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Background: Acculturation affects health, but it has never been studied with kidney disease., Methods: We studied the association of language spoken at home, generation and birth place with kidney function among Hispanics and Chinese in the Multi-Ethnic Study of Atherosclerosis (n = 2999). Kidney function was determined by cystatin C (eGFRcys) and albumin/creatinine ratio (ACR). We evaluated mediators in models: Model 1 = age, sex, income, education; Model 2 = Model 1 + behaviors; and Model 3 = Model 1 + comorbidities., Results: Among Hispanics, speaking mixed Spanish/English was significantly associated with lower eGFRcys (- 2.83 mL/min/1.73 m(2), - 5.69-0.04) and higher ACR (RD 40%, 17-68%) compared with speaking Spanish only; this was mildly attenuated by behaviors (- 2.29, - 5.33-0.75; RD 42%, 18-72%) but not comorbidities (- 3.04, - 5.83 to - 0.23); RD 35%, 14-59%). US-born Hispanics had lower eGFRcys compared with foreign-born Hispanics [1.83 mL/min/1.73 m(2) lower (0.97-1.31) for Generation 1; 1.37 mL/min/1.73 m(2) lower (0.75-1.57) for Generation ≥ 2]. In contrast, Chinese who spoke any English had higher eGFRcys (2.53, 95% CI: - 1.70-6.78), but similar ACR (RD - 5%, 95% CI: - 26-23%) compared with those speaking Chinese only, but associations were not statistically significant., Conclusion: Higher acculturation was associated with worse kidney function in Hispanics, mediated perhaps by behavioral factors but not comorbidities. Associations may be in the opposite direction among Chinese. Future studies are needed to elucidate these mechanisms.