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Authors

Graciela S. Alarcón, Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Gerald McGwin, Section of Trauma, Burns, and Critical Care, Department of Surgery, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Michelle Petri, Division of Rheumatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
Rosalind Ramsey-Goldman, Division of Rheumatology, Northwestern University School of Medicine, Chicago, Illinois, United States of America, 5 Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
Barri J. Fessler, Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Luis M. Vilá, Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
Jeffrey C. Edberg, Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
John D. Reveille, Division of Rheumatology, Department of Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of AmericaFollow
Robert P. Kimberly, Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America

Publication Date

10-1-2006

Journal

PLoS Medicine

Abstract

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE).

METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE.In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcgammaRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model.

CONCLUSIONS: Fcgamma receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.

Keywords

Adult, Cohort Studies, Disease Progression, Female, Genetic Predisposition to Disease, Genotype, HLA Antigens, Humans, Kidney Diseases, Kidney Failure, Chronic, Lupus Erythematosus, Systemic, Male, Middle Aged, Multivariate Analysis, Puerto Rico, Receptors, IgG, Texas, Time Factors

Comments

PMCID: PMC1626549

Link to article in PLoS

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