Challenges and Advances in the Treatment of AKI

Abstract

Treating or preventing AKI requires treating or preventing a rise in serum creatinine as well as the immediate and remote clinical consequences associated with AKI. Because a substantial number of patients with AKI progress to ESRD, identifying patients likely to progress and halting progression are important goals for treating AKI. Many therapies for AKI are being developed, including RenalGuard Therapy, which aims to maintain high urine output; a-melanocyte-stimulating hormone, with anti-inflammatory and antiapoptotic activities; alkaline phosphatase, which detoxifies proinflammatory substances; novel, small interfering RNA, directed at p53 activation; THR-184, a peptide agonist of bone morphogenetic proteins; removal of catalytic iron, important in free-radical formation; and cell-based therapies, including mesenchymal stem cells in vivo and renal cell therapy in situ. In this review, we explore what treatment of AKI really means, discuss the emerging therapies, and examine the windows of opportunity for treating AKI. Finally, we provide suggestions for accelerating the pathways toward preventing and treating AKI, such as establishing an AKI network, implementing models of catalytic philanthropy, and directing a small percentage of the Medicare ESRD budget for developing therapies to prevent and treat AKI and halt progression of CKD.

IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKI

“…To investigate the biocompatibility of CS-IGF-1C hydrogel, 96-well plates were coated with CS or CS-IGF-1C hydrogel and 1310 3 ADSCs were added per well. Cell viability was assessed using a live/dead assay kit (Invitrogen, Carlsbad, CA).…”

“…A total of 1310 3 ADSCs per well were seeded and subcultured for 12 hours. H 2 O 2 was added at concentrations of 50, 100, 200, and 500 mmol and incubated for 2 hours.…”

“…Regenerating damaged renal tissue is important for treatment of AKI, as well as for retarding the progression of CKD to ESRD. [1][2][3] Although the kidney is a delicate organ and has only limited regenerative capacity compared with other organs, recent advances in stem cell research suggest the possibility of using stem cells for kidney regeneration. 2 Several types of stem cells, such as endothelial progenitor cells, mesenchymal stem cells (MSCs), embryonic stem cells, and induced pluripotent stem cells have been applied for renal regeneration.…”

Heme Oxygenase-1 Regulates Myeloid Cell Trafficking in AKI

“…AKI is an intractable clinical condition associated with significant morbidity and mortality. 1,2 Epithelial injury and death, circulatory dysfunction, and immunologic factors from the circulation or within the kidney influence the integrity of the renal parenchyma and determine the outcome of AKI. 3,4 The innate immune system, which includes cells of the myeloid lineage such as neutrophils, circulating monocytes, tissue macrophages, dendritic cells (DCs), and their precursors, is a key contributor to the pathogenesis and resolution of AKI.…”

myo-Inositol Oxygenase: A Novel Kidney-Specific Biomarker of Acute Kidney Injury?

“…There is thus great impetus to develop novel therapies for treatment of AKI. Several agents are currently being tested in phase I/II clinical trials (2 ). Despite these ongoing efforts, no effective therapeutic agents have yet emerged on the clinical scene.…”