Short-term hypothyroidism impairs the daily oscillations of renal circadian clock and function in a sex-dependent manner

Hypothyroidism is associated with the desynchronization of central and peripheral circadian clocks; however, its effects on renal rhythmicity remain unclear. This study investigated the impact of short-term hypothyroidism on renal molecular clock oscillations and daily kidney function in male and female rats. Hypothyroidism was induced by thyroidectomy followed by methimazole and CaCl₂ administration for 21 days. Renal handling of solutes and electrolytes and the expression of core clock components were evaluated every 6 h over 24 h. Urinary levels of creatinine, protein, glucose, and sodium and the clearance and fractional excretion (FE) of these solutes exhibited circadian oscillations in control rats. In males, hypothyroidism abolished the rhythmicity of serum creatinine, creatinine clearance (C_Cr), renal glucose clearance (C_glucose), and fractional excretion of glucose, sodium, and potassium; decreased the mesor and amplitude of protein excretion parameters; reduced mesor and amplitude of <i>Bmal1</i> expression and phase advanced <i>Per2</i> and <i>Nr1d1</i> mRNA expression. In females, hypothyroidism reduced the mesor of urinary creatinine, serum glucose, and CCr while delaying its acrophase; increased the mesor of proteinuria and glucosuria and the mesor and amplitude of C_glucose and FE_glucose; and disrupted the circadian pattern of FE_protein and <i>Per2</i> and <i>Nr1d1</i> expression in kidney and phase advanced <i>Bmal1</i> expression. Sodium and potassium daily handlings were more altered in males than in females. No structural damage was found in the kidney of hypothyroid rats. These findings indicate that short-term hypothyroidism desynchronizes the renal circadian clock and disturbs the daily rhythmicity of several renal parameters in a sex-dependent manner, potentially contributing to early-stage kidney dysfunction.<b>NEW & NOTEWORTHY</b> Hypothyroidism alters the kidney circadian clock machinery and renal function in a sex-dependent manner, potentially contributing to early-stage kidney dysfunction. Female rats exhibited more severe rhythmic impairments under hypothyroid conditions, including reduced creatinine clearance, increased protein and glucose loss in urine over 24 h, and disrupted circadian oscillations in renal clock components, indicating a greater susceptibility of females to hypothyroidism-induced metabolic disturbances associated with circadian disruption.