Net Acid Research Articles

State of knowledge on ammonia handling by the kidney.

The disposal of ammonia, the main proton buffer in the urine, is important for acid-base homeostasis. Renal ammonia excretion is the predominant contributor to renal net acid excretion, both under basal condition and in response to acidosis. New insights into the mechanisms of renal ammonia production and transport have been gained in the past decades. Ammonia is the only urinary solute known to be produced in the kidney and selectively transported through the different parts of the nephron. Both molecular forms of total ammonia, NH3 and NH4+, are transported by specific proteins. Proximal tubular ammoniagenesis and the activity of these transport processes determine the eventual fate of total ammonia produced and excreted by the kidney. In this review, we summarized the state of the art of ammonia handling by the kidney and highlighted the newest processes described in the last decade.

The Role of the Endocrine System in the Regulation of Acid-Base Balance by the Kidney and the Progression of Chronic Kidney Disease.

Systemic acid-base status is primarily determined by the interplay of net acid production (NEAP) arising from metabolism of ingested food stuffs, buffering of NEAP in tissues, generation of bicarbonate by the kidney, and capture of any bicarbonate filtered by the kidney. In chronic kidney disease (CKD), acid retention may occur when dietary acid production is not balanced by bicarbonate generation by the diseased kidney. Hormones including aldosterone, angiotensin II, endothelin, PTH, glucocorticoids, insulin, thyroid hormone, and growth hormone can affect acid-base balance in different ways. The levels of some hormones such as aldosterone, angiotensin II and endothelin are increased with acid accumulation and contribute to an adaptive increase in renal acid excretion and bicarbonate generation. However, the persistent elevated levels of these hormones can damage the kidney and accelerate progression of CKD. Measures to slow the progression of CKD have included administration of medications which inhibit the production or action of deleterious hormones. However, since metabolic acidosis accompanying CKD stimulates the secretion of several of these hormones, treatment of CKD should also include administration of base to correct the metabolic acidosis.

Dietary acid load and cirrhosis-related mortality: a prospective cohort study

As a global health concern, cirrhosis contributes significantly to morbidity and mortality. This prospective cohort study aimed to investigate the association between dietary acid load (DAL) and cirrhosis-related mortality. Present study was conducted on 121 patients with newly diagnosed cirrhosis who were followed up for 48 months. Anthropometric measures, nutritional status and dietary intakes were assessed and DAL was estimated based on potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. Crude and multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazard analyses. Participants in the high PRAL and NEAP scores had significantly higher intakes of grains and lower intakes of fruits and vegetables. Also, the intake of dairy products and legumes, nuts and seeds decreased significantly with increasing NEAP score. After adjustment of all the confounders, the risk of mortality in the second and third tertiles of PRAL was 5.9 times and 10.97 higher than those in the first tertile, respectively (P trend: 0.006). Similarly, comparing the risk of mortality in the second and third tertiles with the first tertile of NEAP showed a 4.46-fold and 12.3-fold increased risk, respectively (P trend: 0.010). Our findings suggested that DAL was significantly associated with cirrhosis-related mortality and highlight the need for further research to understand the underlying mechanisms and establish optimal DAL levels in cirrhotic patients.

Phosphorus Intake and Potential Dietary Influences Examined via 24-Hour Urinary Biomarker Measurements in German Children and Adolescents Over 3 Decades

BackgroundIncreases in phosphorus intake have been observed over the past years in adult populations. However, biomarker-based data are lacking on whether or not phosphorus intake also increased in children. ObjectiveThe aim of this study was to examine 24-hour urinary phosphate excretion (PO4-Ex) and diet-related biomarkers potentially influencing phosphorus status in German children and adolescents from 1985 to 2015. DesignThis longitudinal noninvasive biomarker-based cohort study examined 24-hour urine samples from children and adolescents of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, collected over 3 decades. Participants/settingExamined individuals (n = 1,057) were healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, situated in Dortmund, Germany, who had been asked to collect one yearly 24-hour urine sample. Six thousand seven hundred thirty-seven samples collected from participants aged 3 to 17 years between 1985 (baseline) and 2015, were included. Main outcome measuresphosphorus intake was examined biomarker-based by analyzed PO4-Ex in 24-hour urine samples. Whether acid-base status and intakes of protein, salt, and fruits and vegetables, may have relevantly contributed to PO4-Ex levels was assessed by determining 24-hour excretions of net acid, urea-nitrogen, and sodium as well as specific standardized excretions of potassium plus oxalate. Statistical analyses performedTrend analysis over 30 years and potentially influencing diet factors were examined using linear mixed-effect regression models (PROC-MIXED). Adjustments for sex, age, and body surface area were performed. ResultsNo change was identifiable for PO4-Ex over the 3 decades; neither in 3 to 8, 9 to 13, nor in 14 to 17 year olds. However, sodium excretion increased (P = .001). PROC-MIXED analysis on intraindividual changes in PO4-Ex revealed direct relationships with net acid excretion, urea-nitrogen, and sodium excretion and an inverse relationship with a biomarker of fruit and vegetable intake. ConclusionsDespite a direct relationship between PO4-Ex and a biomarker of industrially processed food consumption; that is, sodium excretion, which showed an increasing time trend, phosphorus intake was found to remain stable over decades in children and adolescents.

Acid-base transporters in the context of tumor heterogeneity.

The copious metabolic acid production and -extrusion by cancer cells render poorly vascularized regions of solid tumors highly acidic. A growing list of proton - and bicarbonate transporters has been suggested to contribute to net acid extrusion from cancer cells, and/or been shown to be dysregulated and favor malignant development in various cancers. The great majority of these roles have been studied at the level of the cancer cells. However, recent advances in understanding of the cellular and physicochemical heterogeneity of solid tumors both enable and necessitate a reexamination of the regulation and roles of acid-base transporters in such malignancies. This review will briefly summarize the state-of-the-art, with a focus on the SLC9A and SLC4A families, for which most evidence is available. This is followed by a discussion of key concepts and open questions arising from recent insights and of the challenges that need to be tackled to address them. Finally, opportunities and challenges in therapeutic targeting of the acid-base transportome in cancers will be addressed.

Antibodies toward Na+,HCO3--cotransporter NBCn1/SLC4A7 block net acid extrusion and cause pH-dependent growth inhibition and apoptosis in breast cancer.

Na+,HCO3--cotransporter NBCn1/Slc4a7 accelerates murine breast carcinogenesis. Lack of specific pharmacological tools previously restricted therapeutic targeting of NBCn1 and identification of NBCn1-dependent functions in human breast cancer. We develop extracellularly-targeted anti-NBCn1 antibodies, screen for functional activity on cells, and evaluate (a) mechanisms of intracellular pH regulation in human primary breast carcinomas, (b) proliferation, cell death, and tumor growth consequences of NBCn1 in triple-negative breast cancer, and (c) association of NBCn1-mediated Na+,HCO3--cotransport with human breast cancer metastasis. We identify high-affinity (KD ≈ 0.14 nM) anti-NBCn1 antibodies that block human NBCn1-mediated Na+,HCO3--cotransport in cells, without cross-reactivity towards human NBCe1 or murine NBCn1. These anti-NBCn1 antibodies abolish Na+,HCO3--cotransport activity in freshly isolated primary organoids from human breast carcinomas and lower net acid extrusion effectively in primary breast cancer tissue from patients with macrometastases in axillary lymph nodes. Inhibitory anti-NBCn1 antibodies decelerate tumor growth in vivo by ~50% in a patient-derived xenograft model of triple-negative breast cancer and pH-dependently reduce colony formation, cause G2/M-phase cell cycle accumulation, and increase apoptosis of metastatic triple-negative breast cancer cells in vitro. Inhibitory anti-NBCn1 antibodies block net acid extrusion in human breast cancer tissue, particularly from patients with disseminated disease, and pH-dependently limit triple-negative breast cancer growth.

Higher Renal Net Acid Excretion, but Not Higher Phosphate Excretion, during Childhood and Adolescence Associates with the Circulating Renal Tubular Injury Marker Interleukin-18 in Adulthood.

High dietary phosphorus intake (P-In) and high acid loads may adversely affect kidney function. In animal models, excessive phosphorus intake causes renal injury, which, in humans, is also inducible by chronic metabolic acidosis. We thus examined whether habitually high P-In and endogenous acid production during childhood and adolescence may be early indicators of incipient renal inflammatory processes later in adulthood. P-In and acid-base status were longitudinally and exclusively determined by biomarker-based assessment in 277 healthy children, utilizing phosphate and net acid excretion (NAE) measurements in 24 h urine samples repeatedly collected between the ages of 3 and 17 years. Standard deviation scores (by sex and age) were calculated for anthropometric data and for the urinary biomarkers available within age range 3-17 years. Multivariable linear regression was used to analyze the relations of phosphate excretion and NAE with the adulthood outcome circulating interleukin-18 (IL-18), a marker of inflammation and kidney dysfunction. After adjusting for growth- and adulthood-related covariates and pro-inflammatory biomarkers to rule out confounding by non-renal inflammatory processes, regression models revealed a significant positive relationship of long-term NAE (p = 0.01), but not of long-term phosphate excretion with adult serum IL-18. Similar significant positive regression results were obtained after replacing NAE with 24 h urinary ammonium excretion as the exposition variable. Our results suggest that even moderate elevations in renal ammonia production, as caused by habitually higher acid loading during growth, may affect the intrarenal pro-inflammatory system in the long-term, known to be boosted by acidosis-induced raised ammoniagenesis.

The impact of forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers.

Although the mechanisms underpinning short-term muscle disuse atrophy and associated insulin resistance remain to be elucidated, perturbed lipid metabolism might be involved. Our aim was to determine the impact of acipimox administration [i.e., pharmacologically lowering circulating nonesterified fatty acid (NEFA) availability] on muscle amino acid metabolism and insulin sensitivity during short-term disuse. Eighteen healthy individuals (age: 22 ± 1 years; body mass index: 24.0 ± 0.6 kg·m-2) underwent 2 days forearm immobilization with placebo (PLA; n = 9) or acipimox (ACI; 250 mg Olbetam; n = 9) ingestion four times daily. Before and after immobilization, whole body glucose disposal rate (GDR), forearm glucose uptake (FGU; i.e., muscle insulin sensitivity), and amino acid kinetics were measured under fasting and hyperinsulinemic-hyperaminoacidemic-euglycemic clamp conditions using forearm balance and l-[ring-2H5]-phenylalanine infusions. Immobilization did not affect GDR but decreased insulin-stimulated FGU in both groups, more so in ACI (from 53 ± 8 to 12 ± 5 µmol·min-1) than PLA (from 52 ± 8 to 38 ± 13 µmol·min-1; P < 0.05). In ACI only, and in contrast to our hypothesis, fasting arterialized NEFA concentrations were elevated to 1.3 ± 0.1 mmol·L-1 postimmobilization (P < 0.05), and fasting forearm NEFA balance increased approximately fourfold (P = 0.10). Forearm phenylalanine net balance decreased following immobilization (P < 0.10), driven by an increased rate of appearance [from 32 ± 5 (fasting) and 21 ± 4 (clamp) preimmobilization to 53 ± 8 and 31 ± 4 postimmobilization; P < 0.05] while the rate of disappearance was unaffected by disuse or acipimox. Disuse-induced insulin resistance is accompanied by early signs of negative net muscle amino acid balance, which is driven by accelerated muscle amino acid efflux. Acutely elevated NEFA availability worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance.NEW & NOTEWORTHY We demonstrate that 2 days of forearm cast immobilization in healthy young volunteers leads to the rapid development of insulin resistance, which is accompanied by accelerated muscle amino acid efflux in the absence of impaired muscle amino acid uptake. Acutely elevated fasting nonesterified fatty acid (NEFA) availability as a result of acipimox supplementation worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance.

A high dietary acid load can potentially exacerbate cardiometabolic risk factors: An updated systematic review and meta-analysis of observational studies

AimsChronic metabolic acidosis has been shown to be associated with cardiometabolic risk factors. The aim of the currently updated meta-analysis was to explore the association between Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) with these risk factors. Data synthesisDatabases were searched up to May 2023. The mean of waist circumference (WC), body mass index (BMI), high- and low-density lipoprotein-cholesterol (HDL-C and LDL-C), triglyceride (TG), total cholesterol (TC), fasting blood sugar (FBS), and systolic- and diastolic blood pressure (SBP and DBP) in highest category vs lowest categories of NEAP and PRAL were recorded. Effect sizes were generated as weighted mean difference (WMD). Results showed that SBP, DBP, and WC had a significant difference in the upper and lower categories of PRAL (WMDSBP: 1.466 mmHg; 95% CI: 2.121, −0.811; P<0.001, WMDDBP: 0.710 mmHg; 95 % CI: 1.170, −0.249; P=0.003, and WMDWC: 0.819 cm; 95% CI: 1.446, −0.192; P=0.010) or NEAP (WMDSBP: 1.690 mmHg; 95% CI: 2.789, −0.591; P=0.003, WMDDBP: 1.076 mmHg, and WMDWC: 1.325 cm; 95% CI: 1.901, −0.749; P<0.001; 95% CI: 1.938, −0.214; P =0.014). The lowest versus highest categories of dietary PRAL were associated with lower BMI (WMDPRAL: 0.297 kg/m2; 95 % CI: 0.440, −0.154; P<0.001) and TG (WMD: 2.280 mg/dl; 95%CI: 3.828, −0.732; P=0.004; I2=99.4 %; P<0.001). ConclusionsHigh DAL can be considered as an independent risk factor for increasing anthropometric indices, blood pressure, and TG.This study registered in the PROSPERO database (Registration No. CRD42023402985).

Primary Sjogren’s syndrome with secondary distal renal tubular acidosis unmasked during pregnancy: A rare presentation

ABSTRACT Renal tubular acidosis (RTA) comprises transport defects in renal reabsorption of bicarbonate, impaired acidification of urine, or both. It is broadly classified into distal, proximal, and hyperkalemic RTA. Distal RTA (dRTA) is characterized by reduced net acid excretion in urine. It can be primary or secondary, and hypokalemia is often a central presenting feature. Hypokalemia may present with flaccid quadriparesis, arrhythmia, and respiratory failure. Hypokalemia also causes nephrogenic diabetes insipidus (NDI) due to the downregulation of vasopressin-responsive aquaporin-2 water channel and inhibition of renal response to vasopressin. Primary Sjogren’s syndrome (pSS) is the most common autoimmune disorder associated with secondary dRTA. Here, we present the case of a 22-year-old critically ill pregnant lady with adverse pregnancy outcomes, diagnosed to be pSS with dRTA, who presented with severe hypokalemia and hypernatremia (due to NDI). Both pSS and chronic acidosis are associated with adverse pregnancy outcomes.

Association of dietary acid-base load with psychological disorders, sleep and circadian rhythm among obese and overweight women: a cross-sectional study

Background: Epidemiological studies have reported that dietary acid load is associated with psychological disorders through different pathways. We aimed to examine the association of dietary acid-base load with psychological disorders, sleep and circadian rhythm. Methods: This study was performed on 404 female subjects aged 18 years and above. We evaluated potential renal acid load (PRAL) and net endogenous acid production (NEAP) score by a validated food frequency questionnaire (FFQ) for Iran which contained 147 items. To assess psychological disorders, an Iranian validated version of the depression, anxiety and stress scale (DASS-21) was used. The Pittsburgh Sleep Quality Index (PSQI) and morning-evening questionnaire (MEQ) were applied to evaluate sleep quality and circadian rhythm status, respectively. Results: After adjustment for a wide range of confounding variables, a significant positive association was observed between dietary acid-base load and severe depression (ORPRAL=1.10, 95% CI=1.01-1.19, p=0.02 and ORNEAP=2.46, 95% CI=1.41-14.61, p=0.02). Women in the high dietary acid base load category had higher anxiety (ORPRAL=1.12, 95% CI=1.02-1.23, p=0.01 and ORNEAP=1.80,95% CI=1.12-10.72, p=0.01). There was a strong positive relationship between dietary acid-base load and sleep disturbance (p&lt;0.05). Additionally, circadian rhythm assessment showed that those with greater commitment to PRAL had 23% higher risk of being completely evening type, while the odds of being completely morning type were decreased by 15% and 12% across higher adherence to PRAL and NEAP. Conclusion: Women with higher dietary acid-base load score had greater odds for depression, anxiety, psychological distress, sleep disturbance and evening-type circadian rhythm compared to lower ones.

Association of Dietary Acid Load With Metabolic Syndrome and Its Components in Iranian Adults: A Cross-Sectional Study.

Introduction Metabolic syndrome (MetS) remains one of the leading health challenges worldwide. A combination of genetic and environmental factors has been implicated in the etiology of MetS. Diet is a changeable environmental risk factor, and dietary modifications could significantly reduce the incidence and mortality of numerous diseases, including MetS. Certain dietary factors may contribute to MetS by affecting the acid-base balance within the body. This study examined the association of dietary acid load (DAL) with MetS and its components in Iranian adults. Materials and methods This cross-sectional study was conducted in 2022 on 6356 Iranian adults aged 35-70 years. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) as two indicators of DAL were calculated based on nutrient intake data from validated food frequency questionnaires. MetS and its components were defined according to the Adult Treatment Panel III criteria. Logistic regression analysis was used to explore the associations between DAL and MetS and its components. Age, energy intake, physical activity, education, marital status, home ownership, socioeconomic status, history of obesity-related disease, and calcium supplements were included in model I. Further adjustment in model II was made for body mass index. Results Higher NEAP scores were associated with increased odds of low high-density lipoprotein cholesterol (HDL-C) in the crude model (OR: 1.26, 95% CI: 1.01-2.56, p trend = 0.06) in women, which was confirmed in the adjusted models. In model I, women in the last quintile of NEAP had 54% greater odds of having hypertriglyceridemia compared to the first quintile (OR: 1.54, 95% CI: 1.007-2.36, p trend = 0.02). This association was still significant and even stronger after further adjustment for BMI (OR: 1.55, 95% CI: 1.01-2.40, p trend = 0.01). In addition, in model I, men in the fourth quintile of NEAP had 5.68-fold greater odds of hyperglycemia compared to the first quintile (OR: 5.68, 95% CI: 1.18-27.25, p trend = 0.11). Similar results were found in the fully adjusted model (OR: 5.89, 95% CI: 1.19-28.99, p trend = 0.54). Conclusion There was no significant association between DAL and MetS. DAL was positively associated with the odds of low HDL-C and hypertriglyceridemia in women. Moreover, moderate DAL (NEAP) was associated with an increased odds of hyperglycemia in men.

Higher dietary acid load is associated with an increased risk of metabolic syndrome

There have been inconsistent reports regarding the association between dietary acid load and Metabolic Syndrome (MetS). We aimed to investigate the association between dietary acid load and MetS in an Iranian adult population. In this cross-sectional study, 1945 participants aged 35–65 years were recruited from MASHAD cohort study. Dietary intakes were assessed using a 24-h dietary recall. Diet-based acidity was assessed as the net endogenous acid production (NEAP), potential renal acid load (PRAL), and dietary acid load (DAL). To define MetS, the International Diabetes Federation (IDF) criteria were used. Multivariable logistic regression models were applied to determine the association between diet-based acid load scores and MetS. Participants' mean age and BMI were 47.13 ± 7.78 years and 27.57 ± 4.48 kg/m2, respectively. Around 57% of the population was female. Overall, 31.9% had MetS. According to the full-adjusted model, there was a significant association between higher quartiles of PRAL, NEAP, and DAL and MetS (Q4 PRAL; OR (95%CI) 1.42(1.05–1.91), Q4 NEAP; OR (95%CI) 1.48(1.11–1.98), Q4 DAL; OR (95%CI) 1.44(1.05–1.91)). This study showed a significant positive association between different dietary acid load indicators (PRAL, NEAP, and DAL) and odds of MetS among Iranian adults.

Biallelic variants in SLC4A10 encoding a sodium-dependent bicarbonate transporter lead to a neurodevelopmental disorder

PurposeSLC4A10 encodes a plasma membrane-bound transporter, which mediates Na+-dependent HCO3− import, thus mediating net acid extrusion. Slc4a10 knockout mice show collapsed brain ventricles, an increased seizure threshold, mild behavioral abnormalities, impaired vision, and deafness. MethodsUtilizing exome/genome sequencing in families with undiagnosed neurodevelopmental disorders and international data sharing, 11 patients from 6 independent families with biallelic variants in SLC4A10 were identified. Clinico-radiological and dysmorphology assessments were conducted. A minigene assay, localization studies, intracellular pH recordings, and protein modeling were performed to study the possible functional consequences of the variant alleles. ResultsThe families harbor 8 segregating ultra-rare biallelic SLC4A10 variants (7 missense and 1 splicing). Phenotypically, patients present with global developmental delay/intellectual disability and central hypotonia, accompanied by variable speech delay, microcephaly, cerebellar ataxia, facial dysmorphism, and infrequently, epilepsy. Neuroimaging features range from some non-specific to distinct neuroradiological findings, including slit ventricles and a peculiar form of bilateral curvilinear nodular heterotopia. In silico analyses showed 6 of 7 missense variants affect evolutionarily conserved residues. Functional analyses supported the pathogenicity of 4 of 7 missense variants. ConclusionWe provide evidence that pathogenic biallelic SLC4A10 variants can lead to neurodevelopmental disorders characterized by variable abnormalities of the central nervous system, including altered brain ventricles, thus resembling several features observed in knockout mice.

Association of Dietary Acid Load with Nonalcoholic Fatty Liver Disease and Advanced Liver Fibrosis in US Adults: Evidence from NHANES 1999-2018.

Evidence for an association between dietary acid load (DAL) and non-alcoholic fatty liver disease (NAFLD) is scarce and controversial. We aimed to address whether an association exists between DAL and NAFLD/advanced liver fibrosis (AHF) among US adults in a nationally representative study. This was a cross-sectional study. We included adult participants from the National Health and Nutrition Examination Survey 1999-2018. Potential renal acid load (PRAL) and estimated net endogenous acid production (NEAP) was calculated from the literature and NAFLD/AHF was diagnosed by noninvasive markers. We comprehensively explored these relationships using multivariate adjusted regression models, restricted cubic spline, stratification analysis, and sensitivity analysis. We enrolled a total of 18,855 participants. All DAL metrics were positively and nonlinearly associated with NAFLD (all p-values < 0.0001), whereas NEAPF and NEAPR may be associated with AHF. In the stratified analysis, we found that the correlation between DAL and NAFLD exists in all ages and genders, but the effect of DAL seems to be more obvious in middle-aged, elderly and women. Similarly, we found that the effect of DAL on AHF was more significant in 45-60-year-olds and women. Sensitivity analyses revealed stability of all results. DAL including PRAL and NEAP were positively associated with NAFLD in a large nationally representative cross-sectional study. NEAPF and NEAPR may be associated with increased odds of AHF. Adjustment for diet-dependent DAL requires age- and sex-specific strategies. Future prospective studies are needed to validate our findings.

The dietary acid load is associated with disease severity inpsoriatic arthritis.

An acidogenic diet, by disrupting the blood pH equilibrium, can contribute to metabolic acidosis and lead to inflammation. Therefore, we hypothesized that dietary acid load (DAL) increases disease activity and inflammation in psoriatic arthritis (PsA) patients. This study was conducted with 58 obese/overweight patients, aged 20-65 years. Dietary intake was assessed using a 3-consecutive-day 24-hour recall. The DAL was evaluated through the PRAL (potential renal acid load) and NEAP (net endogenous acid production) and divided into the low and high groups by their median values. The disease activity assessments, anthropometric measurements, dietary data, and blood parameters of patients were recorded and compared at the low and high DAL groups. We observed that patients in the high NEAP and PRAL groups had worse PsA pattern scores (P < 0.05). Also, PRAL and NEAP scores were positively associated with Disease Activity Index for Psoriatic Arthritis, Health Assessment Questionnaire, and Psoriatic Arthritis Impact of Disease-12 (PSAID-12) scores. After adjusting age, sex, smoking, and body mass index, 1 mEq increase in PRAL and NEAP was associated with an elevation of Disease Activity Index for Psoriatic Arthritis (0.506 and 0.486 points, respectively). These results showed a close relationship between DAL and PsA symptoms. An acidogenic diet may negatively affect PsA prognosis. Healthy eating recommendations should be part of the management of the disease.

Association between Dietary Acid Load and Hypertension in Chinese Adults: Analysis of the China Health and Nutrition Survey (2009).

(1) Background: Current studies show conflicting results regarding the relationship between dietary acid load (DAL) and blood pressure. (2) Methods: The study used data from the Chinese Health and Nutrition Survey (CHNS) 2009. DAL was assessed on the basis of potential renal acid load (PRAL) and net endogenous acid production (NEAP). To examine the link between DAL and the risk of hypertension, a multivariate logistic regression model was utilized. (3) Results: A total of 7912 subjects were enrolled in the study, of whom 2133 participants had hypertension, a prevalence of 27.0%. After accounting for potential covariates, higher PRAL and NEAP scores were associated with a greater likelihood of developing hypertension, with ORs of 1.34 (95% CI, 1.10-1.62) and 1.29 (95% CI, 1.09-1.53) for PRAL and NEAP scores in Q4, respectively, compared with Q1. In the male group, PRAL and NEAP scores were positively linked to hypertension risk, with ORs of 1.33 (95% CI, 1.06-1.67) and 1.46 (95% CI, 1.14-1.85) for PRAL and NEAP scores in Q4, respectively, compared with Q1, while no significant associations were observed in the female group. Correlations between PRAL scores and hypertension risk lacked significance in the subgroup analyses for participants aged <60 years. There was a significant nonlinear connection observed in the dose-response relationship between DAL (based on PRAL) and hypertension; (4) Conclusions: In Chinese adults, higher PRAL and NEAP scores were positively linked to hypertension risk. This implies that a diet with a low DAL may be a favorable dietary pattern for lowering blood pressure.

Dietary acid load and the risk of events of mortality and kidney replacement therapy in people with chronic kidney disease: the Progredir Cohort Study.

The association between dietary acid load (DAL) and chronic kidney disease (CKD) progression remains controversial. Also, there is a gap in the literature on the association between DAL and mortality. In this study, we evaluated the association between NEAP (net endogenous acid production) and PRAL (potential renal acid load) and the risk of events of all-cause mortality and kidney replacement therapy (KRT) in people with CKD. We included 442 patients (250 diabetics) from the Progredir Cohort Study, based in São Paulo, Brazil. We estimated NEAP and PRAL from dietary intake. Events of death before KRT and KRT were ascertained after a median follow-up of 5.8 and 5.1 years, respectively. Cox proportional hazards regression, Weibull regression, and competing risk models were performed. Median NEAP and PRAL were 49.5 and 4.8 mEq/d. There were 200 deaths and 75 KRT events. Neither NEAP nor PRAL were associated with mortality or KRT when all participants were analyzed. After stratification for diabetes, both estimates were positively related to the risk of KRT even after adjustment for age, sex, weight status, glomerular filtration rate, serum bicarbonate, and intakes of protein, phosphorus, and energy (HR 1.31; 95% CI 1.07, 1.60 for NEAP, and HR 1.27; 95% CI 1.04, 1.57 for every 10 mEq/d increments). Competing risk analyses confirmed these findings. DAL estimates were associated with the risk of KRT in people with CKD and diabetes but not in non-diabetics. There was no association between all-cause mortality and DAL.

The Synergistic Effect of Dietary Acid Load Levels and Cigarette Smoking Status on the Risk of Chronic Obstructive Pulmonary Disease (COPD) in Healthy, Middle-Aged Korean Men.

We investigated whether cigarette smoking and dietary acid load (DAL) are associated with a risk of chronic obstructive pulmonary disease (COPD) in healthy, middle-aged Korean men. Healthy men without diagnosed chronic disease (aged 40-64 years) from the KNHANES-VI (2013-2015) were included in the analysis (n = 774) and were subdivided by smoking status and DAL levels, as estimated using the quartile of net endogenous acid production (NEAP). The current smokers tended to have a higher risk of COPD than the never-smokers before and after adjustment. When divided by the DAL quartile, the Q4 group tended to have a higher risk of COPD than the Q1 group. Additionally, the current smokers with lower (Q2), modest (Q3), and the highest NEAP scores (Q4) showed risks of COPD that were more than fourfold higher than those of the never-smokers with the lowest NEAP scores (Q1). The ex-smokers with higher NEAP scores (Q3 and Q4) showed risks of COPD that were more than fourfold higher than those of the Q1 group. Interestingly, the risk of COPD was also more than sixfold higher in the never-smokers with the highest NEAP scores compared to that in the Q1 group. The NEAP scores and smoking status synergistically increased the risk of COPD in healthy, middle-aged Korean men. This suggests that DAL levels are an important factor in the prevention and management of COPD.

Many foods are more acid-forming than acid-alkaline formulas indicate.

Foods contain substances impacting the acid-base balance. The Western diet is often viewed as being overly acid due to its high-level of animal-based protein and low-level of vegetable intake. Meanwhile, with ageing the ability to excrete acid compounds is reduced as kidney function declines and so there is a risk of acid retention and subsequent interstitial acidosis. Two systems used for calculating the Dietary Acid Load (DAL): the potential acid load of foods (PRAL) and the net endogenous acid production (NEAP). This report outlines weaknesses in these formulas and concludes that dietitians and nutritionists lack the necessary tools to research the acid-base hypothesis. Additionally, the report emphasizes the importance of food selection in the ageing population. Background: Foods contain substances impacting the acid-base balance. The Western diet is often viewed as being overly acid due to its high-level of animal-based protein and low-level of vegetable intake. There are concerns that the disproportionate acid intake promotes low-grade metabolic acidosis in the interstitial fluid, interstitial acidosis, and may lead to chronic disease. Two formulas are used for calculating the DAL: the PRAL and the NEAP. Both PRAL and NEAP are based on levels of protein and minerals. Aim: To identify additional food constituents that impact DAL. Methods: Review of the literature concerning the acid-forming and alkaline-forming constituents of foods. Results: Five additional food constituents were identified as potentially having a meaningful impact on DAL. The oxidation of taurine and the metabolism of fructose and purines increase acidity, whereas organic acids increase alkalinity. Additionally, polyphenols affect the microbiota which break down uric acid excreted in the intestinal tract. Conclusions: Neither PRAL nor NEAP provides complete assessments of the impact of foods on DAL. These formulas could be improved by the inclusion of dietary amino acids rather than protein, taurine, purines, fructose, organic acids and polyphenols. Currently, dietitians and nutritionists lack the necessary tools both to research the acid-base hypothesis and recommend managed diets. Managed diets are of particular importance for the elderly because of their reduced kidney function which increases the risk of acid retention and subsequent interstitial acidosis.