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Lupus Nephritis Differential Diagnoses

  • Author: Lawrence H Brent, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Sep 28, 2015
 
 

Diagnostic Considerations

Lupus nephritis usually arises within 5 years of diagnosis of systemic lupus erythematosus (SLE); however, renal failure rarely occurs before American College of Rheumatology criteria for classification are met.

Besides the conditions listed in the differential diagnosis, other problems to be considered include the following:

  • Mesangial glomerulonephritis
  • Glomerulosclerosis

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Genentech; Pfizer; Questcor.

Coauthor(s)

Arati Karhadkar, MBBS Fellow, Division of Rheumatology, Albert Einstein Medical Center

Disclosure: Nothing to disclose.

Eric Bloom, MD Division Chief of Nephrology, Nephrology Fellowship Program Director, Attending Physician, Division of Nephrology, Department of Internal Medicine, Albert Einstein Medical Center

Eric Bloom, MD is a member of the following medical societies: American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ajay K Singh, MB, MRCP, MBA Associate Professor of Medicine, Harvard Medical School; Director of Dialysis, Renal Division, Brigham and Women's Hospital; Director, Brigham/Falkner Dialysis Unit, Faulkner Hospital

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Additional Contributors

Carlos J Lozada, MD Director of Rheumatology Fellowship Training Program, Professor of Clinical Medicine, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine

Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Received honoraria from Pfizer for consulting; Received grant/research funds from AbbVie for other; Received honoraria from Heel for consulting.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Irene Viola, MD, to the development and writing of the source article.

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Mesangial proliferative lupus nephritis with moderate mesangial hypercellularity. International Society of Nephrology/Renal Pathology Society 2003 class II (×200, hematoxylin-eosin).
Focal lupus nephritis. International Society of Nephrology/Renal Pathology Society 2003 class III (×100, hematoxylin-eosin).
Focal lupus nephritis. International Society of Nephrology/Renal Pathology Society 2003 class III (×200, immunofluorescence).
Diffuse lupus nephritis with hypertensive vascular changes. International Society of Nephrology/Renal Pathology Society 2003 class IV (×200, hematoxylin-eosin).
Diffuse lupus nephritis with early crescent formation. International Society of Nephrology/Renal Pathology Society 2003 class IV (×200, hematoxylin-eosin).
Diffuse lupus nephritis with extensive crescent formation (rapidly progressive glomerulonephritis). International Society of Nephrology/Renal Pathology Society 2003 class IV (×200, hematoxylin-eosin).
Membranous lupus nephritis. International Society of Nephrology/Renal Pathology Society 2003 class V (×200, hematoxylin-eosin).
Membranous lupus nephritis showing thickened glomerular basement membrane. International Society of Nephrology/Renal Pathology Society 2003 class V (×200, silver stain).
Advanced sclerosis lupus nephritis. International Society of Nephrology/Renal Pathology Society 2003 class VI (×100, hematoxylin-eosin).
Table 1. Genes Associated With Systemic Lupus Erythematosus
Gene LocusGene NameGene Product
1p13.2PTPN22Lymphoid-specific protein tyrosine phosphatase
1q21-q23CRPCRP
1q23FCGR2A, FCGR2BFcγRIIA (R131), FcγRIIB
1q23FCGR3A, FCGR3BFcγRIIIA (V176), FcγRIIIB
1q31-q32IL10IL-10
1q36.12C1QBC1q deficiency
2q32.2-q32.3STAT4Signal transducer and activator of transcription 4
2q33CTLA4Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
6p21.3HLA-DRB1HLA-DRB1: DR2/*1501, DR3/*0301C1q deficiency
6p21.3C2, C4A, C4BC2, C4 deficiencies
6p21.3TNFTNF-a (promoter, -308)
10q11.2-q21MBL2Mannose-binding lectin
CRP = C-reactive protein; HLA = human leukocyte antigen; IL = interleukin; TNF = tumor necrosis factor.
Table 2. International Society of Nephrology/Renal Pathology Society 2003 Classification of Lupus Nephritis
Class I



Minimal mesangial lupus nephritis



Light microscopy findingsNormal
Immunofluorescence electron microscopy findingsMesangial immune deposits
Clinical manifestationsMild proteinuria
Class II



Mesangial proliferative lupus nephritis



Light microscopy findingsPurely mesangial hypercellularity or mesangial matrix expansion with mesangial immune deposits
Immunofluorescence electron microscopy findingsMesangial immune deposits; few immune deposits in subepithelial or subendothelial deposits possible
Clinical manifestationsMild renal disease such as asymptomatic hematuria or proteinuria that usually does not warrant specific therapy
Class III



Focal lupus nephritis



Class III (A)



Active lesions - Focal proliferative lupus nephritis



Class III (A/C)



Active and chronic lesions - Focal proliferative and sclerosing lupus nephritis



Class III (C)



Chronic inactive lesions - Focal sclerosing lupus nephritis



Light microscopy findingsActive or inactive focal, segmental, or global glomerulonephritis involving < 50% of all glomeruli
Immunofluorescence electron microscopy findingsSubendothelial and mesangial immune deposits
Clinical manifestationsActive generalized SLE and mild-to-moderate renal disease with hematuria and moderate proteinuria in many patients; worsening renal function in significant minority, potentially progressing to class IV lupus nephritis
Class IV



Diffuse lupus nephritis



Class IV-S (A)



Active lesions - Diffuse segmental proliferative lupus nephritis



Class IV-G (A)



Active lesions - Diffuse global proliferative lupus nephritis



Class IV-S (A/C)



Active and chronic lesions - Diffuse segmental proliferative and sclerosing lupus nephritis



Class IV-G (A/C)



Active and chronic lesions - Diffuse global proliferative and sclerosing lupus nephritis



Class IV-S (C)



Chronic inactive lesions with scars - Diffuse segmental sclerosing lupus nephritis



Class IV-G (C)



Chronic inactive lesions with scars - Diffuse global sclerosing lupus nephritis



Light microscopy findingsActive or inactive diffuse, segmental or global glomerulonephritis involving = 50% of all glomeruli; subdivided into diffuse segmental (class IV-S) when = 50% of involved glomeruli have segmental lesions (involving less than half of glomerular tuft) and diffuse global (class IV-G) when = 50% of involved glomeruli have global lesions
Immunofluorescence electron microscopy findingsSubendothelial immune deposits
Clinical manifestationsClinical evidence of renal disease including hypertension, edema, active urinary sediment, worsening renal function, and nephrotic range proteinuria in most cases; active extrarenal SLE in many patients
Class V



Membranous lupus nephritis



Light microscopy findingsDiffuse thickening of glomerular basement membrane without inflammatory infiltrate; possibly, subepithelial deposits and surrounding basement membrane spikes on special stains, including silver and trichrome; may occur in combination with class II or IV; may show advanced sclerosis
Immunofluorescence electron microscopy findingsSubepithelial and intramembranous immune deposits; subendothelial deposits present only when associated proliferative component is present
Clinical manifestationsClinical and laboratory features of nephrotic syndrome, usually without manifestations of active SLE
Class VI



Advanced sclerosis lupus nephritis



Light microscopy findingsAdvanced glomerular sclerosis involving = 90% of glomeruli, interstitial fibrosis, and tubular atrophy, all morphological manifestations of irreversible renal injury
Clinical manifestationsSignificant renal insufficiency or end-stage renal disease in most cases; unlikely to respond to medical therapy
SLE = systemic lupus erythematosus.
Table 3. Active and Chronic Glomerular Lesions
Activity IndexChronicity Index
• Endocapillary hypercellularity with or without leukocyte infiltration; luminal reduction



• Karyorrhexis



• Fibrinoid necrosis



• Rupture of glomerular basement membrane



• Cellular or fibrocellular crescents



• Subendothelial deposits on light microscopy



• Intraluminal immune aggregates



• Glomerular sclerosis; segmental, global



• Fibrous adhesion



• Fibrous crescents



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