Thyroid Functional Disease and Mortality in a National Peritoneal Dialysis Cohort

Abstract

Context and objective: End-stage renal disease patients have a higher risk of thyroid disease compared with those without kidney disease. Although thyroid dysfunction is associated with higher death risk in the general population and those undergoing hemodialysis, little is known about the effect of thyroid disease upon mortality in patients treated with peritoneal dialysis (PD).

Design, setting, participants, and main outcome: We examined the association of thyroid status, assessed by serum TSH, with all-cause mortality among PD patients from a large national dialysis organization who underwent one or more TSH measurements over 5 years (January 2007 to December 2011). Thyroid status was categorized as overt-hyperthyroid, subclinical-hyperthyroid, low-normal, high-normal, subclinical-hypothyroid, and overt-hypothyroid range (TSH < 0.1, 0.1–<0.5, 0.5–<3.0, 3.0–<5.0, 5.0–<10.0, and ≥10.0 mIU/L, respectively). We examined the association between TSH and mortality using case mix–adjusted time-dependent Cox models to assess short-term thyroid function–mortality associations and to account for changes in thyroid function over time.

Results: Among 1484 patients, 7 and 18% had hyperthyroidism and hypothyroidism, respectively, at baseline. We found that both lower and higher time-dependent TSH levels were associated with higher mortality (reference: TSH, 0.5-<3.0 mIU/L): adjusted hazard ratios (95% confidence intervals) 2.09 (1.08-4.06), 1.53 (0.87-2.70), 1.05 (0.75-1.46), 1.63 (1.11-2.40), and 3.11 (2.08-4.63) for TSH levels, <0.1, 0.1-<0.5, 0.5-<3.0, 3.0-<5.0, 5.0-<10.0, and ≥10.0 mIU/L, respectively.

Conclusion: Time-dependent TSH levels < 0.1 mIU/L and ≥ 5.0 mIU/L were associated with higher mortality, suggesting hyper- and hypothyroidism carry short-term risk in PD patients. Additional studies are needed to determine mechanisms underlying the thyroid dysfunction-mortality association, and whether normalization of TSH with treatment ameliorates mortality in this population.

Figures

Figure 1.

Association between time-dependent TSH category with all-cause mortality in peritoneal dialysis patients. Minimally adjusted model adjusted for patient's calendar quarter of entry into the cohort. Case mix–adjusted model adjusted for covariates in the minimally adjusted model, as well as age, sex, race/ethnicity, and baseline diabetes status. Expanded case mix + laboratory test–adjusted model adjusted for covariates in the case-mix model, as well as vintage, cause of ESRD, baseline comorbidities including CHF and atherosclerotic disease, serum albumin, serum bicarbonate, and residual kidney function.

Figure 2.

Association between continuous time-dependent TSH gradations and all-cause mortality in peritoneal dialysis patients. Figures present hazard ratios (short-dashed lines indicate 95% CIs) for TSH analyzed as a spline with knots at the 33rd and 66th percentiles of observed values (TSH levels 1.8 mIU/L and 3.5 mIU/L, respectively). A histogram of observed time-dependent TSH values and a hazard reference ratio of 1 (horizontal solid line) is overlaid. Minimally adjusted model adjusted for patient's calendar quarter of entry into the cohort (A). Case mix–adjusted model adjusted for covariates in the minimally adjusted model, as well as age, sex, race/ethnicity, and baseline diabetes status (B).

Figure 3.

Associations between time-dependent thyroid function with all-cause mortality across clinically relevant subgroups of peritoneal dialysis patients. Multivariable Cox models adjusted for case-mix covariates: patient's calendar quarter of entry into the cohort, age, sex, race/ethnicity, and baseline diabetes status. *, Upper bound of 95% CI exceeds figure limits.