Circulating CTRP9 correlates with the prevention of aortic calcification in renal allograft recipients.

BACKGROUND: Cardiovascular disease (CVD) due to atherosclerosis is a major cause of death in renal allograft recipients. Recently, C1q/TNF-α related protein-9 (CTRP9), which is a paralog of adiponectin (ADPN), has been suggested to be related to the prevention of atherosclerosis and the occurrence of CVD, but this relationship has not been confirmed in renal allograft recipients. SUBJECTS AND METHODS: The relationships among the serum CTRP9 concentration, serum ADPN concentration, and vascular calcification were investigated in 50 kidney transplantation recipients at our hospital. Calcification of the abdominal aorta was evaluated according to the aortic calcification area index (ACAI) calculated from CT images. Changes in the serum CTRP9 and ADPN fractions and ACAI were examined for 8 years. In addition, the expression of CTRP9 and ADPN and their respective receptors AdipoR1 and R2 in muscular arteries of the kidney was examined by immunofluorescence. RESULTS: In renal allograft recipients, the serum CTRP9 concentration at the start of the observation was not significant correlated with eGFR or serum high-molecular-weight (HMW)-ADPN concentration (rS = -0.009, p = 0.950; rS = -0.226, p = 0.114, respectively). However, the change in the serum CTRP9 concentration was positively correlated with the change in the serum HMW-ADPN concentration (rS = 0.315, p = 0.026) and negatively correlated with the change in ACAI (rS = -0.367, p = 0.009). Multiple regression analysis revealed that the serum HMW-ADPN concentration was a significant positive factor for the change in the serum CTRP9 concentration. Moreover, for ACAI, an increase in the serum CTRP9 concentration was an improving factor, but aging was an exacerbating factor. Furthermore, colocalization of CTRP9 and AdipoR1 was noted in the luminal side of intra-renal arterial intima. CONCLUSION: In renal allograft recipients, both CTRP9 and HMW-ADPN were suggested to prevent the progression of aortic calcification through AdipoR1.

Changes in double-strand DNA breaks predict delayed graft function (DGF) in Japanese renal allograft recipients.

BACKGROUND: Although delayed graft function (DGF) is a serious complication following kidney transplantation, a reliable and early diagnostic test is lacking to identify the grade of DGF. METHODS: We investigated changes in double-strand DNA breaks (DSBs), and factors related to DGF, such as ischemic times at transplantation and serum creatinine (sCr) levels. DSBs were detected by phospho-histone H2A.X (γ-H2AX) expression and cellular regeneration by Ki-67 before (0 h) and 1 h after allograft reperfusion (1 h) in each subject. RESULTS: The expression of γ-H2AX or Ki-67 at 0 h showed no difference between the living and deceased donors. γ-H2AX at 1 h decreased in the living donors, but increased in the deceased donors compared with that of 0 h(p = 0.017). Changes (Δ) in γ-H2AX between 0 and 1 h were different among subgroups, i.e., immediate function, slow graft function with dialysis < 7 days, DGF with dialysis < 4 weeks, severe DGF with dialysis > 4 weeks, or primary non-function (PNF) (p = 0.04). Severe DGF and PNF cases showed greater increase in Δγ-H2AX (p = 0.019), and were distinguished by > 12% of Δγ-H2AX at 100% sensitivity and 88.2% specificity (ROC analysis, AUC: 0.922, p = 0.023). In a multivariate regression analysis, donor sCr and Δγ-H2AX were two main predictors of the grade of DGF (p = 0.002). The expression of Ki-67 was very low at both 0 h and 1 h. CONCLUSION: The combination of donor sCr and Δγ-H2AX from 0 to 1 h after reperfusion may predict severe DGF and PNF in the early phase.

High molecular weight adiponectin inhibits vascular calcification in renal allograft recipients.

BACKGROUND: Adiponectin (ADPN) prevents the development/recurrence of cardiovascular events via its anti-atherogenic effects. However, few long-term studies have examined the changes in serum ADPN levels and arterial calcification seen in renal allograft recipients. SUBJECTS AND METHODS: The effects of the serum ADPN level on arterial calcification were examined in 51 Japanese renal allograft recipients. Abdominal aorta calcification was evaluated on computed tomography using the aortic calcification area index (ACAI). The change in the ACAI and serum high-molecular-weight (HMW)-ADPN fractions were studied over an 8-year period. The arterial expression of ADPN, ADPN receptors (AdipoR)1 and 2, and T-cadherin (cadherin-13) were also examined by immunohistochemistry. RESULTS: The change in the ACAI were grouped into quartiles and compared with the alterations in the serum levels of each ADPN fraction over an 8-year period. The change in the ACAI was much lower in the patients with highly elevated HMW-ADPN levels.Multiple regression analysis demonstrated that an advanced age at transplant and a history of cardiovascular complications were associated with an increased change in the ACAI, while higher HMW-ADPN concentrations were associated with improvements in the ACAI. Serum HDL-C level was also identified as a positive factor to increase serum HMW-ADPN level.In immunohistochemical examinations, ADPN was detected on CD31-positive arterial endothelial cells from renal allograft biopsy samples. ADPN co-localized with T-cadherin and AdipoR1, but only partially co-localized with AdipoR2. CONCLUSION: Both HMW-ADPN and HDL-C might inhibit the progression of vascular calcification by promoting ADPN binding to vascular endothelial cells via T-cadherin and AdipoR in Japanese renal allograft recipients.