Cell Biology – Immunology – Pathology

Kidney International (2004) 66, 641–646; doi:10.1111/j.1523-1755.2004.00784.x

Uremia causes endothelial progenitor cell deficiency

KIRSTEN DE GROOT1, FERDINAND HERMANN BAHLMANN1, JOHANNA SOWA, JANA KOENIG, JAN MENNE, HERMANN HALLER and DANILO FLISER

Division of Nephrology, Department of Internal Medicine Hannover Medical School, Hannover, Germany

Correspondence: Kirsten de Groot, M.D, Division of Nephrology, Department of Internal Medicine, Hannover Medical School Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. E-mail:groot.kirsten.de@mh-hannover.de

1Both authors equally contributed to the study.

Received 18 September 2003; Revised 29 December 2003; Re-revised 23 February 2004; Accepted 9 March 2004.

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Abstract

Uremia causes endothelial progenitor cell deficiency.

Background

 

Circulating bone marrow–derived endothelial progenitor cells (EPCs) promote vascular repair. Their number in peripheral blood correlates with endothelial function and cardiovascular risk in humans. We explored whether uremia influences the number of EPCs.

Methods

 

We assessed circulating CD34+ hematopoietic progenitor cells in whole blood using flow cytometry and EPCs (in vitro assay) in 46 patients with advanced renal failure and in 46 age- and gender-matched healthy subjects. Further, the effect of uremia on EPC differentiation was studied in vitro and in vivo.

Results

 

Both in renal patients (r = 0.34, P < 0.02) and in healthy subjects (r = 0.32, P = 0.04) the number of EPCs was significantly correlated to the absolute number of CD34+ hematopoietic progenitor cells. Renal patients had significantly fewer EPCs than healthy subjects, however (167 plusminus 15 cells/high power field vs. 235 plusminus 17 cells/high power field; P < 0.05). Uremic serum significantly (P < 0.05) inhibited EPC differentiation and functional activity in vitro. Amelioration of uremia after institution of renal replacement therapy in patients with terminal renal failure also significantly (P < 0.05) increased the number of EPCs.

Conclusion

 

Uremia inhibits differentiation of EPCs. This may impair cardiovascular repair mechanisms in patients with renal failure.

Keywords:

endothelial progenitor cells, hematopoietic progenitor cells, renal failure, uremia, vascular regeneration

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