Mature form of adrenomedullin is a useful marker to evaluate blood volume in hemodialysis patients.

We investigated the pathophysiological significance of the mature form of adrenomedullin (AM) in hemodialysis (HD) patients. Thirty-nine HD patients were enrolled and divided into two groups: those undergoing ultrafiltration (UF) during an HD session, group I; and those not undergoing UF, group II. We measured mature AM, atrial natriuretic peptide (ANP), endothelin-1, nitric oxide, cyclic guanosine 3',5'-monophosphate, and catecholamine levels at 1-hour intervals during HD sessions. On-line optical measurement of hematocrit was used to estimate change in blood volume during HD. In group II, blood volume did not change significantly during HD, nor did plasma mature AM concentrations estimated at the beginning and end of the HD treatment (3.0 +/- 0.3 and 2.8 +/- 0.2 fmol/mL, respectively). However, blood volume decreased significantly in group I patients (-7.3% +/- 0.6%), as did plasma mature AM concentrations (from 4.4 +/- 0.3 to 3.1 +/- 0.3 fmol/mL; P < 0.01). In contrast to mature AM, plasma ANP concentrations declined in both groups (from 193 +/- 32 to 87 +/- 14 pg/mL in group I and 67 +/- 12 to 46 +/- 8 pg/mL in group II). We conclude that mature AM is a useful marker to evaluate circulating blood volume in HD patients. Circulating blood volume may regulate the conversion of AM from the inactive to the mature form.

The potential of bone marrow-derived cells to differentiate to glomerular mesangial cells.

Bone marrow stem cells (BMC) develop into hematopoietic and mesenchymal lineages but have not been known to differentiate into glomerular cells. To investigate whether such differentiation is possible, a search was made for donor glomerular cells in lethally irradiated C57BL/6j (B6) mice given transplants of BMC from syngeneic mice transgenic for green fluorescence protein (GFP) ([GFP-->B6] mice). After the recipients of donor BMC manifested GFP-positive cells in their glomeruli, the numbers of such cells increased markedly, in a time-dependent manner, from 2 wk to 24 wk after bone marrow transplantation. Immunohistochemical analyses revealed that most GFP-positive cells in the glomeruli were neither macrophages nor T cells. With the use of a laser-scanning confocal microscope, GFP-positive cells were observed within the mesangium of [GFP-->B6] mice. Furthermore, indirect immunofluorescence assays demonstrated that desmin-positive cells in the glomeruli of these chimeric mice were also positive for GFP. Among glomerular cells isolated from [GFP-->B6] mice 24 wk after bone marrow transplantation and then cultured, the majority of cells (approximately 84%) stained for desmin and approximately 60% of the desmin-positive cells expressed GFP. In addition, these GFP-positive cells in the cultures contracted in response to angiotensin II stimulation. These results suggest that bone marrow-derived cells may have the potential to differentiate into glomerular mesangial cells.