A Histology-Guided Approach to the Management of Patients with Lupus Nephritis: Are We There Yet?

Abstract

Renal involvement is a frequent complication of systemic lupus erythematosus (SLE). It occurs in up to two-thirds of patients, often early during the disease course, and is the most important predictor of the morbidity and mortality of SLE patients. Despite tremendous improvements in the approach of the lupus nephritis (LN) therapy, including the recent approval of two new disease-modifying therapies, up to 50% of patients do not obtain a renal response and up to 25% will eventually progress to end-stage renal disease (ESRD) within 10 years of diagnosis. Given the lack of correlation between clinical features and histological lesions, there is an increasing need for a histology-guided approach to the management of patients with LN. Apart from the initial diagnosis of type and severity of renal injury in SLE, the concept of a repeat kidney biopsy (either in a for-cause or a per-protocol scenario) has begun to gain increasing popularity in the nephrology community. Herein, we will provide a comprehensive overview of the most important areas of utility of the kidney biopsy in patients with LN.

Keywords: biomarkers; histology; kidney biopsy; lupus nephritis; protocol biopsy; repeat biopsy.

Figure 1

Patient 1 (A,B). Patient with SLE with normal renal function, 24-h proteinuria of 0.2 g/day, and minimal microscopic hematuria. Kidney biopsy shows severe, proliferative LN with crescent formation, and an activity index of 14 ((A), haematoxylin eosin staining, magnification 20×), with extensive mesangial and subendothelial immune complex deposition ((B), electron microscopy, magnification 11,000×). Patient 2, post-induction repeat biopsy (EUROLUPUS regimen). Initial biopsy, (C) (Masson staining, magnification 20×) and (E) (PAS staining, magnification 20×), show severe, proliferative LN with an activity index of 16 at baseline. Repeat biopsy, (D) (Masson staining, magnification 20×) and (F) (PAS staining, magnification 20×), show a significant histologic improvement with a decrease of the activity index to 2. (Images from the Renal Biopsy Registry of Fundeni Clinical Institute, Bucharest, Romania).

Figure 2

The integration of percutaneous kidney biopsy in the management of patients with SLE and renal involvement (adapted after [2,10,30,31,50,79,80]) (abbreviations: GN, glomerulonephritis; TMA, thrombotic microangiopathy; TIN, tubulo-interstitial nephritis; ATN, acute tubular necrosis; APS, anti-phospholipid syndrome; LN, lupus nephritis; CNI, calcineurin inhibitor; IS, immunosuppression; and RCT, randomized clinical trial).