Relationship between urinary sodium excretion and pioglitazone-induced edema

Akinobu Nakamura, Takeshi Osonoi, Yasuo Terauchi, Akinobu Nakamura, Takeshi Osonoi, Yasuo Terauchi

Abstract

To investigate the factors contributing to pioglitazone-induced edema, we analyzed sodium excretion and several clinical parameters before and after administration of pioglitazone. We analyzed these parameters before and after 8 weeks of administration of pioglitazone to female subjects with type 2 diabetes. When we evaluated whether a significant correlation was found between salt excretion and blood pressure, six patients showed such correlation and 20 patients did not. After 8 weeks of pioglitazone administration, five patients had developed edema, and, surprisingly, such correlation was not found in all five subjects. Salt excretion after administration of pioglitazone was significantly lower in subjects who developed edema and those who showed the correlation, and the hematocrit was significantly lower after administration in the subjects who showed the correlation, but not in the edema group. Pioglitazone-induced edema would be caused not only by fluid retention, but also by other factors, such as vascular permeability. (J Diabetes Invest, doi: 10.1111/ j.2040-1124.2010.00046.x, 2010).

Keywords: Edema; Pioglitazone.

Figures

Figure 1
Figure 1
Changes in (a) salt excretion and (b) hematocrit after administration of pioglitazone to three groups for 8 weeks: a group that had no correlation between salt excretion and blood pressure but had edema (group A: open diamonds), a group that had correlation but did not have edema (group B: filled triangles), and a group that had neither correlation nor edema (group C: filled diamonds). Bars indicate the mean of each group.
Figure 2
Figure 2
Hypothesis on mechanisms of pioglitazone‐induced edema. Administration of pioglitazone to the subjects who developed pioglitazone‐induced edema (group A) caused fluid retention because of sodium reabsorption and increased fluid in the intravascular space would be mobilized to extravascular space because of vascular hyperpermeability. In contrast, administration of pioglitazone caused fluid retention in the subjects that had a correlation between salt excretion and blood pressure (group B); however, increased fluid would be retained in the intravascular space. Administration of pioglitazone to the subjects that had neither correlation nor edema (group C) did not cause fluid retention.

References

    1. Yki‐Järvinen H. Thiazolidinediones. N Engl J Med 2004; 351: 1106–1118
    1. Guan Y, Hao C, Cha DR, et al. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC‐mediated renal salt absorption. Nat Med 2005; 11: 861–866
    1. Kawamori R, Kadowaki T, Onji M, et al. Hepatic safety profile and glycemic control of pioglitazone in more than 20,000 patients with type 2 diabetes mellitus: postmarketing surveillance study in Japan. Diabetes Res Clin Pract 2007; 76: 229–235
    1. Yamasue K, Tochikubo O, Kono E, et al. Self‐monitoring of home blood pressure with estimation of daily salt intake using a new electrical device. J Hum Hypertens 2006; 20: 593–598
    1. Murohara T, Horowitz JR, Silver M, et al. Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin. Circulation 1998; 97: 99–107
    1. Das Evcimen N, King GL. The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 2007; 55: 498–510
    1. Emoto M, Fukuda Y, Nakamori Y, et al. Plasma concentrations of vascular endothelial growth factor are associated with peripheral edema in patients treated with thiazolidinedione. Diabetologia 2006; 49: 2217–2218
    1. Parulkar AA, Pendergrass ML, Granda‐Ayala R, et al. Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med 2001; 134: 61–71
    1. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005; 66: 1279–1289
    1. Hollenberg NK. Considerations for management of fluid dynamic issues associated with thiazolidinediones. Am J Med 2003; 115: 111S–115S

Source: PubMed

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