A composite urine biomarker reflects interstitial inflammation in lupus nephritis kidney biopsies

Zhang, Xiaolan; Nagaraja, Haikady N.; Nádasdy, Tibor; Song, Huijuan; McKinley, Alison M.; Prosek, Jason; Kamadana, Swapna; Rovin, Brad H.

doi:10.1038/ki.2011.354

Cited by 73 publications

(55 citation statements)

References 29 publications

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“…In the acute setting, NGAL appears to be a part of a protective anti-apoptotic mechanism that limits tubule cell damage and enhances proliferation (23). MCP-1 is induced by type I interferons and is known to be a predictive biomarker of LN flares and LN severity (5, 24). There is high expression of MCP-1, especially in the tubular epithelial cells (25) with oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults

Brunner

Bennett

Abulaban

et al. 2016

Arthritis Care & Research

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Background Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histological LN activity. Methods We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n=47) at the time of kidney biopsy. Histological LN activity was measured by the NIH Activity Index (NIH-AI) and the Tubulointerstitial Activity Index (TIAI). High LN-activity status (vs. moderate/low) was defined as NIH-AI scores > 10 (vs. ≤ 10) or TIAI scores >5 (vs. ≤ 5). RAIL algorithms that predicted LN-activityNIH-AI and LN-activityTIAI status were derived by stepwise multivariate logistical regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined. Results The differential excretion of six UBMs (NGAL, MCP-1, ceruloplasmin, adiponectin, hemopexin, KIM-1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activityNIH-AI status with >92% accuracy and LN-activityTIAI status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71 and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses. Conclusion The RAIL is a robust and highly accurate noninvasive measure of LN-activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation.

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Section: Discussionmentioning

confidence: 99%

Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults

Brunner

Bennett

Abulaban

et al. 2016

Arthritis Care & Research

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“…25,26 In fact, extensive Mø-rich interstitial infiltrates, 27,28 inflammation, tubular atrophy, and interstitial fibrosis are accurate morphologic predictors of a poor renal prognosis. 25,29,30 Thus, tracking molecules that mediate tubulointerstitial inflammation and injury are candidates for predicting renal disease outcomes in patients with SLE. We now show that increased serum or urine CSF-1 levels reflect the magnitude of CSF-1 expression in the tubules and Mø-rich inflammation in the interstitium and predict the onset, recurrence, and disease activity of LN.…”

Section: Discussionmentioning

confidence: 99%

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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“…Furthermore, in an effort to cast an even wider net, more comprehensive methods are now being used to identify such biomarkers, including microarray chips [38–40], proteomics [41], and combinations of markers that may together reflect disease activity more accurately than each component in isolation [42•,43,44,45•]. …”

Section: Diagnosis and Disease Monitoringmentioning

confidence: 99%

The pathogenesis, diagnosis and treatment of lupus nephritis

Schwartz

Goilav

Putterman

2014

Current Opinion in Rheumatology

114

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Purpose of review Renal involvement is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). In this review we provide an update on recent discoveries in the pathogenesis, diagnosis, and treatment of lupus nephritis (LN). Recent findings Localized long-lived plasma cells have been identified as playing an important role in LN. In addition, the roles of aberrant expression of microRNAs and pro-inflammatory cytokines have been explored. Early diagnosis is important for effective treatment and multiple biomarkers have been identified; however, none have been yet validated for clinical use. Biomarker panels may turn out to be more accurate than each individual component. Biologic agents for the treatment of LN are being studied, including Belimumab which was recently approved for non-renal SLE. Rituximab has not proven itself in large, placebo-controlled trials, although it is still being used in refractory cases of LN. Summary LN is a potentially devastating complication of SLE. Immune cells, cytokines, and epigenetic factors have all been recently implicated in LN pathogenesis. These recent discoveries may enable a paradigm shift in the treatment of this complex disease, allowing the tailoring of treatment to target specific pathogenic mediators at specific points in time in the progression of disease.

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A composite urine biomarker reflects interstitial inflammation in lupus nephritis kidney biopsies

Cited by 73 publications

References 29 publications

Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults

Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults

Colony-Stimulating Factor-1

The pathogenesis, diagnosis and treatment of lupus nephritis

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