Revolutionizing Renal Replacement: Current Advancements in Development and Transplantation of Bioengineered Kidneys

The rising prevalence of chronic kidney disease represents a major global health burden. Limitations of current renal replacement therapies, including donor organ shortages, rejection, and dialysis-related complications, underscore the need for innovative treatment options. This narrative review assesses the feasibility of bioengineered kidneys as an alternative to current treatments by discussing advances in decellularization, recellularization, and the transplantation of cell-on-scaffold kidneys. We propose that the development of functional bioengineered kidneys follows a hierarchical, staged process, in which vascular patency is the primary prerequisite for graft survival, followed by partial restoration of glomerular filtration, with complete tubular function remaining the final and most challenging milestone. Perfusion-based whole-organ decellularization has made significant progress in preserving the extracellular matrix, enabling the production of acellular human kidney scaffolds. However, complete recellularization of whole kidneys has not yet been achieved. Nevertheless, partially repopulated kidney scaffolds have been shown to withstand physiological blood pressure, produce urine, and exhibit filtration in large-animal models. Complete endothelial coverage of the vascular network proved essential for preventing thrombosis after transplantation. Current work on bioengineered kidneys shows promising results regarding feasibility for clinical application. It is important to note that most of the included studies are proof-of-concept, characterized by small sample sizes and short observation periods. Although these findings are crucial for further research, they cannot be generalized, and larger trials are recommended. In addition to cell-on-scaffold kidneys, 3D bioprinting is a promising technique that could eliminate the need for donor scaffolds.