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Int J Mol Sci ; 22(12)2021 Jun 20.
Article in English | MEDLINE | ID: covidwho-1472414


Acute kidney injury (AKI) and chronic kidney disease (CKD) are rising in global prevalence and cause significant morbidity for patients. Current treatments are limited to slowing instead of stabilising or reversing disease progression. In this review, we describe mesenchymal stem cells (MSCs) and their constituents, extracellular vesicles (EVs) as being a novel therapeutic for CKD. MSC-derived EVs (MSC-EVs) are membrane-enclosed particles, including exosomes, which carry genetic information that mimics the phenotype of their cell of origin. MSC-EVs deliver their cargo of mRNA, miRNA, cytokines, and growth factors to target cells as a form of paracrine communication. This genetically reprograms pathophysiological pathways, which are upregulated in renal failure. Since the method of exosome preparation significantly affects the quality and function of MSC-exosomes, this review compares the methodologies for isolating exosomes from MSCs and their role in tissue regeneration. More specifically, it summarises the therapeutic efficacy of MSC-EVs in 60 preclinical animal models of AKI and CKD and the cargo of biomolecules they deliver. MSC-EVs promote tubular proliferation and angiogenesis, and inhibit apoptosis, oxidative stress, inflammation, the epithelial-to-mesenchymal transition, and fibrosis, to alleviate AKI and CKD. By reprogramming these pathophysiological pathways, MSC-EVs can slow or even reverse the progression of AKI to CKD, and therefore offer potential to transform clinical practice.

Biological Therapy , Extracellular Vesicles/metabolism , Extracellular Vesicles/transplantation , Kidney Diseases/therapy , Mesenchymal Stem Cells/metabolism , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Acute Kidney Injury/therapy , Animals , Apoptosis/drug effects , Biological Therapy/methods , Cell Differentiation , Cell Proliferation/drug effects , Cell Self Renewal , Chemical Fractionation , Disease Management , Disease Susceptibility , Exosomes/metabolism , Humans , Kidney Diseases/etiology , Kidney Diseases/pathology , Mesenchymal Stem Cells/cytology , Protective Agents , Renal Insufficiency/diagnosis , Renal Insufficiency/etiology , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/therapy
J Am Coll Surg ; 232(4): 444-449, 2021 04.
Article in English | MEDLINE | ID: covidwho-1029891


BACKGROUND: Maintaining access to kidney transplantation during a pandemic is a challenge, particularly for centers that serve a large rural and minority patient population with an additional burden of travel. The aim of this article was to describe our experience with the rollout and use of a virtual pretransplantation evaluation platform to facilitate ongoing transplant waitlisting during the early peak of the COVID-19 pandemic. STUDY DESIGN: This is a retrospective analysis of the process improvement project implemented to continue the evaluation of potential kidney transplantation candidates and ensure waitlist placement during the COVID-19 pandemic. Operational metrics include transplantation volume per month, referral volume per month, pretransplantation patients halted before completing an evaluation per month, evaluations completed per month, and patients waitlisted per month. RESULTS: Between April and September 2020, a total of 1,258 patients completed an evaluation. Two hundred and forty-seven patients were halted during this time period before completing a full evaluation. One hundred and fifty-two patients were presented at selection and 113 were placed on the waitlist. In addition, the number of patients in the active referral phase was able to be reduced by 46%. More evaluations were completed within the virtual platform (n = 930 vs n = 880), yielding similar additions to the waitlist in 2020 (n = 282) vs 2019 (n = 308) despite the COVID-19 pandemic. CONCLUSIONS: The virtual platform allowed continued maintenance of a large kidney transplantation program despite the inability to have in-person visits. The value of this platform will likely transform our approach to the pretransplantation process and provides an additional valuable method to improve patient equity and access to transplantation.

COVID-19/epidemiology , Health Services Accessibility/organization & administration , Kidney Transplantation , Patient Selection , Renal Insufficiency/surgery , Telemedicine/organization & administration , Adult , Aged , COVID-19/prevention & control , COVID-19/transmission , Female , Humans , Male , Middle Aged , Referral and Consultation/organization & administration , Renal Insufficiency/diagnosis , Renal Insufficiency/etiology , Retrospective Studies , Waiting Lists