Author + information
- Haruki Sekiguchi, MD, PhD†,‡,§,
- Yoichi Ajiro, MD, PhD†,§,
- Yoshie Uchida, MD†,§,
- Issei Ishida, MD†,§,
- Hisao Otsuki, MD†,§,
- Hidetoshi Hattori, MD†,§,
- Hiroyuki Arashi, MD†,§,
- Yasunori Kobayashi, MD†,
- Kentaro Jujo, MD, PhD§,
- Junichi Yamaguchi, MD, PhD§,
- Masaaki Ii, MD, PhD⋮,
- Kazunori Iwade, MD, PhD†,§,
- Naohide Tanaka, MD, PhD†,§,
- Ken Shimamoto, MD, PhD‡,§,
- Yukio Tsurumi, MD, PhD‡,¶∗ (, )
- Masatoshi Kawana, MD, PhD‡,§,
- Nobuhisa Hagiwara, MD, PhD§,
- for the Yokohama Medical Center Clinical Research Group
- †National Hospital Organization Yokohama Medical Center, Kanagawa, Japan
- ‡Aoyama Hospital Tokyo Women's Medical University, Tokyo, Japan
- §Tokyo Women's Medical University, Tokyo, Japan
- ⋮Group of Translational Stem Cell Research, Department of Pharmacology, Osaka Medical College, Osaka, Japan
- ¶Yokohama General Hospital, Kanagawa, Japan
- ↵∗Heart Center, Yokohama General Hospital, Kanagawa, 2201-5 Kurogane-Cho, Aoba-Ku, Yokohama, Kanagawa 225-0025, Japan
To the Editor:
Despite several conventional preventive strategies, contrast-induced nephropathy (CIN) still occurs in 5% to 10% of cases after coronary angiography in patients with ischemic heart disease. The pathogenesis of CIN is considered a result of a combination of contrast-induced renal ischemia and direct toxic effects on renal tubular cells. In this regard, hydration by isotonic saline solution contributes to sufficient renal plasma flow; however, it does not resolve issues of renal ischemia. As contrast-induced renal damage begins immediately when the contrast passes the kidney, we hypothesized that sufficient oxygenation before contrast medium exposure concomitant with conventional isotonic saline solution hydration may prevent CIN more effectively.
We randomly assigned 426 consecutive patients who underwent elective coronary angiography and/or percutaneous coronary intervention to either an oxygenation group (oxygen administration via nasal cannula; 2 l/min of oxygen from 10 min before the procedure to the end of the procedure; n = 174) or to a control group (room air; n = 175). Continuous infusion of 0.9% saline solution (1 ml/kg/h) was administered 12 h before the procedure until 12 h after the procedure in both groups. Patients with acute coronary syndrome (ACS), end-stage renal failure and receiving dialysis, cardiogenic shock, congestive heart failure, chronic obstructive pulmonary disease, oxygen saturation levels <90% were excluded from the study.
The primary endpoint was the incidence of CIN defined as an increase in serum creatinine concentration ≥25% above the baseline level at 48 h after administration of contrast medium. The ethics committee of the National Hospital Organization Yokohama Medical Center approved the study protocol (NHO11-11), and informed consent was obtained from all patients before study entry. The study was registered at UMIN-CTR with the identifier UMIN000007125. Continuous data were reported as mean ± SD; skewed variables were reported as median and interquartile range. Continuous data were analyzed by using the Student t test or the Mann-Whitney U test or Wilcoxon signed rank test if data were skewed. Categorical data were compared by using the chi-square or Fisher exact test. Predictors of CIN were first evaluated using a logistic regression. Then a multivariable logistic regression model including potential factors identified as significant by univariate analysis was applied.
A total of 349 patients were enrolled in the study. The proportion of subjects older than 70 years of age was 64.8% (n = 226 of 349, average: 70.8 ± 10.4 years). There were no significant differences in patient characteristics between the 2 groups, including contrast volume, serum creatinine concentration, and estimated glomerular filtration rate (eGFR). The Pao2 at the baseline was significantly higher in the oxygen preconditioning group than in the control group (134 ± 28 mm Hg vs. 90 ± 12 mm Hg, p < 0.001). No statistically significant difference was found in concentrations of Pco2, HCO3−, base excess, and lactate between the 2 groups. Thus, systemically higher Pao2 concentrations in arterial blood were achieved before contrast medium administration without CO2 narcosis at an oxygen concentration of 2 l/min. CIN occurred in 10 of the 371 patients (2.9 %). The incidence of CIN was significantly lower in the oxygen preconditioning group than in the control group (1 of 174 [0.6%] vs. 9 of 175 [5.1%], odds ratio [OR]: 0.11, 95% confidence interval [CI]: 0.01 to 0.85, p = 0.01), indicating that oxygen preconditioning concomitant with standard isotonic saline solution hydration suppressed CIN (Fig. 1). The majority of CIN patients (8 of 10, 80%) were chronic kidney disease stage III or worse (eGFR <60 ml/min/1.73 m2). According to the univariate analysis, low eGFR (<60 ml/min/1.73 m2) and low Pao2 (<100 mm Hg) were significantly associated with a high incidence of CIN. Multivariate analysis, restricted to 2 predictors due to the low endpoint count, identified eGFR and Pao2 as statistically significant risk factors of CIN (OR: 4.12, 95% CI: 1.0 to 16.6, p = 0.046 and OR: 12.61, 95% CI: 1.6 to 101.3, p = 0.017, respectively). In 6 of the 10 CIN patients, elevated serum creatinine level did not recover to the baseline level at 6-month observation.
The present study thus demonstrated that 1) oxygen preconditioning concomitant with standard hydration decreased the occurrence of CIN in patients undergoing cardiovascular angiography and 2) this protective effect was more pronounced in patients with chronic renal insufficiency.
The pathogenesis of CIN is not fully illuminated, and little is known about the underlying cellular mechanisms; however, it certainly involves interaction with multiple factors. Although direct tubular and mesangial toxicity, intraluminal obstruction, and immunological injury have been reported, renal hypoxia and concomitant release of reactive oxygen species have also been considered important mechanisms of renal injury mediated by the contrast medium (1). Hypoxia arises from the balance of oxygen supply from renal blood flow and oxygen demand from renal tissue. Regarding the reduction of oxygen supply, several mechanisms have been reported, including the reduction of the effective renal cortical-medullary blood flow by occupying with its own volume in the vessels (2) and the afferent arteriole constriction mediated via the tubuloglomerular feedback from osmotic diuresis (3). Regarding oxygen demand, several mechanisms contributing to an increase in oxygen consumption were reported. The increased reabsorption due to osmotic load accelerates metabolism and results in the increase of oxygen consumption in the kidney (4); the microvascular damage increases oxygen consumption at the renal tubule (5). Therefore, the contrast medium would contribute to intrarenal hypoxia.
In the present study, we demonstrated that the oxygen preconditioning reduced the incidence of CIN without side effects during the procedure in patients undergoing coronary angiography. This simple strategy was more beneficial in patients with comorbid chronic kidney disease.
The authors thank Jun Katada for skillful assistance with statistical analysis.
- 2013 American College of Cardiology Foundation