Acute kidney injury (AKI) is an increasing common clinical disorder affecting more than 20% of patients in hospital.  There are multiple causes for AKI, but one of the most significant is ischemia-reperfusion injury (IRI), characterized by severe renal tubular damage and rapid worsening of renal function.  Untreated, IRI-related kidney injury has high likelihood of developing into chronic kidney disease, primarily due to fibroblast proliferation near the site of the injury and deposition of extracellular matrix. Healing from these injuries hinges on the regeneration of damaged tubular and endothelial cells through de-differentiation of surviving cells and/or the ability of resident progenitor cells to proliferate and differentiate into new renal cells.   Facilitating regeneration is a key component to treating both acute kidney injury and chronic kidney disease.

It has been shown that mesenchymal stromal cells (MSCs) have beneficial paracrine-mediated effects both on the initial acute recovery from IRI and in preventing the development of further chronic kidney disease.   A 2017 study by Ranghino et al.  examine the role MSCs found in the glomeruli have on recovery from kidney injury.   A mouse model of monolateral kidney IRI was developed and used to evaluate the effects of MSCs and their extracellular vesicles on recovery and regeneration of damaged renal tissues.    Kidney function was assessed by measuring creatinine and blood urea nitrogen (BUN, measured using the Arbor Assays Urea Nitrogen Colorimetric Detection Kit which features NIST-Calibration) in plasma samples collected 2 days after injury for all mice and again at 3 weeks post injury for groups of mice kept alive to study longer term outcomes.

48 hours after IRI, serum creatinine and BUN were markedly increased in IRI mice as compared  to healthy controls, sham-operated controls. Histological evidence revealed severe renal tubular damage with necrosis and the presence of proteinaceous casts inside the tubular lumen in the IRI mice.  Injecting mice with MSCs from glomeruli shortly after IRI significantly reduced serum creatinine and BUN and reduced the physical damage observed histologically.   Various other cell types and extracellular vesicles were also administered post IRI.  These also improved kidney function and reduced the physical damage observed, but none were as affective as the MSCs from glomeruli.    Some of the mice were maintained for a further 3 weeks to check for adverse effects of the treatment but none were observed.

This study and others like it demonstrate effective treatment to prevent long term consequences from acute kidney injury may be possible, either through therapeutic cell treatments (as was done here) or through other means of stimulating paracrine response from resident MSCs after injury.   As both chronic kidney disease and acute kidney injury incidents are becoming increasingly common in our aging population, routine monitoring of kidney function, especially among hospitalized patients, along with the ability to respond quickly with treatment in the event of acute kidney injury, is critical to reduce mortality rates and improve quality of life.

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