Chronic Kidney Disease Complications Normal Screening for CKD

Chronic Kidney Disease의 진행과 치료적 접근 Complications Normal Screening for CKD risk factors Increased risk CKD risk reduction; Screening for CKD Damage GFR Diagnosis & treatment; Treat comorbid conditions; Slow progression Estimate progression; Treat complications; Prepare for replacement Kidney failure Replacement by dialysis & transplant CKD death

Prevalence of Abnormalities at each level of GFR *>140/90 or antihypertensive medication p-trend < 0. 001 for each abnormality

Progression of CKD 1. 5 % / 년 Stage 5 Risk factors • intraglomerular HTN & Stage 4 Stage 3 glomerular hypertrophy 0. 5 % / 년 • proteinuria • hyperlipidemia Stage 2 • metabolic acidosis • tubulointerstitial dis. Stage 1

심 혈 관 계 사 망 률 Lancet 2010; 375: 2073– 81

Optimise risk factors • Cardiovascular disease • Proteinuria • Hypertension • Diabetes • Smoking • Obesity • Exercise tolerance

Prevalence of Abnormalities at each level of GFR *>140/90 or antihypertensive medication p-trend < 0. 001 for each abnormality

ACEI/ARB & Reduced Risk of Rapid GFR Decline, Kidney Failure, or Death AASK (N=1094) RENAAL (N=1513) -16 -22 -38 Ramipril vs Metoprolol P = 0. 04 Losartan vs Placebo P = 0. 02 IDNT (N=1722) -20 -23 Irbesartan vs Placebo P = 0. 02 Irbesartan vs Amlodipine P = 0. 006 Ramipril vs Amlodipine P = 0. 004 Wright et al for the AASK Study Group. JAMA. 2002; 288: 2421 -2431. [AASK - African American Study of Kidney Disease and Hypertension] Brenner et al for the RENAAL Study Investigators. N Engl J Med. 2001; 345: 861 -869. [RENAAL = Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan] Lewis et al for the Collaborative Study Group. N Engl J Med. 2001; 345: 851 -860. [IDNT = Irbesartan in Diabetic Nephropathy Trial. ] © 2005 The Johns Hopkins University School of Medicine.

Relationship Between Achieved BP and GFR MAP = Mean Arterial Pressure* r = 0. 69 P<0. 05 Untreated Hypertension 130/80 140/90 *MAP = [SBP + (2 × DBP)]/3 mm Hg. Summary of 9 studies used in figure. Parving et al. 1989; Viberti et al. 1993; Klahr et al. 1993; Hebert et al. 1994; Lebovitz et al. 1994; Moschio et al. 1996; Bakris et al. 1997; GISEN Group. 1997. Bakris et al. Am J Kidney Dis. 2000; 36: 646 -661. © 2005 The Johns Hopkins University School of Medicine.

Six-month change in proteinuria predicts risk for ESRD. AASK - African American Study of Kidney Disease and Hypertension © 2008 by American Society of Nephrology Bakris G L CJASN 2008; 3: S 3 -S 10

Importance of Proteinuria in CKD

심 혈 관 계 사 망 률 Lancet 2010; 375: 2073– 81

CKD에서 단백뇨를 감소시키기 위한 전략 • Low protein diets • Management of BP • Drugs (ACEi/ARB, statin? ) • Low salt diets © 2005 The Johns Hopkins University School of Medicine.

Recommended daily statin dose ranges American journal of kidney diseases vol 41, NO 4, SUPPL 3. April 2003

만성콩팥병 단계에 따른 빈혈 치료 Anemia : A Modifiable and Funded Risk Factor

Anemia Prevalence by CKD Stage Patients With Anemia* (%) NHANES III NHANES 1999 -2000 CKD Stage *NHANES participants aged ≥ 20 y with anemia as defined by WHO criteria: hemoglobin (Hgb) <12 g/d. L for women, and Hgb <13 g/d. L for men. USRDS 2004 Annual Data Report. The data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U. S. government. Available at: www. usrds. org. Accessed 3/28/05. © 2005 The Johns Hopkins University School of Medicine.

Consequences of Anemia in CKD • • • Reduced oxygen delivery to tissues Decrease in Hgb compensated by increased cardiac output Progressive cardiac damage and progressive renal damage 1 Increased mortality risk 2 Reduced quality of life (QOL)3 • Fatigue • Diminished exercise capacity • Reduced cognitive function • Left ventricular hypertrophy (LVH)4 1. Silverberg et al. Blood Purif. 2003; 21: 124 -130. 2. Collins et al. Semin Nephrol. 2000; 20: 345 -349; 3. The US Recombinant Human Erythropoietin Study Group. Am J Kidney Dis. 1991; 18: 50 -59; 4. Levin. Semin Dial. 2003; 16: 101 -105. © 2005 The Johns Hopkins University School of Medicine.

The Cardio-Renal Anaemia Syndrome A vicious circle Hypoxia CKD Anaemia Serum EPO production Apoptosis Renal vasoconstriction Fluid retention Cardiac output Hypoxia Sympathetic activity TNF-α Uraemia CHF=congestive heart failure Adapted from Silverberg et al. Kidney Int Suppl. 2003; (87): S 40 -S 47

CHOIR study Mean Hb 13. 5 g/d. L Mean Hb 11. 3 g/d. L Primary endpoint: death, MI, CHF HR=1. 34, P=0. 03 Singh AK et al. NEJM 355: 2085 -2098, 2006

만성콩팥병 단계에 따른 인 / 부갑상선 호 르몬 이상 치료 Secondary hyperparathyroidism : An Early and Modifiable Complication of CKD

Calcitriol Decline and i. PTH Elevation as CKD Progresses CKD Stage 1 5. 6 million Stage 2 5. 7 million Stage 3 7. 4 million Stage 4 300, 000 40 30 25 300 Low-Normal Calcitriol 200 20 10 0 High-Normal PTH 105 95 85 75 65 55 45 35 25 i. PTH (pg/m. L) Calcitriol 1, 25(OH)2 D 3 (pg/m. L) 50 100 65 15 e. GFR (m. L/min/1. 73 m 2) N = 150. i. PTH = intact PTH. Adapted from Martinez et al. Nephrol Dial Transplant. 1996; 11(suppl 3): 22 -28. © 2005 The Johns Hopkins University School of Medicine.

Prevalence of Abnormalities at each level of GFR *>140/90 or antihypertensive medication p-trend < 0. 001 for each abnormality

Feedback Loops in SHPT Decreased Vitamin D Receptors and Ca-Sensing Receptors PTH Ca++ Bone Disease Fractures Bone pain Marrow fibrosis Erythropoietin resistance Serum P 1, 25 D Calcitriol Systemic Toxicity CVD Hypertension Inflammation Calcification Immunological 25 D Renal Failure Ca = calcium; CVD = cardiovascular disease; P = phosphorus. Courtesy of Kevin Martin, MB, BCh. © 2005 The Johns Hopkins University School of Medicine.

인결합제 • • Should be avoided Ca carbonate Ca acetate • Sevelamer • Lanthanum • Aluminum hydroxide • Mg containing antacid • Calcium citrate © 2005 The Johns Hopkins University School of Medicine.

만성콩팥병의 전해질 장애 : K • 저칼륨식이 • Kalimate (K binding resin) • Dialysis © 2005 The Johns Hopkins University School of Medicine.

만성콩팥병의 산염기 장애 • GFR < 30 m. L/min 이하에서 주로 발생 • 무엇에 나쁜가? - 근육 손실 (catabolism 증가) - 대사성 bone disease 악화 (osteoporosis) • 치료 - Sodium bicarbonate 또는 sodium citrate - t. CO 2 > 22 m. Eq/L © 2005 The Johns Hopkins University School of Medicine.

Exogenous Insulin Endogenous Insulin 30 U/day Clearance 30 ~ 80% Clearance 40 ~ 50%

Can Strict Glycemic Control Reduce the Risk of Cardiovascular Disease even in Late Stage Patients? Yes No DCCT/EDIC ACCORD UKPDS (post-trial monitoring) ADVANCE VADT Glucose Control in Early Stage vs. Glucose Control in Late Stage

ADVANCE & VADT: No Significant Effect ACCORD: Even Increased CV Death? Intensive vs. Standard ACCORD* ADVANCE VADT DM Duration (yrs) 10 8 11. 5 Prior CV events (%) 35 32 40 A 1 c at Baseline (%) 8. 1 7. 5 9. 4 6. 4 vs. 7. 5 † 6. 4 vs. 7. 0 † 6. 9 vs. 8. 4 † 3. 6 vs 4. 6% † 2. 7 vs. 2. 8 6. 3 vs. 6. 1 CV Death (%) 2. 6 vs. 1. 8 † (1. 35 Hazard Ratio) 4. 5 vs. 5. 2 2. 1 vs. 1. 7 Microvascular N/A nephropathy ↓ 21% retinopathy ↓ 5% NS N/A ↓ risk MIs, but ↑ risk death in intensive arm Glucose control has no impact on CV events, but ↓ Microvascular risk Glucose control has no impact on CV events A 1 C (%) Nonfatal MI (%) Key Points *ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial halted intensive glucose group (2/6/08) † significant difference between intensive and standard group ACCORD Study Group, NEJM 2008, 358: 2545 -2559. ADVANCE Collaborative Group, NEJM 2008, 358: 2560 -2572. VADT Study Results ADA Scientific Session San Francisco, 2008 In Press, Diabetes Obesity and Metabolism, 2008

140 100 통풍으로 NSAIDS UTI로 항생제 정상인 관상동맥 조영술 50 GFR ml/분 CKD progression: biology versus “iatrogenesis”? CKD 심부전으로 이뇨제 실제 상황 20 40 60 80 연령 (년)

증례 74 세 여자, 고혈압 10년 s-Cr : 2. 5 mg/d. L e. GFR : 26. 2 ml/min/1. 73 m 2 투여 약제 – piroxicam, tramadol (무릅통증), irbesartan, thiazide BP 110/70 mm. Hg, HR 100. 사용을 중단해야 할 약제는? 1) Piroxicam 2) Irbesartan 3) Thiazide 4) Tramadol

장청결제 종류에 따른 Phosphate 함량 Phosphate content (mmol) Fleets enema (133 ml) Visicol (40 tablets) 90 mmol 432 mmol Mean phosphate 48 / 33 mmol intake USA (men/women) polyethylene glycol 0 mmol OSMOPREP Package Insert, 2007

Phosphate induced nephropathy l Hyperphosphatemia + volume depletion l Acute Phosphate Nephropathy • Ca-phosphate deposits in tubules & interstitium • Leads to AKI/ CKD within days to months Desmeules S, et al. N Engl J Med. 2003

방사선 조영제 신독성 l 위험인자 • CKD (esp. e. GFR <30 ml/min/1. 73 m 2) • Diabetes, CHF, gout • Dehydration • Concurrent use of NSAIDs or RAAS-antagonists • High osmolality agents, large or repeated doses • Intra-arterial injection

MRI 조영제 (Gadolinium) l Linked to nephrogenic systemic fibrosis (NSF) • Rare, but painful debilitating fibrosing disease • Primarily in extremities but may involve lung and heart l l Increased risk w/ decreased kidney function (AKI, CKD, post-transplant) Grobner T and Prischl FC. Kidney Int 2007 l Contraindication in PD l HD patients require immediate HD postexposure x 3 d l No effective treatment available Avoid gadolinium in patients w/ e. GFR <30 ml/min Swaminathan S and Shah S. J Am Soc Nephrol. 2007.

항고혈압 약제: RAAS antagonists l l l Expect rise in SCr ≤ 30% Can lead to AKI, hyperkalemia Risk management • Avoid in patients with renal artery stenosis • Assess e. GFR and serum K+ 1 wk after initiation or ↑dose • Prior to contrast, major surgery, procedures /conditions that predispose to dehydration - consider temporarily d/c • D/C or reduce if SCr increase > 30% or serum K+ > 5. 5 m. Eq/L

증례 74 세 여자, 고혈압 10년 s-Cr : 2. 5 mg/d. L e. GFR : 26. 2 ml/min/1. 73 m 2? 3일전부터 배뇨통, 빈뇨, U/A: WBC 5 -10/HPF 가장 적합한 항생제는? 1. 2. 3. 4. Bactrim Gentamycin Cephalexin Ciprofloxacin

CKD 환자에서 항생제 사용 l Most require renal dose adjustments • Common exceptions: Ceftriaxone, moxifloxacin, macrolides, doxycycline, clindamycin, linezolid l Careful monitoring of drug levels needed for: • Vancomycin. Aminoglycosides l Trimethoprim/ sulfamethoxazole • May ↑SCr slightly due to ↓renal tubular creatinine excretion– no change in GFR. • Distinguish from AKI due to drug allergic interstitial nephritis • Hyperkalemia l Imipenem/ cilastatin • High seizure risk in CKD patients, use carbepenem in CKD

스타틴 사용 l Statins • No renal dose adjustment needed for atorvastatin • Dose adjustments needed when e. GFR <30 ml/min for fluvastatin, lovastatin, pravastatin, rosuvastatin and simvistatin l Fibrates • Associated with AKI esp. in CKD patients • May transiently raise SCr by increased creatinine production rather than decreased GFR KDIGO Guidelines on CKD Diagnosis and Management. Kidney Int. 2013.

위험인자를 줄여야 한다. l 가능한 약의 개수를 줄여라 l 10 – 12 MEDICATIONS PER CKD PATIENT; 17 FOR TRANSPLANTED INDIVIDUALS l 처방시 세심한 주의 l Dosing l Potential interactions l 환자 교육 l OTC meds to avoid (mainly NSAIDs) l Signs/symptoms of potential drug adverse effects