J Korean Med Sci.  2014 Sep;29(Suppl 2):S123-S130. 10.3346/jkms.2014.29.S2.S123.

Urinary Sodium Excretion Has Positive Correlation with Activation of Urinary Renin Angiotensin System and Reactive Oxygen Species in Hypertensive Chronic Kidney Disease

Affiliations
  • 1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. mednep@snubh.org
  • 2Department of Immunology, Seoul National University Postgraduate School, Seoul, Korea.
  • 3Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
  • 4Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
  • 5Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea.
  • 6Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, Korea.
  • 7Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Korea.
  • 8Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
  • 9Research Institute of Salt and Health, Seoul, Korea.
  • 10Seoul K-Clinic, Seoul, Korea.

Abstract

It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P<0.001 for each analysis). When we estimated uAGT/cr in the 24HUna/cr groups by ANCOVA, the uAGT/cr in patients with > or =200 mEq/g cr was higher than in patients with <100 mEq/g cr (708 [95% CI, 448-967] vs. 334 [95% CI, 184-483] pg/mg cr, P=0.014). Similarly, uMDA/cr was estimated as 0.17 (95% CI, 0.14-0.21) pM/mg cr in patients with <100 mEq/g cr and 0.27 (95% CI, 0.20-0.33) pM/mg cr in patients with > or =200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation.

Keyword

Chronic Renal Insufficiency; Sodium Chloride; Renin; Angiotensinogen

MeSH Terms

Adult
Aged
Angiotensinogen/urine
Chemokine CCL2/urine
Creatine/urine
Demography
Female
Follow-Up Studies
Humans
Hypertension/complications
Male
Malondialdehyde/urine
Middle Aged
Reactive Oxygen Species/*metabolism
Renal Insufficiency, Chronic/complications/*pathology
Renin-Angiotensin System/*physiology
Sodium, Dietary/*urine
Urine Specimen Collection
Angiotensinogen
Chemokine CCL2
Creatine
Reactive Oxygen Species
Sodium, Dietary
Malondialdehyde

Figure

  • Fig. 1 Urinary cytokines to creatinine ratio among 24HUna/cr groups. (A) AGT, angiotensinogen. (B) MCP1, monocyte chemoattractant protein-1. (C) MDA, malondialdehyde. 24HUna/cr, the ratio of 24-hr urine sodium to creatinine (mg/g creatinine). The P value was calculated by one-way ANOVA test. *Different from the group with 24HUna/cr<100 mEq/g cr. The bar means 95% confidence interval of each mean value.

  • Fig. 2 The frequency of tertile groups of cytokines according to 24HUna/cr groups. The ratio of 24-hr urine sodium to creatinine (mg/g creatinine) by (A) uAGT/cr, urine angiotensinogen to creatinine ratio (pg/mg cr), (B) uMCP1/cr, urine monocyte chemoattractant protein-1 to creatinine ratio (pg/mg cr), (C) uMDA/cr: urine malondialdehyde to creatinine ratio (pM/mg cr).

  • Fig. 3 The relationship between the changes of 24-hr urine cytokines to creatinine ratio and urine sodium to creatinine ratio during 16 weeks after ARB medication. Frequency of increase in cytokine level: Frequency of increase in 24-hr urinary cytokine to creatinine ratio at 16-week compared to 0-week 25% or more. Increased 24HUna/cr defined as increase of 24HUna/cr ratio 25% or more, Decreased 24HUna/cr defined as decrease of 24HUna/cr ratio 25% or more, and unchanged 24HUna/cr defined as the ratio of 24HUna/cr between -24.9% and 24.9%, at 16-week compared to 0-week. uAGT/Cr: 24-hr urine angiotensinogen to creatinine ratio (pg/mg cr), uMCP1/Cr: 24-hr urine monocyte chemoattractant protein-1 to creatinine ratio (pg/mg cr), uMDA/Cr: 24-hr urine malondialdehyde to creatinine ratio (pM/mg cr).


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