Angiotensin-II Receptor Antibodies Blockade With Losartan in Patients With Lupus Nephritis

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran40 enrolled

Overview

Antibodies directed against angiotensin-II receptor (AT1-Ab) are agonist antibodies previously studied in human diseases such as preeclampsia, transplantation and scleroderma. They act by binding to the AT1 receptor and their effects can be blocked with the use of angiotensin receptor blockers (ARB). In this randomized open clinical trial the investigators will study the effect of the blockade of AT1-Ab with losartan in carotid intima-media thickness progression in patients with lupus nephritis compared to patients treated with enalapril.

Angiotensin-II type 1 receptor antibodies (AT1R-Ab) are agonist antibodies directed against the second loop of the AT1 receptor. These antibodies have been studied in human diseases such as preeclampsia, transplantation and scleroderma. A previous study from the investigators' group found an elevated prevalence of AT1R-Ab in patients with lupus nephritis. As these antibodies have been linked to atherosclerosis development this open randomized clinical trial was designed to evaluate the effect of AT1R-Ab blockade with losartan compared to the use of enalapril in the progression of carotid intima-media thickness (CIMT) in patients with active lupus nephritis. Biopsy-proven lupus nephritis patients who tested positive for AT1R-Ab will be performed a CIMT measurement by Doppler ultrasound at the time of the biopsy and then at 12-months follow up. The primary outcome will be the change in the CIMT in the course of 12 months in both groups.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Atherosclerosis

Eligibility

Sex: ALLMin age: 16 YearsMax age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed consent form for the study * Biopsy-proven lupus nephritis with proteinuria \> 1.5g/g by 24 hour urine protein to creatinine ratio * Need for immunosuppressive induction to remission therapy according to the treatment physician * Systemic lupus erythematosus diagnosis based on at least 4 American College of Rheumatology criteria * Age between 16 and 50 years Exclusion Criteria: * Patient does not want to participate in the study * Comorbid disease such as diabetes mellitus with macro/microangiopathy, previous diagnosis of hypertension \>5 years, scleroderma * Comorbid findings in the histopathological analysis of the renal biopsy

Outcomes

Primary Outcomes

Carotid intima-media thickness change after 12 months of the intervention

Change in carotid intima-media thickness from baseline thickness at study entry to 12 months of follow up measured by Doppler ultrasound

Time frame: 12 months

Secondary Outcomes

Response to treatment

Response to immunosuppressive treatment at 12 months

Time frame: 12 months

Arterial pressure

Arterial pressure control recorded by 24-hour ambulatory blood pressure

Time frame: 12months