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Stenosis of the renal artery causes renovascular hypertension (RVH) and chronic renal ischemia, resulting in kidney damage that can become irreversible. Clinical studies show that the restoration of renal blood flow is the most efficient therapy to normalize the blood pressure (BP) with significant benefits on renal function, however, the damage caused by chronic hypoxia is not fully reversed and renal function may progressively deteriorate over the time. Mesenchymal stem cells (MSC) have produced discreet results in minimizing RVH and improving renal structure and function in the experimental RVH model since the obstruction persists. This study aimed to evaluate the effects of the administration of MSC associated with revascularization in rats submitted to the 2 kidney-1 clip (2K-1C) RVH model by partial obstruction of the left renal artery.
MSC were obtained from tibias and femurs of male Wistar rats. The following groups were evaluated: control (SHAM), hypertensive (2K-1C), hypertensive treated with MSC (MSC), hypertensive subjected to revascularization (REV), and hypertensive subjected to revascularization and treated with MSC (REV+MSC). The MSC group received cell infusions at the 3rd, 5th, 7th and 9th weeks. The REV and REV+MSC groups underwent the procedure for removing the clip on the 6th week and the REV+MSC group, after the procedure received MSC infusion at the 6th and 8th weeks. Tail BP was measured weekly, histological and renal parameters were evaluated.
Clipped animals developed RVH, deterioration of total renal function, and developed significant proteinuria. Treatment with MSC alone had no significant effects on kidney function and BP. REV resulted in normalization of BP and partial reduction of proteinuria, but areas with renal fibrosis persisted. Otherwise, the combination of the two treatments was effective in normalizing all renal parameters as well as proteinuria with a significant restoration of the renal parenchyma.
The results suggest that therapy with MSC associated with revascularization can potentially help in the full recovery of renal function with better preserving of renal tissue in the long terms in patients with RVH.