Efficacy of Low-Protein Rice for Dietary Protein Restriction in CKD Patients: A Multicenter, Randomized, Controlled Study : Kidney360

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Original Investigation: Chronic Kidney Disease

Efficacy of Low-Protein Rice for Dietary Protein Restriction in CKD Patients: A Multicenter, Randomized, Controlled Study

Hosojima, Michihiro1; Kabasawa, Hideyuki1; Kaseda, Ryohei2; Ishikawa-Tanaka, Tomomi2; Obi, Yoshitsugu3; Murayama, Toshiko2; Kuwahara, Shoji4; Suzuki, Yoshiki2; Narita, Ichiei2; Saito, Akihiko4

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Kidney360 3(11):p 1861-1870, November 24, 2022. | DOI: 10.34067/KID.0002982022
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Low-protein diets (LPDs) are recommended worldwide to patients with an advanced stage of CKD (1,2). However, in most clinical trials, patients often struggle to maintain adherence to dietary protein restriction. In a Japanese trial, although the prescribed dietary protein intake (DPI) amounts of the low-protein and control groups were 0.8 and 1.2 g/body weight per day, respectively, actual estimated dietary protein intake (eDPI) did not differ between the two groups (3). Moreover, in a meta-analysis of 779 patients with diabetic nephropathy in 13 randomized, controlled trials, compared with the control group, the dietary protein restriction group showed suppression of the long-term decline in the GFR only when the DPI was properly restricted (4). Therefore, how to help patients with CKD adhere to LPDs is an important issue. One solution may be to use protein-free products. D’Alessandro et al. (5). Concluded that using protein-free products may help to reduce protein, phosphorus, and sodium intake in patients with CKD while supplying adequate energy. Moreover, one of the advantages of using protein-free products is that patients with CKD do not need to drastically modify their food habits. However, in separate research, D’Alessandro et al. (6) also noted that poor palatability and limited choices still represent a barrier to the widespread use of low-protein products.

Rice is a major staple food, especially in Asia, and it is one of the most consumed grains in the world. The worldwide consumption of rice is about 500 million tons per year, with 7.5 million tons consumed per year in Japan compared with 4.5 million tons in the United States (7). According to the National Health and Nutrition Survey in Japan (8), rice is the most consumed plant protein source. This trend is likely to be the same in other Asian countries. In Japan, low-protein rice (LPR) is available in packaged units or in bulk (9). LPR is made from ordinary rice using enzymatic treatment (specifically, protease treatment), lactic acid fermentation, or a combination of the two methods (10). There are several kinds of LPR, which have from 20% to just 3% of the protein content of ordinary rice. They are used in accordance with the needs and preferences of patients and medical staff.

Using LPR could be an easy way to reduce DPI among people who eat a rice-based diet. The low potassium and phosphate concentrations of LPR are also additional benefits for patients with CKD. However, there are few reports on using LPR as part of an LPD in patients with CKD. Therefore, we conducted an open-label, multicenter, randomized, controlled trial to evaluate the efficacy of LPR for helping to reduce DPI in Japanese patients with CKD.

Materials and Methods

Participants and Study Design

This open-label, multicenter, randomized, controlled trial was conducted to compare the efficacy of dietary protein restriction between patients with CKD with and without the use of LPR. We mainly focused on the difference in changes in DPI between the two groups. The study participants were enrolled from February 2015 to June 2017 and were followed up for 24 weeks (by M.H., T.I.-K., H.K., and R.K.) at Niigata University Medical and Dental Hospital or at seven affiliated hospitals in Niigata or Fukushima prefecture, Japan. The inclusion criteria were (1) outpatient status and CKD Kidney Disease Improving Global Outcomes stages G3aA2–G4, (2) no use of low-protein foods during the previous year, (3) body mass index (BMI) >20 and <27 kg/m2, (4) age 20–75 years, and (5) provision of written informed consent on the use of data for the study. The exclusion criteria were (1) nephrotic syndrome or polycystic kidney disease, (2) severe active heart or liver disease, (3) pregnancy or breastfeeding, and (4) ineligibility for the study as judged by an attending physician for medical reasons.

Participants were randomly assigned to the LPR group and the control group (no LPR). During the observation period, stratified block allocation was performed (by Y.O.) according to eDPI, which was calculated from 24-hour urine collection using the Maroni equation (11) as follows: eDPI (grams per day) =6.25× [urinary urea nitrogen (grams per day) +0.031× body weight (kilograms)], where urinary urea nitrogen (grams per day) =0.028× urea excretion (millimoles per 24 hours). Subsequently, 24-hour urine collections were conducted to calculate eDPI at the beginning of the intervention period and every 8 weeks thereafter. Participants in both groups received regular face-to-face counseling using unified resources by dietitians once during the observation period, at the beginning of the intervention period, and every 4 weeks thereafter to meet a target DPI of 0.7 g/kg ideal body weight (IBW) per day in reference to the Japanese guidance for lifestyle and dietary modification in patients with CKD by the Japanese Society of Nephrology (12). The instructed energy intake was 25–35 kcal/kg IBW per day and depended on the patient's body size. The recommended salt intake was also <6 g/d. Apart from the use of LPR, the two groups were given the same nutritional counseling to meet the target DPI of 0.7 g/kg IBW per day. At the beginning of the study, participants were also instructed on how to complete their dietary records. The participants were asked to complete a 7-day dietary record from 7 days before the nutritional counseling every 4 weeks. Nutritional surveys of their dietary intake were conducted on the basis of the dietary records. Then, the average energy, protein, and sodium intakes for 7 days were calculated by a dietitian every 8 weeks. In addition, animal and plant protein intake and protein, fat, and carbohydrate energy ratios were calculated at the baseline and the end of the intervention period.

This trial was approved by the institutional review boards of Niigata University, Shinrakuen Hospital, Nagaoka Red Cross Hospital, Nagaoka Chuo General Hospital, Tachikawa General Hospital, Niigata Rinko Hospital, Sado General Hospital, and Takeda General Hospital in accordance with the principles embodied in the Declaration of Helsinki, and all participants gave written informed consent.

Intervention Food

We used LPR packages (180 g cooked rice per package) produced by Japanese food companies (Kameda Seika Co., Ltd., Sato Foods Co., Ltd., Biotech Japan Corporation, or Forica Foods Co., Ltd.) using enzymatic methods. Each LPR package contained just 0.2 g of protein, which is 4% of the protein (5 g) contained in ordinary rice (protein reduction rate of 1/25). Supplemental Table 1 presents information on the nutritional composition of LPR compared with regular rice. These packages are ready to eat when heated in the microwave. Participants in the LPR group were instructed to use LPR packages for at least two meals per day. As a rule, the participants ate one LPR package per meal. The research office sent the required number of LPR packages to the participants every month free of charge.


The primary outcome was a covariance analysis of eDPI per IBW, which was calculated using the Maroni formula from 24-hour urine collection, adjusted by the eDPI per IBW at the start of the study. Secondary outcomes were as follows: (1) change in estimated energy intake, (2) change in renal parameters (i.e., 24-hour creatinine clearance [CCr] and urinary protein), (3) change in clinical nutritional parameters related to the criteria of protein-energy wasting, (4) change in parameters for phosphorus metabolism and metabolic acidosis, and (5) change in parameters of quality of life (QOL).

Laboratory Methods

BMI was determined by dividing average body weight (kilograms) by height (meters) squared. We used the Japanese IBW defined by a BMI of 22 kg/m2 (13). Midarm circumference, triceps skinfold, and midarm muscle circumference were evaluated as anthropometric measurements.

Blood and urine samples were obtained at the beginning of the intervention period and every 8 weeks thereafter. Routine biochemical parameters were analyzed as well as the levels of transferrin, transthyretin, retinol-binding protein, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact parathyroid hormone (PTH), 1–84 PTH, and intact fibroblast growth factor 23. The routine biochemical parameters were measured at each hospital, and the other parameters were measured at SRL, Inc. (Tokyo, Japan) to assess kidney function, blood electrolytes, glucose metabolism, serum lipid levels, anemia, and inflammation. Transferrin, transthyretin, and retinol-binding protein levels were measured by turbidimetric immunoassay, immunonephelometry, and latex agglutination turbidimetry (Nittobo Medical Co., Ltd., Tokyo, Japan), respectively. Solid-phase and double-antibody radioimmunoassays were used to measure the levels of 25-hydroxyvitamin D (DIAsource ImmunoAssays S.A., Louvain-la-Neuve, Belgium) and 1,25-dihydroxyvitamin D (Immunodiagnostic Systems Ltd., Boldon, United Kingdom), respectively. Levels of intact PTH and 1–84 PTH were measured by electrochemiluminescence immunoassay (Roche Diagnostics K.K., Tokyo, Japan) and chemiluminescent enzyme immunoassay (Fujirebio, Inc., Tokyo, Japan), respectively. Intact fibroblast growth factor 23 levels were measured using an ELISA (Kainos Laboratories, Inc., Tokyo, Japan).

Body composition was assessed by segmental multiple frequency bioelectric impedance measurements at the beginning of the intervention period and every 8 weeks thereafter using tetrapolar eight-point tactile electrodes (InBody S20; BioSpace, Seoul, South Korea).

To assess health-related QOL, we used the Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF) at baseline and at the end of the intervention period (14). The KDQOL-SF includes both general measures and measures specific to patients with kidney disease. On all scales, the scores range from zero to 100, where higher scores indicate better functioning or QOL.

Statistical Analyses

Sample size was calculated from eDPI data obtained in a preliminary survey of 35 outpatients who were not using protein-free products. Mean eDPI was expected to be 0.89 (SD=0.22) g/kg IBW per day with a dietary prescription of 0.7 g/kg IBW per day. Given the expected reduction in DPI with twice-daily LPR use and mean body weight in the preliminary survey, we expected a between-group difference in eDPI of 0.15 g/kg per day. At a two-tailed significance level of 5%, 90 cases were required to achieve 90% statistical power. Assuming a dropout frequency of 10%, it was deemed necessary to enroll 50 participants per group for a total of 100 participants.

Per the prespecified protocol, analysis of covariance was performed with adjustment for the baseline level for all parameters. Moreover, changes in DPI and CCr were evaluated using a mixed effects model with a random slope and random intercept. All statistical analyses were performed using Stata/SE 17.0 (StataCorp LP, College Station, TX), and a two-tailed P=0.05 threshold was considered statistically significant.



We enrolled 104 patients with CKD from Niigata University Medical and Dental Hospital and seven affiliated hospitals. Two participants were subsequently excluded because they did not meet the inclusion criteria. Randomization allocated 51 participants to the LPR group and 51 participants to the control (no LPR) group. Two participants dropped out of the LPR group because they moved or withdrew their participation. One participant dropped out of the control group because of significant weight loss. This left 49 patients in the LPR group and 50 in the control group for analysis (Figure 1).

Figure 1.:
CONSORT diagram: Eligibility, randomization, and follow-up. *Adverse effect leading to patient withdrawal from the control group: significant weight loss. CONSORT, Consolidated Standards of Reporting Trials.

Table 1 shows the clinical characteristics of the 102 participants at baseline. Mean age was 62.5±11.1 years, 30% were women, and mean BMI was 23.8±2.6 kg/m2. The prevalence rates of diabetic kidney disease and chronic GN as the etiology of CKD were about 15% and 57%, respectively. Most participants (83%) used renin-angiotensin-aldosterone system inhibitors.

Table 1. - Participants’ baseline characteristics
Characteristic Low-Protein Rice Group, n=51 Control Group, n=51
Age, yr 60.3±12.7 64.6±8.8
Men, n (%) 34 (67%) 37 (73%)
Height, cm 161.5±9.4 162.1±7.4
Body weight, kg 63.0±10.4 62.6±11.2
BMI, kg/m2 24.0±2.3 23.7±2.9
Systolic BP, mm Hg 130±20 132±15
Diastolic BP, mm Hg 77±13 78±12
Etiology of CKD, n (%)
 Diabetic kidney disease 7 (14%) 8 (16%)
 Chronic GN 32 (63%) 26 (51%)
 Nephrosclerosis 8 (16%) 10 (20%)
 Others 4 (7%) 7 (13%)
Medication, n (%)
 ACE-I, ARB, MRA, or DRI 43 (84%) 42 (82%)
 Calcium channel blockers 31 (61%) 35 (69%)
 Loop or thiazide diuretics 9 (18%) 3 (6%)
 Statins 21 (41%) 30 (49%)
 Steroid 4 (8%) 2 (4%)
 Antihyperuricemic agents 21 (41%) 29 (47%)
 Active vitamin D 4 (8%) 1 (2%)
 Sodium bicarbonate 2 (4%) 0 (0%)
Data are expressed as mean ± SD or as n (%). BMI, body mass index; ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; MRA, mineralocorticoid receptor antagonist; DRI, direct renin inhibitor.

Primary Outcome

After 24 weeks, eDPI decreased from 0.99±0.23 to 0.80±0.20 g/kg IBW per day in the LPR group and from 0.99±0.23 to 0.91±0.21 g/kg IBW per day in the control group (Figure 2). The change was significantly greater in the LPR group than in the control group by 0.11 g/kg IBW per day (95% confidence interval, 0.03 to 0.19; P=0.006). Changes in eDPI on the basis of dietary records showed consistent results: from 1.01±0.24 to 0.77±0.18 g/kg IBW per day in the LPR group and from 1.00±0.25 to 0.90±0.18 g/kg IBW per day in the control group, giving a between-group difference of 0.13 g/kg IBW per day (95% confidence interval, 0.03 to 0.22; P=0.01) (Table 2). Analysis of the weekly dietary journals revealed no significant difference in the change in animal protein intake between the two groups, whereas plant protein intake significantly decreased only in the LPR group (Supplemental Table 2).

Figure 2.:
Change in estimated dietary protein intake. Change in estimated dietary protein intake in the low-protein rice (▪) and control (●) groups from baseline to the end of the treatment at week 24. Data are means and SDs. IBW, ideal body weight.
Table 2. - Changes in estimated energy, sodium, and protein intakes and urine sodium excretion
Intervention Baseline Within-Group Difference Between-Group Difference
n Mean ± SD n Mean ± SD Mean (95% Confidence Interval) P Value
Energy intake, kcal/d (dietary records)
 LPR 51 1709±337 49 8±264 8 (−104 to 119) 0.69
 Control 51 1689±264 50 1±298
Energy intake, kcal/kg IBW per day (dietary records)
 LPR 51 29.9±5.7 49 0.1±4.5 0.1 (−1.9 to 2.0) 0.65
 Control 51 29.3±5.3 50 0.0±5.2
Sodium intake, mg/d (dietary records)
 LPR 51 3584±1333 49 −663±1157 −327 (−771 to 117) 0.14
 Control 51 3162±1017 50 −335±1068
Protein intake, g/kg IBW per day (dietary records)
 LPR 51 1.01±0.24 49 −0.23±0.24 −0.13 (−0.22 to −0.03) 0.01
 Control 51 1.00±0.25 50 −0.11±0.24
Urine sodium excretion, mg/d (24-h urine test)
 LPR 51 3770±1610 49 −691±1439 −720 (−1330 to −137) 0.02
 Control 51 3417±1554 50 28±1483
LPR, low-protein rice; IBW, ideal body weight.

Secondary Outcomes

The change in energy intake from baseline to 24 weeks did not differ between the groups (Table 2). Dietary sodium intake also did not differ between the groups on the basis of dietary records, but 24-hour urine collection did reveal a significant decrease in sodium excretion at 24 weeks in the LPR group versus the control group (Table 2). The change in CCr did not differ between the groups at 24 weeks, although the change tended to be higher in the LPR group at 16 weeks (Figure 3). Moreover, 24-hour urinary protein excretion significantly decreased at 24 weeks in the LPR group (Table 3). Nutritional indices, including diagnostic markers of protein-energy wasting, phosphorus metabolism, metabolic acidosis, and QOL, showed no significant differences between the two groups (Tables 3 and 4, Supplemental Tables 3 and 4). Lean body mass decreased in both groups, although there was no difference between the groups (Table 4). During the intervention period, there were no specific complications associated with the use of LPR.

Figure 3.:
Change in creatinine clearance. Change in creatinine clearance in the low-protein rice (▪) and control (●) groups from baseline to the end of the treatment at week 24. Data are means and SDs.
Table 3. - Changes in laboratory tests
Intervention Baseline Within-Group Difference Between-Group Difference
n Mean±SD or Median (Interquartile Range) n Mean±SD Mean (95% Confidence Interval) P Value
Urinary protein, g/d
 LPR 51 0.78 (IQR, 0.35–1.80) 49 −0.30±0.61 −0.37 (−0.62 to −0.12) 0.004
 Control 51 0.51 (IQR, 0.15–1.38) 50 0.07±0.64
BUN, mg/dl
 LPR 51 26 (IQR, 21–31) 49 −2±7 −1 (−4 to 2) 0.41
 Control 51 25 (IQR, 19–31) 50 −1±7
Total protein, g/dl
 LPR 51 7.1±0.5 49 0±0.3 0.2 (0.0 to 0.2) 0.03
 Control 51 7.2±0.6 50 0.2±0.5
Albumin, g/dl
 LPR 51 4.0±0.4 49 0.1±0.2 0.1 (0.0 to 0.2) 0.14
 Control 51 4.1±0.4 50 0.0±0.3
LDL cholesterol, mg/dl
 LPR 51 107±26 49 −5±17 −7 (−14 to 0) 0.04
 Control 51 95±25 50 2±18
HDL cholesterol, mg/dl
 LPR 51 55 (IQR, 46–64) 49 1±9 1 (−3 to 4) 0.73
 Control 51 53 (IQR, 45–65) 50 1±8
Triglyceride, mg/dl
 LPR 51 134 (IQR, 85–197) 49 4±49 30 (−8 to 68) 0.11
 Control 51 144 (IQR, 99–215) 50 −25±124
Transferrin, mg/dl
 LPR 51 218 (IQR, 202–242) 49 8±22 5 (−3 to 13) 0.18
 Control 51 243 (IQR, 214–272) 50 2±18
Transthyretin, mg/dl
 LPR 51 31.1 (IQR, 28.0–36.7) 49 0.9±4.3 4.9 (−3.3 to 17.3) 0.23
 Control 51 33.2 (IQR, 28.2–36.9) 50 −4.0±28.5
Retinol-binding protein, mg/dl
 LPR 51 5.2±1.2 49 0.2±0.7 0.1 (−0.1 to 0.4) 0.31
 Control 51 5.4±1.6 50 0±0.7
LPR, low-protein rice; IQR, interquartile range.

Table 4. - Changes in anthropometry and body composition parameters
Intervention Baseline Within-Group Difference Between-Group Difference
n Mean±SD or Median (Interquartile Range) n Mean±SD Mean (95% Confidence Interval) P Value
Body weight, kg
 LPR 51 63.0±0.4 49 −0.9±2.1 −0.2 (−1.1 to 0.7) 0.65
 Control 51 62.6±11.2 50 −0.7±2.4
Body mass index, kg/m2
 LPR 51 24.0±2.3 49 −0.3±0.8 −0.1 (−0.4 to 0.3) 0.69
 Control 51 23.7±2.9 50 −0.3±0.9
Skeletal muscle mass, kg
 LPR 51 25.5±5.4 49 −0.4±0.8 −0.2 (−0.5 to 0.1) 0.15
 Control 51 25.2±5.0 50 −0.1±0.7
Skeletal muscle mass index, kg/m2
 LPR 51 9.7±1.2 49 −0.1±0.3 −0.1 (−0.2 to 0.0) 0.24
 Control 51 9.5±1.2 50 −0.1±0.3
Lean body mass, kg
 LPR 51 47.2±9.1 49 −0.8±1.8 −0.3 (−1.0 to 0.4) 0.36
 Control 51 46.7±8.7 50 −0.5±1.6
Lean body mass index, kg/m2
 LPR 51 17.9±2.0 49 −0.3±0.7 −0.1 (−0.4 to 0.2) 0.42
 Control 51 17.6±2.0 50 −0.2±0.6
Appendicular skeletal muscle mass, kg
 LPR 51 19.6±4.4 49 −0.3±0.7 −0.2 (−0.5 to 0.1) 0.14
 Control 51 19.4±4.2 50 −0.1±0.6
Appendicular skeletal muscle mass index, kg/m2
 LPR 51 7.41±1.02 49 −0.11±0.26 −0.06 (−0.16 to 0.04) 0.23
 Control 51 7.30±1.07 50 −0.05±0.24
Midarm circumference, cm
 LPR 50 28.2±2.3 49 −0.1±1.0 0.1 (−0.3 to 0.6) 0.63
 Control 51 28.0±3.0 50 −0.3±1.3
Triceps skinfold, mm
 LPR 50 13.1±4.5 49 −0.6±1.8 −0.2 (−1.0 to 0.6) 0.67
 Control 51 12.0±5.7 50 −0.4±2.1
Midarm muscle circumference, cm
 LPR 50 24.1±2.6 49 0±0.9 0.2 (−0.3 to 0.6) 0.44
 Control 51 24.2±3.2 50 −0.1±1.2
Creatinine excretion, mg/d
 LPR 51 1114±322 49 −49±148 −6 (−72 to 60) 0.86
 Control 51 1108±286 50 −43±180
LPR, low-protein rice.


This is the first randomized, controlled trial to investigate the efficacy of LPR for dietary protein restriction in patients with CKD. The results of this trial show not only that was DPI significantly decreased in the LPR group compared with the control group at 24 weeks but also, that urinary protein and sodium excretion were reduced. There were no obvious adverse events associated with the use of LPR, and very few participants withdrew from the study.

Many reports have shown that frequent nutritional counseling by dietitians improves adherence to dietary protein restriction (15), and the Frontier of Renal Outcome Modifications in Japan study recently suggested that multidisciplinary intervention including dietitians may help to protect kidney function in patients with CKD (16). However, in this trial, eDPI was significantly lower in the LPR group than in the control group, even though the two groups received the same nutritional counseling. Given that new solutions are needed to improve tolerability in order for dietary treatment to be successful (5), LPR could be a candidate. Indeed, even a 0.1– to 0.2–g/kg body weight per day reduction in DPI from baseline seems to result in significant metabolic improvement and longer preservation of kidney health (17,18). We showed a similar difference in DPI of 0.11 g/kg IBW per day between the LPR and control groups at 24 weeks, which was significant. On the other hand, there was no significant difference in CCr between the two groups after 24 weeks. The results of the Modification of Diet in Renal Disease study indicated that there was an initial dip in kidney function in the protein-restricted group after the start of intervention and that proteinuria decreased, suggesting the possibility of renal-protective effects in long-term (3-year) observation (19). In this study, proteinuria significantly decreased after 24 weeks, and CCr showed a downward trend in the LPR group after 16 weeks. We assume that there was a trend toward an initial dip in kidney function in the LPR group. A longer-term study is needed to confirm whether dietary protein restriction using LPR effectively reduces the rate of the decline in kidney function. We are currently conducting a more detailed study of this aspect and hope to report the results in the near future (trial registration identification in the Japan Registry of Clinical Trials: jRCTs031190063). Furthermore, there was a significant decrease in sodium excretion in the LPR group, even though the two groups received the same sodium restriction counseling. A possible reason for this might be that using LPR deepened patients’ understanding of the nutritional counseling they received as a whole and that dietary sodium intake might have actually been decreased in the LPR group, although the dietary records did not show any difference in the sodium intake between the LPR and control groups. We also speculate that the restriction of DPI may be associated with the decrease in urinary sodium and protein excretion. For instance, DPI induces a complex stimulation of renal function that includes an increase in GFR and an acute acceleration of sodium excretion (20). Thus, the initial downward trend in CCr in the LPR group may have been associated with the decrease in urinary protein and sodium excretion. We intend to clarify this point in the above-mentioned study, which is now underway.

The clinical practice guidelines of the Kidney Disease Outcomes Quality Initiative suggest promoting low-protein products in order to simplify nutritional counseling and achieve an LPD (1). Indeed, several reports have shown that low-protein and protein-free products facilitate dietary protein restriction (6,21). In addition, because both such products have energy content similar to their corresponding regular foods, their use, at least in staple foods, does not reduce calorie intake (22). In their review, Piccoli et al. (23) stated that, although the availability of protein-free food makes it easier to reach the ideal caloric intake, the diet may be even more demanding when protein-free food is not available. Furthermore, one of the advantages of these products is that there is no need to change eating habits. One report found that older patients who do not wish to modify their dietary habits tended to start the LPD with aproteic commercial food (24). On the other hand, such products, including LPR, have some disadvantages. For example, some patients may be dissatisfied with the taste and appearance of the food, which are somewhat different from those of regular foods, and they may need to learn cooking techniques and apply some degree of ingenuity to preparing food. Moreover, the LPR contains slightly less dietary fiber and vitamins than regular cooked rice and may need to be supplemented by other foods. In addition, continuous purchase of such products imposes a financial burden, except in Italy where such food is available for free (24). However, in this study, it should be noted that no significant difference in QOL was seen between the groups. One reason why there was no decline in QOL in the LPR group might be that the LPR was provided in a packaged form that could be easily and quickly consumed after heating in the microwave.

It is currently believed that about 50,000 people are using LPR in Japan because the annual consumption is about 18 million packages. However, this represents only about 3% of cases given that there are believed to be about 2 million patients with CKD stages G3b–G5 who would be expected to be prescribed an LPD. Nonetheless, LPR is an easy-to-use tool for helping to maintain adherence to LPDs in patients with CKD in regions where rice is the major staple food, and it may benefit patients when used appropriately according to their individual conditions.

This study has several limitations. First, it was a short-term study conducted at a limited number of locally affiliated sites. Further studies in different institutions and with a longer term and appropriate sample size are needed to verify our findings. Second, we believe that this study presents important findings for regions where rice is the major staple food in the diet but is not generalizable to places where this is not the case.

In conclusion, our findings suggest that LPR is a feasible tool for efficiently reducing DPI in patients with CKD. Long-term studies are needed to investigate the ability of an LPR-based diet to suppress CKD progression.


M. Hosojima reports research funding from Biotech Japan Co., Ltd., Daiichi Sankyo Co., Ltd., Foricafoods Co., Ltd., Kameda Seika Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Sato Foods Co., Ltd., and Taisho Toyama Pharmaceutical.Co., Ltd. and speakers bureau for AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., and Taisho Toyama Pharmaceutical.Co., Ltd. H. Kabasawa reports research funding from Biotech Japan Co., Ltd., Foricafoods Co., Ltd., Kameda Seika Co., Ltd., and Sato Foods Co., Ltd.; speakers bureau for AstraZeneca K.K., Kyowa Hakko Kirin Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Otsuka Pharmaceutical Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd. I. Narita reports research funding from Chugai Pharmaceutical, Daiichi-Sankyo, Kyowa-kirin, Otsuka Pharmaceutical, Sanwa Kagaku Kenkyusho, Sumitomo Pharma, and Terumo; and honoraria from AstraZeneca, Bayer, Kyowa-Kirin, Otsuka, and Sanofi. Y. Obi reports consultancy agreements with Obi Clinic, research funding from Relypsa/Vifor Pharma, honoraria from Kyowa Kirin, and an advisory or leadership role as an editorial board member of Renal Replacement Therapy. A. Saito reports research funding from Denka Company Limited, Daiichi-Sankyo, Kowa Pharmaceutical Company Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co., Ltd, Taisho Toyama Pharmaceutical Co., Ltd., and Torii Pharmaceutical Co., Ltd. and speakers bureau for AstraZeneca K.K., Chugai Pharmaceutical Co., Daiichi-Sankyo, Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., and Ono Pharmaceutical Co., Ltd. All remaining authors have nothing to disclose.


This study received research funding from Biotech Japan Corporation, Forica Foods Co., Ltd., Kameda Seika Co., Ltd., and Sato Foods Co., Ltd.


A draft of this manuscript was edited by ThinkSCIENCE, Inc. (Japan).

An abstract of this research was presented at a meeting of the American Society of Nephrology in San Diego, California in 2018.

Author Contributions

M. Hosojima, H. Kabasawa, I. Narita, A. Saito, and Y. Suzuki conceptualized the study; M. Hosojima and H. Kabasawa were responsible for data curation; M. Hosojima, T. Ishikawa-Tanaka, H. Kabasawa, and R. Kaseda were responsible for investigation; Y. Obi was responsible for formal analysis; M. Hosojima, H. Kabasawa, S. Kuwahara, and T. Murayama were responsible for methodology; M. Hosojima, H. Kabasawa, A. Saito, and Y. Suzuki were responsible for project administration; M. Hosojima and H. Kabasawa were responsible for resources; M. Hosojima and H. Kabasawa were responsible for validation; M. Hosojima and H. Kabasawa were responsible for visualization; M. Hosojima and H. Kabasawa were responsible for funding acquisition; I. Narita, A. Saito, and Y. Suzuki provided supervision; M. Hosojima wrote the original draft; and T. Ishikawa-Tanaka, H. Kabasawa, R. Kaseda, S. Kuwahara, T. Murayama, I. Narita, Y. Obi, A. Saito, and Y. Suzuki reviewed and edited the manuscript.

Data Sharing Statement

Data obtained through this study and presented in this manuscript may be provided to qualified researchers with academic interest.

Supplemental Material

This article contains the following supplemental material online at http://kidney360.asnjournals.org/lookup/suppl/doi:10.34067/KID.0002982022/-/DCSupplemental.

Supplemental Table 1. Composition of the low-protein rice and regular cooked rice.

Supplemental Table 2. Changes in protein, fat, and carbohydrate energy ratios and in animal and plant protein intake (from dietary records).

Supplemental Table 3. Changes in KDQOL-SF score.

Supplemental Table 4. Changes in laboratory tests.


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clinical nephrology; chronic kidney disease; clinical trial; low protein diet; low-protein rice; protein-restricted diet

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