Official reprint from UpToDate

www.uptodate.com 2017 UpToDate

Dietary recommendations for patients with nondialysis CKD

Authors:
Monique E Cho, MD
Srinivasan Beddhu, MD
Section Editor:
Gary C Curhan, MD, ScD
Deputy Editor:
Alice M Sheridan, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2017. | This topic last updated: Sep 30, 2016.

INTRODUCTION Chronic kidney disease (CKD) is common in the United States and worldwide. CKD patients have a
higher mortality than the general population [1]. Mortality is related in part to the progression of kidney disease and its
complications, such as cardiovascular disease (CVD) and protein-energy wasting.

Dietary factors may have an effect on the progression of kidney disease and its complications. Among CKD patients,
overnutrition results in sodium and volume overload, hyperkalemia, hyperphosphatemia, and accumulation of toxic
metabolites of protein degradation. Undernutrition, on the other hand, exacerbates the risk for malnutrition and wasting.

Appropriate dietary interventions may have an effect on clinical outcomes in the CKD population. However, the optimal
approach to nutrition is not known with certainty, and clinical trials have yielded conflicting results.

This topic review provides recommendations for nutrition for predialysis CKD patients. Recommendations for nutrition in
the general public are discussed elsewhere. (See "Dietary assessment in adults" and "Geriatric nutrition: Nutritional issues
in older adults".)

The approach to nutrition in dialysis patients is discussed elsewhere. (See "Assessment of nutritional status in
hemodialysis patients" and "Nutritional status and protein intake in peritoneal dialysis patients".)

OVERVIEW The optimal diet for individual CKD patients varies depending upon the estimated glomerular filtration rate
(eGFR), type of kidney disease (ie, proteinuric or nonproteinuric), and the presence of other comorbidities such as
diabetes, hypertension, or heart failure. For most CKD patients, the optimal diet is one similar to the Dietary Approaches
to Stop Hypertension (DASH) diet, consisting of low sodium, fruits, vegetables, legumes, fish, poultry, and whole grains.
(See "Diet in the treatment and prevention of hypertension", section on 'Dietary Approaches to Stop Hypertension trial'.)

However, among many patients, the diet needs to be modified further depending on specific laboratory values including
serum potassium or serum phosphorus.

We do not suggest any dietary modification for patients with eGFR 60 mL/min/1.73 m2. Such patients should follow the
same dietary recommendations as for the general population. (See "Healthy diet in adults".)

We suggest the following dietary guidelines for most patients with eGFR <60 mL/min/1.73 who are not on dialysis:

A daily protein intake of 0.8 g/kg. We do not recommend very-low-protein intake (<0.6 g/kg/day).
A diet rich in vegetables.
The sodium intake varies depending on individual patient clinical features. Among individuals who are
hypertensive, volume overloaded, or proteinuric, we suggest a sodium intake of <2 g/day (ie, 5 g/day of salt [NaCl]).
 For patients who are not hypertensive, volume overloaded, or proteinuric, sodium restriction to
2.3 g/day (5.75 g/day of salt [NaCl]) may be of benefit. There are no convincing studies of the general population
that have proven that lowering sodium intake to less than 2.3 g per day lowers cardiovascular outcomes or all-cause
mortality. The Institute of Medicine has concluded that there is insufficient evidence to recommend a different
sodium intake for CKD patients as compared with the general US population [2].
The potassium intake should be guided by serum potassium levels. If the potassium concentration is normal, we do
not restrict dietary potassium. If the potassium concentration is high, dietary potassium intake should be restricted.
(See "Treatment and prevention of hyperkalemia in adults", section on 'Prevention' and "Patient education: Low-
potassium diet (Beyond the Basics)", section on 'How do I cut down on potassium?'.)
Some clinicians target a total calcium intake (both dietary and medication sources) 1500 mg/day, whereas others
prefer a more stringent goal of 1000 mg/day.
Maximum phosphorus intake of 0.8 to 1 g/day, even if the serum phosphorus concentration is normal; this is
because some studies suggest that dietary phosphorus intake may alter circulating fibroblast growth factor (FGF)-23
concentrations (see "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)", section on
'Fibroblast growth factor 23'). The dietary phosphorus should be derived from sources of high biologic value, such as
meats and eggs.
Maximum caloric intake of 30 to 35 kcal/kg/day.
Maximum fat intake <30 percent of daily energy intake, with saturated fat limited to <10 percent energy.
Daily dietary fiber intake for 25 to 38 g/day.

These recommendations, along with supporting studies, are individually discussed below.

PROTEIN INTAKE

Non-nephrotic patients For patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 who do not
have nephrotic syndrome, we suggest restricting daily protein intake to 0.8 g/kg. Nutritional studies in patients with
reduced eGFR suggest that protein intake can be safely lowered to 0.6 g/kg per day [3-7], although a very-low-protein diet
has been associated with increased mortality over the long term [8]. A modest restriction is generally well tolerated and
does not lead to malnutrition in patients with CKD providing caloric goals are met, dietary protein is of high biologic value,
and metabolic acidosis is avoided.

Most clinical guidelines, including Kidney Disease: Improving Global Outcomes (KDIGO), suggest restriction in protein
intake for CKD patients [9].

Studies that have examined protein restriction have yielded inconsistent results, but the balance of evidence suggests a
benefit of moderate dietary protein restriction [10,11].

Many early studies suggested that protein restriction may slow progression of CKD [12-18], although more recent and
more rigorous studies suggest that the benefit is modest [8,17-26]. The largest trial to date, the Modification of Diet in
Renal Disease (MDRD) study, analyzed 585 patients with nondiabetic CKD and a mean GFR of 39 mL/min/1.73 m2 (all
patients with GFR less than 55 mL/min/1.73 m2) [22]. Patients were randomly assigned to protein intakes of 1.3 or
0.58 g/kg per day with or without aggressive blood pressure (BP) control and followed for a mean of 2.2 years. The mean
achieved protein intake was approximately 0.7 to 0.75 g/kg/day (approximately 45 to 60 g/day) [11]. This level of protein
intake is substantially below the average protein intake in the United States of 90 to 100 g/day.

Despite good compliance, initially, there appeared to be little overall benefit with the low-protein diet. A biphasic response
was noted: Patients treated with protein restriction had a greater fall in GFR (measured by iothalamate clearance) in the
first four months (that may have reflected a reduction in intraglomerular pressure), followed by somewhat slower
progression over the ensuing months (2.8 versus 3.9 mL/min/year) (figure 1). Interpretation of the MDRD trial is somewhat
limited by this since the trial design did not account for this two-slope change in GFR in the moderate-protein-intake
group. However, even in the later phase, the absolute benefit was approximately 1.1 mL/min per year. A similar lack of
substantial benefit was noted in a second part of this study involving 255 patients with more advanced disease (mean
GFR 19 mL/min/1.73 m2) who were randomly assigned to a low-protein diet or a very-low-protein diet (0.3 g/kg per day)
with a keto acid-amino acid supplement.

Other limitations to the trial are that it included very few diabetic patients (patients with insulin-requiring diabetes were
excluded) and the rate of decline in GFR in the intervention and control groups was slower than expected, which may
have resulted in decreased power to discern potential benefit. As the curves diverged at the end of the study, there is a
possibility that longer-term follow-up of these patients would have revealed a slower progression in the moderate-protein-
intake group.

Indeed, a benefit of moderate protein restriction was suggested by a long-term follow-up analysis of the MDRD study,
which was performed by linking the MDRD study to national registries [23]. In this 12-year study (1989 to 2000), the
authors evaluated outcomes during the first six years after the trial ended (1989 to 1994), the next six-year period (1995 to
2000), and the total 12-year period. Analysis of outcomes after the first six years revealed a significant benefit of low-
protein intake on renal failure and all-cause mortality (hazard ratios [HRs] 0.68, CI 0.51-0.93 and 0.66, CI 0.50-0.87,
respectively). However, there was no benefit of protein restriction when outcomes between 6 and 12 years were analyzed,
but protein intake data were not available following the completion of the randomized study phase. Thus, it is possible that
the early beneficial effects in the first six years dissipated after six years because the study participants were no longer on
the intervention.

These data suggest the need for a longer follow-up period for future studies designed to assess the effects of protein
restriction intervention. In the MDRD study, the average rate of GFR decline was 4 mL/min/1.73 m2 per year during the
mean duration of 2.2 years, and relatively few patients developed renal failure during this period. It is possible that the
study duration was too short to fully appreciate the effect of protein restriction.

Since the initial MDRD report in 1994, several secondary analyses of the MDRD study, as well as other meta-analyses
and controlled trials, have been published [10,11]. Systematic reviews suggest that protein restriction may be beneficial
[27-31]. As an example, a Cochrane review limited to studies that used renal death as an outcome measure (n = 10)
demonstrated a protective effect of protein restriction despite heterogeneity among studies [27]. Renal death in this review
was defined as the need for starting dialysis, the death of the patient, or a kidney transplant. This analysis suggested that
protein restriction decreases the number of patients reaching the defined outcome by approximately 32 percent. This
equates to treating 2 to 56 patients with a low-protein diet to avoid one renal death.

Overall, most experts believe that, despite the absence of observed benefit in the MDRD trial, the balance of evidence
suggests a benefit of moderate dietary protein restriction [10,11]. Some of the MDRD investigators have proposed that the
seemingly small benefit from protein restriction may be clinically important [11]. According to this reasoning, a patient with
a GFR of 40 mL/min who is losing 4 mL/min per year will require dialysis in approximately eight years. However, if the rate
of fall were only 3 mL/min per year, then 11 years would be required to reach the same endpoint. Thus, the absolute
benefit would be three years without dialysis.

In addition, protein restriction may be particularly effective in diseases characterized by hyperfiltration, such as diabetes
and certain glomerulopathies [15,16,18], although one study has suggested that the effects of protein restriction in
advanced renal disease due to polycystic kidney are similar to that due to other causes [11]. Polycystic kidney disease is
not characterized by hyperfiltration and tends to have a very different rate of progression compared with diabetic and
other glomerulopathies.
Limiting protein intake is also associated with favorable laboratory and metabolic effects, including reduction of blood urea
nitrogen levels, uremic toxins, and acid load, in addition to reduced phosphorus load with better control of metabolic bone
disorders [32]. A modest protein restriction to 0.6 to 0.8 g/kg per day appears to be safe. The safety profile of a modest
protein restriction was assessed in an analysis of patients who were enrolled in the MDRD study [4]. Patients were
randomly assigned to a standard-protein diet (1.3 g/kg per day), a low-protein diet (0.58 g/kg per day), or a very-low-
protein diet (0.3 g/kg per day supplemented with a ketoacid-amino acid mixture at 0.28 g/kg per day) based upon their
GFR. Patients assigned to the low-protein diet achieved a protein intake between 0.6 to 0.8 g/kg per day. Patients
assigned to the very-low-protein diet achieved a protein intake between 0.4 to 0.8 g/kg per day.

At a mean follow-up of 2.2 years, a low-protein intake was not associated with increased rates of mortality, hospitalization,
or malnutrition.

We do not recommend very-low-protein intake (<0.6 g/kg/day), due to the safety concerns. Significant health risks are
associated with more severe restrictions over the long term. The MDRD study tested the effects of low-protein diet (0.58 g
per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement in
those with GFR between 13 to 24 mL/min/1.73 m2 on death/end-stage renal disease (ESRD) outcome. While there were
no statistically significant differences between the two groups during the trial, a longer-term, postintervention,
observational follow-up showed a higher risk of death in those assigned to the very-low-protein group (HR 1.92, 95% CI
1.15-3.20) [8].

An important limitation of the observations at 12 years is that measurements of protein intake or nutritional measurements
were not performed beyond nine months after the original MDRD study ended; the number of patients that continued the
prescribed diet is not known [33]. Despite this limitation, these observations suggest that important long-term safety risks
are associated with the very-low-protein diet among patients with advanced CKD.

Patients with CKD who are on a protein-restricted diet should be carefully monitored, with close follow-up every three to
six months for adequate caloric intake and evidence of protein malnutrition. We usually follow the body weight as well as
serum albumin.

Three conditions must be met to avoid malnutrition:

Adequate caloric intake must be maintained (by increasing polyunsaturated fats and by avoiding processed
carbohydrates).
At least 60 percent of the ingested protein must be of high biologic value or contain a high percentage of essential
amino acids (table 1) [3].
Stimulation of skeletal muscle protein breakdown should be prevented to limit net nitrogen loss. Metabolic acidosis
should be treated since metabolic acidosis stimulates skeletal muscle protein breakdown [3,34].
(See "Pathogenesis, consequences, and treatment of metabolic acidosis in chronic kidney disease".) A protein-
restricted diet may, of itself, help to prevent metabolic acidosis. A post-hoc analysis of the MDRD study showed that
a reduction in protein intake resulted in increased serum CO 2 after one year of follow-up [35].

Patients with nephrotic syndrome We do not restrict protein intake among patients with nephrotic syndrome. The
safety of a low-protein diet in nephrotic syndrome is uncertain. In some experimental models of nephrotic syndrome, the
institution of a low-protein diet diminished hepatic albumin synthesis, which suggests protein deficiency [36,37]. However,
in the same study, a low-protein diet also decreased protein excretion, presumably due to a fall in intraglomerular
pressure. The net effect of these opposing factors was no change in the plasma albumin concentration [36,37]. Overall,
studies have not demonstrated conclusive evidence of malnutrition with protein restriction in moderately nephrotic animals
[38].
One study examined this issue in five stable patients with nephrotic syndrome [39]. Despite moderate proteinuria that
averaged 7.2 g/day, nitrogen balance was maintained on a diet that provided 0.8 g/kg per day of protein plus 1 g of
protein for each gram of proteinuria and 35 kcal/kg per day. Positive nitrogen balance was maintained by the inhibition of
amino acid oxidation and protein degradation and by stimulation of protein synthesis during feeding.

These data suggest that protein restriction can be safely implemented in patients with moderate proteinuria, providing
adequate caloric intake is maintained. However, these data do not define the minimum safe protein intake, nor do they
prove that supplementing protein intake for the degree of proteinuria is necessary. In addition, the safety of protein
restriction in patients with massive proteinuria (>15 g/day) or concurrent catabolic states (eg, due to corticosteroids or
systemic lupus erythematosus) is uncertain, even with adequate caloric intake.

Source of protein intake A diet rich in protein from plant sources may be beneficial among CKD patients.
Observational data suggest that such a diet may reduce proteinuria [40,41], slow the progression of CKD [42-46],
decrease the production of uremic toxins [47-52], lower phosphorus intake, lower the endogenous production of acid
[44,45,53,54], and potentially decrease mortality risk [55]. (See "Pathogenesis, consequences, and treatment of metabolic
acidosis in chronic kidney disease", section on 'Choice of therapy'.)

A randomized trial compared a very low plant-based protein diet (0.3 g/kg per day) supplemented with ketoanalogues
(KD) with a mixed-source (plant- and animal-based) low-protein diet (0.6 g/kgper day) among 207 patients with a stable
eGFR <30 mL/min/1.73 m2 [43]. The median achieved protein intake was 0.29 and 0.59 g/kg per day in the KD and low-
protein diet groups, respectively. At 18 months of follow-up, compared with the low-protein diet group, fewer patients in
the KD group reached the composite endpoint of >50 percent reduction in eGFR or initiation of renal replacement therapy
(RRT; 42 versus 13 percent, respectively). Compared with the low-protein diet group, fewer patients in the KD group
required RRT (30 versus 11 percent).

However, caution is warranted in interpreting these results. While there were no differences between groups in
anthropometric or biochemical parameters of nutrition during the duration of this study, in the long-term follow-up of the
MDRD study, there was increased mortality among those randomized to a very-low-protein diet
(0.28 g/kg/day supplemented with a mixture of essential keto acids and amino acids) compared with a low-protein diet
(0.58 g/kg/day) [8] (see 'Non-nephrotic patients' above). Long-term studies of very low plant protein diets that examine
mortality as a predefined outcome are warranted.

Concerns have also been raised about delayed registration of this trial in the public trials registry until after enrollment of
some participants.

Studies that compare protein sources but maintain comparable levels of moderate protein intake (0.6 to 0.8 g/day) are
required before a recommendation could be made for a primarily plant-based source of dietary protein.

SALT INTAKE Salt is nutritionally equivalent to sodium chloride: 1 g salt of contains 0.4 g (17 mEq) of Na ion.
Understanding these units is important for making dietary recommendations to patients.

Among selected CKD patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 who have
hypertension, volume overload, or increased protein excretion, we suggest a sodium intake of <2 g/day (5 g/day of salt).

The approach for patients with reduced eGFR who do NOT have hypertension, volume overload, or increased protein
excretion is not clear. For most patients, we generally advise a mild sodium restriction of 2.3 g/day (5.75 g/day of salt
[NaCl]). An exception is the occasional CKD patient who wastes sodium.
We suggest not reducing sodium to <1500 mg per day (ie, salt <3 g/day). We agree with the conclusion of the US Centers
for Disease Control and Prevention-commissioned Institute of Medicine Committee that there is insufficient evidence to
recommend sodium restriction to 1500 mg/day in high-risk groups (ie, including CKD patients) [2].

In addition, very-low-sodium intake has been associated with increased mortality. In the Prospective Urban Rural
Epidemiology (PURE) study of 101,945 people in 17 countries, compared with the reference range of estimated sodium
excretion of 4 to 5.99 g per day, an estimated sodium excretion that was below 3 g per day was associated with an
increased risk of the composite outcome of death or cardiovascular event (odds ratio [OR] 1.27, 95% CI 1.12-1.44). In the
same study, very high Na intake above 6 g/day was associated with 15 percent higher risk of death or cardiovascular
event [56].

It is unlikely that a large, randomized, controlled trial to conclusively establish the effects of Na intake on cardiovascular
mortality and all-cause mortality will ever be conducted.

Our recommendation for a modest sodium restriction is consistent with the 2012 Kidney Disease: Improving Global
Outcomes (KDIGO) guidelines for the management of CKD [9] and with the European Society of Hypertension. Other
society recommendations are provided (table 2).

Among CKD patients, the benefits of salt restriction might include the following:

Lower blood pressure (BP)

Slower progression to end-stage renal disease (ESRD)
Improved cardiovascular outcomes

These are discussed separately below.

Hypertension Randomized, controlled trials that assess the efficacy and safety of salt restriction in the CKD population
are largely absent. The guidelines for dietary sodium intake in CKD, therefore, are based on expert opinion, observational
studies, and extrapolation from general population studies. Studies overall suggest that salt restriction reduces the risk of
hypertension in the general population. (See "Salt intake, salt restriction, and primary (essential) hypertension".)

A moderate salt restriction also reduces the risk of hypertension among CKD patients [57,58]. (See "Overview of
hypertension in acute and chronic kidney disease", section on 'Benefits of sodium restriction'.)

CKD progression Very few studies have examined the effect of salt restriction on CKD progression. The limited
available data suggest both direct and indirect benefit of sodium restriction on CKD outcomes, mostly regarding its
synergistic effect to lower proteinuria in the setting of renin-angiotensin system inhibition:

A post-hoc analysis of the first and second Ramipril Efficacy in Nephropathy (REIN) trials suggested a potential
benefit of sodium restriction [59]. During four years of follow-up, compared with those with a low-salt intake
(<100 mEq/g urinary sodium/creatinine excretion), the risk of progression to ESRD was greater in those with high-
salt intake (200 mEq/g urinary excretion; 6.1 versus 18.2 per 100 patient-years). A 100 mEq/g higher
urinary sodium/creatinine excretion ratio was associated with a 40 percent increase in the risk of ESRD regardless of
baseline proteinuria and other risk factors. However, the association between salt intake and the risk of ESRD
disappeared after adjustment for changes in proteinuria, suggesting that, in CKD patients treated by angiotensin-
converting enzyme (ACE) inhibitors, the increase in proteinuria is a primary mechanism by which high-sodium intake
accelerates the progression of CKD toward ESRD.
In a small, randomized, double-blind, crossover study that included 20 CKD patients with eGFR 15 to
59 mL/min/1.73 m2, sodium restriction (60 to 80 mEq/day or Na 1.4 to 1.8 g/day),compared with typical sodium
intake (180 to 200 mEq/day or 4.1 to 4.6 g/day), resulted in statistically significant and clinically important reductions
 in BP (mean reduction of 10/4 mmHg; 95% CI 5-15/1-6 mmHg), extracellular fluid volume, albuminuria, and
proteinuria [60]. The magnitude of BP change was more pronounced in this study compared with the magnitude
reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive.

However, despite these benefits, there are concerns that excessive lowering of sodium intake may adversely affect
neurohormonal balance and lipids and generate proinflammatory milieu, which could enhance progression of disease
among CKD patients [61]. A meta-analysis suggested that salt restriction increases plasma levels of renin, aldosterone,
catecholamines, and lipids [62]. When salt intake is reduced, a fall in extravascular volume stimulates the renin-
angiotensin-aldosterone axis and sympathetic system. These physiologic compensatory responses are more pronounced
with sudden and large reduction in salt intake but become minimal with chronic, modest salt reduction. Nonetheless, it has
been argued that these are only short-term responses, and, in the longer term, modest salt restriction over weeks results
in only small increases in plasma levels of renin, aldosterone, and catecholamines, without any effect on the lipids [63].

Cardiovascular disease The effect of salt restriction on cardiovascular outcomes has been difficult to ascertain
definitively due to feasibility and logistic challenges. Evaluating cardiovascular morbidity and mortality requires a large
sample size with extended follow-up. In addition, participants randomized to low-salt intake typically return to regular salt
intake once the trial intervention phase ends, further limiting the ability to accurately assess the effect of long-term salt
restriction.

Suggestive evidence for the cardiovascular protective effect of salt restriction in the general population is provided by the
following:

A meta-analysis of observational studies suggests that a 5 g/day higher salt intake is associated with a 23 percent
increase in stroke risk and a 17 percent increase in cardiovascular disease (CVD) [64].
An observational 10- to 15-year follow-up study of Trials of Hypertension Prevention (TOHP I and II) demonstrated
that net sodium restriction of 33 to 44 mmol/day (0.75 to 1 g/day) in the intervention arm resulted in a 30 percent
reduction lower cardiovascular event after adjustment for baseline sodium excretion and weight [65].

POTASSIUM INTAKE Dietary potassium intake should be individualized based on the serum potassium. In general,
potassium restriction is not required until the estimated glomerular filtration rate (eGFR) decreases to <30 mL/min/1.73 m2.
However, there is variability between patients, and some patients with higher eGFRs and who are on angiotensin-
converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) will require potassium restriction to maintain
a normal serum potassium.

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline recommends potassium
intake between 2 to 4 g/day (51 to 102 mEq/day) for patients with CKD stages 3 to 4 (ie, eGFR 30 to 59 mL/min/1.73 m2),
while recommending no restriction for those in earlier stages of CKD. However, we believe that dietary potassium
recommendations need to be individually tailored based on the level of eGFR and serum potassium levels.

The Institute of Medicine recommends potassium intake of at least 4.7 g/day (120 mEq/day) in apparently healthy adults
to lower blood pressure (BP) [66], blunt the effects of salt, and reduce the risk of kidney stones and bone loss. Moreover,
there was no evidence of chronic excess intakes of dietary potassium in apparently healthy individuals, and, thus, no
upper limit was established.

Observational studies in the general population suggest that higher potassium intake was associated with lower systolic
BP [67-69] and lower risk of stroke. Furthermore, in cross-sectional studies, higher dietary potassium intake was
associated with better bone mineral density in premenopausal, perimenopausal, and postmenopausal women, as well as
older men [70-72]. Similarly, in longitudinal studies, higher dietary potassium intake was associated with significantly less
decline in bone mineral density [72,73].
There are no controlled clinical trials assessing the effect of dietary potassium in the CKD population.

CALCIUM INTAKE Some clinicians target a total calcium intake (both dietary and medication sources)
1500 mg/day, whereas others prefer a more stringent goal of 1000 mg/day. The Kidney Disease Outcomes Quality
Initiative (K/DOQI) guideline (2000) suggests limiting total calcium intake (both dietary and medication sources) to
1500 mg/day [74].

Calcium supplementation of 2 to 4 g/day results in suppression of parathyroid hormone levels in advanced CKD [75].
Administration of calcium-containing phosphorus binders in hemodialysis patients, however, results in increased vascular
calcification [76], raising concerns about the safety of higher calcium intake in predialysis patients.

There are no randomized, controlled trials that established the safe levels of calcium intake in predialysis CKD.

However, in a calcium balance study, both normal individuals and patients with late-stage 3 and stage 4 CKD were in
slightly negative to neutral calcium balance on an 800 mg calcium diet [77]. Normal individuals were in modest positive
calcium balance on the 2000 mg diet, while patients with CKD on the same diet were in marked positive calcium balance.
Furthermore, increased calcium intake significantly decreased 1,25-dihydroxy-vitamin D and intact parathyroid hormone
levels, but did not alter the serum calcium concentration.

These data suggest that a diet of 2000 mg/day of calcium in CKD patients might result in a positive calcium balance, with
the extra calcium deposited in tissues, leading to metastatic calcification.

PHOSPHORUS INTAKE We restrict dietary phosphorus intake to a maximum of 0.8 to 1 g/day or modify the
phosphorous intake to normalize the serum level in patients with an estimated glomerular filtration rate (eGFR)
<60 mL/min/1.73 m2, although it is not clear that dietary restriction significantly alters the serum phosphate concentration
among nondialysis CKD patients. Based on expert opinion and extrapolation from the end-stage renal disease (ESRD)
data, both Kidney Disease: Improving Global Outcomes (KDIGO) and Kidney Disease Outcomes Quality
Initiative (K/DOQI) have recommended dietary phosphorus restriction with or without intestinal phosphorus binders in
nondialysis CKD patients with eGFR<60 mL/min/1.73 m2 [9,74].

The average phosphorus intake in the US population is 1300 mg/day. For healthy adults, the Institute of Medicine
recommends a dietary intake of 700 mg/day of phosphorus, with an upper limit of 4 g/day [78].

Higher serum phosphorus concentrations have been associated with increased cardiovascular risk, both in the general
and CKD populations [79-81]. The association between serum phosphorus levels and cardiovascular risk is independent
of eGFR and other cardiovascular disease (CVD) risk factors, even at modestly increased phosphorus concentrations.

A large meta-analysis of 14 studies showed an 18 percent risk of death for every 1 mg/dL increase in serum phosphorus
(95% CI 1.12-1.25) in the CKD population [81].

Possible mechanisms underlying the increased cardiovascular risk include accelerated vascular calcification and arterial
stiffness and induction of fibroblast growth factor (FGF)-23, which has been implicated in the development of left
ventricular hypertrophy [82]. FGF-23 is also associated with increased risk of coronary heart disease, heart failure, and
cardiovascular mortality independent of traditional cardiovascular risk factors and renal function [83].

Because inorganic phosphate has much higher bioavailability compared with organic phosphate, sources rich in inorganic
phosphate such as highly processed foods should be avoided as much as possible. Organic phosphate (ie, from
unprocessed foods) must be hydrolyzed enzymatically in the gut before it can be absorbed. By contrast, foods that are
highly concentrated in readily absorbable inorganic phosphate, such as preservatives used in processed and precooked
meals, result in much greater absorption of phosphorus.
Dietary phosphate load is closely related to protein content. As noted above, using plant sources of protein may be
beneficial for controlling phosphorus load (see 'Source of protein intake' above). Plant sources have the lowest
bioavailability of phosphorus, with grains yielding only 50 percent bioavailability of phosphorus [84].

However, unlike the dialysis population, in nondialysis CKD patients with eGFR <60 mL/min/1.73 m2, the effect of dietary
phosphorus restriction on the serum level is limited.

A small, crossover study in eight patients with a mean eGFR of 32 mL/min/1.73 m2 demonstrated that allocation to
a vegetarian protein source to reduce absorbable phosphorus led to only a mild reduction in serum phosphorus
(0.3 mg/dL) [53].
Several randomized trials, including the Modification of Diet in Renal Disease (MDRD) study, did not show
statistically significant reduction in the serum phosphorus concentration despite significant reduction in urinary
phosphorus excretion by the use of oral phosphorus binders [85,86] or protein restriction [87].
This may relate to the fact that the studies relied on the morning fasting sample for phosphorus measurement, which
may be less associated with dietary phosphorus absorption than afternoon measurements [88]. Morning fasting
levels remain stable despite a wide fluctuation in dietary phosphorus absorption, making the morning value an
insensitive marker for phosphorus overload.
It is possible that dietary protein restriction or use of phosphorus binders may reduce afternoon serum phosphorus
levels; it remains unknown in the absence of randomized trials, however, if reduction of afternoon phosphorus levels
translates into improved cardiovascular outcomes.
In an analysis of the National Health and Nutrition Examination Survey (NHANES) data, higher dietary phosphorus
intake was not associated with mortality risk in moderate CKD [89].

Although the available literature does not provide evidence that dietary phosphorus restriction results in serum
phosphorus level reduction in nondialysis CKD populations, the association between increased serum phosphorus levels
and adverse cardiovascular outcomes remains robust.

Randomized trials are needed to establish the role of dietary phosphorus restriction in nondialysis CKD patients with
eGFR <60 mL/min/1.73 m2.

CARBOHYDRATE AND FAT INTAKE We suggest that patients with an estimated glomerular filtration rate (eGFR)
<60 mL/min/1.73 who are not undergoing maintenance dialysis consume 30 to 35 kcal/kg/day [74].

Fat should be restricted to <30 percent of daily energy intake, with saturated fat limited to <10 percent energy.

Among CKD patients, obesity is associated with the development and progression of cardiovascular events [90] and
mortality [91].

Observational studies suggest that higher body mass index (BMI) [92-94] and central adiposity [95,96] are also
independent risk factors for progression of CKD and incidence of end-stage renal disease (ESRD) [91,97,98].

The mechanism by which obesity may increase CKD progression is not known. Hemodynamic abnormalities observed in
obese individuals include glomerular hyperfiltration [99], increased renal venous pressure [100], and glomerular
hypertrophy [101]. Diets that contain excessive fat and carbohydrates are associated with accelerated inflammatory
process and oxidative stress in the endothelium, leading to atherosclerosis [102].

Weight loss leads to improved blood pressure (BP) control [103,104] and the reduction of hyperfiltration and proteinuria
[105,106]. Since hypertension, hyperfiltration, and proteinuria are all risk factors for progression of CKD, this suggests that
weight loss in obese CKD patients may slow the progression of kidney disease. Further data to support restriction of
excess caloric intake in the CKD population include:
 High sugar intake and saturated fat intake are associated with albuminuria in cross-sectional studies [107,108].
In the Nurses Health Study, a Western dietary pattern characterized by higher intake of processed and red meats,
refined grains, sweets, and dessert was associated with greater odds of moderately increased albuminuria (formerly
called "microalbuminuria"; odds ratio [OR] 2.17, 95% CI 1.18-3.66), and rapid eGFR decline 3 mL/min/1.73 m2 per
year (OR 1.77, 95% CI 1.03-3.03) [109]. By contrast, also in the Nurses' Health Study, a Dietary Approaches to Stop
Hypertension (DASH)-style diet (higher intake of fruits, vegetables, legumes, fish, poultry, and whole grains) was not
associated with moderately increased albuminuria (OR 0.77, 95% CI 0.44-1.44) and had lower risk of rapid eGFR
decline (OR 0.55, 95% CI 0.38-0.80) [110]. In the same cohort, consumption of two or more servings per day of
artificially sweetened soda was independently associated with a twofold higher odds for eGFR decline [110].
A prospective, cohort study spanning 15 years demonstrated that doubling of relative energy intake, not BMI, is
associated with an increased mortality risk of 48 percent in those with eGFR <60 mL/min/1.73 m2 [111].

Although data from randomized interventional trials are lacking, avoiding excessive caloric intake might reduce the risk of
kidney disease progression and cardiovascular mortality in CKD individuals.

RECOMMENDED FIBER INTAKE The recommended daily dietary fiber intake for CKD patients with estimated
glomerular filtration rate (eGFR) 60 mL/min/1.73 m2 is 5 to 38 g/day, which is the same as for the general population.

Dietary fiber is the nondigestible form of carbohydrates and lignin. Some of the best sources of dietary fiber are beans and
peas, but also include nuts, fruits, and whole grains. The US Department of Agriculture and US Department of Health and
Human Services has recommended a daily intake of 14 g per 1000 calories or 38 g of fiber for men and 25 g for women.

The rationale for the above dietary fiber intake recommendation is based on numerous clinical studies to demonstrate
protective effects against cardiovascular disease (CVD), diabetes mellitus, cancer, and all-cause mortality. (See "Healthy
diet in adults".)

While there are limited data, dietary fiber intake appears to provide similar, if not greater, benefits in the CKD population:

An analysis of National Health and Nutrition Examination Survey (NHANES)-III data (including 14,543 participants
and 5.8 percent with eGFR <60 mL/min/1.73 m2), showed that, for each 10 g/day higher total fiber intake, the odds of
increased serum C-reactive protein was decreased by 38 percent in those with CKD and by 11 percent in those
without kidney disease [112]. Furthermore, the dietary fiber intake was inversely correlated with mortality only in
those with CKD, suggesting that fiber intake may be more important for individuals with CKD.
A six-week study of 13 CKD patients (mean eGFR of 30 mL/min/1.73 m2) demonstrated that the addition of fiber
(23 g/day) was associated with a significant reduction in serum creatinine by a mean of 0.24 mg/dL (p<0.05) from
the baseline value [113]. The change in eGFR corresponded to an increase by approximately 3 mL/min/1.73 m2 from
the baseline.

Based on the available data and extrapolating from the general population, therefore, fiber intake is likely protective
against CKD progression and mortality, and every effort should be made to encourage higher fiber intake in the CKD
population. Because potassium is high in fruits and vegetables, many CKD and dialysis patients are counseled against
taking these. This may further compromise dietary fiber intake in the CKD population. However, fruits and vegetables that
are low in potassium might be consumed in moderation.

The overall nutritional recommendations are described in the table (table 3).

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and
regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults".)

SUMMARY AND RECOMMENDATIONS

 The optimal diet for individual chronic kidney disease (CKD) patients varies depending upon the estimated
glomerular filtration rate (eGFR), type of kidney disease (ie, proteinuric or nonproteinuric), and the presence of other
comorbidities such as hypertension or heart failure. For most CKD patients, the optimal diet is one similar to the
Dietary Approaches to Stop Hypertension (DASH) diet, consisting of fruits, vegetables, legumes, fish, poultry, and
whole grains. (See 'Introduction' above and 'Overview' above and "Diet in the treatment and prevention of
hypertension", section on 'Dietary Approaches to Stop Hypertension trial'.)
We do not suggest any dietary restriction for patients with eGFR 60 mL/min/1.73 m2. Such patients should follow
the same dietary recommendations as for the general population. (See 'Overview' above and "Healthy diet in
adults".)
Among patients with eGFR <60 mL/min/1.73 who are not on dialysis and do not have nephrotic syndrome, we
restrict daily protein intake to approximately 0.8 g/kg. A modest protein restriction may slow the progression of CKD
and is associated with other benefits including reduced blood urea nitrogen, uremic toxins, decreased acid load, and
decreased phosphorus intake. A diet rich in protein from plant sources may be beneficial among CKD patients.
(See 'Protein intake' above.)
The optimal dietary salt intake is not known. Our approach is based upon expert opinion, observational studies,
and extrapolations from general population studies and depends on the individual patient characteristics:
Among patients with eGFR <60 mL/min/1.73 who have hypertension, volume overload, or increased protein
excretion, we restrict sodium intake to <2 g/day (5 g/day of salt).
Among patients with reduced eGFR who do NOT have hypertension, volume overload, or increased protein,
we use a more mild sodium restriction to 2.3 g/day (5.75 g/day of salt) [NaCl]. (See 'Salt intake' above.)
Dietary potassium intake should be individualized based on the serum potassium. In general, potassium restriction
is not required until the eGFR decreases to <30 mL/min/1.73 m2. (See 'Potassium intake' above.)
Among all patients with eGFR <60 mL/min/1.73 m2, we restrict total calcium intake (both dietary and medication
sources) to 1500 mg/day. Some clinicians prefer a more stringent goal of 1000 mg/day. Data suggest that a diet of
2000 mg/day of calcium in CKD patients may cause a positive calcium balance, with the extra calcium deposited in
tissues, leading to metastatic calcification. (See 'Calcium intake' above.)
The optimal dietary phosphorus intake is not known. Our approach depends upon the serum phosphorus
concentration. Among patients with a normal serum phosphate concentration, we restrict dietary phosphorus intake
to 0.8 to 1 g/day. Sources rich in inorganic phosphate, such as highly processed foods, should be avoided as much
as possible.
Among patients with increased serum phosphorus concentration, we try to normalize the serum level with dietary
phosphorus restriction. (See 'Phosphorus intake' above and "Treatment of hyperphosphatemia in chronic kidney
disease", section on 'Phosphate restriction'.)
Among patients with eGFR <60 mL/min/1.73, we suggest caloric intake of 30 to 35 kcal/kg/day. Higher body mass
index (BMI) and central adiposity are independent risk factors for end-stage renal disease (ESRD), cardiovascular
events, and mortality.
Fat should be restricted to <30 percent of daily energy intake, with saturated fat limited to <10 percent energy.
(See 'Carbohydrate and fat intake' above.)
The recommended daily dietary fiber intake for CKD patients with eGFR <60 mL/min/1.73 m2 is 5 to
38 g/day, which is the same as for the general population. (See 'Recommended fiber intake' above.)

ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Ajay K Singh, MD, who contributed
to earlier versions of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES
Cumulative fall in GFR over three years in patients with nondiabetic chronic renal failure (mean baseline GFR 39 mL/min) receiving a

normal (solid line) and low protein (dashed line) diet. Protein restriction had little or no overall beneficial effect. There was a trend

toward more rapid loss of GFR in the first four months followed by a modest slowing of progression during the last 32 months.

GFR: glomerular filtration rate.

Data from Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression

of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med 1994; 330:877.
Graphic 59277 Version 3.0

Table of the biological value of common foods

Food item Biological value

100

96

96

95

90

84

83

79

76

74

72

64

60

49
 41

This table depicts common food items with their BV values. Biological value (BV) is a measure of the proportion of absorbed protein

that is incorporated into the proteins of the body. One method of determining biological value measures absorbed and excreted

nitrogen and determines the ratio of incorporated nitrogen to absorbed nitrogen:

BV = (Nr/Na) x 100.

Nr = nitrogen retained in the body (measured indirectly by nitrogen excretion in the urine and feces).

Na = absorbed nitrogen from dietary protein.

A BV of 100 suggests complete utilization of protein from a particular food. Egg protein has a BV of 100.

BV does not take into account how readily the protein can be digested and absorbed.

Data from: Jolliet P, Pichard C, Biolo G. Enteral nutrition in intensive care patients: a practical approach. Intensive Care Med 1998;

24:848.
Graphic 67821 Version 3.0

Dietary recommendations for salt intake in patients with CKD 3 to 4

F K/DOQI 2000
US Department of Agriculture and Human Services: European Society of
CKD class 1 JNC-7 2003[4]
DGA 2010[3] Hypertension 2007[5]
through 4)[2]

g/day (6 g/day of <2.3 g/day for those ages >2 years <2.3 Na g/day (5.75 g/day of <2 g/day Na (5 g/day of NaCl)

NaCl)
<1.5 g/day for high-risk groups (CKD, black race, HTN, diabetes, 51

years of age)

KDIGO: Kidney Disease: Improving Global Outcomes; NKF: National Kidney Foundation; K/DOQI: Kidney Disease Outcomes Quality

Initiatives; CKD: chronic kidney disease; DGA: Dietary Guidelines for Americans; HTN: hypertension; JNC: Joint National Committee.

References:

1. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney

disease. http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO_BP_GL.pdf (Accessed on November 4, 2015).

2. NKF KDOQI Guidelines 2000. Clinical practice guidelines for nutrition in chronic renal

failure. https://www.kidney.org/sites/default/files/docs/kdoqi2000nutritiongl.pdf (Accessed on November 4, 2015).

3. US Department of Agriculture and US Department of Health and Human Services. Dietary guidelines for Americans. Chapter

3. http://health.gov/dietaryguidelines/dga2010/dietaryguidelines2010.pdf (Accessed on November 4, 2015).

4. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood

pressure. http://www.nhlbi.nih.gov/files/docs/guidelines/jnc7full.pdf (Accessed on November 4, 2015).

5. 2007 guidelines for the management of arterial hypertension. The task force for the management of arterial hypertension of the

European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). http://www.seh-

lelha.org/pdf/guia2007seh.pdf (Accessed on November 4, 2015).

6. Sodium intake in populations: Assessment of Evidence. US Institutes of Medicine. May 14,

2013. http://iom.nationalacademies.org/Reports/2013/Sodium-Intake-in-Populations-assessment-of-Evidence.aspx(Accessed on

December 16, 2015).

 Graphic 105126 Version 1.0

Nutritional recommendations for adults with chronic kidney disease stages 3 to 4

0.8 g/kg/day[1], increase plant source.

<2.3 g/day (<5 g/day of NaCl)[1].

Individualize to keep the serum potassium within a normal range.

1.5 g/day from both dietary and medication sources.*

0.8 to 1 g/day or individualize to keep the value within a normal range.

Increase vegetable source and avoid processed foods as much as possible.

30 to 35 kcal/kg/day; <30% of total calories from fat and <10% of total fat from saturated fat; DASH diet pattern highly recommended.

25 to 38 g/day.

* Some clinicians favor a lower calcium intake of 1 g/day.

References:

1. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3:5.

2. NKF KDOQI Guidelines 2000. Clinical practice guidelines for nutrition in chronic renal

failure. https://www.kidney.org/sites/default/files/docs/kdoqi2000nutritiongl.pdf (Accessed on November 4, 2015).

3. http://health.gov/dietaryguidelines/2010/ (Accessed on November 4, 2015).

Graphic 105127 Version 1.0

Contributor Disclosures
Monique E Cho, MDNothing to discloseSrinivasan Beddhu, MDGrant/Research/Clinical Trial Support: Nourish &
Strengthen LLC [Protein intake (Protein supplement)].Gary C Curhan, MD, ScDGrant/Research/Clinical Trial Support:
Allena Pharmaceuticals [Oxalate]. Consultant/Advisory Boards: Allena Pharmaceuticals [Oxalate, nephrolithiasis];
AstraZeneca [Uric acid and gout (Lesinurad)]; Decibel Therapeutics (Hearing loss. tinnitus). Consultant/Advisory Boards
(spouse/partner): Decibel Therapeutics (Hearing loss, tinnitus)]. Equity Ownership/Stock Options: Allena Pharmaceuticals.
Other Financial Interest: American Society of Nephrology [CJASN Editor-in-Chief].Alice M Sheridan, MDNothing to
disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
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