Circulating Growth Hormone-Releasing Hormone Increases After Kidney Transplantation and Shows Divergent Associations...

The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis is disrupted in chronic kidney disease (CKD), yet its upstream regulator, growth hormone-releasing hormone (GHRH), has never been measured in kidney failure. GHRH receptors are expressed in the kidney, and preclinical studies suggest GHRH agonists exert reno- and vasoprotective effects independent of GH. Whether GHRH changes after kidney transplantation (KTx) or relates to gut-derived uremic toxins is unknown.

Sixty patients with kidney failure were evaluated pre-transplant and at two-year follow-up. GHRH immunoreactivity (GHRH-IR) was measured by competitive ELISA alongside gut-derived uremic toxins p-cresyl sulfate (pCS), phenyl sulfate (PhS), trimethylamine-N-oxide (TMAO), and metabolic, cardiovascular and inflammatory biomarkers. pCS, PhS and TMAO were prespecified primary exposures (Benjamini-Hochberg FDR across six tests).

GHRH-IR increased by 20% after KTx (2.44 ± 0.74 to 2.93 ± 0.55 ng/mL; P < 0.0001), independently of dialysis modality and vintage. PhS inversely associated with baseline GHRH-IR (P_FDR = 0.044); the remaining pCS and PhS associations showed consistent bidirectional trends (P_FDR 0.052-0.072). Among patients with above-median baseline GHRH-IR, those with attenuated dynamics had higher TMAO than responders (112.8 vs 65.1 µM; P = 0.0006, d = 1.03). Apolipoprotein B was the strongest independent predictor of baseline GHRH-IR (β = -0.38, P = 0.002).

Circulating GHRH rises after KTx and shows differential associations with gut-derived uremic toxins. These findings, based on a relative immunoassay index, suggest a link between gut dysbiosis and somatotropic regulation in CKD.