Protocol kidney biopsy in the management of proliferative (class III/IV) lupus nephritis: barking up the wrong tree!

Lupus nephritis represents one of the most severe manifestations of systemic lupus erythematosus. Despite major advances in the therapeutical armamentarium over the last two decades, the number of patients reaching end stage kidney disease or dying has not changed significantly. One of the main reasons is that many patients relapse, and with each relapse, further damage is done to the kidney, contributing to the development of progressive chronic kidney disease. This has led to the increased practice of doing protocol biopsy to guide decision regarding risk for relapses and/or discontinuation of immunosuppression. However, this practice has been based on the assumption that the answer is in the kidney, while in reality the kidney reflects the downgrade effect of what is going on upstream, i.e. the immunological milieu. We provide an in-dept review on the use of repeat protocol kidney biopsies in LN with the hope to demonstrate that this practice is based on faulty evidence and of limited benefit in the management of patients with proliferative class III/IV lupus nephritis. Rather, physicians treating these patients should focus on markers of immunological activity (anti-ds-DNA levels) and clinical activity (C3/C4 complement levels), to better predict risk for relapses and in deciding when to reduce/discontinue immunosuppression. As such, this review represents a paradigm shift in the approach of evaluating activity in patients with LN, that is not done by performing protocol kidney biopsies, but rather by looking at the serological activity instead, and as such proposing a new vision on the subject that we believe will improve patient care and kidney outcomes.