Abstract
Background The therapy of lupus nephritis remains toxic and only partially effective but the benefits in terms of renal and patient survival are clear. However, there is considerable heterogeneity in the prognosis of individual patients and in their response to and tolerance of therapy. Accurate assessment of disease activity to guide therapy is limited by the complex relations between clinical biomarkers - serum creatinine, urine protein and sediment - with histologic activity. Renal biopsy is invasive with well characterised, if rare, risk of haemorrhage. While the initial biopsy confirms the diagnosis, nephritis class and other parameters, prediction of treatment response and long term outcome is limited. The extent to which the cost and risk of repeat biopsy can be justified in terms of improving long term prognosis is unclear resulting in wide variances in current practice and advice. As better targeted therapies become available in parallel with better pathway and target identification in the biopsy there is the potential role for sequential biopsy to influence the type and duration of treatment.
Methods A small number of prospective studies have examined protocol biopsies, with a larger number of observational studies limited by inconsistent indications for repeat biopsy. Outcomes have included descriptions of changes in histologic class, activity and chronicity, associations between histologic activity and clinical biomarkers, impact on treatment decisions, renal prognosis in terms of renal relapse or loss of renal function, and safety.
Results Activity on repeat protocol biopsy has been associated with increased risk of relapse and loss of function.1-3 Trends in change in histologic class have been progression from II to IV-G, from IV to IV + V, and for the subtypes of IV-G and IV-S to remain the same. In a small number of cases a non-lupus renal diagnosis was discovered. When compared to changes in urine protein, one third of complete proteinuric responders had histologic activity, while almost one half of non-proteinuric responder had no histologic activity. The impact of repeat biopsy on therapeutic decision remains controversial with evidence for and against.
Conclusions Repeat renal biopsy studies have contributed to our understanding of the course of nephritis and provide information unavailable from other sources. While arguments in favour of protocol biopsy continue, no long term benefit on hard outcomes has been defined. Clinical utility of repeat biopsy is highest when there is uncertainty on treatment decisions, such as, with persisting proteinuria or falling GFR, in the absence of an apparent treatment response or when treatment withdrawal is contemplated. Until improved blood or urine biomarkers have been developed, repeat biopsy will remain a useful tool for the clinic.
References
Malvar A, Alberton V, Lococo B, et al. Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis. Kidney Int. 2019
De Rosa M, Azzato F, Toblli JE, et al. A prospective observational cohort study highlights kidney biopsy findings of lupus nephritis patients in remission who flare following withdrawal of maintenance therapy. Kidney Int. 2018;94:788–794.
Arriens C, Chen S, Karp DR, et al. Prognostic significance of repeat biopsy in lupus nephritis: Histopathologic worsening and a short time between biopsies is associated with significantly increased risk for end stage renal disease and death. Clin Immunol. 2017;185:3–9.
