Matthew Kennis, David Madison, North Foulon, Kayo Okamura, Zhibin He, Isadore Budnick, Mark Yoder, Brenda Griffin, Benjamin J. Kopecky, Melkon DomBourian, John T. Brinton, Samel Park, Warren H. Capell, Sarah Faubel
KEY POINTS: We identify a novel consequence of continuous KRT: clearance of thyroid-stimulating hormone and thyroid hormone. Severe non-thyroidal illness syndrome occurs in most of the continuous KRT patients and is persistent during continuous KRT. Notably, no patient achieved euthyroid status during continuous KRT therapy. BACKGROUND: AKI and ESKD requiring continuous KRT (CKRT) are associated with a high mortality rate. Solutes up to 40 kDa in size are amenable to CKRT clearance which includes thyroid-stimulating hormone (TSH; 28 kDa), free thyroxine (fT4; 0.78 kDa), and free triiodothyronine (fT3; 0.68 kDa). The effect of CKRT on TSH and thyroid hormone clearance, thyroid function, and the hypothalamic-pituitary-thyroid axis is unknown. METHODS: This prospective, single-center observational study enrolled 50 intensive care unit patients requiring CKRT and 50 control intensive care unit patients. Serum TSH, fT4, fT3, and reverse triiodothyronine were measured before and on days 1, 3, 8, and 14 after CKRT initiation and at the same time points relative to enrollment in control patients; effluent TSH, fT4, and fT3 were measured on days 1, 3, 8, and 14. Thyroid function status was adjudicated on days 1, 3, 8, and 14. Statistical analyses included employment of linear mixed modeling and time-dependent adjustments, and ANOVA with false discovery rate correction. RESULTS: Before and during CKRT, CKRT patients had lower fT4 and fT3 levels compared with controls, with a higher proportion of values below the normal reference range. TSH and fT4 were detected in the CKRT effluent, indicating clearance by CKRT. Severe and persistent non-thyroidal illness syndrome (NTIS) was seen in the CKRT cohort. No patient achieved euthyroid status while receiving CKRT. CONCLUSIONS: This is the first study to assess thyroid function and clearance of TSH and thyroid hormones during CKRT. We demonstrate that severe NTIS-characterized by low levels of fT4 and fT3-occurs in most of the CKRT patients. Furthermore, NTIS is persistent in patients receiving CKRT, which may be influenced by CKRT-mediated TSH and fT4 clearance. These novel complications may contribute to the high mortality rate observed in patients with either AKI or ESKD who receive CKRT.