Introduction
Treat to target (T2T) strategies are becoming the best approach to treat several rheumatic disorders. The T2T concept has been widely used in the treatment of chronic disorders (such as hypertension, diabetes and cardiovascular disease) for many years, and the achievement of accurate therapeutic targets has led to significant good long-term prognoses.1 Adhering to this strategy in clinical practice optimises the outcomes and facilitates the routine follow-up, particularly when targets are as simple as possible.
Considering that lupus nephritis (LN) is a critical condition that can lead to renal impairment, a clear measurable short-term target is desirable. The current American College of Rheumatology (ACR) and European League Against Rheumatism criteria for the partial and complete responses of LN, assessed at 6–12 months, employ a composite measure of creatinine, urinary sediments and proteinuria (PTU).2 3 Both criteria consider the same variables but with different thresholds and relative endpoints (percentages of the initial variable). The use of multiple variables associated with relative endpoints hampers T2T strategies, since there is no clear target to be pursued. There are several other LN response criteria, but all of them hold the same problems.4–6
In the last few years, several LN trials have used short-term measures of renal response to create their own definitions of complete and partial responses.7–10 In 2015, Corapi et al 11 critically reviewed and compared all LN response criteria and endpoints used in LN trials. This article emphasised that there was a need to standardise the definitions of LN response as well as LN trial endpoints.11
Until recently, no simple test could predict renal outcome and guide treatment in LN. Recently, two analyses of important lupus trials, the MAINTAIN Nephritis trial and the Euro-Lupus Nephritis Trial (ELNT), have reported that PTU is the single best predictor of long-term (7 years) renal outcome in lupus patients,12 13 suggesting a possible use of the T2T approach for PTU to prevent renal damage. Both studies assessed the capacity of serum creatinine (SCr) concentration, 24-hour PTU and urinary red blood cell (RBC) counts at several time points to predict long-term renal outcome and concluded that PTU level at the 12-month follow-up was the best measure. The association of SCr or RBC to PTU undermined the predictive power of the model for both studies.12 13
The MAINTAIN Nephritis trial analysis concluded that a PTU <0.7 g/day at 12 months was the best predictor of good long-term renal outcome with a sensitivity of 71%, a specificity of 75%, a positive predictive value (PPV) of 94% and a negative predictive value (NPV) of 29%.13 The ELNT identified a PTU cut-off of 0.8 g/day at 12 months with a sensitivity of 81%, a specificity of 78%, a PPV of 88% and an NPV of 67%.12 According to these two analyses, an early PTU response (assessed at 12 months) seemed to be the best target to focus on in patients with LN.
The generalisation of these results is limited by the fact that the majority of patients were Caucasian with mild/moderate renal involvement at entry in both cohorts.12 13 In addition, adherence to intervention protocols is much higher in clinical trials than in non-research settings.14 Moreover, there is a lack of data regarding the relevance of the proposed PTU predictor in patients of distinct histological classes, races, genders and anti-dsDNA profiles. Therefore, the purpose of this study was to determine, in a real-life situation, if PTU was indeed a good predictor of renal outcome in patients with severe LN in a geographical region with more racial diversity.