Angiotensin II receptor agonist antibodies are associated with microvascular damage in lupus nephritis.

Angiotensin II type 1 receptor agonist antibodies (AT1R-AAs) have been associated with hypertension, atherosclerosis and vascular inflammation in human diseases. The aim of the study was to evaluate the prevalence of AT1R-AAs in active lupus nephritis (LN) patients and their association with vascular damage. One hundred and seven active LN patients underwent a complete clinical examination, measurement of AT1R-AAs, ambulatory blood pressure monitoring, carotid intima-media thickness measurement and morphometric analysis of subintimal fibrosis and medial hyperplasia of the vessels in the kidney tissue. Plasma AT1R-AAs were positive in 58 (54.2%) patients. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, complement C3 and C4 levels and titers of anti-dsDNA antibodies were higher in the group with positive AT1R-AAs compared with those with negative AT1R-AAs. The AT1R-AA titers correlated with anti-dsDNA antibody titers and with complement C3 and C4 serum levels. In the kidney biopsy, the percentage of subintimal fibrosis and the area of medial hyperplasia were greater in the AT1R-AA-positive patients. No differences in arterial pressure, carotid intima-media thickness and response to therapy were detected. In conclusion, AT1R-AAs are prevalent in active LN patients and are associated with histologic features of microvascular damage.

Prognostic significance of renal vascular pathology in lupus nephritis.

We performed a retrospective cohort analysis to define the prognostic significance of vascular lesions documented in renal biopsies of lupus nephritis patients. A total of 429 patients were segregated into five groups: (1) no vascular lesions (NVL), (2) arterial sclerosis (AS), (3) non-inflammatory necrotizing vasculitis (NNV), (4) thrombotic microangiopathy (TMA), and (5) true renal vasculitis (TRV). Renal outcomes were analyzed by Cox regression models, and correlations between vascular lesions and activity/chronicity scores were determined by Spearman's coefficients. A total of 200 (46.6%) had NVL, 189 (44.0%) AS, six NNV (1.4%), 23 (5.4%) TMA, and 11 (2.6%) TRV. Patients with NVL were younger, with higher renal function; patients with TMA and TRV had lower renal function and higher arterial pressure at baseline. Antiphospholipid syndrome and positive lupus anticoagulant were more frequently observed in the TMA group. Five-year renal survival was 83% for NVL, 63% for AS, 67% for NNV, 31% for TMA, and 33% for TRV. NNV and TRV were significantly correlated with activity scores, while AS and chronic TMA were correlated with chronicity scores. Renal vascular lesions are associated with renal outcomes but do not behave as independent factors. The addition of vascular lesions to currently used scores should be further explored.

Renal flare prediction and prognosis in lupus nephritis Hispanic patients.

We performed a retrospective cohort analysis focusing on lupus nephritis renal flare incidence and outcome predictors. One hundred and eighteen patients with biopsy-proven lupus nephritis were segregated by induction/maintenance regimes. The primary outcome was the proportion of patients experiencing renal flare. Secondary assessment included doubling of serum creatinine and development of end-stage renal disease. After a median follow-up of 31 months (interquartile range 21-46) from the date of response to induction therapy, 47 patients (39.8%) developed a renal flare. Azathioprine-maintained patients had a higher risk of renal flare compared with mycophenolate mofetil-maintained patients (hazard ratio 2.53, 95% confidence interval 1.39-4.59, p < 0.01). Age (hazard ratio 0.96, 0.92-0.99, p = 0.03), serum creatinine at presentation (hazard ratio 1.76, 1.13-2.76, p = 0.01), complete remission after induction therapy (hazard ratio 0.28, 0.14-0.56, p < 0.001) and azathioprine maintenance therapy (hazard ratio 4.78, 2.16-10.6, p < 0.001) were associated with renal flare on multivariate analysis. Ten patients progressed to end-stage renal disease (8.5%) by a median 32.5 months. Age (hazard ratio 0.88, 0.77-0.99, p = 0.05), complete remission after induction therapy (hazard ratio 0.08, 0.01-0.94, p = 0.04) and severe nephritic flare (hazard ratio 13.6, 1.72-107.7, p = 0.01) were associated with end-stage renal disease development. Azathioprine maintenance therapy is associated with a higher incidence of relapse in the Mexican-mestizo population. Younger age and nephritic flares predict development of end-stage renal disease.