Chronic kidney disease (CKD) is a global cause of increased morbidity and mortality and CKD-related deaths and years of life lost due to CKD increased between 1990 and 2010 , indicating an ongoing health challenge. Although increased cardiovascular disease (CVD) is a well described contributor to the excess mortality of CKD , excess mortality in patients with nondialysis-dependent CKD is due additionally to increased noncardiovascular causes, particularly malignancy [3▪]. Diet is the largest CKD-related death and disability risk factor  yet there has been little emphasis on dietary strategies to reduce CKD progression and its associated health and economic costs. The quintessential question of ‘Doctor, what can I really eat?’ often goes unanswered in early CKD stages when adoption of a healthier diet might slow glomerular filtration rate (GFR) decline and thereby reduce the prevalence of complete kidney failure . Current kidney protection guidelines recommend control of intake of protein, sodium, and phosphorus and management of metabolic acidosis . We will systematically analyze each recommendation and provide our own opinion-based recommendations.
DIETARY MODIFICATION OF PROTEIN
Target dietary protein intake for people with diabetes and chronic kidney disease stages 1–4 should be the Recommended Daily Allowance of 0.8 g/kg body weight per day. (B)-KDOQI 5.1
The impact of protein restriction in diet was examined in the Modification of Diet in Renal Disease study . The study showed that a low protein diet (0.58 g/kg/day) caused an initial rapid decline in GFR in 1585 patients with stage 3 CKD that slowed after 4 months . In addition, the projected decline in GFR at 3 years was not different from a usual protein diet (1.3 g/kg/day) . The Modification of Diet in Renal Disease study tested if the amount of daily dietary protein intake affected the rate of GFR decline in patients whose GFR was already decreased at baseline. How a low-protein diet might slow GFR decline is incompletely understood, even in animal studies. One possibility is that dietary protein restriction reduces proteinuria, even when given in conjunction with angiotensin-converting enzyme inhibitors . More recent studies support that the character of ingested dietary protein, rather than the daily amount ingested, plays a more important contributory role to the rate of further GFR decline in patients with reduced GFR.
Diets typical of industrialized societies are acid-producing, due mostly to proportionately greater amounts of animal-sourced protein (which is acid-producing) than plant-sourced protein (which is largely base producing) . High acid-producing diets are more likely to induce metabolic acidosis in patients with reduced compared with normal GFR . Metabolic acidosis of CKD increases protein catabolism  mediated through the ATP-dependent ubiquitin-proteasome system . Correction of metabolic acidosis in CKD with oral NaHCO3 decreases protein catabolism, improves protein balance with increased muscle mass, and decreases induction of the ubiquitin-proteasome system . Animal [13,14] and patient [15,16,17▪] studies support correction of metabolic acidosis in CKD with Na+-based alkali (NaHCO3 or Na+ citrate) slows GFR decline. These studies show the importance of dietary acid reduction in slowing nephropathy progression and can be accomplished with oral Na+-based alkali (NaHCO3 or Na+ citrate) or by increased ingestion of base-producing foods like fruits and vegetables (i.e., plant-sourced protein) . We posit that kidney-protective dietary recommendations regarding protein should emphasize ingestion of base-producing, plant-sourced, protein in patients who can tolerate the additional K+ load rather than emphasizing reduced intake of the animal-sourced protein typical of diets of industrialized societies.
These recent studies supporting that plant-sourced protein slows nephropathy progression add to earlier studies supporting its value in CKD. Increasing plant-sourced dietary protein in CKD patients with reduced eGFR improved metabolic acidosis, lowered risk for further nephropathy progression 16%, and lowered blood pressure . More recent studies emphasizing plant-based dietary protein also showed that these diets reduced blood pressure, possibly through reduced sodium and increased potassium intake, as opposed to oral NaHCO3 for dietary acid reduction that did not [17▪,20]. High plant-sourced protein intake was also associated with reduced risk of prevalent CKD in one cross-sectional study . Plant-based dietary protein interventions not only reduced protein catabolism and improved metabolic acidosis associated with CKD as discussed, but also reduced urine parameters of kidney injury , altered gut flora in a way that reduced production of potential uremic toxins , reduced proinflammatory gut flora [23,24▪], reduced body weight [17▪,20,25], and improved cardiovascular outcomes . Together, these data support increasing the proportion of plant-sourced compared with animal-sourced dietary protein in CKD patients who can tolerate the additional K+ load as adjunctive kidney protection.
DIETARY MODIFICATION WITH FRUITS AND VEGETABLES
Kidney Disease Improvement for Global Outcomes 2013  guideline 3.1.13 for CKD patients suggests ‘lowering protein intake to 0.8 g/kg body weight/day in adults with diabetes (‘2C’ level of strength, meaning that this is a suggestion and that its true effect might be substantially different from the estimated effect) or without diabetes (‘2B’ level of strength, meaning that this is a suggestion and its true effect is likely to be close to the estimated effect but there is a possibility that it is substantially different) and GFR less than 30 ml/min/1.73 m2 (GFR categories G4–G5) with appropriate education’. The guidelines suggest that the recommended protein be of ‘high biologic value’ but do not discuss if this includes plant-sourced protein. Guideline 3.1.14 reads ‘we suggest avoiding high protein intake (>1.3 g/kg/body weight/day) in adults with CKD at risk of progression’ (‘2C’ level of strength, as explained above). The qualifications for these two suggestions reflect the need for additional studies to develop more concrete dietary protein recommendations for patients with very low (<30 ml/min/1.73 m2) GFR. In particular, further studies are needed to elucidate the importance of the character compared to the amount of ingested protein, particularly with respect to whether the protein is acid-producing or base-producing when metabolized.
Dietary protein recommendations for CKD patients with GFR greater than 30 ml/min/1.73 m2 and who appear to be at less risk for progression are even less specific. Because most CKD patients have hypertension, Joint National Committee VIII recommendations  apply which include adoption of diets shown to reduce blood pressure  including the Dietary Approaches to Stop Hypertension (DASH) diet . The DASH diet supports inclusion of three to four servings of fruit and vegetables per day, a recommendation similar to the amount of fruit and vegetable intake shown to slow nephropathy progression in small-scale studies [17▪].
A fascinating field of research has uncovered an important connection between diet, the microbiome, CKD, and CVD. Dietary carnitine (present predominately in red meat) and lecithin (phosphatidyl choline) are metabolized by gut microbes to trimethylamine, which in turn is metabolized by liver flavin monoxygenases to form trimethylamine-N-oxide . High levels of trimethylamine-N-oxide in the blood strongly correlate with CVD major adverse cardiovascular events [23,24▪]. This might be a contributing mechanism to the association of fruit and vegetable consumption to lower all-cause, including cardiovascular, mortality .
Because base-producing fruits and vegetables reduce uric acid excretion , addition of these dietary components has been explored as an alternative strategy to NaHCO3 to treat metabolic acidosis. This intervention improves metabolic acidosis in patients with CKD and reduced GFR [17▪,19,20] and slows eGFR decline as discussed. CKD patients with reduced eGFR and metabolic acidosis were given fruits and vegetables in amounts equivalent to 50% of their calculated dietary (acid) H+ load [17▪,18,20]. For most patients, this amounted to adding two to four cups of fruits and vegetables to their daily diets. Participants in these studies were carefully selected to be at very low risk to develop hyperkalemia in response to the increased K+ load that accompanies fruits and vegetables. Clinicians should therefore use caution when considering prescribing fruits and vegetables to their CKD patients, particularly those with very low (<30 ml/min/1.73 m2) GFR.
DIETARY TREATMENT OF METABOLIC ACIDOSIS
Metabolic acidosis is a common complication in CKD and its prevalence increases with declining GFR . Low plasma HCO3 due to metabolic acidosis is directly associated with increased risk for nephropathy progression [32–34] and with increased mortality . Current guidelines recommend treatment with Na+-based alkali (Na+ citrate or NaHCO3) for CKD patients with plasma TCO2 (HCO3) less than 22 mM . Such treatment in patients fitting these criteria slows nephropathy progression as described [15,16]. Nevertheless, the risk for and rate of GFR decline increases in CKD patients as plasma TCO2 decreases due to metabolic acidosis within ranges that include values greater than 22 mM [32–34]. Indeed, oral NaHCO3 also slows nephropathy progression in CKD patients with metabolic acidosis characterized by plasma HCO3 greater than 22 but less than 24 meq/l [17▪], a range for which current guidelines do not recommend Na+-based alkali . Furthermore, increased net endogenous acid production, which is directly related to increased intake of acid-producing food components, is associated with faster nephropathy progression in patients with reduced GFR, even those whose plasma TCO2 is within normal ranges . Furthermore, increased dietary acid intake was associated with greater risk for complete kidney failure in a population study . Relatedly, oral NaHCO3 slowed nephropathy progression in CKD patients with reduced eGFR but no metabolic acidosis . These latter data suggest that patients with reduced GFR but no metabolic acidosis might nevertheless benefit from oral alkali therapy, possibly because such therapy appears to reduce underlying acid retention associated with reduced GFR, even without metabolic acidosis . Further studies will be needed to clarify the proper role for oral Na+-based alkali therapy in patients with CKD.
Dietary H+ reduction can be accomplished by adding oral alkali (typically Na+-based like NaHCO3 or Na+ citrate), by reducing the amount of dietary proteins in the diets typical of industrialized societies that when metabolized yield H+ (mostly animal-sourced protein), and/or by adding dietary proteins that when metabolized yield base (mostly plant-sourced protein such as fruits and vegetables). Dietary acid reduction with oral alkali appears to slow nephropathy progression as described [15,16,17▪]. In the largest randomized control trial to date, reduction of protein intake typical of diets in industrialized societies did not slow nephropathy progression . On the contrary, dietary acid reduction done by adding base-producing fruits and vegetables reduced uric acid excretion [17▪,18,20], improved metabolic acidosis [17▪,20], and slowed the rate of eGFR decline [17▪]. Together, these data support that of the three interventions, the two that not only improve metabolic acidosis and slow nephropathy progression in CKD patients with reduced GFR are dietary acid reduction done with either Na+-based alkali or addition of base-producing, plant-sourced foods. Each strategy for dietary H+ reduction is relatively inexpensive and well tolerated. Dietary acid reduction done with plant-sourced dietary protein has additional advantages as will be discussed subsequently.
The mechanism(s) by which metabolic acidosis exacerbates GFR decline in CKD are not clear but animal studies support contributions from increased ammoniogenesis in the proximal tubule , increased activity of endothelin [41–43], aldosterone , and angiotensin II [44,45] which mediate tubulointerstitial injury. Dietary H+ reduction with oral alkali [40,42,43,45] or base-producing dietary protein [41,42] slows nephropathy progression in animal models of CKD.
DIETARY MODIFICATION OF SODIUM INTAKE
Dietary sodium reduction to 2.3 g/day (100 mmol/day) is recommended based on the Dietary Approaches to Stop Hypertension and Dietary Approaches to Stop Hypertension-sodium diets
CVD remains the leading cause of mortality in CKD  and its risk increases as eGFR declines [24▪,46]. Dietary sodium restriction falls right in the center of this ongoing debate of ‘How much salt is too much and what level of restriction is needed?’. Adults in the USA consume an average of 3400 mg (148 mmol)  of sodium per day, far in excess of the dietary recommended guidelines. Health ABC study examined 2642 older adults aged 70 years and higher and found no association with mortality of low sodium (<1500 mg/day or 65 mmol) intake when compared with 1500–2300 mg/day = 65–100 mmol/day . Also, there was no association between dietary sodium and incident CVD or incident heart failure . Recent evidence supports a J-shaped association between dietary sodium intake and CVD mortality, indicating increased risk with both low and high sodium intakes . On the contrary, review of salt intake and kidney outcomes  showed an association of consumption of more than 4.6 g (200 mmol) of sodium per day with adverse outcomes and higher blood pressure. In the first double-blind randomized controlled trial assessing the impact of sodium restriction on extracellular volume, blood pressure, and proteinuria, in CKD, higher sodium intake induced a greater increase in each parameter and sodium restriction induced a greater decrease in each parameter in CKD patients compared with patients without CKD, suggesting a salt sensitivity of the CKD patients . Because blood pressure control appears to be kidney protective , dietary sodium restriction might be kidney protective through lowering blood pressure. The Institute of Medicine in its report stated that ‘excess’ sodium is harmful, but did not identify any target range or healthy level of sodium . Because sodium reduction in most populations is associated with decreased CKD and CVD disease progression , some level of dietary sodium restriction below current dietary intake appears reasonable but there are not enough data to determine the optimal level of dietary intake to recommend. The Kidney Disease Improvement for Global Outcomes  recommendation (3.1.19) is to lower daily sodium intake to less than 90 mmol (<2 g) in adults, unless otherwise contraindicated. Even though this recommendation is of ‘1 C’ quality (i.e., most clinicians would agree but the true effect may be substantially different from the estimated effect), it seems reasonable until more definitive studies determine a more specific level of dietary sodium restriction for CKD patients.
DIETARY MODIFICATION OF PHOSPHORUS INTAKE
Current guidelines recommend daily phosphorus restriction to 800–1000 mg/day in advanced chronic kidney disease
Patients with advanced CKD are in positive phosphorus balance, but phosphorus levels are maintained in the normal range until advanced CKD stages through phosphaturia induced by increases in fibroblast growth factor(FGF)-23 and parathyroid hormone . Phosphorus metabolism has been linked to increase CVD, vascular calcifications, and morbidity associated with CKD . The role of dietary control of phosphate consumption has again brought into focus the benefit imparted by plant-based diets. Moe and Asplin  showed that 1 week of a 100% vegetarian diet in comparison with a meat protein (animal-sourced) based diet led to lower serum phosphorus levels and decreased Fibroblast Growth Factor (FGF)23 levels. However, the authors recently reported the benefits of a 70% plant-based protein diet  in reducing urinary phosphorus excretion and potentially reducing the phosphate-binding pill burden in the advanced CKD patients. This once again supports that emphasis on dietary protein recommendations for patients with CKD be upon a greater proportion of plant-sourced than animal-sourced protein, assuming these patients can safely tolerate the higher potassium intake associated with plant-sourced protein.
An emerging area of interest highlights the so-called kidney–gut axis as our present day diet of industrialized societies drives a milieu of metabolic abnormalities including uremic toxin production, inflammation, and immunosuppression that ultimately promotes progressive kidney failure and CVD. Patients with advanced CKD appear to have ‘leaky gut’ with translocation of endotoxins and bacterial DNA with downstream consequences of increased inflammation and increased CVD morbidity. This discovery of the kidney–gut axis has created new therapeutic opportunities for nutritional intervention with novel therapeutic strategies for targeting these pathways involving dietary plant-based protein, fiber, prebiotics, etc. These emerging nutritional interventions may ultimately lead to a paradigm shift in the conventional focus of dietary management in CKD [56,57].
CKD has staggering implications in terms of population health, CVD, and overall morbidity and mortality. Clinicians have historically focused heavily on blood pressure control, proteinuria control, lipid control, and glycemic control in diabetics mostly with medications in the management of CKD patients. On the contrary, clinicians have been less focused on dietary interventions as kidney-protection strategies, even though diet has emerged as the single largest CKD-related death and disability risk factor. Data to date support the effectiveness of added plant-sourced protein to diets of CKD patients that accomplishes many interventions shown to be kidney protective including blood pressure reduction and improved metabolic acidosis. It is imperative that clinicians, importantly those providing primary care, recognize the kidney protection benefits of dietary interventions for CKD patients.
The authors thank the nursing, dietary, and clerical staff of the Department of Internal Medicine at Texas Tech University Health Sciences Center and for the Academic Operations division of Baylor Scott and White Health for their assistance and to the Inside Out Community Outreach Program and Food Bank of Lubbock, Texas for making these studies possible.
Financial support and sponsorship
The research done by the authors and reported herein was supported by funds from the Larry and Jane Woirhaye Memorial Endowment in Renal Research the Texas Tech University Health Sciences Center, by the Statistics Department of Scott and White Healthcare, and by the Academic Operations Division of Baylor Scott and White Health.
Conflicts of interest
There are no conflicts of interest.
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