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Abstract: SA-PO926

The Influence of Vascular Endothelial Dysfunction on the Prognosis of CKD and Its Possible Related Influencing Factors

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Qian, Jing, Huashan Hospital , Shanghai, SHanghai, China
  • Liu, Shaojun, Huashan Hospital, Fudan University, Shanghai, China
  • Hao, Chuan-Ming, Huashan Hospital , Shanghai, SHanghai, China
  • Lai, Lingyun, Huashan Hospital, Fudan University, Shanghai, China
Background

Vascular endothelial dysfunction may be involved in progression of renal fibrosis in CKD patients. Asymmetric dimethylarginine(ADMA) is an endogenous nitric oxide synthase(NOS) inhibitor, which plays an important role in the pathophysiological process of endothelial dysfunction. Elevated circulating ADMA level is one of the primary biomarkers of endothelial dysfunction. This study will explore the associated factors leading to endothelial injury in CKD patients and the relationship between vascular endothelial dysfunction and CKD prognosis.

Methods

77 adults in CKD stage 1–5 were enrolled. Baseline demographic data including age, gender and etiology of kidney disease were all recorded. Serum ADMA, α-klotho and phosphorus levels were measured and immunohistochemical staining was carried out. Patients were divided into two groups by the median serum ADMA level and were followed up for 6 years. The primary outcome was initiation of renal replacement therapy.

Results

The mean serum ADMA level of all patients was 64.3±34.6ng/mL. Serum ADMA level increased with declining renal function(r=−0.267, p=0.020). It was negatively correlated with serum α-klotho(r=0.−233, p=0.042) and positively correlated with phosphorus(r=0.243, p=0.037) levels. The expression of α-klotho in renal perforation tissues of CKD patients was decreased by immunofluorescence staining. The expression of sodium-phosphorus synergistic transporter(NaPi) in renal tubules, which promoted phosphorus reabsorption and the expression of dimethylarginine-dimethylamine hydrolase(DDAH), which regulated ADMA level, were significantly decreased, consistent with the clinical results. Kaplan-Meier analyses showed that the incidence of renal replacement therapy initiation in high ADMA group was significantly higher than that in low ADMA group(35.9%vs13.2%, p=0.029, log rank test).

Conclusion

Serum ADMA level increased with deterioration of renal function and increase of CKD stage. Low serum α-klotho and high phosphorus levels are associated with increased circulating ADMA levels, which implies that they may be involved in the pathogenesis of endothelial dysfunction in CKD patients. High serum ADMA level predicts the occurrence of end-stage renal failure. Alleviating endothelial injury and improving endothelial dysfunction in patients with CKD may delay the progress of CKD.