Current management of lupus nephritis: popular misconceptions

Abstract

The management of lupus nephritis is typified by popular misconceptions: that there is a ‘standard of care’, that treatment has well-defined aims and that the optimum length of treatment is established. In reality, however, uncertainties still exist and the evidence base remains weak.

Until recently, initial therapy for class IV lupus nephritis typically involved intravenous cyclophosphamide, yet although cyclophosphamide is superior to azathioprine in improving renal function, it is not superior in terms of mortality. In fact, recent studies show mycophenolate mofetil to be superior to cyclophosphamide in terms of response rate and safety profile and at least as effective as other immunosuppressants. The role of steroids is unclear. Clearly, no standard of care exists in lupus nephritis.

The Euro-Lupus Nephritis Trial found that treatment response at six months, in terms of reduced serum creatinine and proteinuria, was the best predictor of long-term renal outcome. Proteinuria, however, can take a long time to reach baseline levels, and normalization of urine is not the same as loss of histological disease activity. Response to treatment thus is not the same as disease remission. Although treatment should aim to reduce the risk of end-stage renal disease and death, control of proteinuria and prevention of flares are also important.

Patients who have nephritic flares are almost seven times as likely to progress to end-stage renal disease compared with those who do not. Regimens involving maintenance phases have been developed, but uncertainty remains about the risk of flares and how they can be predicted. The optimum duration of treatment has yet to be determined.

Keywords

lupus nephritis treatment cyclophosphamide mycophenolate mofetil kidney disease kidney failure

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References

Cross J , Jayne D . Kidney International Society Abstracts 2001. Autumn Meeting of the UK Renal Association (Abstract 56), 2001.

Flanc RS , Roberts MA , Strippoli GFM , Chadban SJ , Kerr PG , Atkins RC . Treatment of diffuse proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis 2004; 43: 197–208.

Illei GG , Austin III HA , Crane M et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 2001; 135: 248–257.

Moore RA , Derry S . Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther 2006; 8: R182-R182.

Trager J , Ward MM . Mortality and causes of death in systemic lupus erythematosus. Curr Opin in Rheumatol 2001; 13: 345–351.

Cook RJ , Gladman DD , Pericak D , Urowitz MB . Prediction of short-term mortality in systemic lupus erythematosus with time dependent measures of disease activity. J Rheumatol 2000; 27: 1892–1895.

Korbet SM , Lewis EJ , Schwartz MM , Reichlin M , Evans J , Rohde RD . Factors predictive of outcome in severe lupus nephritis. Am J Kidney Dis 2000; 35: 904–914.

Houssiau FA , Vasconcelos C , D'Cruz D et al. Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis. Lessons from long-term follow-up of patients in the Euro-Lupus Nephritis Trial. Arthritis Rheum 2004; 50: 3934–3940.

Ginzler EM , Dooley MA , Aranow C et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005; 353: 2219–2228.

10.

Cross J , Dwomoa A , Andrews P et al. Mycophenolate mofetil for remission induction in severe lupus nephritis. Nephron Clin Pract 2005; 100: c92–c100.

11.

Tumlin S . ASN 2004; J Am Soc of Neph, annual meeting abstract FC046.

12.

Ding L , Zhao M , Zou W , Liu Y , Wang H . Mycophenolate mofetil combined with prednisone for diffuse proliferative lupus nephritis: a histopathological study. Lupus 2004; 13: 113–118.

13.

Schnitzler MA , Craig KE , Hardinger KE , Lowell JA , Brennan DC . Mycophenolate mofetil is associated with less death with function than azathioprine in cadaveric renal transplantation. Nephrol Dial Transplant 2003; 18: 1197–1200.

14.

Shimuzi H , Takahashi M , Takeda S-I et al. Mycophenolate mofetil prevents transplant arteriosclerosis by direct inhibition of vascular smooth muscle cell proliferation. Transplantation 2004; 77: 1661–1667.

15.

Moroni G , Quaglini A , Maccario M , Banfi G , Ponticelli C . ‘Nephritic flares’ are predictors of bad long-term renal outcome in lupus nephritis. Kidney Int 1996; 50: 2047–2053.

16.

Chan TM , Tse KC , Tang CS et al. Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol 2005; 16: 1076–1084.

17.

Cervera R , Khamashta MA , Font J et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine 2003; 82: 299–308.