losartan-potassium and goralatide

The role of the renin-angiotensin system was previously thought to be restricted to the cardiovascular system. It now appears that this system also has important functions in other tissues. Hematopoiesis can be affected by inhibitors of the renin system in patients and in various experimental models. The renin system, particularly angiotensin II, has a role in different stages of hematopoiesis, notably during the first wave in the chick embryo (primitive hematopoiesis) and in the human adult (definitive hematopoiesis). In addition, the renin-angiotensin system in mice is involved in reconstitutive hematopoiesis following experimental irradiation; inhibition of this system improved the hematopoietic recovery in this situation. The clinical relevance and therapeutic applications of these findings offer a new area of clinical research. In this article, we review the evidence for a role for the renin system in the control of hematopoiesis at its different stages.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Chick Embryo; Erythropoietin; Hematopoiesis; Hematopoietic System; Humans; Mice; Oligopeptides; Renin-Angiotensin System

N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a natural inhibitor of pluripotent hematopoietic stem cell proliferation and is normally found in human plasma. Because AcSDKP is partially eliminated in urine, accumulation of AcSDKP due to chronic renal failure may cause anemia. However, the status of plasma AcSDKP level in stable kidney transplant recipients is unknown although some recipients develop anemia after kidney transplantation. In this study, we investigated the relationship between plasma AcSDKP-like immunoreactive substance (IS) level and clinical characteristics associated with renal anemia in stable kidney transplant recipients.. Forty Japanese kidney transplant recipients who underwent transplantation more than 90 days prior to the study were included. Morning blood samples were collected and plasma AcSDKP-IS levels were measured using an enzyme immunoassay.. A significant correlation was observed between plasma AcSDKP-IS level and creatinine clearance. On the other hand, no significant correlation was observed between plasma AcSDKP-IS level and prolyl oligopeptidase activity, angiotensin II, or erythropoietin level. A significant difference in plasma AcSDKP-IS level was observed between recipients with no renal anemia and those with renal anemia.. These results suggest that plasma AcSDKP level may depend largely on renal function and suggest a possibility that accumulation of AcSDKP may be partially involved in the pathogenesis of renal anemia in stable kidney transplant recipients.

Topics: Adolescent; Adult; Aged; Anemia; Angiotensin II; Biomarkers; Creatinine; Erythropoietin; Humans; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Oligopeptides; Postoperative Complications; Prolyl Oligopeptidases; Serine Endopeptidases; Young Adult

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Erythropoiesis; Erythropoietin; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Oligopeptides

N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a physiological inhibitor of hematopoiesis that is maintained at stable levels in normal plasma. Its degradation in vivo and in vitro by angiotensin-converting enzyme (ACE) accounts for the high plasma concentrations of AcSDKP in patients treated with ACE inhibitors. Because ACE inhibitors can induce anemia in some patients, we measured plasma AcSDKP concentrations in 176 patients with chronic renal failure: 120 hemodialysis (HD) and 56 nondialysis (nD) patients, 39 of whom were administered ACE inhibitors. We studied the relationships between AcSDKP levels, hematologic parameters, and recombinant human erythropoietin (rHuEPO) requirements in these patients. AcSDKP levels were significantly greater in HD (10.3 +/- 3.9 pmol/mL) and nD (3.1 +/- 1.8 pmol/mL) patients not administered ACE inhibitors than controls (1.8 +/- 0.2 pmol/mL). In all patients, treatment with ACE inhibitors significantly increased these levels fourfold. HD sessions significantly decreased AcSDKP concentrations by 66% and reduced the predialysis in vitro half-life of AcSDKP (270 +/- 109 minutes) to values (182 +/- 67 minutes) not significantly different from those of controls or nD patients. Most HD patients treated with ACE inhibitors had AcSDKP levels greater than 24 pmol/mL (the greatest concentration found in other nD and HD patients). Only in this group of patients did weekly doses of rHuEPO correlate with AcSDKP levels. Our results show that renal function is essential to maintain stable AcSDKP plasma levels, and at high levels, AcSDKP acts as a uremic toxin causing partial resistance to erythropoietin and inhibiting erythropoiesis.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Cell Count; C-Reactive Protein; Case-Control Studies; Drug Administration Schedule; Erythropoietin; Ferritins; Half-Life; Hemoglobin A; Humans; Kidney Failure, Chronic; Linear Models; Oligopeptides; Parathyroid Hormone; Recombinant Proteins; Renal Dialysis

Topics: Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Drug Interactions; Erythropoiesis; Erythropoietin; Humans; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Oligopeptides; Recombinant Proteins