Suppression of collagen IV alpha-2 subunit by prolyl hydroxylase domain inhibition via hypoxia-inducible factor-1 in chronic kidney disease.

Elevation of hypoxia-inducible factor 1 protein has been shown to be protective in acute kidney injury and HIF1α enhancing drug therapies are currently in clinical trials for the treatment of anemia of chronic kidney disease. Despite its benefits, long-term HIF1 elevation seems to be associated with additional effects in the kidneys such as tubulointerstitial fibrosis. To better understand the effects of prolonged HIF1 exposure, assessment of baseline and post-therapy levels of HIF1α and other related biomarkers is essential. In this study, we assessed the effect of HIF1α enhancement using prolyl hydroxylase inhibitor (PHD-I) DMOG, on a key profibrotic marker of kidney disease. In specific, we examined the change in expression of Collagen 4 subunit A2 in cultured urinary cells of CKD patients pre and post 24-hour exposure to 1mM DMOG. Our results show that besides HIF1α enhancement, COL4A2 protein is suppressed in presence of DMOG. To determine if this effect is mediated by HIF1, we used HIF1α gene silencing in HEK293 cells and examined the effect of DMOG on protein and gene expression of COL4A2 post 24-hour exposure. We showed that silencing HIF1α reverses and amplifies the expression of COL4A2 in HEK293 cells. Our data suggest that HIF1 directly regulates the expression of COL4A2 in kidney cells and that HIF1α enhancing therapy has suppressive effects on COL4A2 that may be clinically relevant and must be considered in determining the safety and efficacy of these drugs in the treatment of anemia.

Multiple listing in kidney transplantation.

The increasing number of patients with end-stage renal disease and the expanding waiting lists for various solid-organ transplants, particularly kidney transplants, has compelled prospective transplant recipients and their care teams to explore novel ways to accelerate this process, initiating the practice of multiple listing. Multiple listing is defined as being listed for an organ transplant at more than 1 transplant center. Current policy allows patients to be listed at more than 1 transplant center in 1 or more organ procurement organization. Multiple listing can be beneficial for different groups of transplant candidates. Current data support a beneficial effect for the patient on multiple waiting lists, most notably portending a survival advantage for transplant recipients. The kidney transplant list has the most patients who are multiply listed (4.7%), followed by the liver transplant list at 3.8%. The main potential downside of multiple listing is its effect on patients not on multiple lists, as well as the cost accrued to achieve multiple listings. With the newly clarified policy of the United Network for Organ Sharing, a pivotal role for nephrologists in educating patients about the option of multiple listing becomes more apparent. In this article, current practices and policies regarding multiple listing are reviewed and opinions and ethics relating to the practice are discussed.

Early diagnosis of stress-induced apical ballooning syndrome based on classic echocardiographic findings and correlation with cardiac catheterization.

Stress-induced apical ballooning has been described as a reversible condition involving the apical left ventricular wall, sparing the base, and causing a ballooning appearance of the left ventricle during systole despite normal coronaries. We are presenting 4 cases of apical ballooning seen at our institution with echocardiographic correlation. Echocardiography showed similar anatomical apical ballooning of the left ventricular apex. The diagnosis of apical ballooning syndrome was suspected based on echocardiography in conjunction with clinical data before cardiac catheterization was performed. In one case, in addition to classic left ventricular apical ballooning, marked right ventricular apical akinesia was present on the initial echocardiographic examination. This makes diagnosis of apical ballooning syndrome most likely in this patient before cardiac catheterization. Therefore, we suggest using echocardiography more often for the early diagnosis of this disease, based on careful anatomic evaluation in conjunction with clinical data. Wall motion analysis should reveal an apical ballooning appearance involving many coronary territories. Furthermore, the additional presence of right ventricular apical akinesia during echocardiographic examination makes the diagnosis of this syndrome more likely.

Contrast-induced nephropathy: a review.

Contrast-induced nephropathy (CIN) is one of the leading causes of renal impairment in the United States and the third cause of hospital-acquired renal failure. Reduction in the incidence of CIN can lead to a decrease in the morbidity, mortality, and length of hospital stay. Although prophylactic hydration has been promising in decreasing the occurrence of CIN, other efforts such as diuretics, calcium channel blockers, theophylline, aminophylline, atrial natriuretic peptide, dopamine, and fenoldopam have been disappointing. The preventive effect of N-acetylcysteine on CIN has not been consistent in the literature. In a recent clinical trial, bicarbonate infusion was more effective than hydration in the prevention of CIN. Mechanical devices are in development to perfuse renal arteries with protective drugs during contrast exposure or for removal of contrast from coronary sinus during coronary angiography. In this article, we have reviewed available data in regards to CIN.