pediatr Dev Pathol 2024; 27:426-458. [PMID: 38745407 DOI: 10.1177/10935266241242669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
The etiologies of podocyte dysfunction that lead to pediatric nephrotic syndrome (NS) are vast and vary with age at presentation. The discovery of numerous novel genetic podocytopathies and the evolution of diagnostic technologies has transformed the investigation of steroid-resistant NS while simultaneously promoting the replacement of traditional morphology-based disease classifications with a mechanistic approach. Podocytopathies associated with primary and secondary steroid-resistant NS manifest as diffuse mesangial sclerosis, minimal change disease, focal segmental glomerulosclerosis, and collapsing glomerulopathy. Molecular testing, once an ancillary option, has become a vital component of the clinical investigation and when paired with kidney biopsy findings, provides data that can optimize treatment and prognosis. This review focuses on the causes including selected monogenic defects, clinical phenotypes, histopathologic findings, and age-appropriate differential diagnoses of nephrotic syndrome in the pediatric population with an emphasis on podocytopathies.
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Affiliation(s)
- Laura S Finn
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine at The University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
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2
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Carvajal Abreu K, Loos S, Fischer L, Pape L, Wiech T, Kemper MJ, Tönshoff B, Oh J, Schild R. Case report: Early onset de novo FSGS in a child after kidney transplantation-a successful treatment. Front Pediatr 2023; 11:1280521. [PMID: 37830056 PMCID: PMC10566293 DOI: 10.3389/fped.2023.1280521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Accepted: 09/14/2023] [Indexed: 10/14/2023] Open
Abstract
Background Early onset de novo focal segmental glomerular sclerosis (FSGS) in the kidney allograft in patients without FSGS in the native kidney is a rare disorder in children. It usually occurs mostly beyond the first year after kidney transplantation and often leads to graft loss. Standardized treatment protocols have not yet been established. Case description We describe a boy with early onset de novo FSGS in the transplanted kidney and non-selective glomerular proteinuria (maximum albumin-to-creatinine ratio of 3.8 g/g; normal range, ≤0.03 g/g creatinine). Manifestation occurred at 30 days posttransplant and was accompanied by a significant graft dysfunction (eGFR 61 ml/min per 1.73 m2). Treatment with 25 sessions of plasmapheresis over 14 weeks and three consecutive days of methylprednisolone pulse therapy (10 mg/kg per day) followed by oral prednisolone as rejection prophylaxis (3.73 mg/m2 per day) led to sustained remission of proteinuria (albumin-to-creatinine ratio of 0.028 g/g) and normalization of graft function (eGFR 92 ml/min per 1.73 m2) after 14 weeks. The follow-up period was 36 months. Conclusions This case underlines the efficacy of immunosuppressive and antibody eliminating therapy in early onset de novo FSGS after kidney transplantation.
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Affiliation(s)
- Karla Carvajal Abreu
- Department of Pediatric Nephrology, Pediatric Hepatology and Pediatric Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sebastian Loos
- Department of Pediatric Nephrology, Pediatric Hepatology and Pediatric Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lutz Fischer
- Department of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lars Pape
- Department of Pediatrics II, University Hospital of Essen, University of Essen-Duisburg, Essen, Germany
| | - Thorsten Wiech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Markus J. Kemper
- Department of Pediatrics, Asklepios Klinik Nord-Heidberg, Hamburg, Germany
| | - Burkhard Tönshoff
- Department of Pediatrics I, University Children’s Hospital Heidelberg, Heidelberg, Germany
| | - Jun Oh
- Department of Pediatric Nephrology, Pediatric Hepatology and Pediatric Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Raphael Schild
- Department of Pediatric Nephrology, Pediatric Hepatology and Pediatric Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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3
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Wang H, Wan C, Jiang M, Zhang C. Non-glomerular Tip Lesion Focal Segmental Glomerulosclerosis as a Negative Predictor in Idiopathic Membranous Nephropathy. Curr Med Sci 2022; 42:1007-1014. [DOI: 10.1007/s11596-022-2628-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 07/05/2022] [Indexed: 11/30/2022]
Abstract
Abstract
Objective
To assess the significance of focal segmental glomerulosclerosis (FSGS) variants on clinicopathological characteristics and short-term outcomes in idiopathic membranous nephropathy (IMN) patients.
Methods
The clinicopathological data of 146 IMN patients diagnosed between December 2016 and March 2019 in our center were collected and analyzed. These patients were divided into the pure IMN group, IMN with glomerular tip lesion (GTL) group, and IMN with non-GTL FSGS group.
Results
The IMN with non-GTL FSGS and IMN with GTL groups both had higher proportions of patients with hypertension, lower serum albumin, and severe proteinuria, while the IMN with non-GTL FSGS group additionally showed higher blood pressure and serum cholesterol, and lower serum IgG than the IMN group (all P<0.05). As for pathology, the IMN with non-GTL FSGS group had higher proportions of patients with acute tubular injury and moderate to severe chronic injuries than the IMN group (all P<0.05). In the IMN, IMN with GTL, and IMN with non-GTL FSGS groups, the overall one-year remission rates were 81.6%, 76%, and 58.8%, respectively. Furthermore, the IMN with non-GTL FSGS group showed the lowest cumulative incidence to reach remission within one year. Multivariate Cox logistic analysis demonstrated that higher level of serum anti-M-type phospholipase A2 receptor antibody and the existence of non-GTL FSGS lesion were independent predictors for no remission in IMN patients.
Conclusion
The non-GTL FSGS lesion was a novel negative predictor in IMN and should be taken into account in the management of IMN.
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Ozeki T, Nagata M, Katsuno T, Inagaki K, Goto K, Kato S, Yasuda Y, Tsuboi N, Maruyama S. Nephrotic syndrome with focal segmental glomerular lesions unclassified by Columbia classification; Pathology and clinical implication. PLoS One 2021; 16:e0244677. [PMID: 33400710 PMCID: PMC7785116 DOI: 10.1371/journal.pone.0244677] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 12/14/2020] [Indexed: 11/30/2022] Open
Abstract
Background The Columbia classification is widely used for diagnosis of focal segmental glomerulosclerosis (FSGS). In practice, we occasionally encounter segmental glomerular lesions unclassified as Columbia classification. We analyzed the clinical implication of unclassified segmental lesions comparing with Columbia-classified FSGS. Methods A retrospective cohort study from 13 local hospitals in Japan. From 172 biopsy cases diagnosed with FSGS or minimal change disease (MCD)/FSGS spectrum with unclassified segmental lesions, adult patients with nephrotic syndrome who received immunosuppressive therapies were included. The cases are classified by pathology, i.e., typical FSGS lesions sufficiently classified into subgroups of Columbia classification: collapsing (COL), tip (TIP), cellular (CEL), perihilar (PH), and not otherwise specified (NOS), and unclassified by the Columbia classification into three subgroups: “endothelial damage,”; “simple attachment,”; and “minor cellular lesion,”. The response to immunosuppressive treatment and 30% decline of eGFR were compared. Results Among 48 eligible cases, all were Japanese, 34 were typical FSGS; 13 TIP, 15 CEL, 6 NOS, and no COL or PH cases. Fourteen were unclassified cases: endothelial damage (n = 6), simple attachment (n = 5), and minor cellular lesion (n = 3). The median age of overall patients was 60 years old and the median of eGFR and urinary protein creatinine ratio was 51.5 mL/min/1.73m2 and 7.35, respectively. They received similar therapeutic regimen. Kaplan-Meier analysis revealed no significant difference in treatment response between typical FSGS and unclassified cases. Evaluating among the subgroups, endothelial damage, simple attachment and minor cellular lesion showed similar treatment response to TIP or CEL. No significant difference was also observed in the 30% decline of eGFR. Conclusions Japanese adult patients with nephrotic syndrome showing unclassified segmental lesions as Columbia classification may be equivalent clinical impact as Columbia classification of FSGS.
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Affiliation(s)
- Takaya Ozeki
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Michio Nagata
- Faculty of Medicine, Kidney and Vascular Pathology, University of Tsukuba, Tsukuba, Japan
| | - Takayuki Katsuno
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Koji Inagaki
- Department of Nephrology, Chutoen General Medical Center, Kakegawa, Japan
| | - Kazunori Goto
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Sawako Kato
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshinari Yasuda
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Naotake Tsuboi
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shoichi Maruyama
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- * E-mail:
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5
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Kuppe C, Leuchtle K, Wagner A, Kabgani N, Saritas T, Puelles VG, Smeets B, Hakroush S, van der Vlag J, Boor P, Schiffer M, Gröne HJ, Fogo A, Floege J, Moeller MJ. Novel parietal epithelial cell subpopulations contribute to focal segmental glomerulosclerosis and glomerular tip lesions. Kidney Int 2019; 96:80-93. [PMID: 31029503 PMCID: PMC7292612 DOI: 10.1016/j.kint.2019.01.037] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Revised: 01/23/2019] [Accepted: 01/31/2019] [Indexed: 10/27/2022]
Abstract
Beside the classical flat parietal epithelial cells (PECs), we investigated proximal tubular epithelial-like cells, a neglected subgroup of PECs. These cells, termed cuboidal PECs, make up the most proximal part of the proximal tubule and may also line parts of Bowman's capsule. Additionally, a third intermediate PEC subgroup was identified at the junction between the flat and cuboidal PEC subgroups at the tubular orifice. The transgenic mouse line PEC-rtTA labeled all three PEC subgroups. Here we show that the inducible Pax8-rtTA mouse line specifically labeled only cuboidal and intermediate PECs, but not flat PECs. In aging Pax8-rtTA mice, cell fate mapping showed no evidence for significant transdifferentiation from flat PECs to cuboidal or intermediate PECs or vice versa. In murine glomerular disease models of crescentic glomerulonephritis, and focal segmental glomerulosclerosis (FSGS), intermediate PECs became more numerous. These intermediate PECs preferentially expressed activation markers CD44 and Ki-67, suggesting that this subgroup of PECs was activated more easily than the classical flat PECs. In mice with FSGS, cuboidal and intermediate PECs formed sclerotic lesions. In patients with FSGS, cells forming the tip lesions expressed markers of intermediate PECs. These novel PEC subgroups form sclerotic lesions and were more prone to cellular activation compared to the classical flat PECs in disease. Thus, colonization of Bowman's capsule by cuboidal PECs may predispose to lesion formation and chronic kidney disease. We propose that tip lesions originate from this novel subgroup of PECs in patients with FSGS.
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Affiliation(s)
- Christoph Kuppe
- Division of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany.
| | - Katja Leuchtle
- Division of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany
| | - Anton Wagner
- Division of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany
| | - Nazanin Kabgani
- Division of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany
| | - Turgay Saritas
- Division of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany
| | - Victor G Puelles
- Division of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany; Cardiovascular Program, Monash Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, School of Biomedical Sciences, and Centre for Inflammatory Diseases, Monash University, Melbourne, Victoria, Australia; Department of Nephrology, Monash Health, Melbourne Australia
| | - Bart Smeets
- Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Samy Hakroush
- Institute of Pathology, University Medical Center, Göttingen, Germany
| | - Johan van der Vlag
- Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Peter Boor
- Division of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany; Institute of Pathology, RWTH University of Aachen, Aachen, Germany
| | - Mario Schiffer
- Department of Nephrology and Hypertension, University of Erlangen, Erlangen, Germany
| | - Hermann-Josef Gröne
- Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany
| | - Agnes Fogo
- Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jürgen Floege
- Division of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany
| | - Marcus Johannes Moeller
- Division of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany.
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6
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Goto D, Ohashi N, Takeda A, Fujigaki Y, Shimizu A, Yasuda H, Ohishi K. Case of human immunodeficiency virus infection presenting as a tip variant of focal segmental glomerulosclerosis: A case report and review of the literature. World J Nephrol 2018; 7:90-95. [PMID: 30090707 PMCID: PMC6081390 DOI: 10.5527/wjn.v7.i4.90] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 06/28/2018] [Accepted: 06/30/2018] [Indexed: 02/06/2023] Open
Abstract
The incidence of the collapsing variant of focal segmental glomerulosclerosis (FSGS) as a human immunodeficiency virus (HIV)-associated nephropathy has reduced since the introduction of antiretroviral therapy (ART). However, the incidence of other variants of FSGS, except for the collapsing variant, is increasing, and its therapeutic strategies remain uncertain. A 60-year-old HIV infected man in remission with ART was admitted for progressive renal insufficiency and nephrotic-ranged proteinuria. Renal biopsy revealed a tip variant of FSGS and his clinical manifestations resolved with corticosteroid therapy. HIV infected patients might develop non-collapsing FSGS, including tip variant of FSGS and corticosteroid therapy might be effective for them. A renal biopsy might be essential to determine the renal histology and to decide on corticosteroid therapy.
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Affiliation(s)
- Daiki Goto
- Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Naro Ohashi
- Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Asumi Takeda
- Division of Nephrology, Hamamatsu Medical Center, Hamamatsu 432-8580, Japan
| | - Yoshihide Fujigaki
- Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan
| | - Akira Shimizu
- Department of Pathology, Nihon University School of Medicine, Tokyo 113-8602, Japan
| | - Hideo Yasuda
- Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Kazuhisa Ohishi
- Division of Nephrology, Hamamatsu Medical Center, Hamamatsu 432-8580, Japan
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Trivedi M, Pasari A, Chowdhury AR, Abraham-Kurien A, Pandey R. The Spectrum of Focal Segmental Glomerulosclerosis from Eastern India: Is It Different? Indian J Nephrol 2018; 28:215-219. [PMID: 29962672 PMCID: PMC5998723 DOI: 10.4103/ijn.ijn_115_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Focal segmental glomerulosclerosis (FSGS) is a disease that is defined entirely by its histopathological appearance. The recent Columbian classification has grouped this disease into various types based on the light microscopic description. There is a paucity of data describing the distribution of its various subtypes from the Indian subcontinent. This study was undertaken with the aim to throw light on the epidemiology and clinical features of primary FSGS in Eastern India. This retrospective study includes our cohort of biopsy-proven FSGS who presented to us from June 2009 to July 2011 and the analysis of their presenting clinical and histopathological features from our center in East India. Out of 347 patients diagnosed with FSGS in this period, 224 patients were included in the study. A total of 167 cases were of not otherwise specified (NOS) variant (74.5%), 30 tip variant (13.39%), 14 perihilar (6.25%), 8 cellular (3.57%), and 5 to the collapsing variant (2.23%). The maximum proteinuria at presentation was seen with the tip variant (7.98 ± 6.6 g/24 h), and the renal functions were most deranged at presentation with the collapsing variant. These findings were different from those described in other populations including higher prevalence of the tip and the perihilar variant, significant difference in the degree of hypertension, proteinuria, and renal dysfunction among the different variants. The Columbian classification has helped to stratify the outcomes of this glomerular disease with respect to its clinical presentation as well as histopathological features. However, the characteristics of the various variants do show a distinctive pattern in various populations based on ethnicities.
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Affiliation(s)
- M Trivedi
- Department of Nephrology, P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - A Pasari
- Department of Nephrology, Orange City Hospital, Nagpur, Maharashtra, India
| | - A R Chowdhury
- Department of Nephrology, IPGMER, Kolkata, West Bengal, India
| | - A Abraham-Kurien
- Centre for Renal and Urological Pathology Pvt Ltd., Chennai, Tamil Nadu, India
| | - R Pandey
- Department of Nephrology, IPGMER, Kolkata, West Bengal, India
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8
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Practical Application of Columbia Classification for Focal Segmental Glomerulosclerosis. BIOMED RESEARCH INTERNATIONAL 2016; 2016:9375753. [PMID: 27247945 PMCID: PMC4876206 DOI: 10.1155/2016/9375753] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/24/2015] [Accepted: 04/06/2016] [Indexed: 11/29/2022]
Abstract
Focal segmental glomerulosclerosis (FSGS) is a heterogeneous clinicopathological entity. Two frameworks for the classification of FSGS have been described: etiologic and morphologic. The etiologic classification is distinguished among genetic, adaptive, virus-associated, drug-induced, and idiopathic types. Morphologic classification is commonly referred to as the Columbia classification published in 2004, which distinguishes five variants: collapsing, tip, cellular, perihilar, and not otherwise specified (NOS). This classification is based on light microscopic patterns with rigorously defined specific criteria, which can be applied to primary and secondary forms of FSGS, and has been widely used over the past 10 years both as a diagnostic and as a prognostic clinical tool. This paper defines common histopathological features of FSGS, distinguished characters among five variants, and points out the confusion about terminology of variants, because most were proposed in the past with different definitions. Despite good interobserver reproducibility of this classification system, difficulty in its application may arise in the interpretation of lesions with mixed features of more than one variant in the same tissue specimen and with late lesions, because other variants may evolve into the NOS variant over time.
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Bomback AS, Perazella MA, Choi MJ. American Society of Nephrology Quiz and Questionnaire 2015: Glomerular Diseases. Clin J Am Soc Nephrol 2016; 11:884-890. [PMID: 26847362 PMCID: PMC4858496 DOI: 10.2215/cjn.12871215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and kidney transplantation. Complex cases representing each of these categories, along with single-best-answer questions, were prepared and submitted by the panel of experts. Before the meeting, training program directors of United States nephrology fellowship programs and nephrology fellows answered the questions through an Internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using their cell phones with a special app with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.
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MESH Headings
- Aged
- Educational Measurement
- Female
- Glomerulonephritis, IGA/complications
- Glomerulonephritis, IGA/diagnosis
- Glomerulonephritis, IGA/drug therapy
- Glomerulosclerosis, Focal Segmental/diagnosis
- Glomerulosclerosis, Focal Segmental/drug therapy
- Glomerulosclerosis, Focal Segmental/pathology
- Hematuria/etiology
- Humans
- Male
- Nephrology/education
- Proteinuria/etiology
- Surveys and Questionnaires
- Vasculitis, Leukocytoclastic, Cutaneous/complications
- Vasculitis, Leukocytoclastic, Cutaneous/diagnosis
- Vasculitis, Leukocytoclastic, Cutaneous/pathology
- Young Adult
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Affiliation(s)
- Andrew S. Bomback
- Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, New York
| | - Mark A. Perazella
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut; and
| | - Michael J. Choi
- Division of Nephrology, Johns Hopkins University, Baltimore, Maryland
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11
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Mungan S, Turkmen E, Aydin MC, Saglam AE, Baydar DE. Tip lesion variant of primary focal and segmental glomerulosclerosis: clinicopathological analysis of 20 cases. Ren Fail 2015; 37:858-65. [PMID: 25857429 DOI: 10.3109/0886022x.2015.1033635] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The glomerular tip lesion (GTL) is a distinctive histopathologic lesion which is regarded as a variant of focal and segmental glomerulosclerosis (FSGS). The prognostic significance of GTL among other FSGS variants has been disputed. In order to define the clinical features and outcome of GTL, we retrospectively reviewed the presenting clinical features, laboratory and biopsy findings and surveillance in our cohort of GTL, which consisted of 20 adults with native kidneys (mean age 46 years) with follow-up data ranging from 3 to 137 months. At presentation, mean urine protein, serum albumin and cholesterol levels were 5.17 g/d, 2.6 g/dL and 312.9 mg/dL, respectively, and none had renal insufficiency. Microscopic hematuria was detected in five patients. At biopsy, glomerular segmental lesions consisted of GTL without perihilar or collapsing lesions. GTL was observed in a variable proportion of glomeruli from 2.6% to 100%. Mesangial proliferation was seen in nine cases, at a moderate degree in two and mild in the rest. Three biopsies showed mild, two showed moderate interstitial fibrosis/tubular atrophy. Eleven patients received steroids alone and eight received sequential therapy with steroids and a cytotoxic agent. At a mean follow-up of 40.6 months, 17 patients (85%) achieved complete remission of nephrotic syndrome, 15% had partial remission. Four of 17 suffered from recurrences. No patient progressed to end-stage renal disease. Serum albumin at diagnosis was the only predictor of a recurrence (p = 0.037). Microscopic hematuria correlated with incomplete remission (p = 0.045). Our study demonstrates a clearly favorable prognosis in patients with FSGS-GTL variant.
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Affiliation(s)
- Sevdegul Mungan
- a Department of Pathology , Karadeniz Technical University, School of Medicine , Trabzon , Turkey
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12
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Trivedi M, Pasari A, Chowdhury AR, Abraham A, Pandey R. Tip variant of focal segmental glomerulosclerosis: is it truly a benign variant? Ren Fail 2015; 37:763-8. [PMID: 25721429 DOI: 10.3109/0886022x.2015.1014755] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Even though frequently described as a benign entity, the outcomes of the tip variant of focal segmental glomerulosclerosis (FSGS) have proven to be unclear. METHODS This retrospective study includes a cohort of tip variant cases who presented to us from 2009 to 2012 and the analysis of their presenting clinical, histopathological features and treatment outcomes in comparison to the not otherwise specified (NOS) variants from our center in East India. RESULTS Of the 224 biopsies of primary FSGS, 30 cases were the tip variant (13.39%). The mean age of presentation was around 29 years, with 57% being males. A nephrotic presentation was seen in 87% of cases, with 20% showing a presentation at <18 years of age for the first time. Global sclerosis, interstitial fibrosis, tubular atrophy and arteriolar hyalinosis were seen more commonly in the NOS variant. Twenty five patients of tip variant received steroid therapy and eight received alternative immunosuppression. Around 87% of the tip variant cases achieved some form of remission in proteinuria and 13.3% had a doubling of creatinine at a median follow-up of 2 years in comparison to NOS group in which 80% achieved some form of remission and 20% had a doubling of creatinine. CONCLUSION Though the histopathological features and treatment responsiveness of the tip variant appear to be better than the NOS variety, the prognostic outcome does not seem to be as favorable as implicated previously with an important percentage of patients showing progressive worsening of renal function within a relatively short time span (2 years) in our cohort.
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Affiliation(s)
- Mayuri Trivedi
- a Department of Nephrology , Institute of Postgraduate Medical Education and Research , Kolkata , India and
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Ling C, Liu X, Shen Y, Chen Z, Fan J, Jiang Y, Meng Q. Urinary CD80 levels as a diagnostic biomarker of minimal change disease. Pediatr Nephrol 2015; 30:309-16. [PMID: 25142334 DOI: 10.1007/s00467-014-2915-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Revised: 06/16/2014] [Accepted: 07/14/2014] [Indexed: 11/28/2022]
Abstract
BACKGROUND Early diagnosis of minimal change disease (MCD) in nephrotic syndrome (NS) patients remains challenging. Doctors often make a diagnosis of MCD using invasive renal biopsy. CD80, a transmembrane protein, is present on podocytes in a number of experimental models of NS. Urinary CD80 levels are significantly elevated in MCD but not in focal segmental glomerulosclerosis (FSGS) or other glomerulopathies. The purpose of this study was to investigate the feasibility of using urinary CD80 levels as a biomarker for the diagnosis of MCD. MATERIALS AND METHODS A total of 165 subjects, 129 men and 36 women, were enrolled in this study. Urinary samples were collected from 37 patients with MCD, 27 patients with FSGS, 30 patients with other glomerulopathies, and 71 healthy people. Using ELISA, experimental values were compared with those produced by kidney biopsy samples. RESULTS The concentration of urinary CD80 was significantly higher in the active MCD group (689.66 ± 378.21 ng/g creatinine) than in the FSGS group (123.49 ± 167. 88 ng/g creatinine, P < 0.00), other glomerulopathies group (152.37 ± 220. 14 ng/g creatinine, P < 0.001) and the control group (81.83 ± 23.01 ng/g creatinine; P < 0.001). A cutoff value of 328.98 (ng/g creatinine) was proposed, with a sensitivity of 81.1 % and specificity of 94.4 %. The area under the receiver operating characteristic (ROC) curve for the urinary CD80 to diagnose MCD was 0.925 (95 % confidence interval: 0.873-0.978). CONCLUSIONS This experiment has preliminarily confirmed urinary CD80 as a non-invasive diagnostic biomarker. It may have significant value in the diagnosis of MCD.
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Affiliation(s)
- Chen Ling
- Department of Nephrology, Beijing Children's Hospital affiliated to Capital Medical University, West District Nan Li Shi Lu 56th, Beijing, 100045, China
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Abstract
Kidney diseases are morphologically heterogeneous. Pathologic classifications of renal disease permit standardization of diagnosis and may identify clinical-pathologic subgroups with different outcomes and/or responses to treatment. To date, classifications have been proposed for lupus nephritis, allograft rejection, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic antibody -related glomerulonephritis, and diabetic glomerulosclerosis. These classifications share several limitations related to lack of specificity, reproducibility, validation, and relevance to clinical practice. They offer a standardized approach to diagnosis, however, which should facilitate communication and clinical research.
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Affiliation(s)
- M Barry Stokes
- Department of Pathology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, VC14-224, New York, NY 10032, USA.
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Stokes MB, D'Agati VD. Morphologic variants of focal segmental glomerulosclerosis and their significance. Adv Chronic Kidney Dis 2014; 21:400-7. [PMID: 25168828 DOI: 10.1053/j.ackd.2014.02.010] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Accepted: 02/05/2014] [Indexed: 11/11/2022]
Abstract
Focal segmental glomerulosclerosis (FSGS) comprises a group of clinical-pathologic syndromes characterized by heavy proteinuria and segmental obliteration of glomerular capillaries by extracellular matrix. FSGS lesions display morphologic heterogeneity with respect to their relationship to the glomerular vascular and tubular poles, the presence of capillary collapse, and endocapillary and extracapillary hypercellularity. A working proposal, commonly referred to as the Columbia Classification, distinguishes 5 mutually exclusive morphologic variants: collapsing, tip, cellular, perihilar, and not otherwise specified (NOS), which can be applied to primary and secondary forms of FSGS. Several studies have documented significant differences in baseline clinical characteristics and outcomes between morphologic variants of primary FSGS, supporting that this classification may provide useful prognostic information. The association of certain variants with particular secondary causes of FSGS suggests pathogenetic relevance.
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Shimizu A, Higo S, Fujita E, Mii A, Kaneko T. Focal segmental glomerulosclerosis after renal transplantation. Clin Transplant 2011; 25 Suppl 23:6-14. [PMID: 21623907 DOI: 10.1111/j.1399-0012.2011.01452.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic syndrome of proteinuria, usually of nephrotic range, associated with focal and segmental sclerotic glomerular lesions. Therefore, FSGS is diagnosed by clinical features and histopathological examination of renal biopsy. The natural history of the condition varies, and although it may respond to treatment, FSGS is an important disease in the etiology of end-stage renal disease (ESRD). Furthermore, after kidney transplantation, approximately 30% of patients with FSGS develop recurrent FSGS. The risk factors for recurrence of FSGS include childhood onset and age <15 yr, rapid progression of the primary FSGS to ESRD, recurrence of FSGS in a previous allograft, diffuse mesangial hypercellularity in the native kidney, collapsing FSGS, and podocin gene mutation. In addition, after kidney transplantation, de novo FSGS also develops in approximately 10-20% of allografts, associated with a complication of hyperfiltration injury, chronic transplant glomerulopathy, and calcineurin inhibitor toxicity. FSGS is considered a podocyte disease, and the pathology is characterized by segmental FSGS lesion with glomerular epithelial hypercellularity. The pathological diagnosis of FSGS is based on the 2004 Columbia classification system. In the present minireview, we discuss the pathology of recurrence and de novo FSGS after kidney transplantation.
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Affiliation(s)
- Akira Shimizu
- Department of Pathology (Analytic Human Pathology), Nippon Medical School, Tokyo, Japan.
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17
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Howie AJ. Problems with 'focal segmental glomerulosclerosis'. Pediatr Nephrol 2011; 26:1197-205. [PMID: 21125407 DOI: 10.1007/s00467-010-1701-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2010] [Revised: 10/18/2010] [Accepted: 10/21/2010] [Indexed: 12/15/2022]
Abstract
The term 'focal segmental glomerulosclerosis (FSGS)' has been applied to many different conditions. All classifications of 'FSGS', including those describing 'variants', perpetuate the misconceptions that the entities included have something in common and that the term 'FSGS' has some value. With a rigorous approach to renal biopsies showing segmental lesions, especially with knowledge of clinical circumstances and with detailed analysis of features such as the appearance of lesions and their position within glomeruli, a pathologist can provide information that is clinically more useful than merely the bald diagnosis 'FSGS'. More precise terms should be used. 'Overload changes' can be used to describe the changes seen in reduced renal mass. 'Tip changes' can be seen in many conditions and are not a disease in themselves. 'The glomerular tip lesion as originally defined' means the occurrence of tip changes in otherwise normal glomeruli, in the nephrotic syndrome. 'Early classical segmental sclerosing glomerulopathy' is the combination of tip changes and otherwise abnormal glomeruli, in the nephrotic syndrome. 'Late classical segmental sclerosing glomerulopathy' means segmental lesions at various sites within glomeruli, in the nephrotic syndrome. 'Collapsing glomerulopathy' is distinctive, and its inclusion in classifications emphasises the lack of specificity of 'FSGS'.
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Affiliation(s)
- Alexander J Howie
- Department of Pathology, University College London, London, WC1E 6JJ, UK.
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18
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Arias LF, Franco-Alzate C, Rojas SL. Tip variant of focal segmental glomerulosclerosis: outcome and comparison to 'not otherwise specified' variant. Nephrol Dial Transplant 2010; 26:2215-21. [PMID: 21068139 DOI: 10.1093/ndt/gfq668] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The clinical significance of focal segmental glomerulosclerosis (FSGS) tip variant remains unclear. With the aim to determine its clinical and histological features, and natural history, we studied our cases of patients with this glomerular lesion. METHODS This is a retrospective analysis. All native renal biopsies from patients diagnosed as FSGS, between 1998 and 2006, were revised for cases with tip variant. Glomerulosclerosis (GS), segmental lesions and interstitial fibrosis (IF) were quantified. We analysed clinical and follow-up data and compared with cases of FSGS not otherwise specified (NOS). RESULTS In 248 primary FSGS cases, 37 corresponded to tip variant (14.9%). Median age was 17 years (range 1-65); 13 (35.1%) patients were <15 years old, and 56.8% were males. All patients had nephrotic proteinuria. At diagnosis, there were no significant differences for age, renal function and proteinuria between cases with NOS and tip variant. IF, GS and percentage of glomeruli with segmental lesions were higher in NOS than GTL (P < 0.01). At follow-up (n = 25), 15 patients received steroids alone, and 10 steroids and a cytotoxic agent. At a median follow-up of 48.7 months (24.3-86.7), 7 patients (28.0%) progressed to chronic kidney disease (CKD), 4 (16.0%) developed end-stage renal disease (ESRD) and 9 (36.0%) had complete remission. In NOS patients (n = 93), 48 (51.6%) developed CKD (P = 0.04), 20 (21.5%) developed ESRD (P = 0.54%) and 13 (14.0%) had complete remission (P = 0.02). CONCLUSIONS Our work does not demonstrate a clearly favourable prognosis in a group of patients with FSGS tip variant. Although in the tip variant there are less chronic renal tissue damage and CKD, and more frequent complete remission of the nephrotic syndrome, there is an important percentage of patients who develop CKD and ESRD.
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Affiliation(s)
- Luis F Arias
- Department of Pathology, Faculty of Medicine, University of Antioquia, Medellín, Colombia.
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19
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Kim MJ, Kim D, Lim BJ, Jeong HJ. An Analysis of Focal Segmental Glomerulosclerosis according to Morphologic Subtypes. KOREAN JOURNAL OF PATHOLOGY 2010. [DOI: 10.4132/koreanjpathol.2010.44.6.589] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Min Ju Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Dokyung Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Jin Lim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Hyeon Joo Jeong
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
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20
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Thomas DB. Focal segmental glomerulosclerosis: a morphologic diagnosis in evolution. Arch Pathol Lab Med 2009; 133:217-23. [PMID: 19195965 DOI: 10.5858/133.2.217] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2008] [Indexed: 11/06/2022]
Abstract
CONTEXT The diagnosis of focal segmental glomerulosclerosis (FSGS) is a descriptive pathologic diagnosis that in certain clinical situations (ie, primary or idiopathic) becomes its own disease. The clinical diversity, varied histology, and nonspecific morphologic features of FSGS all contribute to the complexity and problematic nature in making a pathologic diagnosis of FSGS. The definitions of the disease and of the morphologic features have evolved during the last century. OBJECTIVE To review historic and morphologic features of FSGS in order to demonstrate a practical approach in achieving a pathologic diagnosis of FSGS on kidney tissue. DATA SOURCES In 2004 a working proposal on the pathologic (morphologic) classification of FSGS was published in an attempt to unify the complexity of diagnosing FSGS, and it has shown to be both reproducible and with unique clinical implications for each defined FSGS variant. CONCLUSIONS An accurate diagnosis of FSGS can be challenging. During the last few decades, numerous new scientific discoveries have enriched our knowledge of pathogenetic mechanisms of nephrotic syndrome. Thus, it is expected there will be a need for a further modification to a morphologic classification and that the pathologist's role in diagnosing FSGS will remain in evolution. This review recapitulates the history of the pathologic diagnosis of FSGS and a current morphologic classification, hopefully opening up a discussion for further modifications that reflect the status of knowledge evolving in the 21st century.
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Affiliation(s)
- David B Thomas
- Nephrocor, 100 Charles Lindbergh Blvd., Uniondale, NY 11553, USA.
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21
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Abstract
PURPOSE OF REVIEW Focal segmental glomerulosclerosis (FSGS) is a disease with diverse histologic patterns and etiologic associations. Genetic, toxic, infectious and inflammatory mediators have been identified. This review will focus on new evidence supporting the potential mechanistic basis underlying the histologic variants and their clinical relevance. RECENT FINDINGS Evidence from animal models and in-vitro studies suggests that injury inherent within or directed to the podocyte is a central pathogenetic factor. Disruption of signaling from any of the podocyte's specialized membrane domains, including slit diaphragm, apical and basal membranes, or originating at the level of the actin cytoskeleton, may promote the characteristic response of foot process effacement. Irreversible podocyte stress leading to podocyte depletion through apoptosis or detachment is a critical mechanism in most forms of FSGS. In the collapsing variant, podocyte dysregulation leads to podocyte dedifferentiation and glomerular epithelial cell proliferation. SUMMARY Translation studies in humans and new evidence from animal models have provided mechanistic insights into the diverse phenotypes of FSGS.
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22
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Howie AJ, Agarwal A, Sebire NJ, Trompeter RS. Glomerular tip changes in childhood minimal change nephropathy. Pediatr Nephrol 2008; 23:1281-6. [PMID: 18446377 DOI: 10.1007/s00467-008-0823-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2008] [Revised: 02/27/2008] [Accepted: 03/03/2008] [Indexed: 10/22/2022]
Abstract
Segmental glomerular lesions at the tubular opening, or tip changes, are found in the renal biopsies of adults in many disorders, including some initially considered to show minimal change nephropathy. The hypothesis was that similar tip changes occurred in children. We reviewed a consecutive series of 50 biopsies, diagnosed as minimal change nephropathy, from 49 children. Segmental lesions were found in five biopsies. One biopsy showed lesions at the glomerular hilum. The patient was in remission at follow-up. Four biopsies showed only tip changes. Three patients were in remission, two on no treatment at follow-up, and one on ciclosporin. The other had chronic hepatitis B infection, with persistent proteinuria and segmental lesions at different sites in glomeruli. The other 44 children were nearly all in remission, 18 without treatment at follow-up, and the rest on various immunosuppressants, but one had persistent proteinuria and multiple segmental lesions. Series of childhood minimal change nephropathy, similar to this one, are likely to include cases of the glomerular tip lesion, under the original definition of minimal change nephropathy plus tip changes. This should make little difference in clinical practice, because the clinical course should resemble that of minimal change nephropathy.
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23
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Vas T, Degrell P, Pintér I, Késoi I, Kovács T, Nagy J. [Focal segmental glomerulosclerosis]. Orv Hetil 2008; 149:243-8. [PMID: 18238713 DOI: 10.1556/oh.2008.28264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Focal segmental glomerulosclerosis is a glomerular injury with typical morphology detectable by light microscopy. It has different histological subtypes and clinical symptoms. These different subtypes were recently systematized (Columbia classification). Focal segmental glomerulosclerosis is considered as the major type of podocytopathies, because podocytes are affected at each type of glomerular injury. Besides the primary forms of focal segmental glomerulosclerosis, an increased number of the secondary types are recognized. The wide use of drugs for renal protection in general and the long term administration of steroid therapy in some primary (idiopathic) cases are new elements among the therapeutic possibilities.
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Barisoni L, Schnaper HW, Kopp JB. A proposed taxonomy for the podocytopathies: a reassessment of the primary nephrotic diseases. Clin J Am Soc Nephrol 2007; 2:529-42. [PMID: 17699461 DOI: 10.2215/cjn.04121206] [Citation(s) in RCA: 182] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
A spectrum of proteinuric glomerular diseases results from podocyte abnormalities. The understanding of these podocytopathies has greatly expanded in recent years, particularly with the discovery of more than a dozen genetic mutations that are associated with loss of podocyte functional integrity. It is apparent that classification of the podocytopathies on the basis of morphology alone is inadequate to capture fully the complexity of these disorders. Herein is proposed a taxonomy for the podocytopathies that classifies along two dimensions: Histopathology, including podocyte phenotype and glomerular morphology (minimal-change nephropathy, focal segmental glomerulosclerosis, diffuse mesangial sclerosis, and collapsing glomerulopathy), and etiology (idiopathic, genetic, and reactive forms). A more complete understanding of the similarities and differences among podocyte diseases will help the renal pathologist and the nephrologist communicate more effectively about the diagnosis; this in turn will help the nephrologist provide more accurate prognostic information and select the optimal therapy for these often problematic diseases. It is proposed that final diagnosis of the podocytopathies should result from close collaboration between renal pathologists and nephrologists and should whenever possible include three elements: Morphologic entity, etiologic form, and specific pathogenic mechanism or association.
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Affiliation(s)
- Laura Barisoni
- Department of Pathology, New York University School of Medicine, New York, New York, USA
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25
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Thomas DB, Franceschini N, Hogan SL, Ten Holder S, Jennette CE, Falk RJ, Jennette JC. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 2006; 69:920-6. [PMID: 16518352 DOI: 10.1038/sj.ki.5000160] [Citation(s) in RCA: 165] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Histologic variants of idiopathic focal segmental glomerulosclerosis (FSGS) may have prognostic value. A recent working classification system has distinguished five FSGS variants. We evaluated a cohort of adult patients with biopsy-proven FSGS diagnosed between March 1982 and July 2001 to determine if subtypes were associated with renal outcome. Renal biopsies were reviewed by two pathologists. Demographic and clinical data were obtained from charts. Outcomes were partial and complete remission of the nephrotic syndrome, and renal failure. The frequency of FSGS variants was: 3% cellular (N=6), 11% collapsing (N=22), 17% tip lesion (N=34), 26% perihilar (N=52), and 42% not otherwise specified (NOS) (N=83). Collapsing FSGS affected younger and more often black patients. Black race was uncommon in tip variant. Collapsing and tip variants had higher proteinuria and lower serum albumin than perihilar and NOS variants. Better renal function and less severe tubulointerstitial injury were observed in patients with tip variant. These patients were more likely to receive steroids and more often achieved complete remission (50%). After a median follow-up of 1.8 years, 23% of patients were on dialysis and 28% had renal failure. Collapsing FSGS had worse 1-year (74%) and 3-year (33%) renal survival compared to other variants (overall cohort renal survival at 1 and 3 years: 86 and 67%). Different histologic variants of FSGS have substantial differences in clinical features at the time of biopsy diagnosis and substantial differences in renal outcomes.
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Affiliation(s)
- D B Thomas
- UNC Nephropathology Laboratory, Department of Pathology and Laboratory Medicine, University of North Carolina, 409 Brinkhous-Bullitt Building, CB #7525, Chapel Hill, NC 27599, USA.
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Sekhon I, Munjal S, Croker B, Johnson RJ, Ejaz AA. Glomerular tip lesion associated with nonsteroidal anti-inflammatory drug-induced nephrotic syndrome. Am J Kidney Dis 2005; 46:e55-8. [PMID: 16183408 DOI: 10.1053/j.ajkd.2005.05.034] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2005] [Accepted: 05/31/2005] [Indexed: 11/11/2022]
Abstract
Glomerular tip lesion and its relation to different glomerular diseases is a subject of controversy. The therapeutic and prognostic clinical implications of glomerular tip lesions are ambiguous. We present a case of glomerular tip lesion associated with nonsteroidal anti-inflammatory drug-induced nephrotic syndrome that further complicates this issue. To our knowledge, this is the first case report of glomerular tip lesion associated with nonsteroidal anti-inflammatory drug-induced nephrotic syndrome.
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Affiliation(s)
- Inderpreet Sekhon
- Division of Nephrology, Hypertension, and Transplantation, Department of Pathology, University of Florida, Gainesville, FL 32610-0224, USA
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Howie AJ, Pankhurst T, Sarioglu S, Turhan N, Adu D. Evolution of nephrotic-associated focal segmental glomerulosclerosis and relation to the glomerular tip lesio11See Editorial by Haas,P. 1188. Kidney Int 2005; 67:987-1001. [PMID: 15698437 DOI: 10.1111/j.1523-1755.2005.00162.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Several entities or variants within focal segmental glomerulosclerosis (FSGS) have been described, but their changes with time and interrelationships are undetermined. METHODS Changes with time were studied in two series of segmental sclerosing lesions in the nephrotic syndrome, one of 22 specimens from ten patients in a trial, the other of 176 specimens from 121 consecutive patients. RESULTS The earliest lesions were probably all at the tubular origin, equivalent to the tip variant of FSGS. In some patients, lesions remained at this site, but progression to renal failure was accompanied by morphologic progression, with development of lesions at various sites, equivalent to FSGS, not otherwise specified (NOS). Progression was more likely if there were large lesions, abnormal mesangium, and extensive acute tubular damage. Patients with lesions at the tubular origin at presentation had a shorter duration of symptoms and less chronic renal damage than those with multiple lesions, were more likely to have a complete response of the nephrotic syndrome, and were less likely to progress to renal failure. Recurrent nephrotic syndrome occurred in 12 of 14 allografts at risk, and was usually accompanied by lesions at the tubular origin, then multiple lesions. CONCLUSION At least some patients with FSGS (NOS) have evolved from the tip variant. The tip variant has been considered a distinct entity. Another interpretation is that it includes two conditions, one an early form of classic FSGS, and the other closely related to minimal change nephropathy (MCN), equivalent to the glomerular tip lesion as originally defined.
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Affiliation(s)
- Alexander J Howie
- Department of Pathology, University of Birmingham, Birmingham, United Kingdom.
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Stokes MB, Markowitz GS, Lin J, Valeri AM, D'Agati VD. Glomerular tip lesion: a distinct entity within the minimal change disease/focal segmental glomerulosclerosis spectrum. Kidney Int 2004; 65:1690-702. [PMID: 15086908 DOI: 10.1111/j.1523-1755.2004.00563.x] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The glomerular tip lesion (GTL) is a distinctive but controversial histopathologic lesion occurring in patients with idiopathic nephrotic syndrome. The relationship of GTL to minimal change disease (MCD) and idiopathic focal segmental glomerulosclerosis (FSGS) has been disputed. METHODS In order to define the clinical features and natural history of GTL, we retrospectively reviewed the presenting clinical features, biopsy findings and outcome of 47 cases. Presenting clinical features of GTL were compared to those of controls with MCD (N= 61) or idiopathic FSGS (N= 50). RESULTS The cohort of GTL consisted of 45 adults and two children (mean age 47.5 years; range 12 to 79 years), including 76.6% Caucasians and 53% males. At presentation, 93.6% of patients had edema, 89.1% had nephrotic syndrome (mean urine protein 8.31 g, mean serum albumin 2.27 g/dL, and mean cholesterol 340.6 mg/dL), and 34.8% had renal insufficiency. Mean time from onset of renal disease to biopsy was 2.4 months. At biopsy, glomerular segmental lesions included GTL alone in 26%, GTL and peripheral lesions in 6%, GTL and indeterminate lesions in 36%, and GTL with peripheral and indeterminate lesions in 32%. No initial biopsy contained perihilar sclerosis and most (81%) segmental lesions were cellular. Follow-up data were available in 29 patients, of whom 21 received steroids alone and eight received sequential therapy with steroids and a cytotoxic agent. At a mean follow-up of 21.5 months, 58.6% of patients achieved complete remission of nephrotic syndrome, 13.8% had partial remission, and 27.6% had persistent nephrotic proteinuria. Only one patient progressed to end-stage renal disease (ESRD). Predictors of nonremission included severity of proteinuria at presentation and % peripheral lesions. When compared to controls with MCD and idiopathic FSGS, GTL more closely resembled MCD with respect to high incidence of nephrotic syndrome (P < 0.001), severity of proteinuria (P < 0.05), short duration from onset to biopsy (P < 0.001), and absence of chronic tubulointerstitial disease (P < 0.0054). CONCLUSION Within the MCD/FSGS spectrum, GTL is a distinctive and prognostically favorable clinical-pathologic entity whose presenting features and outcome more closely approximate those of MCD.
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Affiliation(s)
- M Barry Stokes
- Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
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D'Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis 2004; 43:368-82. [PMID: 14750104 DOI: 10.1053/j.ajkd.2003.10.024] [Citation(s) in RCA: 494] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Franceschini N, Hogan SL, Falk RJ. Primum non nocere: Should adults with idiopathic FSGS receive steroids? Semin Nephrol 2003; 23:229-33. [PMID: 12704583 DOI: 10.1053/snep.2003.50021] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Corticosteroids have been widely recommended for the treatment of patients with idiopathic focal segmental glomerulosclerosis (FSGS), despite the lack of evidence-based data to support the use of steroids in this disease. The published studies have a number of limitations. They primarily have been retrospective, have included few patients, and have not been uniform with respect to the steroid treatment protocol. Furthermore, side effects associated with corticosteroid use have not been well documented. The Glomerular Disease Collaborative Network's experience with steroids in idiopathic FSGS has shown a low rate of remission even when steroids were used in the recommended doses and for prolonged periods. Recommendations regarding a specific subset of patients who may benefit from steroid treatment are discussed. The controversies regarding steroids in idiopathic FSGS will only be resolved with data from controlled clinical trials.
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Affiliation(s)
- Nora Franceschini
- Division of Nephrology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Abstract
Focal segmental glomerulosclerosis (FSGS) is defined as a clinical-pathologic syndrome manifesting proteinuria and focal and segmental glomerular sclerosis with foot process effacement. The pathologic approach to the classification of FSGS is complicated by the existence of primary (idiopathic) forms and multiple subcategories with etiologic associations, including human immunodeficiency virus (HIV)-associated nephropathy, heroin nephropathy, familial forms, drug toxicities, and a large group of secondary FSGS mediated by structural-functional adaptations to glomerular hyperfiltration. A number of morphologic variants of primary and secondary focal sclerosis are now recognized, including FSGS not otherwise specified (NOS), perihilar, cellular, tip, and collapsing variants. The defining features of these morphologic variants and of the major subcategories of FSGS are discussed with emphasis on distinguishing light microscopic patterns and clinical-pathologic correlations.
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Affiliation(s)
- Vivette D'Agati
- Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, USA.
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Abstract
Renal diseases unique to the tropics are those that occur in association with infectious diseases including dengue hemorrhagic fever, typhoid fever, shigellosis, leptospirosis, lepromatous leprosy, malaria, opisthorchiasis, and schistosomiasis. These renal complications can be classified on the basis of their clinical and pathologic characteristics into acute transient reversible glomerulonephritis, chronic progressive irreversible glomerulonephritis, amyloidosis, and acute renal failure (ARF) resulting from acute tubular necrosis, acute tubulointerstitial nephritis, and thrombotic microangiopathy. Certain primary glomerular diseases including immunoglobulin (Ig) M nephropathy and focal segmental and global glomerulosclerosis are prevalent in some tropical countries. Renal complications of venomous snakebites also are common in the tropics. This article discusses and summarizes important works in the literature in respect to the clinical syndromes, pathologic features, and pathogenesis of tropical renal diseases both in humans and experimental animal models.
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Haas M, Yousefzadeh N. Glomerular tip lesion in minimal change nephropathy: a study of autopsies before 1950. Am J Kidney Dis 2002; 39:1168-75. [PMID: 12046027 DOI: 10.1053/ajkd.2002.33386] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The clinical significance of the glomerular tip lesion, characterized by podocyte prominence, capsular adhesion, and/or intracapillary foam cells at or adjacent to the urinary pole, remains unclear. It has been postulated that this lesion simply represents a response to heavy proteinuria, and cases of nephrotic syndrome with tip lesions, but no other histological abnormalities, may represent a form of minimal change nephropathy (MCN). However, others have reported that such lesions have a clinical course similar to that of primary focal segmental glomerulosclerosis (FSGS), and the tip lesion often is included among histological variants of FSGS. To determine whether tip lesions may be seen in MCN, we examined histological slides of kidneys from pre-1950 autopsies of patients with a diagnosis of lipoid nephrosis, a term that at that time comprised MCN and FSGS. Before the introduction of antibiotics and corticosteroid therapy, patients with nephrotic syndrome frequently died of sepsis. Eight such cases, with autopsies performed from 1924 to 1943, were identified in which no glomeruli had changes typical of classic FSGS or membranous nephropathy. More than 400 glomeruli were present in each case. Patient ages ranged from 3 to 45 years (six patients <11 years), all had marked edema (duration, 2 weeks to 21 months) and heavy proteinuria, and each died of sepsis and/or pneumonia (pneumococcal in six patients). Glomerular tip lesions were found in five of these eight cases (range, 3 to 26 lesions per case; 0.3% to 4.4% of total glomeruli present), with no predilection for the deep, middle, or superficial cortex. No tip lesions were seen in kidneys from autopsies of age-matched patients without a history of glomerular disease. These findings suggest that the glomerular tip lesion can occur in MCN and most likely represents a response to heavy proteinuria that is not disease specific.
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Affiliation(s)
- Mark Haas
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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Sato M, Hotta O, Taguma Y. Glomerulo-tubular junction stenosis as a factor contributing to glomerular obsolescence in IgA nephropathy. J Pathol 2002; 197:14-9. [PMID: 12081198 DOI: 10.1002/path.1085] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Periglomerular fibrosis (PF) is an interstitial injury observed in various renal diseases. It is speculated that this lesion, by occluding the glomerulo-tubular junction (GTJ) and causing atubular glomeruli, may result functionally in a reduction of the glomerular filtration rate (GFR) and may be a factor contributing to the progression of renal disease. In the present study, 340 renal biopsy specimens were analysed to determine whether or not there was nephron injury derived from such a mechanism, as well as direct glomerular injury, in IgA nephropathy (IgAN). The patients were divided into five groups according to the degree of glomerular sclerosis. The average age was lower in groups with milder sclerosis and serum creatinine (Cr) was elevated in groups with more severe sclerosis. Because the GTJ was assumed to disappear when an atubular glomerulus was formed, the ratio of the number of glomeruli with discernible GTJ to the total number of glomeruli was evaluated. As glomerular sclerosis progressed, discernible GTJ reduced significantly (p <0.001) and the degree of PF increased significantly (p <0.05). By serial section study in cases with pronounced PF, transitions between the stages of stenosis of the GTJ and atubular glomeruli were observed. It is speculated that the occlusion of the GTJ eventually hyalinizes the glomerulus; in such cases, glomerular obsolescence of the collapse type might be formed. On the other hand, obsolescence of the mesangial proliferative type might be formed in the hyalinization derived from direct glomerular injury. In this context, glomerular obsolescence of the collapse type was observed more frequently and was accompanied by more increased PF than obsolescence of the mesangial proliferative type (p <0.001). These results suggest that in addition to direct glomerular injury, nephron injury derived from interstitial damage of this type plays an important contributory role in the progression of IgAN.
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Affiliation(s)
- Mitsuhiro Sato
- Department of Nephrology, Sendai Shakaihoken Hospital, Japan.
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KORBET1 SM, SCHWARTZ2 MM. Primary focal segmental glomerulosclerosis: a treatable lesion with variable outcomes. Nephrology (Carlton) 2001. [DOI: 10.1046/j.1440-1797.2001.00037.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Schwartz MM. The role of podocyte injury in the pathogenesis of focal segmental glomerulosclerosis. Ren Fail 2000; 22:663-84. [PMID: 11104157 DOI: 10.1081/jdi-100101955] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The podocyte has diverse functions including glomerular filtration, biosynthesis and maintenance of the glomerular capillary architecture. It discharges these functions by virtue of a unique morphology, an intimate relationship with the capillary wall, and diverse synthetic and membrane specializations. Despite the complex role that it plays in glomerular function, the clinical manifestations of podocyte dysfunction are limited to proteinuria and renal insufficiency. Recurrent focal segmental glomerulosclerosis (FSGS) in renal transplants provides a unique opportunity to study the pathogenesis of FSGS in human beings, because the patients are monitored carefully to identify the onset of disease, the recurrence is presumed to have the same etiology as the primary disease, renal biopsy is a tool to study the pathogenesis of the lesion, and therapeutic intervention provides a mechanism to test pathogenesis. Pathologic studies have identified a proliferative lesion of the podocytes as the first sign of recurrent disease. The glomerular lesions evolve to form segmental glomerular scars with time. These findings and studies in experimental models of FSGS implicate podocyte injury in the pathogenesis of the recurrent disease. The cellular lesion (similar to the proliferative lesion of podocytes in recurrent FSGS), seen early in the course of primary FSGS suggests that the pathogenic sequence in recurrent FSGS also applies to primary FSGS. A soluble circulating factor that increases glomerular permeability and correlates with recurrence of FSGS has been identified in the pretransplant serum of patients with end-stage FSGS, but the mechanism of podocyte injury by this factor remains speculative. In any case, podocytes in the cellular lesion undergo morphologic changes and lose specialized functions seen in the normal mature cell, and these structural and functional abnormalities cause the permeability changes associated with proteinuria and destruction of glomerular filtration surface by scarring associated with loss of glomerular function.
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Affiliation(s)
- M M Schwartz
- Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, 60612, USA.
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Abstract
A distinctive segmental glomerular abnormality is confined to the region of the tubular opening. The hypothesis was that this followed prolapse of the tuft into the tubule. Analysis was made of 39 renal biopsy specimens with acute postinfective glomerulonephritis, later material from ten cases, four specimens from three women with pre-eclampsia, and 21 control specimens, with morphometry of glomeruli and immunohistological examination for immunoproteins and monocytes/macrophages. Prolapse was found in 14 specimens with acute postinfective glomerulonephritis, associated in eight with adhesion to Bowman's capsule and local alterations in the tuft, which together constitute early tip changes. Another three had early tip changes only and eight others had thin adhesions between the tuft and capsule next to the tubular opening. Later material confirmed this order of development and showed another late change, with sclerosed and hyaline material in the tuft and adhesion at the tubular origin. Findings in pre-eclampsia were comparable. Glomeruli were significantly larger in acute postinfective glomerulonephritis than in controls and were shown by others to be larger in pre-eclampsia than in normal pregnancy. Immunohistology showed IgM and a few foamy monocytes/macrophages in early tip changes but not in prolapsed loops. Glomerular prolapse appears to be a temporary consequence of acute enlargement of the tuft, probably causes mechanical damage to epithelial cells, and is a precursor of permanent structural changes near the tubular origin. This gives a unifying hypothesis to explain how these changes can be seen in acute postinfective glomerulonephritis, pre-eclampsia, and many other human and experimental renal disorders.
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Affiliation(s)
- A J Howie
- Department of Pathology, University of Birmingham, Birmingham B15 2TT, UK.
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Cattran DC, Appel GB, Hebert LA, Hunsicker LG, Pohl MA, Hoy WE, Maxwell DR, Kunis CL. A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group. Kidney Int 1999; 56:2220-6. [PMID: 10594798 DOI: 10.1046/j.1523-1755.1999.00778.x] [Citation(s) in RCA: 189] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
UNLABELLED A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. BACKGROUND A clinical trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis (FSGS) was conducted. Despite the fact that it is the most common primary glomerulonephritis to progress to renal failure, treatment trials have been very limited. METHODS We conducted a randomized controlled trial in 49 cases of steroid-resistant FSGS comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone. All patients were followed for an average of 200 weeks, and the short- and long-term effects on renal function were assessed. RESULTS Seventy percent of the treatment group versus 4% of the placebo group (P < 0. 001) had a partial or complete remission of their proteinuria by 26 weeks. Relapse occurred in 40% of the remitters by 52 weeks and 60% by week 78, but the remainder stayed in remission to the end of the observation period. Renal function was better preserved in the cyclosporine group. There was a decrease of 50% in baseline creatinine clearance in 25% of the treated group compared with 52% of controls (P < 0.05). This was a reduction in risk of 70% (95% CI, 9 to 93) independent of other baseline demographic and laboratory variables. CONCLUSIONS These results suggest that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of FSGS. Although a high relapse rate does occur, a long-term decrease in proteinuria and preservation of filtration function were observed in a significant proportion of treated patients.
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Affiliation(s)
- D C Cattran
- Department of Medicine, University of Toronto, Ontario, Canada.
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Gibson IW, Downie TT, More IA, Lindop GB. Tuft-to-capsule adhesions and their precursors: differences between the vascular and tubular poles of the human glomerulus. J Pathol 1998; 184:430-5. [PMID: 9664911 DOI: 10.1002/(sici)1096-9896(199804)184:4<430::aid-path1226>3.0.co;2-c] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Human glomerular capillary tufts were removed by microdissection and scanning electron microscopy was used to examine the surface of the capillary tuft and the interior of its Bowman's capsule in order to identify connections between the tuft and capsule. Glomeruli were examined in histologically normal renal cortex from 12 kidneys removed for tumour and 12 renal allografts removed for end-stage rejection. In normal kidney, the glomerular tuft was connected to Bowman's capsule by single podocytes and their processes. At the vascular pole, these were predominantly associated with parietal podocytes which lined Bowman's capsule. At the tubular pole, occasional podocytic processes derived from the capillary tuft bridged Bowman's space and connected to Bowman's capsule where there were no parietal podocytes. These podocytic connections were also found in all rejected transplants, but in addition adhesions were identified which consisted of thicker connections between the tuft and capsule. At the vascular pole, tuft-to-capsule adhesions were found in all 12 kidneys; these were always associated with parietal podocytes. Tubular pole adhesions were identified in ten of the 12 transplants. They were associated with abnormal squamous cells, but not with parietal podocytes. When the capillary tuft herniated into the proximal tubule, the tuft sometimes formed an adhesion with the origin of the proximal tubule. These observations suggest that podocyte connections between the glomerular tuft and Bowman's capsule may be precursors of glomerular adhesions at the vascular pole. Since tuft-to-capsule adhesions at the vascular pole differ morphologically from those at the tubular pole, this may reflect different pathogenetic mechanisms at the opposite poles of the glomerulus.
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Affiliation(s)
- I W Gibson
- University of Glasgow Department of Pathology, Western Infirmary, U.K
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Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis 1997; 30:621-31. [PMID: 9370176 DOI: 10.1016/s0272-6386(97)90485-6] [Citation(s) in RCA: 278] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Data compiled during the 1970s and early 1980s indicated that during these periods, membranous nephropathy was the most common cause of unexplained nephrotic syndrome in adults, followed in order of frequency by minimal-change nephropathy and focal segmental glomerulosclerosis (FSGS). However, we and others recently reported an increase in the incidence of FSGS over the past two decades, and the number of cases of FSGS diagnosed by renal biopsies in these centers now exceeds the number of cases of membranous nephropathy. Nonetheless, as a substantial fraction of patients with FSGS do not have the nephrotic syndrome, it remained unclear as to what extent the relative frequencies of FSGS and other glomerulopathies as causes of the nephrotic syndrome have changed over this time. To address this concern, we reviewed data from 1,000 adult native kidney biopsies performed between January 1976 and April 1979 and from 1,000 biopsies performed between January 1995 and January 1997, identified all cases with a full-blown nephrotic syndrome of unknown etiology at the time of biopsy, and compared the relative frequencies with which specific diseases were diagnosed in these latter cases between the two time intervals. The main findings of this study were that, first, during the 1976 to 1979 period, the relative frequencies of membranous (36%) and minimal-change (23%) nephropathies and of FSGS (15%) as causes of unexplained nephrotic syndrome were similar to those observed in previous studies during the 1970s and early 1980s. In contrast, from 1995 to 1997, FSGS was the most common cause of this syndrome, accounting for 35% of cases compared with 33% for membranous nephropathy. Second, during the 1995 to 1997 period, FSGS accounted for more than 50% of cases of unexplained nephrotic syndrome in black adults and for 67% of such cases in black adults younger than 45 years. Third, although the relative frequency of nephrotic syndrome due to FSGS was two to three times higher in black than in white patients during both study periods, the frequency of FSGS increased similarly among both racial groups from the earlier to the later period. Fourth, the frequency of minimal-change nephrotic syndrome decreased from the earlier to the later study period in both black and white adults. Fifth, the relative frequency of membranoproliferative glomerulonephritis as a cause of the nephrotic syndrome declined from the 1976 to 1979 period to the 1995 to 1997 period, whereas that of immunoglobulin A nephropathy appeared to increase; the latter accounted for 14% of cases of unexplained nephrotic syndrome in white adults during the latter study period. Finally, 10% of nephrotic adults older than 44 years had AL amyloid nephropathy; none of these patients had multiple myeloma or a known paraprotein at the time of renal biopsy.
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Affiliation(s)
- M Haas
- Department of Pathology, The University of Chicago, IL 60637, USA
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DANILEWICZ M, WAGROWSKA-DANILEWICZ M. Morphometric insights into nephrotic syndrome in children: Are we any wiser? Nephrology (Carlton) 1997. [DOI: 10.1111/j.1440-1797.1997.tb00222.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Valeri A, Barisoni L, Appel GB, Seigle R, D'Agati V. Idiopathic collapsing focal segmental glomerulosclerosis: a clinicopathologic study. Kidney Int 1996; 50:1734-46. [PMID: 8914044 DOI: 10.1038/ki.1996.493] [Citation(s) in RCA: 180] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
A review of all native kidney biopsies at our center from 1974 to 1993 identified 43 cases of idiopathic focal segmental glomerulosclerosis (FSGS) with predominantly collapsing features and lacking evidence of HIV-1 infection or intravenous drug use. No case was identified before 1979 and the incidence of this entity has progressively increased over the past two decades. Compared to 50 age-matched controls of idiopathic FSGS with typical perihilar scars, the group of idiopathic collapsing FSGS displayed black racial predominance, a higher serum creatinine and more severe features of nephrotic syndrome at biopsy. Morphologic features of visceral epithelial cell hypertrophy and hyperplasia, tubular microcysts, tubular epithelial degenerative and regenerative features and interstitial edema were more prevalent and severe in collapsing FSGS. Median time to ESRD was rapid in collapsing FSGS versus controls (13.0 months vs. 62.5 months, P < 0.05). Correlates of progression to ESRD included a higher initial serum creatinine and failure to undergo remission of proteinuria. Both glomerulosclerosis and certain features of tubular damage were independent predictors of the level of renal function at time of biopsy, but not of the rate of progression of renal insufficiency. Although three patients had partial or complete spontaneous remissions, none of 26 patients treated with steroids alone responded. Idiopathic collapsing FSGS is a variant of FSGS with increasing incidence, distinct clinicopathologic features, black racial predominance, a rapidly progressive course and relative steroid resistance.
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Affiliation(s)
- A Valeri
- Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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Abstract
Disorders of glomerular structure and function are encountered frequently in clinical medicine. Many arise as part of a well-defined multisystem or multi-organ disease process, while in others the clinical and laboratory manifestations are consequent to the sole or predominant involvement of glomeruli. The latter are known as the primary glomerulopathies. These disorders can evoke a variety of clinical syndromes, including acute glomerulonephritis, rapidly progressive glomerulo-nephritis, nephrotic syndrome, "symptomless" hematuria and/or proteinuria, and chronic glomerulonephritis. The identification of underlying morphology, through the application of renal biopsy techniques, can provide useful information for both prognosis and treatment. Pathogenic mechanisms involved in the primary glomerulopathies are varied, but immunologic perturbations underlie many disease entities. This article describes the clinical features, pathology, natural history, and treatment of the main categories of primary glomerulonephritis, with emphasis on recent developments and practical aspects of diagnosis and management.
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Affiliation(s)
- R J Glassock
- Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, USA
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Howie AJ, Lee SJ, Sparke J. Pathogenesis of segmental glomerular changes at the tubular origin, as in the glomerular tip lesion. J Pathol 1995; 177:191-9. [PMID: 7490686 DOI: 10.1002/path.1711770213] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Segmental abnormalities at the glomerulo-tubular junction, or tip changes, are a common and early feature in several experimental and human renal disorders. Scanning and transmission electron microscopic study of an experimental model, Lewis rats given anti-glomerular basement membrane antibodies, showed that at 5 days there were monocytes/macrophages in glomerular capillary loops next to the tubular origin, with abnormalities of visceral epithelium, including prolapse of groups of these cells into the tubular origin. At 12 days, there was contact and adhesion between glomerular capillary loops and Bowman's capsule. Transmission electron microscopic study of human renal biopsies showed that the human tip changes resembled the later lesions seen in rats, with intracapillary foam cells confirmed by immunohistological study to be monocytes/macrophages. These findings show that abnormalities of the glomerular tuft precede adhesion to Bowman's capsule and that the earliest changes recognized by light microscopy in human renal biopsies are relatively late in their natural history, meaning at least several days old. Prolapse of visceral epithelial cells into the tubular origin may explain the characteristic site of tip changes.
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Affiliation(s)
- A J Howie
- Department of Pathology, University of Birmingham, U.K
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Schwartz MM, Korbet SM, Rydell J, Borok R, Genchi R. Primary focal segmental glomerular sclerosis in adults: prognostic value of histologic variants. Am J Kidney Dis 1995; 25:845-52. [PMID: 7771480 DOI: 10.1016/0272-6386(95)90566-9] [Citation(s) in RCA: 53] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Primary focal segmental glomerular sclerosis (FSGS) is a clinicopathologic syndrome in which variable amounts of proteinuria are associated with the renal biopsy finding of segmental glomerular scarring in some, but not all, of the glomeruli. Additional histologic features have been described in FSGS, including the position of the scar relative to the vascular and tubular pole of the glomerulus, foam cells, hyalinosis, mesangial deposits of immunoglobulin M, diffuse mesangial hypercellularity, glomerular visceral epithelial cell hyperplasia and hypertrophy, and the extent of associated interstitial fibrosis and tubular atrophy. We performed a retrospective study on 81 patients with biopsy-proven, primary FSGS to determine whether any of the histologic features of FSGS correlated with renal function at the time of biopsy and the incidence of end-stage renal disease at follow-up. Sixty patients were nephrotic and 21 had nonnephrotic proteinuria. Only the degree of interstitial fibrosis correlated with the initial serum creatinine (r = 0.536) and none of the histologic features predicted the presence of nephrotic-range proteinuria at the time of biopsy. Segmental scars involved 21% +/- 14% of the glomeruli per biopsy specimen, but their position within the glomerulus was uniform in only 13% of the cases. Diffuse mesangial hypercellularity was present in 17% of the biopsy specimens, and glomerular epithelial cell lesions were present in 57% of the biopsy specimens. Multivariate analysis showed that only the degree of interstitial fibrosis predicted end-stage renal disease in all 81 patients and in the 60 patients with nephrotic-range proteinuria. The current data do not support different therapeutic approaches in primary FSGS based on histologic subtypes.
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Affiliation(s)
- M M Schwartz
- Department of Pathology, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL 60612, USA
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48
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Affiliation(s)
- V D'Agati
- Renal Pathology Laboratory, College of Physicians and Surgeons of Columbia University, New York, New York 10032
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49
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Korbet SM, Schwartz MM, Lewis EJ. Primary focal segmental glomerulosclerosis: clinical course and response to therapy. Am J Kidney Dis 1994; 23:773-83. [PMID: 8203357 DOI: 10.1016/s0272-6386(12)80128-4] [Citation(s) in RCA: 162] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Primary focal segmental glomerulosclerosis (FSGS) is a lesion associated with a poor prognosis and results in end-stage renal disease after 5 to 10 years. Based on past experience, many nephrologists have considered primary FSGS a lesion that is steroid resistant and therefore are reluctant to offer steroids as treatment. Recent data, however, have demonstrated that patients with primary FSGS have a response to steroid therapy that is considerably better than had been described. Thus, it may be that nephrologists have been more "steroid reluctant" than the lesion is steroid resistant. To better understand this issue we review the clinical course and response to therapy in patients with primary FSGS.
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Affiliation(s)
- S M Korbet
- Department of Medicine, Rush Presbyterian St Lukes Medical Center, Chicago, IL 60612
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50
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Detwiler RK, Falk RJ, Hogan SL, Jennette JC. Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis. Kidney Int 1994; 45:1416-24. [PMID: 8072254 DOI: 10.1038/ki.1994.185] [Citation(s) in RCA: 225] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Sixteen patients with renal biopsy findings of extensive focal glomerular capillary collapse, visceral epithelial cell hypertrophy and hyperplasia, and variable degrees of tubulointerstitial injury in the absence of evidence for human immunodeficiency virus (HIV) infection or intravenous drug abuse were prospectively identified by renal biopsy. The pathologic process was designated collapsing glomerulopathy to distinguish it from other patterns of focal glomerular sclerosis. The clinical and pathologic characteristics of these 16 patients were analyzed and compared to a group of 25 patients with noncollapsing focal segmental glomerulosclerosis (FSGS). Thirteen of 16 patients with collapsing glomerulopathy were black as compared with 11 of 25 with FSGS (P = 0.018). The most common findings at presentation were hypertension and manifestations of the nephrotic syndrome. Although the duration of symptoms prior to presentation was no longer in the collapsing glomerulopathy group, the presenting mean serum creatinine was higher in patients with collapsing glomerulopathy than in those with noncollapsing FSGS (3.5 +/- 3.4 mg/dl vs. 1.3 0.6 mg/dl, P = 0.001). Twenty-four-hour urine protein excretion was also higher in the collapsing glomerulopathy group (13.2 +/- 7.7 g/day vs. 4.6 +/- 4.5 g/day FSGS, P = 0.005). The collapsing glomerulopathy patients had a mean age of 41.4 +/- 19.1 (range 19 to 81), a male-to-female ratio of 11:5 and a black-to-white ratio of 13:3. Renal survival, evaluated by life-table analysis, was markedly worse in collapsing glomerulopathy patients than in FSGS patients (P = 0.0004). It is proposed that collapsing glomerulopathy is a distinct entity characterized by black racial predominance, massive proteinuria, relatively rapidly progressive renal insufficiency, and distinctive pathologic findings.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- R K Detwiler
- Department of Medicine, University of North Carolina, Chapel Hill
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