Urinary high-mobility group box-1 associates specifically with lupus nephritis class v

N. R. Jog, Irene Blanco, I. Lee, Chaim Putterman, R. Caricchio

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Introduction High-mobility group box 1 protein (HMGB-1) has been implicated in the pathogenesis of lupus nephritis (LN). There is increased HMGB-1 expression in the kidneys and increased levels are observed in serum and urine of patients with LN. This study was performed to determine whether the increased urinary HMGB-1 was specific for active lupus or secondary to renal damage. Methods Urine from 61 lupus patients (32 had active LN and 29 had systemic lupus erythematosus (SLE) with no evidence of LN) and 14 control proteinuric patients (all with hypertension and eight also with diabetes) were included in this study. HMGB-1 was detected by Western blot. Urine protein was normalized to urine creatinine to account for volume of the specimen. Results Median normalized urine HMGB-1 levels were significantly elevated in LN patients compared to lupus patients without kidney disease (53.81 vs 9.46, p < 0.001). A difference in median levels was seen between LN classes, with a significant difference between proliferative and membranous disease (33.4 vs 138.8, p = 0.003). Urine protein to urine creatinine ratio (P/C) correlated with urinary HMGB-1 (r = 0.52, p < 0.001), but across the classes this was true only for membranous disease (r = 0.71, p = 0.022, proliferative, p = 0.63; mixed, p = 0.34). Conclusions HMGB-1 is elevated in the urine of patients with active LN. Levels are associated with LN class, and higher levels of urinary HMGB-1 are seen in patients with class V when compared to both proliferative and mixed classes. Therefore, urinary HMGB-1 may be suggestive of membranous LN and warrants further evaluation in a large lupus cohort.

Original languageEnglish (US)
Pages (from-to)1551-1557
Number of pages7
JournalLupus
Volume25
Issue number14
DOIs
StatePublished - Dec 1 2016

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HMGB1 Protein
Lupus Nephritis
Urine
Creatinine
Kidney
Kidney Diseases
Systemic Lupus Erythematosus
Proteins
Western Blotting
Hypertension

Keywords

  • HMGB-1
  • lupus nephritis
  • membranous nephritis

ASJC Scopus subject areas

  • Rheumatology

Cite this

Urinary high-mobility group box-1 associates specifically with lupus nephritis class v. / Jog, N. R.; Blanco, Irene; Lee, I.; Putterman, Chaim; Caricchio, R.

In: Lupus, Vol. 25, No. 14, 01.12.2016, p. 1551-1557.

Research output: Contribution to journalArticle

Jog, N. R. ; Blanco, Irene ; Lee, I. ; Putterman, Chaim ; Caricchio, R. / Urinary high-mobility group box-1 associates specifically with lupus nephritis class v. In: Lupus. 2016 ; Vol. 25, No. 14. pp. 1551-1557.
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abstract = "Introduction High-mobility group box 1 protein (HMGB-1) has been implicated in the pathogenesis of lupus nephritis (LN). There is increased HMGB-1 expression in the kidneys and increased levels are observed in serum and urine of patients with LN. This study was performed to determine whether the increased urinary HMGB-1 was specific for active lupus or secondary to renal damage. Methods Urine from 61 lupus patients (32 had active LN and 29 had systemic lupus erythematosus (SLE) with no evidence of LN) and 14 control proteinuric patients (all with hypertension and eight also with diabetes) were included in this study. HMGB-1 was detected by Western blot. Urine protein was normalized to urine creatinine to account for volume of the specimen. Results Median normalized urine HMGB-1 levels were significantly elevated in LN patients compared to lupus patients without kidney disease (53.81 vs 9.46, p < 0.001). A difference in median levels was seen between LN classes, with a significant difference between proliferative and membranous disease (33.4 vs 138.8, p = 0.003). Urine protein to urine creatinine ratio (P/C) correlated with urinary HMGB-1 (r = 0.52, p < 0.001), but across the classes this was true only for membranous disease (r = 0.71, p = 0.022, proliferative, p = 0.63; mixed, p = 0.34). Conclusions HMGB-1 is elevated in the urine of patients with active LN. Levels are associated with LN class, and higher levels of urinary HMGB-1 are seen in patients with class V when compared to both proliferative and mixed classes. Therefore, urinary HMGB-1 may be suggestive of membranous LN and warrants further evaluation in a large lupus cohort.",
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N2 - Introduction High-mobility group box 1 protein (HMGB-1) has been implicated in the pathogenesis of lupus nephritis (LN). There is increased HMGB-1 expression in the kidneys and increased levels are observed in serum and urine of patients with LN. This study was performed to determine whether the increased urinary HMGB-1 was specific for active lupus or secondary to renal damage. Methods Urine from 61 lupus patients (32 had active LN and 29 had systemic lupus erythematosus (SLE) with no evidence of LN) and 14 control proteinuric patients (all with hypertension and eight also with diabetes) were included in this study. HMGB-1 was detected by Western blot. Urine protein was normalized to urine creatinine to account for volume of the specimen. Results Median normalized urine HMGB-1 levels were significantly elevated in LN patients compared to lupus patients without kidney disease (53.81 vs 9.46, p < 0.001). A difference in median levels was seen between LN classes, with a significant difference between proliferative and membranous disease (33.4 vs 138.8, p = 0.003). Urine protein to urine creatinine ratio (P/C) correlated with urinary HMGB-1 (r = 0.52, p < 0.001), but across the classes this was true only for membranous disease (r = 0.71, p = 0.022, proliferative, p = 0.63; mixed, p = 0.34). Conclusions HMGB-1 is elevated in the urine of patients with active LN. Levels are associated with LN class, and higher levels of urinary HMGB-1 are seen in patients with class V when compared to both proliferative and mixed classes. Therefore, urinary HMGB-1 may be suggestive of membranous LN and warrants further evaluation in a large lupus cohort.

AB - Introduction High-mobility group box 1 protein (HMGB-1) has been implicated in the pathogenesis of lupus nephritis (LN). There is increased HMGB-1 expression in the kidneys and increased levels are observed in serum and urine of patients with LN. This study was performed to determine whether the increased urinary HMGB-1 was specific for active lupus or secondary to renal damage. Methods Urine from 61 lupus patients (32 had active LN and 29 had systemic lupus erythematosus (SLE) with no evidence of LN) and 14 control proteinuric patients (all with hypertension and eight also with diabetes) were included in this study. HMGB-1 was detected by Western blot. Urine protein was normalized to urine creatinine to account for volume of the specimen. Results Median normalized urine HMGB-1 levels were significantly elevated in LN patients compared to lupus patients without kidney disease (53.81 vs 9.46, p < 0.001). A difference in median levels was seen between LN classes, with a significant difference between proliferative and membranous disease (33.4 vs 138.8, p = 0.003). Urine protein to urine creatinine ratio (P/C) correlated with urinary HMGB-1 (r = 0.52, p < 0.001), but across the classes this was true only for membranous disease (r = 0.71, p = 0.022, proliferative, p = 0.63; mixed, p = 0.34). Conclusions HMGB-1 is elevated in the urine of patients with active LN. Levels are associated with LN class, and higher levels of urinary HMGB-1 are seen in patients with class V when compared to both proliferative and mixed classes. Therefore, urinary HMGB-1 may be suggestive of membranous LN and warrants further evaluation in a large lupus cohort.

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