Hyperthyroidism exacerbates ischemic reperfusion injury in the kidney.

Thyroid hormones are critical regulators of vertebrate development and metabolism. Under hyperthyroid conditions, excess thyroid hormones induce expression of several enzymes and activities via activation of ligand-bound thyroid hormone receptors (TRs). Arginase (ARG) is downstream of a ligand-bound TR and overexpression of ARG2 induces the production of reactive oxygen species and subsequent exacerbation of kidney ischemia/reperfusion (I/R) injury. To clarify the association between I/R-induced kidney injury and hyperthyroidism, mice were pretreated with L-thyroxine (LT4) or vehicle alone, then subjected to I/R. Proximal tubular cell-specific conditional knockout of thyroid hormone receptor ß (TRßcKO) mice was generated and the effects of I/R were analyzed. Hyperthyroidism enhanced tubular damage and fibrosis in the kidneys of mice after I/R. Hyperthyroidism induced tubular cell necroptosis following inflammatory cell accumulation in the kidney after I/R. ARG2 expressions and reactive oxygen species accumulated in the kidneys of hyperthyroid mice after I/R, but these changes were ameliorated in the kidneys of TRßcKO mice. Hyperthyroidism-enhanced kidney injury was ameliorated in the kidney of TRßcKO mice after I/R. These results suggest that excess thyroid hormones are disadvantageous for the kidney under ischemic stress. Overt hypothyroidism represents a severe thyroid hormone deficiency disease that requires LT4 treatment, while overreplacement or iatrogenic thyrotoxicosis might cause kidney injury.

Association between the Cardio-Ankle Vascular Index and Diabetes Mellitus-Related Peripheral Arterial Disease in Chronic Hemodialysis Patients.

BACKGROUND: Peripheral arterial disease (PAD) has increased in association with the increase in the numbers of patients with kidney disease or diabetes. The aim of this study was to assess the prevalence of PAD in hemodialysis patients with diabetes. METHODS: To examine the usefulness of the cardio-ankle vascular index (CAVI) to screen for the presence of PAD, cross-sectional studies of 100 patients undergoing chronic hemodialysis were performed. The CAVI and other inflammatory markers were evaluated. RESULTS: The CAVI was markedly elevated in patients with a history of PAD or cardiovascular disease. When dialysis patients were classified on the basis of CAVI quartiles, increased CAVI was associated with other risk factors for PAD. CONCLUSION: The prevalence of PAD is high in elderly diabetic patients on hemodialysis. The present findings suggest that the CAVI can be a useful index that predicts the occurrence of macrovascular complications in dialysis patients with diabetes.