Kidney international
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Kidney international · Jul 2013
ReviewGlomerular diseases seen with cancer and chemotherapy: a narrative review.
Glomerular lesions have been recognized in a number of malignant diseases. Membranous nephropathy is the most common glomerular pathology associated with solid tumors. In Hodgkin's disease, the most common lesion is minimal change disease, reflecting possibly an anomaly of T-cell function. ⋯ Failure to recognize certain paraneoplastic glomerular diseases can lead to potentially unnecessary therapies. This review describes the association of glomerular diseases with solid tumors, hematological malignancies, stem cell transplantation, and chemotherapeutic agents. We also describe the pitfalls in diagnosis and the dilemma in treating these entities.
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Kidney international · Jul 2013
The volatile anesthetic isoflurane induces ecto-5'-nucleotidase (CD73) to protect against renal ischemia and reperfusion injury.
The volatile anesthetic isoflurane protects against renal ischemia and reperfusion injury by releasing renal tubular TGF-β1. As adenosine is a powerful cytoprotective molecule, we tested whether TGF-β1 generated by isoflurane induces renal tubular ecto-5'-nucleotidase (CD73) and adenosine to protect against renal ischemia and reperfusion injury. Isoflurane induced new CD73 synthesis and increased adenosine generation in cultured kidney proximal tubule cells and in mouse kidney. ⋯ The TGF-β1-neutralizing antibody or the CD73 inhibitor attenuated isoflurane-mediated protection against HK-2 cell apoptosis. Thus, isoflurane causes TGF-β1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. Modulation of this pathway may have important therapeutic implications to reduce morbidity and mortality arising from ischemic acute kidney injury.
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Kidney international · Jun 2013
Cyst expansion and regression in a mouse model of polycystic kidney disease.
Autosomal-dominant polycystic kidney disease is characterized by progressive cyst formation and fibrosis in the kidneys. Here we describe an orthologous Pkd1(nl,nl) mouse model, with reduced expression of the normal Pkd1 transcript, on a fixed genetic background of equal parts C57Bl/6 and 129Ola/Hsd mice (B6Ola-Pkd1(nl,nl)). In these mice, the first cysts develop from mature proximal tubules around birth. ⋯ After an initial increase in blood urea within the first 4 weeks, renal function remained stable over time and the mice were able to survive up to a year. Also, in kidneys of ADPKD patients collapsed cysts were observed, in addition to massive fibrosis and immune infiltrates. Thus, B6Ola-Pkd1(nl,nl) mice show regression of cysts and renal volume that is not accompanied by a reduction in blood urea levels.
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Kidney international · Jun 2013
ReviewTargeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease.
Oxidative stress and inflammation are mediators in the development and progression of chronic kidney disease (CKD) and its complications, and they are inseparably linked as each begets and amplifies the other. CKD-associated oxidative stress is due to increased production of reactive oxygen species (ROS) and diminished antioxidant capacity. The latter is largely caused by impaired activation of Nrf2, the transcription factor that regulates genes encoding antioxidant and detoxifying molecules. ⋯ Clinical trials of the potent Nrf2 activator bardoxolone methyl showed significant improvement in renal function in CKD patients with type 2 diabetes. However, due to unforeseen complications the BEACON trial, which was designed to investigate the effect of this drug on time to end-stage renal disease or cardiovascular death in patients with advanced CKD, was prematurely terminated. This article provides an overview of the role of impaired Nrf2 activity in the pathogenesis of CKD-associated oxidative stress and inflammation and the potential utility of targeting Nrf2 in the treatment of CKD.