Free Thyroxine Shows Protective Effect Against Renal Progression in IgA Nephropathy

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Findings from a recent study are calling attention to free thyroxine’s protective effect against renal progression in IgA nephropathy (IgAN), also highlighting its utility in combination with tubular atrophy/interstitial fibrosis for predicting poor IgAN prognosis.¹

The study, coined by investigators as the first to explore the relationship between thyroid hormones and IgAN prognosis, found patients with IgAN and lower free thyroxine levels had worse renal outcomes. Specifically, results showed those with free thyroxine ≥15.18pmol/L had better renal survival.¹

“The prognosis of IgAN varies greatly, and the prognosis of individual patients remains difficult to predict. More indicators are urgently needed to predict the prognosis of IgAN patients to improve treatment strategies,” Bixia Yang, of the department of nephrology at The Third Affiliated Hospital of Soochow University in China, and colleagues wrote.¹ “Free thyroxine is an important member of the thyroid hormone, but its effect on IgAN has not been studied.”

The main hormone released into the bloodstream by the thyroid gland, thyroxine plays a vital role in regulating various bodily functions in combination with triiodothyronine.² Thyroid hormones have been linked to chronic kidney disease prognosis, but their role in IgAN is not well understood.¹

To evaluate the impact of free thyroxine on IgAN prognosis, investigators conducted a retrospective study of patients with biopsy-proven IgAN admitted to the First People’s Hospital of Changzhou from January 1, 2018, to December 31, 2021. For inclusion, they were required to have an estimated glomerular filtration rate (eGFR) > 15 ml/min·1.73 m 2 during renal biopsy and complete baseline data.¹

General data and laboratory test results at the time of IgAN diagnosis were collected from the clinical medical record system as baseline data. Follow-up was performed through the hospital medical record system or by telephone, with the follow-up period ending in August 2023.¹

The renal composite outcomes were end-stage renal disease (ESRD), defined as eGFR < 15 ml/min·1.73 m2 or initiation of renal replacement therapy; serum creatinine doubled from baseline; and eGFR decreased by > 50% from baseline.¹

In total, 223 patients with IgAN were enrolled in the study. Among the cohort, the median age was 39 (Interquartile range [IQR], 30–50) years, 55.2% of patients were male, and 39.5% had hypertension. The median serum creatinine at renal biopsy was 94 (IQR, 70–121) µmol/l and the median 24h urine protein was 2 (IQR, 1.13–3.43) g/day.¹

After 38 (IQR, 26–54) months of follow-up, 23 (10.3%) patients experienced renal composite outcomes. Compared with the renal survival group (n = 200), the non-renal survival group had lower levels of free triiodothyronine and free thyroxine as well as greater levels of serum creatinine and 24-hour urinary protein. In addition, investigators pointed out the non-renal survival group had a significantly greater proportion of anemia (56.5% vs 12.5%; P <.001), hypoalbuminemia (39.1% vs 16.0%; P = .015), and hyperuricemia (69.6% vs 44.0%; P = .020), but a lower proportion of ACEI/ARB using to reduce urinary protein (26.1 vs 55.5%; P = .007).¹

Kaplan-Meier survival curve analysis showed the renal survival rate of patients with IgAN and free thyroxine <15.18pmol/L was lower than with free thyroxine ≥15.18pmol/L (P <.001). Multivariate Cox regression analysis showed free thyroxine was a protective factor for IgAN patients when considered as a continuous variable or a categorical variable (Hazard ratio [HR], 0.68; 95% CI, 0.51–0.90; P = .007).¹

The risk in IgAN patients with free thyroxine ≥15.18pmol/L is 0.04 times that in patients with free thyroxine <15.18pmol/L (HR, 0.04; 95% CI, 0.01–0.20; P <.001). Investigators noted greater levels of serum creatinine and thyroid-stimulating hormones were independently associated with renal composite outcomes, and ROC curve analysis showed free thyroxine combined with t score had a high predictive value for predicting renal outcomes in patients with IgAN (AUC, 0.881; P <.001).¹

Investigators cited the single-center, retrospective study design as a potential limitation to these findings, calling attention to the impact of selection bias and a center-specific effect. Thus, they called for further prospective, multi-center studies with a larger sample size and longer follow-up to validate their findings.¹

“Free thyroxine was a protective factor for renal progression of IgAN patients. In addition, free thyroxine combined with tubular atrophy/interstitial fibrosis had a high predictive value for poor prognosis of IgAN,” investigators concluded.¹

References:

1. ^{Yang B, Zhou W, Cui L, et al. The predictive value of free thyroxine combined with tubular atrophy/interstitial fibrosis for poor prognosis in patients with IgA nephropathy. Front. Endocrinol. 15:1372824. doi:10.3389/fendo.2024.1372824}
2. ^{Cleveland Clinic. T4 (Thyroxine) Test. Diagnostic & Testing. October 3, 2022. Accessed June 14, 2024. https://my.clevelandclinic.org/health/diagnostics/24235-thyroxine-t4-test}