慢性腎臟病 (CKD) 醫療處置 劉宏祥醫師 臺灣腎臟護理學會 腎臟疾病照護基礎課程研習會
慢性腎臟病之發生率與盛行率
美國成人慢性腎臟病之分期及其盛行率 期別說明腎絲球濾過率盛行率 GFR (ml/min/1.73 m 2 ) 個案數 % 1 腎功能正常持續性蛋白尿 90 5,900,000 3.3 % 2 輕度腎衰竭 60 ~ 89 5,300,000 3.0 % 3 中度腎衰竭 30 ~ 59 7,600,000 4.3 % 4 重度腎衰竭 15 ~ 29 400,000 0.2 % 5 末期腎病 < 15 372,000 0.1 % 總計 19,572,000 10.9 % K/DOQI, Am J Kidney Dis 2004
臺美腎臟病 ( 第 1~5 期 ) 盛行率之比較 盛行率 (%) GFR Stage Description (ml/min/1.73m 2 ) 美國臺灣 1 Kidney damage 90 3.3 1.02 with normal or GFR 2 Kidney damage 60-89 3.0 3.79 with mild or GFR 10.9% 11.9% 3 Moderate GFR 30-59 4.3 6.81 4 Severe GFR 15-29 0.2 0.22 5 Kidney failure < 15 or dialysis 0.1 0.10 K/DOQI, Am J Kidney Dis 2004; Wen et al, Lancet 2008
美臺腎臟病 ( 第 3~5 期 ) 盛行率之比較 GFR 盛行率 (%) Stage Description (ml/min/1.73m 2 ) 美國臺灣 1 Kidney damage 90 3.3 1.02 with normal or GFR 2 Kidney damage 60-89 3.0 3.79 with mild or GFR 3 Moderate GFR 30-59 4.3 6.81 4 Severe GFR 15-29 4.6% 0.2 7.1% 0.22 5 Kidney failure < 15 or dialysis 0.1 0.10 K/DOQI, Am J Kidney Dis 2004; Wen et al, Lancet 2008
GFR (ml/min/1.73m 2 ) 臺灣人腎臟病 ( 第 3~5 期 ) 之盛行率 < 15 15~29 30~59 60~89 6.4 % N=6599, an estimate of 1.15 million population aged over 15 to be CKD patients 90 Hwang et al, 2002 TW3H surveillance 0 1000 2000 3000 4000 Case number
慢性腎臟病之現況
美國成人慢性腎臟病盛行率,1988-1994 與 1999-2004 之比較 CKD Prevalence, % (95 Cl) Prevalence ratio for Estimated No. of Stage NHANES 1988-1994 NHANES 1999-2004 NHANES 1999-2004 US Adults in 2000, to 1988-1994 (95% CI) No. in Millions (85% Cl) 1 1.71 (1.28-2.18) 1.78 (1.35-2.25) 1.05 (0.85-1.30) 3.6 (2.7-4.5) 2 2.70 (2.17-3.24) 3.24 (2.61-3.88) 1.21 (1.03-1.41) 6.5 (5.2-7.8) 3 5.42 (4.89-5.95) 7.69 (7.02-8.36) 1.42 (1.25-1.62) 15.5 (14.1-16.8) 4 0.21 (0.15-0.27) 0.35 (0.25-0.45) 1.70 (1.11-2.51) 0.7 (0.5-0.9) 5 NA NA NA NA Total 10.03 (9.16-10.91) 13.07 (12.04-14.10) 1.30 (1.19-1.43) 26.3 (24.2-28.3) Coresh et al, JAMA 2007
% 泰國成人慢性腎臟病之盛行率,1985~1997 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 Defined by the presence of GFR <60 ml/min/1.73m 2 using the modified MDRD formula 1.7 6.8 1985 1997 A cohort study over a period of 12 years (1985~1997) in 3499 employees of the Electric Generation Authority of Thailand; GFR= 186.3 X (SCr) -1.154 X age -0.203 X (0.742 for women) Domrongkitchaiporn et al, J Am Soc Nephrol 2005
美國人腎臟病之盛行率 (I) Age 20-29 30-39 40-49 50-59 60-69 70-79 80+ Total Whole population Number 3071 2928 2330 1680 2078 1524 1011 14622 Microalbuminuria 5.4% 5.0% 5.1% 9.6% 12.9% 18.9% 28.0% 8.3% Macroalbuminuria 0.3% 0.5% 0.8% 1.1% 1.7% 2.3% 4.7% 1.0% Albuminuria 5.7% 5.5% 5.9% 10.7% 14.6% 21.2% 32.7% 9.2% Diabetic population Number 47 91 149 194 325 257 129 1192 Microalbuminuria 13.1% 22.9% 24.6% 22.9% 32.2% 35.8% 36.1% 28.1% Macroalbuminuria 1.3% 4.6% 7.4% 5.3% 5.4% 6.8% 12.5% 6.1% Albuminuria 14.4% 27.5% 32.0% 28.2 % 37.6% 42.6% 48.6% 34.2% Garg et al, Kidney Int 2002 NHANES III: 1988-1994
美國人腎臟病之盛行率 (II) Age 20-29 30-39 40-49 50-59 60-69 70-79 80+ Total Non-diabetic hypertensive population Number 329 536 661 645 1033 841 641 4686 Microalbuminuria 5.4% 4.7% 6.8% 13.6% 14.9% 20.8% 31.1% 12.8% Macroalbuminuria 0.7% 0.9% 1.7% 1.5% 1.7% 1.8% 4.8% 1.7% Albuminuria 6.2% 5.5% 8.4% 15.2% 16.5% 22.6% 35.9 14.5% Non-diabetic non-hypertensive population Number 2621 2272 1503 829 710 417 233 8585 Microalbuminuria 5.3% 4.6% 3.5% 4.8% 4.7% 7.5% 14.9% 4.8% Macroalbuminuria 0.2% 0.3% 0.1% 0.2% 0.7% 1.2% 0.5% 0.3% Albuminuria 5.6% 4.9% 3.6% 5.1% 5.4% 8.7% 15.5% 5.1% Garg et al, Kidney Int 2002 NHANES III: 1988-1994
全球糖尿病腎病變導致尿毒症比率排行榜,2007 USRDS, ADR, Am J Kidney Dis 2010
慢性腎臟病不斷增加的理由
左心室肥厚 / 心衰竭 冠心症 / 腦血管疾病 慢性腎臟病 糖尿病 高血壓
Increasing event rate 60 45-59 30-44 15-29 <15 60 45-59 30-44 15-29 <15 60 45-59 30-44 15-29 <15 Rates per 100 person years Rates per 100 person years Rates per 100 person years 非透析慢性腎臟病病人腎功能衰退之不利影響 住院率 心血管疾病發生率 死亡率 150 40 15 100 50 30 20 10 10 5 0 0 0 GFR (ml/min/1.73m 2 ) Decreasing GFR GFR (ml/min/1.73m 2 ) GFR (ml/min/1.73m 2 ) Go et al, N Engl J Med 2004
慢性腎臟病對高血壓 糖尿病及中風 盛行率的影響 50 44.6% 40 Hypertension DM % 30 Stroke 20 16.5% 10 10.9% 3.9% 1.1% 3.6% 0 CKD - CKD + Data from TW3H Surveillance
Survival rate 慢性腎臟病與非慢性腎臟病病人存活率之比較 (n=200,000) 1.00 0.99 0.98 0.97 0.96 0.95 0.94 0.93 0.92 Non CKD CKD 0 Months Kuo et al, data from 1% dataset of NHI Taiwan 2007 12 24 36 48
全球末期腎病變發生率排行榜,2008 USRDS, ADR, Am J Kidney Dis 2011
全球末期腎病變盛行率排行榜,2008 USRDS, ADR, Am J Kidney Dis 2011
如何治療慢性腎臟病
慢性腎臟病的治療方法 血壓及降低蛋白尿 治療高血脂症 維持鈣磷平衡及治療次發性副甲狀腺亢進 控制血糖 矯正貧血 避免酸中毒 使用低蛋白飲食 戒菸 早期轉介給腎臟專科醫師
台灣人高血壓 高血糖及高血脂盛行率 Gender (%) Age (%) Year Female Male 19-44 45-64 65+ 19+ N Hypertension 1996 19.6 28.5 13.9 37.5 56.0 24.0 4893 2002 19.3 26.6 7.9 32.0 56.6 22.7 6536 Hyperglycemia 1996 5.5 3.2 0.8 9.2 14.8 4.4 4898 2002 7.2 8.8 2.2 12.1 20.7 8.0 6155 Hypercholesterolemia 1996 19.0 15.2 8.1 21.1 26.4 17.2 2782 2002 11.5 11.6 5.8 17.0 21.5 11.6 6206 Hypertriglyceridemia 1996 16.4 19.0 11.4 21.0 22.6 17.6 2560 2002 11.9 21.7 11.7 20.6 25.9 16.6 6172 Data from Nnational Nutritional Health Survey (1993-1996) and DOH (2002)
Effect of Long-Term Therapy With Captopril on Proteinuria and Renal Function in Patients With Non-Insulin Dependent Diabetes and With Non- Diabetic Renal Diseases Hung-Hsiang Liou, M.D. ( 劉宏祥醫師 ) Liou et al, Nephron 1995
Renoprotective Effect of ACEI, CCB, or In Combination In Patients With Type 2 Diabetic Nephropathy Hung-Hsiang Liou, M.D. ( 劉宏祥醫師 )
Long-Term Effect of A HMG-CoA Reductase Inhibitor, Pravastatin, in Primary Glomerulonephritis Patients with Hyperlipidemia: An 18-Month Experience Hung-Hsiang Liou, M.D. ( 劉宏祥醫師 )
世界各國腎骨病變治療準則比較表 Target Ca Target phosphorus Target intact PTH (mg/dl) (mg/dl) (pg/ml) Stage 3-4 Stage 5 Stage 3-4 Stage 5 Stage 3-4 Stage 5 CKD CKD CKD CKD CKD CKD Europe 8.8-11.0 8.8-11.0 2.5-4.6 4.6-5.6 85-170 85-170 (2000) Australia Within N 8.4-9.6 Within N 2.5-5.0 No recom- 2-3 times CARI Lab Ref Lab Ref mendation upper limit (2006) of normal K/DOQI Normal 8.4-9.5 3.0-4.6 3.5-5.5 35-110 150-300 (2003, 2005) KDIGO Within N Within N Within N Toward N Not known 2-9 times (2009) Lab Ref Lab Ref Lab Ref Lab Ref upper limit Data from Am J kidney Dis 2004; Nephrology 2006; Kidney Int 2009 of normal
腎骨病變之最新定義
Secondary Hyperparathyroidism in Patients With Mild, Moderate and Severe Renal Failure A Cross-Sectional Analysis From 220 Cases Hung-Hsiang Liou, Mei-Chyn Liu, Yao-Ping Lin, Chuan Yao, Tung-Po Huang Section of Nephrology, Department of Medicine, Veterans General Hospital-Taipei & National Yang-Ming University
Relationship Between Sr P and FE P According to egfr Gutierrez et al, J Am Soc Nephrol 2005
高血磷對次發性副甲狀腺亢進的影響 HYPERPARATHYROIDISM DIRECT INDIRECT 1. Hyperplasia P.T. Glands 2. PTH Synthesis (Postranscriptional) Mechanism 3. PTH Secretion HYPER PHOSPHATEMIA 1. Calcitriol Levels 2. ICa 3. Skeletal Resistance Slatopolsky et al, Am J Kidney Dis 2001
高血磷對血液透析病人死亡率的影響 Block et al, J Am Soc Nephrol 2004
A Great Link Among Renal Bone Disease Mineral Metabolism Arterial Calcification Cardiovascular Disease
高血磷與高血鈣是慢性腎臟病病人心血管疾病的新危險因子 Traditional Risk Factors Older age Male sex Hypertension Higher LDL cholesterol Lower HDL cholesterol Diabetes Smoking Physical inactivity Menopause Family history of CVD LVH Uremia-Related Risk Factors Albuminuria Hyperhomocysteinemia Anemia Abnormal calcium/phosphate metabolism Extracellular fluid volume overload and electrolyte imbalance Oxidative stress Inflammation Malnutrition Thrombogenic factors Sleep disturbances Altered nitric oxide/endothelin balance Sarnak et al, Am J Kidney Dis 2003
Effect of Intravenous Calcitriol on Secondary Hyperparathyroidism in Chronic Hemodialysis Patients Hung-Hsiang Liou, M.D. ( 劉宏祥醫師 ) Liou et al, Chin Med J 1994
The Comparative Effect of Oral or Intravenous Calcitriol on Secondary Hyperparathyroidism in Chronic Hemodialysis Patients Hung-Hsiang Liou, M.D. ( 劉宏祥醫師 ) Liou et al, Miner Electrolyte Metab 1994
Meta-Analysis of Oral Versus Intravenous Calcitriol on PTH Suppression Indridason et al Caravaca et al. Liou et al. ( 劉宏祥醫師 ) Fisher and Harris Summary Effect Size K/DOQI, Am J Kidney Dis 2003, 2005-2 P.O. 0 I.V.
維他命 D 對腎臟病的影響
Percent of Patients with reduction in dipstick proteinuria 新型維他命 D 可以減少慢性腎臟病病人的尿蛋白 60 50 40 30 20 10 Paricalcitol Placebo p= 0.004 p= 0.025 0 Overall group ACEI/ARB users Agarwal et al, Kidney Int 2005
Number (millions) 全球糖尿病盛行率之影響 Increasing Prevalence of Diabetes Complications of Diabetes Worldwide 2007 2025 400 350 300 250 200 150 246 380 Fourth leading cause of death from disease Leading cause of blindness and amputation in developed countries Risk of developing cardiovascular disease is 2 to 4 times higher 100 50 0 Prevalence Adapted from International Diabetes Foundation. 2007
英國大型研究,United Kingdom Prospective Diabetes Study, UKPDS 對第二型糖尿病慢性併發症的防治結果 英國前瞻性糖尿病大型研究 (United Kingdorn Prospective Diabetes Study, UKPDS) 以 sulfonylurea(chloroprapamide, glyburide) 和 insulin 積極治療第二型糖尿病人, 將 HbA1c 控制在 7% 以下, 經過 10 年發現積極治療有下列結果 : (1) 減少眼底病變發生率 21% (2) 減少白蛋白尿發生率達 32% (3) 減少心肌梗塞發生率達 16%, 但未達統計學上辭意義的差異 (p<0.052)
UKPDS 對第二型糖尿病慢性併發症的防治結果 0-10 -20-30 -33-25 p<0.01-21 p=0.02-16 p=0.05-12 p=0.03-40 -50 p<0.01 Microalbuminuria at 12 yrs Retinopathy Any DM endpoint Microvascular complications Myocardial Infarction Over 10 years, HbA 1c was 7.0% (6.2-8.2) in the intensive group (n=2,729) compared with 7.9% (6.9-8.8) in the conventional group (n=1,138). UKPDS Group, Lancet 1998
Patients with anemia (%) 貧血在慢性腎臟病病人的盛行率 50 45 40 35 30 25 20 15 10 5 0 Anemia defined as Hb <12 g/dl in men, <11 g/dl in women; 1.8 1.3 90 60-89 30-59 15-29 5.2 GFR (ml/min per 1.73 m 2 ) 44.1 Astor et al, Arch Intern Med 2002
Patients on dialysis (%) 貧血對慢性腎臟病的不利影響 60 50 40 30 20 10 Baseline Hgb by quartile (Q, g/dl) Q1: 6.8-11.3 Q2: 11.3-12.5 Q3: 12.5-13.8 Q4: 13.8-18.0 *P<0.05 versus Q4 Q1 (n=378)* Q2 (n=377)* Q3 (n=363)* Q4 (n=395) 0 0 1 2 3 4 Time (years) Mohanram et al, Kidney Int 2004
貧血對慢性腎臟病病人的影響 慢性腎臟病病人的貧血會加速腎功能的退化 慢性腎臟病病人的貧血往往併發心血管疾病 慢性腎臟病貧血的病人接受輸血的機率會增加 慢性腎臟病貧血病人的活動量與質會受限 認知功能及性功能會受損, 因此生活品質會變差 慢性腎臟病病人的貧血會增加住院率 致病率以及死亡率
貧血對慢性腎臟病病人存活率的影響 1 0.9 0.8 0.7 0.6 Log rank 37.48 p< 0.001 0 2 4 6 8 10 12 Hb> 12 g/dl (0.92) 11-12 g/dl (0.89) 10-11 g/dl (0.82) < 10 g/dl (0.76) Survival time (months) Portoles et al, Nephrol Dial Transplant 2007
Subjective Global Assessment Dietary interview, dietary recall Biochemistry Nutritional Evaluation in CKD Patients Bio-impedance vectorial analysis Anthropometry Muscle tests
% 台灣血液透析病人血中白蛋白的分佈圖 50 40 Mean: 3.91 ± 0.45 g/dl Albumin 36.2 40.4 30 20 10 0 11.2 9.8 0.6 2.2 < 2.5 2.5-3.0 3.0-3.5 3.5-4.0 4.0-4.5 >=4.5 (g/dl) Taiwan Society of Nephrology, 2001
An Analysis of Nutritional Status in 101 Hemodialysis Patients Hung-Hsiang Liou, M.D. Division of Nephrology, Department of Medicine, Hsin-Zen Hospital
What Does The Word Malnutrition Mean? 營養不良? 營養不夠?
營養不良的定義 True malnutrition Acidosis Toxic metabolites Fatigue Loss of weight & muscle mass Low serum proteins Inflammation Dialysis Diabetes / insulin resistance Mitch et al, J Clin Invest 2002
低蛋白飲食在慢性腎臟病病人的使用建議 Group Protein Energy Phosphorus (g/kg per d) (Kcal/Kg per d) (mg/kg per d) Chronic renal failure GFR (ml/min) > 60 Protein restriction not usually recommended 35 No restriction 25 to 60 0.6 g/kg per d including 0.35 g/kg per d of HBV 35 10 5 to 25 (1) 0.6 g/kg per d including 0.35 g/kg per d of HBV or 35 10 (2) 0.3 g/kg per d supplemented with EAA or KA 35 9 Nephrotic syndrome GFR (ml/min) < 60 (1) 0.8 g/kg per d (plus 1 g protein/g proteinuria) 35 12 (2) 0.3 g/kg per d supplemented with EAA or KA 35 9 (plus 1 g protein/g proteinuria) Maroni et al, J Am Soc Nephrol 1998
低蛋白飲食在慢性腎臟病病人的治療目標 延緩慢性腎臟病症狀及徵候的進行 減少慢性腎臟病含氮廢物的累積及代謝異常 確認能提供足量的蛋白並避免發生營養不良
Keto-/Amino Acid Supplemented Low Protein Diet in Patients With CKD This is a Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study to compare the Effects Between Keto-/Amino Acid Supplemented Low Protein Diet and Non-Supplemented Low Protein Diet in Patients With Stage Ⅴ Chronic Kidney Disease Tze-Wah Kao, M.D., Master, Principal Investigator, National Taiwan University Hosp ( 高芷華醫師 )
An Attempt to Emphasize The Multifactorial and Complex Nature of Progressive Renal Failure Genetic predisposition Inadequate access to health care Low birth weight Lower economic status High protein diet Lower educational achievements Hyperlipidemia Cardiovascular disease Smoking Analgesic & NSID abuse Drug and alcohol dependence HIV and other viral and bacterial infections Obesity Diabetes Systemic hypertension Endothelin Arachidonic acid metabolites Oxygen free radicals AGEs-related oxidative and carbonyl stress Nitric oxide Renin, Angiotensin & Aldosterone Cytokines, growth factors Progressive Renal Failure Salahudeen et al, Nephrol Dial Transplant 2002