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BACKGROUND & AIMS: Acid-base disturbances are common in short bowel (SB) patients due to increased intestinal bicarbonate loss. However, the resulting systemic acid load has not been quantified. Base excess is used to monitor metabolic acid-base disturbances but inadequately reflects the acid load. Our aim was to investigate the systemic acid/base load in SB-patients to obtain quantitative estimates to guide the composition of parenteral support. METHODS: We calculated total acid load in SB patients by summing 24-h urinary net acid excretion (NAE) and the provision of base equivalents in parenteral support. We then compared differences among anatomical SB-types: jejunostomy (SB-J), jejunocolostomy (SB-JC), and jejunoileostomy (SB-JIC). 47 urine samples from 34 SB patients were analyzed for bicarbonate (HCO3-), ammonium (NH4+), and titratable acid (TA) concentrations. NAE was calculated as (TA + NH4+) - HCO3-. Mixed-effects repeated-measures models were used to statistically examine differences between SB-types and associations with parenteral nutrition and NAE. A healthy cohort served as control. RESULTS: In comparison to SB-J, SB-JC patients had a 4.1 mmoL/l lower base excess (95% CI: -6.3 to -1.8) and an 84.5 mmol/day higher total acid load (CI: 41.3 to 127.7). There were no significant differences between SB-JIC and SB-J regarding base excess, NAE, or total acid load. Higher amounts of infused acetate, sodium, and chloride, but not the acetate/chloride ratio, were associated with lower NAE and higher base excess. CONCLUSIONS: Due to increased colonic bicarbonate loss, patients with SB-JC have a ∼4.4-fold higher acid load than healthy controls. The ion transport mechanisms mediating this bicarbonate loss from the remaining colon need further experimental investigation. NAE could be a useful tool to adjust base infusion in SB.

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OBJECTIVES: We tested whether 100 g/day of dried fruit (vs. no supplemental fruit control) for 6 months alters 24-hr urinary net acid excretion (NAE), bone resorption, weight, body composition, muscle performance, and diet quality. We explored consistency of self-selected dietary composition and potential renal acid load (PRAL). METHODS: This randomized, single-blind, 2-armed study included 83 normal- and over-weight men and postmenopausal women (age ≥50 years) on self-reported low fruit diets. Endpoints included group differences in NAE (primary), 24-hr urinary N-telopeptide (NTX), weight, body composition, muscle performance, and diet quality. RESULTS: At baseline, mean (±SD) age was 69 ± 8 years; 86% were Caucasian; body mass index was 24.5 ± 2.8 kg/m2; 46% female, and NAE was 32.4 ± 23.1 mmol with no significant baseline group differences. No significant group differences were noted in NAE (primary), NTX, weight, body composition, muscle performance or diet quality at 6 months. In the cohort as a whole, 6-month change in NAE was positively associated with change in NTX, but no significant associations were noted in other outcomes. PRAL on the day of the urine collection was positively associated with NAE. Comparison of two consecutive baseline 24-hr diet recalls revealed wide intra-individual variability in PRAL in self-selected diets in our participants. CONCLUSION: In this field study of older adults consuming self-selected diets, making one change to the diet by adding 100 g/day of dried fruit (equivalent to 4 servings per day) had no significant impact on NAE when compared to a no supplemental fruit control. This null finding may be attributable to the high day-to-day variability in consumption of foods affecting NAE. Added fruit also had no significant effect on weight, fat, muscle, or bone outcomes over a 6-month period.

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Eating a net acid-producing diet can produce an "acid stress" of severity proportional to the diet net acid load, as indexed by the steady-state renal net acid excretion rate. Depending on how much acid or base is ingested or produced from endogenous metabolic processes and how well our homeostatic mechanisms can buffer or eliminate the additional acids or bases, we can alter our systemic acid-base balance. With increasing age, the kidney's ability to excrete daily net acid loads declines (a condition similar to that of mild CKD), invoking increased utilization of potential base stores (eg, bone, skeletal muscle) on a daily basis to mitigate the acid accumulation, thereby contributing to development of osteoporosis, loss of muscle mass, and age-related renal insufficiency. Patients suffering from more advanced CKD often present with more severe acid stress or metabolic acidosis, as the kidney can no longer excrete the entire acid load. Alkaline diets based on fruits and vegetables may have a positive effect on long-term preservation of renal function while maintaining nutritional status. This chapter discusses the biochemistry of dietary precursors that affect acid or base production.

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Ammonium is a major urinary buffer that is necessary for the normal excretion of the daily acid load. Its urinary rate of excretion (UNH4) may be increased several fold in the presence of extrarenal metabolic acidosis. Therefore, measurement of UNH4 can provide important clues about causes of metabolic acidosis. Because UNH4 is not commonly measured in clinical laboratories, the urinary anion gap (UAG) was proposed as its surrogate about 4 decades ago, and it is still frequently used for that purpose. Several published studies strongly suggest that UAG is not a good index of UNH4 and support the concept that direct measurement of UNH4 is an important parameter to define in clinical nephrology. Low UNH4 levels have recently been found to be associated with a higher risk of metabolic acidosis, loss of kidney function, and death in persons with chronic kidney disease, while surrogates like the UAG do not recapitulate this risk. In order to advance the field it is necessary for the medical community to become more familiar with UNH4 levels in a variety of clinical settings. Herein, we review the literature, searching for available data on UNH4 under normal and various pathological conditions, in an attempt to establish reference values to interpret UNH4 results if and when UNH4 measurements become available as a routine clinical test. In addition, we present original data in 2 large populations that provide further evidence that the UAG is not a good predictor of UNH4. Measurement of urine NH4 holds promise to aid clinicians in the care of patients, and we encourage further research to determine its best diagnostic usage.

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Models of acid-base balance include acid production from (1) oxidation of sulfur atoms on amino acids and (2) metabolically produced organic acid anions. Acid load is balanced by alkali from metabolism of GI anions; thus, net acid production is equivalent to the sum of urine sulfate and organic anion (measured by titration in urine), minus GI anion. However, the relative contributions of these three sources of acid production in people eating free choice diets, and presumably in acid-base balance, have not been well studied. We collected 26 urines from 18 normal subjects (10 male) and 43 urine samples from 34 stone formers (17 male) and measured sulfate, organic anion, and components of GI anion and acid excretion in each; values were expressed as mEq/mmol creatinine. Mean values of the urine components, except creatinine and pH, did not differ between the sexes or groups. Urine organic acid and acid production varied directly with age (p ≤ 0.03). In a general linear model of acid excretion, the coefficients for sulfate, organic anion, and GI anion were 0.34 ± 0.09, 0.49 ± 0.12, and -0.51 ± 0.06, respectively, p ≤ 0.005, and the model accounted for 54% of the variance. A model for urine ammonia gave similar results. Urine organic anion is a significant contributor to total acid production and may be responsible for an increase in acid production with age.

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RATIONALE & OBJECTIVE: Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This study compared NAE in participants with and without CKD, as well as the NAE, blood pressure (BP), and metabolomic response to bicarbonate supplementation. STUDY DESIGN: Randomized order, cross-over study with controlled feeding. SETTING & PARTICIPANTS: Participants consisted of 8 patients with CKD (estimated glomerular filtration rate 30-59mL/min/1.73m2 or 60-70mL/min/1.73m2 with albuminuria) and 6 patients without CKD. All participants had baseline serum bicarbonate concentrations between 20 and 28 mEq/L; they did not have diabetes mellitus and did not use alkali supplements at baseline. INTERVENTION: Participants were fed a fixed-acid-load diet with bicarbonate supplementation (7 days) and with sodium chloride control (7 days) in a randomized order, cross-over fashion. OUTCOMES: Urine NAE, 24-hour ambulatory BP, and 24-hour urine and plasma metabolomic profiles were measured after each period. RESULTS: During the control period, mean NAE was 28.3±10.2 mEq/d overall without differences across groups (P=0.5). Urine pH, ammonium, and citrate were significantly lower in CKD than in non-CKD (P<0.05 for each). Bicarbonate supplementation reduced NAE and urine ammonium in the CKD group, increased urine pH in both groups (but more in patients with CKD than in those without), and increased; urine citrate in the CKD group (P< 0.2 for interaction for each). Metabolomic analysis revealed several urine organic anions were increased with bicarbonate in CKD, including 3-indoleacetate, citrate/isocitrate, and glutarate. BP was not significantly changed. LIMITATIONS: Small sample size and short feeding duration. CONCLUSIONS: Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis. In CKD, acid excretion decreased further, but base excretion (eg, citrate) increased in response to alkali. Urine citrate should be evaluated as an early and responsive marker of impaired acid-base homeostasis. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases and the Duke O'Brien Center for Kidney Research. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02427594.

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Ammonia generated within the kidney is partitioned into a urinary fraction (the key buffer for net acid excretion) and an aliquot delivered to the systemic circulation. The physiology of this partitioning has yet to be examined in a kidney model, and that was undertaken in this work. This involves explicit representation of the cortical labyrinth, so that cortical interstitial solute concentrations are computed rather than assigned. A detailed representation of cortical vasculature has been avoided by making the assumption that solute concentrations within the interstitium and peritubular capillaries are likely to be identical and that there is little to no modification of venous composition as blood flows to the renal vein. The model medullary ray has also been revised to include a segment of proximal straight tubule, which supplies ammonia to this region. The principal finding of this work is that cortical labyrinth interstitial ammonia concentration is likely to be several fold higher than systemic arterial ammonia. This elevation of interstitial ammonia enhances ammonia secretion in both the proximal convoluted tubule and distal convoluted tubule, with uptake by Na+-K+-ATPases of both segments. Model prediction of urinary ammonia excretion was concordant with measured values, but at the expense of greater ammoniagenesis, with high rates of renal venous ammonia flux. This derives from a limited capability of the model medulla to replicate the high interstitial ammonia concentrations that are required to drive collecting duct ammonia secretion. Thus, renal medullary ammonia trapping appears key to diverting ammonia from the renal vein to urine, but capturing the underlying physiology remains a challenge.NEW & NOTEWORTHY This is the first mathematical model to estimate solute concentrations within the kidney cortex. The model predicts cortical ammonia to be several fold greater than in the systemic circulation. This higher concentration drives ammonia secretion in proximal and distal tubules. The model reveals a gap in our understanding of how ammonia generated within the cortex is channeled efficiently into the final urine.

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A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney's capacity for net acid excretion (NAE). There is increasing evidence, not only for patients with type 2 diabetes but also for healthy individuals, that higher body fatness or waist circumference (WC) has a negative impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules might mediate this relation between adiposity and renal acid excretion function. Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18-25 yr old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny's (B&K's) steps to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24-h pH relationship after strictly controlling for laboratory-measured NAE. In B&K's mediation analysis, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), and adiponectin significantly associated with the outcome 24-h pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the "natural indirect effects" of WC on 24-h pH via leptin (P = 0.01) and adiponectin (P = 0.03) to be significant, with a trend for sICAM-1 (P = 0.09). The calculated proportions mediated by leptin, adiponectin, and sICAM-1 were 64%, 23%, and 12%, respectively. Both mediation analyses identified an inflammatory cytokine (leptin) and an anti-inflammatory cytokine (adiponectin) along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity.

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BACKGROUND: The 'Western diet' typically consumed in industrialized countries is characterized by high amounts of processed cereal grains and animal products while being low in vegetables, tubers, and fruits. This dietary behavior leads to imbalances of acid-base status in favor of the acids and may cause low-grade metabolic acidosis (LGMA) that is associated with negative effects on health in the long run, including urolithiasis, bone loss, and even cardiometabolic diseases. Therefore, it has become of great interest to find dietary strategies that can be used to neutralize the acid load associated with Western diets. OBJECTIVE: The aim of this study was to investigate whether the diet-dependent net acid load can be reduced by the daily consumption of mineral waters with different bicarbonate content and different potential renal acid load (PRAL). METHODS: A single-centered, randomized trial including 129 healthy men and women aged from 18 to 75 years was conducted. Participants consumed 1,500-2,000 mL of one of four mineral waters with different bicarbonate content and different PRAL values daily for 4 weeks: low bicarbonate, high PRAL (LBHP, HCO3 -: 403.0 mg/L, PRAL: 10.7); medium-high bicarbonate, medium PRAL (MBMP, HCO3 - : 1816.0 mg/L, PRAL: -10.8); high bicarbonate, low PRAL (HBLP, HCO3 -: 2451.0 mg/L, PRAL: -19.3); medium-high bicarbonate, low PRAL (MBLP, HCO3 -: 1846.0 mg/L, PRAL: -22.1). Throughout the study, participants were asked to maintain their usual dietary habits. The primary outcome was the net acid excretion (NAE) measured in the 24-h urine output. RESULTS: Consumption of the three mineral waters: MBMP, HBLP, and MBLP led to a significant decrease in NAE values. Within the MBMP group, the NAE could be reduced by 48% (P = 0.001), while consumption of HBLP led to a reduction of 68% (P < 0.001) and MBLP to a reduction of 53% (P = 0.001). Moreover, a slight increase in serum bicarbonate could also be observed in the groups that drank HBLP (P = 0.057) and MBLP (P = 0.001). CONCLUSION: Daily consumption of at least 1,500-2,000 mL of mineral water rich in bicarbonate (>1800.0 mg/L) with medium or low PRAL (<-11 mEq/L) can effectively reduce the NAE level by reducing the dietary acid load under free-living conditions in healthy adults.

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Urine pH (UpH) and net acid excretion (NAE) are used to monitor the degree of systemic acidification and predict the magnitude of resultant hypercalciuria when feeding an acidogenic ration to control periparturient hypocalcemia in dairy cattle. The objectives of this study were to evaluate the diagnostic performance of urine dipstick and pH paper for measuring UpH, and to characterize the UpH-NAE relationship and the association of urine Ca concentration ([Ca]) with UpH and NAE. Urine samples (n = 1,116) were collected daily from 106 periparturient Holstein-Friesian cows fed an acidogenic ration during late gestation. Net acid excretion was measured by titration, and UpH was measured by a glass-electrode pH meter (reference method), Multistix-SG urine dipsticks (Siemens Medical Solutions Inc., Ann Arbor, MI), and Hydrion pH paper (Micro Essential Laboratory Inc., Brooklyn, NY). Diagnostic performance was evaluated using Spearman correlation coefficient (rs), Bland-Altman plots, and logistic regression. Urine pH measured by urine dipstick (rs = 0.94) and pH paper (rs = 0.96) were strongly associated with UpH. Method-comparison studies indicated that the urine dipstick measured an average of 0.28 pH units higher, and pH paper 0.10 pH units lower, than UpH. Urine [Ca] was more strongly associated with UpH (rs = -0.65) than NAE (rs = 0.52). Goals for controlling periparturient hypocalcemia under the study conditions were UpH <6.22 and <6.11, based on achieving urine [Ca] ≥5 mmol/L and estimated urinary Ca excretion ≥4 g/d, respectively. Urine pH was as accurate at predicting urine [Ca] as NAE when UpH >6.11. We conclude that pH paper is an accurate, practical, and low-cost cow-side test for measuring UpH and provides a clinically useful estimate of urine [Ca].

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Metabolic acidosis is a frequent complication of chronic kidney disease. Although it is known to appear at advanced stages, many studies suggest a state of "global protonic retention" starting at early stages of the disease, responsible of tissue damage, particularly musculoskeletal, alteration of protidic metabolism and endocrine disorders, promoting malnutrition and chronic inflammation, and finally increasing mortality. The majority of international recommandations suggest of supplementation by alkali, most of the time by sodium bicarbonate, to struggle against this complication. An interesting alternative to correct acidosis would consist on the modulation of the endogenous production of acid by playing with the alimentary incomes. In fact, it has been demonstrated that some different types of food produce or consume protons during their metabolism. Low protein diet and rich fresh fruits and vegetables diet would manage to correct at least as well as the supplementation by sodium bicarbonate the metabolic acidosis, and to struggle against its complications, noteworthy by slowing the decline of glomerular filtration rate by limiting the toxic adaptative fibrotic mechanisms, demonstrated by the decrease of urinary tubulo-interstitial suffering markers. Of the condition of being well led, those diets do not seem to expose patients to an over-risk of malnutrition or hyperkaliemia. They therefore appear to be an attractive alternative, efficiency and safe, to fight against chronic kidney disease metabolic acidosis and its complications.

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BACKGROUND: Reduced net acid excretion (NAE) capacity indicates a decrease in renal function. This reduction manifests as a disproportionally low 24-h urine pH in relation to the sum of actually excreted ammonium and titratable acidity by the kidney. OBJECTIVE: The aim of this study was to test the hypothesis that higher body fatness is one determinant of kidney function impairment with a lowered urine pH even at a young age. METHODS: NAE, pH, urea, and creatinine were measured in 24-h urine samples from 524 healthy children and adolescents (aged 6-17 y) participating in the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. Body fatness was assessed anthropometrically by body mass index-standard deviation score (BMI-SDS), fat mass index (FMI), body fat % (BF%), and waist circumference (WC). Multivariable linear and mixed linear regressions were used to examine cross-sectionally (n = 524 urine samples; age groups: 6-8, 9-11, 12-14, 15-17 y) and longitudinally (n = 1999 urine samples) the associations of body fatness with 24-h urine pH as the outcome variable, respectively. RESULTS: After adjusting for the kidneys' total net acid load (24-h urinary NAE) and further relevant covariates, FMI showed significant inverse relations with urinary pH in all 4 age groups, and BMI-SDS, BF%, and WC each in 3 out of these 4 groups (P ≤ 0.02). Longitudinal results substantiated these interindividual relations and further showed intraindividual increases in body fatness to be paralleled by urine pH decreases (P ≤ 0.0002). CONCLUSIONS: Independent of underlying acid load, an early increase in body fatness is associated with increased free proton excretion, and thus with a decline in the kidney's acid excretion function, which could potentiate the risk of renal nephrolithiasis.

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RATIONALE & OBJECTIVE: Higher urine net acid excretion (NAE) is associated with slower chronic kidney disease progression, particularly in patients with diabetes mellitus. To better understand potential mechanisms and assess modifiable components, we explored independent predictors of NAE in the CRIC (Chronic Renal Insufficiency Cohort) Study. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: A randomly selected subcohort of adults with chronic kidney disease enrolled in the CRIC Study with NAE measurements. PREDICTORS: A comprehensive set of variables across prespecified domains including demographics, comorbid conditions, medications, laboratory values, diet, physical activity, and body composition. OUTCOME: 24-hour urine NAE. ANALYTICAL APPROACH: NAE was defined as the sum of urine ammonium and calculated titratable acidity in a subset of CRIC participants. 22 individuals were excluded for urine pH < 4 (n = 1) or ≥7.4 (n = 19) or extreme outliers of NAE values (n = 2). From an analytic sample of 978, we identified the association of individual variables with NAE in the selected domains using linear regression. We estimated the percent variance explained by each domain using the adjusted R2 from a domain-specific model. RESULTS: Mean NAE was 33.2 ± 17.4 (SD) mEq/d. Multiple variables were associated with NAE in models adjusted for age, sex, estimated glomerular filtration rate (eGFR), race/ethnicity, and body surface area, including insulin resistance, dietary potential renal acid load, and a variety of metabolically active medications (eg, metformin, allopurinol, and nonstatin lipid agents). Body size, as indicated by body surface area, body mass index, or fat-free mass; race/ethnicity; and eGFR also were independently associated with NAE. By domains, more variance was explained by demographics, body composition, and laboratory values, which included eGFR and serum bicarbonate level. LIMITATIONS: Cross-sectional; use of stored biological samples. CONCLUSIONS: NAE relates to several clinical domains including body composition, kidney function, and diet, but also to metabolic factors such as insulin resistance and the use of metabolically active medications.

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Prolonged effects of dietary acid intake on acid-base status and kidney function have not yet been studied in an intervention study in healthy subjects. Dietary acid load can be estimated by calculating the potential renal acid load (PRAL) of foods. Effects of low-PRAL and moderate-PRAL diets on acid-base status and kidney function were investigated during a 12-week exercise training period. Healthy, 20-50-year-old men (n = 21) and women (n = 25) participated in the study and were randomly divided into low-PRAL and moderate-PRAL groups. Before (PRE), mid-phase (MID) and after the intervention (POST), the subjects participated in measurement sessions, where a 12-h urine sample and fasting blood samples were collected, and a submaximal cycle ergometer test was performed. Net acid excretion was significantly lower after 12 weeks of the low-PRAL diet as compared to the moderate-PRAL diet, both in men and women. In low-PRAL females, capillary pH and bicarbonate were significantly higher at 75% of VO2max at POST as compared to PRE. Glomerular filtration rate decreased over the study period in moderate-PRAL men and women. The results of the present study suggest that an acidogenic diet and regularly training together may increase the acidic load of the body and start to impair the kidney function in recreationally active subjects.

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Regulation of acid-base metabolism maintains the pH of body fluids within a tight range. Urine pH (UpH) is also regulated under normal conditions. Median pH of 24-h urines is ~6, but others have noted that UpH in women is higher than men, which has been attributed to differences in diet. If true, it would help to explain the fact that calcium phosphate stones, which form at higher urine pH, are much more common in women than in men. We studied 14 normal subjects (7 men and 7 women) fed identical meals in a Clinical Research Center. Urine and blood samples were collected during fasting and after meals. UpH of women (6.74 ± 0.11) exceeded that of men (6.07 ± 0.17) fed, but not fasting, and UpH rose significantly with meals in women but not men. Serum and urine total CO2 rose with meals in women but not men, and in women net acid excretion fell to zero during the fed period. In a general linear model adjusted for age, sex, and weight, net gastrointestinal anion uptake was the main predictor of UpH and was significantly higher in women (3.9 ± 0.6) than men (1.8 ± 0.7) in the fed period. Urine citrate, an anion absorbed by the gastrointestinal tract, was higher in women than men in the fed state, and fractional excretion of citrate was higher in women than men. The higher fed UpH in women is related to a greater absorption of food anions and raises 24-h UpH.

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Several studies suggest that neutralizing acid load in the diet with alkali had favorable effects on intermediate markers of musculoskeletal health. We examined whether alkali supplementation with potassium bicarbonate [(KHCO3); 81 mmol/d; n = 12] vs placebo (n = 12) for 84 days altered serum microRNAs, potential biomarkers associated with innumerable biological processes including bone and muscle metabolism. Serum microRNAs, urinary net acid excretion (UNAE), urinary N-telopeptide (UNTX), urinary calcium (UCa), urinary nitrogen (UN), glomerular filtration rate, serum procollagen type 1 amino-terminal propeptide (P1NP), serum insulin-like growth factor-1 (IGF-1), and its serum binding protein IGFBP3 were measured at baseline and day 84. Baseline characteristics and measurements were similar in the two treatment groups. Eighty-four-day changes in UNAE differed by group (KHCO3, -47 ± 9 mmol; placebo, -5 ± 5 mmol; P < 0.01). KHCO3 significantly reduced UNTX, UCa, and serum P1NP but did not affect UN, serum IGF-1, or IGFBP3 levels compared with placebo over 84 days. Fold change in serum circulating microRNA (c-miR)-133b differed significantly by group (KHCO3, 2.26 ± 0.85; placebo, -1.23 ± 0.69; P < 0.01); there was a similar trend in c-miR-21-5p. Fold changes in c-miR-133b and c-miR-21-5p were inversely associated with changes in UNAE and UNTX; fold change in c-miR-21-5p was inversely associated with change in UCa, with a similar trend with c-miR-133b. In summary, reducing renal acid load with KHCO3 was associated with increased expressions of c-miR-133b and c-miR-21-5p. Furthermore, increases in c-miRNA-133b and c-miR-21-5p were inversely associated with bone resorption markers UNTX and UCa consistent with potential beneficial effects on bone in older adults. However, the broader significance of c-miRNAs as musculoskeletal biomarkers is still under investigation, and larger studies are needed to verify these preliminary results.

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Resumen La aproximación físico-química para determinar el pH urinario es relativamente nueva y no se ha usado en condiciones patológicas en animales. En el presente artículo, el objetivo principal fue demostrar la validez de esta teoría en la orina de ovinos con alcalosis metabólica hipoclorémica. Se realizó un estudio de tipo experimental para la inducción de la alcalosis metabólica hipoclorémica en ovinos. Durante el periodo de control y de inducción se determinaron en la orina: pH calculado, pH medido, excreción neta de ácido, amonio y diferencia de iones fuertes en la orina (SID) cada 24 h hasta el desarrollo de la aciduria paradójica o el deterioro físico de los sujetos. Se determinó la correlación de Pearson (p) entre el pH medido y calculado a partir del modelo del SID en la orina. Se observó una correlación alta entre el pH urinario medido y el calculado usando el SID calculado con base en la excreción neta de ácido (p = 0,874). La correlación entre SID calculado y pH en orina fue significativa (p = 0,839). Sin embargo, la correlación entre el SID y el pH medido de la orina fue moderada (p = 0,588). Se concluye que existe una alta correlación entre el pH calculado a partir del SID usando la excreción neta de ácido y el pH medido en la orina de ovinos con alcalosis metabólica hipoclorémica. Esto indica que el pH urinario depende fuertemente del SID y, por lo tanto, la reducción en el pH puede ser explicada por la disminución del SID.

Abstract The physical-chemical approach to determine urinary pH is relatively new and has not yet been used in pathological conditions in animals. The main objective of this paper was to demonstrate the validity of this theory in the urine of sheep with hypochloremic metabolic alkalosis. An experimental-type study was conducted to induce hypochloremic metabolic alkalosis in sheep. During the control and induction periods, calculated pH, measured pH, net acid excretion, ammonium and strong ion difference (SID) in urine were examined every 24 hours until development of paradoxical aciduria or physical deterioration of subjects. Pearson's correlation (p) was determined between measured and calculated pH based on SID in urine. A high correlation between measured and calculated urine pH was observed using SID calculated from net acid excretion (p = 0.874). The correlation between calculated SID and urine pH was significant (p = 0.839). However, the correlation between SID and measured urine pH was moderate (p = 0.588). It is concluded that there is a high correlation between pH calculated from SID using net acid excretion and pH measured in the urine of sheep with hypochloremic metabolic alkalosis. This indicates that urine pH depends strongly on SID and, therefore, a reduction in pH can be explained by a decrease in SID.

Resumo A aproximação físico-química para determinar o pH urinário é relativamente nova e não tem sido usado em condições patológicas em animais. Neste artigo, o objetivo principal foi demonstrar a validez desta teoria na urina de ovinos com alcalose metabólica hipoclórica. Realizou-se um estudo de tipo experimental para a indução da alcalose metabólica hipoclórica em ovinos. Durante o período de controle e de indução determinaram na urina: pH calculado, pH medido, excreção neta de ácido, amônio e diferença de íons fortes na urina (SID) cada 24 horas hasta o desenvolvimento da aciduria paradoxal ou a deterioração física dos sujeitos. Determinou-se a correlação de Pearson (p) entre o pH medido e calculado a partir do modelo do SID na urina. Observou-se uma correlação alta entre o pH urinário medido e o calculado usando o SID calculado a partir da ex creção líquida de ácido (p = 0,874). A correlação entre SID calculado e pH em urina foi significativa (p = 0,839). Contudo, a correlação entre o SID e o pH medido da urina foi moderada (p = 0.588). Conclui-se que existe uma alta correlação entre o pH calculado a partir do SID usando a excreção líquida de ácido e o pH medido na urina de ovinos com alcalose metabólica hipoclórica. Isto indica que o pH urinário depende fortemente do SID e, portanto, a redução no pH pode ser explicada pela diminuição do SID.

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BACKGROUND & AIMS: Dietary sodium, protein, acid precursors, and water have been linked to cyst growth in polycystic kidney disease; yet, no studies in patients have examined the feasibility of using a dietary intervention that controls all of these factors. The aim of this study was to determine if a diet, appropriate for persons of most ages, reduces the excretion of sodium, urea, acid, and decreases mean urine osmolality while gaining acceptance by patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: Twelve adults with ADPKD enrolled in a pre-post pilot feasibility study and served as their own controls. Individuals consumed their usual diet for one week then for four weeks followed an isocaloric diet lower in sodium and protein and higher in fruits, vegetables, and water. Three-day diet records and two 24-h urine samples were collected at baseline, week 2, and week 4 visits; blood pressure, weight, and serum were obtained at all three visits. A modified nutrition hassles questionnaire was completed on the last visit. RESULTS: During the dietary intervention, subjects (n = 11) consumed less sodium, protein, and dietary acid precursors 36%, 28%, and 99%, respectively, and increased fluid intake by 42%. Urinary sodium, urea, net acid excretion, osmoles, and osmolality decreased 20%, 28%, 20%, 37%, and 15%, respectively; volume increased 35%. Urine changes were in accord with the diet record. Ninety-one percent of participants reported that none of the hassles were worse than "somewhat severe", and most participants felt "somewhat confident" or "very confident" that they could manage the new diet. CONCLUSIONS: A majority of adult patients with ADPKD successfully prepared and followed a composite diet prescription with decreased sodium, protein, acid precursors, and increased fluid intake. This trail was registered at ClinicalTrials.gov (NCT01810614).

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The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance.

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The kidney's maintenance of the metabolic component of acid-base homeostasis is critical for normal health. The study by Esche and colleagues in this issue of Kidney International shows that normal children with higher levels of renal net acid excretion and of dietary acid loads have stimulation of glucocorticoid hormone metabolism. Thus, normal variations in dietary acid intake and renal net acid excretion have important biological correlates.

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