Incident Lupus Nephritis. Predictive and Protective Factors - - PowerPoint PPT Presentation

Incident Lupus Nephritis. Predictive and Protective Factors

Ana-Maria Orbai, MD Rheumatology Fellow Johns Hopkins University School of Medicine

Background

• Lupus nephritis (LN) develops in 50 to 70%
• f patients with systemic lupus erythematosus

(SLE) in their lifetime and is a major cause of morbidity (Petri 1991, Bastian 2002, Pons-Estel 2004)

• Early treatment of LN is the single most

important predictor

• f

preserving renal function (Austin 1986)

Background –ctd.

• Hydroxychloroquine (HCQ) and LN:

–delayed LN progression (LUMINA Study Group, Arthritis &

Rheumatism 2009)

–predicted LN remission at 12 months on immunosuppressive therapy (Kasitanon 2006)

Background – ctd.

• ACE inhibitors and LN:

– delayed LN onset independent of blood pressure reduction (S. Duran-Barragan,

Rheumatology 2008)

Aims

• 1. To study if HCQ, ACE inhibitor or the

combination of the two, are associated with a lower incidence of LN

• 2. To

identify predictor variables for incident LN

Novelty

• HCQ has not been studied in the

prevention of LN

Hypotheses

• 1. HCQ protects SLE patients from

developing LN

• 2. HCQ and ACE inhibitors have added

benefit in protecting SLE patients from LN

Methods

• Patients:

–JH lupus cohort: longitudinal study of

• utcomes in SLE patients from the

Baltimore area –quarterly follow-up

• Setting: academic center
• Design: prospective cohort

Outcome

• New onset LN:
• Proteinuria
• 3 or 4+ on dipstick urinalysis or urine

protein >500 mg on spot urine or 24h collection

• reproducible at 3 months
• Biopsy diagnosis

JH Lupus Cohort Patients, 2047 No renal involvement, 1300 Renal involvement at cohort entry, 747 Incident proteinuria No proteinuria Lupus Nephritis Other pathology No biopsy

1986 Present

Statistical analysis

• Estimation of relative risk of incident LN with

the variable of interest (including HCQ, ACE inhibitor, both)

• Pooled logistic regression to estimate the

association between characteristics and rates, adjusting for confounding by other variables

Statistical analysis – ctd.

• Other covariates:

–Demographics –Comorbidities (HTN, diabetes, hypercholesterolemia) –Clinical and serologic variables –Steroid use –NSAID use –Immunosuppressant use

Limitations

• HCQ blood levels were not measured (to

account for inter-individual pharmacokinetic variability or non-adherence)

• Single center study
• Academic center

Future directions

• Prevention of LN would have significant

impact on the morbidity of patients with SLE

• The effects of HCQ could be studied in a

randomized controlled trial of different dose ranges

Acknowledgements

• Michelle Petri M.D. M.P.H., Director of the Hopkins

Lupus Cohort

• Laurence S. Magder Ph.D. M.P.H., Department of

Epidemiology and Public Health, University of Maryland

Acknowledgements

• Tariq Shafi M.D. M.H.S., Division of Nephrology, Johns

Hopkins University

• Mark Woodward Ph.D., Department of Epidemiology,

Bloomberg School of Public Health

Members of my small group

Evelyn Gathecha M.D. Justin Lafreniere M.D. Tamorah Lewis M.D. Melanie Nies M.D. Gaurav Raman M.D.