Does thyroid dysfunction affect the Albumin (ACR) to Creatinine Ratio, a measure of kidney function?

Does Thyroid Dysfunction Affect ACR?

Yes, thyroid dysfunction directly affects kidney function and can alter ACR measurements, but the ACR itself remains a valid marker for kidney disease risk assessment regardless of thyroid status.

Direct Effects on Kidney Function

Thyroid hormones have direct renal effects that alter glomerular filtration rate and proteinuria:

• Hypothyroidism decreases GFR and is associated with increased serum creatinine, which can affect the creatinine component of the ACR calculation 1.

• Hyperthyroidism increases GFR and causes mild proteinuria in most thyrotoxic patients, with significantly elevated urinary protein/creatinine and albumin/creatinine ratios compared to euthyroid states 2.

• Treatment normalizes kidney function: When thyroid dysfunction is corrected with appropriate therapy, kidney function parameters typically return to baseline, demonstrating the reversibility of these effects 3, 1.

Impact on ACR Measurement Components

The albumin-to-creatinine ratio can be affected through multiple mechanisms:

• Albumin excretion increases in hyperthyroidism: Hyperthyroid patients demonstrate significantly elevated albumin/creatinine ratios that normalize with treatment, though this proteinuria does not appear to represent true glomerular or tubular injury 2.

• Creatinine production remains stable: Importantly, 24-hour urinary creatinine secretion does not change with thyroid dysfunction, meaning creatinine-based measurements remain reliable 3.

• Higher FT4 levels predict kidney disease: Elevated free thyroxine (FT4) is independently associated with 1.88-fold increased risk of incident CKD and 1.64-fold increased risk of rapid eGFR decline, suggesting thyroid hormones have long-term effects on kidney health 4.

Clinical Interpretation Pitfalls

Critical caveat: While thyroid dysfunction affects ACR values, the ACR remains the preferred test for assessing albuminuria in these patients:

• Avoid cystatin C-based GFR estimates in thyroid dysfunction, as cystatin C is strongly influenced by thyroid function and produces inaccurate results (overestimates GFR in hypothyroidism, underestimates in hyperthyroidism) 3, 5.

• Use creatinine-based eGFR calculations as the recommended kidney function test in patients with thyroid disorders, since creatinine production is not altered by thyroid status 3, 5.

• ACR retains prognostic value: Despite being affected by thyroid status, ACR remains the preferred marker because it accurately predicts kidney and cardiovascular risks in population studies and is more sensitive for detecting clinically important albuminuria 6.

Practical Management Algorithm

When encountering elevated ACR in a patient with known or suspected thyroid dysfunction:

1. Confirm the ACR elevation with a first morning void sample to exclude transient causes 7.

2. Assess thyroid function with TSH and free T4 if not recently checked, as thyroid dysfunction is a reversible cause of altered kidney parameters 1.

3. Treat thyroid dysfunction first if present, then reassess ACR after achieving euthyroid state for at least 4 months 2.

4. Monitor ACR at least annually in CKD patients regardless of thyroid status, as recommended by KDIGO guidelines 6.

5. Initiate renoprotective therapy (ACE inhibitor or ARB) if ACR remains ≥30 mg/g after thyroid correction, as the prognostic significance of albuminuria persists 8, 7.

Bottom Line for Clinical Practice

Thyroid dysfunction transiently alters ACR values through hemodynamic and metabolic effects on the kidney, but these changes are reversible with treatment. The ACR remains the gold standard for albuminuria assessment even in thyroid disease, while cystatin C-based estimates should be avoided. Always consider thyroid status when interpreting kidney function tests, but do not delay renoprotective interventions if significant albuminuria persists after achieving euthyroid state.