Roughly 1/3rd of patients with membranous nephropathy experience a progressive deterioration in renal function over time. Thanks to Pradeep for bringing a new RCT from Lancet to our attention, which focuses on this subpopulation of MN with declining renal function. This trial randomized patients to conservative treatment, cyclosporine x 12 months, or alternating montly chlorabucil/prednisolone. Patients in the chlorambucil/prednisolone group had a lower risk (hazard ratio 0.44 [0.7-1.95]) of reaching the primary endpoint of a 20% further decline in renal function, as compared to the other two groups. Notably, the chlorambucil group, but not the cyclosporine group, received steroids. The authors concluded "For the subset of patients with idiopathic membranous nephropathy and deteriorating excretory renal function, 6 months’ therapy with prednisolone and chlorambucil is the treatment approach best supported by our
evidence. Ciclosporin should be avoided in this subset."
Kiran Goli adds: The original ponticelli protocol still holds good and has a very good response rate. Chlorambucil was originally
used in the study but most of the physicians use cyclophosphamide since studies
revealed similar efficacy with less toxicity (most worrisome is malignancy).
Some may choose CNI particularly in young patients with unfinished families for
whom fertiility is important...Kiran.
what about Rituximab, when to use? It has shown promising results given toxicity profile should Rituximab be considered before prednisolone and chlorambucil?
ReplyDeleteClin J Am Soc Nephrol 4: 734–744, 2009. doi: 10.2215/CJN.05231008
Kidney International (2008) 73, 117–125; doi:10.1038/sj.ki.5002628
Not yet - not until we have some controlled studies. We discussed the Ruggenenti studyin a journal club back in September - this was an uncontrolled study reporting one center's experience using rituxan in a heterogeneous group of patients (some first-line therapy, some second-line). I think we need a randomized controlled trial of the same caliber as the CSA and CTX trials before using rituxan as first-line. Definitely would consider it as second-line in patients with persistent nephrotic syndrome after CTX or CSA. By the way - in the US we never use chorambucil, as Kiran mentioned a few days ago here its cyclophosphamide.
DeleteAnd I definitely would encourage my patients to consider rituxan in the setting of a research protocol. I took a quick look, there is an NIDDK trial (NCT00977977, PI=Meryl Waldman) recruiting patients now, but it looks like its just in DC.
DeleteThanks Dr. Maynard for clarification.
ReplyDelete