조영제 신증 예방법 – 누구를, 어떻게 ? Sejoong Kim Nephrology, Internal Medicine 2018년 분당서울대학교병원 내과 연수강좌 14:15~14:45 조영제 신증 예방법 – 누구를, 어떻게 ? Sejoong Kim Nephrology, Internal Medicine Seoul National University Bundang Hospital

Constrast Induced Acute Kidney Injury 미국 조영제 사용 관상동맥조영술 연간 102만건 말초동맥조영술, CT 3000만건 SNUH CT + 20000/yr 대표적인 부작용: CIAKI 신기능 저하, 입원일수 증가, 사망율증가

CIAKI After Contrast-Enhanced CT ~5% Am J Kidney Dis 55:1018-1025

Nephrology's Bogeymen. The first study, the benefit of hydration in CIN prevention Solomon et al. (Semin Nephrol 1998 18(5) 551-7) Forced diuresis to be inferior to hydration with 0.45% saline. Fluids with different compositions and tonicity have since been studied, as well as the addition of bicarbonate and mannitol. Normal saline has been found to be superior to 1/2 saline Its enhanced ability to produce intravascular volume expansion. Prevents renin-angiotensin activation Maintains increased renal blood flow. Bogeyman  (아이들에게 겁을 줄 때 들 In terms of route of administration, oral fluids, while beneficial, have not been considered as effective as intravenous hydration. [33, 34]  먹이는) 귀신[부기맨]

IV NS, 1 L, during 4 hr before CT, + 1 L during 4 hr after CT and 1,200 mg of NAC orally every 12 hours for 4 doses 13 (2.5%) Am J Kidney Dis 55:1018-1025

DM, Kidney survival Kidney survival Am J Kidney Dis 55:1018-1025

61 (3.7%) Medicine 95(18):e3560

Risk Factors for CIAKI Medicine 95(18):e3560

Threshold baseline kidney function for increased risk of CT-CIAKI Age, sex, BMI, history of diabetes mellitus, history of hypertension, use of statins, ACE inhibitors or ARBs, and serum albumin level Medicine 95(18):e3560

Mortality and renal survival after propensity score matching. Medicine 95(18):e3560

Clinical practice guidelines for CIAKI

급성신손상 가이드라인 조영제 유발 급성 신손상의 정의, 역학, 예후 혈관 내 조영제를 투여 후 발생한 급성 신손상의 정의와 병기는 본 진료지침의 권고에 따른다. (Opinion, not graded) 혈관 내 조영제를 투여 후 신장 기능의 변화가 나타난 환자에서 조영제 유발 급성 신손상 뿐만 아니라 급성 신손상을 일으킬 수 있는 가능한 다른 원인에 대한 평가가 필요하다. (Opinion, not graded) 조영제 유발 급성 신손상의 위험인자에 대한 평가 요오드화 조영제의 혈관 내 (정맥 내 또는 동맥 내) 투여가 필요한 모든 환자에서 조영제 유발 급성 신손상의 위험을 평가해야 하고, 특히 기존 신기능 장애가 있는 환자를 선별해야 한다. (Opinion, not graded) 조영제 유발 급성 신손상 발생 위험이 높은 환자에게 대체 영상검사법을 고려한다. (Opinion, not graded)

급성신손상 가이드라인 (초안) 조영제 유발 급성 신손상의 예방법 조영제 유발 급성 신손상 발생 위험이 있는 환자에게 가능한 적은 용량의 조영제를 사용한다. (Opinion, not graded) 조영제 유발 급성 신손상 발생 위험이 높은 환자에게 삼투압이 높은(high osmolar) 조영제 대신 등장성(iso-osmolar) 혹은 저삼투압(low osmolar) 조영제를 사용할 것을 권고한다. (IB) 조영제 유발 급성 신손상 발생 위험이 높은 환자에게 등장성 식염수(isotonic sodium chloride) 또는 중탄산나트륨 수액(sodium bicarbonate solutions)을 정맥 내로 투여하여 용적을 팽창시킬 것을 권고한다. (IA) 조영제 유발 급성 신손상 발생 위험이 높은 환자에게 경구 수분 섭취만 하지 않을 것을 권고한다. (IC) Oral hydration may be beneficial than fasting 조영제 유발 급성 신손상 발생 위험이 높은 환자에게 정맥 내 등장성 정질 수액(isotonic crystalloids) 투여와 함께 경구 N-acetylcysteine을 사용할 것을 제안한다. (2D) Not of proven benefit, 2B KHA-CARI) Not using oral N-acetylcysteine as the only method

Risk stratification Low risk At risk Highest risk +60 near-normal renal function DM Comorbidities (HF, LF, MM) 45-60 AU > 300 mg/day PU > 500 mg/day 30-45 No PU, DM, others PU, DM, others 30> All patients Avoidance and/or correction of volume depletion. IV fluid (2C) if no Cix* IV fluid (1B) if no Cix* *In the absence of contraindications to volume expansion, Literature review current through: Jul 2017

Isotonic crystalloid solution, RCT

Fluid administration Either isotonic bicarbonate or isotonic saline may be used, Saline is less expensive and there is no risk of compounding errors. Timing and rate of administration are independent of fluid type and vary between inpatients and outpatients Among outpatients, 3 mL/kg over 1 hour + 1 - 1.5 mL/kg/hour during and for 4 - 6 hours (at least 6 mL/kg postprocedure) Among inpatients, 1 mL/kg/hour for 6 - 12 hours preprocedure, intraprocedure, and for 6 - 12 hours postprocedure. isotonic sodium bicarbonate solutions, to avoid compounding errors in preparing solutions The CIN Consensus Working Panel found that adequate intravenous volume expansion with isotonic crystalloids (1-1.5 mL/kg/h), 3-12 hours before the procedure and continued for 6-24 hours afterward, decreases the incidence of CIN in patients at risk. The panel studied 6 clinical trials with different protocols for volume expansion. The studies differed in the type of fluid used for hydration (isotonic vs half-normal saline), route, duration, timing, and amount of fluid used. [37] For hospitalized patients, volume expansion should begin 6 hours prior to the procedure and be continued for 6-24 hours postprocedure. For outpatients, administration of fluids can be initiated 3 hours before and continued for 12 hours after the procedure.

Diagnosis: Biomarker Tohoku J Exp Med. 2012;228(2):109-17.

eGFR 45 - 59 + 2 RFs eGFR 30 to 45 2–6 days post-contrast Previously, there have been no studies comparing no prophylaxis vs hydration. However, data from the recent  phase 3 trial AMACING  found no prophylaxis to be non-inferior and cost-saving in preventing contrast-induced nephropathy compared with intravenous hydration. [35] No prophylactic hydration (n = 332) or guidelinebased, standard prophylactic IV hydration with a standard (0.9% NaCl, 3 to 4 mL/kg/h, 4 h before and after contrast administration) or long protocol (0.9% NaCl, 1 mL/kg/h for 12 h before and after contrast administration) (n = 328).

eGFR 45 - 59 + DM/2 RFs eGFR 30 to 45 RF: age >75 years; anaemia; CVD; NSAID; diuretics MM/ lymphoma with small chain proteinuria 2–6 days post-contrast IV NS 3–4 mL/kg/h 4 h before and 4 h after contrast IV NS 1 mL/kg/h during 12 h before and 12 h after Lancet 2017; 389: 1312–22

J Am Heart Assoc. 2016;5:e003777

RenalGuard System RenalGuard System (PLC Medical Systems, Milford, Massachusetts) delivers intravenous fluids matched to urine output Normal saline at an initial dose bolus + a low dose of furosemide and continuous monitoring for a urine output flow of >300 ml/h sustained for 6 h a minimum 1 h time period prior to the first dose of contrast a 250 ml bolus of 0.9% normal saline (NS) Furosemide IV bolus dose of 0.5 mg/kg over 5 min Additional doses of furosemide could be given if, during the catheterization and/or up to 3 h after the catheterization, the calculated urine output fell below 300 ml/h (maximum dose of 2.0 mg/kg).

Meta-Analysis Comparing the Effects of RenalGuard Therapy Versus Control Group on Post-Operative Contrast-Induced Acute Kidney Injury and Need for Renal Replacement Therapy Diuretics on their own are not recommended but a recent meta-analysis suggested that furosemide with matched hydration by the RenalGuard System may reduce the incidence of contrast-induced acute kidney injury in high-risk patients undergoing percutaneous coronary intervention or transcatheter aortic valve replacement. [36] a urine output of 150 mL/h should guide the rate heart failure (CHF) high-risk patients undergoing percutaneous coronary intervention or transcatheter aortic valve replacement. 

Hydration Therapy in Heart failure Compensated CHF: at lower rates. Uncompensated CHF: hemodynamic monitoring + diuretics In emergency situations, adequate postprocedure hydration should be carried out. Postprocedure volume expansion is more important than preprocedure hydration. Medscape 2017

Real world in SNUBH GFR < 45 ml/min/1.73m2 + RF; GFR < 30 ml/min/1.73m2 Normal saline 1cc/kg/hr ivs for 12 hours before and after the study 시술후 NS 는 I/O 확인후 진행여부 결정해 주세요 (+ 요량 유지되면 NS 1cc/kg/hr ivs for 12 hours after the study) prn) lasix ivs (volume overload 되면 이뇨제 추가 혹은 NS 속도 감량 해주세요) Small volume: NS 3ml/kg/hr for 1 hr + NS 1.5 mg/kg/hr for 4 hr Outpatients: NS 250 ml over 1 hr + NS 500 ml over 2 hr

Real world in SNUBH Anemia correction, (+- RBC transfusion) Metabolic acidosis isotonic sodium bicarbonate 3ml/kg for 1hr before CT, 1ml/kg/h for 6 hr after CT isotonic sodium bicarb (5% dextrose 850ml + sodium bicarb 150 ml) Hypoalbuminemia 20% albumin 25 ml for 1hr before procedure, 75 ml for 6 hr after procedure

Effective Hydration for CIAKI prevention Risk Evaluation eGFR and risk factors Guidelines and new evidences Type and amount of fluid Personalized regimens