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

Tamar Rubinstein; Milena Pitashny; Benjamin Levine; Noa Schwartz; Julie Schwartzman; Elena Weinstein; Jose M. Pego-Reigosa; Tim Y.T. Lu; David Isenberg; Anisur Rahman; Chaim Putterman

doi:10.1093/rheumatology/kep468

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

Tamar Rubinstein
, Milena Pitashny
, Benjamin Levine
, Noa Schwartz
, Julie Schwartzman
, Elena Weinstein
, Jose M. Pego-Reigosa
, Tim Y.T. Lu
, David Isenberg
, Anisur Rahman
, Chaim Putterman

Bar-Ilan University - Azrieli Faculty of Medicine

Albert Einstein College of Medicine

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

Abstract

Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis. Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort. uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort. 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.

Original language	English
Pages (from-to)	960-971
Number of pages	12
Journal	Rheumatology
Volume	49
Issue number	5
DOIs	https://doi.org/10.1093/rheumatology/kep468
State	Published - May 2010

Bibliographical note

Funding Information:
Funding: This publication was made possible by the CTSA Grants UL1 RR025750 and KL2 RR025749 and TL1 RR025748 from the National Centre for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its content is solely the responsibility of the authors and does not necessarily represent the official view of the NCRR or NIH. This research was also supported by an NIH grant AR48692 (to C.P.). T.R. and N.S. were supported by Medical Student Research Preceptorship Awards from the American College of Rheumatology Research and Education Foundation and grants from the New York Chapter of the Arthritis Foundation. J.M.P.-R. was supported by grants from the Instituto de Salud Carlos III (Spanish Ministry of Health and Consume) and the Fundación Española de Reumatología (Spanish Society of Rheumatology).

Funding

Funding: This publication was made possible by the CTSA Grants UL1 RR025750 and KL2 RR025749 and TL1 RR025748 from the National Centre for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its content is solely the responsibility of the authors and does not necessarily represent the official view of the NCRR or NIH. This research was also supported by an NIH grant AR48692 (to C.P.). T.R. and N.S. were supported by Medical Student Research Preceptorship Awards from the American College of Rheumatology Research and Education Foundation and grants from the New York Chapter of the Arthritis Foundation. J.M.P.-R. was supported by grants from the Instituto de Salud Carlos III (Spanish Ministry of Health and Consume) and the Fundación Española de Reumatología (Spanish Society of Rheumatology).

Funders	Funder number
Spanish Ministry of Health and Consume
National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases	R56AR048692
National Center for Research Resources
American College of Rheumatology Research and Education Foundation
Arthritis Foundation
Instituto de Salud Carlos III
Sociedad Española de Reumatología
Fundación Española de Reumatología

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title = "Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis.",

abstract = "Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis. Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort. uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort. 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.",

author = "Tamar Rubinstein and Milena Pitashny and Benjamin Levine and Noa Schwartz and Julie Schwartzman and Elena Weinstein and Pego-Reigosa, \{Jose M.\} and Lu, \{Tim Y.T.\} and David Isenberg and Anisur Rahman and Chaim Putterman",

note = "Funding Information: Funding: This publication was made possible by the CTSA Grants UL1 RR025750 and KL2 RR025749 and TL1 RR025748 from the National Centre for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its content is solely the responsibility of the authors and does not necessarily represent the official view of the NCRR or NIH. This research was also supported by an NIH grant AR48692 (to C.P.). T.R. and N.S. were supported by Medical Student Research Preceptorship Awards from the American College of Rheumatology Research and Education Foundation and grants from the New York Chapter of the Arthritis Foundation. J.M.P.-R. was supported by grants from the Instituto de Salud Carlos III (Spanish Ministry of Health and Consume) and the Fundaci{\'o}n Espa{\~n}ola de Reumatolog{\'i}a (Spanish Society of Rheumatology).",

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AU - Rubinstein, Tamar

AU - Pitashny, Milena

AU - Levine, Benjamin

AU - Schwartz, Noa

AU - Schwartzman, Julie

AU - Weinstein, Elena

AU - Pego-Reigosa, Jose M.

AU - Lu, Tim Y.T.

AU - Isenberg, David

AU - Rahman, Anisur

AU - Putterman, Chaim

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PY - 2010/5

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N2 - Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis. Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort. uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort. 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.

AB - Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis. Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort. uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort. 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.

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

Abstract

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