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慢性腎臟病簡介
高雄榮總腎臟科
方華章
USRDS
KDOQI CKD Guidelines
KDOQI CKD Guidelines
KDOQI CKD Guidelines
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.
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.
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.
KDOQI CKD Guidelines
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.
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.
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
KDOQI CKD Guidelines
Definitions and Clinical Indicators for Testing for Proteinuria/Albuminuria
KDOQI CKD Guidelines
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 in
hypertensive 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
KDOQI CKD Guidelines
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.
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.
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.
Hazard ratio for all cause mortality
Impact of the clinical conditions at dialysis initiation on mortality in incident
haemodialysis patients: a national cohort study in Taiwan
3
2.5
2
1.5
1
0.5
0
Q5
Q4
Q3
Q2
Q1
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
Nephrol Dial Transplant. 2010 Jun 2. [Epub ahead of print
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
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.
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.
Women, older age, hypertension, and diabetes
were significantly associated with increased risks
of the development of ESR
Am J Kidney Dis. 2010 Mar;55(3):507-18. Epub 2010 Feb 8.
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
慢性腎衰竭對藥物動力學的影響
1.Absorption & bioavailability
2.Protein binding & Volume of distribution
3.Metabolism and Toxicity
4.Half life and clearance rate
5.Effect of hemodialysis
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
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Barbiturates
Dicloxacillin
Digoxin
Cephalosporins
Clofibrate
Doxepin
Loop diuretics
Oxazepam
Penicillins
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Pentobarbital
Phenobarbital
Phenytoin
Sulfonamides
Salicylate
Temazepam
Theophyline
Valproic acid
Warfarin
Metabolism and toxicity
• Drug metabolism
– Phase I reaction
• Oxidation
• Reduction
• Hydrolysis
– Phase II reaction
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Glucuronidation
Sulfation
Methylation
Acetylation
Glutathione conjugation
Amino acid conjugation
Toxicity
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Active metabolites
Toxic metabolites
Effect of renal failure on Metabolism
Drug metabolism

Phase I reaction
 Oxidation
 Reduction 
 Hydrolysis 
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Phase II reaction
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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
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Estimate GFR
Avoid nephrotoxic agents
Adjust dosage
Drug removal by dialysis
Monitoring drug level
Estimating GFR
• Cockcroft-Gault equation:
Ccr=
(140-Age)×BW
72×Scr
(× 0.85 if female)
• Abbreviated MDRD Study equation:
Ccr=186×Scr -1.154 ×Age -0.203 ×0.742 (if
female)×1.210 (if African-American)
CKD
Nephrotoxic agents
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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 leveldecrease dosage
• Insufficient trough levelshorten interval
慢性腎衰竭常用藥物劑量
Anti-hypertensive agents
Dialysis removal of antihypertensive agents(1)
Dialysis removal of antihypertensive agents(2)
Dialysis removal of antihypertensive agents(3)
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
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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
Serum prealbumin
4.0 g/dL
30 mg/dL
serum creatinine
10 mg/dL
Serum cholesterol
150 to 180
mg/dL
nPNA
1.0g prot/kg
23.6 and 24.0 23 kg/m2
kg/m2
BMI
4.0 g/dL
30 mg/dL
American Journal of Kidney Diseases, Vol 35, No 6, Suppl 2 (June), 2000: pp S17-S104
Laurent J, Fitsum GE, Denis F. Néphrologie & Thérapeutique (2010) 6, S2-S6
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
Management of Protein and Energy Intake
• 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
Management of Protein and Energy Intake
• 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
Management of Protein and Energy Intake
• 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
可選用下列蛋白質含量低而熱量高的食品做為補充
低蛋白 冬粉、細米粉、粉條、米苔目、粉圓、西谷米
澱粉類
、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。
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.
•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).
Block GA, et al. J Am Soc Nephrol 2004;15(8):2208–18
• 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
Organic P and Dietary Protein
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
Association between the
baseline dietary protein
intake, represented by 13week 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