慢性腎臟病簡介高雄榮總腎臟科方華章. USRDS KDOQI CKD Guidelines

慢性腎臟病簡介

高雄榮總腎臟科方華章

USRDS

KDOQI CKD Guidelines




2002 台灣三高調查 moderate to severe CKD prevalence

高醫黃尚志教授

All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan.

Lancet. 2008 Jun 28;371(9631):2173-82.


Lancet. 2008 Jun 28;371(9631):2173-82.


Lancet. 2008 Jun 28;371(9631):2173-82.


Epidemiological features of CKD in Taiwan.

Am J Kidney Dis. 2007 Jan;49(1):46-55

Epidemiological features of CKD in Taiwan.

Am J Kidney Dis. 2007 Jan;49(1):46-55

Prevalence and risk factors for CKD in spouses and relatives of hemodialysis patients

Am J Kidney Dis. 2010 May;55(5):856-66. Epub 2010 Feb 13.





Strategies for Early Detection and Intervention

Diabetes mellitus

Hypertension

Central obesity

Advanced age

African Americans

Hispanics

Native Americans

Pacific Islanders

A family history of cardiovascular or renal disease


Definitions and Clinical Indicators for Testing for Proteinuria/Albuminuria


Management & Treatment of CKD

Treatment of underlying diseases

Identification & modification of risk factors

Treatment of complications

Identification and avoidance of offending agents

Slowing down of renal impairment progression (ACEI or ARB)

Regeneration therapy (growth factors or stem cell-based therapy)

Strategies for Early Detection and Intervention to Slow down Renal Impairment Progression

Blood pressure control: The goal is a sitting blood pressure of less than 130/85; 125/75 mm Hg is preferable.

Angiotensin-converting enzyme inhibitor therapy: Therapy with an angiotensin II receptor antagonist is recommended in those patients who are intolerant of angiotensin-converting enzyme inhibitors.

Dietary salt restriction: A high-salt diet can override the antiproteinuric effects of angiotensin-converting enzyme inhibitors. Salt restriction is particularly important inhypertensive patients with proteinuria.

Dietary protein restrictions: Moderate (0.8 g/kg body weight) restriction is recommended in proteinuric patients to assist in reducing the degree of proteinuria and probably reduce the rate of progression of renal disease. y history of cardiovascular or renal disease


Multidisciplinary predialysis education decreases the incidence of dialysis and reduces mortality--a controlled cohort study based on the NKF/DOQI guidelines.

Nephrol Dial Transplant. 2009 Nov;24(11):3426-33. Epub 2009 Jun 2.





Impact of the clinical conditions at dialysis initiation on mortality in incident haemodialysis patients: a national cohort study in Taiwan

Nephrol Dial Transplant. 2010 Jun 2. [Epub ahead of print

Haz

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orta

lity

Quintiles of eGFR at the start of dialysis

In 23 551 incident HD patients from 2001 to 2004. The median eGFR at dialysis initiation : 4.7 mL/min/1.73 m(2)The mortality in the first year of dialysis: 13.2/100 patient-year, 95% CI = 12.8-13.7

Probable Causes of High Incidence & Prevalence of ESRD in Taiwan

Increasing prevalence of metabolic syndrome (DM)

Ageing of population

Insurance system

Drug exposure

Earlier dialysis

Better care and longer survival

Less kidney transplantation

USRDS


Lancet. 2008 Jun 28;371(9631):2173-82.

Incidence, prevalence and mortality trends of dialysis end-stage renal disease in Taiwan from 1990 to 2001: the impact of national health insurance.

Nephrol Dial Transplant. 2008 Dec;23(12):3977-82. Epub 2008 Jul 15.

Risks of kidney failure associated with consumption of herbal products containing Mu Tong or Fangchi: a population-based case-control study.

Am J Kidney Dis. 2010 Mar;55(3):507-18. Epub 2010 Feb 8.

Women, older age, hypertension, and diabetes were significantly associated with increased risks of the development of ESR

透析病患用藥安全臨床常見的藥物副作用

高雄榮總腎臟科許智揚

大綱

• 慢性腎衰竭對藥物動力學的影響• 慢性腎臟病患處方注意事項• 慢性腎衰竭常用藥物劑量

1.Absorption & bioavailability

2.Protein binding & Volume of distribution

3.Metabolism and Toxicity

4.Half life and clearance rate

5.Effect of hemodialysis

慢性腎衰竭對藥物動力學的影響

Effect of renal failure on Absorption-Decrease absorption

• Loss of gastric acidity:– Urea urease gastric pH (Ex: Iron absorption)– Oral phosphate binders (Ex: digoxin,antibiotics)

• Motility dysfunction of GI tract:– Gastroparesis, prolonged gastric emptying(DM)

delay drug absorption– Diarrhea decrease gut transit time diminish drug

absorption– Nausea, vomit

• Edema:– Decrease transdermal delivery

Bioavailability

• Definition: The amount that enters the central circulation and the rate at which the active moiety (drug or metabolite) enters systemic circulation

First-pass effect Decrease bioavailability in oral drugs

Effect of renal failure on bioavailability

• Increase bioavailability: – Uremia decrease first-pass effect

amount of active drugs in circulation

Protein binding (PB) and Volume of distribution(VD)

• VD= dose/blood concentration• Small VD: (Ex: ibuprofen)

– High serum protein-binding agents– water-soluble agents

• High VD: (Ex: digoxin, TCA)– High tissue protein-binding agents– Lipid-soluble agents

• The higher VD, the longer half-life

Effect of renal failure on PB and VD

• Edema: VD on small VD agents drug level

• Dehydration: VD on small VD agents drug level

• Decrease protein binding drug level– Accumulation of protein-bound organic acids

(hippurate, indoxyl sulfate) PB in acidic drugs

– Hypoalbuminemia albumin affinity

Drugs with decrease protein binding in dialysis patients

• Barbiturates

• Dicloxacillin

• Digoxin

• Cephalosporins

• Clofibrate

• Doxepin

• Loop diuretics

• Oxazepam

• Penicillins

• Pentobarbital

• Phenobarbital

• Phenytoin

• Sulfonamides

• Salicylate

• Temazepam

• Theophyline

• Valproic acid

• Warfarin

Metabolism and toxicity

• Drug metabolism– Phase I reaction

• Oxidation• Reduction • Hydrolysis

– Phase II reaction• Glucuronidation• Sulfation• Methylation• Acetylation• Glutathione conjugation• Amino acid conjugation

Toxicity Active

metabolites Toxic metabolites

Effect of renal failure on Metabolism

Drug metabolism Phase I reaction

Oxidation Reduction Hydrolysis

Phase II reaction Glucuronidation Sulfation Methylation Acetylation Glutathione conjugation Amino acid conjugation

Toxicity Active metabolites

Toxic metabolites

Half life and clearance rate

• T1/2=(0.693x VD)/clearance

• Uremia clearance T1/2

Effect of dialysis

• Drug– Molecular weight, water solubility, Vd, protein binding

• Hemodialysis– Blood flow, dialysate flow

– Membrane material, permeability, surface area

• Peritoneal dialysis• Continuous renal replacement therapy• Residual renal function

慢性腎臟病患處方注意事項

• Estimate GFR

• Avoid nephrotoxic agents

• Adjust dosage

• Drug removal by dialysis

• Monitoring drug level

Estimating GFR

• Cockcroft-Gault equation:

• Abbreviated MDRD Study equation: Ccr=186×Scr -1.154 ×Age -0.203 ×0.742 (if

female)×1.210 (if African-American)

(140-Age)×BW72×Scr (× 0.85 if female)Ccr=

CKD

Nephrotoxic agents• Contrast medium• Aminoglycoside• Cisplatin• NSAIDs• Cyclosporin• Lithium• Foscarnet• Methotrexate• Fleet, oral sodium phosphate products (OSPs)• ACE inhibitors / ARB

Adjust dosage

• Loading dose= Vd X IBW X Cp

• Dose in CKD = Normal dose X Df

• Dose interval in CKD = Normal dose interval / Df

• Df= t 1/2normal / t 1/2 renal failure

Vd: Volume of distribution (L/kg); IBW: ideal body weight (Kg); Cp: desired steady-state plasma drug concentration; Df: the fraction of the normal dose to be given

Drug removal by dialysis

• Drug clearance by hemodialysis (Cld)

– Cld=Clurea X (60/MWdrug)

– Cld=Qb(Ci-Co)/Ci

– Cld=S X UFRavg ;S = Cuf/ Ci

Clurea: 150~200ml/min; Qb:blood flow rate; Ci: Inflow concentration; Co: outflow concentration; S: sieving coefficient; Cuf: concentration in filtrate

Drugs that were easily removed by dialysis

• Molecular weight <500 Da

• High water solubility

• Small volume of distribution

血液透析後需要補充劑量的藥物

Monitoring drug level

• Peak level– 1~2 hr after taking oral drugs– 30~60 min after infusing IV drugs

• Trough level:– Before next dosage

• Exceeding peak leveldecrease dosage• Insufficient trough levelshorten interval

慢性腎衰竭常用藥物劑量

Anti-hypertensive agents

Dialysis removal of antihypertensive agents(1)



Hypoglycemic agents

Antibiotics(1)

Antibiotics(2)

Antibiotics(3)

Antibiotics(4)

Antibiotics(5)

statins

Others

Meperidine (demerol)

• Metabolite: Normeperidine (T1/2: 35 h in CKD pt)• S/S: Hallucination, delirium, psychosis, nervousness,

tremor, multifocal myoclonus, and seizure• Cannot be reversed by naloxone

1. Successful treatment of normeperidine neurotoxicity by hemodialysis. Am J Kidney Dis. 2000 Jan;35(1):146-9.

2. Meperidine associated mental status changes in a patient with chronic renal failure. J Fla Med Assoc. 1996 May;83(5):315-9.

3. Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure of cancer. Ann Intern Med. 1977 Jun;86(6):738-41

Famotidine (Gaster)

• Confusion, agitation, delirium, irritability, and hallucinations

1. Central nervous system reactions associated with famotidine: report of five cases. J Clin Gastroenterol. 1998 Oct;27(3):253-4

2. Use of famotidine in adult patients with end-stage renal disease: assessment of dosing and mental status changes Am J Med Sci. 2005 Jul;330(1):8-10

Metoclopramide (primperan)

• Dopamine antagonist• Extrapyramidal reaction, neuroleptic malignant

syndrome, parkinsonism, tardive dyskinesia

1. Metoclopramide in a patient with renal failure may be an increased risk of neuroleptic malignant syndrome Intensive Care Med. 1996 Jul;22(7):717

2. Metoclopramide-induced parkinsonism in hemodialysis patients. Report of two cases Arch Intern Med. 1986 Oct;146(10):2070-1

3. Metoclopramide-associated tardive dyskinesia in hemodialysis patients with diabetes mellitus. Two case reportsGen Hosp Psychiatry. 1992 Nov;14(6):416-9

Antibiotics

Hypnotics

• Flurazepam, diazepam, lorazepam• Altered consciousness, asterixis, abnormal electroencephalogram• Reversible

1. Drug-induced encephalopathy in patients on maintenance haemodialysis Lancet. 1976 Oct 2;2(7988):704-5

2. Impaired elimination of lorazepam following subchronic administration in two patients with renal failure. Br J Clin Pharmacol. 1981 Nov;12(5):749-51

結論

• 有絕對適應症的藥物才使用• 選擇沒有或極少腎毒性的藥物• 使用腎衰竭專用劑量調整表開立處方• 必要時可監測血中濃度• 使用自己熟悉的藥物• 監測藥物效果及副作用

謝謝聆聽 , 敬請指教

慢性腎臟病人營養衛教

高雄榮總王雅君

Introduction

• PROTEIN-ENERGY malnutrition (PEM) is very common among patients with advanced chronic renal failure (CRF) and those undergoing maintenance dialysis (MD) therapy worldwide.

• Different reports suggest that the prevalence of this condition varies from roughly 18% to 70% of adult MD patients.

Introduction• There are many causes of PEM in patients with

advanced CRF. These include:• Inadequate food intake . • the catabolic response to superimposed illnesses.• the dialysis procedure itself, which may promote

wasting by removing such nutrients as amino acids, peptides, protein, glucose, water-soluble vitamins, and other bioactive compounds, and may promote protein catabolism, due to bioincompatibility

Introduction

• conditions associated with chronic renal failure.

• loss of blood.

• endocrine disorders of uremia.

• possibly the accumulation of endogenously formed uremic toxins or the ingestion of exogenous toxins.

Nutrition assessment

Assessment

American Journal of Kidney Diseases, Vol 35, No 6, Suppl 2 (June), 2000: pp S17-S104

Recommended

KDOQI 2000 European 2007

Serum albumin 4.0 g/dL 4.0 g/dLSerum prealbumin 30 mg/dL 30 mg/dL

serum creatinine 10 mg/dL

Serum cholesterol 150 to 180 mg/dL

nPNA 1.0g prot/kgBMI 23.6 and 24.0

kg/m223 kg/m2

Laurent J, Fitsum GE, Denis F. Néphrologie & Thérapeutique (2010) 6, S2-S6

American Journal of Kidney Diseases, Vol 35, No 6, Suppl 2 (June), 2000: pp S17-S104

Assessment

• SGA is a valid and clinically useful measure of protein-energy nutritional status in maintenance dialysis patients. (Evidence)

Panels of Nutritional Measures for Nondialyzed Patients

• For individuals with CRF (GFR <20 mL/min) protein-energy nutritional status should be evaluated by serial measurements of a panel of markers including at least one value from each of the following clusters: (1) serum albumin; (2) edema-free actual body weight, percent standard (NHANES II) body weight, or subjective global assessment (SGA); and (3) normalized protein nitrogen appearance (nPNA) or dietary interviews and diaries. (Evidence and Opinion)

KDOQI 2000

Management of Protein and Energy Intake

• The recommended DPI for clinically stable MHD patients is 1.2 g/kg body weight/d. (Evidence and Opinion)

• At least 50% of the dietary protein should be of high biological value.

KDOQI 2000


• Removal of amino acids (about 10 to 12 g per HD) some peptides, low amounts of protein (1 to 3 g per dialysis, including blood loss), and small quantities of glucose (about 12 to 25 g per dialysis if glucose-free dialysate is used) may contribute to PEM.

KDOQI 2000


• The recommended DPI for clinically stable CPD patients is 1.2 to 1.3 g/kg body weight/d. (Evidence)

• Peritoneal protein losses average about 5 to 15 g/24 hours, and during episodes of peritonitis, dialysate protein may be considerably higher. Peritoneal amino acid losses average about 3 g/d,and some peptides are dialyzed.

KDOQI 2000


• The recommended daily energy intake for maintenance hemodialysis or chronic peritoneal dialysis patients is 35 kcal/kg body weight/d for those who are less than 60 years of age and 30 to 35 kcal/kg body weight/d for individuals 60 years or older. (Evidence and Opinion)

KDOQI 2000

Dietary Protein Intake for Nondialyzed Patients

• For individuals with chronic renal failure (GFR <25 mL/min) who are not undergoing maintenance dialysis, the institution of a planned low-protein diet providing 0.60 g protein/kg/d should be considered. For individuals who will not accept such a diet or who are unable to maintain adequate DEI with such a diet, an intake of up to 0.75 g protein/kg/d may be prescribed. (Evidence and Opinion)

KDOQI 2000

Dietary Energy Intake (DEI) for Nondialyzed Patients

• The recommended DEI for individuals with chronic renal failure (CRF; GFR <25 mL/min) who are not undergoing maintenance dialysis is 35 kcal/kg/d for those who are younger than 60 years old and 30 to 35 kcal/kg/d for individuals who are 60 years of age or older. (Evidence and Opinion)

KDOQI 2000

蛋白質

• 其中 50 ～ 75% 來自高生物價之動物性蛋白質，如雞、鴨、魚、豬、牛、羊等肉類、蛋、牛奶，其餘的蛋白質由米、麵粉及其製品、蔬菜、水果供給。

• 限制蛋白質的同時，必須配合足夠的熱量，才可維持良好的營養狀況。

補充熱量

低蛋白澱粉類

冬粉、細米粉、粉條、米苔目、粉圓、西谷米、粉皮、藕粉、水晶餃皮、玉米粉、太白粉、地瓜粉、澄粉、低蛋白米粒（粉）

純糖類各種純糖、冰糖、水果糖、蜂蜜、果糖、糖飴、麥芽糊精

純油脂沙拉油等植物油、低鹽瑪琪淋、奶精、三多高熱能

其　他加糖或蜂蜜之仙草、愛玉、洋菜凍等。

可選用下列蛋白質含量低而熱量高的食品做為補充

鉀離子

• 限鉀時機：– K ＞ 5mg/dl or 排尿量 < 1000 cc/ 天 ( 血鉀高或尿少時 )– K-sparing medications are used (as ACEI and ARB)

• 鉀離子易溶於水，普遍存於各類食物中，蔬菜切小片以熱水燙過撈起，再以油炒或油拌可以減少鉀的攝取量。

• 食物經煮熟後，鉀會流失於湯汁中故勿食湯汁。 • 市售低鈉或薄鹽醬油或半鹽、低鹽等，含鉀量高不宜

任意飲用。• 咖啡、濃茶、人蔘、中藥材 ( 草 ) 、精力湯、蔬果汁

鈉離子

• 過量的鹽份會造成腎衰竭患者高血壓或水腫，一天建議攝取的鹽量約為 3 ～ 5公克。

• 烹調時可採用糖醋（白糖、白醋、檸檬汁、鳳梨等）或添加香辛料如蔥、薑、蒜、花椒、胡椒、香菜等方式來增加食物的可口性。

• 限制鹽份攝取有助於改善血壓Diabetes Care, 2006, 29 (9): 2140-2157

水份

• 體內水份過多會導致呼吸急促、高血壓、充血性心臟衰竭及肺積水，腎衰竭者尤需注意每日體重勿增減太多。

• 當日水份攝取＝前一日尿量排出＋ 500 ～ 700毫升。（排出量包括嘔吐、腹瀉或引流）

• 水份控制的技巧：1.儘量少吃醃製及加工製品，味精最好不要用，以免容易口渴。 2.先將一日可以喝的水，用固定容器裝好，並且將這些水平均分配

飲用。 3. 可將一日可飲用的水，分一部份混合檸檬汁結成冰塊，口渴時含

一粒在口中，讓冰塊慢慢溶化。

dP 0.05.

eP 0.0001.

retrospective United States Renal Data System Waves Study of 14,829 patients who were on hemodialysis on December 31, 1993, were examined.Slinin Y, Foley RN, Collins AJ. J Am Soc Nephrol 2005;16 (6):1788–93.

Block GA, et al. J Am Soc Nephrol 2004;15(8):2208–18

•Cohort study, 40,538 hemodialysis patients.

•After adjustment for case mix and laboratory variables, serum phosphorus concentrations 5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and 9.0 mg/dl).

• An 8-week randomized, double-blind study in 100 hemodialysis patients.

•Calcium acetate reduced mean serum phosphorus below the target level of 5.5 mg/dL by the third week of treatment, and maintained serum phosphorus below the target level until week 8. In the sevelamer hydrochloride treatment group, mean serum phosphorus never fell below the target level throughout the 8-week treatment period. （ A ）

•Observed and modelestimated percent of subjects achieving goal serum phosphorus level (≤5.5 mg/dL) by treatment group and week (B).Qunibi WY, et al. Kidney Int 2004;65(5):1914–26.

The CKDKAT-N was used to evaluate MD patient nutrition knowledge. This questionnaire is composed of 25 multiple-choice questions reflecting knowledge of 4 nutrients relevant to MD patients: phosphorus, protein, sodium, and potassium. Fifteen questions concern phosphorus, and the remaining 10 test the domains of protein, sodium, and potassium.

Judson BP, Jonathan BJ. J Ren Nutr. 2007 ; 17(5): 323–328.

Judson BP, Jonathan BJ. J Ren Nutr. 2007 ; 17(5): 323–328.

Understanding Sources of Dietary Phosphorus in the Treatment of Patients with Chronic Kidney Disease

• Organic P and Dietary Protein• P Intake from Plant Foods: The Role of Phytate• Inorganic P in Additives

Daily P and protein intake in 107 maintenance hemodialysis (MHD) who participated in the Nutritional and Inflammatory Evaluation of Dialysis Patients (NIED) Study

Colman S, et al. J Ren Nutr 15: 231–243, 2005

Organic P and Dietary Protein

Organic P and Dietary Protein

Association between the baseline dietary protein intake, represented by 13-week averaged nPNA (nPCR) and 13- week averaged serum P, in 30,075 DaVita MHD patients (P< 0.001 for trend).

Shinaberger CS, et al. Am J Clin Nutr 88: 1511–1518, 2008

Kamyar KZ,et al. Clin J Am Soc Nephrol 5: 519–530, 2010.

P Intake from Plant Foods: The Role of Phytate

• P in plants, especially in beans, peas, cereals, and nuts, is mostly in the form amount of dietary P from either animal or plant foods, urinary P excretion is higher with the meat-based diet.

• the role of phyate in inhibiting the intestinal P absorption, plant foods are somewhat less likely to increase P burden.

• Even with a lower fractional rate of intestinal absorption with such foods as beans, a large bean intake can still lead to an excessive P burden.

Inorganic P in Additives

Inorganic P in Additives

Implications of P Burden from Additives

• it is believed that 90% of inorganic P may be absorbed in the intestinal tract, as opposed to only 40 to 60% of the organic P present in natural foods.

• In the early 1990s, P additives contributed approximately 500 mg/d P to the American diet, whereas today P additives may contribute as much as 1000 mg/d P to the average American diet.

Sullivan CM, Leon JB, Sehgal AR. J Ren Nutr 17: 350–354, 2007

Conclusions

• the P burden from food additives in fast foods, soft drinks, and processed cheese and snacks is disproportionately high relative to its dietary P content compared with natural P sources from animal and plant protein.

• high protein intake and a concurrent low P intake and normal serum P seems to be associated with the lowest mortality in patients with ESRD during long hemodialysis treatment.

Kamyar KZ,et al. Clin J Am Soc Nephrol 5: 519–530, 2010

Documents

慢性腎臟病簡介 高雄榮總腎臟科 方華章. USRDS KDOQI CKD Guidelines

慢性腎臟病簡介高雄榮總腎臟科方華章. USRDS KDOQI CKD Guidelines