Retrospective study of the efficacy of oral potassium supplementation in cats with kidney disease.

OBJECTIVES: The aim of this study was to assess the effect of three oral potassium supplements (potassium gluconate tablets [PGT], potassium gluconate granules [PGG] and potassium citrate granules [PCG]) on hypokalemia and serum bicarbonate in cats with chronic kidney disease (CKD). METHODS: Medical records (2006-2016) were retrospectively searched for cats that had been prescribed an oral potassium supplement for management of their CKD-associated hypokalemia. For inclusion, laboratory work had to be available at the time of hypokalemia diagnosis, and at recheck within 1-6 weeks. Treatment response was defined in three ways: any increase in potassium, an increase in potassium to within the normal reference interval, and an increase to >4 mEq/l. RESULTS: Thirty-seven cats met inclusion criteria (16 PGT, 11 PGG, 10 PCG). Dosing ranged from 0.21 to 1.6 mEq/kg/day for PGT, from 0.25 to 1.48 mEq/kg/day for PGG and from 0.04 to 1.34 mEq/kg/day for PCG. After supplementation, 36/37 cats had an increase in potassium, 34/37 increased to within the reference interval and 24/37 had an increase in potassium to >4 mEq/l. There was a statistically significant difference in serum potassium post-supplementation for all three treatments: PGT (P = 0.0001), PGG (P = 0.001) and PCG (P = 0.002). There was a positive correlation between PGT dose and change in potassium concentration (P = 0.04), but there was no significant correlation for PGG or PCG. In cats that had data available, serum bicarbonate increased >2 mEq/l in 1/6 PGT, 1/6 PGG and 3/4 PCG cats. CONCLUSIONS AND RELEVANCE: All three potassium supplements were effective in treating hypokalemia secondary to CKD in the majority of cats despite variable dosing. Data were limited to assess the alkalinizing effect and prospective studies are needed.

Potassium citrate and metabolic acidosis in children with epilepsy on the ketogenic diet: a prospective controlled study.

AIM: To investigate if potassium citrate, a mild alkaline compound, can prevent metabolic acidosis in children with epilepsy treated with the ketogenic diet without reducing antiepileptic efficacy. METHOD: In this prospective controlled study, we investigated the frequency of initial uncompensated metabolic acidosis in 51 participants. There were 22 participants with and 29 without potassium citrate supplementation. The ketogenic diet was used as add-on treatment to children with drug resistant epilepsy. We also estimated the proportion of participants with a greater than 50% seizure reduction after 7 months. RESULTS: None of the 22 participants (15 males, seven females; median age 1y 7mo, interquartile range [IQR] 3y 3mo) with, and 10 of 29 (12 males, 17 females; median age 6y 1mo, IQR 4y 8mo) without potassium citrate developed metabolic acidosis (odds ratio=0.04, 95% CI 0.00-0.75 [p<0.01]); median pH 7.32 vs 7.24; [p<0.001]), and median bicarbonate 19.7mmol/L vs 14.0mmol/L (p<0.001). The number of seizures was reduced by more than 50% in 9 of 22 with potassium citrate and 8 of 29 participants without potassium citrate, 7 months after introducing a ketogenic diet (p=0.4). INTERPRETATION: In the ketogenic diet, potassium citrate supplementation can prevent metabolic acidosis, without reducing antiepileptic efficacy. WHAT THIS PAPER ADDS: Citrate supplementation prevents metabolic acidosis in children treated with a ketogenic diet. Efficacy of the ketogenic diet is not affected by supplementation with citrate. Citrate supplementation does not affect beta-hydroxybuturate concentration. Potassium citrate reduces the time needed to reach an optimal ketogenic ratio. This article is commented on by Schoeler on page 8 of this issue.

Alkalinizing Agents: A Review of Prescription, Over-the-Counter, and Medical Food Supplements.

Introduction: Kidney stones affect 1 in every 11 people in the United States each year. There is a significant high recurrence rate without a stone prevention protocol. Alkali citrate is beneficial in decreasing stone recurrence, but because of the cost and gastrointestinal side effects there is a low adherence rate. This study aims to serve as a review of some of the most commonly used alkalizing over-the-counter supplements that are advertised to prevent and treat kidney stones. Methods: Data were gathered by a comprehensive online literature search and company inquiries for kidney stone prevention supplements. An additional informal poll of the authors selected supplements that are most commonly taken by their patients. A total of eight supplements were evaluated for cost, alkali equivalent provided, dosing, and regulatory information. Results: Eight of the most commonly used supplements were reviewed with a focus on alkalizing agents. Information reviewed revealed dosing recommendations resulting in decreased citrate alkali equivalents per day compared with prescription-strength potassium citrate. Cost, peer-reviewed study results, and regulatory data were reviewed, tabulated, and analyzed. Cost per alkali equivalent was substantially decreased for each supplement compared with the prescribed drug. All supplements were found to be readily available online. Conclusion: Over-the-counter alkalizing agents are available to patients and may be an appropriate alternative to cost-prohibitive potassium citrate when treating urolithiasis patients. Additional testing will be necessary in the future to determine the efficacy of these supplements in the treatment and prevention of urinary stone disease.

Effect of lemon water soluble extract on hyperuricemia in a mouse model.

Lemon is a healthy fruit with high medicinal value. This study found that lemon water soluble extract (LET) can reduce uric acid levels in mice with potassium oxonate induced hyperuricemia. Histopathological analysis suggested that LET caused little damage to the kidneys of mice. It affected mABCG2 and mGLUT9 mRNA expression only in hyperuricemic mice, but not in healthy mice. Our further results show that potassium citrate, rather than citric acid, is the main ingredient in LET with a hypouricemic effect. This study also indicates that lemon does have unique medicinal value for the treatment of hyperuricemia, and that potassium citrate has the potential to be developed as a drug for hyperuricemia. Lowering uric acid through LET and potassium citrate may directly promote the degradation of excessive uric acid in patients with hyperuricemia.

Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats.

BACKGROUND: The pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats. METHODS: To test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks. RESULTS: Potassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not. CONCLUSIONS: In genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality.

Potassium Citrate Supplementation Decreases the Biochemical Markers of Bone Loss in a Group of Osteopenic Women: The Results of a Randomized, Double-Blind, Placebo-Controlled Pilot Study.

The relationship involving acid-base imbalance, mineral metabolism and bone health status has previously been reported but the efficacy of the alkalizing supplementation in targeting acid overload and preventing bone loss has not yet been fully elucidated. In this randomized, double-blind, placebo-controlled study, the hypothesis that potassium citrate (K citrate) modifies bone turnover in women with postmenopausal osteopenia was tested. Three hundred and ten women were screened; 40 women met the inclusion criteria and were randomly assigned to the treatment or the placebo group. They were treated with K citrate (30 mEq day-1) or a placebo in addition to calcium carbonate (500 mg day-1) and vitamin D (400 IU day-1). At baseline and time points of 3 and 6 months, serum indicators of renal function, electrolytes, calciotropic hormones, serum bone turnover markers (BTMs), tartrate-resistant acid phosphatase 5b (TRACP5b), carboxy-terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (BAP), procollagen type 1 N terminal propeptide (PINP)), and urine pH, electrolytes, and citrate were measured. The follow-up was completed by 17/20 patients in the "K citrate" group and 18/20 patients in the "placebo" group. At baseline, 90% of the patients exhibited low potassium excretion in 24 h urine samples, and 85% of cases had at least one urine parameter associated with low-grade acidosis (low pH, low citrate excretion). After treatment, CTX and BAP decreased significantly in both groups, but subjects with evidence of low-grade acidosis gained significant benefits from the treatment compared to the placebo. In patients with low 24h-citrate excretion at baseline, a 30% mean decrease in BAP and CTX was observed at 6 months. A significant reduction was also evident when low citrate (BAP: -25%; CTX: -35%) and a low pH (BAP: -25%; CTX: -30%) were found in fasting-morning urine. In conclusion, our results suggested that K citrate supplementation improved the beneficial effects of calcium and vitamin D in osteopenic women with a documented potassium and citrate deficit, and a metabolic profile consistent with low-grade acidosis.

Medical and dietary interventions for preventing recurrent urinary stones in children.

BACKGROUND: Nephrolithiasis, or urinary stone disease, in children causes significant morbidity, and is increasing in prevalence in the North American population. Therefore, medical and dietary interventions (MDI) for recurrent urinary stones in children are poised to gain increasing importance in the clinical armamentarium. OBJECTIVES: To assess the effects of medical and dietary interventions (MDI) for the prevention of idiopathic urinary stones in children aged from one to 18 years. SEARCH METHODS: We searched multiple databases using search terms relevant to this review, including studies identified from the Cochrane Central Register of Controlled Trials (CENTRAL, 2017, Issue 1), MEDLINE OvidSP (1946 to 14 February 2017), Embase OvidSP (1980 to 14 February 2017), International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Additionally, we handsearched renal-related journals and the proceedings of major renal conferences, and reviewed weekly current awareness alerts for selected renal journals. The date of the last search was 14 February 2017. There were no language restrictions. SELECTION CRITERIA: Randomized controlled trials of at least one year of MDI versus control for prevention of recurrent idiopathic (non-syndromic) nephrolithiasis in children. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. Titles and abstracts were identified by search criteria and then screened for relevance, and then data extraction and risk of bias assessment were carried out. We assessed the quality of evidence using GRADE. MAIN RESULTS: The search identified one study of 125 children (72 boys and 53 girls) with calcium-containing idiopathic nephrolithiasis and normal renal morphology following initial treatment with shockwave lithotripsy (SWL). Patients were randomized to oral potassium citrate 1 mEq/kg per day for 12 months versus no specific medication or preventive measure with results reported for a total of 96 patients (48 per group). This included children who were stone-free (n = 52) or had residual stone fragments (n = 44) following SWL. Primary outcomes:Medical therapy may lower rates of stone recurrence with a risk ratio (RR) of 0.19 (95% confidence interval (CI) 0.06 to 0.60; low quality evidence). This corresponds to 270 fewer stone recurrences per 1000 (133 fewer to 313 fewer) children. We downgraded the quality of evidence by two levels for very serious study limitations related to unclear allocation concealment (selection bias) and a high risk of performance, detection and attrition bias. While the data for adverse events were incomplete, they reported that six of 48 (12.5%) children receiving potassium citrate left the trial because of adverse effects. This corresponds to a RR of 13.0 (95% CI 0.75 to 224.53; very low quality evidence); an absolute effect size estimate could not be generated. We downgraded the quality of evidence for study limitations and imprecision.We found no information on retreatment rates. SECONDARY OUTCOMES: We found no evidence on serum electrolytes, 24-hour urine collection parameters or time to new stone formation.We were unable to perform any preplanned secondary analyses. AUTHORS' CONCLUSIONS: Oral potassium citrate supplementation may reduce recurrent calcium urinary stone formation in children following SWL; however, our confidence in this finding is limited. A substantial number of children stopped the medication due to adverse events. There is no trial evidence on retreatment rates. There is a critical need for additional well-designed trials in children with nephrolithiasis.

Effect of dietary supplements in reducing probability of death for uremic crises in dogs affected by chronic kidney disease (masked RCCT).

Chitosan and alkalinizing agents can decrease morbidity and mortality in humans with chronic kidney disease (CKD). Whether this holds true in dog is not known. Objective of the study was to determine whether a commercial dietary supplement containing chitosan, phosphate binders, and alkalinizing agents (Renal), compared to placebo, reduces mortality rate due to uremic crises in dogs with spontaneous CKD, fed a renal diet (RD). A masked RCCT was performed including 31 azotemic dogs with spontaneous CKD. Dogs enrolled in the study were randomly allocated to receive RD plus placebo (group A; 15 dogs) or RD plus Renal (group B; 16 dogs). During a first 4-week period, all dogs were fed an RD and then randomized and clinically evaluated up to 44 weeks. The effects of dietary supplements on mortality rate due to uremic crises were assessed. At 44 weeks, compared to group A, dogs in group B had approximately 50% lower mortality rate due to uremic crises (P = 0.015). Dietary supplementation with chitosan, phosphate binders, and alkalinizing agents, along with an RD, is beneficial in reducing mortality rate in dogs with spontaneous CKD.

The effects of the hydroalcohol extract of Rosa canina L. fruit on experimentally nephrolithiasic Wistar rats.

This research evaluated the possible therapeutic potential of Rosa canina (RC) as a preventive agent in experimentally induced calcium oxalate (CaOx) nephrolithiasis with ethylene glycol (1% EG) in rats. In this experiment, 50 Wistar rats were divided randomly into five groups (n = 10). These groups received tap drinking water (group I), 1% EG (group II), 250 mg/kg RC + 1% EG (group III), 500 mg/kg RC + 1% EG (group IV), or 2.5 g/kg potassium citrate + 1% EG (group V) for a period of 30 days. Blood and urine were collected for biochemical analysis, and the liver and kidneys were prepared for total lipid peroxides, calcium content and histological evaluation. The extract was analysed for total phenolics, flavonoids, ascorbic acid, citric acid and radical scavenger activity. The supplementation of the hydromethanol RC extract contributed to reducing the kidney and liver lipid peroxides to optimum levels in rats that had been treated with EG-induced CaOx lithiasis. The extract also decreased renal and urinary calcium contents, decreased the size and number of CaOx calculi in the kidneys, and significantly increased citrate excretion without changing the volume, pH, or urinary concentrations of oxalate in comparison with the control group. According to these results, RC can be useful as a preventive agent against the formation of CaOx kidney stones.

Splenda® improves tolerance of oral potassium citrate supplementation for prevention of stone formation: results of a randomized double-blind trial.

BACKGROUND AND PURPOSE: Oral citrate supplements have been shown to decrease kidney stone recurrence rates in both laboratory and clinical studies. The taste of the citrate supplements, however, is poor, and long-term compliance is low. Our objective was to determine if Splenda(®) added to potassium citrate (KCit) improves palatability without changing 24-hour urine parameters. PATIENTS AND METHODS: 12 subjects were randomly assigned to receive either KCit alone for 3 days or KCit + Splenda in a double-blind trial. The 24-hour urine collections were performed before and after 3 days of therapy. After 1 week, the two groups switched treatments. After each treatment, a visual analog taste scale was completed to gauge the taste and palatability. The 24-hour urine parameters of kidney stone risk factors were compared between groups. The primary end points were to determine whether Splenda improved palatability of citrate supplementation and whether it altered 24-hour urine parameters. RESULTS: Taste was judged to be 2.5 ± 0.9 points better in the Splenda + KCit compared with KCit alone (P=0.02). The 24-hour Cit, K, and pH were significantly higher in the KCit and KCit + Splenda groups compared with baseline, but not significantly different from each other. CONCLUSION: Splenda significantly improves the palatability of KCit therapy and does not alter the beneficial effects of KCit on 24-hour urine Cit, K, or pH. The addition of Splenda altered the average taste score from one that might prohibit compliance to one that would not.

Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet.

OBJECTIVE: Kidney stones are an adverse event with the ketogenic diet (KD), occurring in approximately 6% of children who are started on this therapy for intractable epilepsy. Potassium citrate (Polycitra K) is a daily oral supplement that alkalinizes the urine and solubilizes urine calcium, theoretically reducing the risk for kidney stones. METHODS: Children who started the KD from 2000 to 2008 at Johns Hopkins Hospital, with at least 1 month of follow-up, were evaluated (N = 313). From 2000 to 2005, children were treated with daily Polycitra K at 2 mEq/kg per day only in the setting of identified hypercalciuria, whereas, since 2006, it has been started for all children empirically at KD onset. RESULTS: Polycitra K was administered to 198 children preventatively overall, 4 (2.0%) of whom developed kidney stones, compared with 11 (10.5%) of 105 who did not receive Polycitra K (P = .003). Two children since 2006 refused Polycitra K, 1 of whom developed a kidney stone. Successful empiric administration of Polycitra K at KD onset resulted in a kidney-stone incidence of 0.9% (1 of 106) compared with administration only because of hypercalciuria, 6.7% (13 of 195; P = .02). Polycitra K resulted in less acidic urine (mean pH: 6.8 vs 6.2; P = .002) but not reduced serum acidosis. No adverse effects of oral citrates were reported. CONCLUSIONS: Oral potassium citrate is an effective preventive supplement against kidney stones in children who receive the KD, achieving its goal of urine alkalinization. Universal supplementation is warranted.

Effect of potassium citrate supplementation or increased fruit and vegetable intake on bone metabolism in healthy postmenopausal women: a randomized controlled trial.

BACKGROUND: Alkali provision may explain why fruit and vegetables benefit bone health. OBJECTIVE: We aimed to determine the effects of alkali-providing potassium citrate (double-blind) and fruit and vegetable intake (single-blind) on bone turnover over 2 y. DESIGN: We conducted a randomized placebo-controlled trial in 276 postmenopausal women (aged 55-65 y). Women were randomly assigned to 4 groups: high-dose potassium citrate (55.5 mEq/d), low-dose potassium citrate (18.5 mEq/d), placebo, and 300 g additional fruit and vegetables/d (equivalent of 18.5 mEq alkali). Serum and fasted urine for bone markers were collected at baseline and at 3, 6, 12, 18, and 24 mo. An additional urine sample was collected at 4-6 wk. Bone mineral density (BMD) was measured at baseline and 2 y. RESULTS: Repeated-measures ANOVA showed no difference between groups for urinary free deoxypyridinoline cross-links relative to creatinine (fDPD/Cr), serum N-terminal propeptide of type 1 collagen, or beta C-terminal telopeptide, although, at 4-6 wk, fDPD/Cr was lower in the high-dose potassium citrate group (P = 0.04). Mean +/- SD spine BMD loss in the placebo group (1.8 +/- 3.9%) did not differ significantly from that in the treatment groups (2.1 +/- 3.2%; P = 0.88). Hip BMD loss in the placebo and low-dose potassium citrate groups was 1.3 +/- 2.3% and 2.2 +/- 2.3%, respectively (P = 0.14). CONCLUSIONS: Two-year potassium citrate supplementation does not reduce bone turnover or increase BMD in healthy postmenopausal women, which suggests that alkali provision does not explain any long-term benefit of fruit and vegetable intake on bone.

Citraturic, alkalinizing and antioxidative effects of limeade-based regimen in nephrolithiasis patients.

Potassium citrate has long been used as a prophylactic remedy for nephrolithiasis recurrence. Lemonade consumption is also suggested as an option. We compared the efficacy of consumption of solution containing manufactured lime powder with that of potassium citrate, on the improvement of metabolic risk factors, oxidative stress and renal tubular damage in nephrolithiasis patients. Patients with kidney stone were enrolled and randomly assigned to three treatment programs for 3 month period consisting of consumption of solution containing lime powder (Group 1, n=13), potassium citrate (Group 2, n=11) and lactose as placebo regimen (Group 3, n=7). Lime powder and potassium citrate contained equal amounts of potassium (21 mEq) and citrate (63 mEq). After treatment, there was an increase in urinary pH, potassium and citrate in Group 1 and 2. Increased plasma potassium and red blood cell glutathione (R-GSH) and decreased urinary malondialdehyde were found in Group 1, but not observed in Group 2. R-GSH was decreased in Group 2. Urinary N-acetyl-beta-glucosaminidase activity and fractional excretion of magnesium, as renal tubular damage indicators, were decreased only in Group 1. In Group 3, all measured parameters were unaltered except for an increased urinary chloride. In conclusion, consumption of our in-house lime powder exerted citraturic and alkalinizing actions as efficient as consumption of potassium citrate. In addition, it provided an antioxidative effect and was able to attenuate renal tubular damage. These pharmacological properties may be clinically useful to diminish the stone-forming potential in kidney stone patients and hence for preventing recurrent calculi.

Long-term intake of a high-protein diet with or without potassium citrate modulates acid-base metabolism, but not bone status, in male rats.

High dietary protein intake generates endogenous acid production, which may adversely affect bone health. Alkaline potassium citrate (Kcit)(2) may contribute to the neutralization of the protein-induced metabolic acidosis. We investigated the impact of 2 levels of protein intake and Kcit supplementation on acid-base metabolism and bone status in rats. Two-month-old Wistar male rats were randomly assigned to 4 groups (n = 30 per group). Two groups received a normal-protein content (13%) (NP) or a high-protein (HP) content diet (26%) for 19 mo. The 2 other groups received identical diets supplemented with Kcit (3.60%) (NPKcit and HPKcit). Rats were pair-fed based on the ad libitum intake of the HP group. At 9, 16, and 21 mo of age, 10 rats of each group were killed. The HP diet induced a metabolic acidosis characterized by hypercalciuria, hypermagnesuria, and hypocitraturia at all ages. Kcit supplementation neutralized this effect, as evidenced by decreased urinary calcium and magnesium excretion by the HPKcit rats. Femoral bone mineral density, biomechanical properties, bone metabolism biomarkers (osteocalcin and deoxypyridinoline), and plasma insulin-like growth factor 1 levels were not affected by the different diets. Nevertheless, at 21 mo of age, calcium retention was reduced in the HP group. This study suggests that lifelong excess of dietary protein results in low-grade metabolic acidosis without affecting the skeleton, which may be protected by an adequate calcium supply.

The effect of a dietary supplement of potassium chloride or potassium citrate on blood pressure in predominantly normotensive volunteers.

Blood pressure (BP) shows a continuous relationship with the risk of CVD. There is substantial evidence that dietary potassium exerts an anti-pressor effect. Most clinical trials have used KCl. However, the chloride ion may have a pressor effect and in foods potassium is associated with organic anions. In a double-blind randomized placebo-controlled trial we explored the effect on BP of two salts of potassium, KCl and potassium citrate (K-cit), in predominantly young healthy normotensive volunteers. The primary outcome was the change in mean arterial pressure as measured in a clinic setting. After 6 weeks of supplementation, compared with the placebo group (n 31), 30 mmol K-cit/d (n 28) changed mean arterial pressure by -5.22 mmHg (95% CI -8.85, -4.53) which did not differ significantly from that induced by KCl (n 26), -4.70 mmHg (-6.56, -2.84). The changes in systolic and diastolic BP were -6.69 (95% CI -8.85, -4.43) and -4.26 (95% CI -6.31, -2.21) mmHg with K-cit and -5.24 (95% CI -7.43, -3.06) and -4.30 (95% CI -6.39, -2.20) mmHg with KCl, and did not differ significantly between the two treatments. Changes in BP were not related to baseline urinary electrolytes. A greater treatment-related effect was observed in those with higher systolic BP. Increasing dietary potassium could therefore have a significant impact on the progressive rise in BP in the entire population.

Effects of plant food potassium salts (citrate, galacturonate or tartrate) on acid-base status and digestive fermentations in rats.

Potassium (K) organic anion salts, such as potassium citrate or potassium malate in plant foods, may counteract low-grade metabolic acidosis induced by western diets, but little is known about the effect of other minor plant anions. Effects of K salts (chloride, citrate, galacturonate or tartrate) were thus studied on the mineral balance and digestive fermentations in groups of 6-week-old rats adapted to an acidogenic/5 % inulin diet. In all diet groups, substantial amounts of lactate and succinate were present in the caecum, besides SCFA. SCFA were poorly affected by K salts conditions. The KCl-supplemented diet elicited an accumulation of lactate in the caecum; whereas the lactate caecal pool was low in rats fed the potassium tartrate-supplemented (K TAR) diet. A fraction of tartrate (around 50 %) was recovered in urine of rats fed the K TAR diet. Potassium citrate and potassium galacturonate diets exerted a marked alkalinizing effect on urine pH and promoted a notable citraturia (around 0.5 micro mol/24 h). All the K organic anion salts counteracted Ca and Mg hyperexcretion in urine, especially potassium tartrate as to magnesuria. The present findings indicate that K salts of unabsorbed organic anions exert alkalinizing effects when metabolizable in the large intestine, even if K and finally available anions (likely SCFA) are not simultaneously bioavailable. Whether this observation is also relevant for a fraction of SCFA arising from dietary fibre breakdown (which represents the major organic anions absorbed in the digestive tract in man) deserves further investigation.

Organic potassium salts or fibers effects on mineral balance and digestive fermentations in rats adapted to an acidogenic diet.

BACKGROUND: Fibers and potassium (K) organic salts in plant foods are liable to affect Ca and Mg balance at digestive and renal levels, respectively. K organic salts could counteract the acidifying effects of western diets and consequences of excess NaCl. AIM OF THE STUDY: To study this question, male rats were adapted to a basal acidifying low-K (LK) diet, or to diets supplemented with a fiber mix (LK/F), or K citrate (HK) or both (HK/F). RESULTS: HK and HK/F diets displayed a marked alkalinizing effect in urine and promoted citraturia, but this effect was not modulated by fibers. The effect of fibers on Ca digestive absorption was more potent than K citrate effect on Ca renal excretion. In contrast, K citrate effect on kidney Mg excretion was more effective than that of fibers on Mg digestive absorption, a maximal effect on Mg balance was observed in rats fed the HK/F diet. Digestive fermentations in rats fed the LK/F diet were characterized by high-propionic acid fermentations and succinate accumulation. In rats adapted to the HK/F diet, K citrate supplementation depressed succinate and increased butyrate concentrations. CONCLUSION: Organic anions arising from digestive fermentations seem to be not directly involved in the alkalinizing effects of plant foods. Fibers and organic K salts exert distinct effects on Ca and Mg metabolism, but with interesting interactions as to Mg balance, digestive fermentations and urine pH.

Excess casein in the diet is not the unique cause of low-grade metabolic acidosis: role of a deficit in potassium citrate in a rat model.

This study examined the effects of a dietary model of protein excess and K anion salt deficit on the occurrence of metabolic acidosis in rat. Rats were adapted to diets containing either 13 or 26% casein, together with mineral imbalance, through lowering K/increasing sodium/omitting alkalinizing anions. For each protein level, a group of rats was supplemented with K citrate. Dietary K citrate resulted in neutral urinary pH, whatever the protein level. Urea excretion was higher in rats adapted to 26% casein than 13% casein diets, but K citrate enhanced this excretion and suppressed ammonium elimination. No citraturia could be observed in acidotic rats, whereas K citrate greatly stimulated citraturia and 2-ketoglutarate excretion. In conclusion, low-grade metabolic acidosis can occur with a moderate protein level in the diet. K citrate was apparently less effective in rats adapted to the 26% casein level than in those adapted to the 13% casein level with regard to magnesium, citrate and 2-ketoglutarate concentrations in urine.

Hypocitraturia despite potassium citrate tablet supplementation.

Citrate supplementation is widely used in the prevention of recurrent nephrolithiasis with hypocitraturia. Potassium citrate is the most commonly used citrate agent for this indication. In patients with chronic diarrheal syndromes, the absorption of potassium citrate can be affected. We describe a patient who presented with recurrent nephrolithiasis and chronic diarrhea and was found to have severe hypocitraturia despite citrate supplementation with potassium citrate tablets, likely due to inadequate gastrointestinal absorption of citrate from the slow-release wax-matrix tablets.