The kidney biopsy in lupus nephritis: is it still relevant?

Abstract

The kidney biopsy is the standard of care for diagnosis of lupus nephritis and remains necessary to ensure accurate diagnosis and guide treatment. Repeat biopsy should be considered when therapy modifications are necessary, as in cases with incomplete or no response, or when stopping therapy for those in remission. There are several promising biomarkers of kidney disorders; however, these markers need to be validated in a prospective clinical trial before being applied clinically. Molecular analysis may provide the information presently lacking from current evaluation of kidney disorders and may better inform on prognosis and treatment considerations.

Keywords: Kidney biopsy; Lupus nephritis; Systemic lupus erythematosus.

Figure 1

Urine findings of glomerular hematuria in lupus nephritis. A. Acanthocytes are a type of dysmorphic red blood cell that is specific for glomerular hematuria. The arrow indicates a bleb that distorts the normal biconcave disc appearance of the red blood cell. B. Red blood cell casts also indicate glomerular bleeding.

Figure 2

Algorithm for kidney biopsy in lupus nephritis. A diagnostic kidney biopsy should be done to guide therapy when a lupus patient presents with clinical evidence of new kidney injury. A repeat biopsy should be done to confirm complete histologic remission in patients who have achieved complete clinical renal response so maintenance immunosuppression may be stopped. A repeat biopsy should be done to guide changes in therapy for patients who have incompletely responded. A repeat kidney biopsy should be considered at LN flare if there is suspicion that histology changed and therapy may need to be modified.

Figure 3

Application of biomarkers of kidney pathology in lupus nephritis. The rationale for identifying biomarkers of pathology and how these biomarkers are expected to improve the management of LN are shown. In this schema the biomarkers of kidney pathology reflect the presence and severity of specific lesions such as glomerular crescents, interstitial inflammation or interstitial fibrosis. Lesion-specific biomarkers measured serially and frequently would provide an understanding of how kidney injury evolves in real-time during and after LN treatment.

Figure 4

Clinical validation of kidney pathology biomarkers. Patients with biopsy-proven LN are randomized to a usual-care treatment strategy or a biomarker-based treatment strategy. The usual-care strategy will follow the induction and maintenance recommendations of the 2013 ACR treatment guidelines. The biomarker-based arm will begin treatment in the same way, but duration and intensity of treatment will be modified monthly based how biomarkers of active pathologic lesions are responding. For example, if biomarkers are normalizing, induction could be shortened and maintenance started early; if lesions are not responding well, induction could be lengthened. Maintenance could be discontinued if the biomarkers indicated a complete histologic remission. All patients would be followed for 12 months and at that time outcomes between the arms would be compared. The outcomes to be measured are indicated in the figure. Complete renal response (CRR) would be adjudicated clinically on the basis of kidney function and proteinuria, as is currently done, and also compared to complete histologic response.

Figure 5

Principle component analysis of kidney biopsy transcriptional profiles. RNA was harvested from archived kidney biopsies performed at LN flare, and for which kidney outcomes after treatment were known. Pre-implantation living transplant donor biopsies were considered normal. Immune gene expression was measured by Nanostring technology. Principle component analysis (PCA) was done on the RNA expression data. PCA shows that at renal flare patients clustered by the type of renal response they had long-term. CR = complete renal responder; PR = partial renal responder; NR = non-responder.