Thyroid hormone in the treatment of post-transplant acute tubular necrosis (ATN). A trial of thyroxine in acute renal failure.
Delayed graft function (DGF) in cadaver kidney transplants is a common problem and is often due to acute tubular necrosis (ATN). DGF in transplants may have a deleterious effect on long-term graft survival. Since thyroid hormone has been shown to hasten recovery from ATN in experimental models, we designed a trial to determine if a defined course of triiodothyronine (T3) would improve the short- or long-term outcome of patients with DGF in cadaveric transplants. A prospective, randomized, placebo controlled, double blind trial of T3 was carried out in patients with DGF in cadaveric renal transplants. End-points were percentage requiring dialysis, percentage recovering function, time to recovery and length of hospital stay. Long-term outcomes were percentage grafts functioning at 1 year and mean serum creatinine at 1 year. Forty-four patients were randomized to receive either T3 or placebo. Three patients were dropped from each group when early biopsies disclosed that DGF was due to rejection. The groups were well matched by age, cold ischemia time of the graft, and percentage reactivity to a random panel of antigens. Baseline thyroid function studies, including T3, reverse T3 (rT3), and thyroid stimulating hormone (TSH) levels, were similar between the two groups and typical of 'euthyroid-sick syndrome'. T3 had no effect on percentage requiring dialysis, time to recovery, percentage recovering function, or length of stay. At 1 year follow-up, graft function was similar in both groups and significantly lower than that seen in patients with good initial function. Thyroid hormone, given early in the course of DGF in cadaver kidney recipients, had no effect on the course of DGF. Long-term graft function is impaired in patients who experience post-transplant DGF compared to those who have good initial function. A trial of thyroxine in acute renal failure.
                Acute renal failure (ARF) remains a serious medical problem with a high mortality rate. Efforts to shorten the course of ARF might reduce this mortality. Since thyroxine has been shown in experimental models to shorten the course of ARF, we designed a trial to determine if a defined course of thyroxine would alter the course or change the mortality of clinical ARF.
                A prospective, randomized, placebo-controlled, double-blind trial of thyroxine was carried out in patients with ARF. End points were the percentage requiring dialysis, the percentage recovering renal function, time to recovery, and mortality.
                Fifty-nine patients were randomized to receive either thyroxine or placebo. The groups were well matched in terms of basal and entry creatinines, age, sex, APACHE II scores at entry, and percentage oliguric. Baseline thyroid functions, including T3, T4, rT3, and thyroid stimulating hormone (TSH) levels, were equal between the two groups and typical of patients with euthyroid sick syndrome. Thyroxine resulted in a progressive and sustained suppression of TSH levels in the treated group, but had no effect on any measure of ARF severity. Mortality was higher in the thyroxine group than the control group (43 vs. 13%) and correlated with suppression of TSH.
                In contrast to the beneficial effects seen in experimental ARF, thyroxine has no effect on the course of clinical ARF and could have a negative effect on outcome through prolonged suppression of TSH. Critically ill euthyroid sick patients should not be replaced with thyroid hormone.
We found a paucity of large, high quality studies to inform analysis of thyroid hormone interventions for the treatment of people with AKI. Current evidence suggested that thyroid hormone therapy may be associated with worse outcomes for patients with established AKI; therefore, its use for these patients should be avoided. The role of thyroid hormone therapy in preventing AKI has not been adequately investigated and may be considered in future clinical studies.