To the Editor:
Regarding the Consensus Document published in this magazine last February on the diagnosis and treatment of lupus nephritis (LN)1, I want to congratulate the group for such exquisite work, from which we hope to optimise treatment of patients with this pathology. From reading this piece two thoughts emerged:
1. Houssiau2 refers, in an editorial accompanying the ALMS3 study release, that among patients who received maintenance therapy with mycophenolate (MMF), the ones who had previously received cyclophosphamide (CYC) induction obtained better results on the main variable outcome of the maintenance phase (11 vs. 21% in death, doubling of baseline creatinine, advanced chronic kidney disease, renal flare or salvage therapy), but with no significant differences. This is also a subgroup analysis, which binds us to be cautious of interpretations. Another subgroup analysis, with the same cautious interpretation3, emphasizes that patients receiving CYC induction did significantly better with MMF compared to azathioprine (AZT) in maintenance (4.7 vs. 14.5 in relative risk of treatment failure). Along the same lines, though without achieving statistical significance, subjects who received MMF induction also presented better results with MMF than with AZT (relative risk 10.1 vs. 20.1 on treatment failure). On the American Nephrology Congress (November 2011, Philadelphia, USA) Appel GB mentioned, regarding the ALMS study, that "patients who were treated with CYC induction presented less treatment failure on the maintenance phase than patients treated with MMF, independently from the drug received on this second phase". I believe this is the part you mentioned on the Consensus Document. This statement would make us conclude that CYC induction adds an additional benefit regardless the immunosuppressive maintenance option. This a theme to be debated, although it can be subject to future research, and we should examine it with discretion given that it originated from a subgroup analysis.
2. There are few studies on the best immunosuppression in patients with LN and renal clearance (ClCr) <30ml/min, probably because reference studies with CYC excluded patients that presented stage 4 renal failure (RF), except for some involving a patient with creatinine of 4.8mg/dl4 with not many details and no results subanalysis. Even so, we have relied on the suitability of CYC in patients with severe LN and RF, and thus have been captured in the Consensus Document.
The ALMS study5 rated with a 4-5 score on the Jadad scale, included a total of 32 patients (8.7%) with ClCr <30ml/min, 20 (10.8%) in the MMF branch and 12 (6.5%) on CYC. In the total group of 370 patients, 122 had scarring on renal biopsy, 66 (35.7%) on the MMF branch and 56 (30%) on the CYC branch. Regardless the data, no differences were found between both groups in the main variable results, which measured the efficacy of immunosuppressive treatment in inducing response. Based on this data, every day more of us begin induction treatment for LN class III-IV-V still with stage 4 RF with MMF and especially if the patients are women in their childbearing years. Besides, this kind of patients are treated with steroid pulses, which will act more rapidly and effectively in reducing the acute inflammation in the renal parenchyma, awaiting the additional benefit and hoping that they would add the non-steroid immunosuppressants.
If we continue to recommend CYC in patients with creatinine >3mg/dl (or with crescents/fibrinoid necrosis on biopsy), I believe that we will be depriving them from the opportunity of treatment with a drug free of gonadal toxicity and preventing the possibility of obtaining evidence with MMF on cases of important reduction of glomerular filtration rate, as long as it is a individualized responsible decision.
Conflicts of interest
The authors have no conflict of interests to declare.
