A discrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis.

Carolina Landolt-Marticorena,Babak Noamani,Paul R Fortin,Dennisse Bonilla,Paul C Boutros,Carmen Avila-Casado,Stephenie D Prokopec,James Scholey,Joan Wither,Heather Reich,Stacey Morrison

doi:10.1186/s13075-016-1120-0

Abstract

BackgroundManagement of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN.MethodsUrine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels. Data were analyzed by linear modeling and non-parametric statistics, with corrections for multiple comparisons. A second cohort of 33 active LN, 16 active non-LN, and 30 remission LN SLE patients was used to validate the results.ResultsForty-four analytes were identified that were significantly increased in active LN as compared to active non-LN. This included a number of unique proteins (e.g., TIMP-1, PAI-1, PF4, vWF, and IL-15) as well as known candidate LN biomarkers (e.g., adiponectin, sVCAM-1, and IL-6), that differed markedly (>4-fold) between active LN and non-LN, all of which were confirmed in the validation cohort and normalized in remission LN patients. These proteins demonstrated an enhanced ability to discriminate between active LN and non-LN patients over several previously reported biomarkers. Ten proteins were found to significantly correlate with the activity score on renal biopsy, eight of which strongly discriminated between active proliferative and non-proliferative/chronic renal lesions.ConclusionsA number of promising urinary biomarkers that correlate with the presence of active renal disease and/or renal biopsy changes were identified and appear to outperform many of the existing proposed biomarkers.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1120-0) contains supplementary material, which is available to authorized users.

Highlights

Management of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity
LN-associated proteinuria frequently persists for years after renal injury, normalizing in less than 50 % of patients within 2 years [6], and often a renal biopsy is the only way to distinguish between persistent activity and a chronic inactive lesion
A cluster of urinary proteins identifies patients with active LN Urinary concentrations of 128 analytes were determined in systemic lupus erythematosus (SLE) patients with ALN or active SLE patients without LN (ANLN), and healthy controls (HC), and normalized to urinary creatinine. Both SLE groups were comparable with respect to age, sex, and disease activity, patients with ALN were on higher mean doses of prednisone and more immunosuppressive medications as compared with ANLN (Table 1)

Summary

Introduction

Management of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Proteinuria and other measures of renal function falter as accurate markers of immunemediated renal injury. As these measures reflect kidney damage, reliance on proteinuria as a marker of renal inflammation leads to delayed initiation of treatment. LN-associated proteinuria frequently persists for years after renal injury, normalizing in less than 50 % of patients within 2 years [6], and often a renal biopsy is the only way to distinguish between persistent activity and a chronic inactive lesion. There has been tremendous interest in the identification of biomarkers that accurately indicate the extent, type, and course of renal inflammation in LN

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