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Abstract Background SLE manifestations after ESRD may be underdiagnosed and undertreated, contributing to increased morbidity and mortality. Whether specific symptoms persist after ESRD or a shift towards new manifestations occurs has not been extensively studied, especially in the non-Caucasian patients in the United States. In addition, hydroxychloroquine (HCQ) prescribing patterns post-ESRD have not been described. The objective of this study was to assess lupus activity and HCQ prescribing before and after ESRD development. Knowledge gained from this study may aid in the identification of SLE manifestations and improve medication management post-ESRD. Methods We performed a retrospective cohort study of SLE patients with incident ESRD between 2010 and 2017. SLE-related symptoms, serologic markers of disease activity, and medication use were collected from medical records before and after ESRD development. Results Fifty-nine patients were included in the study. Twenty-five (43%) patients had at least one clinical (non-renal) SLE manifestation documented within 12 months before ESRD. Of them, 11/25 (44%) continued to experience lupus symptoms post-ESRD; 9 patients without clinical or serological activity pre-ESRD developed new symptoms of active SLE. At the last documented visit post-ESRD, 42/59 (71%) patients had one or more clinical or serological markers of lupus activity; only 17/59 (29%) patients achieved clinical and serological remission. Thirty-three of 59 (56%) patients had an active HCQ prescription at the time of ESRD. Twenty-six of the 42 (62%) patients with active SLE manifestations post-ESRD were on HCQ. Patients who continued HCQ post-ESRD were more likely to be followed by a rheumatologist (26 [87%] vs 17 [61%], p = 0.024), had a higher frequency of documented arthritis (10 [32%] vs 1 [4%], p = 0.005), CNS manifestations (6 [20%] vs 1 [4%], p = 0.055), and concurrent immunosuppressive medication use (22 [71%] vs 12 [43%], p = 0.029). Conclusions Lupus activity may persist after the development of ESRD. New onset arthritis, lupus-related rash, CNS manifestations, low complement and elevated anti-dsDNA may develop. HCQ may be underutilized in patients with evidence of active disease pre- and post ESRD. Careful clinical and serological monitoring for signs of active disease and frequent rheumatology follow up is advised in SLE patients both, pre and post-ESRD.