Citrate Excretion Research Articles

Citrate in autosomal dominant polycystic kidney disease: biomarker or therapeutic agent?

Purpose of review This review highlights the latest findings regarding hypocitraturia in autosomal dominant polycystic kidney disease (ADPKD), from both experimental and clinical studies, exploring the underlying pathophysiology and potential therapeutic approach. Recent findings Experimental studies have shown that the lodging of microcrystals in the tubules can trigger cyst formation and growth in polycystic kidney disease (PKD). ADPKD patients are prone to developing hypocitraturia in early stages, which could predispose to calcium microcrystal formation. Low urinary citrate excretion has been associated with a more rapid decline in eGFR and poorer renal survival in ADPKD patients. Animal studies employing citrate supplementation have shown promising effects on preserving the decline in estimated glomerular filtration rate (eGFR) and cyst growth. Summary Current knowledge suggests that urinary citrate could be incorporated into existing prognostic markers for disease progression and potential adjuvant therapy in ADPKD, but further clinical studies to support such hypothesis must be undertaken.

A Metabolome-Wide Association Study of fruit and vegetable consumption and associations with cardiovascular risk factors: the INTERMAP study

BackgroundEpidemiological evidence linking blood pressure (BP) and body weight-lowering effects with fruit and vegetable consumption mostly relies on self-reported dietary assessment prone to misreport and under- or overestimation of relationships. We characterized objective 24-hr urinary metabolites and a derived metabolite score associated with fruit and vegetable intake and assessed their associations with BP and body mass index (BMI), with validation across cohorts. MethodsWe used untargeted proton nuclear magnetic resonance spectroscopy (1H NMR) of two timed repeated 24-hr urine collections from free-living participants from the US (n=2,032) and the UK (n=449) of the cross-sectional International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP). We evaluated correlations between fruit and vegetable intake assessed by 24-hr dietary recalls with 7,100 1H NMR features, adjusted for confounders and multiple testing. We related identified metabolites and a metabolite score with BP and BMI using extensively adjusted multiple linear regression models. ResultsWe characterized eleven 1H NMR-derived 24-hr urinary metabolites related to fruit and vegetable intake, reproducible across multiple 24-hr urine collections of both cohorts. Proline betaine, citrate, N-methylproline, scyllo-inositol, 2-hydroxy-2-(4-methyl cyclohex-3-en-1-yl) propoxyglucuronide, and proline were associated with fruit intake, specifically with Rutaceae intake, while S-methyl-L-cysteine sulfoxide and S-methyl-L-cysteine sulfoxide metabolite were associated with Brassicacea intake. The metabolite score, explaining 39.8% of fruit and vegetable intake, was inversely associated with systolic BP (-1.65 mmHg; 95% confidence interval (CI): -2.68,-0.62, P<0.002) and BMI (-1.21 kg/m2; 95% CI: -1.62,-0.78, P<0.0001). These associations were to a large extent explained by urinary citrate excretion. ConclusionWe identified 1H NMR-derived urinary metabolites associated with fruit and vegetable consumption, consistent and reproducible between urine collections and across populations. A higher fruit and vegetable-related metabolite score showed associations with lower systolic BP and BMI, mainly mediated by citrate, but would need confirmation in further studies. Study registrationThis study was registered at the clinicaltrials.gov registration (https://clinicaltrials.gov/study/NCT00005271?term=NCT00005271&rank=1) as NCT00005271.

Unraveling the role of gut microbiota by fecal microbiota transplantation in rat model of kidney stone disease

Emerging research on the microbiome highlights the significant role of gut health in the development of kidney stones, indicating that an imbalance in gut bacteria or dysbiosis can influence the formation of stones by altering oxalate metabolism and urinary metabolite profiles. In particular, the overabundance of specific bacteria such as Enterococcus and Oxalobacter spp., which are known to affect oxalate absorption, is observed in patients with urolithiasis. This study investigates the effects of gut dysbiosis on urolithiasis through fecal microbiota transplantation (FMT) from patients to rats and its impact on urinary mineral excretion and stone formation. Fecal samples from eight patients with calcium oxalate stones and ten healthy volunteers were collected to assess the gut microbiome. These samples were then transplanted to antibiotic-pretreated Wistar rats for a duration of four weeks. After transplantation, we evaluated changes in the fecal gut microbiome profile, urinary mineral excretion rates, and expression levels of intestinal zonula occluden-1 (ZO-1), SLC26A6 and renal NF-κB. In humans, patients with urolithiasis exhibited increased urinary calcium and oxalate levels, along with decreased citrate excretion and increased urinary supersaturation index. The fecal microbiota showed a notable abundance of Bacteroidota. In rodents, urolithiasis-FMT rats showed urinary disturbances similar to patients, including elevated pH, oxalate level, and supersaturation index, despite negative renal pathology. In addition, a slight elevation in the expression of renal NF-κB, a significant intestinal SLC26A6, and a reduction in ZO-1 expression were observed. The gut microbiome of urolithiasis-FMT rats showed an increased abundance of Bacteroidota, particularly Muribaculaceae, compared to their healthy FMT counterparts. In conclusion, the consistent overabundance of Bacteroidota in both urolithiasis patients and urolithiasis-FMT rats is related to altered intestinal barrier function, hyperoxaluria, and renal inflammation. These findings suggest that gut dysbiosis, characterized by an overgrowth of Bacteroidota, plays a crucial role in the pathogenesis of calcium oxalate urolithiasis, underscoring the potential of targeting the gut microbiota as a therapeutic strategy.

AN IN VITRO EVALUATION OF ANTI-UROLITHIASIS POTENTIAL OF SIDDHA FORMULATION SAGALANOI CHOORANAM USING STRUVITE CRYSTAL GROWTH INHIBITION ASSAY

Renal calculus is a rising concern, with a prevalence of 12% across the world and 12% in India, which is around 2 million people affected by Urolithiasis. The rise in the ratio has been correlated to genetic predisposition, working in high temperatures, high caffeine intake, lack of physical activity, and groundwater consumption. Yet the major risk factor is a diet that consists of excess animal proteins, which reduces urinary PH and citrate excretion, leading to the formation of Renal calculi. The main aim of this article is to evaluate the anti-urolithiatic potential of a polyherbal Siddha formulation Sagalanoi chooranam obtained from the classical Siddha text Brahmamuni Karukidai Soothiram 380. From the results, it was concluded that the drug has a high potential as an alternative for the management of renal calculus in Siddha. The ingredients efficiently manage renal calculus due to their potent anti-urolithiasis activity, diuretic and anti-inflammatory activity as cited in modern research articles and by mitigating azhal and Vata humour as mentioned in classical Siddha texts. The effect of Sagalanoi chooranam on struvite crystal growth inhibition assay through a significant reduction in the crystal size further validates the drug's efficiency in managing Renal calculus. In such a scenario, the Siddha drug Sagalanoi chooranam can be used as an individual drug or alongside Biomedicine in the management of Renal calculi.

Urinary Response to Consuming Plant-Based Meat Alternatives in Persons with Normal Kidney Function: The SWAP-MEAT Pilot Trial.

Consuming excess animal meat may exacerbate kidney disorders such as urinary stone disease and chronic kidney disease. Plant-based meat alternatives imitate animal meat, and replace animal with vegetable protein, but it is unclear whether eating plant-meat confers similar health benefits as eating whole vegetables. We hypothesized that eating plant-meat when compared with animal meat decreases dietary acid load but increases dietary phosphorus and nitrogen. SWAP-MEAT was a randomized eight-week, crossover trial (NCT03718988) of participants consuming >2 servings/day of either plant-meat or animal meat for each eight-week phase. We measured urine sulfate, ammonium, pH, phosphorus, urea nitrogen, citrate, and creatinine concentrations, and serum creatinine and bicarbonate concentrations from stored participant samples from each phase. At a single site, we enrolled 36 generally healthy participants (mean±SD age 50.2 ± 13.8 years, 67% women, and 69% White). Eating the plant-meat diet vs. eating the animal meat diet was associated with lower mean concentration of urine sulfate (-6.7 mEq/L; 95% CI -11.0, -2.4), urine ammonium (-4.2 mmol/L; 95% CI -8.2, -0.1), urine phosphorus (-9.0 mg/dL; 95% CI -17.5, -0.5), and urine urea nitrogen (-124.8 mg/dL; 95% CI -226.9, -22.6). Eating plant-meat compared with eating animal meat was associated with higher mean urine pH (+0.3 units; 95% CI 0.2, 0.5) and mean urine citrate/creatinine ratio (+111.65; 95% CI 52.69-170.60). After participants consumed a plant-meat diet compared with when they consumed an animal meat diet, mean serum creatinine concentration was lower (-0.07 mg/dL, 95% CI -0.10, -0.04), whereas mean serum bicarbonate concentration was not different. Eating plant-based meat products, compared with eating animal meat, was associated with lower urinary excretion of sulfate, ammonium, phosphorus, and urea nitrogen and higher urinary excretion of citrate. Our findings provide rationale for examining whether plant-based meat will benefit patients with kidney disease.

Effect of magnesium oxide or citrate supplements on metabolic risk factors in kidney stone formers with idiopathic hyperoxaluria: a randomized clinical trial.

Magnesium is one of the recommended treatments for calcium stone formers (CSFs) with hyperoxaluria. In this study, we compared the effect of magnesium oxide (MgO) or magnesium citrate (MgCit) with placebo on 24-hour urine (24-U) metabolites and the calcium oxalate supersaturation index (CaOx SS). In a randomized, double-blind, placebo-controlled clinical trial, 90 CSFs with idiopathic hyperoxaluria were recruited from a tertiary stone prevention clinic. Patients were randomly assigned into three groups: 120mg MgO, 120mg MgCit or placebo (supplements were taken three times per day, with meals). Finally, 76 patients were included in the final analysis. Analyses of 24-U were performed at baseline and after eight weeks. Study outcomes included changes in 24-U oxalate, magnesium, citrate, and CaOx SS. Dietary factors were controlled by 24-hour food recalls. Repeated measure ANOVA was used to compare the results. After the intervention, both MgO and MgCit supplements decreased 24-U oxalate excretion (-8.13±16.45 in the MgO group and -16.99±18.02 in the MgCit group) and CaOx SS compared to the placebo, with the effects of MgCit reaching statistical significance (p=0.011 and p=0.010, respectively). An increasing trend was observed for 24-U magnesium and citrate excretion without significant differences among groups. Interestingly, MgCit exhibited a significantly greater inhibitory effect on 24-U oxalate in patients with normal urine magnesium levels (p=0.021). Clinically, both MgO and MgCit reduced 24-U oxalate and CaOx SS compared to placebo. However, MgCit demonstrated a greater effect, especially in patients with normal urine magnesium levels.

Medical treatment of uric acid kidney stones.

The prevalence of uric acid stones increases regularly due to its high correlation with obesity, hypertension, metabolic syndrome, type 2 diabetes, and aging. Uric acid stone formation is mainly due to an acidic urinary pH secondary to an impaired urinary ammonium availability responsible for uric acid rather than soluble urate excretion. Alkalization of urine is therefore advocated to prevent uric acid crystallization and considered effective therapy. We report a large series of 120 patients with uric acid kidney stones who were successfully treated with potassium citrate (K-citrate) for stone dissolution without any urologic intervention to prevent stone recurrence, with a median 3.14 years followup. The K-citrate was diluted in 1.5 L of water, avoiding gastrointestinal disorders. Among 75 patients having stones in their kidney at initiation of therapy, a complete chemolysis was obtained in 88% of cases. Stone risk factors decreased under treatment, mainly due to increased diuresis, urinary pH, and citrate excretion. Treatment was stopped in only 2% of patients due to side effects, with no hyperkalemia onset despite a median urinary potassium increase of 44 mmol/day. Contrary to other reports, our data show that medical treatment of uric acid kidney stones is well-tolerated and efficient if regular monitoring of urinary pH is performed.

MAGNESIUM SUPPLEMENTATION INCREASES URINE MAGNESIUM AND CITRATE IN STONE FORMERS WITH HYPOMAGNESURIA

To compare the effects of magnesium repletion by a foods-alone approach or by magnesium supplementation on urinary magnesium and citrate excretion in patients with urine magnesium <70 mg/day. We reviewed medical records of patients in our stone prevention practice who were advised to start a magnesium supplement (Sup), 250-500 mg/d, or increase dietary magnesium consumption. We included adults with 24h UMg <70 mg, those who received magnesium recommendations (corroborated by the dietitian's clinical notes), and those with a follow-up 24h urine collection ≤18 months. Urine results were assessed by group. Groups [No Sup (n=74) and Sup (n=56)] were not different for age, gender, stone history, malabsorption, or other clinical indices. All patients raised UMg (53 to 69 and 47 to 87 mg/d for No Sup and Sup, respectively); however, the increase was significantly higher in the Sup group. Moreover, while 88% of Sup patients achieved UMg ≥70 mg/d, only 58% in the No Sup group did so. Within-group increases in urine citrate were significant only in the Sup group. Among patients with low UMg, both higher consumption from foods and magnesium supplementation significantly increased UMg. However, those who supplemented were significantly more likely to reach or exceed UMg 70 mg/d and achieved higher mean UMg. The change in urine citrate was significant only among those in the Sup group.

#2827 Beyond the scale: unveiling the kidney stone risk after bariatric surgery

Abstract Background and Aims Nephrolithiasis is a prevalent condition, with calcium oxalate being the primary component found in kidney stones. Both obesity and gastric bypass surgery pose as risk factors for nephrolithiasis. Malabsorptive bariatric procedures alter 24-hour urine profiles, leading to increased urinary oxalate and reduced urinary citrate levels. This study aims to evaluate the risk factors for calcium oxalate lithiasis in a population after gastric bypass surgery at our center. Method We performed a monocentric retrospective study to evaluate hyperoxaluria and urinary lithiasis in patients who underwent gastric bypass surgery between 2020 and 2021. We assessed urinary oxalate excretion, urinary citrate excretion, and urinary sodium excretion between 4 and 28 months after surgery. To confirm the adequacy of the collection, a comparison was made with the expected urinary creatinine value (20 to 25 mg/kg ideal weight for men and 15 to 20 mg/kg ideal weight for women). We developed a risk score: citraturia &amp;lt; 288 mg/24 h (1 point); oxaluria &amp;gt; 45 mg/L (1 point) and natriuresis &amp;gt; 97.75 mmol/24 h (1 point). Patients were classified as without risk (0 points), at low risk (1 point), at high risk (2 points), and at very high risk (3 points). Additionally, the patients’ historical incidence of lithiasis was examined, both preoperatively and postoperatively, using clinical records. Post-surgery assessments included imaging evidence of lithiasis (when available) or clinical episodes of renal colic. Results Fifty-six patients underwent a 24-hour urine collection. Twenty-two were excluded due to incomplete urine collection, determined by the expected urinary creatinine value and a time lapse exceeding 28 months between surgery and analytical assessment. The median time elapsed between surgery and analytical evaluation was 9.5 months [IQR 6.3 - 12] months. A total of 34 patients were included in the study, 8.8% were male and the median age of the patients was 51.5 [IQR 42.3–57.8] years. The median body mass index decreased from 43.1 [IQR 39.7–46.3] kg/m2 before to 31.8 [IQR 28.6–35.7] kg/m2 six months after surgery. The low risk for calcium oxalate lithiasis in the examined patient sample was 52.9% (n = 18); high risk 20.6% (n = 7), no risk 26.5% (n = 9) and very high risk 0%. We detected 3 (8.8%) patients with concentration hyperoxaluria, 20 (58.8%) patients with natriuresis &amp;gt; 97.75 mmol/24 h and 8 (23.5%) patients with reduced urinary citrate levels. All patients exhibited normal kidney function. The median follow-up duration was 27 months. Out of the total number of patients, only 3 reported renal colic episodes, and imaging evidence of lithiasis was found in just 2 of them before surgery. Among those with a risk score &amp;gt; 0, only 1 had a history of lithiasis. Throughout the follow-up period, none of the patients experienced new lithiasis post-surgery. Regarding the limitations of our study, we highlight the relatively brief duration of follow-up, which may pose challenges in comprehensively evaluating outcomes such as lithiasis. Additionally, the absence of imaging screening represents a notable constraint, impeding the comprehensive assessment of patients with asymptomatic lithiasis. Conclusion This study concludes that within the bariatric surgery population, a specific subgroup is at an elevated risk for renal lithiasis. Recognizing this subgroup promptly and instituting heightened preventive measures may prove advantageous within this demographic.

Increased risk of nephrolithiasis: an emerging issue in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

PurposeTo investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease.MethodsThis study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed.ResultsThe incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0–25.1) ng/mL; T1: 7.1 (1.8–19.9) ng/mL; T2: 5.9 (2.0–20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3–2.5) ng/mL; T1: 0.3 (0.3–1.1) ng/mL; T2: 0.5 (0.3–1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis.Conclusionsour data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.

The Association Between &lt;i&gt;Sodium Citrate Cotransporter (NaDC-1)&lt;/i&gt; Gene Polymorphism and Urinary Citrate Excretion in Patients with Calcium-containing Kidney Stones

The Association Between &lt;i&gt;Sodium Citrate Cotransporter (NaDC-1)&lt;/i&gt; Gene Polymorphism and Urinary Citrate Excretion in Patients with Calcium-containing Kidney Stones

A combination of β-hydroxybutyrate and citrate ameliorates disease progression in a rat model of polycystic kidney disease.

Our research has shown that interventions producing a state of ketosis are highly effective in rat, mouse, and cat models of polycystic kidney disease (PKD), preventing and partially reversing cyst growth and disease progression. The ketone β-hydroxybutyrate (BHB) appears to underlie this effect. In addition, we have demonstrated that naturally formed microcrystals within kidney tubules trigger a renoprotective response that facilitates tubular obstruction clearance in healthy animals but, alternatively, leads to cyst formation in PKD. The administration of citrate prevents microcrystal formation and slows PKD progression. Juvenile Cy/+ rats, a nonorthologous PKD model, were supplemented from 3 to 8 wk of age with water containing titrated BHB, citrate, or in combination to find minimal effective and optimal dosages, respectively. Adult rats were given a reduced BHB/citrate combination or equimolar control K/NaCl salts from 8 to 12 wk of age. In addition, adult rats were placed in metabolic cages following BHB, citrate, and BHB/citrate administration to determine the impact on mineral, creatinine, and citrate excretion. BHB or citrate alone effectively ameliorates disease progression in juvenile rats, decreasing markers of cystic disease and, in combination, producing a synergistic effect. BHB/citrate leads to partial disease regression in adult rats with established cystic disease, inhibiting cyst formation and kidney injury. BHB/citrate confers benefits via multiple mechanisms, increases creatinine and citrate excretion, and normalizes mineral excretion. BHB and citrate are widely available and generally recognized as safe compounds and, in combination, exhibit high promise for supporting kidney health in polycystic kidney disease.NEW & NOTEWORTHY Combining β-hydroxybutyrate (BHB) and citrate effectively slows and prevents cyst formation and expansion in young Cy/+ rats using less BHB and citrate than when used alone, demonstrating synergy. In adult rats, the combination causes a partial reversal of existing disease, reducing cyst number and cystic area, preserving glomerular health, and decreasing markers of kidney injury. Our results suggest a safe and feasible strategy for supporting kidney health in polycystic kidney disease (PKD) using a combination of BHB and citrate.

Abstract 11900: Potassium Magnesium Citrate is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone

Thiazide-type diuretics (TD) are the first-line treatment of hypertension in many guidelines because of its consistent benefit in lowering BP and cardiovascular risk. TD is also known to cause excess risk of diabetes mellitus (DM), which may limit its long-term use. Although hypokalemia was thought to be the main mechanism of TD-induced dysglycemia, potassium (K) supplementation alone does not consistently prevent TD-induced elevation in fasting plasma glucose (FPG). In addition to reducing serum K, TD triggers magnesium (Mg) depletion. However, it is unknown if Mg supplementation attenuates metabolic side effects of TD. Accordingly, we conducted a randomized double-blinded clinical trial in 60 hypertensive patients without DM to compare effects of KCl (40 meq daily) vs. KMgCitrate (Cit) powder containing identical amount of K, 20 meq of Mg, and 74 meq of Cit daily during chlorthalidone (CTD) treatment. Each patient received CTD alone (25 mg/day) for 3 weeks prior to randomization. The primary endpoint was the change in FPG after 4-month of treatment from baseline (CTD alone) after adjusting for baseline FPG as a covariate. The mean age of subjects was 59±11 years (45% Female, 30% Black participants). We found that CTD induced a significant rise in FPG, insulin, and a significant fall in serum K and 24-h urinary citrate excretion (all p &lt; 0.05). We found that KMgCit significantly increased serum K, 24-hour urinary Mg, and 24-hour urinary Cit excretion; and attenuated the rise in FPG which was not observed with KCl (Figure 1 A-C). There were no significant differences in liver fat by MRI or fasting plasma insulin between the 2 groups. In conclusion, our study showed beneficial effects of magnesium supplementation in maintaining serum K and reversing effects CTD on plasma glucose, which may improve safety profile and optimize long-term cardiovascular outcomes in hypertensive patients.

Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone.

Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TD has not been investigated. Therefore, we aim to determine the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat by magnetic resonance imaging during TD therapy. Accordingly, we conducted a double-blinded RCT in 60 nondiabetic hypertension patients to compare the effects of KCl versus KMgCit during chlorthalidone treatment. Each patient received chlorthalidone alone for 3 weeks before randomization. Primary end point was the change in fasting plasma glucose after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone. The mean age of subjects was 59±11 years (30% Black participants). Chlorthalidone alone induced a significant rise in fasting plasma glucose, and a significant fall in serum K, serum Mg, and 24-hour urinary citrate excretion (all P<0.05). KMgCit attenuated the rise in fasting plasma glucose by 7.9 mg/dL versus KCl (P<0.05), which was not observed with KCl. There were no significant differences in liver fat between the 2 groups. KMgCit is superior to KCl, the common form of K supplement used in clinical practice, in preventing TD-induced hyperglycemia. This action may improve tolerability and cardiovascular safety in patients with hypertension treated with this drug class.

Low pH stress activates several genes for lateral root formation and detoxification of aluminum ions in Cotton plants

In low pH condition of soils (pH<5), Al is solubilized into a phytotoxic form Al(H2O)63+ and inhibits the plant root growth and development. Precisely, during low pH stress (e.g., pH 4.75), aluminum compound converts into its ionic form and becomes higher in level which is a limiting factor for plant root growth and seedling formation. Under aluminum (Al) toxic conditions, the organic acid transporters for example citrate and malate transporters in plasma membrane are involved in organic acid release and form non phytotoxic stable complexes with Al3+ in the rhizosphere. The study showed that, the cotton seedlings exhibited very sensitive phenotypes to low pH stress conditions due to high accumulation of ionic Al stress, the seedlings displayed retarded primary, secondary root growth and small cotyledons. These results indicated that cotton plants are susceptible to low pH condition.. As a whole without fine divisions the root system becomes corraloid in structure which will be having squat secondary roots. Plant has developed a natural defense mechanism in order to combat this unfavorable environment. Expression profile and Al complexation with organic acid exudates studies clearly revealed that both GhALMT1 and GhALS3 genes are involved in Al3+detoxification mechanisms. The remarkable expression was detected for GhALS3 under both low pH and aluminum stress condition in comparison to wild type untreated control whereas GhALMT1 expression was only activated under Al3+ stress condition. Our study, displayed enhanced citrate and malate excretion values in the wild type plants which are treated with Al and H+ stress. Thus, it can be clearly mentioned that GhALMT1 and GhALS3 is playing a significant role in low pHstress tolerance of cotton plant.

Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease.

Patients with kidney stone disease are at higher risk for bone disease. Hypocitraturia is common in patients with kidney stone disease and a key risk factor for stone recurrence. In this retrospective cohort study, we sought to determine whether hypocitraturia is also a risk factor for incident bone disease in patients with kidney stone disease. We used nationwide data from the Veterans Health Administration and identified 9025 patients with kidney stone disease who had a 24-hour urine citrate measurement between 2007 and 2015. We examined clinical characteristics of patients by level of 24-hour urine citrate excretion (<200, 200-400, and >400 mg/d) and the time to osteoporosis or fracture according to 24-hour urine citrate excretion level. Almost one in five veterans with kidney stone disease and a 24-hour urine citrate measurement had severe hypocitraturia, defined as <200 mg/d. Patients with severe hypocitraturia were at risk for osteoporosis or fracture (hazard ratio [HR] = 1.23; confidence interval [CI] 1.03-1.48), but after adjustment for demographic factors, comorbid conditions, and laboratory abnormalities associated with hypocitraturia, the association was no longer statistically significant (HR = 1.18; CI 0.98-1.43). Our results in a predominantly male cohort suggest a modest association between hypocitraturia and osteoporosis or fracture; there are likely to be other explanations for the potent association between kidney stone disease and diminished bone health. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Determinants on urinary excretion of oxalate and other key factors related to urolithiasis among patients with chronic kidney disease: a single center study

PurposeUrolithiasis is a known risk factor for chronic kidney disease (CKD). However, how CKD might affect the risk of incidence of urolithiasis is not widely studied.MethodsUrinary excretion of oxalate as well as other key factors related to urolithiasis was analyzed in a single center study of 572 patients with biopsy-proven kidney disease.ResultsThe mean age of the cohort was 44.9 years and 60% were males. The mean eGFR was 65.9 ml/min/1.73 m2. Median urinary excretion of oxalate was 14.7 (10.4–19.1) mg/24-h and associated with current urolithiasis (OR 12.744, 95% CI: 1.564–103.873 per one logarithm transformed unit of urinary oxalate excretion). Oxalate excretion was not associated with eGFR and urinary protein excretion. Oxalate excretion was higher in patients with ischemia nephropathy as compared with patients with glomerular nephropathy and tubulointerstitial nephropathy (16.4 vs 14.8 vs 12.0 mg, p = 0.018). And ischemia nephropathy (p = 0.027) was associated with urinary oxalate excretion on adjusted linear regression analysis. Urinary excretion of calcium and uric acid was correlated with eGFR and urinary protein excretion (all p < 0.001), with ischemia nephropathy and tubulointerstitial nephropathy associated with uric acid excretion (both p < 0.01) as well. Citrate excretion was correlated with eGFR (p < 0.001) on adjusted linear regression.ConclusionExcretion of oxalate and other key factors related to urolithiasis was differentially associated with eGFR, urinary protein, and pathological changes in CKD patients. The influence of these intrinsic traits of the underlining kidney disease should be considered when evaluating urolithiasis risk in patients with CKD.

Effect of preoperative metabolic profiling to reduce the risk of kidneystones after bariatric surgery in patients with a historyofstoneformation.

Roux-en-Y gastric bypass (RYGB) is associated with an increased risk of kidney stone formation. This is not observed after sleeve gastrectomy (SG). Aim of this study was to assess whether preoperative metabolic profiling is helpful in selecting the most optimal bariatric procedure for patients with a kidney stone history. General hospital, the Netherlands. Patients with a kidney stone history and in the run up to bariatric surgery were screened with non-contrast abdominal computed tomography (CT), serum profiling, and 24-hour urine analysis. Those with stones on radiologic imaging and/or high preoperative urinary oxalate were advised to undergo SG instead of RYGB. Pre- and postoperative urine and serum profile differences between both groups were evaluated retrospectively. Postoperatively, RYGB (N = 28, M:F = 8:20) was associated with a 23.5% reduction in urinary volume, a 85% increase in urinary oxalate excretion with a 230% increase in calcium oxalate (CaOx) supersaturation and a 62% decrease in urinary citrate. Although SG (N = 30, M:F = 12:18) was also associated with a reduction in urinary volume, it had no adverse effects on urinary oxalate and citrate excretion, nor on calcium oxalate supersaturation (CaOx-SS). Both RYGB and SG showed favorable effects on postoperative sodium, calcium, uric acid, and phosphate excretion. This study indicates that preoperative metabolic profiling is important to select the optimal bariatric procedure in patients with an a priori increased risk of kidney stone development. These patients should be strongly encouraged to undergo SG instead of RYGB to prevent progressive or recurrent kidney stone disease.

Associations between Net Gastrointestinal Alkali Absorption, 24-Hour Urine Lithogenic Factors, and Kidney Stones.

It is not clear whether kidney stone formers have an abnormal handling of alkali and acid precursors in the gut, which might affect urine composition and ultimately stone formation. In this study, we aimed to investigate the determinants of net gastrointestinal alkali absorption and its associations with key urinary parameters in a large group of stone formers and non-stone formers. Data were collected from three independent cohorts with at least one 24-hour urine collection. We explored potential determinants of net gastrointestinal alkali absorption and the association between net gastrointestinal alkali absorption, urinary parameters, and stone former status. Finally, we estimated the proportion of the association between urine parameters and stone former status explained by differences in net gastrointestinal alkali absorption. The analysis included 6067 participants (1102 men and 4965 women; 698 and 1804 of whom were stone formers, respectively). Average net gastrointestinal alkali absorption values were consistently lower in stone formers across the three cohorts (from -15.0 to -4.9 mEq/d). Age was directly associated with net gastrointestinal alkali absorption, whereas body mass index and net endogenous acid production were inversely associated. Net gastrointestinal alkali absorption was inversely associated with supersaturation for calcium oxalate, uric acid, and renal net acid excretion and directly associated with supersaturation for calcium phosphate, urine pH, and citrate. The odds of being a stone former was 15% (13%-17%) lower per 10 mEq/24 hours higher net gastrointestinal alkali absorption. Differences in net gastrointestinal alkali absorption explained a modest amount of the differences between stone formers and non-stone formers for supersaturation for calcium oxalate (6.3%) and a sizable amount for supersaturation for uric acid (15.2%), urine pH (38.3%), citrate (26.2%), and renal net acid excretion (63.4%). Kidney stone formers have lower net gastrointestinal alkali absorption, and this explains differences in urine composition and the likelihood of stone formation.

Is hyperuricosuria really a risk factor for calcium oxalate stone formation?

In the seventies of the last century the term hyperuricosuric calcium oxalate (CaOx) urolithiasis has been coined. Allopurinol significantly decreased the recurrence in CaOx stone formers. Nevertheless, the role of hyperuricosuria has been questioned. Other mechanisms could have decreased the risk for recurrence. The underlying mechanisms are not clear. All these studies have been performed with only a limited number of patients. We studied n=2,480 consecutive patients with CaOx stones. For stone analysis, x-ray diffraction was used. The following parameters were examined in all patients: age, sex, body mass index (BMI), arterial blood pressure, stone episodes, diabetes mellitus; blood: creatinine, glucose, uric acid, calcium, sodium and potassium; urine: pH, volume, calcium, uric acid, citrate, ammonia and urea. According to the uric acid excretion (UAE), patients were divided into two groups: 1. UAE &gt; 4 mmol/d (hyperuricosuria), 2. UAE ≤ 4 mmol/d (normouricosuria). We observed significant correlations between UAE and sex, age, BMI, blood pressure, serum values of creatinine, sodium, urine volume, urine levels of calcium, citrate, urea and ammonia as well as serum calcium. No significant correlations were seen to the stone frequency (number of stone episodes), serum potassium and urine pH. In group 1 (n=741), there were 87.2% male and 12.8% female patients; in group 2 (n=1,739), the ratio was 60.6:39.4%. In the hyperuricosuric group, there were significantly more males than in the normouricosuric collective. Hyperuricosuric subjects had a higher BMI, higher blood levels of uric acid and glucose, a higher diuresis, a higher excretion of calcium, urea and ammonium, but a lower excretion of citrate than normouricosuric patients. All the other parameters did not show any significant differences. Especially the number of stone episodes was not different. We concluded that hyperuricosuria went along with many other risk factors for CaOx stone formation, but was not associated with an increased risk for recurrence. Therefore, UAE is not a prognostic marker in CaOx urolithiasis. It is unlikely that hyperuricosuria is a real risk factor for CaOx stone formation and hyperuricosuric CaOx urolithiasis is an own entity.