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The Treatment of Lupus Nephritis: Revisiting Galen
The therapeutic approach to the patient with lupus nephritis is controversial. The medical literature contains a surfeit of expert opinion and scant scientific evidence. Many opinions about the treatment of lupus nephritis are based on faith rather than valid observation. When faith rather than evidence is used to support clinical decisions, the treatment chosen becomes, like religion, a matter of personal preference.
Despite continuing improvement in outcomes, renal failure and death remain common among patients with lupus nephritis (1). The literature is burdened with clinical anecdotes and suboptimally designed clinical studies. Few controlled clinical trials have been reported, and meta-analyses are plagued by a lack of uniformity in the samples and outcome measures of existing studies. In this issue, Illei and colleagues (2) report a clinical trial comparing parenteral methylprednisolone, parenteral cyclophosphamide, and a combination of these two treatments, all in addition to low-dose oral prednisone. Their study raised hope that a more definitive answer to ideal therapy is on the horizon. Unfortunately, it too has important limitations.
Those who study lupus nephritis disagree on the optimal approach to therapy. Although it may have serious adverse effects, including gonadal toxicity, therapy with cytotoxic agents plus high-dose prednisone has become the standard of care for patients with lupus nephritis, most of whom are young. Two meta-analyses support this approach (3, 4). Of the currently available immunosuppressive agents, cyclophosphamide appears to have an advantage in terms of early therapeutic response. The dramatically improved long-term outcome observed in patients whose disease entered early remission has led to use of this cytotoxic agent as “induction therapy” (5).
Cyclophosphamide was developed for oral use, but disagreement exists about the preferred route of administration. While this argument may superficially appear pedantic, …
