4.8 9.

Review

Plant-Dominant Low-Protein Diet

for Conservative Management of
Chronic Kidney Disease

Kamyar Kalantar-Zadeh, Shivam Joshi, Rebecca Schlueter, Joanne Cooke, Amanda Brown-Tortorici,
Meghan Donnelly, Sherry Schulman, Wei-Ling Lau , Connie M. Rhee, Elani Streja et al.

Special Issue
Renal Nutrition and Metabolism
Edited by
Prof. Dr. Piergiorgio Messa

https://doi.org/10.3390/nu12071931
 nutrients
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 8,9 and
Csaba P. Kovesdy 10
1 Department of Medicine, Division of Nephrology Hypertension and Kidney Transplantation, University of
California 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.: +1-714-456-5142




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 is
costly and associated with functional impairments, worse health-related quality of life, and high
early-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 meat intake 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 the risk of constipation with resulting
hyperkalemia from the typical low fiber intake. A plant-dominant, 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 the centerpiece of a conservative and preservative
CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

Nutrients 2020, 12, 1931; doi:10.3390/nu12071931 www.mdpi.com/journal/nutrients

Nutrients 2020, 12, 1931 2 of 25

Keywords: plant-dominant; low-protein; dietary protein intake; glomerular hyperfiltration

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 reach kidney
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 kidney transplantation [1–4].
However, ESKD patients who transition to dialysis often have poor clinical outcomes. 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 the purported 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 and preserving 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 paramount importance
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 dietary intervention
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 importance of preventive
CKD measures and reiterates the critical, yet underappreciated role of leveraging dietary interventions
in optimizing kidney health [12]. This review article highlights past and contemporary 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 the cornerstone 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 body
weight 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 and
Nutrition 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 high
in protein and animal fats, are gaining popularity across different healthcare systems throughout the
world 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 long-term
health [21]. Furthermore, previous and emerging data (Table 1) suggest that high DPI in these diets,
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].
Nutrients 2020, 12, 1931 3 of 25

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

Duration Of
Study (Year) Cohort, [N] (Country) Findings
Follow Up
Alpha Omega Cohort ↑ DPI 0.1 g/kg/day associated with ↑
Esmeijer [22] (2020) 41 mo
(2255) (Netherlands) eGFR decline of −0.12 ml/min/year
3.5-fold ↑ risk of hyperfiltration.
Jhee [23] (2020) South Korea (9226) 14 yrs
1.3-fold ↑ faster decline
Jackson Heart (USA) ↑ DPI density associated with ↑ eGFR
Malhotra [24] (2018) 8 yrs
(5301) decline
Farhadnejad [24] Healthy Iranian adults
6.1 yrs 48% ↑ risk of incident CKD in high DPI
(2018) (1797)

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 each trial
(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 and
others 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
amino-acid or keto-analogue supplements to avoid protein-energy wasting (PEW). For persons without
established 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 diet
and 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 some
mixed 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, were considered
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-based sources. Due
to the impractical aspects of prior LPD regimens, and in part to the marginal effects of an LPD in the
MDRD, which did not achieve statistical significance, LPD has not been adopted in most 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-centered intervention, especially with a
newer focus on plant-dominant diet regimens.
Nutrients 2020, 12, 1931 4 of 25

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 and Fouque,
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].
Nutrients 2020, 12, 1931 5 of 25

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

Duration of
Study (Year) Participants Diet (g/kg/day) Results
Follow Up
Rosman (1984) 0.90–0.95 vs. 0.70–0.80 Significant CKD slowing
247 CKD 3–5 pts 4 yrs
[35,36]. vs. unrestricted in LPD in male pts.
LPD (0.6) vs. higher Loss of GFR in control vs.
Ihle (1989) [37] 72 CKD 4–5 pts 18 mo
DPI (0.8) LPD (p < 0.05). Wt loss
Decreased phos. with
Lindenau (1990) LPD vs. sVLPD (0.4) w
40 CKD 5 pts 12 mo sVLPD and improved
[38] KA
bone health
Williams (1991) No differences, minor Wt
95 CKD 4–5 LPD (0.7) vs. 1.02–1.14 18 mo
[39] loss
Locatelli (1991) Trend for difference in
456 CKD 3–4 0.78 vs. 0.9 2 yrs
[40] renal outcomes (p = 0.059).
MDRD Klahr No difference in GFR
585 CKD 3–4 1.3 vs. 0.6 27 mo
(1994) [41] decline at 3 years.
Montes-Delgado Slower eGFR decline with
33 CKD 3–5 LPD vs. sLPD 6 mo
(1998) [42] supplements
sVLPD (0.3) KA vs. Decreased SUN lean body
Malvy (1999) [43] 50 CKD 4–5 3 yrs
LPD (0.65) mass and fat in sVLPD
Teplan (2001) [44] 105 CKD 3b–4 LPD w vs. w/o KA 3 yrs Slower CKD progression
Prakash (2004)
34 CKD 3b–4 0.6 vs. 0.3 w KA 9 mo Faster decline in LPD
[45]
Brunori (2007) 56 > 70 yrs old sVLPD (0.30) w KA vs. Similar survival but more
27 mo
[46] CKD 5 dialysis hospitalizations in dialysis
Mircescu (2007) sVLPD (0.3) vegan w Less dialysis initiation in
53 CKD 4–5 48 wks
[47] KA vs. LPD sVLDP
Cianciaruso Reduced urinary urea, Na,
423 CKD 4–5 0.55 vs. 0.80 18 mo
(2008) [48] phos
Di Iorio (2009) 32 CKD w 58% greater reduction in
VLPD vs. LPD 6 mo
[49] proteinuria proteinuria
Jiang (2009 and LPD vs. sLPD w KA vs. RKF decreased in the LPD
60 PD w RKF 12 mo
2011) [50,51]. HPD and HPD.
Garneata (2016) LPD (0.6) vs. sVLPD w
207 CKD 4–5 15 mo Less dialysis initiation
[52] KA
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 sources from
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
Nutrients 2020, 12, 1931 6 of 25

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 and found 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 showed that red and processed meat were associated with higher
CKD risk, while nuts, low-fat dairy products, and legumes were protective against the development of
CKD) and Chen et al. [66] (who showed 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 which should
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 established metabolic
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, grant high 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 of at least 25–30 g/day,
and adequate dietary energy intake (DEI) of 30–35 Cal/kg/day, assuming that the 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, preferentially
unprocessed 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 body
weight. Note that serum B12 should be monitored after three years of vegan dieting.
Nutrients 2020, 12, 1931 7 of 25

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
an effective strategy in controlling uremia and delaying dialysis initiation [28].
(2) Synergism with RAAS and SGLT2 inhibitors, since LPD reinforces the pharmaco-therapeutic
effect of lowering 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 risk of 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 this
alkalization 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
the presence 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 Potential Challenges of LPD

• Lowering intra-glomerular pressure • Risk of protein-energy wasting (PEW)
• Synergistic effect with RAASi and SGLT2i • Inadequate essential amino acids
• Controlling uremia and delaying dialysis • Undermining obesity management
• Preventing cardiovascular harms of meat • High glycemic index
• Less absorbable phosphorus • High potassium load and hyperkalemia
• Lowering acid-load with less acidogenicity • Low palatability and adherence
• High dietary fiber enhancing GI motility • Inadequate fish intake if vegan
• Favorable changes in microbiome
• Less TMA N-oxide (TMAO), leading to less kidney fibrosis
• Less inflammation and oxidative stress

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 less total protein of 0.6–0.8 g/kg/day but it also includes 50% to 70% of plant-based sources
for this restricted DPI goal. Hence, an 80 kg person with CKD, for instance, would be recommended
to have 46 to 64 g of DPI per day, out of which 24 to 45 g will be from plant-based sources, while
the rest is according to patient choice and preferences. As shown in Table 4, the total amount of
Nutrients 2020, 12, 1931 8 of 25

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 the standard diet, but the patient also has the choice of being nearly or totally plant-based.
There are different 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 ovo-vegetarian 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
of meat [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 the
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.

LPD >50% Plant-based

Protein Metric Standard Diet
Sources (PLADO)
Proportion of plant-based protein, % 20–30% 50–70% *
Total protein per kg IBW, g/kg/day >0.8, usually 1.2–1.4 0.6–0.8
Total protein intake, g/day 96 to 112 g 48 to 64 g
Protein density, g/100 Cal 4.4–5.1 2.2–2.9
Proportion of energy from protein, % 16–19% 8–11%
Total plant-based protein, g/day 24–34 24–45
Total animal-based protein, g/day 68–83 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 opposed
to the American Heart Association’s suggested <2.3 g/day given the lack of strong evidence for the
latter [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 we recommend 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 with daily
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 the
adequacy and safety of this type of dietary management of CKD patients. The risks of PEW and
sarcopenia 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 the
targeted 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, and indeed, 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].
Nutrients 2020, 12, 1931 9 of 25

Another frequently stated concern is the perceived risk of hyperkalemia. We are not aware of
scientific 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,
and sauces 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 management of 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
sources 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 non-plant
sources of the dietary protein. Likewise, concerns about B12 deficiency associated with meatless diets
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 then
translocate back across the leaky gut barrier into the systemic circulation and promote inflammation and
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, p-cresyl 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, and improve physical function
scores [116], but the investigators did not examine CKD progression or levels 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 pragmatic
and 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 hard outcomes,
the premise of PLADO is based on its expected effects on both hard endpoints and patient-centered
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 not considered in
the MDRD Study.
Nutrients 2020, 12, 1931 10 of 25

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 of proteinuria
regardless of etiology [118], as well as to late-stage CKD populations, including those with 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 ), and which 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 patients with 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].

10. Role of Dietitians in PLADO

The successful implementation of plant-based restricted protein diets is dependent on the
engagement 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 by
both periodic dietary assessments and 24-h urine collections to estimate dietary intakes of macro- and
micronutrients 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 and
habit 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 are important
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 and comprehensible
and consistent dietary information and skills, which fosters ownership and self-monitoring in kidney
health management such as healthy kitchen approaches [122,123].
Unfortunately, however, an overwhelming majority of CKD patients never meet with a
CKD-specialized dietitian prior to dialysis initiation, and most patients remain uninformed about the
role of diet in disease progression and management. Among clinicians and patients, lack of awareness
about 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 a registered
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 under-utilization 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 through integrated care including medical nutrition
therapy [124], and the advocacy of renal dietitians for patient-centric LPD regimens containing fewer
animal products and more plant-based sources of protein such as PLADO [125]. This is a sharp contrast
to prior LPD recommendations with less flexible 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.
Nutrients 2020, 12, 1931 11 of 25

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 to dietary
recommendations (adapted from the Supplementary-Appendix-Figure S4. Under Kalantar-Zadeh 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 × UUN + 0:03 × 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 for men. ‡ 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 can be 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, 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.

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 dietary
assessment should be conducted and patient’s progress in reaching the goals should be examined.
In line with the pragmatic nature of PLADO regimens, the dietary re-education and follow-up visits can
be performed in parallel with routine follow-up CKD clinic visits on the same days of the ambulatory
Nutrients 2020, 12, 1931 12 of 25

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 and
adherence 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 3-day diet assessments,
respectively. Complementary dietary education of the patients and their care-partners 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% plant-based
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 red interactance [128–130],
(5) The Malnutrition-Inflammation Score (MIS) [131–134], including Subjective Global Assessment [135],
and (6) Handgrip strength test [136]. The dietary education along with 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.
Nutrients 2020, 12, 1931 13 of 25

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

“Run-in” Year 1 Years 2+

Timeline of for PLADO Therapy Visits Needed Time
Period (Quarterly) (Semi-Annual)
PALDO Months 0 1 3 6 9 12 18 24 30 36
History and physical examination with updates on clinical and dietary
X x x x x X x x X x 10–20 min
status
Routine lab panel: CMP/LFT, anemia, MBD, A1c X x x x X x x X x <10 min
Spot urine, urinalysis, protein, albumin, creatinine X x x x X x x X x <5 min
Lab tests
24 hr urine: Nitrogen, Na, K, creatinine, alb, prot. X x x x X x x X x Collected at
eGFR assessment and creatinine and urea clearance X x x x X x x X x home
Dietary education for LPD >50% plant based X x x x x X x x X X 10–20 min
Dietary assessment, three-day diet diary with interview X x x x x X x x X X 10–20 min
Anthropometry: triceps and biceps skinfolds, mid-arm circumference * X x x x X x x X X 2–4 min
Dietitian visit
Body fat estimation * X x x x X x x X X 1–2 min
Malnutrition-inflammation score * X x x x X x x X x 2–5 min
Handgrip strength test * X x x x X x x X x 1–2 min
Phone calls to reinforce PLADO education, adherence, and meal
x x x x x X x x X x 10–30 min
preparation
Diet palatability and appetite questionnaire x x x X x X x x X x 15–30 min
Food Frequency Questionnaire * x x X x x X x 15–30 min
Questionnaires Quality of life: KDQOL™ including SF36 quest * x x x x X x x X x 10–15 min
Uremic symptoms questionnaire x x x x X x x X x 10–15 min
Self-Perception and Relationship Questionnaire * x x x x X x x X x 10–15 min
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.
Nutrients 2020, 12, 1931 14 of 25

12. Concurrent Pharmacotherapy and Other Interventions

Regardless of the type of the dietary regimen, participation in the PLADO plan does not interfere
with 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 expected that
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 over time.

13. Laboratory Tests for Nutritional Management of CKD

Consistent 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 typically as
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 bone disorders
(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 the first AM
urine of Day 1, collecting the first AM urine of Day 2 as the last collection component, and the 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 the nephrologist 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- and over-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 all of
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 diet assessment of the
HEMO Study [139]. (2) Quality of life KDQOL™ including SF36: This has been used and validated
extensively [133]. (3) Uremic symptoms questionnaire: This questionnaire is derived from the
“Symptom Assessment Instrument” by Weisbord et al. [140], which was created and 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).
Nutrients 2020, 12, 1931 15 of 25

15. Diet Safety and Transient Dietary Regimen Suspension

Once a patient has completed the 3-month run-in period including dietary education and food
preparation training and adjustments, there should be periodic (every 3–6 months) ambulatory visits
with 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 can
resume 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-rich components 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 the administration
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
be hazardous 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 is
necessary for appropriate education on culinary strategies to reduce excessive potassium content
while preserving flavor and nutrition. Physicians should take appropriate actions including the use of
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 with
added 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 is in
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, the
reasonably 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
of diabetes [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 associated
with untoward consequences in disease and health [21]. Complex carbohydrates, including whole
and minimally processed foods, are high in fiber and antioxidants and can reduce insulin resistance
and 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 are
also more cost-effective than meat-dominant foods [149]. Indeed, plant-based foods are less expensive
Nutrients 2020, 12, 1931 16 of 25

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 for CKD”
and patients and their care-partner should gain experience in implementing patient-centered dietary
interventions for CKD management. Careful and balanced industry partnership can be sought to
develop innovative “Healthy Kidney Diet Plans” to help people with CKD change their diet 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 is
highly 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 this
review 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
the cultural 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 have
recently 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 clinical and
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 dialysis-centered
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 quality of life.
Whereas well-designed, pragmatic randomized controlled trials are warranted to verify the efficacy
of PLADO in achieving improvement in clinical end points, this dietary regimen can be used safely
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 of nephrologists
and dietitians during routine ambulatory nephrology assessments, providing unique feasibility to
conduct CKD management successfully. Finally, examining mastery of self-management 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 kidney disease [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 this
project. All authors have read and agreed to the published version of the manuscript.
Nutrients 2020, 12, 1931 17 of 25

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.
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), Astra-Zeneca,
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 declared by other authors.

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