A review authored by Kalantar-Zadeh and Fouque (2017), cited clinical trials that found low protein diets mitigated symptoms of uremia, and maintained GFR, effectively delaying or avoiding dialysis therapy among chronic kidney disease (CKD) patients.
Low protein diets initially result in incremental decreases in GFR, followed by diminished glomerular damage, and stabilization in the long term. In addition to stabilizing GFR, LPD (0.6-0.8g/kg/day) mitigates proteinuria among adults with moderate-to-advanced kidney disease (eGFR, <45 ml per minute per 1.73 m2 of body surface area). The table below summarizes findings involving the effect of low protein diets on proteinuria, uremia, metabolic acidosis, mineral and bone disease, protein energy wasting (PEW), cardiovascular and metabolic health, glycemic control and insulin response, quality of life, mortality, hypertension, and microbiome (table 1).
|Measure||Potential Benefits of LPD||Challenges and Risks of LPD||Comments|
|CKD Progression||Lowers intraglomerular pressure to preserve GFR||Initial short term drop in GFR||Inconclusive results in MDRD study, but small effect size in meta-analyses|
|Proteinuria||Antiproteinuric effect||LPD is contrary to the notion that protein intake must be increased||Some data suggest that even larger effect may be achieved with daily protein intake of <0.6 g/kg/day|
|Uremia||LPD mitigates uremia||If caloric intake is not maintained, may result in protein energy wasting (PEW)||Patients at increased risk for PEW may benefit from supplements (e.g., EAA or KA)|
|Metabolic Acidosis||H+ generation decreased with LPD||Need for >50% high biologic value protein may result in higher intake of non-plant-based foods that are acidogenic||Although >50% HBV protein is recommended, the remainder can be from plant-based foods|
|Mineral and Bone disease||Lower phosphorus content of LPD improves measures of mineral bone disease||Higher calcium content in some ketoacid preparations may increase calcium load||Additional improvements in bone health are possible by alleviating acidosis|
|PEW||If energy intake is adequate, may ameliorate hypoalbuminemia in patients with proteinuria may help neutralize circulating inflammatory compounds||Weight loss may occur; the habit of LPD intake may continue after starting thrice-weekly hemodialysis, when higher protein intake is recommended||Half of dietary protein source should be HBV protein; liberalize diet during correction of PEW|
|Glycemic control and insulin response||Improvement in insulin resistance is likely||With LPD or VLPD, higher carbohydrate and fat intake (to achieve DEI 30–35 kcal/kg/day) may worsen glycemic control||Given increased insulin half-life and “burnt-out diabetes” with CKD progression, preventing hypoglycemic episodes is prudent|
|Cardiovascular and metabolic health||Lower protein intake is associated with lower dietary salt and saturated fat intake and may be less atherogenic, given higher proportion of plant-based food||Higher dietary fat intake (to achieve DEI of 30–35 kcal/kg/day) may confound the goal of achieving a heart-healthy diet||Higher proportions of unsaturated fat and complex carbohydrates Recommended|
|Quality of life and adherence to LPD||Enhanced patient-centeredness, given that many patients seek nutritional therapies and dietary advice||Challenges with adherence; diet fatigue, poor palatability, and cravings reported||Recommend creative recipes and strategies to engage patients|
|Mortality||There are no convincing data to suggest reduced mortality, although dialysis deferral is a potential mechanism, given high mortality during early dialysis||Increased mortality highly unlikely with DPI of 0.6–0.8 g/kg/day unless severe PEW emerges and is uncorrected||Consider supplements or other corrective strategies whenever PEW is suspected or diagnosed|
|Hypertension management||MDRD and other data suggest improved BP control||Reduction in BP is more likely a result of concomitant lower salt intake than of LPD itself||Higher potassium intake from more plant-based foods may be a potential mechanism|
|Microbiome modulation||Improved microbiome profile may be achieved through reduced uremic toxin generation||Possibility of promoting unfavorable microbiome milieu cannot be excluded||Uremia itself can lead to unfavorable microbiome|
Based on 12 observational cohort studies, Mathew et al. (2018) provides evidence that incremental hemodialysis (HD, twice per week) may preserve residual kidney function (RKF) and decrease arteriovenous fistulas incidents and need for grafts among CKD patients. Additionally, consideration of LPD (0.6-0.8g/kg/day) on non-dialysis days may arrest the decline of RFK among selected HD patients. For example, in a prospective cohort study, 38 patients were assigned a very low protein diet.
Caria et. al. (2014) performed a multicenter, prospective controlled study following CKD patients on dialysis for 6-12 months, with hospitalization and survival rates followed up for 24 months. This Among the 68 patients, 38 began a Combined Diet Dialysis Program (CDDP) and 30 chose the standard thrice-a-week hemodialysis (THD). GFR loss was 0.13mL/min/month in the CDDP group, compared to 1.53mL/min/month in the THD group. During the 24 month follow up, survival rate for the CDDP group was 95%, vs 87% and hospitalizations were for 3.7 days/patient and 6.1 days/patient for CDDP and THD respectively.
In a systematic review, and meta-analysis involving 16 controlled trials with 2771 patients (median: 84 patients/study) of LPD on CKD (stages 3-5), Rhee et al (2018) compared diets with protein intake of >0.8g/kg/day, and restricted protein intake of <0.6g/kg/day. Based on the pooled data, diets with the lower protein intake resulted in higher serum bicarbonate levels, lower phosphate levels, lower azotemia, lower progression to end-stage renal disease (ESRD), and lower mortality. Diets with further restriction in protein intake (<0.4g/kg/day) exhibited greater preservation of kidney function, and further reduction to ESRD.
- Kalantar-Zadeh, K., and Fouque, D. Nutritional Management of Chronic Kidney Disease. New England
- Journal of Medicine, 2017; 377:1765-76.
- Cupisti, A., Brunori, G., Raffaele Di Iorio, B., et al. Nutritional treatment of advanced CKD: twenty consensus statements. Journal of Nephrology, 2018; https://doi/org/10.1007/s40620-018-0497-z.
- Mathew, A.T., Obi, Y., Rhee, C.M., et al. Incremental dialysis for preserving residual kidney function – Does one size fit all when initiating dialysis? Seminars in Dialysis, 2018; 31:343-352.
- Caria, S. Cupisti, A., Sau, G., et al. The incremental treatment of ESRD: a low-protein diet combined with weekly hemodialysis may be beneficial for selected patients. BMC Nephrology, 2014; 15: 172.
- Rhee, C.M., Ahmadi, S.F., Kovesdy, C.P., et al. Low-protein diet for conservative management of chronic kidney disease: a systematic review and meta-analysis of controlled trials. Journal of Cachexia, Sarcopenia and Muscle, 2018; 9: 235-245.