Background The relapsing and remitting nature of lupus nephritis (LN) poses a challenge to clinicians who must balance the risk of long term kidney damage with the side effects of treatment. Management of this condition would be greatly aided by the identification of biomarkers that accurately reflect and predict treatment responses. We previously identified and validated a panel of urinary biomarkers that are specifically elevated in SLE patients with active LN as compared to active patients without LN or LN patients in remission.
Objectives To determine whether changes in the levels of these urinary biomarkers predict treatment responses.
Methods 21 SLE patients with biopsy-proven LN were followed longitudinally for a minimum of 2 years after treatment. Levels of 15 urinary biomarkers including Clusterin, Cystatin C, NGAL, PF4, vWF,sVCAM-1, GM-CSF, GRO, IL-15, IL-6, MCP-1, Adiponectin, PAI-1, MMP-7, and TIMP-1, were measured by Luminex. Patients were classified as having a complete response (n=12), partial response (n=4), or treatment (Tx) failure (n=5) at 2 years following initiation of treatment, based upon previously established criteria. Urinary biomarker levels were considered abnormal if they were >2 SD above the mean for 24 healthy controls. Data were analyzed using non-parametric statistics.
Results At 3–6 months following treatment, the changes in biomarker levels from the first visit were not significantly different between complete responders and partial responders or Tx failures. However, at 1 year (11–16 months) following treatment, 5 urinary biomarkers, sVCAM-1, Adiponectin, IL-15, vWF, and MCP-1, demonstrated significantly different changes from baseline in complete responders as compared to Tx failures, with the majority of responders demonstrating improvement and the majority of Tx failures demonstrating worsening. As urinary biomarker levels not corrected for urinary osmolality correlated best with clinical outcomes, subsequent analyses were done with the uncorrected values. Normalization of urinary Adiponectin by 11–16 months was the best predictor of a complete response, with 11 of 12 patients who normalized being complete responders and 1 a partial responder. Similar but slightly less discriminative results were obtained for the other 4 urinary biomarkers. Conversely, the presence of an abnormal urinary vWF at 11–16 months was the strongest predictor of an adverse outcome with 4 of 6 patients with abnormal levels being Tx failures. Notably, all patients that were Tx failures that had normal levels of urinary biomarkers at 11–16 months subsequently developed abnormal levels, whereas patients who were complete responders eventually normalized the majority of these 5 biomarkers. Partial responders demonstrated normalization with delayed kinetics.
Conclusions Measurement of urinary biomarkers can provide valuable insight into treatment responses in lupus nephritis.
Disclosure of Interest None declared
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