Renal Net Acid Excretion Research Articles

On the mechanism of growth hormone-induced stimulation of renal acidification in humans: effect of dietary NaCl

Sustained administration of growth hormone (GH) to human subjects with NH(4)Cl-induced chronic metabolic acidosis (CMA) results in a large (4.5+/-0.5 mmol/l) increase in the plasma HCO(3-) concentration, as mediated by a large increase in renal net acid excretion. The renal mechanism(s) responsible for the potent stimulation of renal hydrogen ion secretion by GH remain to be elucidated. Accordingly, we have assessed the Na(+) dependence of prolonged GH-stimulated renal acidification in four normal NaCl-restricted subjects (Na(+) intake 0.3 mmol x kg(-1) x day(-1)) during CMA (4.2 mmol of NH(4)Cl x kg(-1) x day(-1) for 7 days), CMA plus GH (0.1 unit/kg every 12 h for 5 days) and then CMA plus GH plus NaCl (1.7 mmol x kg(-1) x day(-1) for 6 days). During CMA, urine Na(+) excretion averaged 22.4+/-4.1 mmol/24 h. In response to GH administration, urinary net acid excretion was essentially unchanged, and the accumulated increment over 5 days of GH treatment was not different from zero (14+/-12 mmol; not significant). The plasma HCO(3)(-) concentration increased only slightly, from 14.2+/-0.8 to 15.0+/-1.1 mmol/l (P<0.05). Despite the constraint on net acid excretion imposed by NaCl restriction, renal ammonia production increased, as suggested by increases in urine pH from 5.58+/-0.05 to 5.82+/-0.04 (P<0.005) and unchanged NH(4)(+) excretion (202+/-17 to 211+/-19 mmol/24 h; not significant). In response to dietary NaCl, urine pH decreased to 5.27+/-0.1 (P<0.001) and a large increment in net acid excretion accumulated (233+/-20 mmol; P<0.05), in association with an increase in plasma HCO(3-) to 18.7+/-1.3 mmol/l (P<0.001), a plasma HCO(3-) value similar to that reported previously in salt-replete, NH(4)Cl- fed subjects. These results demonstrate for the first time in any species that the acid excretory effect of GH administration is critically dependent on the availability of a surfeit of Na(+) for tubular reabsorption. GH and/or insulin-like growth factor-1 affect renal acid excretion proximally (by stimulation of NH(3) production) and by a Na(+)-transport-dependent mechanism in the collecting duct (voltage-driven acidification) in humans. The present results indicate that an isolated increase in renal NH(3) production is insufficient to obligate an increase in net acid excretion.

Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents

Normal adult humans eating Western diets have chronic, low-grade metabolic acidosis, the severity of which is determined in part by the net rate of endogenous noncarbonic acid production (NEAP), which varies with diet. To prevent or reverse age-related sequelae of such diet-dependent acidosis (eg, bone and muscle loss), methods are needed for estimating and regulating NEAP. Because NEAP is difficult to measure directly, we sought a simple method to estimate it from diet-composition data. We focused on protein and potassium contents because the production of sulfuric acid from protein metabolism and bicarbonate from dietary potassium salts of organic acids are the major variable components of NEAP. Using steady state renal net acid excretion (RNAE) as an index of NEAP in 141 normal subjects eating 20 different diets, we found by multiple linear regression analysis that RNAE [mEq/d x 10460 kJ diet (mEq/d 2500 kcal)] was predictable (R2 = 0.62) from protein [g/d x 10460 kJ diet (g/d 2500 kcal); positive regression coefficient, P < 0.001] and potassium [mEq/d x 10460 kJ diet (mEq/d x 2500 kcal): negative regression coefficient, P = 0.001] contents, which were not themselves correlated. Among diets, 71% of the variation in RNAE could be accounted for by the ratio of protein (Pro) to potassium (K) content: RNAE = 62Pro/K - 17.9 (r = 0.84, R2 = 0.71, P < 0.001). Thus, by considering both the acidifying effect of protein and the alkalinizing effect of potassium (organic anions), NEAP can be predicted with confidence from the readily available contents of only 2 nutrients in foods. Provisionally, these findings allow estimation and regulation of NEAP through diet modification.

Effects of a single bout of resistance exercise on calcium and bone metabolism in untrained young males.

Although resistance exercise training appears to increase bone mineral density in the long term, a single bout of resistance exercise could paradoxically induce bone homeostasis disturbance, secondary to metabolic acidosis. To examine this, we obtained fasting blood and 24-hour urine samples from untrained male subjects for 5 subsequent days (control day, exercise day, and three post-exercise days), and investigated the effects of a single bout of resistance exercise on urinary calcium excretion and bone metabolism as indicated by sensitive biomarkers of bone formation and resorption. After an intense bout of resistance exercise, blood and urine became more acidic and renal net acid excretion significantly increased by 44% on the exercise day. Urinary calcium excretion significantly increased by 48% on the exercise day. Plasma procollagen type-I C-terminal concentration significantly decreased by 12% on the next day of the exercise and serum bone-specific alkaline phosphatase activity also significantly decreased by 13% and 9% on days 2 and 3, respectively, after the exercise. There was no significant change in serum osteocalcin concentration. Serum tartrate-resistant acid phosphatase activity significantly decreased by 15% on the day after the exercise and urinary deoxypyridinoline excretion decreased by 22% and 27% on days 1 and 3, respectively, after the exercise. These results suggest that the early response of bone to a bout of resistance exercise in untrained individuals was transient decreases in bone formation and resorption, whereas urinary calcium excretion increased.

Renal acid excretion in early infancy.

In early infancy, complex disorders of acid base metabolism are more frequent than in any other age group, with a predisposition to metabolic acidosis due to an age-related low renal capacity for acid excretion and an unphysiologically high actual renal acid load in nutrition with common formulas. Recently in preterm and small-for-gestational-age infants, persistent maximum renal net acid excretion (NAE) with subnormal or normal blood acid base status, impaired weight gain, and adaptive hormonal reactions have been observed. Incipient late metabolic acidosis is one example of a mixed disorder of acid base metabolism with maximum renal NAE in early infancy. Alkali therapy is highly effective and can be realized both on an individual basis, using urine pH screening as a diagnostic criterium for maximum renal acid stimulation, or on a general preventive level using modified standard formula with a reduced actual renal NAE similar to that seen on alimentation with human milk. From an integrated point of view, the low glomerular filtration rate and renal capacity for acid excretion beyond the developmental age of more than 44 weeks, may well be interpreted as the result of a specific adaptation to breast feeding sparing energy, and thus an evolutionary advantage for the survival of mother and child.

Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline.

In 64 apparently healthy adult humans (ages 17-74 yr) ingesting controlled diets, we investigated the separate and combined effects of age, glomerular filtration rate (GFR, index of age-related renal functional decline), renal net acid excretion [NAE, index of endogenous acid production (EAP)], and blood PCO2 (PbCO2, index of respiratory set point) on steady-state blood hydrogen ion ([H+]b) and plasma bicarbonate concentration ([HCO3-]p). Independent predictors of [H+]b and [HCO3-]p were PbCO2, NAE, and either age or GFR, but not both, because the two were highly correlated (inversely). [H+]b increased with increasing PbCO2, NAE, and age and with decreasing GFR. [HCO3-]p decreased with increasing NAE and age but increased with increasing PbCO2 and GFR. Age (or GFR) at constant NAE had greater effect on both [H+]b and [HCO3-]p than did NAE at constant age (or GFR). Neither PbCO2 nor NAE correlated with age or GFR. Thus two metabolic factors, diet-dependent EAP and age (or GFR), operate independently to determine blood acid-base composition in adult humans. Otherwise healthy adults manifest a low-grade diet-dependent metabolic acidosis, the severity of which increases with age at constant EAP, apparently due in part to the normal age-related decline of renal function.

Dietary protein as a modulator of the renal net acid excretion capacity: Evidence that an increased protein intake improves the capability of the kidney to excrete ammonium

To test the hypothesis that increments in protein intake increase the capacity of the kidney to excrete ammonium (NH4+), two strictly controlled diet studies (both repeated-measures design with n = 6 healthy adult subjects) were performed. In study I, comprising two 5-day diet periods (A and B, protein intake: 120 and 95 g/day, respectively), the urine pH was adjusted to a low pH level by administration of L-methionine (20 mmol/day) along with diet B. In study II, comprising three 4-day diet periods (C1–C3: C1, basic diet containing 50 g protein/day; C2, basic diet + 32 g of egg white protein/day; C3, basic diet + 10 mmol L-methionine/day), the urine pH was adjusted to a high pH level by sodium citrate (6.67 mmol/day) administered with diets C2 and C3. Urine pH constancy, which guarantees a constant tubular NH4+ transfer, was achieved for either study (diets A, B: 5.5 ± 0.2, 5.4 ± 0.2; diets C1, C2, C3: 6.7 ± 0.1, 6.8 ± 0.1, 6.7 ± 0.1), thus allowing assessment of urinary NH4+ excretion rates as an index of the renal NH4+ production capacity. With the higher protein intake on diet A compared with diet B, a significantly elevated NH4+ excretion (82.8 ± 11.4 vs. 73.6 ± 7.2 mmol/day; P < 0.01) was observed. NH4+ excretion also increased from 29.4 ± 5.5 mmollday (C1) to 34.8 ± 5.1 mmollday (C2) in study II (P < 0.05) after the protein intake was raised with egg protein. When methionine was administered instead of egg protein as a different source of sulfur (C3), no effect on renal NH4+ output occurred, thus demonstrating that protein as a whole has a specific impact. It is concluded that the renal capacity to excrete excess acidity as NH4+ is modulated (independently of the underlying level of the respective renal acid load) by the amount of protein ingested.

Potential Renal Acid Load of Foods and its Influence on Urine pH

The purpose of this study was to calculate the potential renal acid load (PRAL) of selected, frequently consumed foods. A physiologically based calculation model was recently validated to yield an appropriate estimate of renal net acid excretion (NAE); the model depends primarily on nutrient intake data. When nutrient data from actual food composition tables were used, the calculation model yielded PRAL values that ranged from an average maximum of 23.6 mEq/100 g for certain hard cheeses over 0 mEq/100 g for fats and oils to an average minimum of approximately −3 mEq/100 g for fruits and fruit juices and vegetables. By means of these PRAL data (summed according to the amounts of foods and beverages consumed daily and by an estimate of excretion of organic acids [based on body size]), the daily NAE can be calculated. This calculation methodology, primarily based on PRAL, allows an appropriate prediction of the effects of diet on the acidity of urine. For practical applicability in dietetic prevention of recurrent urolithiasis or in other fields of dietetics, the additionally determined correlation ( r=.83; P<.001) between NAE and urine pH can be used to ascertain NAE target values for a desired urine pH modification. J Am Diet Assoc. 1995; 95:791-797.

Effects of a high protein intake on renal acid excretion in bodybuilders

Bodybuilders often prefer a high protein diet to achieve maximum skeletal muscle hypertrophy. In this study the effect of a high protein diet on renal acid load and renal handling of proton excretion was studied comparing dietary intake and urinary ionograms in 37 male bodybuilders and 20 young male adults. Energy intake (+ 7%), protein intake (128 vs 88 g/d/1.73 m2), and renal net acid excretion (95 vs 64 mmol/d/1.73 m2) were higher in the bodybuilders than in the controls, however, urine-pH was only slightly lower (5.83 vs 6.12). In the bodybuilders renal ammonium excretion was higher at any given value of urine pH than in the controls. In a regression analysis protein intake proved to be an independent factor modulating the ratio between urine-pH and renal ammonium excretion. The concomitant increase of renal net acid excretion and maximum renal acid excretion capacity in periods of high protein intake appears to be a highly effective response of the kidney to a specific food intake leaving a large renal surplus capacity for an additional renal acid load.

Acid-base status and intracellular pH regulation in lymphocytes from rats with genetic hypertension.

This article reviews work from this laboratory dealing with acid-base status and intracellular pH (pHi) regulation in rat genetic models of hypertension. With freshly isolated thymic lymphocytes, pHi and its regulation were examined in the spontaneously hypertensive rat (SHR). In this rat model, pHi was found to be reduced as compared with that of lymphocytes from normotensive Wistar-Kyoto (WKY) rats. The activity of the Na+/H+ antiporter assessed after stimulation by acute cell acidification was similar in lymphocytes from SHR and WKY rats both in the nominal absence of HCO3- and in media containing HCO3- (22 mM). The kinetic properties of the Na+/H+ antiporter, examined as a function of pHi with the Hill kinetic model, revealed no significant differences between lymphocytes from SHR and WKY rats. The kinetic properties of the Na(+)-dependent and Na(+)-independent Cl(-)-HCO3- exchangers, examined as a function of external Cl-, were also virtually identical in lymphocytes from SHR and WKY rats. Unlike the Na(+)-H+ exchanger and the Na(+)-independent Cl(-)-HCO3- exchanger, which had their highest activities at extremes of pHi (low pHi, Na(+)-H+ exchanger; high pHi, Na(+)-independent Cl(-)-HCO3- exchanger), the Na(+)-dependent Cl(-)-HCO3- exchanger had its maximal activity near steady-state pHi. In Dahl/Rapp salt-sensitive rats with hypertension, the pHi of thymic lymphocytes was also reduced as compared with that of normotensive salt-resistant animals. In this model, renal net acid excretion in salt-sensitive rats was augmented as compared with that of salt-resistant rats. The increase in renal acid excretion was due to an increase in both ammonium and titratable acid excretion and was observed while animals were placed on high, normal and low salt diets. The findings of intracellular acidosis and enhanced renal acid excretion suggest that cellular acid overproduction is augmented in salt-sensitive hypertension.

Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein

The object of this study was to determine whether it is possible to reliably estimate the renal net acid excretion (NAE) produced by adults consuming different amounts of dietary protein. A physiologically based calculation model that corrects for intestinal absorption of minerals and sulfur-containing protein and assumes a rate of urinary excretion of organic acids proportional to body surface area was used to estimate NAE. Urinary excretion of different minerals and NAE was measured during the last 48 h of each of four separate 5-d diet periods in six healthy adults. On the basis of food tables, the four nearly isoenergetic diets (one lacto-vegetarian and one high- and two moderate-protein diets) were estimated to yield the following NAE values: 3.7, 117.5, 62.2, and 102.2 mEq/d, respectively. The analytically determined urinary NAE (24.1 +/- 10.7, 135.5 +/- 16.4, 69.7 +/- 21.4, and 112.6 +/- 10.9 mEq/d) corresponded reasonably well to these estimates, suggesting that the calculation model is appropriate to predict the renal NAE from nutrient intake and anthropometric data.

Low renal net acid excretion, high calciuria and biochemical signs of sodium deficiency in low-birth-weight infants fed a new low-phosphorus formula.

In 11 infants (birth weight greater than 1800 g) fed a new type of humanized formula with a low phosphorus (P) content (calcium (Ca) 11 mmol/l, P 7.2 mmol/l, sodium (Na) 8.3 mmol/l) biochemical parameters of blood, serum and urine were determined. In nine boys Ca and P balances were evaluated also. Renal net acid excretion was low (0.85 mmol/kg/day). Mean concentrations of P and Ca in urine were 0.34 mmol/kg/day (10.5 mg/kg/day) and 0.1 mmol/kg/day (4 mg/kg/day), respectively. In four infants, Ca concentration in urine was, however, greater than 0.15 mmol/kg/day) (6 mg/kg/day). In infants with birth weights greater than 1800 g fed the new, low-P formula, the low renal net acid excretion, the normal P and the high Ca concentrations in urine were comparable to term infants fed human milk. The high calciuria in several infants may be normal physiologic values. However, it remains to be established that the urinary solubility product of infants fed the new, low-P formula is in the same range as those for infants fed human milk. Unexpectedly, low urinary Na excretion (0.26 mmol/kg/day) and increased urinary excretion of aldosterone-18-glucuronide indicated biochemical evidence of Na deficiency secondary to low Na intake and a high weight gain. If the new, low-P formula is to be fed to infants with a birth weight as low as 1800 g. Na content should be higher than in mature human milk because of the often relatively higher weight gain.

Renal net acid and electrolyte excretion in an experimental model of hypochloremic metabolic alkalosis in sheep

SUMMARY Renal electrolyte and net acid excretion were characterized during generation and maintenance of hypochloremic metabolic alkalosis in a ruminant model. Two phases of renal response with regard to sodium and net acid excretion were documented. An initial decrease in net acid excretion was attributable to increase in bicarbonate excretion with associated increase in sodium excretion. As the metabolic disturbance became more advanced, a second phase of renal excretion was observed in which sodium and bicarbonate excretion were markedly decreased, leading to increase in net acid excretion and development of aciduria. Throughout the metabolic disturbance, chloride excretion was markedly decreased; potassium excretion also decreased. These changes were accompanied by increase in plasma renin and aldosterone concentrations. There was apparent failure to concentrate the urine optimally during the course of the metabolic disturbance, despite increasing plasma concentration of antidiuretic hormone.

Effect of Calcium Supplementation on Calcium and Phosphorus Balance and Renal Net Acid Excretion in Preterm Infants Fed a Standard Formula

In 19 preterm infants fed a standard formula for prematures (calcium (Ca) 13.5 mmol/l; phosphorus (P) 12.9 mmol/l), biochemical parameters of blood, serum and urine were determined before and during supplementation with Ca-L-lactate (final Ca concentration 20 mmol/l). In 8 preterm boys Ca and P balance were evaluated in addition. During Ca supplementation, the serum Ca levels, urine pH (without supplement 6.31, with supplement 6.73), and calciuria (46 mumol/kg/d vs. 98 mumol/kg/d) were increased, and urinary P (1.05 mmol/kg/d vs. 0.65 mmol/kg/d) and net acid excretion (1.70 mEq/kg/d vs. 0.89 mEq/kg/d) were decreased. Balance studies showed increased net intestinal Ca absorption during supplementation (37% vs. 56%) as well as improved Ca (0.8 mmol/kg/d vs. 1.85 mmol/kg/d) and P retention (0.97 mmol/kg/d vs. 1.45 mmol/kg/d). These data show that increased Ca intake given to optimize the Ca:P ratio improves mineral retention in preterm infants fed a standard formula. Ca and P intake should be thoroughly balanced to avoid side-effects like hypercalciuria or high renal net acid excretion.

Effects of Two Levels of Intake of Chloride, Potassium, and Calcium on Mineral and Acid‐Base Metabolism in Premature Infants

SummaryGrowth (weight, length, mid‐upper arm circumference), acid‐base status, serum electrolyte levels, and selected parameters of urine (creatinine and electrolyte levels, urine pH, renal net acid excretion, levels of metabolites of aldosterone) were determined serially from the 10th to the 32nd days for 4 weeks in 21 premature infants (birth weight, 1,100–2,000 g) fed either formula A or formula B (formula B was formula A supplemented with chloride, potassium, and calcium). Premature infants fed formula B showed a higher weight gain (31 versus 28.2 g/day), a higher increment of middle‐upper arm circumference (0.31 versus 0.24 cm/week), and a decreased renal net acid excretion (1.24 versus 1.92 mEq/ kg/day). Almost all premature infants fed formula A and some with a high growth rate receiving formula B showed hypochloruria corresponding to chloride deficiency. Premature infants fed unsupplemented humanized formulas may have an inadequate intake of minerals.

Effects of two levels of intake of chloride, potassium, and calcium on mineral and acid-base metabolism in premature infants.

Growth (weight, length, mid-upper arm circumference), acid-base status, serum electrolyte levels, and selected parameters of urine (creatinine and electrolyte levels, urine pH, renal net acid excretion, levels of metabolites of aldosterone) were determined serially from the 10th to the 32nd days for 4 weeks in 21 premature infants (birth weight, 1,100-2,000 g) fed either formula A or formula B (formula B was formula A supplemented with chloride, potassium, and calcium). Premature infants fed formula B showed a higher weight gain (31 versus 28.2 g/day), a higher increment of middle-upper arm circumference (0.31 versus 0.24 cm/week), and a decreased renal net acid excretion (1.24 versus 1.92 mEq/kg/day). Almost all premature infants fed formula A and some with a high growth rate receiving formula B showed hypochloruria corresponding to chloride deficiency. Premature infants fed unsupplemented humanized formulas may have an inadequate intake of minerals.

Dietary NaCl determines severity of potassium depletion–induced metabolic alkalosis

It is uncertain whether, in humans, potassium depletion can cause or sustain metabolic alkalosis of clinically important degree in the absence of coexisting known alkalosis-producing conditions. Previously we found, in normal humans ingesting abundant NaCl, that dietary K+ depletion alone can induce and sustain a small decrease in blood acidity and increase in plasma bicarbonate concentration; we hypothesized that more severe alkalosis was prevented by mitigating mechanisms initiated by renal retention of dietary NaCl that was induced by K+ depletion. To ascertain the acid-base response to dietary K+ depletion under conditions in which the availability of NaCl for retention is greatly limited, in the present study of six normal men we restricted dietary K+ as in the previous study except that intake of NaCl was maintained low (2 to 7 mEq/day, Low NaCl Group) instead of high (126 mEq/day, High NaCl Group). Plasma acid-base composition and renal net-acid excretion (NAE) did not differ significantly between groups during the control period. In the steady state of K+ depletion (days 11 to 15 of K+ restriction), neither plasma K+ concentration (2.9 +/- 0.9 mEq/liter vs. 3.0 +/- 0.1 mEq/liter) nor cumulative K+ deficit (399 +/- 59 mEq vs. 466 +/- 48 mEq) differed significantly between groups. During K+ restriction, persisting metabolic alkalosis developed in both groups, which was more severe in the Low NaCl Group: increment in [HCO3-]p, 7.5 +/- 1.0 mEq/liter versus 2.0 +/- 0.3 mEq/liter, P less than 0.001; decrement in [H+]p, 5.5 +/- 0.6 nEq/liter versus 2.9 +/- 0.4 nEq/liter, P less than 0.003. A significantly more severe alkalosis in the Low NaCl Group was evident at all degrees of K+ deficiency achieved during the course of the 15 days of K+ restriction, and the severity of alkalosis in the Low NaCl Group correlated with the degree of K+ deficiency. During the generation of alkalosis (days 1 to 7 of K+ restriction), NAE increased in the Low NaCl Group whereas it decreased in the High NaCl Group. During the maintenance of alkalosis (days 11 to 15), NAE stabilized in both groups after it returned to values approximating the control values. In both groups, urine Cl- excretion decreased during K+ restriction even though Cl- intake had not been changed, with the result that body Cl- content increased negligibly in the Low NaCl Group (28 +/- 6 mEq) and substantially in the High NaCl Group (355 +/- 64 mEq).(ABSTRACT TRUNCATED AT 400 WORDS)

The importance of renal net acid excretion as a determinant of fasting urinary calcium excretion

To evaluate the effects of changing rates of fixed acid production on fasting urine Ca/creatinine, we studied five healthy men fed constant diets during control conditions (serum HCO3 27.3 +/- 2.6 SD mEq/liter and blood H+ 40.4 +/- 1.5 microEq/liter) and then during the administration of NH4Cl 3.0 mEq/kg/day (serum HCO3 22.5 +/- 4.9 mEq/liter; P less than 0.025, and H+ 46.8 +/- 2.3 mEq/liter; P less than 0.005). In addition to the expected increase in daily urinary Ca excretion from 5.2 +/- 2.0 to 12.5 +/- 3.0 mmole/day; P less than 0.001 as daily urinary net acid excretion was increased from 48 +/- 32 to 257 +/- 33 mEq/day; P less than 0.001 we observed that fasting urinary net acid/creatinine excretion also increased from 2.9 +/- 1.2 to 11.1 +/- 1.2 mEq/mmole creatinine; P less than 0.001 and fasting urine Ca/creatinine increased from 0.158 +/- 0.111 to 0.456 +/- 0.109 mmole/mmole creatinine; P less than 0.005. The additional Ca appearing in the urine during acidosis ultimately reflected augmented net bone resorption since daily urinary hydroxyproline excretion was increased from 0.232 +/- 0.062 to 0.377 +/- 0.108 mmole/day; P less than 0.01. Since variations in diet composition can cause fixed acid production and thus renal net acid excretion to vary from about zero to 200 mEq/day, such a range could cause fasting Ca/creatinine to vary from 0.09 to 0.37 mmole/mmole (0.03 to 0.13 mg/mg) and should be taken into account in the evaluation of fasting Ca/creatinine.

Nutrition support of inborn errors of amino acid metabolism

Programs for nutrition support of patients with phenylketonuria, maternal phenylketonuria, branched chain ketoaciduria and vitamin B-6 non-responsive homocystinuria were written in BASIC. These programs plan diets to fill diet prescriptions using natural foods, available amino acid-free or restricted elemental products, milk or infant proprietary formulae and protein-free fat and carbohydrate sources. Emphasis is placed on satisfying the amino acid and protein prescriptions simultaneously. The final semisynthetic formula is evaluated for vitamins, minerals, renal solute load and renal net acid excretion. Fluid requirement is estimated. The paper describes how the conventional protocols are enhanced by computerization and details the requisite calculations.

Hypophosphaturia impairs the renal defense against metabolic acidosis

It is known that Pi normally provides the major source of non-NH3 urinary buffer and that Pi-buffered renal H+ excretion (titratable acidity, TA) accounts for a large fraction of daily renal net acid excretion (NAE). Whether the presence of luminal non-NH3 buffers is a prerequisite to normal renal regulation of systemic acid-base equilibrium under any conditions has not been investigated. Accordingly, I investigated whether chronic renal regulation of plasma (p) [HCO3] might be impaired under conditions of normophosphatemic hypophosphaturia (NHP) produced by short-term dietary Pi restriction. During a steady-state of HCl-induced acidosis in NaCl-replete NHP dogs (group 1A, N = 6), [HCO3-]p averaged 14.1 +/- 0.6 mEq/liter and arterial (a) [H+] averaged 54 +/- 2 nEq/liter. Substitution K+ 2.5 mEq/kg as neutral Pi for equivalent dietary KCl for 7 to 8 days resulted in significant amelioration of acidosis (delta [HCO3-]p + 2.2 +/- 0.5 mEq/liter, P less than 0.01; delta [H+]a -6 +/- 2 nEq/liter, P less than 0.01) in association with a cumulative increment (sigma delta) in TA excretion (+ 103 mEq, P less than 0.001) and NAE (+ 22 mEq). To investigate whether Pi-induced amelioration of acidosis was related to enhanced urinary buffer capacity, an additional group (group 1B, N = 5) with NHP and chronic HCl acidosis was administered the non-Pi buffer, neutral creatinine (5.0 mmoles/kg daily). As with Pi, acidosis was ameliorated by creatinine administration and sigma delta NAE increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of diet on plasma acid-base composition in normal humans

AbstractEffect of diet on plasma acid-base composition in normal humans. Steady-state plasma and urine acid-base composition was assessed in 19 studies of 16 normal subjects who ingested constant amounts of one of three diets that resulted in different rates of endogenous noncarbonic acid production (EAP) within the normal range. Renal net acid excretion (NAE) was used to quantify EAP since the two variables are positively correlated in normal subjects. A significant positive correlation was observed between plasma [H+] and plasma PCO2, and between plasma [HCO3-] and plasma PCO2, among the subjects. Multiple correlation analysis revealed a significant interrelationship among plasma [H+], plasma PCO2, and NAE (r = 0.71, P < 0.001), and among plasma [HCO3-], plasma PCO2, and NAE (r = 0.77, P < 0.001). The partial correlation coefficients indicated a significant positive correlation between plasma [H+] and NAE, and a significant negative correlation between plasma [HCO3-] and NAE, when plasma PCO2 was held constant. These findings indicate that two factors influence the level at which plasma [H+] is maintained in normal subjects: (1) the steadystate rate of endogenous noncarbonic acid production, and (2) the setpoint at which plasma PCO2 is regulated by the respiratory system. Plasma [HCO3-] is also co-determined by these two factors. In disease states, therefore, both factors must be known before a disturbance in acid-base homeostasis can be excluded.Effet du régime sur la composition acido-basique plasmatique chez des sujets humains normaux. La composition acido-basique plasmatique et urinaire à l'équilibre a été déterminée dans 19 études de 16 sujets normaux qui ingéraient des quantités constantes de l'un de trois régimes aboutissant à différents taux de production endogène d'acides non carboniques (EAP) à l'intérieur de la normale. L'excrétion rénale nette d'acides (NAE) a été utilisée pour quantifier l'EAP puisque les deux variables sont positivement corrélées chez des sujets normaux. Une corrélation significative positive a été observée entre le [H+] plasmatique et la PCO2 plasmatique, et entre le [HCO3-] plasmatique et PCO2 plasmatique, parmi ces sujets. Une analyse par corrélations multiples a révélé une interrelation significative entre [H+] plasmatique, PCO2 plasmatique et NAE (r = 0,71, P < 0,001), et entre [HCO3-] plasmatique, PCO2 plasmatique et NAE (r = 0,77, P < 0,001). Les coefficients de corrélation partielle ont indiqué une corrélation significative positive entre [H+] plasmatique et NAE, et une corrélation significative négative entre [HCO3-] plasmatique et NAE, lorsque PCO2 plasmatique était maintenue constante. Ces résultats indiquent que deux facteurs influencent le niveau auqeal [H+] plasmatique est maintenu chez des sujets normaux: (1) le taux de production à l'équilibre d'acides non carboniques endogènes, et (2) le point d'équilibre auquel PCO2 plasmatique est régulée par le système respiratoire. [HCO3-] plasmatique est également codéterminé par ces deux facteurs. Ainsi, dans les états pathologiques, les deux facteurs doivent être connus avant de pouvoir exclure une perturbation de l'homéostasie acido-basique.