Deterioration of renal function by chronic heart failure is associated with congestion and oxidative stress in the tubulointerstitium.

Abstract

OBJECTIVE:

We examined the hypothesis that renal congestion is responsible for the decline in renal function in patients with heart failure (HF) via tubulointerstitial inflammation.

METHODS:

First, in a longitudinal study, we retrospectively examined the relationship between cardiac functions and the decline of renal function during a period of 6.4±3.2 years in 20 patients who had a left ventricular ejection fraction of <40% and an estimated glomerular filtration ratio (eGFR) of <60 mL/min/1.73 m(2). Second, we compared the renal histology in autopsy cases of HF-induced renal dysfunction (HF-RD), cases of nephrosclerosis (NSC) and cases of neither RD nor HF (controls) in a cross-sectional study. Third, we retrospectively examined renal function in HF patients with predominantly right, but not left, ventricular dysfunction. Results eGFR decreased at 9.4±4.6%/year in the cohort of the longitudinal study. The rate of eGFR decline was correlated with blood pressure and with diameter of the inferior vena cava (IVCd) (r=0.5) measured at the initial work-up. Multivariate analysis indicated that the IVCd is an independent determinant of decline of eGFR in HF. In the cross-sectional study, fibrosis, Rac1 expression, protein nitrosylation, and number of CD68-positive cells were increased in the tubulointerstitium in both cases of HF-RD and NSC. Peritubular capillaries in HF-RD were dilated by 35% without any change in density compared with those in the controls. In right sided HF, the reduction of IVCd after treatment was associated with improvement of eGFR.

CONCLUSION:

Venous congestion may contribute to HF-induced deterioration of renal function by augmenting oxidative stress-mediated inflammation in the tubulointerstitium.

• Authors: Marenao Tanaka, Hideaki Yoshida, Masato Furuhashi, Nobuhiko Togashi, Masayuki Koyama, Satoshi Yamamoto, Tomohisa Yamashita, Yusuke Okazaki, Shutaro Ishimura, Hideki Ota, Tadashi Hasegawa, Tetsuji Miura
• Journal: Internal medicine (Tokyo, Japan) (Intern Med) Vol. 50 Issue 23 Pg. 2877-87 ( 2011) ISSN: 1349-7235 [Electronic] Japan
• PMID: 22129502 (Publication Type: Journal Article)

Topics

• Adult
• Aged
• Chronic Disease
• Cross-Sectional Studies
• Female
• Heart Failure (metabolism, pathology)
• Humans
• Hyperemia (metabolism, pathology)
• Kidney Function Tests (methods)
• Longitudinal Studies
• Male
• Middle Aged
• Nephritis, Interstitial (metabolism, pathology)
• Oxidative Stress
• Retrospective Studies