HDCN Abstract:  ASN Annual Meeting -- San Francisco  

H”mme M, Bloch J, Sch„fer J, et al.

Bicarbonate-Based Peritoneal Dialysis Fluid Increases Expression of Aquaporins 1 and 3 and Enhances Cell Migration in Human Peritoneal Mesothelial and Endothelial Cells.

ASN Annual Meeting -- San Francisco
J Am Soc Nephrol (Nov) 18:690A 2007

Aquaporins (AQP) modulate not only water transport, but also cell migration, neoangiogenesis and CO2 transport across cell membranes. We recently observed upregulation of AQP1, 3 and 11 in peritoneal mesothelial cells by bicarbonate - but not by lactate-buffered peritoneal dialysis solutions. To further investigate the underlying mechanisms and functional consequences of this effect, human primary (HPMC) and immortalized mesothelial cells (Met5a) and human umbilical vein endothelial cells (HUVEC) were incubated with bicarbonate-buffered (BicaVera, BPDF) or lactate-buffered PD fluid (Balance, LPDF).

In HPMC, BPDF time- and dose-dependently increased AQP1, 3 and 11 mRNA (after 24h: +231128, 24521585 and 14573% relative to medium) and decreased AQP9 (-6017%), whereas LPDF had no effect on AQPs. In HUVEC, AQP1, 3 and 9 expression was increased by 397320, 235113 and 300182% respectively, and AQP11 decreased to 149% upon incubation with BPDF compared to LPDF.

The regulation of AQP1 and 3 was mainly driven by the bicarbonate concentration and to a minor degree by pH or CO2. It was reproduced by increasing medium glucose to at least 2.3% and bicarbonate to 34 mM, and by adding at least 24 mmolar bicarbonate to LPDF containing 2.3% glucose. The regulation of AQP1 and 3 was confirmed on the protein level.BPDF induced ERK1/2 phosphorylation in HPMC; ERK inhibition reduced the BPDF-induced upregulation of AQP3. In addition, PKC inhibitor BIS subtotally inhibited the BPDF-induced upregulation of AQP1 and 3. BPDF augmented mesothelial cell migration by 18949 compared to medium and by 35566% compared to LPDF (both p<0.001). We speculate that this effect was related to the upregulation of AQPs.

In summary, bicarbonate-based PDF specifically increases mesothelial and endothelial cell AQP1 and 3 expression and enhances cell migration. The buffer compound of PD fluids may thus have important implications with respect to peritoneal membrane functions such as wound healing and neoangiogenesis.

© Copyright 2007-2008, American Society of Nephrology. Reproduced with permission.
Until September of 2008, all ASN abstracts from the 2007 Annual Meeting are available at this link.

Disclaimer: Abstracts often have errors, both typographical and otherwise. This posting is an electronic translation of submitted abstracts which has not been verified against the original submitted abstract nor with the authors for accuracy. As a result, there may be errors, especially with regard to drug doses, but not limited to these. Abstracts undergo only limited review, and data often are changed as a result of the peer review process, so their reliability is less than manuscripts published in peer-reviewed journals. In using these summaries, you are agreeing that you are aware of these limitations.

The materials are provided on an as-is basis without any warranty of any kind, either express or implied. In addition to errors, the information presented may be incomplete or outdated. The information contained is not intended nor recommended as a substitute for professional medical advice. You are advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each device to be used or drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other health care professional, relying on independent experience and knowledge of the patient, to determine drug, disease, and the best treatment for the patient.

To the fullest extent permitted by law, HDCN, ASN and their affiliates and suppliers disclaim all warranties, express or implied, including, but not limited to, any warranty of merchantability, non- infringement or fitness for a particular purpose.

In no event shall HDCN, ASN, or their affiliates or suppliers be liable for any damages whatsoever (including, but not limited to, direct, indirect, incidental, consequential, punitive or exemplary damages, or any damages for loss of profits, use, data, goodwill or other intangibles) arising from or in any way relating to these terms, the materials, or any information, goods or services obtained from or referred to in the materials, whether based on warranty, contract, tort (including, but not limited to, negligence), or any other legal theory, and whether or not any or all of the limited entities is advised of the possibility of such damages.