Lupus nephritis (LN) is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE). In fact, there is renal involvement in the vast majority of patients with SLE at some time during the disease course—estimated between 66%-90% of the cases of SLE. The presence of subendothelial deposits in glomerular capillaries is crucial in initiating severe renal damage and they correlate with endocapillary proliferation, necrosis, karyorrhexis, and crescents. Renal disease is one of the highest causes of mortality in SLE and warrants much more consideration in the management of LN/SLE patients.1
The pathogenesis of LN involves a variety of extrarenal and intrarenal mechanisms—from epigenetic factors to immune cells and cytokines.2
Loss of immune tolerance in SLE occurs with production of antinuclear antibodies. Recognizing nucleic acids, toll-like receptor 7 (TLR7) and
Intrarenal autoantigens trigger the in situ formation of immune complexes, which ultimately activate complement and injure adjacent cells, thereby leading to LN. Attracting leukocytes into the glomerulus and interstitium, local chemokine and cytokine production continually contributes to increased intrarenal inflammation as well as cell and nephron loss.3
Signs & Symptoms
Signs and symptoms of LN may include:5
Patient presentation may range from no symptoms or proteinuria exclusively to acute nephritic syndrome or end-stage renal disease. Similarly variable, LN clinical course ranges from a steady subclinical disease to one that is much more aggressive and rapidly progressing.6 Patients may experience flares,4 and the presentation of clinical features in LN is not always indicative of renal histology. As such, renal biopsy is key to thoroughly evaluating SLE patients who develop renal disease.5
Disease & Clinical Trial Tools
For years, it has been challenging for clinicians to accurately measure lupus disease activity and how it changes over time. As a consequence, healthcare providers need more finely tuned and comprehensive assessment tools to improve patient care and develop effective treatments for the disease. Below are two common activity monitoring tools.7
The National Institutes of Health (NIH) Activity and Chronicity Indexes are commonly used to evaluate kidney biopsies and assess LN disease severity.
The NIH Activity Index (NIH-AI) quantifies specific histologic features indicative of active inflammation, including cellular proliferation, fibrinoid necrosis, cellular crescents, hyaline thrombi, leukocyte infiltration, and mononuclear-cell infiltration.
The NIH Chronicity Index (NIH-CI), on the other hand, quantifies features of permanent kidney damage, such as glomerular sclerosis, fibrous crescents, interstitial fibrosis, and tubular atrophy.
There are no standard criteria for “complete” or “partial” renal response to LN therapy; a range of definitions pull from various clinical and laboratory measures and can vary significantly. Nonetheless, research has shown the predictive value of evaluating such endpoints. Whether complete or partial, response can be associated with improved renal function and extended patient survival.