Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis

Abstract

Objective To investigate the relationship of urinary biomarkers (UBM) and established measures of renal function (EMRF) to the histological findings with lupus nephritis (LN); and to test whether certain combinations of the above mentioned laboratory measures are diagnostic of specific histological features of LN. Methods Urine samples of 76 patients were collected within 2 months of a kidney biopsy and assayed for the UBM: lipocalin-like prostaglandin-D synthetase (LPGDS), α1-acid-glycoprotein (AAG), transferrin (TF), ceruloplasmin (CP), neutrophil-gelatinase associated lipocalin (NGAL), and monocyte chemotactic factor 1 (MCP1). Using non-parametric analyses, UBM and EMRF levels were compared to histological features seen with LN: mesangial expansion, capillary proliferation, crescent formation, necrosis, wire loops, fibrosis, tubular atrophy, and epimembranous deposits. The area under the receiver operating characteristic (AUC) curve was calculated to predict LN activity, chronicity or membranous LN. Results There was a differential increase of the UBM that formed a pattern reflective of specific histological features seen with active LN. The combination of MCP1, AAG, CP plus protein:creatinine ratio were excellent in predicting LN activity (AUC=0.85). NGAL together with creatinine clearance plus MCP1 was an excellent (AUC=0.83) and MCP1, AAG, creatinine clearance plus C4 (AUC=0.75) a good diagnostic test of LN chronicity and membranous LN, respectively. Conclusions Select UBM are associated with specific tissue changes observed with LN activity and chronicity. Especially in combination with select EMRF, UBM are well-suited to non-invasively quantify LN activity, LN chronicity, and the presence of membranous LN.

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

“…Thus, investigations have recently evolved toward discovery and validation of lupus biomarker 'panels'. One approach in this regard has been technology-driven with the use of microarrays or proteomics for identifying novel gene or protein 'biosignatures' of SLE such as that discussed above for lupus nephritis [Brunner et al 2012]. Additional ongoing developments on this front are discussed briefly here.…”

Nephrotic Syndrome and End-stage Kidney Disease Accompanied by Bicytopenia due to Copper Deficiency

“…Moreover, Cp is expressed by glomerular parietal epithelial cells and secreted into the urine in aging rats fed a high-calorie diet (25). Finally, Cp is also secreted into the urine in patients with early diabetic nephropathy (26), early IgA glomerulonephritis (27) and lupus nephritis (28). Cp may be a urinary biomarker in these diseases, and previous reports suggest that the antioxidant Cp expression in the kidney, mainly in Bowman's capsule, protects podocytes and downstream nephrons from the toxic effects of filtered molecules.…”

Is Urinary Tumor Necrosis Factor-like Weak Inducer of Apoptosis a Biomarker of Lupus Nephritis?

“…However, further longitudinal studies with larger sample size need to be conducted to confirm the clinical significance of urinary TWEAK as a novel biomarker that can reflect histological activity and determine treatment response. Brunner and colleagues reported that combinational analysis of anti-dsDNA antibody, serum C3, C4, creatinine, urinary protein creatinine ratio, and urinary biomarkers such as MCP-1, NGAL, lipocalin-type prostaglandin D-synthetase, α1-acid-glycoprotein, transferrin, and ceruloplasmin is useful in predicting activity, chronicity, and pathology of LN [18]. Therefore, it might be helpful to study the benefit of combining the urinary TWEAK and established biomarkers in LN patients.…”