We evaluated the difference in proteinuria after levothyroxine treatment in patients with overt hypothyroidism. We found that the 24-hour urinary protein excretion and plasma creatinine decreased with the replacement therapy.
Several studies reveal that thyroid hormones affect renal function directly, however, they affect cardiovascular and systemic hemodynamic pathways indirectly. Experimental studies document that kidney size, weight, and structure are all affected by thyroid hormone both during development and adult life. Thyroid hormones have also an impact on the proximal and distal tubule and medullary thick ascending limb, according to the histologic studies (18–20). Decreased cardiac output and renal perfusion as a result of hypotension and bradycardia were observed in thyroid hormone receptor-deficient animals (5). Rats with hypothyroidism also demonstrate an increased renal sodium excretion (7, 8). Congenital hypothyroidism decreases renal mass and renal and urologic abnormalities are more prevalent in these patients (21). Thyroid hormones have direct effect on the expression and/or activity of several ion channels and transporters in the kidney (3). Decreased capacity in urinary dilution and urinary concentrating ability as well as raised urinary excretion of sodium, higher degree of fractional sodium excretion, and impaired tolerance of sodium restriction are observed animals with hypothyroidism (22). Hypothyroidism especially due to autoimmune thyroiditis in animals as well as children and adults is associated with isolated cases of reversible proteinuria and glomerulonephritis (23). Thyroid hormones have also very important influences on the cardiovascular system by affecting cardiac myocytes, vascular smooth muscle tone, and reactivity (4).
Thyroid hormone treatment in rats with hypothyroidism recovered sodium reabsorption in proximal tubule via increased Na+/H + anti-porter activity (9), which provides volume extension (10). Moreover, thyroid hormone replacement therapy also relaxes arteries and decreases resistance in arteries (6). These actions of thyroid hormone treatment leads to an increase in GFR (10). A study showed that levothyroxine replacement therapy in subclinical hypothyroid patients and chronic kidney disease decreased the rate of reduction in GFR when compared to individuals not receiving treatment (24, 25). Even in patients with subclinical hypothyroidism, thyroid hormone treatment decreases edema, albumin permeability in capillaries, and osmotic pressure of plasma, which suggests lack of thyroid hormone can increase vascular permeability of proteins (14).
Although there are many pieces of evidence for the potential association between hypothyroidism and proteinuria, the literature regarding proteinuria in hypothyroid patients remained restricted to just few case reports and studies. Connor A et al. described two cases of hypothyroidism-induced renal impairment as an initial finding. In these cases, thyroid hormone treatment provided nearly complete improvement in kidney function. The authors concluded that hypothyroidism could be an unheeded reason for renal impairment (26). In a recent case report of 2 patients with severe hypothyroidism (TSH > 100 U/L at diagnosis in both cases), the authors defined significant proteinuria greater than 1gr mg/day at presentation which gradually normalized over 4–6 months after starting replacement treatment (27). Chou et al demonstrated that serum creatinine decreased and GFR increased at 3 months after thyroxine replacement in hypothyroid patients (28). That GFR decreases in patients with hypothyroidism, which increases via levothyroxine treatment was revealed in some studies (29, 30). The decrease in GFR could be explained by a reduction in renal blood flow in hypothyroidism (31). Patients with reduced GFR have higher prevalence of subclinical or overt hypothyroidism (32, 33). A recent study found a decrease in proteinuria and creatine level with the levothyroxine treatment in hypothyroid patients with TSH greater than 50 µIU/mL. Proteinuria level decreased and creatinine levels increased via thyroid hormone treatment in our patients. Our results were very similar to results of the study in question however, there are some differences. We included milder degrees of hypothyroidism cases the lowest TSH level for our and abovementioned studies: 16 and 50 µIU/mL, respectively. Additionally, repeat biochemical measurements were performed at the time of euthyroidism in our study whereas they were not achieved in all subjects in the study in question. It is well-known that weight, blood pressure, cardiovascular markers ,and lipid parameters decrease via thyroid hormone treatment (34, 35). In our study, weight, waist circumference, systolic and diastolic blood pressures, lipid parameters, and CRP level decreased with treatment.
Being a single-center study, the absence of a great sample size and a control group are the limitations of our study.
In conclusion, thyroid hormones affect development, structure, and hemodynamics of kidney, GFR, the function of several transport systems throughout the nephron, and sodium and water homeostasis. Fortunately, most of the renal manifestations of hypothyroidism are reversible with treatment. Hypothyroidism may lead to a decrease in GFR, hence evaluating thyroid hormone levels should take into consideration for patients with unexplained elevations in serum creatinine. Additionally, urinary protein amount and plasma creatinine decreased via thyroid hormone replacement in patients with hypothyroidism. According to our findings, hypothyroidism might be a new risk factor for kidney dysfunction, which is reversible and often unmined. Investigation of underlying mechanisms and longer follow-up of hypothyroid patients may provide a more logical interpretation of these observations.