A pilot trial on the effect of levothyroxine on proteinuria in patients with advanced chronic kidney disease

Abstract Introduction Thyroid hormones can directly affect kidney function; elevated levels of TSH and CKD are associated with proteinuria, decreased eGFR and progression to ESRD. Our hypothesis is that in patients with CKD and TSH at levels considered to be in the low subclinical hypothyroidism (SCH) range, lowering TSH with levothyroxine (LVX) improves the clinical parameters of renal function. Clinical trial registration number: NCT03898622 Methods This is a double-blind, pilot randomized clinical trial in patients with proteinuric CKD (eGFR 150 mg/day) performed at the Hospital Civil de Guadalajara, with the intention of lowering TSH (levels between 1.25 and 2.5 μIU/L) in patients with TSH (levels between 2.6 and 9.9 μIU/mL with FT4 in the range of 0.7-1.8 ng/dL). Patients were randomized 1:1 to receive LVX or placebo for 12 weeks. The main objective was to evaluate absolute levels of proteinuria at the beginning compared to the end of the study and, as a secondary objective, the changes in sCr, eGFR, cholesterol, triglycerides, LDL and blood pressure and to assess the tolerability and safety of LVX. Results Between March and November 2018, 163 patients were assessed for eligibility; 119 patients did not meet the inclusion criteria or were excluded, and 32 patients were randomized. The demographic and clinical characteristics of the 2 study groups were essentially not different. Subjects were 66.87 (SD 12.19) years old, 62.5% were female, 75% were , eGFR was 23.55 (+/-12.91) ml/min/1.73 m2, TSH was 5.37 +/- 2.13 μIU/mL, proteinuria in 24-hour urine collection was 1.52 +/- 1.12, and all of them were taking ACEIs or ARBs. Proteinuria at 12 weeks in the LVX group was 0.89 SD +/- 1.28 grams/day, and in the placebo group, it was 1.35 SD +/- 0.85 g/day; when compared to placebo, LVX showed a significant decrease in proteinuria of 1.1 g/day(p = 0.0011). eGFR in the LVX group showed an improvement of 4 ml/min/1.73 m2 (p=0.049); in the placebo group, there was a decrease of 1.98 ml/min/1.73 m2. sCr, cholesterol, triglycerides, LDL, SBP and DBP were not different between groups. Adverse events were present in the LVX group in 7.14% of patients and in 11.11% of patients in the placebo group; none left the study because of adverse effects, and there were no severe adverse events. Conclusion This single-center, randomized, double-blind, placebo-controlled pilot clinical trial study in patients with advanced proteinuric CKD who already used ACEIs or ARBs demonstrated that administering LVX to obtain a TSH range close to 2.5 μIU/mL decreased proteinuria and improved eGFR. Future research is needed to confirm our results and to determine whether our findings generalize to patient groups not explicitly enrolled in this small pilot RCT.