Early proteinuria response: a valid real-life situation predictor of long-term lupus renal outcome in an ethnically diverse group with severe biopsy-proven nephritis?

Abstract

ObjectiveTwo recent important lupus nephritis trials reported that proteinuria was a good predictor of renal outcome in Caucasians, but data on real-life situation, other races and severe nephritis are lacking to substantiate this finding as a simple test to guide clinical practice. The aim of this study was to validate proteinuria as a predictor of long-term renal outcome in real-life situation in a racially diverse group of patients with severe nephritis.MethodsProteinuria, serum creatinine (SCr) and urine red blood cells were assessed at baseline and after 3, 6 and 12 months, as early predictors of long-term renal outcome (SCr <1.5 mg/dL at 7 years), in 94 patients with biopsy-proven lupus nephritis. The parameter performance and cut-off values were computed by receiver operating characteristic curves. Kaplan-Meier curves were used to validate the parameter.ResultsA proteinuria <0.8 g/24 hours at 12 months was the best single predictor of long-term renal outcome (sensitivity 90%, specificity 78%, positive predictive value 67%, negative predictive value (NPV) 94% and area under the curve 0.86; p<0.001). Addition of other variables to proteinuria such as SCr and haematuria at 12 months did not improve its performance. The proteinuria cut-off value of 0.8 g/24 hours at 12 months was a good predictor of 7-year renal survival (years free of dialysis) for patients with pure membranous (p=0.005) and proliferative nephritis (p=0.043), as well as black (p=0.002) and white race (p=0.001), anti-dsDNA positive (p=0.001) and anti-dsDNA negative (p=0.04) and male (p=0.028) and female (p=0.003) patients.ConclusionWe provided novel evidence that, in a real-life situation, proteinuria at 12 months of follow-up was the single best predictor of renal outcome at 7 years for an ethnically diverse group of patients with severe nephritis and a valid parameter for distinct histological classes, races, genders and anti-dsDNA profiles. The remarkably high NPV obtained reinforces its recommendation as the ideal predictor for clinical practice, since it is of low cost, easy to interpret, non-invasive and widely available.

Establishing Surrogate Kidney End Points for Lupus Nephritis Clinical Trials: Development and Validation of a Novel Approach to Predict Future Kidney Outcomes

“…Additionally, a proteinuria level of 0.7-0.8 gm/day after 12 months of treatment was recently identified as the best predictor of long-term kidney survival compared to serum creatinine and urinary RBC status in a post hoc analysis of the Euro-Lupus Nephritis Trial and MAINTAIN LN trials (18,19). These results were verified in an independent, ethnically diverse LN cohort (20). Similarly, proteinuria is a key component of all of our risk models, whereas urinary RBCs are not.…”

2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis

“…Post hoc analyses from the MAINTAIN and Euro-Lupus Nephritis Trials suggest that proteinuria at 12 months represents the best single predictor for long-term renal outcome (ie, risk for end-stage kidney disease (ESKD) or doubling of serum creatine after 10 years). [23][24][25][26][27] Accordingly, therapy should aim for proteinuria <0.5-0.7 g/24 hours by 12 months (complete clinical response), although up to 50% of patients not reaching this milestone may still have stable longterm kidney function. 25 28 Evidence of improvement in proteinuria (with GFR normalisation/stabilisation) should be noted by 3 months, 29 30 and at least 50% reduction in proteinuria (partial clinical response) by 6 months.…”

Prediction of prognosis and renal outcome in lupus nephritis

“…By contrast, early decrease of proteinuria levels over 6 months of treatment has shown ability to predict a more favourable long-term renal outcome compared with patients with persistently high-grade proteinuria,16 and a recent series of three studies of similar design concluded that the most useful clinical predictor of good long-term renal outcome (defined using a cut-off for serum concentrations of creatinine at 7 years after the LN episode) is proteinuria levels <0.7–0.8 g/day at month 12 from treatment initiation 14 15 17. Nevertheless, while this clinical target could identify patients who had a good renal outcome with a high positive predictive value, it could not predict the outcome of patients who did not achieve the target since the negative predictive value of this proteinuria cut-off was low in two of the three investigations 14 15.…”