-
Urolithiasis Feb 2019Careful phenotyping of patients to classify those with kidney stones has a long and important history in revealing the chemical basis for stone formation. Advances in... (Review)
Review
Careful phenotyping of patients to classify those with kidney stones has a long and important history in revealing the chemical basis for stone formation. Advances in our genetic understanding of kidney stones will lead to incredible insights regarding the pathophysiology of this common disorder. At this time, both evaluation of urine chemistry and genotyping of patients are extremely useful in the setting of a university and research-based kidney stone clinic. For much of the world, in a more clinically focused setting, these techniques are neither available nor absolutely necessary. Careful implementation of an empiric prescription based on stone composition would have an important effect to reduce stone recurrence in the world's many stone formers. Increased fluid intake, generic dietary manipulations, and prescription of potassium citrate and thiazides are all appropriate empiric therapies for people with calcium and uric acid kidney stones.
Topics: Calcium; Diet, Sodium-Restricted; Dietary Approaches To Stop Hypertension; Fluid Therapy; Genetic Testing; Humans; Kidney Calculi; Potassium Citrate; Recurrence; Thiazides; Treatment Outcome; Uric Acid
PubMed: 30478476
DOI: 10.1007/s00240-018-1090-6 -
Nature Reviews. Nephrology Sep 2016The most common presentation of nephrolithiasis is idiopathic calcium stones in patients without systemic disease. Most stones are primarily composed of calcium oxalate... (Review)
Review
The most common presentation of nephrolithiasis is idiopathic calcium stones in patients without systemic disease. Most stones are primarily composed of calcium oxalate and form on a base of interstitial apatite deposits, known as Randall's plaque. By contrast some stones are composed largely of calcium phosphate, as either hydroxyapatite or brushite (calcium monohydrogen phosphate), and are usually accompanied by deposits of calcium phosphate in the Bellini ducts. These deposits result in local tissue damage and might serve as a site of mineral overgrowth. Stone formation is driven by supersaturation of urine with calcium oxalate and brushite. The level of supersaturation is related to fluid intake as well as to the levels of urinary citrate and calcium. Risk of stone formation is increased when urine citrate excretion is <400 mg per day, and treatment with potassium citrate has been used to prevent stones. Urine calcium levels >200 mg per day also increase stone risk and often result in negative calcium balance. Reduced renal calcium reabsorption has a role in idiopathic hypercalciuria. Low sodium diets and thiazide-type diuretics lower urine calcium levels and potentially reduce the risk of stone recurrence and bone disease.
Topics: Apatites; Calcium; Humans; Hypercalciuria; Kidney Calculi
PubMed: 27452364
DOI: 10.1038/nrneph.2016.101 -
Journal of Nephrology 2010The formation of various types of kidney stones is strongly influenced by urinary pH. An alkaline pH favors the crystallization of calcium- and phosphate-containing... (Review)
Review
The formation of various types of kidney stones is strongly influenced by urinary pH. An alkaline pH favors the crystallization of calcium- and phosphate-containing stones, whereas and acidic urine pH promotes uric acid or cystine stones. The activity of many transport processes involved in calcium, citrate and phosphate handling are sensitive to changes in systemic or local pH as shown for several phosphate transporters, the citrate transporter NaDC1 and the TRPV5 calcium channel. Defects in urinary acidification (excretion of inappropriately alkaline or acidic urines, respectively) contribute to kidney stone disease. The low excretion of ammonium in patients with metabolic syndrome has been linked to more acidic urine and a higher incidence of uric acid stones. In this state, insulin resistance may reduce ammonium excretion by the proximal tubule. On the other hand, defensive mechanisms may protect from kidney stone formation in conditions such as hypercalciuria where high luminal calcium concentrations stimulate urinary acidification and reduce urinary concentration via a calcium-sensing receptor, resulting in the excretion of acidic and diluted urine. This review will discuss a few aspects that relate to the capacity of the kidney to regulate pH and its impact on the excretion of solutes that participate in the formation or prevention of stones.
Topics: Acidosis; Animals; Calcium; Humans; Hydrogen-Ion Concentration; Kidney; Kidney Calculi; Metabolic Syndrome; Quaternary Ammonium Compounds; Uric Acid
PubMed: 21170875
DOI: No ID Found -
Critical Care (London, England) Jan 2019Regional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Regional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure as one of the contraindications for citrate anticoagulation. However, some studies suggested that the use of citrate for CRRT in liver failure patients did not increase the risk of citrate-related complications. The purpose of this systematic review is to summarize the current evidences on the safety and efficacy of RCA for CRRT in liver failure patients.
METHODS
We performed a comprehensive search on PubMed, Embase, and the Cochrane Library databases from the inception to March 1, 2018. Studies enrolled adult (age > 18 years) patients with various levels of liver dysfunction underwent RCA-CRRT were included in this systematic review.
RESULTS
After the study screening, 10 observational studies with 1241 liver dysfunction patients were included in this systematic review. The pooled rate of citrate accumulation and bleeding was 12% [3%, 22%] and 5% [2%, 8%], respectively. Compared with the baseline data, the serum pH, bicarbonate, and base excess (BE), the rate of metabolic alkalosis, the serum ionized calcium (ionCa) and total calcium (totCa) level, and the ratio of total calcium/ionized calcium (totCa/ionCa) significantly increased at the end of observation. However, no significant increase was observed in serum citrate (MD - 65.82 [- 194.19, 62.55]), lactate (MD 0.49 [- 0.27, 1.26]) and total bilirubin concentration (MD 0.79 [- 0.70, 2.29]) at the end of CRRT. Compared with non-liver failure patients, the live failure patients showed no significant difference in the pH (MD - 0.04 [- 0.13, 0.05]), serum lactate level (MD 0.69 [- 0.26, 1.64]), and totCa/ionCa ratio (MD 0.03 [- 0.12, 0.18]) during CRRT. The median of mean filter lifespan was 55.9 h, with a range from 22.7 to 72 h.
CONCLUSIONS
Regional citrate anticoagulation seems to be a safe anticoagulation method in liver failure patients underwent CRRT and could yield a favorable filter lifespan. Closely monitoring the acid base status and electrolyte balance may be more necessary during RCA-CRRT in patients with liver failure.
Topics: Acid-Base Equilibrium; Adult; Anticoagulants; Citric Acid; Hemorrhage; Humans; Liver Failure; Renal Replacement Therapy
PubMed: 30678706
DOI: 10.1186/s13054-019-2317-9 -
BMC Medicine Dec 2023Solute carrier family 13 member 5 (SLC13A5) is a Na-coupled citrate co-transporter that mediates entry of extracellular citrate into the cytosol. SLC13A5 inhibition has...
BACKGROUND
Solute carrier family 13 member 5 (SLC13A5) is a Na-coupled citrate co-transporter that mediates entry of extracellular citrate into the cytosol. SLC13A5 inhibition has been proposed as a target for reducing progression of kidney disease. The aim of this study was to leverage the Mendelian randomization paradigm to gain insight into the effects of SLC13A5 inhibition in humans, towards prioritizing and informing clinical development efforts.
METHODS
The primary Mendelian randomization analyses investigated the effect of SLC13A5 inhibition on measures of kidney function, including creatinine and cystatin C-based measures of estimated glomerular filtration rate (creatinine-eGFR and cystatin C-eGFR), blood urea nitrogen (BUN), urine albumin-creatinine ratio (uACR), and risk of chronic kidney disease and microalbuminuria. Secondary analyses included a paired plasma and urine metabolome-wide association study, investigation of secondary traits related to SLC13A5 biology, a phenome-wide association study (PheWAS), and a proteome-wide association study. All analyses were compared to the effect of genetically predicted plasma citrate levels using variants selected from across the genome, and statistical sensitivity analyses robust to the inclusion of pleiotropic variants were also performed. Data were obtained from large-scale genetic consortia and biobanks, with sample sizes ranging from 5023 to 1,320,016 individuals.
RESULTS
We found evidence of associations between genetically proxied SLC13A5 inhibition and higher creatinine-eGFR (p = 0.002), cystatin C-eGFR (p = 0.005), and lower BUN (p = 3 × 10). Statistical sensitivity analyses robust to the inclusion of pleiotropic variants suggested that these effects may be a consequence of higher plasma citrate levels. There was no strong evidence of associations of genetically proxied SLC13A5 inhibition with uACR or risk of CKD or microalbuminuria. Secondary analyses identified evidence of associations with higher plasma calcium levels (p = 6 × 10) and lower fasting glucose (p = 0.02). PheWAS did not identify any safety concerns.
CONCLUSIONS
This Mendelian randomization analysis provides human-centric insight to guide clinical development of an SLC13A5 inhibitor. We identify plasma calcium and citrate as biologically plausible biomarkers of target engagement, and plasma citrate as a potential biomarker of mechanism of action. Our human genetic evidence corroborates evidence from various animal models to support effects of SLC13A5 inhibition on improving kidney function.
Topics: Humans; Biomarkers; Calcium; Citrates; Creatinine; Cystatin C; Drug Development; Genome-Wide Association Study; Kidney; Mendelian Randomization Analysis; Renal Insufficiency, Chronic; Symporters
PubMed: 38110950
DOI: 10.1186/s12916-023-03227-5 -
Food Chemistry Jan 2022Strontium chloride added to aqueous suspensions of metastable calcium citrate tetrahydrate increased calcium ion activity measured electrochemically without transition...
Strontium chloride added to aqueous suspensions of metastable calcium citrate tetrahydrate increased calcium ion activity measured electrochemically without transition of metastable tetrahydrate to stable calcium citrate hexahydrate as shown by DSC. Calcium activity increase was explained by lower solubility of strontium citrate pentahydrate formed (8.9 × 10 M at 25 °C) increasing with temperature compared to calcium citrate tetrahydrate (1.6 × 10 M) decreasing with temperature. Strontium binding to citrate was found endothermic, ΔH = 45 kJ∙mol at 25 °C, while calcium binding shows variation from ΔH = 94 kJ∙mol at 10 °C becoming exothermic above physiological temperature with ΔH = -9 kJ∙mol at 45 °C as determined from temperature and concentration variation in electric conductivity. These differences in solution thermodynamics and pH effect on complex formation between calcium and strontium citrate are discussed in relation to biomineralization.
Topics: Calcium; Calcium Citrate; Solubility; Strontium; Thermodynamics
PubMed: 34343801
DOI: 10.1016/j.foodchem.2021.130674 -
Urolithiasis Oct 2018The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also...
The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also prevents stone formation acting via regulation of apical dicarboxylate and citrate transport. Urinary citrate, partially reabsorbed as a dicarboxylate in the proximal tubule lumen, inhibits stone formation by complexing calcium. We previously demonstrated a novel apical calcium-sensitive dicarboxylate transport system in OK proximal tubule cells. This calcium-sensitive process has the potential to modulate the amount of citrate available to complex increased urinary calcium. Using isotope labeled succinate uptake in OK cells along with various pharmacologic tools we examined whether the CaSR alters apical dicarboxylate transport and through which signal transduction pathways this occurs. Our results indicate that in the proximal tubule CaSR adjusts apical dicarboxylate transport, and does so via a CaSR → G → PKC signaling pathway. Thus, the CaSR may decrease the propensity for stone formation via actions in both proximal and distal nephron segments.
Topics: Animals; Biological Transport; Calcium; Cells, Cultured; Citric Acid; Dicarboxylic Acids; Kidney Tubules, Distal; Kidney Tubules, Proximal; Opossums; Receptors, Calcium-Sensing; Renal Elimination
PubMed: 29383416
DOI: 10.1007/s00240-018-1035-0 -
International Journal of Preventive... 2017Nephrolithiasis is a common health problem across the globe with a prevalence of 15%-20%. Idiopathic hypercalciuria is the most common cause of nephrolithiasis, and... (Review)
Review
Nephrolithiasis is a common health problem across the globe with a prevalence of 15%-20%. Idiopathic hypercalciuria is the most common cause of nephrolithiasis, and calcium oxalate stones are the most common type of stones in idiopathic hypercalciuric patients. Calcium phosphate stones are frequently associated with other diseases such as renal tubular acidosis type 1, urinary tract infections, and hyperparathyroidism. Compared with flat abdominal film and renal sonography, a noncontrast helical computed tomography scan of the abdomen is the diagnostic procedure of choice for detection of small and radiolucent kidney stones with sensitivity and specificity of nearly 100%. Stones smaller than 5 mm in diameter often pass the urinary tract system and rarely require surgical interventions. The main risk factors for stone formation are low urine output, high urinary concentrations of calcium, oxalate, phosphate, and uric acid compounded by a lower excretion of magnesium and citrate. A complete metabolic workup to identify the risk factors is highly recommended in patients who have passed multiple kidney stones or those with recurrent disease. Calcium oxalate and calcium phosphate stones are treated by the use of thiazide diuretics, allopurinol, and potassium citrate. Strategies to prevent kidney stone recurrence should include the elimination of the identified risk factors and a dietary regimen low in salt and protein, rich in calcium and magnesium which is coupled with adequate fluid intake.
PubMed: 28966756
DOI: 10.4103/ijpvm.IJPVM_17_17 -
Clinical Kidney Journal Dec 2021There is an unmet need to develop safe and successful heparin-free regional anticoagulation modalities in haemodialysed patients at risk of bleeding. Whether the...
BACKGROUND
There is an unmet need to develop safe and successful heparin-free regional anticoagulation modalities in haemodialysed patients at risk of bleeding. Whether the addition of citrate as a prefilter injection or in the dialysate itself is required to reach anticoagulation objectives when calcium-free dialysate is used as regional anticoagulation remains unclear.
METHODS
In this monocentric retrospective study, we report our experience of 908 dialysis sessions performed with a calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance, without additional heparin.
RESULTS
Premature termination for filter clotting occurred in 20 sessions (2.2%) and duration of session was >4.5 h in 135 (15%; maximum duration 6 h). In addition, we could investigate the citrate, calcium and acid-basis status during haemodialysis sessions performed with (citrate group, = 20 sessions) or without (citrate-free group, = 19 sessions) citrate in the dialysate. In 20 sessions performed in patients with underlying liver disorders and using calcium-free citrate-containing dialysate, patients' ionized calcium (iCa) and serum citrate levels were stable and remained within the normal range, respectively. Post-filter iCa was below 0.4 mmol/L in 19/20 sessions and citrate was 0.304 mmol/L (range: 0.011; 0.548). In 19 sessions that used calcium and citrate-free dialysate, post-filter iCa was 0.41 mmol/L (0.34; 0.5) and all sessions extended to 4 h or beyond.
CONCLUSIONS
Regional anticoagulation of haemodialysis with a calcium-free dialysate and calcium reinjection according to the ionic dialysance is safe. Adding citrate to the dialysate is not mandatory to prevent dialysis circuit clotting in most patients.
PubMed: 34950464
DOI: 10.1093/ckj/sfab087 -
Reproduction, Nutrition, Development 2005The salt of milk constitutes a small part of milk (8-9 g.L(-1)); this fraction contains calcium, magnesium, sodium and potassium for the main cations and inorganic... (Review)
Review
The salt of milk constitutes a small part of milk (8-9 g.L(-1)); this fraction contains calcium, magnesium, sodium and potassium for the main cations and inorganic phosphate, citrate and chloride for the main anions. In milk, these ions are more or less associated between themselves and with proteins. Depending on the type of ion, they are diffusible (cases of sodium, potassium and chloride) or partially associated with casein molecules (cases of calcium, magnesium, phosphate and citrate), to form large colloidal particles called casein micelles. Today, our knowledge and understanding concerning this fraction is relatively complete. In this review, the different models explaining (i) the nature and distribution of these minerals (especially calcium phosphate) in both fractions of milk and (ii) their behaviour in different physico-chemical conditions, are discussed.
Topics: Animals; Calcium; Caseins; Cattle; Chelating Agents; Female; Food Handling; Hydrogen-Ion Concentration; Magnesium; Micelles; Milk; Minerals; Particle Size; Phosphates; Salts
PubMed: 16045895
DOI: 10.1051/rnd:2005030