Lupus nephritis is the most common severe manifestation of SLE and is associated with increased mortality, chronic kidney disease and end stage renal failure. Outcomes are improved by early diagnosis and institution of effective therapy. A high index of suspicion is required for early indications of renal disease in all lupus patients and renal biopsy remains the definitive diagnostic procedure. Current histological classification focuses on glomerular pathology but vascular and tubulo-interstitial disease, and the effects of secondary anti-phospholipid syndrome should also be considered.
The goals of therapy are to achieve renal response (50% reduction in proteinuria) then renal remission (proteinuria <0.5g/24hr, with normal glomerular filtration rate), and to prevent renal relapse (doubling of proteinuria, or haematuria with falling GFR). Early normalisation of low complement levels and falls in proteinuria are predictive of renal response at six months. Achievement of a renal response is predictive both of subsequent renal remission and of long term stability of renal function. Rates of renal remission are low, around 20%, at six months, but rise to 60-70% by two years.
There is good consensus that initial therapy should combine high dose glucocorticoids with either a mycophenolic acid agent (MPA) or cyclophosphamide (CYC). Once a response is achieved, relapse is prevented by long term treatment with MPA, or azathioprine, and low dose glucocorticoids. The optimal duration of treatment is uncertain but probably several years. Regular monitoring of SLE, renal and serological variables is required along with strategies to minimise treatment related toxicity, such as fertility preservation. Urinary abnormalities do not correlate well with histological changes, especially after the onset of therapy, and there is a role for repeat renal biopsy for the assessment of changes in activity and chronicity, to detect new patterns of inflammation and for prognosis.
Progressive disease after institution of therapy or failure to achieve a renal response indicates refractory disease and is managed with high dose glucocorticoids and either switching of MPA to CYC, or vice versa, or the introduction of rituximab. Plasma exchange may have a role in rapidly progressive disease.
Management of patients with lupus nephritis should take place in centres with experience of the multi-system manifestations of SLE, of the various patterns of lupus nephritis, and of the range of medications employed in its treatment. Patient education and adherence are key factors in achieving optimal results.
Disclosure of Interest D. Jayne Grant/Research support from: Roche/Genentech, Consultant for: BIOGEN, GSK, Merck Serono, Roche/Genentech