Free Thyroxine Level as an Independent Predictor of Infection-Related Mortality in Patients on Peritoneal Dialysis: A Prospective Multicenter Cohort Study

Abstract

BackgroundPrevious studies have reported the relationship between thyroid hormone levels and mortality in dialysis patients. However, little is known about the association of free thyroxine (fT4) and mortality in patients on peritoneal dialysis (PD). This study investigated the association between basal and annual variation in fT4 level and mortality in PD patients.MethodsPatients on maintenance PD were enrolled from a prospective multicenter cohort study in Korea; their serum triiodothyronine, fT4, and thyroid-stimulating hormone levels were measured 12 months apart. Patients with overt thyroid disease and those receiving thyroid hormone replacement therapy were excluded from the analysis. Patients were divided into two groups based on the median levels of fT4. The differences of all-cause, infection-related, and cardiovascular mortalities were analyzed between the two groups. The association of basal levels and annual variation with mortality was investigated with Kaplan–Meier curves and Cox proportional hazard models.ResultsAmong 235 PD patients, 31 (13.2%) deaths occurred during the mean follow-up period of 24 months. Infection (38.7%) was the most common cause of death. Lower basal fT4 levels were an independent predictor of all-cause and infection-related death (hazard ratio [HR] = 2.74, 95% confidence interval [CI] 1.27–5.90, P = 0.01, and HR = 6.33, 95% CI 1.16–34.64, P = 0.03, respectively). Longitudinally, patients with persistently lower fT4 levels during the 12-month period had significantly higher all-cause mortality than those with persistently higher levels (HR = 3.30, 95% CI 1.15–9.41, P = 0.03). The area under the receiver operating characteristic curve of fT4 for predicting all-cause and infection-related mortality was 0.60 and 0.68, respectively.ConclusionsfT4 level is an independent predictor of mortality and is especially attributable to infection in PD patients. This predictor was consistent when considering both baseline measurements and annual variation patterns. Close attention to infection in PD patients with relatively lower fT4 levels should be considered.

High Prevalence of Diastolic Dysfunction in Incident Patients on Peritoneal Dialysis: Association with Low Thyroid Hormones

“…However, we did not measure the amount of TH in the dialysis effluent to support this finding. No differences in plasma levels of TH were found in other studies [40] . Third, diabetes might affect cardiovascular system in other ways just as low TH would.…”

Thyroid hormones regulate both cardiovascular and renal mechanisms underlying hypertension

“…Studies held in patients on peritoneal dialysis revealed that low levels of T3 predict higher mortality in such patients and high levels of T3 decrease the risk of death 80 . T4 demonstrated the same trend in another study on peritoneal dialysis patients 81 …”

Thyroid Functional Disease and Mortality in a National Peritoneal Dialysis Cohort

“…Although three small studies have shown that low T 3 and/or T 4 levels are associated with higher mortality in PD patients, inference from these studies is limited by their 1) exclusion of patients with known thyroid functional disease (25) or biochemical evidence of overt hypothyroidism or hyperthyroidism (25)(26)(27), or 2) reliance upon thyroid functional metrics confounded by mortality determinants (ie, T 3 levels are influenced by malnutrition, inflammation, and uremia) (28 -30) or that have impaired performance in advanced CKD (ie, in low protein states or conditions where circulating substances such as uremic toxins impair hormone-protein binding, routinely-used free T 4 assays may result in spurious levels) (8). Although some TSH alterations may be observed in uremia (31,32), it is the most sensitive and specific metric of thyroid function given its negative logarithmic association with T 3 /T 4 (14).…”