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LUPUS NEPHRITIS
Lupus Nephritis and Related Conditions
Acknowledgment: In this session of GlomCon, Dr. Rennke reviewed Lupus Nephritis and related conditions focusing on nephropathology. These notes are derived from his live presentation.
By Dr. Pravir Baxi Assistant Professor of Medicine Division of Nephrology Rush Medical College
Key Points:
The cardinal signs of glomerular dysfunction include:
Hematuria – this can be via glomerulitis as a result of inflammation (as a result of various mechanisms of both classical and alternative complement activation, antibody-dependent cell cytotoxicity, and/or cell-mediated immune mechanisms) or capillary fragility (basement membrane collagen defects)
Proteinuria
Loss of glomerular filtration rate
The current classification of Lupus Nephritis (ISN/RPS classification) is based on the findings from the kidney biopsy in patients with SLE. The presence of subendothelial and mesangial immune complex formation found in Lupus Nephritis (LN) is postulated to be due to 1) sequential deposition of endogenous antigen and circulating autoantibodies and 2) entrapment of preformed immune complexes from the circulation. IgG dominant “full house”(positive IgG, IgA, IgM, C1q) glomerular deposits on immunofluorescence (IF) is seen in LN (but not only specific to LN).
Class I: Minimal Mesangial Lupus Nephritis
Presentation (varies): preserved renal function, normal urinalysis or minimal hematuria/proteinuria, and no HTN
Biopsy findings: normal light microscopy (LM), immune complex deposits in the mesangium by IF, and electron microscopy (EM)
Class II: Mesangial Lupus Nephritis
Presentation (varies): preserved renal function, microscopic hematuria, and non-nephrotic proteinuria, and no HTN
Biopsy findings: mesangial expansion/hypercellularity (mononuclear cells), mesangial deposits on IF
Class III: Focal Lupus Nephritis
Presentation (varies): normal to elevated serum creatinine, microscopic hematuria, and proteinuria (active urinary sediment), and can have HTN
Biopsy Findings: active or inactive lesions in <50% of glomeruli, subendothelial and mesangial deposits on IF and EM
This class has been typically further subclassified as Active (A), Active/Chronic lesions (A/C), or Chronic (healed/scared lesions). It has been proposed that this further classification is not needed, but an overall index of activity and chronicity be assigned.
Class IV: Diffuse Lupus Nephritis
Presentation (varies): normal to elevated serum creatinine, microscopic hematuria and proteinuria (active urinary sediment, can be nephrotic range proteinuria), and HTN
Biopsy findings: active lesions in >50% of glomeruli, subendothelial and mesangial deposits typically seen on IF and EM
This class has been typically subdivided into segmental (S) and global (G) lesions, with again activity and chronicity (A, A/C, C). Similar to Class III, it has been proposed that this further classification is not needed, but an overall index of activity and chronicity be assigned.
Class V: Membranous Lupus Nephritis (a non-inflammatory form of LN)
It can be seen in combination with Class III, IV, or VI
Presentation (varies): in the pure class V, patients have proteinuria, which can be in the nephrotic range but with preserved renal function, no HTN, may have hematuria but normal complements
Biopsy findings: no inflammation (if pure class V), thickened capillary walls, sufficient granular immune deposits (on IF) corresponding to subepithelial electron-dense deposits on EM
New literature suggests that exostosin (EXT) 1/2 is the target antigen in SLE patients
Class VI: Advanced Sclerosing Lupus Nephritis
Defined by ≥90% global sclerosis without signs of activity
There are other forms of kidney involvement in SLE patients that are not part of the above classification:
Podocyte Injury
Lupus podocyotopathy – presents as “minimal change” in patients with SLE -IF findings can show “fine dusting” of IgG on the podocyte
Collapsing glomerulopathy in patients of African descent with SLE and CKD with risk alleles of APOL1
Podocyte-infolding-glomerulopathy
Immune-complex mediated interstitial nephritis in SLE
Vasculitis or Vasculopathy
Antiphospholipid Antibody Syndrome and Thrombotic Microangiopathy (TMA)