Dietary cation-anion balancing to control urolithiasis (Proceedings)

Due to the poor prognosis and expense associated with clinical cases of obstructive urolithiasis as well as the herd or flock implications of the disease, considerable focus should be placed on prevention. Dietary control strategies remain a mainstay of preventative efforts. Risk factors to address in dietary preventative strategies include high dietary phosphorus:calcium ratio, high dietary magnesium, low fiber content of rations, low urine output and an alkaline urine pH.

The role of urine pH in urolithiasis is well documented and various sources recommend urine pH goals of 5.5 to 6.5, based on the solubilities of the common stone compositions. Due to an ability to alter acid-base balance and body water balance, salts have been widely used and recommended for the prevention of urolithiasis. Anionic salts containing primarily chlorides have been popular and used extensively, as they reduce urine pH, increase urine output, and, ultimately prevent urolithiasis. Sodium chloride (1-4%), calcium chloride (1-2%) and ammonium chloride (0.5-2%) have been traditionally added to as percentages of rations to increase water intake and produce acidic urine, with inconsistent results.

The traditional addition of these salts as a simple percentage of the diet without consideration for the components of the total ration may lead to inconsistent and unsuccessful maintenance of low urinary pH. The concept of DCAD states that with increased cations in the diet, alkalotic tendencies will occur. Conversely, increased anions in the diet have acidifying potential. Different commercial diets are commonly formulated using various commodities and these commodities are interchanged regularly in feed preparation based on availability. If a feedstuff of a particular batch of feed is higher in cations, or anionic salts are fed in conjunction with a high-potassium forage, the DCAD of the diet will be raised and urinary acidification may not occur, despite the addition of the standard dose of anions. This one-dose-fits-all method may be the major cause of sporadic urolith formation in animals being fed anionic salts. The use of DCAD balancing for goats and urolithiasis is mentioned as a recommendation in some sources, and it is recommended that high cation-containing feedstuffs such alfalfa and molasses should be avoided.

The strong ion difference is a non-traditional approach to acid-base balance analysis formulated by Dr. Peter Stewart in the early 1980s. It counters the traditional approach, based on the Henderson-Hasselbach equation, by taking into account many factors which contribute to acid-base balance, rather than simply pH, PCO2 and HCO3-. It is quite complicated in its original form and involves seven equations that can be combined as a single, 3rd order quadratic equation that can be solved for [H+]. This is much more complex than is required in the clinical setting and for a basic understanding of the physiology.

In a biological system, electroneutrality must be maintained and there is conservation of mass. Therefore, the number of moles of cations equals the number of moles of anions and [H+] x [OH-] = 1x10-14 . Therefore, the body regulates acid and base such that when there are increased cations added to plasma, there is a compensatory increase in OH- and a decrease in H+. Conversely, when there is an increase in anions added to plasma, there is a compensatory decrease in OH- and an increase in H+.

The strong ion difference theory states that acid base balance is determined by three independent variables and two dependent variables. The independent variables are strong ion difference [SID], PCO2 and total weak acids [ATOT]. The dependent variables, which do not determine acid-base balance directly, are pH and bicarbonate. This is in contrast to the traditional approach.

The PCO2 is analogous to the respiratory component of the traditional approach and with increases in PCO2 there is respiratory acidosis and with decreases, a respiratory alkalosis.

The ATOT represents the sum of the activity of the non-volatile weak acids in solution. This includes albumin, globulin and phosphate, with albumin the being the primary contributor. Increases in albumin result in decreases in bicarbonate and increases in H+. Decreases in albumin result in increasing bicarbonate and decreasing H+.

The strong ions are primarily Na+, K+, Ca++, Mg++, Cl-, S=, P—-. They only alter the SID if they are absorbed into the systemic circulation and therefore their relative bioavailability must be considered when analyzing each ion and its effect on acid base balance. They primarily enter the gastrointestinal system, therefore making diet the primary determinant of SID. These ions are then regulated by the kidneys, being excreted and resorbed to maintain electroneutrality and conserve mass. The organic acids, such as lactate, ketoacids and volatile fatty acids, are undissociated and are quickly metabolized by the liver, resulting in a small effect on pH. The formula for the SID is, based on measured plasma levels, (Na+ + K+) – (Cl-+lactate). Additional constituents are generally not considered as they are frequently not measured or are typically inconsequential in the clinical setting. When the SID increases, there is a compensatory increase in bicarbonate and metabolic alkalosis occurs. With decreases in SID, a metabolic acidosis is created.

Dietary cation anion difference is defined as the difference between the summation of the major biologic cations and anions of a diet. It is traditionally illustrated as [(Na+K)-(C1+S)], expressed in mEq/kg, mEq/lb or mEq/100g of feed. Additional formulas have been proposed, including (Na + K + 0.15 Ca + 0.15 Mg) – (Cl + 0.20 S + 0.30 P), which accounts for additional ions and their relative bioavailability.

The DCAD has traditionally been controlled by adding physiologic anions, generally chlorides and sulfates, to a ration. As stated in the strong ion difference theory, this addition of anions will result in an increase in extracellular hydrogen ions and induction of a metabolic acidosis. The higher the DCAD, or excess of cations, the more alkalogenic the diet. This method of ration formulation is primarily utilized for transition dairy cows as a means of prevention for milk fever. Metabolic acidosis increases the available extracellular pool of calcium by improving the activity of parathyroid hormone and vitamin D. This results in an increase in intestinal absorption of calcium and an increase in calcium resorption from the bone. The appropriate level of metabolic acidosis is achieved when cattle consume a diet of DCAD level -150 mEq/kg to -50 mEq/kg, which is associated with significantly decreased incidence of milk fever.

One of the problems associated with DCAD balancing is that different commercial diets are commonly formulated using various commodities and these commodities are interchanged regularly in feed preparation based on cost and availability. If a particular brand or batch of feed is higher in cations, or fed in conjunction with a high potassium forage, the DCAD of the diet will be altered and will not induce metabolic acidosis to the desired degree, rendering the preventive measure ineffective. Physiologically, the excess H+ in the extracellular fluid as a result of lower DCAD is excreted by the kidney to maintain electroneutrality, producing urine of a lower pH.

Two different studies in goats have concluded that a DCAD of 0 mEq/kg results in urine pH reduction which is consistent with stone dissolution. [Stratton-Phelps et al, 2004; Jones et al, 2009] The first of these studies utilized a commercially-available anion source, while the second used ammonium chloride salt. Jones et al, 2009 showed that this reduction in urine pH may occur as early as day 5 after diet initiation and that the pH of urine 5-7 hours after initial daily feeding best represented the daily urine pH mean, although samples 1-3 hours after feeding represented the mean 92.86% of the time. These time frames, then, should serve as guides for home monitoring of urine pH.

DCAD balancing is performed by first obtaining mineral analysis of all feedstuffs (including hay and supplemental feeds). In general, it is not believed that water sources contribute significantly to dietary mineral intake, although this may be considered. The author uses a beef cattle ration formulation program which automatically provides DCAD level of feeds (http://apps.depts.ttu.edu/afs/home/mgalyean/ - TTU Diet Formulation Spreadsheet). Within this program, a herd or flocks feeds may be added, percentages adjusted, and salts added to achieve a target DCAD.

A major concern with anionic salt supplementation, is reduced palatability and decreased feed intake. Studies in cattle and sheep have shown increased times for ration consumption and variable effects on feed intake. There is also evidence of bone loss due to long-term ingestion of acidified diets. In humans, gastrointestinal irritation is a side effect of ammonium chloride administration. For these reasons, it is important to appropriately balance DCAD, utilize other dietary modifications, and monitor urine pH to prevent both over- and under- acidification.

Additional references available upon request from Dr. Jones