Lupus and Renal Disease

This site is intended for healthcare professionals as a useful source of information on the diagnosis, treatment and support of patients with lupus and related connective tissue diseases.
Renal involvement, ranging from a small amount of proteinuria to acute glomerulonephritis and renal failure, affects up to 40-75% of lupus patients. All patients need screening for renal involvement with regular checks of serum creatinine and urine dipstick for protein and haematuria. Often lupus nephritis will present early in the course of the disease, sometimes within the first five years. The prognosis for patients with lupus nephritis has improved with advances in treatment. This is due to earlier diagnosis, access to treatment pathways including immunosuppression and high dose steroids (where indicated).

Renal biopsy is of value especially in disease classification. This is most important where there is evidence of glomerular disease. Renal biopsy tissue sample enables the clinician to categorise the disease activity and offer therapeutic options as well as providing prognostic information. Patients with proliferative glomerulonephritis (WHO III and IV) tend to have a worse outcome for renal function and evidence of severe active and chronic histological changes on renal biopsy are reported to adversely affect outcome. The classification of lupus nephritis by the World Health Organisation is listed in the table below.

A greater probability of lupus nephritis has been associated with black race, low heamatocrit, raised serum creatinine, high urinary protein excretion, low C3 complement and poor socioeconomic status. However, developments in treatments have meant most patients with lupus nephritis respond well to treatment, following this regime:-

1. Close monitoring of blood pressure and early treatment. This may require more than one agent and target range for blood pressure should be 125/75
2. Avoid nephrotoxic drugs such as NSAIDs
3. eGFR can be useful but is not always completely accurate, always refer for a biopsy if there is a fall in eGFR
4. Remember there is limited renal reserve in ageing patients
5. Smoking is a risk factor for progression of renal disease

The World Health Organisation Classification of Lupus Nephritis

Class I: Normal or minimal change disease (1%-4%)

      a. Nil (by all techniques)
      b. Normal by light microscopy but deposits by electron or immunofluorescence microscopy

Class II: Mesangial glomerulonephritis (20%)

      a. Mesangial widening and/or mild hypercellularity
      b. Moderate hypercellularity

Class III: Focal proliferative glomerulonephritis (25%)

      a. "Active" necrotizing lesions
      b. "Active and sclerosing lesions"
      c. Sclerosing lesions

Class IV: Diffuse proliferative glomerulonephritis (37%)

      a. Without segmental lesions
      b. With "active" necrotising lesions
      c. With "active" and sclerosing lesions
      d. With sclerosing lesions

Class V: Membranous glomerulonephritis (13%)

      a. Pure membranous glomerulonephritis
      b. Associated with lesions of category II (a or b)
      c. Associated with lesions of category III (a - c)*
      d. Associated with lesions of category IV (a - d)*

*Alternatively, cases in these subcategories may be classified under category IV

Early diagnosis and treatment is essential for favourable outcomes. Treatment options include steroids (remember bone protection with calcium and vitamin D plus an oral bisphosphonate) and immunosuppression. Mycophenolate Mofetil is being used more widely in specialist units and can be considered to be superior to Cyclophosphamide. Both membranous and proliferative lupus nephritis respond to B cell depletion and the monoclonal antibody Rituximab is proving to be very effective in these groups of patients. For those that fail immunosuppression and develop end-stage renal failure, renal transplantation has been performed successfully.