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Reducing the Dietary Acid Load: How a More Alkaline Diet Benefits Patients With Chronic Kidney Disease
降低膳食酸负荷:碱性饮食如何使慢性肾病患者受益

Caroline Passey, BSc, RD, PhD
Caroline Passey,理学学士,RD,博士

Abstract 抽象

It has been proposed that a low-protein diet will slow progression of chronic kidney disease although studies have not always supported this belief. The accepted practice is that to of protein comes from high biological value (HBV) protein, but this limits patient choice and patients struggle to follow the diet. When a diet with only HBV protein was trialed, there was a significant increase in serum bicarbonate, and patients preferred the diet. The dietary advice given in predialysis clinics was changed. HBV protein was restricted to approximately of total protein, bread and cereal foods were allowed freely, and fruits and vegetables (F&V) were encouraged. Patients who followed the diet have seen a slowing of progression and occasionally regression of their renal function. Both observations and scientific literature indicate that this is because of a reduction in the acid content of the diet. When foods are metabolized, most proteins produce acid, and most F&V produce alkali. A typical -century diet produces 50 to per day which the kidney is challenged to excrete. Acid is excreted with phosphate and is limited to about per day. With chronic kidney disease, this falls progressively to below per day. Historically, ammonium excretion was believed to be excretion of acid , but it is now understood to be a by-product in the neutralization of acid by glutamine. The remaining acid is neutralized or stored within the body. Bone and muscle are lost in order to neutralize the acid. Acid also accumulates within cells, and serum bicarbonate falls. The author postulates that reducing the acid load through a low-protein diet with greater use of vegetable proteins and increased F&V intake will slow progression or occasionally improve renal function while maintaining the nutritional status of the individual.
有人提出,低蛋白饮食会减缓慢性肾病的进展,尽管研究并不总是支持这一观点。公认的做法是蛋白质 来自高生物价值 (HBV) 蛋白质,但这限制了患者的选择,患者难以遵循饮食。当试验仅 含有HBV蛋白的饮食时,血清碳酸氢盐显着增加,患者更喜欢这种饮食。透析前门诊的饮食建议发生了变化。HBV蛋白被限制在总蛋白的大约 范围内,面包和谷类食品被允许自由食用,水果和蔬菜(F&V)被鼓励。遵循饮食的患者已经看到他们的肾功能进展减慢,偶尔消退。观察和科学文献都表明,这是因为饮食中酸含量的降低。当食物被代谢时,大多数蛋白质会产生酸,大多数F&V会产生碱。典型的 世纪饮食每天产生 50 到 肾脏排泄的挑战。酸用磷酸盐排泄,限制在每天左右 。对于慢性肾病,这一数字逐渐下降到每天以下 。从历史上看,铵的排泄被认为是酸 的排泄,但现在它被理解为谷氨酰胺中和酸的副产物。剩余的酸被中和或储存在体内。骨骼和肌肉流失以中和酸。酸也会在细胞内积聚,血清碳酸氢盐会下降。 作者假设,通过低蛋白饮食、更多地使用植物蛋白和增加 F&V 摄入量来减少酸负荷将减缓进展或偶尔改善肾功能,同时保持个体的营养状况。

๑ 2016 by the National Kidney Foundation, Inc. All rights reserved.
๑ 2016 年由美国国家肾脏基金会保留所有权利。

Introduction 介绍

L OW-PROTEIN DIETS (LPDS) have been used in the management of chronic kidney disease (CKD) for more than 100 years. Originally these diets were prescribed to reduce uremic symptoms and improve well-being. Since the 1980s, these diets have been prescribed to slow progression of CKD. The composition of these diets has been debated over the years with regard to both the quantity and type of protein consumed and even whether they should be prescribed at all. Since the late 1960s, the most widely used LPD has been the protein diet or protein per kilogram ideal body weight (IBW). It has been recommended that to of the protein should come from high biological value (HBV) proteins to ensure that the diet provides sufficient essential amino acids to meet protein requirements. Studies using this diet did not show significant slowing of progression and,
100 多年来,L 蛋白饮食 (LPDS) 一直用于慢性肾脏病 (CKD) 的治疗。最初,这些饮食是为了减轻尿毒症症状和改善健康状况。自 1980 年代以来,这些饮食已被规定用于减缓 CKD 的进展。 多年来,这些饮食的组成一直在争论所消耗 的蛋白质的数量和类型,甚至是否应该开处方。 自 1960 年代后期以来,使用最广泛的 LPD 是 蛋白质饮食或 每公斤理想体重 (IBW) 的蛋白质。有人建议 ,蛋白质应来自高生物价值(HBV)的蛋白质,以确保饮食提供足够的必需氨基酸来满足蛋白质需求。 使用这种饮食的研究没有显示进展明显减慢, 并且,
Nutrition and Dietetic Department, Wessex Kidney Centre, Portsmouth Hospitals NHS Trust, Portsmouth, Hampshire, United Kingdom.
英国汉普郡朴茨茅斯医院NHS信托基金威塞克斯肾脏中心营养和饮食部。
Support: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
支持:这项研究没有从公共、商业或非营利部门的资助机构获得任何具体资助。
Financial Disclosure: The authors declare that they have no relevant financial interests.
财务披露:作者声明他们没有相关的财务利益。
Address correspondence to Dr Caroline Passey, BSc, RD, PhD, Lead Renal Dietitian, Queen Alexandra Hospital, Southwick Hill Road, Portsmouth, Hampshire PO6 3LY, United Kingdom. E-mail: caroline.passey@porthosp.nhs.uk
地址:Caroline Passey博士,BSc,RD,PhD,首席肾脏营养师,Queen Alexandra Hospital, Southwick Hill Road, Portsmouth, Hampshire PO6 3LY, United Kingdom。电子邮件: caroline.passey@porthosp.nhs.uk
(C) 2016 by the National Kidney Foundation, Inc. All rights reserved.
(C) 2016 年由美国国家肾脏基金会 (National Kidney Foundation, Inc.) 提供。保留所有权利。
http://dx.doi.org/10.1053/j.jrn.2016.11.006 therefore, many dietitians and medical practitioners may be reluctant to advocate their use.
http://dx.doi.org/10.1053/j.jrn.2016.11.006 因此,许多营养师和医生可能不愿意提倡使用它们。
The recommendation that to of the protein should come from HBV proteins means that most of the protein comes from animal foods and limits the consumption of bread and cereal (low biological value protein or LBV) foods resulting in low energy intake. Special lowprotein foods and energy supplements are used to meet the recommended energy intakes IBW/ IBW). However, patients do not like these special foods, and most patients struggle to follow the diet.
建议 蛋白质应来自HBV蛋白,这意味着大部分蛋白质来自动物性食物,并限制了面包和谷物(低生物价值蛋白质或LBV)食物的消费,导致能量摄入量低。特殊的低蛋白食物和能量补充剂用于满足推荐的能量摄入 量 IBW/ IBW)。然而,患者不喜欢这些特殊食物,大多数患者都难以遵循饮食习惯。
Study and observation of a newly defined LPD with more LBV protein foods has allowed improved dietary flexibility and compliance, but also highlighted the importance of dietary acid load in CKD. This is very significant (Fig. 1). A reduced ability to excrete acid in CKD causes an ongoing accumulation of acid within the body with deleterious effects on muscle mass and bone disease. By reducing the acid load, through a LPD with greater use of LBV proteins and increased fruit and vegetable (F&V) intake, the author postulates that progression to end-stage renal disease can be slowed or improved, while maintaining the nutritional status of the individual. Patients also feel better and have improved appetite.
研究和观察含有更多LBV蛋白食物的新定义的LPD可以提高饮食的灵活性和依从性,但也强调了膳食酸负荷在CKD中的重要性。 这非常重要(图 1)。慢性肾病患者排泄酸的能力降低会导致体内酸持续积聚,对肌肉质量和骨骼疾病产生有害影响。通过减少酸负荷,通过更多地使用LBV蛋白和增加水果和蔬菜(F&V)摄入量的LPD,作者假设可以减缓或改善终末期肾病的进展,同时保持个体的营养状况。患者也感觉好转,食欲也有所改善。
The approach used for this article has been based on personal observations of several hundred patients following an adapted LPD. These observations were not measured or quantified. They were carried out in a clinical setting
本文使用的方法基于对数百名患者在适应 LPD 后的个人观察。这些观察结果没有被测量或量化。它们是在临床环境中进行的
Figure 1. Consequences of a diet with a high dietary acid content in patients with CKD.
图 1.CKD患者饮食酸含量高的后果。
with patients who were showing subtle changes in health which were difficult to quantify. However, when these patients are seen over many years and personally known to the dietetic team, a confidence arose that there would be a scientific reason behind these observations. This led to the exploration of the alkaline diet.
患者表现出难以量化的健康状况的微妙变化。然而,当这些患者被观察多年并为饮食团队所熟知时,人们相信这些观察结果背后是有科学原因的。这导致了对碱性饮食的探索。

A New LPD 新的LPD

A new LPD ( protein IBW/day) was designed with only protein from HBV proteins, and nitrogen balance studies were used to compare this diet with the conventional LPD in a group of patients with CKD. On the new LPD, essential amino acid requirements were met, and nitrogen balance was not significantly different although 5 of the 7 patients were in more positive nitrogen balance on the new LPD. Serum bicarbonate increased significantly with the new LPD but all other biochemical and hematological parameters were unchanged. Total energy intake was similar on both diets, but energy obtained from normal foods increased from day day) to day day; on the new LPD. In addition, patients preferred the flexibility of the new diet.
设计了一种新的LPD( 蛋白质 IBW/天),仅 使用来自HBV蛋白的蛋白质,并使用氮平衡研究将这种饮食与一组CKD患者的常规LPD 进行比较。 在新的LPD上,满足必需氨基酸要求,并且氮平衡没有显着差异,尽管7名患者中有5名在新的LPD上处于更积极的氮平衡状态。血清碳酸氢盐随着新LPD的升高而显著 增加,但所有其他生化和血液学参数均未改变。两种饮食的总能量摄入量相似,但从正常食物中获得的能量从 一天 一天 都在增加; 在新的 LPD 上。此外,患者更喜欢新饮食的灵活性。

Encouraging Observations in the Predialysis Clinic
透析前临床的令人鼓舞的观察结果

In 2008, after the positive response from patients to the new LPD, the diet was adapted for routine use in patients attending our predialysis clinics (glomerular filtration rate [GFR] minute). HBV proteins are restricted to approximately of protein intake (0.6-0.8 g protein/ IBW), bread and cereal foods are allowed freely for energy, and F&V actively encouraged. It is observed that many patients in the predialysis clinics have low intakes of ; however, their consumption is essential to help reduce the acid load. Patients who followed the new diet reported improved appetite and well-being. Subtle improvements with regard to progression of CKD were noticed (personal observation), and more patients had stable (Fig. 2), or occasionally, improved renal function (Fig. 3). The positive effect on patients following the revised LPD has prompted the investigation of acid-base balance in greater detail and the crucial role played by diet.
2008 年,在患者对新 LPD 的积极反应之后,该饮食被调整为就诊透析前诊所的患者的常规使用(肾小球滤过率 [GFR] 分钟)。HBV蛋白被限制在大约 蛋白质摄入量(0.6-0.8克蛋白质/ IBW),面包和谷类食品可以自由获取能量,并积极鼓励F&V。据观察,透析前门诊的许多患者摄入 量较低;然而,它们的消耗对于帮助减少酸负荷至关重要。遵循新饮食的患者报告说食欲和幸福感有所改善。注意到CKD进展的细微改善(个人观察),更多的患者病情稳定(图2),或偶尔改善肾功能(图3)。修订后的 LPD 对患者的积极影响促使人们更详细地研究酸碱平衡以及饮食所起的关键作用。

Background 背景

The acid and alkaline nature of food were recognized more than a century ago. Sherman et al. quantified the potential amounts of acid and alkali by measuring the alkaline ash content of a variety of foods. They suggested that the acid and alkaline elements of the diet should balance each other. Early "nephrologists" (1920s and 1930s) recognized that kidney patients suffered from an excess of acidity. Alkaline diets were used successfully in the treatment of chronic nephritis and hypertension, and patients felt better. However, this aspect of diet seems to have disappeared from mainstream medicine and nutrition, although continued to be advocated by the popular press. Recently, following extensive studies in animal CKD models, Wesson et al. developed the hypothesis that increasing consumption reduces kidney damage and slows progression of CKD. This has been substantiated by them in a number of human studies.
一个多世纪前,人们就认识到食物的酸性和碱性。Sherman等人通过测量各种食物的碱性灰分含量来量化酸和碱的潜在量。 他们建议饮食中的酸性和碱性元素应该相互平衡。早期的“肾病学家”(1920 年代和 1930 年代)认识到肾病患者的酸度过高。碱性饮食成功用于治疗慢性肾炎和高血压,患者感觉好转。 然而,饮食的这一方面似乎已经从主流医学和营养学中消失了,尽管大众媒体继续提倡。 最近,在对动物CKD模型进行广泛研究后, Wesson等人提出了一个假设,即增加 消费可以减少肾脏损伤并减缓CKD的进展。他们在一些人体研究中证实了这一点。

Acid and Alkaline Foods
酸性和碱性食物

When foods containing protein are metabolized, most proteins release acid hydrogen ions) because of the metabolism of amino acids. The amount of acid depends on which amino acids are present: some amino acids are neutral, some acidic, and some alkaline. Lysine, arginine, and histidine are acidic, and when metabolized in the liver generate hydrochloric acid (plus glucose and urea). The amino acids, cysteine and methionine, contain sulfur and are converted to sulfuric acid:
当含有蛋白质的食物被代谢时,由于氨基酸的代谢,大多数蛋白质会释放酸 性氢离子。酸的量取决于存在的氨基酸:有些氨基酸是中性的,有些是酸性的,有些是碱性的。赖氨酸、精氨酸和组氨酸呈酸性,在肝脏代谢时生成盐酸(加上葡萄糖和尿素)。半胱氨酸和蛋氨酸氨基酸含有硫并转化为硫酸:
Figure 2. Patient 1 (female, 77 years with hypertension, Type II diabetes, previous stroke and myocardial infarction, osteoarthritis and single functioning kidney) attended predialysis clinic in December 2012 (glomerular filtration rate: minute). Her diet was high in protein (large portions with main and snack meal) with moderate portions of fruits and vegetables. Protein portions were reduced (urea fell from 27 to in 2 months) and vegetable portions increased including regular salads. The patient has remained well, although troubled by her arthritis, for almost 4 years (recent GFR minute) and is no longer seen in predialysis clinics.
图2.患者1(女,77岁,高血压,II.型糖尿病,既往卒中和心肌梗死,骨关节炎和单功能肾)于2012年12月到透析前门诊就诊(肾小球滤过率: 分钟)。她的饮食中蛋白质含量高(主餐和零食占大部分),水果和蔬菜适量。蛋白质份量减少(尿素 从27份下降到2个月),蔬菜份量增加,包括普通沙拉。尽管受到关节炎的困扰,但患者一直保持良好状态近 4 年(最近的 GFR 分钟),并且不再在透析前诊所就诊。

Most F&V when metabolized produce alkali which neutralizes the acid. contain organic acids such as citric acid and organic salts, for example, potassium citrate. The organic acids, when metabolized, produce equal amounts of hydrogen and base ions, but the organic salts contain base ions but no hydrogen and, therefore, "mop up" hydrogen ions on their metabolism to carbon dioxide and water. This reduces the acid load:
大多数F&V在代谢时会产生碱,从而中和酸。 含有有机酸,如柠檬酸和有机盐,如柠檬酸钾。有机酸在代谢时会产生等量的氢和碱离子,但有机盐含有碱离子但不含氢,因此,氢离子在代谢过程中“清除”为二氧化碳和水。这减少了酸负荷:
Foods which contain phosphate, whether naturally or from food additives, can add acid to the diet. The acidity depends not on the phosphate anion but on the cation to which it is attached and the of the food. For example, phosphoric acid in cola drinks is acidic as is released, whereas the food additive trisodium phosphate is alkaline and will remove .
含有磷酸盐的食物,无论是天然的还是来自食品添加剂的,都会在饮食中增加酸。酸度不取决于磷酸根阴离子,而是取决于它所附着的阳离子和 食物的酸度。例如,可乐饮料中的磷酸 在释放时 是酸性的,而食品添加剂磷酸三钠 是碱性的,会去除
excreted as in the urine
像尿液 一样 排泄
in urine)  在尿液中)
Fats and sugars, unless incompletely metabolized, have only a small effect on acid-base balance.
脂肪和糖,除非代谢不完全,否则对酸碱平衡的影响很小。
Net endogenous acid production (NEAP) can be estimated from dietary constituents together with an estimation of organic acids generated from diet and metabolism and excreted in the urine. A number of formulae exist for
内源性酸净产生量(NEAP)可以从膳食成分中估算出来,也可以从饮食和新陈代谢中产生并从尿液中排出的有机酸的估算值。存在许多公式

Figure 3. Patient 2 (male, 74 year old, with ischemic/hypertensive nephrosclerosis, severe cardiac dysfunction, and previous myocardial infarction) attended predialysis clinic in June 2009 (glomerular filtration rate [GFR]: minute). His diet was high in protein with some fruit but few vegetables and no potatoes. He was advised on a lowprotein diet with added vegetables but no other changes in treatment were made. Protein intake reduced (urea fell from 36 to over the first year) and GFR began to improve. Improvements in cardiac function were also noted and he remained relatively well, until dying from a chest infection 4 years 6 months after his first clinic visit (GFR: minute).
图3.患者2(男,74岁,缺血性/高血压性肾硬化、严重心功能不全、既往心肌梗死)于2009年6月到透析前门诊就诊(肾小球滤过率[GFR]: 分钟)。他的饮食中蛋白质含量高,有一些水果,但蔬菜很少,也没有土豆。医生建议他采用低蛋白饮食和添加蔬菜,但治疗没有做出其他改变。蛋白质摄入量减少(尿素从36 下降到第一年),GFR开始改善。还注意到心脏功能的改善,他一直保持相对健康,直到他第一次门诊就诊后 4 年 6 个月死于胸部感染(GFR: 分钟)。
Table 1. Estimation of Net Endogenous Acid Production (NEAP)
表 1.内源酸净产量(NEAP)估算
Acid production can be estimated from diet or measured in the urine: Estimated NEAP = NAE (all mEq/d)
胃酸的产生可以从饮食中估计或在尿液中测量:估计的 NEAP = NAE(所有 mEq/d)
Diet: Several formulae have been proposed to estimate NEAP. Two of these are as follows:
饮食:已经提出了几种公式来估计NEAP。其中两个如下:
Frassetto NEAP protein potassium
Frassetto NEAP蛋白
Remer NEAP (mEq/d) PRAL + OA
Remer NEAP (mEq/d) PRAL + OA
where PRAL day protein phosphorus potassium
其中PRAL 蛋白
magnesium calcium
镁钙
or  
Urine:  尿:
BSA, body surface area; BW, body weight; , bicarbonate; NAE, net acid excretion; NEAP, net endogenous acid production; , ammonium; , estimate of organic acid production; PRAL, potential renal acid load; TA, titratable acid.
BSA, 体表面积;BW, 体重; 碳酸氢盐;NAE, 净酸排泄;NEAP, 内源酸净产量; 铵; ,有机酸产量的估计;PRAL,潜在肾酸负荷;TA,可滴定酸。
this (Table 1). In Remer's formula, the potential renal acid load (PRAL) of foods is estimated and this is a useful tool to compare foods (Table 2). A typical -century diet releases 50 to per day (PRAL of diet (vegan) to +50 (diet rich in animal protein/cereal foods and low F&V) plus from endogenous metabolism]).
这(表1)。 在Remer的公式中,估计了食物的潜在肾酸负荷(PRAL),这是比较食物的有用工具(表2)。典型的 世纪饮食每天释放 50 至 (饮食 的 PRAL (素食主义者) 至 +50(富含动物蛋白/谷物食品和低 F&V 的饮食)加上 内源性代谢])。

The Role of the Kidney in Maintaining Acid-Base Balance
肾脏在维持酸碱平衡中的作用

The kidney helps maintain acid-base balance by 3 main mechanisms: (1) excretion of acid, (2) neutralization of acid and (3) excretion of anions.
肾脏通过3种主要机制帮助维持酸碱平衡:(1)酸的排泄,(2)酸的中和和(3)阴离子的排泄。

Excretion of Acid 酸的排泄

Dietary acid has to be excreted by the kidney. Phosphate is the primary buffer in the urine and accepts ions . The quantity of phosphate excreted is mainly dependent on dietary phosphate and usually varies between 10 and day. About of the phosphate filtered at the glomerulus is in the monohydrate form and will remove ions. The remaining phosphate is already present in the diprotic form and therefore unable to remove additional hydrogen. When the of the urine falls, creatinine, urate, and other anions filtered at the glomerulus act as urinary buffers, removing additional hydrogen ions. Acid excreted with phosphate and other urinary buffers is known as titratable acid (TA).
膳食酸必须由肾脏排泄。磷酸盐是尿液中的主要缓冲液,接受 离子 。磷酸盐排泄量主要取决于膳食磷酸盐,通常在10天和 10天之间变化。 在肾小球处过滤的磷酸盐大约 是一水合物形式 ,将去除 离子。剩余的磷酸盐已经以二质子子形式 存在,因此无法去除额外的氢。 当尿液下降时,在肾小球过滤的肌酐、尿酸盐和其他阴离子充当尿液缓冲器,去除额外的氢离子。用磷酸盐和其他尿液缓冲液排泄的酸称为可滴定酸 (TA)。

Neutralization of Acid 酸的中和作用

Historically, it was believed that ammonia was also a urinary buffer accepting and thus increasing acid excretion. However, it is now recognized that the remaining acid is not excreted but only neutralized within the kidney and ammonium is a by-product of this. Neutralization of acid occurs through the metabolism of glutamine. In the proximal tubule of the kidney, glutamine is taken from the blood stream and broken down to alphaketoglutarate and ammonium. consumes on its metabolism to glucose, thus reducing the acid
从历史上看,人们认为氨也是一种尿液缓冲剂,可以接受 并增加酸排泄。然而,现在人们认识到,剩余的酸不会排泄,而只会在肾脏内中和,而铵是其副产品。 酸的中和是通过谷氨酰胺的代谢发生的。在肾脏的近端肾小管中,谷氨酰胺从血流中取出并分解为α酮戊二酸 和铵。 消耗其代谢为葡萄糖,从而减少酸
Table 2. The Potential Renal Acid Load (PRAL) of Food (mEq/3.5 oz [100 g] and per Average Portion Size)
表 2.食物的潜在肾酸负荷 (PRAL)(mEq/3.5 oz [100 g] 和每份平均份量)
Food Type
PRAL mEq per