Should cyclophosphamide be a first-line medication for class V lupus nephritis? Comment on the article by Hahn et al

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Should Cyclophosphamide be a First-Line Medication for Class V Lupus Nephritis? Comment on the Article by Hahn et al

To the Editor:

We read with interest the guidelines for the screening, treatment, and management of lupus nephritis (LN) recently published in Arthritis Care & Research (1). This article provided insightful guidance on the management of LN. However, there are some comments we would like to make.

Class V LN occurs in one-fifth of biopsy-proven cases of systemic lupus erythematosus. In the Recommendations for Induction of Improvement in Patients With Class V “Pure Membranous” LN section of the guidelines, the Task Force Panel recommended that patients with pure class V LN with nephrotic range proteinuria be started on prednisone plus mycophenolate mofetil (MMF; level A evidence, defined as evidence representing data derived from multiple randomized controlled trials or a meta-analysis). However, cyclophosphamide (CYC) is not recommended and graded in the guidelines. In an analysis of 2 large randomized controlled multicenter trials of patients with class V LN, MMF taken orally at a total daily dose of 2–3 gm plus daily prednisone for 6 months resulted in improvement similar to that of intravenous CYC plus prednisone, with 0–30% of patients having nephrotic range proteinuria after 6 months (2). These results are from a pooled analysis of patients with class V LN from the 2 prospective randomized controlled multicenter trails (2–4), not a retrospective analysis as mentioned by the guideline authors. The authors of this pooled analysis even argue that retrospective power analyses are very controversial and should be avoided (2). If this study is a retrospective analysis, the evidence level should not be level A, but rather level C (defined as evidence representing data from consensus, expert opinion, or case series) at most. The Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group published guidelines for glomerulonephritis almost simultaneously in June 2012 (5), and in section 12.5: Class V LN (membranous LN), MMF is graded level 2D (defined as a suggestion based on a very low quality of evidence) after CYC (level 2C, a suggestion based on a low quality of evidence) and calcineurin inhibitors (level 2C). In fact, the KDIGO Glomerulonephritis Work Group missed the evidence level A pooled analysis study (2), and it was not included in the reference list (5). Moreover, a recent mini review concluded that MMF and CYC should now be considered standard first-line therapy for severe LN (class III/focal proliferative, class IV/diffuse proliferative, and class V/membranous) (6). In view of this, it would be more appropriate for both MMF and CYC to be recommended as first-line medications for class V LN (level A evidence).

Xin Du MD*, Dinglei Su MD*, Changchun Cao MD, PhD*, * Nanjing First Hospital and Nanjing Medical University, Nanjing, China.

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