Carbamylated Erythropoietin Outperforms Erythropoietin in the Treatment of AKI-on-CKD and Other AKI Models.

Erythropoietin (EPO) may be a beneficial tissue-protective cytokine. However, high doses of EPO are associate with adverse effects, including thrombosis, tumor growth, and hypertension. Carbamylated erythropoietin (CEPO) lacks both erythropoietic and vasoconstrictive actions.

Kidney protection and regeneration following acute injury: progress through stem cell therapy.

Acute kidney injury (AKI) is a common clinical entity with high morbidity and mortality rates and ever increasing medical costs. A large number of patients who are hospitalized with morbidities such as diabetes, vascular disease, or chronic kidney disease are at high risk to develop AKI due to ischemic and nephrotoxic insults. The pathophysiology of ischemic and toxic forms of AKI is complex and includes tubular and vascular cell damage and inflammation.

Protective actions of administered mesenchymal stem cells in acute kidney injury: relevance to clinical trials.

Current therapies for acute kidney injury remain primarily supportive and have failed to reduce morbidity, mortality (>50%), and associated costs. This prompted our studies in which rats with bilateral ischemia/reperfusion-induced acute kidney injury were treated with bone marrow-derived, culture-expanded allogeneic mesenchymal stem cells. Their administration into the suprarenal aorta after reflow significantly protected renal function and hastened repair, mediated by complex antiapoptotic, mitogenic, anti-inflammatory, and immune modulating actions that were not elicited by isogeneic fibroblasts.

Role of SDF-1 as a regulatory chemokine in renal regeneration after acute kidney injury.

Both the homing of hematopoietic stem cells (HSCs) to the bone marrow and their engraftment in recipients of bone marrow transplants are primarily mediated by the chemokine stromal-derived factor-1 (SDF-1) or CXCL12, which activates CXCR4, its cognate receptor on HSCs. We showed that the recruitment and temporary attachment of CXCR4-expressing cells, such as HSCs and a fraction of mesenchymal stem cells (MSCs), to the kidney, following ischemia/reperfusion acute kidney injury, are similarly mediated by robustly upregulated SDF-1 in the kidney, indicating that such organ injury appears to lead to the transient expression of a facultative stem cell niche. This SDF-1 response of the injured kidney facilitates both the mobilization from the bone marrow and homing of precursor cells, and other CXCR4-expressing cells such as administered MSCs, to the kidney, where they aid in its protection and repair.

Mesenchymal stem cells: a new therapeutic tool for AKI.

Acute kidney injury (AKI) is a common clinical complication, associated with poor outcomes and the development of chronic kidney disease. Despite major advances in the understanding of its pathophysiology, available therapies for AKI are only supportive; therefore, adequate functional recovery from AKI must predominantly rely on the kidney's own reparative ability. An extensive body of preclinical data from our own and from other laboratories has shown that administration of adult multipotent marrow stromal cells (commonly referred to as mesenchymal stem cells [MSCs]), effectively ameliorates experimental AKI by exerting paracrine renoprotective effects and by stimulating tissue repair.

Extent of glomerular tubularization is an indicator of the severity of experimental acute kidney injury in mice.

Background: Acute kidney injury (AKI) secondary to ischemia continues to be a major clinical problem due to its high morbidity and mortality, and limited treatment options. Animal models are critical to both the study of the pathophysiology of AKI and the development of new interventions. Although histological changes at the glomerulotubular junction have been described in AKI, we examined here whether the extent of glomerular tubularization correlates with the degree of renal insufficiency in this condition.

Cytoprotective doses of erythropoietin or carbamylated erythropoietin have markedly different procoagulant and vasoactive activities.

Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a potential therapy for prevention of injury and restoration of function in nonhematopoietic tissues. However, the minimum effective dose required to mimic and augment these normal paracrine functions of erythropoietin (EPO) in some organs (e.g.