Induction treatment of lupus nephritis: to pulse or not to pulse? Whether ’tis nobler to universally or selectively prescribe

Objective Although treatment guidelines recommend pulse steroids, induction treatment of lupus nephritis (LN) varies significantly among providers. This paper aims to explore evidence that intravenous pulse provides pharmacological benefits along with improved clinical efficacy without greater toxicity compared with high-dose oral glucocorticoids justifying inclusion for all active LN. Methods We conducted a systematic literature review (SLR) using the term ‘pulse glucocorticoids in LN’ in order to identify studies that summarise the pharmacologic mechanisms of glucocorticoids, reviewed the historical use of glucocorticoids in SLE, and compared pulse therapy with high-dose oral treatment related to their efficacy and toxicities. Results SLR demonstrated that non-genomic mechanisms of action are more associated with pulse than oral steroids. Some observational studies reported improved renal responses with pulse steroids but in exchange for more adverse metabolic bone disease effects (eg, osteoporosis and avascular necrosis) as well as infections and, importantly, mortality. Conclusions Current guidelines promoting pulse therapy for all forms of proliferative LN (and in the case of American College of Rheumatology 2024 treatment guidelines, even isolated class V membranous LN) rely on structured evidence grading processes, including expert consensus and observational data, but are not based on head-to-head randomised controlled trial comparisons. Therefore, there can be an ongoing debate regarding the best approach. The SLR identifies a distinct pharmacological benefit unique to pulse treatment, though without direct evidence necessary for the treatment of LN; includes observational studies with evidence of superior efficacy, but not consistently; and identifies a higher risk of adverse effects. In our opinion, the data advocates for a more selective approach to treatment, foregoing universal treatment with pulse steroids, based on a toxicity versus benefit assessment that patients with mild disease do not require the additional risks.