Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis

Rubinstein, Tamar; Pitashny, Milena; Levine, Benjamin; Schwartz, Noa; Schwartzman, Julie; Weinstein, Elena; Pego-Reigosa, José María; Lu, Tim; Isenberg, David; Rahman, Anisur; Putterman, Chaim

doi:10.1093/rheumatology/kep468

Cited by 100 publications

(93 citation statements)

References 27 publications

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“…20,21 In a cross-sectional single-cohort study using a modest sampling of patients with LN, we previously reported that serum or urine CSF-1 was elevated in patients with LN compared with those who had other noninflammatory kidney diseases and healthy controls; in that study we also found that amplified CSF-1 levels correlated with more severe clinical disease activity. 8 Another study indicated that flares were more likely in patients with persistently increased regulated upon activation normal T cell expressed and presumably secreted or M-CSF (also known as CSF-1) levels in urine after induction therapy using group survival curve analysis.…”

Section: Discussionmentioning

confidence: 62%

“…Urinary, but not serum, neutrophil gelatinase-associated lipocalin predicted renal flares in patients with LN and is reportedly a more sensitive forecaster of flares in patients with a history of LN than are dsDNA antibody titers, but its predictive value was not superior to that of C3c and C4 in patients with LN. 21,24 By comparison, our longitudinal analysis of individual patients suggests that elevated serum and urine CSF-1 levels may predict LN recurrences, and elevated serum CSF-1 may herald the onset of LN in advance of glomerular dysfunction and multiple clinical LN measures, including dsDNA. Thus, our current study indicates that monitoring serum or urine CSF-1 offers a potential individualized approach to the management of patients with LN.…”

Section: Discussionmentioning

confidence: 97%

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Colony-Stimulating Factor-1

Menke¹,

Amann

Cavagna

et al. 2015

Journal of the American Society of Nephrology

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A noninvasive means to predict the onset and recurrence of lupus nephritis (LN) before overt renal injury is needed to optimize and individualize treatment. Colony-stimulating factor-1 (CSF-1) is expressed by kidney tubules at the onset of LN, increases with disease progression, and spills into the circulation in lupus-prone mice. We tested the hypothesis that amplified expression of CSF-1 detected in the serum or urine correlates with intrarenal CSF-1 expression and histopathology (increased macrophage accumulation, activity indices) and clinical kidney disease activity and predicts the onset and recurrence of nephritis in patients with systemic lupus erythematosus (SLE). We found increased serum or urine CSF-1 levels in patients with cutaneous, serositis, and musculoskeletal disease; however, the increase in CSF-1 levels was far greater in LN. Moreover, an elevation in serum or urine CSF-1 levels correlated with increasing intrarenal CSF-1 expression and histopathology. By longitudinally tracking patients, we found that elevated serum CSF-1 heralded the initial onset of disease, and a rise in serum or urine CSF-1 predicted recurrences of LN before clinical evidence of glomerular dysfunction and conventional serologic measures, even in patients with other manifestations of SLE. These findings indicate that serial monitoring for a rise in serum or urine CSF-1 levels in patients with SLE reflects kidney histopathology and may predict renal disease activity and the onset and recurrence of LN more accurately than conventional laboratory measures. 26: 379-389, 201526: 379-389, . doi: 10.1681 Lupus nephritis (LN) is the main cause of morbidity and mortality for patients with systemic lupus erythematosus (SLE). 1 Despite current treatment, ESRD is frequent in patients with LN (up to 26%). 2 Moreover, relapses or flares of LN are common (27%-66%) and contribute to mortality. 3,4 Current methods for diagnosing LN in patients with SLE include proteinuria, active sediment, and a decrease in GFR with confirmation by a renal biopsy. 5 Clearly, identification of a biomarker that heralds LN before structural renal damage and the loss of renal function would provide a window to treat early and obviate renal tissue injury. J Am Soc NephrolColony-stimulating factor-1 (CSF-1) is largely responsible for Mø development, survival, proliferation, and activation. 6 We hypothesize that amplified expression of CSF-1 in serum or urine reflects the magnitude of intrarenal CSF-1 and histopathology, correlates with LN clinical disease activity, and heralds the onset and recurrence of LN.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 97%

Colony-Stimulating Factor-1

Menke¹,

Amann

Cavagna

et al. 2015

Journal of the American Society of Nephrology

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“…Validation in large longitudinal studies that also include recently described urinary biomarkers for disease activity in childhood LN [4,[36][37][38], correlations with the activity and chronicity scores in renal biopsy, and lupus Fig. 4 High levels of complement split products in active LN.…”

Section: Discussionmentioning

confidence: 99%

Markers of childhood lupus nephritis indicating disease activity

et al. 2010

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Current treatment regimens for childhood lupus nephritis (LN) are associated with significant side-effects and toxicity in vulnerable phases of growth and development. The paucity of biomarkers particularly in childhood impedes the appropriate clinical management and the development of new therapeutics. We analyzed markers of immune system (BAFF, RANTES), complement (Bb, C1q, C3d-CIC, C5a) and endothelial cell activation (sVCAM-1) in children with LN (n=22, mean age 14.8±4.7 years), nephrotic syndrome (n =13) and age-matched healthy controls (n=20) to define parameters that correlate with LN activity. Complement fragments of the alternative (Bb, p=0.0004) classical (C3d-CIC, p<0.0001) and common pathway (C5a, p<0.0001) and the levels of BAFF (p< 0.0001), RANTES (p=0.0002) and sVCAM-1 (p=0.0004) were significantly higher in active compared to inactive LN. Activation of complement was associated with the occurrence of anti-C1q antibodies and reduced complement

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“…Potential biomarkers include IL-6 (2), IL-18 (3), MCP-1 (4), VCAM-1 (5, 6), NGAL (7,8), and TWEAK (9,10). Indeed urine may be by far the best source for screening biomarkers for kidney diseases for several reasons.…”

Section: Systemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

“…Given the fact that ϳ60% of lupus patients eventually develop kidney disease (1), there is an urgent need to find solutions to these challenges. In recent years, there have been several studies demonstrating association of urine biomarkers with lupus nephritis, including CSF-1 (28), ICAM-1 (6); NGAL (8) , FIG. 4.…”

Section: Urinary Angiostatin Reflects Renal Chronicity Changes In Lupmentioning

confidence: 99%

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis

Han

et al. 2013

Molecular & Cellular Proteomics

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There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ϳ280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n ‫؍‬ 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r ‫؍‬ 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin. Molecular & Cellular

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Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis

Abstract: uNGAL predicts renal flare in patients with a history of biopsy-proven nephritis with high sensitivity and specificity. Furthermore, uNGAL is a more sensitive and specific forecaster of renal flare in patients with a history of lupus nephritis than anti-dsDNA antibody titres.

Cited by 100 publications

References 27 publications

Colony-Stimulating Factor-1

Colony-Stimulating Factor-1

Markers of childhood lupus nephritis indicating disease activity

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis

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