Kidney Transplantation-Induced Reduction in Myocardial Fibrosis and Modulation of Plasma Proteome: Results of a Pilot...

Kidney transplantation (KT) improves cardiovascular outcomes in patients with kidney failure, yet the biological mechanisms underlying post-KT myocardial recovery remain unclear.

Prospective observational cohort study with matched controls.

Fifty participants were enrolled at 2 transplant centers: 28 received a living KT, and a cardiac magnetic resonance imaging (CMRI) scan assessment of interstitial myocardial fibrosis with T1 maps before and nine months post-KT; 22 matched waitlisted controls had baseline and 9-month CMRI scans. The groups were matched using baseline characteristics and T1 values.

Receipt of kidney transplantation.

Change in native T1 mapping CMRI scan, a surrogate marker of interstitial myocardial fibrosis.

Regression models were used to estimate the effect of KT versus no KT (the waitlisted control group) on interstitial myocardial fibrosis, adjusted for demographic characteristics, comorbidities, blood pressure, and medications. Plasma collected at baseline was analyzed using SomaScan v.4.1 (6,472 unique proteins). Regression models were used to identify proteins associated with baseline and longitudinal changes in T1, adjusted for clinical covariates and corrected for multiple testing.

KT recipients had reduced interstitial myocardial fibrosis compared with waitlisted controls (-47.49 ± 81.63 vs +13.77 ± 62.13 ms, P = 0.01). Forty-three plasma proteins were significantly associated with baseline T1 values; macrophage colony-stimulating factor displayed the greatest retest reproducibility (80%) and positive association with T1 (P = 3.1 × 10^-4). Pathway enrichment analyses identified 17 interconnected fibrosis-related proteins with biological relevance to cardiac remodeling.

A modest sample size and a single time-point proteomic assessment. External validation is needed.

KT leads to regression of interstitial myocardial fibrosis within 9 months, supporting a structural cardiac benefit of transplantation. Pretransplant proteomic signatures, particularly macrophage colony-stimulating factor, reflect underlying fibrotic burden and may serve as a predictive biomarker to monitor post-KT cardiac recovery.