*2.5. Phosphorus*

Phosphorus plays a critical role in bone formation, acid–base balance, and energy production [48]. The body's ability to maintain phosphate balance is achieved by excreting excess phosphate in the urine. As CKD progresses, declining renal function prevents the kidneys from excreting enough phosphorus needed for phosphorus homeostasis [18]. The 2020 NKF guidelines recommended CKD 1–5 and HD patients receive an intake of phosphorus that keeps serum phosphorus levels within normal ranges (3.4–4.5 mg/dL) and to restrict dietary phosphate in the case of hyperphosphatemia [18,55] (Table 2). Hyperphosphatemia may lead to critical pathogenic consequences, including renal osteodystrophy, cardiovascular and soft tissue calcification, secondary hyperthyroidism, cardiac disease, and mortality in ESRD patients [56]. Phosphorus requirements depend on the stage of renal failure combined with the consideration to not restrict phosphorus intake to the point of malnutrition, which is mainly relevant to HD patients [57]. Despite the KDOQI revision for phosphorus intake in CKD, nephrologists recommend a phosphorus restriction of 800–1000 mg/d [10]; however, adequate studies are lacking that demonstrate the efficacy of 800–1000 mg dietary phosphorus restriction and the outcomes in CKD patients [18].

The three sources of dietary phosphorus are organic phosphorus from plant foods (bioavailability 20–40%), organic phosphorus from animal protein (bioavailability 40–60%), and inorganic phosphorus found in additives and processed foods (bioavailability ≈100%) [58]. Humans lack phytase, which is the enzyme that degrades phytates in plant foods, and this is why the bioavailability is the lowest of the three sources [58]. Inorganic phosphorus (additives) is almost entirely absorbed and may add up to 1000 mg/d of phosphorus from additives alone [26]. Choosing phosphorus-containing foods lower in bioavailability and without phosphate additives is recommended [17]. A study by Moe et al. that included CKD-4 patients reported lower phosphate levels in patients fed a 7-day vegetarian diet than patients fed a 7-day animal-based diet [25]. About 100 mg of phosphorus is found in 100 mL of milk and >500 mg per 100 g of cheese; the content of phosphorus is high in dairy products [59]. One study reported higher dietary phosphorus intake and a higher phosphorus to protein ratio in HD patient's diets was associated with increased mortality risk in the preceding years, even after adjusting for phosphate binders [60]. Sources containing only organic phosphorus are more nutrient-dense than foods with phosphate additives, which are usually processed and high in sodium [30].


**Table 2.** Daily requirements for electrolytes in chronic kidney disease (CKD) patients.

\* Phosphate recommendations recently changed; previously 800 mg, ↑ increased/high, ↓: decreased/lowered.

#### *2.6. Potassium*

Potassium (K) is the most abundant intracellular ion with a concentration of about 98%; it has many biological functions such as cellular metabolism and acid–base homeostasis [69]. It is also vital for cardiac function, neural transmission, muscular contractions, and glucose metabolism [67,70]. If potassium balance is disrupted by increased serum potassium, the patient is at risk for developing hyperkalemia (Table 2). Hyperkalemia is a severe metabolic

condition that is often experienced in patients with CKD. The kidneys' ability to excrete potassium is inversely related to a GFR function [69]. Hyperkalemia alters the nervous system's function, causing electrophysiological dysfunctions [64,71], presenting clinical manifestations such as muscle weakness, paresthesia, paralysis, nausea, hypotension, cardiac arrhythmias, and cardiac arrest [67,70]. As CKD progresses, potassium levels are monitored closely; patients are advised to limit dietary potassium intake to maintain serum potassium levels within normal range (3.5–5.5 mEq/L) [17]. Potassium is rich in many foods such as vegetables, dark leafy greens, potatoes, tomatoes, fruit, coffee and tea, and citrus. CKD nutrition therapy recommends vegetables and fruits that are low in potassium and high in fiber along with [17] other nutrients, and to boil vegetables to decrease potassium concentration [17].

The ideal potassium intake is difficult to determine because of factors that influence serum potassium levels, such as medications, hydration level, acid–base status, glycemic control, adrenal function, and gastrointestinal complications [17]. It is essential to consider these factors when assessing the appropriate intake of potassium for a CKD patient, as the recommendations for potassium are individualized based on other preexisting health conditions the patient might have or be at risk for. The DASH diet is widely used as nutrition therapy for hypertension because of its effectiveness in lowering blood pressure, preventing and managing hypertension, and reducing cardiovascular risk [72]. The DASH diet may be protective against the progression of CKD, but its effectiveness in delaying the progression of the disease in CKD patients has not been established [72]. The DASH diet is high in potassium and low in sodium; it suggests four to five servings of fruits and vegetables a day, which sums up to about 4700 mg/d of potassium [72]. Studies on the DASH diet with CKD patients are scarce, and the few existing studies include CKD patients with serum potassium levels in normal range at the start of the study [62]. This is a limitation of the study for determining the efficacy of the DASH diet for CKD patients [73]. Another diet currently being studied for its benefits in CKD is the Mediterranean Diet (MedDiet). Instead of its focus being on low sodium and high potassium, it focuses on healthy fats, lean meats, and plant-based foods, which naturally offer a diet low in sodium. MedDiet studies began in the 1960s, and since then, increasing evidence supports the MediDiet to be protective against CKD and DM [51]. The MedDiet is rich in plant-based foods and low in processed and red meat [74]. It is moderate in seafood, eggs, dairy, and red wine; and olive oil is the main source of added fat [75]. Adherence to the MedDiet helps prevent and manage CVD and DM [71,76], which would in turn help prevent CKD. However, the role of the MedDiet in delaying CKD progression remains uncertain due to insufficient data on patients with pre-existing CKD or dialysis [70].

Additionally, Kalemic control is further compounded by extensive use of the renin– angiotensin–aldosterone system inhibitor (RAASI) therapy in CKD patients [77]. Development of hyperkalemia in CKD patients requires lowering the dose or discontinuation of the RAASI therapy to protect patients from developing cardiovascular events and end stage kidney disease.

The true benefit of potassium restriction in CKD is not clear, considering that a diet with a high content of potassium-rich foods, such as plant-based low-protein diets, can be as beneficial on the prognosis. Potassium levels in serum can further be improved using the new K-binders, whose benefits and efficacy are shown in randomized control trials [78,79], allowing implementing plant-based low-protein diets with lower risk of hyperkalemia. Further research investigating the effect of a low-potassium diet and the progression of renal disease are required. It is unclear whether a potassium-restricted diet can slow CKD progression; however, research shows that it may reduce all-cause mortality in CKD [79].

#### *2.7. Sodium*

Sodium overload in advanced CKD patients induces extracellular volume, which may lead to hypertension and heart failure. Hypertension is a known risk factor for the progression and mortality of CVD; however, the effect of sodium on the advancement of CKD

remains inconclusive [18]. A recent working hypothesis suggests that the accumulation of sodium in interstitial space induces inflammatory toxicity that is independent of volume, and it is mediated by immune cells [80]. Sodium accumulation in the body increases as the GFR declines over time [81].

A low sodium diet is central to the management of hydro-saline homeostasis, reducing systolic and diastolic blood pressure as well as proteinuria [82]. Nevertheless, a lowsalt diet must be carefully monitored in older patients, considering they are at higher risk for acute kidney injury and damaged renal autoregulation [51]. The efficacy of low sodium intake and the reduction in BP in hypertensive patients dates to 1948 [83,84], currently reaching a worldwide understanding of the relationship between sodium and hypertension [85,86]. Patients with hypertension have a 75% increased risk of developing CKD than normotensive individuals [83,87] and a 25% increased risk of developing a decline in GFR among pre-hypertension patients [84,87]. The McMahon et al. study assessed the effects of high- vs. low-sodium diets on BP, 24 h protein and albumin excretion, and fluid status in 20 hypertensive stage 3–4 CKD adult patients [66]. The study concluded that the low-sodium diet resulted in statistical and clinically significant declines in BP, extracellular fluid volume, albuminuria, and proteinuria in study patients [66].

Nonetheless, sodium restriction is protective for the onset of hypertension. There is plentiful and strong evidence in the efficacy to prescribing a sodium-restricted diet for disease management in CKD [85]. For CKD stages 3–5, the most recent sodium intake recommendation is a maximum of 2.3 g/d and to make sodium restriction a lifestyle for controlling fluid volume and maintaining a desirable weight for CKD 3–5D [17] (Table 2). Effective habits to reduce sodium may be achieved by identifying high-sodium foods such as processed foods, canned vegetables, pickled and fermented foods, soups, chips, salted nuts and seeds, processed foods, and restaurant items. Simple modifications such as choosing unprocessed foods, choosing frozen over canned vegetables, avoiding soups and pickled and fermented foods, choosing unsalted nuts and seeds, and requesting no additional salt when ordering out are beneficial for achieving a restricted sodium diet.
