A paper published in The Lancet journal, as part of a series on renal medicine, has questioned if kidney regeneration may be possible in human beings as it is in fish and other lower vertebrates. The work is part of an ongoing EU-funded research project on the possibilities of kidney regeneration, and was carried out by a team from the Mario Negri Institute for Pharmacological Research in Bergamo, Italy.
The study is part of the 3-year, 10-partner STAR-T REK (Set up and comparison of multiple stem cell approaches for kidney repair) project, which received EUR 3 million under the Health Theme of the Seventh Framework Programme (FP7). The aim of the project is to examine how kidney regeneration could be accomplished, a treatment that is becoming imperative given the increasing rates of end-stage renal failure.
Organ regeneration occurs in both the plant and animal worlds. Fish can regenerate a kidney and the axolotl, a type of salamander found in Mexico, can regenerate an entire lost limb by converting adult tissue near the amputated area into progenitor cells which reform the limb.
Human kidneys, however, have a restricted ability to regenerate. The focus of the STAR-T REK project, therefore, is to investigate possible treatments to trigger kidney regeneration, including the use of bone marrow-derived stem cells, renal adult stem cells and foetal renal stem cells.
"Improved understanding of the mechanisms of kidney repair has stimulated researchers to clarify whether supplementary cells injected into an acutely damaged kidney might aid repair and regeneration of injured tissue, thus accelerating and augmenting the ongoing natural healing process," the authors write in the journal. "Adult stem cells, either derived from bone marrow or of renal origin, might participate in cellular repair and tissue remodelling after acute renal injury."
However, the study questions whether chronic kidney damage, which has many different causes, can be repaired. It discusses the relative merits of different drug treatments for kidney damage including the importance of using angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type I receptor blockers (ARBs) in the prevention of kidney damage.
Recent parallel research has shown that eight-year ACE inhibitor therapy stabilised kidney function in six patients with type 1 diabetes who would otherwise have progressed to end-stage kidney disease within six months. This provides evidence that ACE inhibitor therapy might be useful for kidney repair and regeneration treatment.
The authors also suggest that this therapy could be extended by using ACE 1 inhibitors at much higher doses than is usually recommended for blood pressure control with an ARB and a diuretic. This treatment has been trialled on 112 patients and resulted in only 2 out of 56 patients progressing to end-stage kidney disease compared with 17 out of 56 controls.
The authors conclude: "Studies in man will improve the understanding of the genetics governing progression and regression of chronic kidney disease and genes associated with favourable outcomes. Enhanced understanding of mechanisms of action of already available drugs with renoprotective capacity will pave the way to unravel novel pathways that are possibly relevant to renal repair.
"Together, insights from human genetics and mechanistic studies on renoprotection will contribute to the design of molecules targeted to genes relevant to the pathophysiology of regeneration, with the goal of kidney regeneration instead of dialysis or renal transplantation."
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