Kidney biopsy represents the gold standard for the diagnosis of lupus nephritis (LN) and is used to stratify patients for the various therapy options. Kidney biopsy is a mandatory for LN trials, as a gold standard for biomarker studies, and for research on pathophysiology. However, can the initial biopsy really tell us anything about the immunopathogenesis of lupus in spleen and lymph nodes or about which drugs to choose or if the patient will respond to an adequate therapy? Will the recent discovery of EXT1/EXT2 deposits in about 1/3 of patients with Class V LN help to define subgroups of patients with unique phenotypes and prognosis? Isn`t the scientific attention to a biopsy that confirms the diagnosis and grossly defines intensity of treatment a bit irrational?

Too few kidney biopsies? Serum and urine biomarkers are used to guide immunosuppressive treatment of lupus nephritis, although there is compelling evidence that they poorly indicate persistent LN even in patients with a complete clinical response. The same problem in kidney allograft recipients is addressed by protocol biopsies, why is this not so in LN? A repeat biopsy at 12 months may be of utmost value to guide treatment and to predict long-term prognosis, something the first diagnostic biopsy hardly can do. The REBIOLUP trial will address this question. Other important repeat biopsy indications are the ‘partial responder biopsy’, the ‘smoldering lupus nephritis biopsy’, the ‘chronic kidney disease progression biopsy’ and the ‘drug withdrawal biopsy’.

Too many kidney biopsies? The least useful re-biopsy maybe when the patient flares as flare biopsies in patients with a previous Class III-V hardly ever affect treatment decisions. When patients with LN ‘flare’, drug non-adherence or recent reductions in drug doses are the most common cause, rather than a switch of the underlying disease. Systemic lupus erythematosus (SLE) is chronic autoimmune disease with continued disease activity, albeit at different levels in different patients. Therefore, LN does not require ‘induction’ and ‘maintenance’ therapy, but a constant long-term treatment usually with a combination of immunosuppressive drugs. SLE is heterogenous across individuals but not within an individual. Repeat biopsies are needed to detect inflammation when you are not sure about it, not when it is obvious.

Learning Objectives

• Explain the importance of not overestimating the potential of the first diagnostic biopsy as a source of insights into pathophysiology and predictive power beyond what is known

• Describe the value of treatment response as the main predictor for outcome and the potential use of a protocol biopsy at 1 year in this context because serum and urine markers are unreliable

• Discuss and question the value of a ‘flare repeat biopsy’, because it rarely affects treatment decisions

• Discuss the use of repeat biopsies in non- or partial responders, smoldering lupus nephritis, CKD progression and before drug withdrawal

• Explain the important concept that SLE is a chronic autoimmune disease that requires constant long-term treatment usually with a drug combination (not transient ‘induction and maintenance therapy’ with single drugs), identical to how we control persistent alloimmunity in kidney transplant recipients