The Bioartificial Kidney and Bioengineered Membranes in Acute Kidney Injury

Ding, Feng; Humes, H. David

doi:10.1159/000142936

Cited by 33 publications

(20 citation statements)

References 31 publications

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“…24,25 Our study has realized the successful construction of the Epo-expressing RAD, whereas no effect was found on other functions of renal tubular epithelial cells. This device can replace the majority of functions of the kidney and also provide a new approach and ideas for the future treatment of ARF and CRF.…”

Section: Discussionmentioning

confidence: 90%

Construction of an Erythropoietin-Expressing Bioartificial Renal Tubule Assist Device

et al. 2011

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Methods: A eukaryotic expression vector pcDNA3.1-hEpo was constructed by standard cloning methods. G418 was applied to select for a stable erythropoietin (Epo) expression cell clone. Cell viability and cell growth curve were generated with MTT chromatometry. HK-2 cells were transfected with pcDNA3.1-hEpo, cultured, and then seeded into the hollow fibers of high-flux hemofilters. The expression levels of Epo in the culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA). The inulin leak rate and the transport of Na + and glucose (Glu) of the Epo-expressing bioartificial renal tubule assist device (RAD) were determined and compared with the conventional RAD. The specific inhibition of the transport by ouabain and phlorizin was determined. Results: The Epo expression plasmid pcDNA3.1-hEpo was successfully constructed and generated. Stable expression of Epo was obtained by selection of G418 after HK-2 cells were transfected. There was no obvious difference about cell growth curves between the transfected and untransfected HK-2 cells (p > 0.05). High levels of Epo expression were observed in both intra-and extraluminal culture media in the novel RAD. There was no significant difference about the inulin leak rate and the transport rate of Na + and Glu between the novel and conventional RADs (p > 0.05 for each). And the transport function of the novel and conventional RADs was significantly inhibited by ouabain and phlorizin (p < 0.01 for each). Conclusions: A novel RAD that can express Epo was successfully constructed in vitro, in which other functions of the RAD were not affected by the transfection of pcDNA3.1-hEpo.

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Section: Discussionmentioning

confidence: 90%

Construction of an Erythropoietin-Expressing Bioartificial Renal Tubule Assist Device

et al. 2011

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“…On the other hand, in the control group, Na + and glucose were transported via physical filtration, which could not be abolished by ouabain or phlorizin. [15][16][17][18] In this study, we modified Humes's method by using renal tubular epithelial cell line NRK-52E and seeding them into antiluminal space of hollow fibers. This way, over 80% Na + and glucose transport rates were accomplished in the RAD group.…”

Section: Discussionmentioning

confidence: 99%

Construction of bioartificial renal tubule assist device In Vitro and its function of transporting sodium and glucose

Dong

Chen

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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To explore a new way of constructing bioartificial renal tubule assist device (RAD) in vitro and its function of transporting sodium (Na(+)) and glucose and to evaluate the application of atomic force microscope in the RAD construction, rat renal tubular epithelial cell line NRK-52E was cultured in vitro, seeded onto the outer surfaces of hollow fibers in a bioreactor, and then cultured for two weeks to construct RAD. Bioreactor hollow fibers without NRK-52E cells were used as control. The morphologies of attached cells were observed with scanning electron microscope, and the junctions of cells and polysulfone membrane were observed with atomic force microscope. Transportation of Na(+) and glucose was measured. Oubaine and phlorizin were used to inhibit the transporting property. The results showed that NRK-52E cells and polysulfone membrane were closely linked, as observed under atomic force microscope. After exposure to oubaine and phlorizin, transporting rates of Na(+) and glucose were decreased significantly in the RAD group as compared with that in the control group (P<0.01). Furthermore, when the inhibitors were removed, transportation of Na(+) and glucose was restored. It is concluded that a new RAD was constructed successfully in vitro, and it is able to selectively transport Na(+) and glucose.

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“…The membrane addition of cultured proximal tubular cells, immortalized and yet still biologically active remains a technique which has met with mixed reviews. Initial success in both phase I and early phase II studies [25] were followed with less than convincing data in a prospective randomized phase II evaluation [26]. However, with the recognition of organ-to-organ crosstalk, this approach perhaps applied early in the process of AKI might not only uncover valuable information of cellular repair but promote an attenuated AKI process both in severity as well as length of dysfunction.…”

Section: Toxin-related Systemsmentioning

confidence: 99%

Renal Replacement Therapy for Acute Renal Injury: We Need Better Therapy

Demirjian¹,

Paganini²

2011

Contributions to Nephrology

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Dialytic support of patients with acute kidney injury (AKI) has taken on an important aspect of critical care medicine. Increased morbidity and mortality associated with the AKI syndrome and the lack of great improvement despite the addition of differing dialytic techniques (and intensity) speaks to the need for a re-evaluation of renal support. Continuous therapies have brought greater control of urea, volume, acid/base status and enhanced hemodynamic stability over the traditional intermittent approaches. However, the incremental efficiency achieved by intense dialysis has not improved outcome in patients with AKI. We need to move beyond urea-based decision-making and pursue clinically relevant goal-targeted therapies. The latter will invariably lead to re-evaluation of the timing, intensity and duration of therapy, which traditionally have been mainly solute driven. Whether this will be via specifically designed membrane extracorporeal support or focused drug or cell-based therapies is currently under consideration. Volume determination and variability remain another moving target for therapy. Machine-generated feedback mechanisms responding to specific endpoints or compartmental changes are also under development. Improved diagnostic criteria, especially in septic-induced renal dysfunction, may allow for specific adsorption techniques using a variety of membrane-imbedded substances from activated charcoal to polymyxin B to newer resins. Cascade apheretic techniques have been attempted in specific disease entities to capture a larger group of potential toxins, while nanoporous membranes have been developed to remove a specific sized entity. Bio-artificial systems utilizing functioning cells should help with the recovery of injured cell and cell protection in those yet viable. Simple maneuvers to reduce the cost of delivered therapy, and the development of a more robust severity scoring system to help address the futile use of technology would be of great help. Greater attention to elements lost during intervention which may require supplementation, as well as the development of on-line replacement technology and coagulation friendly systems, will help eliminate much of the current cost of therapy.

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The Bioartificial Kidney and Bioengineered Membranes in Acute Kidney Injury

Cited by 33 publications

References 31 publications

Construction of an Erythropoietin-Expressing Bioartificial Renal Tubule Assist Device

Construction of an Erythropoietin-Expressing Bioartificial Renal Tubule Assist Device

Construction of bioartificial renal tubule assist device In Vitro and its function of transporting sodium and glucose

Renal Replacement Therapy for Acute Renal Injury: We Need Better Therapy

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