Effect of Continuous Kidney Replacement Therapy (CRKT) on Thyroid Function

Background: Thyroxine (T4) and triiodothyronine (T3) are low molecular weight proteins (0.78 and 0.65kDa, respectively) amenable to removal by CKRT. Herein, we quantified T3/T4 clearance during CKRT and tested the hypothesis that CKRT would affect the hypothalamic-pituitary-thyroid (HPT) axis and cause a rise in serum thyroid stimulating hormone (TSH). Methods: In 24 patients undergoing continuous veno-venous hemodialysis, we measured CKRT effluent and serum levels of TSH, free T4 (FT4), free T3 (FT3), and reverse T3 (rT3) on Days 1, 3, 8 and 14 of CKRT. Baseline TSH and FT4 was measured <12 hours prior to CKRT initiation. In all cases, fresh samples were measured in the clinical lab. On each day of CKRT, sieving coefficient (SCx=[x]effluent/[x]serum), clearance (liters cleared=SCx*total effluent volume in prior 24 hours), and Sequential Organ Failure Assessment (SOFA) scores were calculated. Thyroid function tests were interpreted by an endocrinologist using prespecified definitions of euthyroid sick syndrome (ESS) and hypothyroidism. Results: Mean SC of TSH, FT4, and FT3 was 0.15 (n=48), 0.27 (n=46), and 1.04 (n=49), respectively and did not change between days on CKRT. SOFA scores were similar on each day. Serum TSH was higher on D8 vs. D3, D8 vs. D1, D8 vs. Pre-CKRT and D3 vs. D1 (Figure 1A). Serum T4 decreased on D3 and D1 of CKRT, relative to pre-CRKT (Figure 1B). TSH, FT4, and FT3 clearance is shown in Figure 1E-F. One patient met criteria for hypothyroidism, with the remaining patients in various stages of ESS. Conclusion: T3 and T4 removal occurs during CKRT. To our knowledge this is the first report to quantify T3 and T4 removal during CKRT and the first to describe the development of hypothyroidism after CKRT initiation (n=1). Even in patients with ESS (n=23), a physiologic effect of T3 and T4 removal on the HPT axis is suggested by the significant rise in TSH. These data suggest that hypothyroidism is a novel complication of CKRT.