15th July 2024

Lupus Nephritis

Background

Lupus nephritis is a severe manifestation seen in over 50% of patients with systemic lupus erythematosus (SLE) and is the main contributor to morbidity and mortality through its propensity to cause end-stage renal disease. The 2019 ACR and EULR classification criteria for SLE includes various features of renal involvement as its most heavily weighted diagnostic domain, in addition to a positive ANA titre of >1:80. The pathogenesis of lupus nephritis is complex with abnormalities in T-cell, B-cell and complement cascade pathways, but ultimately it is characterised by immune complex deposition in the glomeruli and inflammation throughout the kidneys.

Lupus nephritis has an affinity for young adults, particularly those of Asian and African American origin.  It is 12 times more likely to affect females than males.  Patients may present with a variety of symptoms depending on the class of disease.

Diagnosis and Classification

Any sign of renal involvement, e.g. reproducible proteinuria, haematuria or urinary casts should prompt referral for renal biopsy.  The majority of patients with SLE will demonstrate histological evidence of lupus nephritis on renal biopsy (even in the absence of symptoms). A biopsy is required for diagnosis with changes in the glomerulus allowing for classification into the stages below:

Class IV disease (diffuse proliferative glomerulonephritis) is the commonest and severest form of lupus nephritis. The renal biopsy will typically demonstrate glomeruli with endothelial and mesangial cellular proliferation.  If severe, a ‘wire-loop’ appearance and thickening of the capillary walls secondary to immune complex deposition may be seen (also noted on electron microscopy examination).

Management

Without intervention, lupus nephritis will likely approach end stage renal disease.  Early recognition of disease and prompt induction of aggressive immunosuppression with corticosteroids is key to improving outcomes. Considering the chronicity of SLE, the dosage should be limited to prevent long term side-effects, and osteoporosis prophylaxis should be offered.  Immunosuppressants such as Cyclophosphamide and Azathioprine have a major role in maintaining remission. Co-existent hypertension should be treated.

References

• Kimmel P, Rosenberg M.  Chronic Renal Disease. 2ⁿᵈ ed. Massachusetts. Academic Press; Aug 2020
• Whittall Garcia LP, Gladman DD, Urowitz M, Touma Z, Su J, Johnson SR. New EULAR/ACR 2019 SLE Classification Criteria: defining ominosity in SLE. Ann Rheum Dis. 2021 Jan 15:annrheumdis-2020-218670. doi: 10.1136/annrheumdis-2020-218670. Epub ahead of print. PMID: 33452003
• Tamirou F, Houssiau FA. Management of Lupus Nephritis. J Clin Med. 2021 Feb 9;10(4):670. doi: 10.3390/jcm10040670. PMID: 33572385; PMCID: PMC7916202