Lupus Nephritis – Causes, Signs & Symptoms

Lupus Nephritis – Causes, Signs & Symptoms

1The term “lupus erythematosus” was introduced during 19th century to describe skin lesions produced by the bite of the wolf.  In 1941, Klemperer, Pollack and Baehr first described systemic lupus erythematosus (SLE) as one of the Connective Tissue Disease.  Systemic lupus erythematosus is an autoimmune disease in which organs and cells undergo damage initially mediated by tissue binding autoantibodies and immune complexes. Lupus Nephritis is of the most serious manifestations of systemic lupus erythromatosus (SLE )which usually arises within 5 years of diagnosis. Females greatly outnumber males by 8–13 : 1. However, males with SLE have the same incidence of kidney disease as do females.

Pathophysiology

Autoimmunity plays a major role renal manifestation of systemic lupus erythromatosus. Various immunologic mechanisms lead to production of autoantibodies against nuclear elements  The characteristics of the nephritogenic autoantibodies associated with lupus nephritis are :

  1. Antigen specificity directed against nucleosome or double-stranded DNA (dsDNA) – Some anti-dsDNA antibodies cross-react with the glomerular basement membrane.
  2. Higher-affinity autoantibodies may form intravascular immune complexes, which are deposited in glomeruli.
  3. Cationic autoantibodies have a higher affinity for the anionic glomerular basement membrane.
  4. Autoantibodies of certain isotypes (immunoglobulin IgG 1 and IgG 3) readily activate complement.

 

 

Etiology : What causes Lupus Nephritis?

There are multiple susceptibility factors  resulting  in abnormal immune responses leading to production of auto antibodies . These factors may be genetic factors, immunologic factors and environmental factors. These factors vary among different patients.

Genetic factors

Genetic predisposition plays an important role in the development of both systemic lupus erythromatosus (SLE) and lupus nephritis. Multiple genes, many of which are not yet identified, mediate this genetic predisposition Some of those include Human leukocyte antigen (HLA) class II genes, Complement genes, FcγR genes and others.

Immunologic and Environmental  factors

Patients with SLE have poor clearance mechanisms for cellular debris. Nuclear debris from apoptotic cells induces plasmacytoid dendritic cells to produce interferon-α, which is a potent inducer of the immune system and autoimmunity. Autoreactive B lymphocytes, which are normally inactive, become active in SLE because of a malfunction of normal homeostatic mechanisms, resulting in escape from tolerance. This leads to the production of autoantibodies.  Anti-dsDNA antibodies, develop through a process of epitope spreading.

Environmental factors  may also affect the occurrence and expression of SLE. Although alterations of the immune system induced by viral or bacterial antigens have been proposed, their role in SLE induction remains far from clear. However, exposure to sunlight, UV radiation, EPV, Silica Dust and certain medications can all predispose to the development of SLE.

 

 

Clinical features- Symptoms

Although SLE predominantly affects young females, the clinical manifestations are similar in both sexes and in adults and children.  Organ systems commonly involved include the kidneys, joints, serosal surfaces including pleura and pericardium, central nervous system, and skin.

  1. Asymptomatic clinically
  2. Symptoms of active systemic lupus erythematosus (SLE), including fatigue, fever, lupus rash, arthritis, nephritis, serositis, or central nervous system (CNS) disease.
  3. Symptoms related to active nephritis may include peripheral edema secondary to hypertension or hypoalbuminemia.
  4. Other symptoms directly related to hypertension that are commonly associated with diffuse lupus nephritis include headache, dizziness, visual disturbances, and signs of cardiac decompensation.

 

Clinical features: Signs of Lupus Nephritis

  • Focal and diffuse lupus nephritis:  Evidence of generalized active SLE with the presence of a rash, oral or nasal ulcers, synovitis, or serositis. Signs of active nephritis are also common.
  • Active lupus nephritis: Hypertension, peripheral edema, and, occasionally, cardiac decompensation.
  • Membranous lupus nephritis: Signs of an isolated nephrotic syndrome are common. These include peripheral edema, ascites, and pleural and pericardial effusions without hypertension.

clincoimmuno

The patient is diagnosed having systemic lupus erythromatosus (SLE) if the patient has biopsy-proven lupus nephritis with ANA or anti-dsDNA or the patient satisfies four of the criteria, including at least one clinical and one immunologic criterion.

 

 

Differential Diagnoses : Other possibilities mimicking Lupus Nephritis

Lupus has a variable natural history and broad range of clinical manifestations. The differentials includes various glomerulopathies of various etiologies as well as vasculitis. The common ones include:

  • Chronic Glomerulonephritis
  • Diffuse Proliferative Glomerulonephritis
  • Granulomatosis with Polyangiitis (Wegener Granulomatosis)
  • Membranous Glomerulonephritis
  • Polyarteritis Nodosa (PAN)
  • Rapidly Progressive Glomerulonephritis

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REFERENCES

1.
W. Taal M, M. Chertow G, A. Marsden P, Skorecki K, S. L. Yu A, M. Brenner B. Brenner and Rector’s The Kidney. Elsevier Health Sciences; 2011.
2.
Turner N, Lameire N, Goldsmith DJ, Winearls CG, Himmelfarb J, Remuzzi G, eds. Oxford Textbook of Clinical Nephrology. Oxford University Press; 2015. doi:10.1093/med/9780199592548.001.0001
3.
L. Kasper D, J. Larry J, Hauser S, Loscalzo J, S. Fauci A, Longo D. Harrison’s Principles of Internal Medicine 19/E (Vol.1 & Vol.2). McGraw-Hill Education / Medical; 2015.