Chronic kidney disease (CKD) poses a significant global public health challenge, with environmental toxins potentially contributing to its prevalence. In Taiwan, where arsenic (As) contamination is endemic in certain areas, assessing its impact on renal health is crucial due to the country's high rates of unexplained CKD. This cross-sectional study assessed associations between urinary As species and early renal impairment biomarkers-the microalbumin-to-creatinine ratio (ACR) and β2-microglobulin (B2MG)-in 248 young Taiwanese adults (aged 20-29 years). We measured urinary As species (including arsenite [As3+], arsenate [As5+], monomethylarsonic acid [MMA], and dimethylarsinic acid [DMA]) and early renal impairment biomarkers (urinary microalbumin and B2MG levels). Median concentrations of urinary As3+, As5+, MMA, DMA, inorganic As (iAs), and the sum of inorganic and methylated As species (iSumAs) were 1.43, 1.02, 3.79, 31.53, 2.82, and 39.22 μg/g creatinine (Cre.), respectively. We also evaluated the first methylation ratio (FMR) and the second methylation ratio (SMR). After adjusting for potential confounding factors, a multivariate linear regression showed significant associations between B2MG and urinary As5+ (β = 0.299, 95% confidence interval [CI]: 0.113-0.485) and iAs (β = 0.281, 95% CI: 0.061-0.502) concentrations. A generalized additive model revealed non-linear relationships among As5+, iAs, and B2MG concentrations. Moreover, there were elevated risks associated with the highest tertile of B2MG concentrations compared to the highest tertile of urinary As5+ (odds ratio [OR] = 2.366, 95% CI: 1.196-4.682), MMA (OR = 1.917, 95% CI: 1.002-3.666), DMA (OR = 1.952, 95% CI: 1.015-3.753), and iSumAs (OR = 2.302, 95% CI: 1.182-4.483). These results indicated that exposure to As was associated with early renal impairment, particularly evidenced by increased urinary B2MG concentrations.
The Acute Promyelocytic Leukemia (APL) Asian Consortium analyzed a contemporaneous cohort of newly diagnosed patients with APL treated with and without frontline arsenic trioxide (ATO) in 6 centers. The objectives were to define the impact of ATO on early deaths and relapses and its optimal positioning in the overall treatment strategy. In a 21.5-year period, 324 males and 323 females at a median age of 45.5 years (range, 18.1-91.8; low/intermediate risk, n = 448; high risk, n = 199) were treated. Regimens included frontline all-trans retinoic acid (ATRA)/chemotherapy and maintenance with/without ATO (n = 436), ATRA/IV-ATO/chemotherapy (ATRA/IV-ATO; n = 61), and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; n = 150). The ATRA/chemotherapy group had significantly more frequent early deaths within 60 days (8.3% vs 3.3%; P = .05), inferior 60-day survival (91.7% vs 98.4%/96%; P < .001), inferior 5-year relapse-free survival (RFS; 76.9% vs 92.8%/97.8%; P < .001), and inferior 5-year overall survival (OS; 84.6% vs 91.4%/92.3%; P = .03) than ATO-containing groups (ATRA/IV-ATO and oral-AAA). The addition of oral-ATO maintenance partly mitigated the inferior 5-year RFS resulting from the omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance vs ATRA/chemotherapy/ATO maintenance vs ATRA/IV-ATO vs oral-AAA, 71.1% vs 87.9% vs 92.8% vs 97.8%; P < .001). The favorable survival impacts of ATO were observed in all risk groups. In conclusion, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. This trial was registered at www.clinicaltrials.gov as #NCT04251754.