Time to renal disease and end-stage renal disease in PROFILE: a multiethnic lupus cohort.
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).


RESULTS
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.
Alarcón
Graciela S
GS
Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America. graciela.alarcon@ccc.uab.edu
McGwin
Gerald
G
Petri
Michelle
M
Ramsey-Goldman
Rosalind
R
Fessler
Barri J
BJ
Vilá
Luis M
LM
Edberg
Jeffrey C
JC
Reveille
John D
JD
Kimberly
Robert P
RP
D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011647:Puerto Rico / Q000208:ethnology; D017452:Receptors, IgG / Q000235:genetics; D013781:Texas / Q000208:ethnology; D013997:Time Factors
C496124:FCGR3A protein, human; D006680:HLA Antigens; D017452:Receptors, IgG