A DPI of 0.6-0.8 g/kg/d, achieved when following an LPD with sufficient calorie intake (at least 30 kcal/kg/d), is optimum for patients with stage 3-4 CKD. This can improve azotaemia, reduce metabolic acidosis and related clinical symptoms, and may possibly delay the progress of CKD [5,11−14]. However, the DPI is usually higher in patients with stage 3-4 CKD in the absence of dietary interventions. For example, the reported baseline DPI of patients with stage 3-4 CKD was 1.0 g/kg/d in the MDRD study [1]. Moreover, a large US sample survey with 16,830 respondents showed a DPI of 1.22 g/kg/d and 1.13 g/kg/d for patients with stage 3 and 4 CKD, respectively. These levels are much higher than the recommended standards and pose a substantial clinical and mortality risk [13].
There are several challenges to consider for a successful LPD as a CKD intervention. One important factor is the recommendation and medical judgment of the nephrologist with regard to an LPD. Some physicians do not actively recommend an LPD because it not only requires the additional support of clinical renal dietitians but may also cause malnutrition when combined with the many possible complications of CKD. Another factor depends on the patient’s persistence in adhering to an LPD. An LPD changes the eating habits of patients with CKD and requires long-term maintenance. In addition, the necessity of calculating calories for each food item accurately within the LPD intervention may confuse patients and lead to suboptimal dietary adherence [13, 19].
In our study, the patients’ mean baseline DPI was 0.88±0.20 g/kg/d, reflecting the standard situation of patients with stage 3-4 CKD in the absence of intervention. The mean DPI showed no obvious change during the first 12 weeks of following an LPD, similar to the results of the MDRD study [3]. The following reasons may account for these results. (1) For most patients, no current standard method can efficiently maintain adherence to an LPD. Traditional methods, though being effective and low cost, are difficult for patients to tolerate for a prolonged duration. (2) It is challenging for most patients to change their dietary habits. (3) The amount of attention required to maintain an LPD effectively under the direction of a professional dietitian is challenging for most patients. Low compliance to an LPD is a subjective factor that more often than not continues to occur following objective efforts.
In order to solve these difficulties, we focused on the LPSF intervention evaluated here for managing patients’ DPI, which is a simpler, more patient-friendly method for reaching the LPD target [15, 16]. For a patient who weighs 60 kg, the daily intake of 250 g protein in the LPSF intervention should be 0.3 g/kg less compared with normal protein staple food, if absorption is 100%. According to the research plan, the patients were requested to consume LPSF while retaining all other foods included in the 12-week LPD intervention. We expected that the patients would have a DPI decrease of 0.2-0.3 g/kg/d by consuming LPSF instead of regular staple food daily.
As expected, in our study after consuming LPSF for 12 weeks, both the mean DPI and nPNA of these patients significantly reduced as compared to before. Meanwhile the proportion of DPI below 0.8 g/kg/d increased from 48–84%, though DPI and nPNA reduced after 12 weeks of consuming LPSF, which strongly supports that LPD compliance improved with the inclusion of LPSF. In a Japanese study on low-protein rice consumed mainly as the staple food, 9 patients with CKD showed not only a decrease in their protein intake, but also a reduction in the reciprocal serum creatinine slope during the study period (mean of 7 months) [17]. In the current study, no change in kidney function was observed, perhaps due to our short observation time.
It is known that insufficient DEI may trigger PEW in patients with CKD, especially among those with inflammation, acidosis, and endocrine disorders. Differing from traditional malnutrition, the diagnostic criteria of PEW include low blood biochemical indicators (albumin, prealbumin, and total cholesterol), changes in body composition (reduced BMI, body fat percentage, and weight), decreased muscle mass, and insufficient dietary intake (low DPI and insufficient calories) [20, 21]. The development of PEW depends on a number of factors. Residual renal function decreases concurrently with DPI and DEI, which may cause more complicated diseases and induce PEW. In the MDRD study involving 1,785 patients with middle and advanced stage CKD, the researchers found that their DPI, energy intake, and general nutritional status decreased simultaneously with a decrease in GFR [22]. Another study found that patients with stage 3-4 CKD had an increased risk of low levels of serum albumin and muscle mass accompanied by a low DEI after following an LPD (0.7 g/kg/d) for 6 weeks [21]. In addition, with sufficient calorie intake, the nutritional indices in the group with a mean DPI of 0.55 g/kg/d were similar to that in the group with a mean DPI of 0.8 g/kg/d, with no PEW occurrence [23].
Regarding this evidence, we paid special attention to calorie intake in the patients following an LPD. An important objective of the LPSF intervention in our study was for patients to achieve a 50% higher biological value for protein intake (mainly from animal proteins). To this end, the patients were encouraged to consume high-quality protein sources, such as milk, eggs, and meat, to increase their total calorie intake. After the patients switched to the LPSF intervention in our study, their average DPI decreased although their DEI did not show a clear reduction (28.6±5.44 vs 26.9±5.01, P>0.05). The proportion of high biological value protein increased owing to the decrease in low biological value protein consumption from staple food. It can thus be concluded that the LPSF intervention more easily achieves a lower DPI, with an unchanged DEI and high biological value protein intake in patients with stage 3-4 CKD. The PEW indicators, such as serum albumin, total cholesterol, BMI, body fat, weight, and muscle volume showed no significant change (Table 1), indicating that the LPSF diet had no influence on PEW.
Potassium and phosphorus levels in LPSF are approximately 2.3% and 40% of those of ordinary rice, respectively. Given the low amount of phosphorus and potassium in staple food, even within a standard diet, the impact on blood phosphorus and potassium levels can be ignored even if these levels are significantly reduced.
We have also solved some issues regarding the administration of the LPSF diet, including (1) providing single servings of packaged rice from the cooperating factory to simplify cooking for the LPSF intervention, (2) developing low-protein dumpling flour and noodles to enrich LPSF varieties, and (3) allowing some patients to combine LPSF with different ratios of ordinary staple food in the study to give them comfort. It is difficult for patients to maintain the LPSF intervention at each meal, and ordinary staple food alternated with LPSF is a practical and optimal option.
This study has some limitations. First, the sample size of the study population was small. Second, the short duration of the trial did not permit conclusions on the long-term safety of LPSF therapy. It would take several years of observation to conclude that LPSF therapy can avoid malnutrition. Moreover, selection biases were unavoidable in this case-crossover study. Therefore, randomized controlled double-blind trials are more conducive to avoiding the bias of the research subjects.