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Lupus Nephritis and Related Conditions

Updated: May 21, 2023


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:

  1. 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)

  2. Proteinuria

  3. 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)




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