The Ponticelli Protocol

When one is just beginning as a nephrology fellow, it may seem as if all the major glomerular diseases (e.g., membranous nephropathy, FSGS, lupus, etc) are all treated with the same protocols and same immunosuppressive agents: steroids, Cytoxan, Imuran, MMF, Rituxan, etc. To some extent this represents the relative dearth of randomized controlled trials within the field of nephrology.

However if we use the evidence available to us, there are certain protocols which are specific to certain diseases. Not everything responds to steroids–for example, while it is reasonable to attempt a course of steroids alone for FSGS, there is good data to suggest that steroids alone does NOT have an effect in individuals with IgA Nephropathy.

One of the landmark protocols for glomerular disease is the so-called “Ponticelli Protocol”, used in the treatment of idiopathic membranous nephropathy. The 1992 NEJM paper describes the randomization of a group of patients with biopsy-proven membranous nephropathy to one of two regiments: (a) a 6-month course of steroids alone, or (b) a 6-month course of alternating monthly steroids and chlorambucil. The rate of remission was significantly lower in the steroids/chlorambucil group, thus giving rise to the first effective therapy for this disease.

In present day nephrology (at least at the fellowship program at which I am training) chlorambucil is seldom used–too many side effects (e.g. bone marrow suppression)–and instead a different cytotoxic agent–namely cyclophosphamide (Cytoxan) is used. A typical regimen (the “modified Ponticelli protocol”, JASN 1988; 9:444) is shown below:

Months 1, 3, and 5: Solumedrol 1000mg iv daily x 3 days then prednisone 0.4 mg/kg/d x 27 days.

Months 2, 4, and 6: CTX 2.5mg/kg PO daily x 30 days.

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