Urine proteome scans uncover total urinary protease, prostaglandin D synthase, serum amyloid P, and superoxide dismutase as potential markers of lupus nephritis.

To identify potential biomarkers in immune-mediated nephritis, urine from mice subjected to an augmented passive model of anti-glomerular basement membrane (GBM)-induced experimental nephritis was resolved using two-dimensional gels. The urinary proteome in these diseased mice was comprised of at least 71 different proteins. Using orthogonal assays, several of these molecules, including serum amyloid P (SAP), PG D synthase, superoxide dismutase, renin, and total protease were validated to be elevated in the urine and kidneys of mice during anti-GBM disease, as well as in mice with spontaneously arising lupus nephritis. Among these, urinary protease was the only marker that appeared to be exclusively renal in origin, whereas the others were partly serum-derived. Longitudinal studies in murine lupus demonstrated that total urinary protease had better predictive value for histologically active nephritis (r = 0.78) compared with proteinuria (r = -0.04), azotemia (r = 0.28), or the other markers examined, whereas urine SAP emerged as the single most predictive marker of histological glomerulonephritis. Collectively, these studies uncover total urinary protease, PG D synthase, SAP, and superoxide dismutase as novel biomarkers of anti-GBM disease and lupus nephritis, with stronger correlation to renal disease compared with currently employed biomarkers. These findings could have important diagnostic and prognostic ramifications in the management of these renal diatheses.

Urinary excretion of pentraxin-3 correlates with the presence of renal scar following acute pyelonephritis in children.

PURPOSE: Acute pyelonephritis is associated with considerable morbidity and potential for renal scarring. Pentraxin3 (PTX3) is a recently discovered mediator of inflammation. The objective of this study was to investigate the changes in serum and urine PTX3 levels in children who had a history of pyelonephritis and were diagnosed with renal parenchymal scar (RPS) and/or vesicoureteral reflux (VUR). METHODS: The study included 88 children (31 males, 57 females) aged between 3 months and 18 years. The children included in the study were divided into four groups: VUR with RPS (Group 1), RPS without VUR (Group 2), VUR without RPS (Group 3), and healthy children without a history of hydronephrosis or UTI history (Group 4). After the initial evaluation, the participants were further divided into two more groups and re-evaluated: Children with RPS (Group 1 + 2), children without RPS (Group 3 + 4), children with VUR (Group 1 + 3), and children without VUR (Group 2 + 4). RESULTS: We found that urine pentraxin 3 (uPTX3) and uPTX3/Creatinine levels were significantly higher in the groups with renal scar with or without VUR than the ones without RPS [mean uPTX3, 3.5 pg/ml (min-max 0.0022-12.3668) vs. 2.2 pg/ml (min-max 0.0022-18.5868) and uPTX3/creatinine, 10.5 pg/mg (min-max 0.0035-51.1) vs. 5.8 pg/mg (min-max 0.0004-78.7), p < 0.01]. uPTX3 levels were not different among the groups with and without VUR. In addition, serum PTX3 levels were not different among the groups. CONCLUSIONS: We showed that urinary PTX3 increased only in patients with scarred kidneys. These results might be helpful to predict RPS due to past pyelonephritis.

Proteomic characterization of novel serum amyloid P component variants from human plasma and urine.

Serum amyloid P component (SAP) is a human plasma protein that has been widely studied for its influence on amyloid plaque formation and stabilization. SAP was characterized directly from human plasma and urine samples via novel affinity mass spectrometry-based proteomic technology that is able to readily discriminate between mass-altered protein variants. These analyses were able to identify several variants of SAP that have not been previously reported. These variants include microheterogeneity of the glycan structure, from the loss of one or both terminal sialic acid residues, as well as the loss of the C-terminal valine residue. Moreover, the analysis of urine allowed for the consistent identification of serum amyloid P component as a normal constituent of the urine proteome.