| Background: With the development of coronary angiography(CAG) and percutaneous coronary intervention(PCI), the morbidity of contrast-induced nephropathy(CIN) associated with contrast medium(CM) is increasing. CIN was defined as a relative(≥25%) or absolute(≥0.5mg/d L; 44μmol/L) increase in serum creatinine from baseline value occurring within 48 hours after contrast exposure. In case of CIN, Scr typically rises within the first 24-48 hours after exposition, and returns near to baseline within 7-10 days. However, irreversible renal function losses and short dialysis occur in rare cases. The incidence of CIN ranges between 0-20%, with an increased incidence if concomitant with more risk factors such as baseline renal dysfunction, diabetes, heart failure, hypotension, large amount of CM etc. It has been proved that CIN leads to not only prolonged hospitalization, requirement for dialysis but also increased mortality. Currently, little agent has been proved to be effective for treating CIN, so prophylaxis is vital important. To date, many methods can make certain effect, but are still under controversy besides hydration. But for cardiovascular patients, especially heart failure patients, hydration may increase cardiac load. Therefore, CIN has become the third difficult problem after PCI besides stent thrombosis and stent restenosis.The morbidity of coronary heart disease complicated with choronic kidney disease is increasing year by year. It has reported the incidence ranges between 20-40%. This part of patients receiving the CAG or PCI also increases year by year. So, how to reduce the incidence of CIN and seek for effective prevention measures will be an important topic for cardiovascular physicians.Brain natriuretic peptide(BNP) is an endogenously produced hormone secreted largely by the cardiac ventricles in response to pressure and volume overload. The physiological action of BNP is as follows: direct and indirect effect of vasodilatation; reduction of cardiac preload and afterload; inhibition of cardiac remodeling; inhibition of renin-angiotensin-aldosterone system(RAAS) and sympathetic nervous system(SNS); direct effects on renal hemodynamic and tubular function, such as increasing glomerular filtration rate, reducing sodium reabsorption in the proximal tubule and in the collecting duct. Therefore BNP may benefit renal function in peri-operative period of CAG or PCI and may be considered as a promising candidate for the prevention of CIN. Some data has suggested a potential beneficial role of BNP on renal function in patients undergoing abdominal or cardiac surgery. But the study about its effect on renal function in peri-operative period of CAG or PCI is limited. Part Ⅰ Analysis of the incidence and risk factors of contrast-inducednephropathy in patients undergoing coronary angiography ornon-emergent percutaneous coronary interventionObjective: The aim of this study is to determine the incidence of CIN and discuss the risk factors in patients with unstable angina undergoing CAG or non-emergent PCI.Methods: 500 patients with unstable angina enrolled into the study after local ethic committee approval and written informed consent were obtained. General conditions including age, gender, hypertension history, diagnosis etc were collected in all the patients. All patients received 0.9% Na Cl with 1.0ml/kg/h for 12 h before and 12 h after contrast contrast administration. Cystatin C(Cys C), serum creatinine levels(Scr) and estimated glomerular filtration rate(e GFR) were collected before and at 24 h, 48 h, 72 h and at 7 days after CAG or non-emergent PCI to estimate the incidence of CIN and the change of renal function in CIN group. In order to discuss the risk factors of CIN, Mehran score was used to stratify the risk of CIN.Results:(1) The incidence of CIN was 14.4%, and it was significantly higher in patients undergoing PCI than those undergoing CAG(16.9% vs 9.7%, P < 0.05). The total study population was divided to CIN group and no CIN group according to definition of CIN. After compare the general characteristics between the two groups, we found that rates of CIN were differed between the two groups with respect to age, baseline Cys C, baseline Scr, baseline e GFR, hypertension history, diabetic history, severity of coronary lesions, type of procedure, the amount of CM and Mehran score. The difference was statistically significant(P < 0.05).(2) Significant changes in Scr and e GFR at 24 h, 48 h and 72 h after procedure can be observed in CIN group as compared with pre-procedure. However, the level of Cys C increased earlier than Scr. Significant changes in Cys C at 24 h, and 48 h can be observed, but not at 72 h. All biomarkers recovered to baseline at day 7 in both groups.(3) After exploring individual predictors of CIN, we found that patients who developed CIN were more likely to receive more CM(OR=3.57,95%CI 1.25~5.88,P < 0.05), have history of diabetes(OR=1.92,95%CI 0.88~3.36,P < 0.05), have high Cys C(OR=2.20,95%CI 1.62~4.11,P < 0.05), have low e GFR(OR=3.10,95%CI 1.99~5.48,P < 0.05), have high Mehran score(OR=4.46,95%CI 2.16~6.88,P < 0.01), and the most relevant risk factor is Mehran score.Conclusion: In brief, our research suggests that CIN is prevalent in patient undergoing CAG or non-emergent PCI. Cys C is able to detect CIN earlier and was more sensitive than Scr. The detection rate will be increased if Cys C and Scr are combined. Diabetes, baseline renal dysfunction, the amount of CM and Mehran score are individual risk factors of CIN, and the most relevant risk factor is Mehran score. So, it is important to stratify the risk of CIN by Mehran score before CAG or non-emergent PCI. We should reduce the contrast volume if possible to reduce the incidence of CIN in patients with UA who undergo CAG or non-emergent PCI. Part Ⅱ The pathogenesis of recombinant human brain natriureticpeptide for prevention of contrast-induced nephropathy inpatients undergoing coronary angiography or non-emergentpercutaneous coronary interventionObjective: To investigate whether use of recombinant human brain natriuretic peptide(rh BNP) before CAG or non-emergent PCI can reduce the incidence of CIN in patients with unstable angina.Methods: 1000 patients with unstable angina were prospectively evaluated. All patients enrolled were randomly divided into two groups: group A [used Isotonic normal saline(Na Cl 0.9%) for 12 h before and 12 h after CAG or PCI] and group B(rh BNP 0.005μg/kg/min) for 24 h before CAG or PCI. Cystatin C(Cys C), serum creatinine(Scr) levels and estimated glomerular filtration rate(e GFR) were collected before CAG or PCI, at 24 h, 48 h, 72 h and at 7 days after CAG or PCI to estimate the incidence of CIN and recovery of renal function. Then we compared the incidence of CIN in the two groups and evaluate the effect of rh BNP on CIN. Except that, tumor necrosis factor α(TNF-α) and aldosterone(Adl) were also collected before and 24 h after CAG or PCI to explore the pathogenesis of rh BNP on CIN.Result: Baseline characteristics of patients were similar for both groups. The incidence of CIN was significantly lower in patients on rh BNP infusion than those on hydration(5.6% vs 14.4%, P < 0.01). The renal function had a short-term decrease in both groups as compared with pre-procedure, but it was less evident in patients on rh BNP. In patients with CIN, the Scr was higher at 24 h and 48 h than pre-procedure in both groups, but it was lower and recovered faster in patients on rh BNP. The pre-procedure mean TNF-α and Adl were similar between the two groups(P > 0.05). There were higher TNF-α and Adl at 24 h after procedure as compared with pre-procedure in both groups but they were less evident in BNP group.Conclusion: CIN is prevalent in patients with UA undergoing CAG or non-emergent PCI in spite of the hydration treatment. Exogenous administration of low dose of rh BNP before CAG or non-emergent PCI has a protective effect on renal function and can significantly decrease the incidence of CIN. In addition to that, it can also reduce renal impairement and promote the recovery of renal function. The pathogenesis of rh BNP for prenventing CIN may be inhibiting RAAS and inflammation. Part Ⅲ The pathogenesis of recombinant human brain natriureticpeptide for prevention of further renal damage in patients withchronic kidney disease undergoing coronary angiography ornon-emergent percutaneous coronary interventionObjective: To investigate the effect of rh BNP for prevention of CIN in unstable angina patients with moderate chronic kidney disease(CKD) undergoing coronary angiography(CAG) or non-emergent percutaneous coronary intervention(PCI).Methods: Patients with moderate CKD(30ml/min/1.73m2 ≤e GFR< 60ml/min/1.73m2) who would receive CAG or elective PCI were randomly assigned to BNP group(0.005μg/kg/min within 24 hours before contrast media exposure; n=106) and the control group( hydration with saline for 12 h before and 12 h after procedure, n=103). Cystatin C(Cys C), serum creatinine(Scr) levels and estimated glomerular filtration rate(e GFR) were collected before procedure, at 24 h, 48 h, 1 week and 1 month after procedure. The primary outcome was CIN incidence defined by a relative(≥25%) or absolute(≥0.5 mg/dl; 44μmol/L) increase in serum creatinine from baseline within 48 hours. The secondary endpoint was the changes in the Cys C, SCr and e GFR, before and after procedure. Then TNF-α and Adl were collected before and 24 h after CAG or PCI to explore the pathogenesis of rh BNP on CIN.Results: Baseline characteristics of patients were similar for both groups. The incidence of CIN was significantly lower in patients on rh BNP infusion than those on hydration(8.5% vs 23.3%, P < 0.01). There was a more significant deterioration in the control group than in the rh BNP group of e GFR, Cys C and Scr from 48 hour to 1 week(P < 0.05). The e GFR gradually deteriorated in both groups, but it was lower and recovered faster in patients on rh BNP. The pre-procedure mean TNF-α and Adl were similar between the two groups(P > 0.05). There were higher TNF-α and Adl at 24 h after procedure as compared with pre-procedure in both groups but they were less evident in BNP group.Conclusion: CIN is more commom in unstable angina patients with moderate CKD undergoing CAG or non-emergent PCI in spite of the hydration treatment and using isotonic contrast agents. Exogenous administration of low dose of rh BNP before CAG or non-emergent PCI has a protective effect on renal function and can significantly decrease the incidence of CIN. In addition to that, it can also reduce renal impairement and promote the recovery of renal function. The pathogenesis of rh BNP for prenventing CIN may be inhibiting RAAS and inflammation. |
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