RESUMEN
Background: Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). Interstitial fibrosis/tubular atrophy (IFTA) on kidney biopsies strongly predicts progression to end-stage renal disease. However, factors associated with progression of IFTA are not known. The objective of this study was to evaluate the demographic, clinical, and histopathological factors at the time of index kidney biopsies that are associated with worsening IFTA on repeat biopsies. Methods: Patients with LN Class I to V or mixed LN on index biopsies who underwent a clinically indicated repeat biopsy between 2004 and 2020 were identified. None-mild IFTA was defined as < 25% acreage of the interstitium affected by fibrosis and atrophy, and moderate-severe IFTA was defined as ≥ 25% of the interstitium affected. Patients with none-mild IFTA on index biopsies who progressed to moderate-severe IFTA on repeat biopsies were defined as progressors. Patients with none-mild IFTA on both biopsies were defined as non-progressors. Results: Seventy-two patients who underwent clinically indicated repeat kidney biopsies were included, and 35 (49%) were identified as progressors. Compared to non-progressors, progressors had a higher proportion of proliferative LN (20 [57%] vs. 6 [17%], p = 0.002) and crescents (9 [26%] vs. 3 [8%], p = 0.045) on index biopsies. There was no difference regarding the time to repeat biopsy or the baseline characteristics, including eGFR, presence of hypertension and diabetes, urine protein to creatinine ratio, or the initial treatments. Conclusions: Proliferative LN and the presence of crescents on index biopsies were associated with subsequent IFTA progression on repeat biopsies. This association indicates that glomerular damage is one of the major drivers of tubulointerstitial scarring in SLE. IFTA progression may, in turn, be the driving factor of poor treatment response and progression to chronic kidney disease.
RESUMEN
OBJECTIVE: To determine whether hydroxychloroquine (HCQ) dose is associated with adverse cardiac outcomes in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE taking HCQ and with ≥1 echocardiogram followed at a tertiary care center in the Bronx, New York between 2005 and 2021 were included. The HCQ weight-based dose at the HCQ start date was the main exposure of interest. The outcome was incident all-cause heart failure with reduced ejection fraction (HFrEF), life-threatening arrhythmia, or cardiac death. We used Fine-Gray regression models with death as a competing event to study the association of HCQ dose with the outcome. Due to a significant interaction between smoking and HCQ exposure, models were stratified by smoking status. Propensity score analysis was performed as a secondary analysis. RESULTS: Of 294 patients, 37 (13%) developed the outcome over a median follow-up time of 7.9 years (interquartile range [IQR] 4.2-12.3 years). In nonsmokers (n = 226), multivariable analysis adjusted for age, body mass index, hypertension, chronic kidney disease, diabetes mellitus, and thromboembolism showed that higher HCQ weight-based doses were not associated with an increased risk of the outcome (subdistribution hazard ratio [HR] 0.62 [IQR 0.41-0.92], P = 0.02). Similarly, higher baseline HCQ doses were not associated with a higher risk of the outcome among smokers (n = 68) (subdistribution HR 0.85 [IQR 0.53-1.34] per mg/kg, P = 0.48). Propensity score analysis showed comparable results. CONCLUSION: Higher HCQ doses were not associated with an increased risk of HFrEF, life-threatening arrhythmia, or cardiac death among patients with SLE and may decrease the risk among nonsmokers.