The effect of renal transplantation on adiponectin and its isoforms and receptors

Abstract

Insulin resistance (IR) and other proatherogenic risk factors associated with end-stage kidney disease (ESKD) are improved by renal transplantation. Adiponectin is a protein with insulin-sensitizing, anti-inflammatory, and antiatherogenic properties. It exists in several isoforms, but the high molecular weight (HMW) isoform correlates best with insulin sensitivity. Paradoxically, the levels of this protein and its HMW isoform are increased in ESKD. We measured the homeostasis model assessment for insulin resistance (HOMA-IR), plasma adiponectin and its isoforms, and messenger RNA for adiponectin receptors (AdipoR1 and AdipoR2) on peripheral blood mononuclear cells in 54 stable transplant recipients, 50 patients established on hemodialysis, and 52 controls; groups were matched for body mass index and sex. HOMA-IR values were significantly higher in patients with ESKD compared with controls ( P < .0005) and transplant patients ( P < .05) but there was no difference between the latter 2 groups. Adiponectin levels were also higher in patients with ESKD compared with controls ( P < .0005), and although levels were lower in the transplant group, they remained higher than in controls ( P < .0001). However, although the absolute amount of HMW isoform in transplant patients remained higher than in controls ( P < .0001), the proportion was similar, and less than in patients with ESKD ( P < .005). The absolute amount of the HMW isoform correlated with superior metabolic indices in all 3 cohorts. AdipoR1 and AdipoR2 messenger RNA levels after transplantation were significantly lower than those of ESKD subjects ( P < .0001, P < .01), but transplant patients had less AdipoR1 than controls, although their AdipoR2 levels were higher. AdipoR1 correlated with AdipoR2 in all 3 cohorts. We conclude that HOMA-IR was lower in the transplant group compared with the group on hemodialysis and this coincided with lower total adiponectin levels and absolute amount of the HMW isoform and AdipoR on peripheral blood mononuclear cells. Lower AdipoR after transplantation may be secondary to immunosuppression and/or an improvement in glomerular filtration rate and the uremic milieu.