Table 2.
Urinary proteins identified in lupus nephritis via discovery proteomics and subsequent validation studies.
| Discovery Proteomic Study: Publication (n = SLE patients) | Targeted Proteomic Study: | ||
|---|---|---|---|
| Marker | Publication (n = SLE patients) | Findings | |
| Zinc alpha-2 glycoprotein (ZAG) | Oates, 2005 (n = 20) [69] Varghese, 2007 (n = 11) [62] Somparn, 2012 (n = 10) [64] |
Somparn, 2012 (n = 56) [64] | Elevated in active LN and non-LN glomerular disease vs inactive LN. Not specific for LN. |
| Transferrin (Tf) | Varghese, 2007 (n = 11) [62] Suzuki, 2007 (n = 32) [33] |
Suzuki, 2009 (n = 98) [36] | Elevated in active LN vs inactive LN and control. AUC 0.8 for active LN. Elevated 3 mo prior to LN flare and remained high during flare. |
| Brunner, 2012 (n = 76) [80] | Not correlated with rSLEDAI. Combined Tf + GFR + C4 + MCP-1 + AGP = AUC 0.75 for detecting membranous LN. | ||
| Smith, 2017 (n = 30) [70] | Discriminated between active and non-LN. Combined AGP + CP + PGDS + TF = AUC 0.991 for active LN. | ||
| Urrego, 2018 (n = 120) [71] | Elevated in active LN vs inactive and non-LN. Correlated with SLEDAI and proteinuria. | ||
| Alpha-1 glycoprotein (AGP) | Oates, 2005 (n = 20) [69] Suzuki, 2007 (n = 32) [33] |
Suzuki, 2009 (n = 98) [36] | Elevated in active LN vs inactive LN and controls. AUC 0.76 for active LN. Elevated 3 mo prior to LN flare and remained high during flare. |
| Brunner, 2012 (n = 76) [80] | Correlated with rSLEDAI. Combined MCP1 + Cp + AGP + PCr = 0.85 for activity index. AGP + CP + PGDS + TF = AUC 0.991 for active LN. | ||
| Watson, 2012 (n = 60) [72] | Elevated in active LN vs inactive LN and healthy controls. | ||
| Prostaglandin D-synthase (PGDS) | Suzuki, 2007 (n = 32) [33] Somparn, 2012 (n = 10) [64] |
Suzuki, 2009 (n = 98) [36] | Elevated in active LN vs inactive LN and controls. AUC 0.71 for active LN. Elevated 3 mo prior to LN flare and remained high during flare. |
| Somparn, 2012 (n = 56) [64] | Elevated in active LN vs inactive LN, non-LN glomerular disease and healthy controls. AUC 0.73 for active LN. | ||
| Brunner, 2012 (n = 76) [80] | Correlated with rSLEDAI. Combined AGP + CP + PGDS + TF = AUC 0.991 for active LN. | ||
| Go, 2018 (n = 121) [67] | Elevated in active LN vs inactive LN. Higher in inactive LN vs non-LN. Correlated with urine PCr and rSLEDAI. | ||
| Alpha-1 antitrypsin (A1AT) | Varghese, 2007 (n = 11) [62] Zhang, 2008 (n = 19) [65] |
NA | NA |
| Hepcidin | Zhang, 2008 (n = 19) [73] | Mohammed2014 (n = 60) [74] | Elevated in active LN vs non-LN. Among LN, elevated hepcidin in class IV LN vs class II/III. |
| Zhang, 2012 (n = 61) [75] | Elevated in tubulointerstitial inflammation. Poor performance to classify the severity of interstitial inflammation when used alone. | ||
| Transthyretin | Varghese, 2007 (n = 11) [62] Go, 2018 (n = 8) [67] |
Go, 2018 (n = 121) [67] | Elevated in active LN vs inactive LN. Higher in inactive LN vs non-LN. Correlated with urine PCr and rSLEDAI. |
| Retinol-binding protein (RBP) | Varghese, 2007 (n = 11) [62] Somparn, 2012 (n = 10) [64] |
Sesso, 1994 (n = 70) [76] Marks, 2005 (n = 21) [77] |
Elevated in active LN vs inactive and non-LN patients. Elevated in active LN vs inactive LN. |
| Aggarwal, 2017 (n = 88) [66] Go, 2018 (n = 8) [67] |
Aggarwal, 2017 (n = 88) [66] | Elevated in active LN vs inactive LN, RA and healthy controls. AUC 0.7 for active LN. Decreased at 6 & 12 mo upon follow-up. | |
| Go, 2018 (n = 121) [67] | Elevated in active LN vs inactive LN. Higher in inactive LN vs non-LN. Correlated with urine PCr and rSLEDAI. Baseline level lower in patients achieving remission within 12 months. | ||
| Vitamin D binding protein (VDBP) | Go, 2018 (n = 8) [67] | Go, 2018 (n = 121) [67] | Elevated in active LN vs inactive LN. Correlated with rSLEDAI. Baseline level predictive of flare upon follow-up. |
| Haptoglobin | Varghese, 2007 (n = 11) [62] Aggarwal, 2017 (n = 88) [66] |
Aggarwal, 2017 (n = 88) [66] | Elevated in active LN vs inactive and non-LN. Correlated with SLEDAI and rSLEDAI. AUC 0.86 for active LN. |
| Ceruloplasmin (Cp) | Suzuki, 2007 (n = 32) [33] | Suzuki, 2009 (n = 98) [36] | Elevated in active LN vs inactive LN and control. AUC 0.68 for active LN. Not consistent with flare cycle. |
| Urrego, 2018 (n = 120) [71] | Elevated in active LN vs inactive and non-LN. | ||
| Angiostatin | Wu, 2013 (n = 5) [68] | Wu, 2013 (n = 100) [68] | Elevated in active LN vs inactive LN. Correlated with SLEDAI, rSLEDAI, SLICC and chronicity index. Highest in class IV LN. |
| Mok, 2018 (n = 227) [78] | Elevated in active LN vs active SLE, stable SLE and healthy controls. AUC 0.87. Correlated with SLEDAI, rSLEDAI, and PCr. No correlation with histology. | ||