Evaluation of clinical, histological and biomarker response after initial therapy of lupus nephritis

To evaluate histopathological renal response in re-biopsy after induction therapy and to correlate with the Target Renal Response (TRR) and secondary objective: to correlate serum and urinary biomarkers with creatinine, 24-hour proteinuria, histological class, activity index and chronicity index.

Open, longitudinal, multicentre study in lupus nephritis (LN) confirmed through renal biopsy. Two kidney biopsies (T1 and T2) were performed. Laboratory evaluations included urinary sediment examination, renal function, 24-hour proteinuria, serum C3/C4, anti-dsDNA, antinucleosome, anticardiolipin immunoglobulin M/immunoglobulin G, other serum (anti-C1q, monocyte chemoattractant protein 1 (MCP-1), lipocalin-associated neutrophil gelatinase (NGAL) and kidney injury molecule 1 (KIM-1)) and urinary biomarkers (tumour necrosis factor-related weak inducer of apoptosis (TWEAK), anti-interleukin 16, activated leucocyte cell adhesion molecule, MCP-1, NGAL, KIM-1, adiponectin, haemopexin and ceruloplasmin).

24 patients (mean age 32.5±8.2 years) were studied. After induction therapy, 18 patients achieved TRR. Among six patients who did not reach TRR, three failed to meet the 24-hour proteinuria criterion, two to the creatinine criteria and one to both criteria. Histological response was achieved by 14 patients; among these, four patients did not reach the TRR. We found 12 discordances between clinical and histological responses. Eight patients achieved TRR without histological response and four patients achieved histological response without TRR. Serum NGAL and serum KIM-1 showed correlation with urea and with creatinine and higher levels of urinary TWEAK were found in patients who remained with abnormal haematuria at T2. However, no correlation of these new biomarkers was found with activity score or histological class in this study.

Discordance between clinical and histological response was confirmed, more patients achieved clinical response than histological response and, even in patients with histological response, not everyone presented clinical response. In a short interval of time, we observed early reduction in proteinuria and change in histological class after induction therapy. The lack of correlation between biomarkers and baseline histological parameters, which is inconsistent with prior studies, renders the biomarker findings inconclusive.