Cardiovascular disease (CVD) is the main cause of death in patients with kidney disease. Hypoxia plays a crucial role in the progression of chronic kidney disease (CKD) and cardiovascular disease, which is associated with fibrosis, inflammation, and oxidative injury. Previous studies have indicated that prolyl hydroxylase (PHD) inhibitors, stabilizers of hypoxia-inducible factors (HIFs), can be used to treat acute organ injuries such as renal ischemia-reperfusion, myocardial infarction, and, in some contexts, CKD. However, the effects of PHD inhibitors on cardiovascular complications in CKD remain unknown. In the present study, we investigated whether HIF activation has a beneficial effect on kidney and cardiovascular outcomes in the remnant kidney model. We used the 5/6 nephrectomy model with the nitric oxide synthase inhibitor Nω-nitro-l-arginine (20 mg/L in the drinking water). Rats received diet with 0.005% enarodustat (PHD inhibitor) or vehicle for 8 wk starting 2 wk before 5/6 nephrectomy. Activation of HIF by the PHD inhibitor reduced cardiac hypertrophy and ameliorated myocardial fibrosis in association with restored capillary density and improvement in mitochondrial morphology. With regard to kidneys, enarodustat ameliorated fibrosis in association with reduced proinflammatory cytokine expression, reduced apoptosis, and restored capillary density, even though renal endpoints such as proteinuria and serum creatinine levels were not significantly affected by enarodustat, except for blood urea nitrogen levels at 4 wk. In addition, cardiac hypertrophy marker genes, including atrial natriuretic peptide, were suppressed in P19CL6 cells treated with enarodustat. These findings suggest that PHD inhibitors might show beneficial effects in cardiovascular complications caused by CKD.

Although the use of icodextrin PD solution was approved for only 1 exchange daily, a number of centers have, during the last few years, begun to use 2 exchanges daily either as a glucose-sparing policy as suggested by Gobin et al. (1), or to improve ultrafiltration (UF) as suggested by Sav et al.(2) in an elegant 3-month prospective controlled study.In a retrospective analysis of 9 patients using 2 daily icodextrin exchanges over a 6-month period (3), we also documented the beneficial effects of such an approach for UF failure. We were pleased that Ballout et al. (4) confirmed those findings, although we are disappointed that they did not quote our work that appeared in International Urology and Nephrology as an advanced publication in February 2010.The use of 2 icodextrin exchanges daily for 8-hour durations has now become a treatment option in our unit for patients with UF failure. Sav et al. and Ballout et al. both observed an increase in icodextrin metabolite levels that were not statistically significant, either because of the short duration in the former study or the small number of patients in the latter. By contrast, Gobin et al. observed a doubling of blood icodextrin levels (1). We believe that this issue and other possible side effects of the long-term use of 2 icodextrin exchanges should be kept in mind until long-term controlled studies establish the safety of that practice.

Recent epidemiologic studies revealed a correlation between acute kidney injury (AKI) episodes and the progression to chronic kidney disease (CKD). Although the severity and duration of the initial insult likely predict the development of CKD, information regarding tissue markers predictive of early development of renal fibrosis is limited. We investigated key markers in fibrotic kidney in rats and mice. Seven‐ to eight‐week‐old male Sprague–Dawley rats underwent bilateral ischemia–reperfusion injury (IRI). Kidney tissues were collected to determine the markers correlated with the severity of kidney fibrosis. In a separate set, a specific chemokine (C‐C motif) receptor 2 (CCR2) inhibitor, RS‐102895, was administered to 9‐week‐old male C57BL/6J mice that underwent unilateral IRI (9.2 mg/kg/day in drinking water for 17 days) to investigate whether blockade of the monocyte chemotactic protein‐1 (MCP‐1) signaling was sufficient to prevent fibrosis. Among candidate tissue markers, neutrophil gelatinase‐associated lipocalin (NGAL) and MCP‐1 mRNA expressions were correlated with kidney fibrosis. Studies on macrophage polarity showed that mRNA expression of M2, but not M1 macrophage markers, were correlated with acute‐phase serum creatinine and fibrosis. Pharmacological blockade of the MCP‐1–CCR2 signaling downregulated CCR2, which was insufficient to improve fibrosis in mouse unilateral IRI model, suggesting that additional, redundant pathways contribute to fibrosis. These findings suggested that tissue NGAL expression and M2 macrophage markers are promising markers that show severity of kidney fibrosis. Mechanistic involvement of these markers in CKD pathogenesis warrant additional investigation.

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We report the case of a 53-year-old hemodialysis patient with severe aortic stenosis, who developed acute systemic hypoperfusion after arteriovenous fistula (AVF) construction. He presented with hypotension and repeated syncope soon after distal radiocephalic AVF construction, and finally developed a respiratory arrest. His blood pressure and hemodynamics recovered promptly by sub-emergent aortic valve replacement surgery. In the present case, the heart with severe aortic stenosis could not increase cardiac output in response to the reduction in peripheral vascular resistance caused by the AVF. High-output heart failure, a relatively rare AVF-associated disorder, occurs with an excessive AVF flow, usually more than 3 L/min or 30% of cardiac output. However, heart failure may develop soon after construction of an AVF with a moderate blood flow if a patient's cardiac function is severely impaired. In addition, heart failure may improve with AVF preservation if the underlying heart disease is treatable.