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3857 The hematopoietic microenvironment (niche) plays a key role in the maintenance of hematopoietic stem cells (HSC). The bone lining-osteoblast has been identified as a crucial component of the stem cell niche and regulates the number of HSC in the niche via a variety of membrane-bound and secreted molecules. Chronic Kidney Disease (CKD) is marked by a specific Mineral Bone Disease (CKD-MBD), due to a sustained parathyroid hormone (PTH) release. This chronical hyperparathyroidy results in increased bone turnover due to increased osteoblast activity. We have established a mouse model of CKD to study the relationship between disturbed bone metabolism and hematopoiesis. C57Bl/6 mice underwent surgically-induced CKD (thermocauterisation-nephrectomy). Twelve weeks after CKD-induction, bone structure was analyzed by micro-CT scan to confirm CKD-MBD. Indeed, all mice showed the features of CKD including significantly increased urea levels, increased trabecular bone volume, and a decrease in span incurvation and cortical thickness. In addition, CKD mice developed anemia. Subsequently, bone marrow cells (BMC) were harvested from CKD mice and sham-operated controls. Long-term HSC and short-term hematopoietic progenitor cells (HPC) were analyzed phenotypically by flowcytometry and functionally by cobblestone area forming cell (CAFC) assays and colony assays (CFU-C). The frequencies of long-term repopulating LinnegSca1posc-KitHI (LSK) CD135negCD34neg HSC were significantly decreased in CKD mice compared to sham-operated controls (0.0028% ± 0.001 vs 0.0049% ± 0.001, p<0.05; n=5 per group), whereas the frequencies of HPC (LSK CD135negCD34pos) and multipotent progenitors (MPP; LSK CD135posCD34pos) remained stable. Also, total LSK cell number correlated positively with trabecular bone volume. However, CAFC analysis showed a decrease in both HSC and HPC frequencies (0.5 ± 0.1 vs 1.4 ± 0.7 CAFC week 5 per 105 BMC, p<0.05; 0.6 ± 0.002 vs 1.5 ± 0.2 CAFC week 3 per 105 BMC, p<0.05 for CKD vs controls respectively; n=4 per group), indicating a functional defect in their repopulating capacity. The colony-forming capacity of BMC obtained from CKD mice and controls was similar (4.4 × 104 ± 1.5 × 104 vs 4.6 × 104 ± 1.7 × 104 CFU-C per femur for CKD vs controls respectively; n=5). In contrast, a 3.6-fold increase in the frequency of peripheral blood CFU-C was found in CKD mice compared to sham-operated controls (42.7 ± 2.6 vs 11.8 ± 1.6 CFU-C per ml for CKD vs controls respectively; n=5). CKD mice showed a 2.8-fold reduction in G-CSF-induced HSC/HPC mobilization compared to controls (355 ± 281 vs 1005 ± 476 CFU-C per ml peripheral blood for CKD vs controls respectively; n=5 per group). Analysis of BM extracellular fluid showed a 2.3-fold reduction in elastase activity and an increase of the protease inhibitor a1-antitrypsin in CKD mice compared to controls. No differences in MMP-9 activity were observed between the groups. Together, our data show that in CKD 1) LSK CD135negCD34neg HSC frequencies are significantly decreased 2) LSK CD135negCD34pos HPC and LSK CD135posCD34pos MPP remain at similar levels 3) CAFC-week 3 HPC and CAFC week 5 HSC are significantly decreased 4) BMC CFU-C remain at similar levels, while peripheral blood CFU-C are increased and 5) G-CSF-induced stem cell mobilization is impaired in CKD. We hypothesize that the observed changes in the hematopoietic compartment are due to increase osteoblast activity. Disclosures: Massy: Amgen: Honoraria, Research Funding; SHIRE: Honoraria, Research Funding; Genzyme: Honoraria, Research Funding; Baxter: Research Funding; INEOS: Honoraria, Research Funding.