Review

Plant-Dominant Low-Protein Diet for Conservative
Management of Chronic Kidney Disease
Kamyar Kalantar-Zadeh 1,2,*, Shivam Joshi 3, Rebecca Schlueter 4, Joanne Cooke 5,
Amanda Brown-Tortorici 1, Meghan Donnelly 6, Sherry Schulman 7, Wei-Ling Lau 1,
Connie M. Rhee 1, Elani Streja 1,2, Ekamol Tantisattamo 1, Antoney J. Ferrey 1, Ramy Hanna 1,
Joline L.T. Chen 2, Shaista Malik 7, Danh V. Nguyen 1, Susan T. Crowley 8,9and Csaba P. Kovesdy 10
Department of Medicine, Division of Nephrology Hypertension and Kidney Transplantation, University ofCalifornia Irvine (UCI), Orange, CA 90286, USA; amandab@uci.edu (A.B.-T); wllau@uci.edu (W.-L.L.);
crhee1@uci.edu (C.M.R.); estreja@uci.edu (E.S.); etantisa@hs.uci.edu (E.T.); ferreya@uci.edu (A.J.F.);
ramyh1@uci.edu (R.H.); danhvn1@uci.edu (D.V.N.)
2 Tibor Rubin VA Long Beach Healthcare System, Long Beach, CA 90822, USA; jolinec@uci.edu
3 Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA;shivam.joshi@nyulangone.org
4 Lexington VA Healthcare System, Lexington, KY 40502, USA; rebecca.schlueter@va.gov
5 Kansas City VA Medical Center, Kansas City, MO 64128, USA; Joanne.Cooke@va.gov
6 Flavis/Dr. Schar USA, Inc., Lyndhurst, NJ 07071, USA; meghan.donnelly@drschar.com
7 UCI Health Susan Samueli Center Integrative Health Institute, Irvine, CA 92626, USA;sschulm1@hs.uci.edu (S.S.); smalik@hs.uci.edu (S.M.)
8 VA Connecticut Healthcare System, West Haven, CT 06516, USA; Susan.Crowley@va.gov
9 Division of Nephrology, Yale University School of Medicine, New Haven, CT 06516, USA
10 Division of Nephrology, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA;ckovesdy@uthsc.edu* Correspondence: kkz@uci.edu; Tel.: +714-456-5142
1

Received: 31 May 2020; Accepted: 22 June 2020; Published: 29 June 2020

Abstract: Chronic kidney disease (CKD) affects >10% of the adult population. Each year,
approximately 120,000 Americans develop end-stage kidney disease and initiate dialysis, which iscostly and associated with functional impairments, worse health-related quality of life, and highearly-mortality rates, exceeding 20% in the first year. Recent declarations by the World Kidney Day
and the U.S. Government Executive Order seek to implement strategies that reduce the burden of
kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic
dietary interventions may have a role in improving CKD outcomes and preventing or delaying
dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet
(PLADO) of 0.6–0.8 g/kg/day composed of >50% plant-based sources, administered by dietitians
trained in non-dialysis CKD care, is promising and consistent with the precision nutrition. The
scientific premise of the PLADO stems from the observations that high protein diets with high meatintake not only result in higher cardiovascular disease risk but also higher CKD incidence and faster
CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat
intake increases production of nitrogenous end-products, worsens uremia, and may increase therisk of constipation with resulting hyperkalemia from the typical low fiber intake. A plantdominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome,
which can modulate uremic toxin generation and slow CKD progression, along with reducing
cardiovascular risk. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be thecenterpiece of a conservative and preservative CKD-management strategy that challenges theprevailing dialysis-centered paradigm.
Keywords: plant-dominant; low-protein; dietary protein intake; glomerular hyperfiltration
Nutrients 2020, 12, 1931; doi:10.3390/nu12071931

www.mdpi.com/journal/nutrients

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1. The Burden of Chronic Kidney Disease
Chronic kidney disease (CKD) has no cure and affects more than 10% of the adult population
throughout the world [1]. If persons with CKD survive long enough, many will inevitably reachkidney failure, also known as end-stage kidney disease (ESKD), which is not compatible with life
without kidney replacement therapy in the form of maintenance dialysis treatment or kidneytransplantation [1–4]. However, ESKD patients who transition to dialysis often have poor clinicaloutcomes. Cardiovascular morbidity and mortality of CKD are exceptionally high with an overall
five-year survival less than 50% [5,6]. In the United States (US), total Medicare and Veterans
Administrations (VA) spending for CKD continues to increase [4]. Each year, approximately 120,000
Americans develop ESKD and initiate dialysis [5], including 12,000 U.S. Veterans [5–8]. Despite thepurported life-prolonging effects of dialysis [9], 10% of these patients die in the first 90 days after
dialysis transition and >20% in the first year [6]. In addition to the high rates of early dialysis
mortality, a large proportion of elderly patients experience major functional decline after transition
to dialysis therapy [10]. Hence, delaying or preventing kidney failure to avoid kidney replacement
therapy may improve clinical outcomes while averting the high costs of dialysis therapy andpreserving limited resources.
The World Kidney Day steering committee declared 2020 and 2021 as the years of CKD
prevention and living well with CKD, respectively. These declarations underscore the paramountimportance of both primary CKD prevention as well as secondary and tertiary interventions for early
diagnosis of CKD and treatment to control progression to ESKD and its complications, respectively[1,11]. Among the core components of the preventative strategies are nutritional and dietaryintervention as featured in this review article. Moreover, in July 2019, an unprecedented Executive
Order by the U.S. President, known as the “Advancing American Kidney Health Initiative,” sought
to reduce the number of Americans developing kidney failure by 25% by 2030 through improved
efforts to slow the progression of CKD [12]. This timely executive order underscores the importanceof preventive CKD measures and reiterates the critical, yet underappreciated role of leveraging
dietary interventions in optimizing kidney health [12]. This review article highlights past andcontemporary data on the dietary management of CKD with focus on the role of plant-based,
restricted protein diets based on the premise that feasible dietary approaches should be thecornerstone of non-pharmacologic strategies in slowing CKD progression and avoiding or delaying
ESKD [13].
2. High Protein Diets May Be Harmful to Kidney Health
While the U.S. National Academy of Medicine has maintained that Recommended Dietary
Allowance (RDA) of dietary protein intake (DPI) should be 0.8 g per kilogram of the ideal bodyweight per day (g/kg/day), Americans on average consume much higher amounts of protein, i.e., 1.2
to 1.4 g/kg/day, mostly from animal sources, according to analyses from the National Health andNutrition Examination Survey (NHANES) [14]. In recent practice, higher DPI has been recommended
to combat obesity and diabetes [15,16], despite recent data suggesting higher risk of CKD incidence
and progression with higher DPI, especially from red meat [17–19]. Keto-diets, which are also highin protein and animal fats, are gaining popularity across different healthcare systems throughout theworld as a recommended dietary intervention for adults with diabetes [20]. Despite its immediate
appeal for the use of type 2 diabetes, the ketogenic diet has not been as effective for glycemic control
or weight loss in randomized, controlled trials as often touted and may carry additional risks to longterm health [21]. Furthermore, previous and emerging data (Table 1) suggest that high DPI in thesediets, by way of causing increased intra-glomerular pressure with resultant glomerular
hyperfiltration, may adversely affect kidney health over time across populations with or at-risk for
CKD [17].

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Table 1. Selected studies of high-protein and kidney function. DPI: dietary protein intake; CKD:
chronic kidney disease.
Study (Year)

Cohort, [N] (Country)

Esmeijer [22](2020)

Alpha Omega Cohort (2255)(Netherlands)
South Korea(9226)

Jhee [23] (2020)
Malhotra [24](2018)
Farhadnejad [24](2018)

Duration of
Follow up
41 mo
14 yrsFindings↑ DPI 0.1 g/kg/day associated with ↑ eGFR declineof -0.12 ml/min/year
3.5-fold ↑ risk of hyperfiltration. 1.3-fold ↑ faster
declineJackson Heart (USA) (5301)

8 yrs↑ DPI density associated with ↑ eGFR decline

Healthy Iranian adults (1797)

6.1 yrs

48% ↑ risk of incident CKD in high DPI

3. A Low Protein Diet Preserves Kidney Function
A low protein diet (LPD), defined as DPI 0.6–0.8 g/kg/day, has consistently been shown to lower
intra-glomerular pressure (Figure 1) [25]. This effect, if exerted consistently, may preserve long-term
kidney function as corroborated in both animal models and in human studies of CKD, including
several meta-analyses [24,26–29]. The scientific premise for these DPI targets was presented in a
recent critical review and meta-analysis of 16 dietary trials with more than 30 CKD patients in eachtrial (Figure 2) [28], and also discussed in a 2017 New England Journal of Medicine review paper [25].
These data highlight the utility of LPD for the management of CKD (Table 2), suggesting that an LPD
of 0.6–0.8 g/kg/day vs. higher amounts is associated with lower ESKD risk, higher serum bicarbonate
and lower serum phosphorus levels, less azotemia, and lower mortality trends [28]. Whereas we andothers have recommended DPI of 0.6–0.8 g/kg/day, some other investigators including Metzger et al.
[30] showed that a DPI of <0.6 g/kg/day may result in even slower CKD progression; however, a DPI
of 0.6–0.8 g/kg/day is considered the most pragmatic and safest target when used without aminoacid or keto-analogue supplements to avoid protein-energy wasting (PEW). For persons withoutestablished CKD but who are at high risk of CKD, such as those with a solitary kidney or diabetic
glomerular hyperfiltration, it is recommended that a high dietary protein intake >1.0 g/kg/day should
be avoided [31], especially since patients with diabetes develop more severe hyperfiltration in
response to high DPI [32].
Evidence suggests that safety and adherence to an LPD is equivalent to a normal protein dietand that there is no risk of the malnutrition or PEW that might occur with very-low protein diets (DPI
0.3–0.6 g/kg/day), even sans supplementation with essential amino acids or their keto-analogues [28].
However, while most studies suggest that an LPD ameliorates CKD progression, there are also somemixed findings [33,34], including the primary analyses of the Modification of Diet in Renal Disease(MDRD) study. Most trials except for the MDRD were small, used surrogate endpoints, wereconsidered less rigorous compared to MDRD, used dietary interventions that were labor-intensive,
were not patient-centered, and were not aligned with contemporary culture of more plant-basedsources. Due to the impractical aspects of prior LPD regimens, and in part to the marginal effects ofan LPD in the MDRD, which did not achieve statistical significance, LPD has not been adopted inmost CKD clinics. Thus, there remains an unmet need for more contemporary, well-powered,pragmatic randomized controlled trials that apply LPD as a convenient and patient-centeredintervention, especially with a newer focus on plant-dominant diet regimens.

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Figure 1. Effects of a plant-dominant low-protein diet on afferent arteriole contraction leading to
reduced intra-glomerular pressure and nephron longevity (adapted from Kalantar-Zadeh andFouque, N Engl J Med 2017) [25]..

Figure 2. Meta-analysis of the randomized controlled trials with low protein diet suggesting efficacy
of diet in lowering the risk of kidney failure. This meta-analysis includes six (out of 16) randomized
control trials of low protein diet (adapted from Rhee et al., J Cachexia Sarcopenia Muscle 2018) [28].

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Table 2. Low protein diet (LPD)-controlled trials with greater than 30 participants in each study[25]..
Study (Year)

Participants

Rosman (1984)[35,36].

247 CKD 3–5 pts

Ihle (1989) [37]72 CKD 4–5 pts

Lindenau ( 1990)[38]
Williams (1991)[39]
Locatelli (1991) [40]
MDRD Klahr(1994) [41]Montes-Delgado(1998) [42]40 CKD 5 pts

12 mo

456 CKD 3–4

0.78 v s . 0.9

2 yrs

585 CKD 3–4

1.3 vs. 0.6

27 mo

33 CKD 3–5

LPD vs. sLPD

6 mo

105 CKD 3b–4
34 CKD 3b–4
56 > 70 yrs old
CKD 5

Jiang (2009 and2011) [50,51].
Garneata (2016)
[52]

18 mo

18 mo

Teplan (2001) [44]Prakash (2004) [45]Di Iorio (2009) [49]

4 yrs

LPD (0.7) vs. 1.02–1.14

50 CKD 4–5

Mircescu (2007)[47]
Cianciaruso (2008)[48]

0.90– 0.95 vs. 0.70–0.80
vs. unrestricted
LPD (0.6) vs. higher DPI(0.8)
LPD vs. sVLPD (0.4) w
KA

Duration offollow up

95 CKD 4–5

Malvy (1999) [43]Brunori (2007) [46]Diet (g/kg/day)

53 CKD 4–5

sVLPD (0.3) KA vs. LPD(0.65)LPD w vs. w/o KA
0.6 vs. 0.3 w KA
sVLPD (0.30) w KA vs.
dialysissVLPD (0.3) vegan w KA
vs. LPD

3 yrs
3 yrs
9 mo
27 mo

Trend for difference in renal
outcomes (p = 0.059).
No difference in GFR decline at 3
years.
Slower eGFR decline with
supplements
Decreased SUN lean body massand fat in sVLPD
Slower CKD progression
Faster decline in LPD
Similar survival but more
hospitalizations in dialysis

Reduced urinary urea, Na, phos

18 mo

32 CKD w
proteinuria

VLPD vs. LPD

6 mo

207 CKD 4–5

No differences, minor Wt loss

Less dialysis initiation in sVLDP

0.55 vs. 0.80

LPD vs. sLPD w KA vs.
HPD
LPD (0.6) vs. sVLPD w
KA

Significant CKD slowing in LPD
in male pts.
Loss of GFR in control vs. LPD (p< 0.05). Wt loss
Decreased phos. with sVLPD and
improved bone health48 wks423 CKD 4–5

60 PD w RKF

Results

12 mo
15 mo

58% greater reduction inproteinuria
RKF decreased in the LPD and
HPD.
Less dialysis initiation

Abbreviations: Pts.: patients, yrs: years, mo: months, Et: weight, phos.: phosphorus, sVLPD:
supplemented very low protein diet.

4. Plant-Based Foods Have a Favorable Impact on Kidney Health
The typical American diet contains 15–20% protein with less than one-third of protein sourcesfrom plants [53]. While human trials on the effects of high protein intake have yield mixed findings,
animal models are relatively consistent with evidence of histological damage, including a 60–70%
increase in renal and glomerular volumes, 55% more fibrosis, and 30% more glomerulosclerosis [54].
A recent comprehensive and critical review of the literature concluded that daily red meat
consumption over years may increase CKD risk, whereas fruit and vegetable proteins may be renal
protective [18]. Prior studies summarized by some of the authors of this article [31,33,34,55–61]
suggest that animal-based protein is harmful to kidney health, while a plant-dominant diet may slow
CKD progression. A landmark study was presented by Kontessis et al. [62], who studied volunteers
fed for 3 weeks with a vegetable-based diet (N = 10), an animal protein diet (N = 10), or an animal
protein diet supplemented with fiber (N = 7), all with the same amount of total protein; animal-based
protein diets increased GFR more than similar amounts of plant-based proteins, i.e., higher
glomerular hyperfiltration was observed with more meat and less vegetable-derived proteins [62].
Other important studies supporting the benefit of a plant-dominant diet in slowing CKD progression
include the study by Lin et al. [63] (who examined 3348 women in the Nurses’ Health Study andfound that the highest quartile of meat intake was associated with 72% higher risk of
microalbuminuria), Kim et al. [64] (who showed that in 14,686 middle-aged adults, higher adherence
to a plant-based diet was associated with favorable kidney outcomes), Haring et al. [65] (who showedthat red and processed meat were associated with higher CKD risk, while nuts, low-fat dairy

Nutrients 2020, 12, 1931

6 of 24products, and legumes were protective against the development of CKD) and Chen et al. [66] (whoshowed lower mortality in CKD patients on diet with higher plant sources).
5. Benefits of a Plant-Dominant Low Protein Diet
We define a plant-dominant LPD, also referred to as PLADO, as a type of LPD with DPI of 0.6–
0.8 g/kg/day with at least 50% plant-based sources to meet the targeted dietary protein, and whichshould preferably be whole, unrefined, and unprocessed foods (Figure 3). This is consistent with the
RDA of DPI of 0.8 g/kg/day, which has a high safety margin, given that based on establishedmetabolic studies [13], the lowest DPI requirement to avoid catabolic changes is 0.45 to 0.5 g/kg/day.
It has been suggested that ≥50% of DPI should be of “high biologic value” with high gastrointestinal
absorbability to ensure adequate intake of essential amino acids [3]. However, other metrics,
including the “protein digestibility-corrected amino-acid score,” which is a more accurate method
recommended by the Food and Agricultural Organization and the World Health Organization, granthigh scores to many plant-based sources and may be a more appropriate measure of protein quality[34]. Other features of PLADO include relatively low sodium intake <3 g/day, higher dietary fiber ofat least 25–30 g/day, and adequate dietary energy intake (DEI) of 30–35 Cal/kg/day, assuming thatthe DEI calculations are based on the ideal body weight, similar to the approach to calculating DPI(Figure 3).

Figure 3. Overview of the plant-dominant low-protein diet (PLADO) for nutritional management of
CKD, based on a total dietary intake of 0.6–0.8 g/kg/day with >50% plant-based sources, preferentiallyunprocessed foods, relatively low dietary sodium intake <3 g/day (but the patient can target to avoid>4 g/day if no edema occurs with well controlled hypertension), higher dietary fiber of at least 25–30
g/day, and adequate dietary energy intake of 30–35 Cal/kg/day. Weight is based on the ideal bodyweight. Note that serum B12 should be monitored after three years of vegan dieting.

There are multiple pathways by which an LPD with at least 50% plant-based protein sources
ameliorates CKD progression, in addition to reducing glomerular hyperfiltration [33] (Table 3):(1). Reduction in nitrogenous compounds leads to less production of ammonia and uremic toxins as aneffective strategy in controlling uremia and delaying dialysis initiation [28].

Nutrients 2020, 12, 1931

7 of 24(2). Synergism with RAAS and SGLT2 inhibitors, since LPD reinforces the pharmaco-therapeutic effect oflowering intra-glomerular pressure through complementary mechanisms (Figure 1) [67].
(3). Attenuation of metabolites derived from gut bacteria that are linked with CKD and CV disease: Animal
protein ingredients including choline and carnitine are converted by gut flora into trimethylamine (TMA)
and TMA N-oxide (TMAO) that are associated with atherosclerosis, renal fibrosis [68], and increased riskof CV disease and death [69]. The favorable impact on the gut microbiome [70] similarly leads to lower
levels of other uremic toxins such as indoxyl sulfate and p-cresol sulfate [71].
(4). Decreased acid load: plant foods have a lower acidogenicity in contrast to animal foods, and thisalkalization may have additional effects beyond mere intake of natural alkali [72].
(5). Reduced phosphorus burden: there is less absorbable phosphorus in plant-based proteins given thepresence of indigestible phytate binding to plant-based phosphorus. Fruits and vegetables are less likely
to have added phosphorus-based preservatives that are often used for meat processing [59,73–75].
(6). Modulation of advanced glycation end products (AGE’s): higher dietary fiber intake results in a favorable
modulation of AGE [76], which can slow CKD progression [77], enhance GI motility, and lower the
likelihood of constipation that is a likely contributor to hyperkalemia.
(7). Favorable effects on potassium metabolism: a plant-based diet based on more whole fruits and vegetables
lessens the likelihood of potassium-based additives that are often found in meat products [78,79].
(8). Anti-inflammatory and anti-oxidant effects: there is a decreased risk of CKD progression and CV disease
due to higher intake of natural anti-inflammatory and antioxidant ingredients, including carotenoids,
tocopherols, and ascorbic acid [80,81].
Table 3. Benefits and challenges of LPD with >50% plant-based protein sources.
Benefits of LPD with >50% Plant Sources
Lowering intra-glomerular pressureSynergistic effect with RAASi and SGLT2i
Controlling uremia and delaying dialysis
Preventing cardiovascular harms of meatLess absorbable phosphorus
Lowering acid-load with less acidogenicity
High dietary fiber enhancing GI motility

Favorable changes in microbiomeLess TMA N-oxide (TMAO), leading to lesskidney fibrosisLess inflammation and oxidative stress

Potential Challenges of LPD
Risk of protein-energy wasting (PEW)
Inadequate essential amino acids

Undermining obesity management
High glycemic index
High potassium load and hyperkalemia
Low palatability and adherence
Inadequate fish intake if vegan

6. Features of PLADO Regimens
As stated above, the plant-dominant restricted protein diet consists of an LPD amounting to 0.6–
0.8 g/kg/day with at least 50% of the dietary protein being from plant-based sources. Table 4 compares
PLADO with a standard diet in the USA, in that the total amount and proportion of plant-based
protein is usually 1.2–1.4 g/kg/day and 20–30%, respectively, whereas the PLADO not only has lesstotal protein of 0.6–0.8 g/kg/day but it also includes 50% to 70% of plant-based sources for thisrestricted DPI goal. Hence, an 80 kg person with CKD, for instance, would be recommended to have46 to 64 g of DPI per day, out of which 24 to 45 g will be from plant-based sources, while the rest isaccording to patient choice and preferences. As shown in Table 4, the total amount of animal-based
protein under PLADO regimen is 14 to 32 g/day, which is less than half of the 68 to 83 g/day in thestandard diet, but the patient also has the choice of being nearly or totally plant-based. There aredifferent types of vegetarian diets [33]: (1) Vegan, or strict vegetarian (100% plant-based), diets that
not only exclude meat, poultry, and seafood but also eggs and dairy products; (2) Lacto- and/or ovovegetarian diets that may include dairy products and/or eggs; (3) Pesco-vegetarian diets that include
a vegetarian diet combined with occasional intake of some or all types of sea-foods, mostly fish; and(4) Flexitarians, which is mostly vegetarian of any of the above types with occasional inclusion ofmeat [33]. The PLADO does not require adherence to any of these strict diets, but is a flexible LPD of
0.6–0.8 g/kg/day range with 50% or more plant-based sources of protein based on the patient’s choice(Table 4). Whereas some nephrologists may promote a pesco-lacto-ovo-vegetarian LPD with >50%
plant sources, patients have the ultimate discretion to decide about the non-plant-based portion ofNutrients 2020, 12, 1931

8 of 24the protein ad lib. Based on our decades-old experience in running LPD clinics, most CKD patients
will adhere to 50–70% plant-based sources, while some may choose >70% or strictly plant-based diets.
Table 4. Comparing Low Protein Diet (LPD) >50% plant-based protein sources. Known as PLADO,
versus standard diet, based on 2400 Cal/day in an 80-kg person.
Protein Metric
Proportion of plant-based protein, %Total protein per kg IBW, g/kg/day
Total protein intake, g/day
Protein density, g/100 Cal
Proportion of energy from protein, %Total plant-based protein, g/day
Total animal-based protein, g/day

Standard Diet
20–30%>0.8, usually 1.2–1.4
96 to 112 g
4.4–5.1
16–19%
24–34
68–83

LPD >50% Plant-based Sources (PLADO)
50–70% *0.6–0.8
48 to 64 g
2.2–2.9
8–11%
24–45
14–32 (or none *)* up to 100% vegan is allowed based on patient choice.

We recommend a daily sodium intake <3 g/day for a more pragmatic approach [25], as opposedto the American Heart Association’s suggested <2.3 g/day given the lack of strong evidence for thelatter [25]. The PLADO regimen is CKD-patient-centric and flexible with respect to the targeted
dietary goals, and is constructed based on the preferences of the patient as opposed to strict dietary
regimens, with the dietitian working with patients and their care-partners to that end. Whereas werecommend a moderately low sodium intake of <3 g/day under the PLADO regimen, in those without
peripheral edema and well-controlled hypertension, we have allowed slightly higher sodium intake
but not greater than 4 g/day given that recent large cohort studies showed poor CKD outcomes withdaily urinary sodium excretion >4 g/day [82] (Figure 3).
7. Safety and Adequacy of a Plant-Dominant Low-Protein Diet
Potential challenges of PLADO are outlined in Table 3, which will be largely related to theadequacy and safety of this type of dietary management of CKD patients. The risks of PEW andsarcopenia are the leading concerns, although there is little evidence for these sequelae. As discussed
above and based on the U.S. recommended RDA for safe DPI ranges, it is highly unlikely that thetargeted DPI of 0.6–0.8 g/kg/day with >50% plant sources will engender PEW in clinically stable
individuals. No PEW was reported in 16 LPD trials cited above [13,28], including the MDRD trial[13], although PEW per se is a risk of poor CKD outcomes including faster CKD progression [83].
However, it is prudent that in patients who may develop signs of PEW or acute kidney injury (AKI),
higher DPI targets should be temporarily used until PEW or AKI is resolved. On the other hand, if
there is concern related to the likelihood of obesity and hyperglycemia, patients and providers should
be reassured that LPD therapy in CKD has not been shown to be associated with such risks, andindeed, an LPD with plant-based sources has salutary effects on insulin resistance and glycemic
index, as long as total calorie intake remains within the targeted range of 30–35 kcal/kg/day [34,55].
Another frequently stated concern is the perceived risk of hyperkalemia. We are not aware ofscientific evidence to support the cultural dogma that dietary potassium restriction in CKD improves
outcomes [84]. Evidence suggests that dietary potassium, particularly from whole, plant-based foods,
does not correlate closely with serum potassium variability [85,86]. Indeed, a high-fiber diet enhances
bowel motility and likely prevents higher potassium absorption, and alkalization with plant-based
dietary sources also lowers risk of hyperkalemia [87–91]. Of note, dried-fruit, juices, smoothies, andsauces of fruits and vegetables require additional consideration given their high potassium
concentrations. Moreover, newly available potassium-binders, which were not FDA-approved
during the era of prior LPD trials such as the MDRD, may be used in the contemporary managementof CKD patients at the discretion of clinicians [92].
Diet palatability and adherence to LPD or meatless diets are often cited as dietary management
challenges. Based on our extensive experience in running patient-centered LPD clinics for hundreds
of CKD patients [3], and given prior data on dietary adherence research [3,93], the suggested PLADO
with DPI of 0.6–0.8 g/kg/day and >50% plant-based sources is feasible and well-accepted among
patients with CKD [3]. Patients have the opportunity to choose the contribution of protein plantNutrients 2020, 12, 1931

9 of 24sources between 50% and 75% or >75%, and these two strata along with palatability, appetite [94],and adherence should be monitored closely in CKD clinics. If there is concern about inadequate fish
intake, given data on the benefits of higher fish intake including fish oil in CKD [95–97], treated CKD
patients can be reminded of the opportunity to consume more fish products for their remaining nonplant sources of the dietary protein. Likewise, concerns about B12 deficiency associated with meatlessdiets can be mitigated by the use of oral supplements as needed [98].
8. Impact of PLADO on Microbiome in CKD
Eating a plant-dominant, fiber-rich LPD may lead to favorable alterations in the gut microbiome,
which can modulate uremic toxin generation and slow CKD progression, along with reducing
cardiovascular risk in CKD patients [25,99–101]. Uremic plasma impairs barrier function and depletes
the tight junction protein constituents of intestinal epithelium [102]. The influx of retained uremic
solutes from the bloodstream per se induces changes in the microbial population simultaneous with
gut wall inflammation and breakdown of epithelial junctions [103–114]. Bacterial-derived toxins thentranslocate back across the leaky gut barrier into the systemic circulation and promote inflammationand multi-organ dysfunction [103,115]. At least five major gut-derived uremic toxins have been
associated with cardiovascular disease and mortality in CKD: indoxyl sulfate, indole-3 acetic acid, pcresyl sulfate, TMAO, and phenylacetylglutamine [115]. In a small study that included nine CKD
patients per group, which had a short duration of 6 months, LPD with or without inulin prebiotic
supplementation was reported to modify the gut microbiome, increase serum bicarbonate, andimprove physical function scores [116], but the investigators did not examine CKD progression orlevels of gut-derived uremic toxins. Future studies should examine the role of PLADO regimens on
gut microbiome in CKD patients.
9. Similarities and Distinctions between PLADO and other CKD Diets
In contrast to other diets used for the management of CKD, the PLADO offers a more pragmaticand patient-centered nutritional management which is aligned with contemporary dietary
management goals. Unlike the diets used in the MDRD study and other studies that focused on hardoutcomes, the premise of PLADO is based on its expected effects on both hard endpoints and patientcentered outcomes, including health-related quality of life, uremic symptoms, and diet palatability,
while safety and adequacy remain among important goals. It is important to note that the MDRD
Study was conducted in the early 1990s under dietary practices that are not relevant to contemporary
practice. While high-protein diets such as keto, Atkins, and Paleo diets are popular in contemporary
culture, there has been growing interest in plant-based diets across the lay and scientific communities
and professional societies including the National Kidney Foundation [117], which were notconsidered in the MDRD Study.
Restricted protein diets that are partially to entirely plant-based are more broadly generalizable
to the adult populations as compared to the prior LPD trials, including the MDRD study. PLADO
can be safely recommended to both patients with early CKD, including those with any degree ofproteinuria regardless of etiology [118], as well as to late-stage CKD populations, including thosewith an eGFR <45 mL/min/1.73 m2, without a lower eGFR limit, to take advantage of the effects of
LPDs in controlling uremia and averting the need for dialysis. This stands in sharp contrast to the
MDRD study, whose participants had relatively high eGFRs (eGFR 25 to 55 mL/min/1.73 m2), andwhich focused on slowing the progression of moderate CKD. Indeed, in the MDRD study, patients
did not have diabetes [119], whereas PLADO can be non-differentially prescribed to both patientswith and without diabetes with any degree of severity of CKD, consistent with the broader unmet
need in the adult CKD population. It is important to note that polycystic kidney disease (PKD)
patients, who usually have slower CKD progression rates, comprised 24% of the MDRD study
participants [119].

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10. Role of Dietitians in PLADO
The successful implementation of plant-based restricted protein diets is dependent on theengagement of dietitians who are well trained in the field of non-dialysis CKD [120]. Dietitians should
assess regularly the dietary protein and energy as well as micronutrient intakes of CKD patients byboth periodic dietary assessments and 24-h urine collections to estimate dietary intakes of macro- andmicronutrients and to evaluate and improve adherence to dietary recommendations (Figure 4) [25].
Behavior change counseling by dietitians is a key skill set that is critical in successful lifestyle andhabit modifications. Registered dietitians who specialize in the field of renal nutrition are usually
trained to use the 24-h urine data, which may have an impact on accurate interpretation of daily
nutrient intake estimates and assessment of patients adherence to the recommended medical
nutrition therapy [121]. Both dietitians and other healthcare providers use telehealth increasingly
frequently since the inception of COVID-19 pandemic [122]. Easy-to-use telehealth alternatives areimportant to overcome existing and emerging challenges in dietetic education including under the
COVID-19 pandemic and other restrictions, so that patients are provided with pragmatic tools andcomprehensible and consistent dietary information and skills, which fosters ownership and selfmonitoring in kidney health management such as healthy kitchen approaches [122,123].

Figure 4. An algorithm and steps for the approach to the nutritional management of patients with
CKD. Note that in addition to direct dietary assessments, periodic 24-h urine collections should be
used to estimate dietary protein, sodium, and potassium intakes in order to assess adherence todietary recommendations (adapted from the Supplementary-Appendix-Figure S4. Under KalantarZadeh and Fouque, N Engl J Med. 2017) [25]. * Comprehensive metabolic and glycemic panels include
electrolytes, SUN, creatinine, glucose, hemoglobin A1c, liver function tests, and the lipid panel. † The
full equation is: DPI = 6:25 x UUN + 0:03 x IBW † Add the amount of daily proteinuria in grams if
proteinuria >5 g/d. Calculate the creatinine index (24-hr urine creatinine divided by actual weight or
IBW if obese) and compare it to the expected value of 1–1.5 g/kg/d for women and 1.5–2 g/kg/day formen. ‡ Dietary supplements can be added to provide additional sources of energy and/or protein
including—but not limited to—CKD specific supplements, essential amino-acids, or keto-analogues(ketoacids) of amino-acids. ¶ To ensure adequate DEI of at least 30–35 Cal/kg/d, higher fat intake canbe considered, e.g., non-saturated fats, omega 3-rich flaxseed, canola, and olive oil. ‡‡ If worsening
uremic signs and symptoms occur, DPI < 0.6 g/kg/d with supplements can be considered.
Abbreviations: BMI: body mass index, CKD: chronic kidney disease, d: day, DEI: dietary energy
intake, DPI: dietary protein intake; eGFR: estimated glomerular filtration rate, GI: gastrointestinal,Nutrients 2020, 12, 1931

11 of 24

HBV: high biologic value, IBW: ideal body weight, ISRNM: International Society of Renal Nutrition
and Metabolism, K: potassium; MIS: malnutrition–inflammation score; Na: sodium; Phos.:
phosphorus; PTH: parathyroid hormone, PEW: protein energy wasting, SGA: subjective global
assessment, SUN: serum urea nitrogen, UUN: urine urea nitrogen.

Unfortunately, however, an overwhelming majority of CKD patients never meet with a CKDspecialized dietitian prior to dialysis initiation, and most patients remain uninformed about the roleof diet in disease progression and management. Among clinicians and patients, lack of awarenessabout the benefits of plant-dominant, low protein dietary interventions (other than low potassium
diets) and available insurance reimbursement for medical nutrition therapy under guidance of aregistered dietitian are significant barriers. In many regions, especially in North America and Europe,
the focus and expertise of the dietitians have traditionally been centered on dialysis patient care as
opposed to preventative non-dialysis dependent CKD. Past and recent reports suggest underutilization of dietetic manpower and expertise for the purpose of non-dialysis CKD care [3]. A
collective groundswell of events has recently occurred which aim to improve CKD care: the World
Kidney Day focuses on reduction of the onset and progression of CKD through primary, secondary.
and tertiary measures [1]; the U.S. Presidential Executive Order, “Advancing American Kidney
Health” [12], refocuses kidney care from dialysis incentives to avoidance of kidney failure; the US
Veterans Health Administration issued Directive 1053, “Chronic Kidney Disease: Prevention, Early
Recognition, and Management,” establishes federal policy targeting CKD prevention throughintegrated care including medical nutrition therapy [124], and the advocacy of renal dietitians forpatient-centric LPD regimens containing fewer animal products and more plant-based sources ofprotein such as PLADO [125]. This is a sharp contrast to prior LPD recommendations with lessflexible regimens such as strict plant-based dieting or very low DPI of <0.4 g/kg/day combined with
supplements, that may be less palatable, unsustainable, and non-pragmatic for broad application in
the real-world scenarios of CKD patient care.
11. Recommendations for Practical Implementation of PLADO
After the first 3 months, which includes preliminary education on LPD regimens with >50%
plant sources and acquiring food preparation skills, participating CKD patients should be assessed
every 3 to 6 months by the dietitian. During each visit, dietary re-education along with dietaryassessment should be conducted and patient’s progress in reaching the goals should be examined. Inline with the pragmatic nature of PLADO regimens, the dietary re-education and follow-up visits canbe performed in parallel with routine follow-up CKD clinic visits on the same days of the ambulatory
clinic appointments, thus avoiding the burden of additional diet-related travels to the CKD clinic. In
addition to in-person visits, there could be monthly to tri-monthly telephone calls with the CKD
patients under CKD therapy, or even more frequently if needed, to reinforce diet planning andadherence and to answer questions about preparation of plant-dominant meals and cooking
questions. Adherence to PLADO should be evaluated by comparing the LPD goals, i.e., 0.6–0.8
g/kg/day and >50% plant sources, to the estimated DPI using 24-hr urine nitrogen (see below) and 3day diet assessments, respectively. Complementary dietary education of the patients and their carepartners should be provided both during the face-to-face visits and via phone calls.
The specialized knowledge and services of a renal dietitian ensure accurate nutrition education,
meal planning and evaluation of body composition to sustain health. Components of a CKD nutrition
evaluation may include the following (see Table 5): (1) Dietary education for LPD with >50% plantbased protein sources, (2) Dietary assessment using a three-day diet diary with interview, (3)Simplified anthropometry that includes triceps and biceps skinfolds [126] and mid-arm
circumference [127], (4) Body fat estimation using either bioimpedance analyses or near-infra redinteractance [128–130], (5) The Malnutrition-Inflammation Score (MIS) [131–134], including
Subjective Global Assessment [135], and (6) Handgrip strength test [136]. The dietary education alongwith the above evaluations usually take 30 min to one hour of the dietitian’s time during each visit
according to our previous and ongoing nutritional clinic operations.

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Table 5. Overview of the recommended ambulatory visits and tests under the PLADO regimen (* these items are more relevant to sophisticated centers or underresearch protocols).
Timeline of for PLADO Therapy Visits

Lab tests

Dietitian visit

Questionnaires

PALDO Months
History and physical examination with updates on clinicaland dietary status
Routine lab panel: CMP/LFT, anemia, MBD, A1c
Spot urine, urinalysis, protein, albumin, creatinine
24 hr urine: Nitrogen, Na, K, creatinine, alb, prot.
eGFR assessment and creatinine and urea clearance
Dietary education for LPD >50% plant based
Dietary assessment, three-day diet diary with interview
Anthropometry: triceps and biceps skinfolds, mid-arm
circumference *Body fat estimation *Malnutrition-inflammation score *Handgrip strength test *Phone calls to reinforce PLADO education, adherence, andmeal preparation
Diet palatability and appetite questionnaire
Food Frequency Questionnaire *Quality of life: KDQOL™ including SF36 quest *Uremic symptoms questionnaire
Self-Perception and Relationship Questionnaire *“Run-in”
Period013Year 1(Quarterly)
6912Years 2+ (Semiannual)
18
24
30

36

X

Needed Time

x

x

x

x

X

x

x

X

x

10–20 min

x
x

x
x
x
x
x
x

x
x
x
x
x
x

x
x
x
x
x
x

X
X
X
X
X
X

x
x
x
x
x
x

x
x
x
x
x
x

X
X
X
X
X
X

x
x
x
x
X
X

<10 min<5 minCollected athome
10–20 min10–20 min

X

x

x

x

X

x

x

X

X

2–4 min

X
X
X

x
x
x

x
x
x

x
x
x

X
X
X

x
x
x

x
x
x

X
X
X

X
x
x

1–2 min
2–5 min
1–2 min

X
X
X
X
X
X

x

x

x

x

x

X

x

x

X

x

10–30 min

x
x
x
x
x

x

x

X
x
x
x
x

x

X
X
X
X
X

x
x
x
x
x

x
x
x
x
x

X
X
X
X
X

x
x
x
x
x

15–30 min15–30 min10–15 min10–15 min10–15 min

x
x
x

x
x
x

Abbreviations: RD: Registered dietitian, CMP: comprehensive metabolic panel, LFT: liver function tests, MBD: Mineral and bone disease markers, Na: sodium, K:
potassium, Na, K, creatinine, alb: albumin, prot.: protein, KDQOL: Kidney disease quality of life, SF36: Short Form with 36 items of quality of life.

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12. Concurrent Pharmacotherapy and Other Interventions
Regardless of the type of the dietary regimen, participation in the PLADO plan does not interferewith any other aspects of the CKD patient care including prescribed medications such as angiotensin
pathway modulators, other anti-hypertensive medications, anti-diabetic medications such as SGLT2
inhibitors, phosphorus binders, potassium binders, sodium bicarbonate, etc. Indeed, it is expectedthat dietary protein restriction will have a synergistic effect on these pharmacotherapies [67]. The
inclusion of plant-based foods should not necessitate a reduction in any of these medications overtime.
13. Laboratory Tests for Nutritional Management of CKDConsistent with the pragmatic and cost-efficient nature of the PLADO regimen, all relevant
laboratory tests are performed in the clinical laboratories of the respective medical centers typicallyas part of routine CKD care. With the exception of a semi-annual serum vitamin B12 level, quarterly
to semi-annual laboratory tests include routine chemistry panels (including serum Na, K, CO2, Cl,urea, creatinine, glucose), liver function tests, hemoglobin A1c, anemia and mineral and bonedisorders (MBD) parameters including calcium, phosphorus, and parathyroid hormone. Urinalysis
and spot urine for urinary protein/albumin and creatinine should be tested, and eGFR is calculated[137]. Participating patients are instructed to collect 24-h urine samples according to the directions
that should be repeated during each ambulatory visit and/or each phone call, i.e., not collecting thefirst AM urine of Day 1, collecting the first AM urine of Day 2 as the last collection component, andthe entire micturition in-between. The 24-hr urine should include measurements of urine urea
nitrogen (UUN), sodium (UNa), potassium UK, creatinine (UCr), albumin, and protein, as well as
urine volume (UV). The following measures should be calculated and reviewed by both thenephrologist and dietitian during each visit [25]:(1). Creatinine clearance: UCr*UV/SCr in ml/min, and to compare to eGFR;(2). Creatinine index: UCr/Weight (mg/kg), to identify 24-h urine collection inaccuracies including under- andover-collections by comparing it to the expected value of 1–2 mg/kg/d for women and 1.5–2.5 mg/kg/day
for men;(3). Estimated DPI (eDPI): UUN*6.25+0.03*weight (in g/kg/day); for patients with substantial proteinuria >3
g/day, the daily proteinuria amount is added to the above eDPI [3,25];(4). Estimated dietary Na intake: UNa in mmol/44 (g/day);(5). Estimated dietary K intake: UK in mmol/25 (g/day);(6). 24-h urinary protein and albumin excretion (mg/day).

See Table 5 for the overview of the laboratory tests.
14. Suggested Self-Administered Questionnaires
Based on the goals and the extent of the operation and resources of the CKD clinic, some to allof the following self-administered questionnaires can be used during each or alternating ambulatory
visit: (1) Diet, Palatability, and Appetite Questionnaire: the appetite component allows grading
appetite and recent changes [138]. The palatability component includes 12 items and grades
palatability and feasibility of dietary intervention [138]. These items are combined with dietassessment of the HEMO Study [139]. (2) Quality of life KDQOL™ including SF36: This has beenused and validated extensively [133]. (3) Uremic symptoms questionnaire: This questionnaire isderived from the “Symptom Assessment Instrument” by Weisbord et al. [140], which was createdand validated in US veterans with stage 5 CKD. (4) Self-Perception and Relationship Questionnaire:This item will assess the psychosocial-spiritual well-being using the 28-item scale [141]. (5) Food
Frequency Questionnaire (FFQ) [142]: this questionnaire has been developed by Kalantar-Zadeh et
al. using the Block FFQ from UC Berkeley, and can be used semi-annually to annually (see Table 5).

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15. Diet Safety and Transient Dietary Regimen Suspension
Once a patient has completed the 3-month run-in period including dietary education and foodpreparation training and adjustments, there should be periodic (every 3–6 months) ambulatory visitswith continued data collection and review. If PEW signs are observed, or in case of an event that
requires suspension of the LPD such as hospitalization with AKI, regardless of dialysis need, or major
adverse cardiovascular events (MACE), the LPD can be transiently suspended, and the patient canresume the LPD and the study protocol at a later time, usually within 90 days of the suspension of
the dietary regimen participation if deemed safe. Serum potassium levels >5.5 mEq/L will
preferentially be managed by potassium-binders (first line) and/or reducing the potassium-richcomponents of the diet (second line), as opposed to the current standard of care in that traditional
low-potassium dietary adjustments are pursued as the main approach, followed as needed by theadministration of potassium-binders.
16. Challenges and Pitfalls of the Dietary Management of CKD
As stated above, the proposed plant-dominant diet may cause hyperkalemia and could thus behazardous to patients with advanced CKD. Nephrologists and dietitians should closely monitor
patients during the 3-month run-in period and thereafter for adverse events. Dietitian support isnecessary for appropriate education on culinary strategies to reduce excessive potassium content
while preserving flavor and nutrition. Physicians should take appropriate actions including the useof potassium-binders or suspension of the patient’s participation if this should be the safest approach.
We do not expect that most patients on plant-based diets will develop hyperkalemia, as these diets
are alkalinizing and alter intestinal transit time (see above), especially if dried fruit, juices, smoothies,
and sauces can be minimized or avoided along with judicious avoidance of processed food withadded potassium-based additives and preservatives [92]. Those who are extremely prone to develop
hyperkalemia would display this early in the course of the intervention and the PLADO would be
discontinued if hyperkalemia cannot be controlled. Less constipation as a result of PLADO is
associated with favorable cardiovascular and renal outcomes [143,144].
It is important to note that the emerging standard of care in CKD is a restricted protein diet of
0.55–0.6 g/kg/day for non-diabetic CKD and 0.6–0.8 g/kg/day for diabetic CKD according to the
updated KDOQI nutrition guidelines as of September 2020 [145], and if this is implemented, this isin support of our PLADO regimen. Whereas it is true that an LPD should be the stated goal according
to the 2020 KDOQI guidelines, this is typically not followed in everyday clinical practice, where
dietary interventions are driven by biochemical abnormalities such as hyperkalemia or
hyperphosphatemia. Indeed, prior KDOQI guidelines had recommended DPI of 0.8 g/kg/day
without any clear range, which is rarely pursued in a real-world scenario.
It could be argued that under the PLADO regimen there is no clear meal plan. However, thereasonably wide dietary protein range of 0.6–0.8 g/kg/day along with the recommended plant-based
proportion of 50% or higher ensures the intended flexibility and pragmatism of the PLADO regimen,
so that further adjustments to individualized characteristics of different patients can be implemented
according to the principles of the “precision nutrition” as also shown for the dietary management ofdiabetes [146]. Some health care providers, as well as patients, may express concerns that the
carbohydrates burden of plant-dominant diets confounds dietary management of obesity, metabolic
syndrome, or diabetes. However, different types of carbohydrates have different glycemic indices,and high protein or ketogenic diets, which may be recommended for these conditions, are associatedwith untoward consequences in disease and health [21]. Complex carbohydrates, including wholeand minimally processed foods, are high in fiber and antioxidants and can reduce insulin resistanceand improve glycemic control by a variety of biologically plausible mechanisms [147]. Indeed, whole
food plant-based diets can help reduce weight in overweight and obese persons and help improve
the lipid profile and other risk factors related to cardiovascular disease or diabetes [148], and they arealso more cost-effective than meat-dominant foods [149]. Indeed, plant-based foods are lessexpensive than animal based foods, including meat and poultry, in terms of cost per serving [150].
The patient and the dietitian should work together in establishing a patient-specific “Healthy KitchenNutrients 2020, 12, 1931

15 of 24for CKD” and patients and their care-partner should gain experience in implementing patientcentered dietary interventions for CKD management. Careful and balanced industry partnership canbe sought to develop innovative “Healthy Kidney Diet Plans” to help people with CKD change theirdiet to delay the progression of the disease and to defer and prevent kidney failure.
It has been argued that many people with CKD enjoy eating high amounts of meat, and it ishighly unlikely that they will adopt an LPD with >50% plant-sources, especially since many dietitians
recommend a high protein diet as an approach against obesity and diabetes. Several authors of thisreview paper, including both nephrologists and dietitians, have successfully implemented an LPD
and plant-dominant diet education in CKD in their respective medical centers. They are aware of thecultural and dietary challenges, including in Americans and other Westerners, as described in their
published reports [3], and have been able to introduce and implement the PLADO regimens as
described here.
Another potential challenge is the misconception related to the definition of the conservative
management of advanced CKD, which is often confused with palliative and supportive care towards
the end of life and without requiring special diets. This incorrect assumption is the result of confusing
different types of conservative management of CKD, and their similarities and distinctions that haverecently been better clarified [9], in that a dietary approach including PLADO is a “preservative”
management of CKD and a life-sustaining and kidney rejuvenating alternative.
17. Anticipated Impact and Future Steps
Our proposed PLADO regimen, which has been successfully implemented in several centers in
the USA, reinvigorates the role of diet and nutrition in CKD management and may have major clinicaland public health implications among numerous populations who are at risk for or have underlying
CKD, as well as millions of Americans and people around the world with these conditions. The
discussions about plant-dominant diets such as PLADO will also lead to a generation of critical data
about the efficacy and safety of plant-dominant regimens, and will challenge the prevailing dialysiscentered paradigm. It is also aligned with recent US national directives, such as the 2020 VA CKD
Directive, promoting medical nutrition therapy, and the July 2019 Executive Order’s restructuring of
the ESKD program by preemptively involving patients and dietitians in earlier phases of CKD care,rather than dialysis preparation. This model stands in sharp contrast to the current payment system
whereby the renal dietitians’ focus of work is in the dialysis units, while patients at risk of kidney
failure have little or no access to nutritional support. The PLADO regimen also innovatively
emphasizes the important skillset provided by trained dietitians and other healthcare providers in
CKD patient care outside the dialysis arena. Averting and delaying dialysis will also result in major
cost benefits to health care systems and likely improve patient longevity and health-related qualityof life.
Whereas well-designed, pragmatic randomized controlled trials are warranted to verify theefficacy of PLADO in achieving improvement in clinical end points, this dietary regimen can be usedsafely for the management of CKD. PLADO has the advantage of considering both dietary protein
quantity (LPD) and quality (>50% plant-based), instead of quantity alone or being solely plant-based.
Its unique pragmatic design efficiently leverages CKD clinic visits and hands-on involvement ofnephrologists and dietitians during routine ambulatory nephrology assessments, providing unique
feasibility to conduct CKD management successfully. Finally, examining mastery of selfmanagement skills through “Teach-to-Goal” under the “Healthy Kidney through your Kitchen”
program by dietitians enable patients with CKD to more effectively self-manage their diet and kidneydisease [3].
Author Contributions: K.K.-Z., S.J., R.S., J.C., A.B.-T., M.D., S.S., W.-L.L., C.M.R., E.S., E.T., A.J.F., R.H., J.L.T.C.,
S.M., D.V.N., S.T.C. and C.P.K. contributed in all stages of designing and writing this manuscript including
reviewing and amending its different versions. Additionally, K.K.-Z. and C.P.K. contributed to funding for thisproject. All authors have read and agreed to the published version of the manuscript.
Funding: This work was partially supported by KKZ’s research grants from the National Institutes of Health,National Institute of Diabetes, Digestive and Kidney Disease grant K24-DK091419.

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Acknowledgments: The authors of this manuscript certify that they comply with the ethical guidelines for
authorship and publishing in the Journal.
Conflicts of Interest: K. Kalantar-Zadeh has received honoraria and/or support from Abbott, Abbvie, ACI
Clinical (Cara Therapeutics), Akebia, Alexion, Amgen, Ardelyx, ASN (American Society of Nephrology), AstraZeneca, Aveo, BBraun, Chugai, Cytokinetics, Daiichi, DaVita, Fresenius, Genentech, Haymarket Media, Hofstra
Medical School, IFKF (International Federation of Kidney Foundations), ISH (International Society of
Hemodialysis), International Society of Renal Nutrition & Metabolism (ISRNM), JSDT (Japanese Society of
Dialysis Therapy), Hospira, Kabi, Keryx, Kissei, Novartis, OPKO, NIH (National Institutes of Health), NKF(National Kidney Foundations), Pfizer, Regulus, Relypsa, Resverlogix, Dr Schaer, Sandoz, Sanofi, Shire, VA(Veterans’ Affairs), Vifor, UpToDate, ZS-Pharma. No relevant sources of conflict of interest have been declaredby other authors.

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