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Updated: Jan 5, 2026
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
Dissociation between hypertrophy and fibrosis in the left ventricle early after experimental kidney transplantation
Merle M Krebber1, Diana A Papazova1,2, Nynke R Oosterhuis1
1Department of Nephrology & Hypertension, University Medical Center Utrecht.
Insights
Kidney transplantation normalized left ventricular hypertrophy in chronic kidney disease (CKD) patients, but cardiac fibrosis persisted. This dissociation highlights the complex cardiac remodeling in CKD, suggesting persistent fibrosis despite improved kidney function.
Area of Science:
- Nephrology
- Cardiology
- Transplantation Science
Background:
- Left ventricular (LV) hypertrophy is common in chronic kidney disease (CKD).
- Kidney transplantation can normalize LV hypertrophy but its effect on LV fibrosis is unclear.
Purpose of the Study:
- To investigate the causal effects of kidney graft and recipient health on LV hypertrophy, fibrosis, and inflammation.
- To understand the dissociation between LV hypertrophy and fibrosis post-transplantation in CKD.
Main Methods:
- Cross-kidney transplantation in rats with induced CKD.
- Groups included healthy-healthy, CKD-healthy, healthy-CKD, and CKD-CKD recipient-graft combinations.
- Analysis of mean arterial pressure (MAP), LV mass index (LVMI), LV fibrosis, and cardiac gene expression via RNA sequencing.
Main Results:
- CKD kidneys increased MAP and LVMI regardless of recipient health.
- LV fibrosis was more severe in CKD recipients irrespective of graft quality.
- MAP and creatinine correlated with LVMI, but not LV fibrosis.
- Cardiac RNA sequencing revealed significant transcriptional changes related to fibrosis, extracellular matrix, and inflammation.
Conclusions:
- LVMI and MAP normalized after healthy kidney transplantation, but LV fibrosis persisted.
- LV hypertrophy and fibrosis dissociated within 6 weeks post-transplantation.
- Targeting cardiac extracellular matrix dynamics may be a promising therapeutic strategy for CKD patients.
Objective:
Left ventricular (LV) hypertrophy is the most common cardiac alteration in patients with chronic kidney disease (CKD). Normalization of hypertension in CKD patients receiving a healthy kidney allograft often reverses LV hypertrophy, but effects on LV fibrosis remain unclear. To study causal interactions between graft and environment on LV hypertrophy, fibrosis and inflammation, we applied cross-kidney transplantation METHODS:: Orthotopic transplantation was performed after inducing CKD in rats by two-third bilateral ablation of kidney mass: Healthy kidney (K) donor to healthy heart (H) recipient (healthy-K→healthy-H); CKD-K→healthy-H; healthy-K→CKD-H; CKD-K→CKD-H; N= 6 per group.
Results:
At week 6 after transplantation, mean arterial pressure (MAP) and LV mass index (LVMI) increased in CKD-K versus healthy-K irrespective of recipient. Contrarily, LV fibrosis was more severe in CKD-H versus healthy-H recipients irrespective of graft. Indeed, MAP and plasma creatinine correlated with LVMI but not with LV fibrosis. Increased LVMI in CKD-K→CKD-H not accompanied by cardiomyocyte cross-sectional area gain is consistent with eccentric remodelling. Cardiac RNA sequencing found a strong transcriptional response associated with LV fibrosis but only sparse changes associated with LV hypertrophy. This response was, among others, characterized by changes in extracellular matrix (ECM) and inflammatory gene expression.
Conclusion:
LVMI reversed and MAP and renal function were normalized early after transplantation of a healthy kidney. However, LV fibrosis persisted, dissociating LV hypertrophy from LV fibrosis within 6 weeks. Elucidating cardiac ECM dynamics in CKD patients, although challenging, appears promising.
