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PubMedDate not supplied

The effects of citrate on fMLP-induced polymorphonuclear leukocyte stimulation and locomotion.

Citrate reduces the incidence of corneal ulceration and perforation in alkali burned eyes and prevents polymorphonuclear leukocyte (PMN) accumulation in certain inflamed ocular tissues. Chelation of Ca2+ and Mg2+ by citrate appears to be the mechanism causing strong inhibition of in vitro PMN stimulation by opsonized zymosan. It is important to know if other activating agents of PMNs, with differing sensitivity to divalent cations, are inhibited by citrate. Citrate (12 mM) partially inhibits fMLP stimulation of the respiratory burst (50%) and degranulation (65%) of PMNs in a divalent cation free media, while having no effect or only a small effect in the presence of 1 mm Ca2+. Citrate also caused significant inhibition of fMLP (12 mM = 50%) induced locomotion of PMN when incubated in media containing 500 microM Ca2+ and 600 microM Mg2+ in a modified Boyden chamber. When used together, Ca2+ (6 mM) and Mg2+ (6 mM) reduced this inhibition to only 20%. Citrate apparently inhibits fMLP-induced stimulation in cation free media by chelating CA2+ effluxed from intracellular storage sites. In the chemotactic studies, citrate probably chelates extracellular Ca2+ and Mg2+. The divalent cation requirements of the activating agents and/or the PMN function may determine the degree of inhibition by citrate. It is therefore important to identify the mediators in alkali burned corneas as well as other inflammatory conditions.

Calcium↗
PubMed1994

Effect of concentration of trisodium citrate anticoagulant on calculation of the International Normalised Ratio and the International Sensitivity Index of thromboplastin.

The aim of this study was to determine whether the concentration of trisodium citrate used to anticoagulate blood has an effect on the INR of the sample and the ISI of the thromboplastin. Five thromboplastins including and Australian reference material were used to measure the prothrombin time of normal and patient samples collected into two concentrations of trisodium citrate--109 mM and 129 mM. There was no effect of citrate concentration on the INRs determined with the reference material. However for the other four thromboplastins there was a significant difference between INRs for the two citrate groups. The prothrombin times of the samples collected into 129 mM were longer than those collected into 109 mM. This difference was only slight in normal plasma but more marked in patients receiving oral anticoagulants, causing the INRs for patient plasmas collected into 129 mM citrate to be higher then the corresponding samples collected into 109 mM citrate. From orthogonal regression of log prothrombin times by the reference method against each thromboplastin, we found that the ISI for each thromboplastin was approximately 10% lower when determined with samples collected into 129 mM citrate than with samples collected into 109 mM. These results suggest that the concentration of trisodium citrate used for collection of blood samples can affect the calculation of the INR and the calibration of the ISI of thromboplastin. This was found both for commercial thromboplastins prepared by tissue extraction and for a recombinant tissue factor.

Anticoagulants↗
PubMed1993

[Citrate and kidney stones].

Citrate is an important naturally occurring inhibitor of calcium stone formation in urine. Urinary citrate excretion was examined in 43 consecutive patients with recurrent idiopathic calcium nephrolithiasis and in 50 normal controls by a specific enzymatic technique. Hypocitraturia (< 1.6 mmol/24h) was found in 14 (33%) stone formers compared to 6 (12%) normal controls (p = 0.03). Citrate excretion expressed as citrate-creatinine ratio in 24 hour urine samples was significantly lower in the stone formers than in the healthy controls (p = 0.03), and significantly lower in healthy men, compared to healthy females (p = 0.006). There was a great variability in urinary citrate levels in both groups, and a considerable overlap in the urinary citrate excretion between normal subjects and stone formers. Factors other than urinary citrate excretion must therefore be of importance in the pathophysiology of calcium stone formation. Citrate-calcium ratio in urine proved to be a reliable index in discriminating stone formers from healthy subjects.

Adult↗
PubMed1993

[Effect of high-dose thiazide treatment and low-K diet on citrate uptake by rat renal brush border membrane vesicles (BBMV)].

In order to study the effect of high-dose thiazide treatment and low-K diet on citrate uptake by rat renal brush border membrane, we measured citrate uptake by rat renal brush border membrane vesicles (BBMV) and analyzed the acid-base balance of non-treated rats, high-dose thiazide-treated rats and low-K diet rats. Seven-week male Wistar rats (Jcl) were housed in metabolic cages, given 10 mg/Kg BW/day hydrochlorothiazide (HCTZ) by a gastric tube once a day for 3 weeks (high-dose thiazide treated rats) or a low-K diet for 3 weeks (low-K diet rats). Arterial blood was taken from the aorta and BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by a Millipore rapid membrane filtration technique. High-dose thiazide treatment for 3 weeks showed a significant metabolic alkalosis and increase of urinary citrate excretion. However, it had no significant effect on citrate uptake by BBMV. On the other hand, low-K diet for 3 weeks showed significant hypokalemia, metabolic alkalosis and decrease in urinary citrate excretion. Moreover, it increased the maximal activity (Vmax) with no difference in citrate affinity (Km). These data suggested that urinary citrate excretion was more affected by the K depletion than by the acid-base balance.

Animals↗
PubMed1993

[Effect of thiazide on urinary citrate excretion].

In order to study the effect of thiazide on urinary citrate excretion, we measured sodium dependent citrate uptake by rat renal cortical brush border membrane vesicles (BBMVs) and analyzed acid-base balance with or without thiazide treatment. 5-weeks male Wistar rats (Jcl) were housed in metabolic cages, given 0.1 mg/100 g BW/day hydrochlorothiazide (HCTZ) by a gastric tube once a day for 3 weeks (thiazide treated rats). Arterial blood was taken from aorta and BBMVs were prepared with divalent cation precipitation method. Citrate uptake was measured by a Millipore rapid membrane filtration technique. Oral treatment of HCTZ for 3 weeks showed a significant increase of urinary citrate excretion in both concentration and daily excretion. The sodium dependent citrate transport was observed in rat renal brush border membrane (BBM). But no significant effect of oral HCTZ was observed on acid base balance and sodium dependent citrate uptake in rat renal BBM. These data suggested that the stimulative effect of thiazide on citrate excretion was not via sodium dependent citrate transport in rat renal BBM.

Animals↗
PubMed1995

Signal transfer through three compartments: transcription initiation of the Escherichia coli ferric citrate transport system from the cell surface.

Transport of ferric citrate into cells of Escherichia coli K-12 involves two energy-coupled transport systems, one across the outer membrane and one across the cytoplasmic membrane. Previously, we have shown that ferric citrate does not have to enter the cytoplasm of E. coli K-12 to induce transcription of the fec ferric citrate transport genes. Here we demonstrate that ferric citrate uptake into the periplasmic space between the outer and the cytoplasmic membranes is not required for fec gene induction. Rather, FecA and the TonB, ExbB and ExbD proteins are involved in induction of the fec transport genes independent of their role in ferric citrate transport across the outer membrane. The uptake of ferric citrate into the periplasmic space of fecA and tonB mutants via diffusion through the porin channels did not induce transcription of fec transport genes. Point mutants in FecA displayed the constitutive expression of fec transport genes in the absence of ferric citrate but still required TonB, with the exception of one FecA mutant which showed a TonB-independent induction. The phenotype of the FecA mutants suggests a signal transduction mechanism across three compartments: the outer membrane, the periplasmic space and the cytoplasmic membrane. The signal is triggered upon the interaction of ferric citrate with FecA protein. It is postulated that FecA, TonB, ExbB and ExbD transfer the signal across the outer membrane, while the regulatory protein FecR transmits the signal across the cytoplasmic membrane to FecI in the cytoplasm. FecI serves as a sigma factor which facilitates binding of the RNA polymerase to the fec transport gene promoter upstream of fecA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1985

Characterization of citrate lyase from Clostridium sporosphaeroides.

Cells of Clostridium sporosphaeroides which were grown on citrate contained citrate lyase and citrate lyase acetylating enzyme, but no detectable citrate synthase and citrate lyase deacetylase activities. Citrate lyase from C. sporosphaeroides was purified to homogeneity as judged by polyacrylamide gel electrophoresis and high performance liquid chromatography. In contrast to the enzyme from Clostridium sphenoides, the addition of L-glutamate was not necessary for activity and stabilization of the enzyme. The purified enzyme had a specific activity of 34 U/mg protein and was comparable to other citrate lyases with respect to its molecular weight and subunit composition. Electron microscopic investigations showed that similar to the lyase from C. sphenoides and in contrast to all other citrate lyases examined so far, the majority of the enzyme molecules was present in "star" form.

Catalysis↗
PubMed1996

Synergistic iron reduction and citrate dissimilation by Shewanella alga and Aeromonas veronii

Two bacterial isolates from Great Bay Estuary, New Hampshire, in co-culture carried out anaerobic dissimilation of citric acid with Fe(III) as the terminal electron acceptor. Neither isolate oxidized citrate with Fe(III) anaerobically in axenic culture. The Fe(III) reducer, Shewanella alga strain BrY, did not grow anaerobically with citrate as an energy source. The citrate utilizer, Aeromonas veronii, did not reduce iron axenically with a variety of electron donors including citrate. The onset of iron reduction by the co-culture occurred after initiation of citrate dissimilation and just prior to initiation of growth by either organism (as measured by viable plate counts). Anaerobic culture growth rates and final cell densities of each bacterial strain were greater in co-culture than in axenic cultures. By 48 h of growth, the co-culture had consumed 27 mM citrate as compared with 12 mM dissimilated by the axenic culture of A. veronii. By 48 h the co-culture produced half as much formate (6 mM) and twice as much acetate (40 mM) as did A. veronii grown axenically (12 mM and 20 mM, respectively). Formate produced from citrate by A. veronii appeared to have supported growth and Fe(III) reduction by S. alga.Although not obligatory, nutrient coupling between these two organisms illustrates that fermentative (A. veronii-type) organisms can convert organic compounds such as citrate to those used as substrates by dissimilatory Fe(III) reducers, including S. alga. This synergism broadens the range of substrates available for iron reduction, stimulates the extent and rate of organic electron donor degradation (and that of iron reduction) and enhances the growth of each participant.

Journal Article↗
PubMed2002

Functional characterization of CitM, the Mg2+-citrate transporter.

The CitM transporter from Bacillus subtilis transports citrate as a complex with Mg2+. In this study, CitM was functionally expressed and characterized in E. coli DH5a cells. In the presence of saturating Mg2+ concentrations, the Km for citrate in CitM was 274 mM, similar to previous studies using whole cells of B. subtilis. CitM has a high substrate specificity for citrate. Other di- and tricarboxylic acids including succinate, isocitrate, cis-aconitate and tricarballylic acid did not significantly inhibit the uptake of citrate in the presence of Mg2+. However, CitM accepts complexes of citrate with metal ions other than Mg2+. The highest rate of citrate transport was seen in the presence of Mg2+, followed in order of preference by Mn2+, Ba2+, Ni2+, Co2+ and Ca2+. Citrate transport by CitM appears to be proton coupled. The transport was inhibited in transport buffers more alkaline than pH 7.5 and not affected by pH at acidic values. Transport was also inhibited by ionophores that affect the transmembrane proton gradient, including FCCP, TCC and nigericin. Valinomycin did not affect the uptake by CitM, suggesting that transport is electroneutral. In conclusion, the cloned CitM transporter from B. subtilis expressed in E. coli has properties similar to the transporter in intact B. subtilis cells. The results support a transport model with a coupling stoichiometry of one proton coupled to the uptake of one complex of (Mg2+-citrate)1-.

Bacillus subtilis↗
PubMed2003

The metabolism of aluminum citrate and biosynthesis of oxalic acid in Pseudomonas fluorescens.

(13)CNMR and (1)HNMR studies revealed that aluminum citrate (Al-citrate) was metabolized intracellularly and that oxalic acid was an important product in the Al-stressed cells. This dicarboxylic acid was produced via the oxidation of glyoxylate, a precursor generated through the cleavage of isocitrate. In the control cells, citrate was biotransformed essentially with the aid of regular tricarboxylic cycle (TCA) enzymes. However, these control cells were able neither to uptake nor to metabolize Al-citrate. Al-stressed cells obtained at 38-40 h of growth showed maximal Al-citrate uptake and biotransforming activities. At least a fourfold increase in the activity of the enzyme isocitrate lyase (ICL, E. C. 4.1.3.1) has been observed in the Al-stressed cells compared with the control cells. The transport of Al-citrate was sensitive to p-dinitrophenol and sodium azide, but not to dicyclohexylcarbodiimide. Experiments with the dye 9-aminoacridine revealed that the translocation of Al-citrate led to an increase in intracellular pH. Thus, it appears that after the uptake of Al-citrate, this complex is metabolized intracellularly.

Biodegradation, Environmental↗
PubMed1984

Induction of luteal phase defect with clomiphene citrate.

The effect of clomiphene citrate and progesterone on luteal function in infertile women was studied. Endometrial biopsies were performed in 103 women immediately prior to menstruation. Group 1 (n = 62) had secretory endometrium with a histologic lag time of greater than or equal to 48 hours with respect to the subsequent menses, that is, luteal phase defect. Group 2 (n = 10) had normal histologic characteristics of the secretory phase. Group 3 (n = 31) had anovulatory endometrium. The last group was subdivided into those with polycystic ovary syndrome (n = 9) and those without the characteristic gonadotropin pattern of polycystic ovary syndrome (n = 22). Clomiphene citrate at doses of 50 to 250 mg daily for 5 days was administered for induction of ovulation, timing of ovulation, or treatment of luteal phase defect. An endometrial biopsy was obtained after three ovulatory treatment cycles. Only one fourth of the women with prior luteal phase defect had normalization of the biopsy specimen with clomiphene citrate, while one half of those treated with progesterone had normal specimens. Half of the normally ovulating women had induction of a luteal phase defect with clomiphene citrate. Only women with polycystic ovary syndrome had consistently well-timed endometrial histologic features with clomiphene citrate therapy. Despite successful induction of ovulation, 16 of the other 22 previously anovulatory women had endometrial histologic findings compatible with luteal phase defect. Increasing the clomiphene citrate dosage was unsuccessful in improving endometrial maturation. These results suggest that the use of clomiphene citrate may be associated with a high rate of luteal phase defect induction, except among women with polycystic ovary syndrome. Clomiphene citrate, even at high doses, appears to be ineffective therapy for luteal phase defect.

Anovulation↗
PubMed1996

Synthesis of citrate from phosphoenolpyruvate and acetylcarnitine by mitochondria from rabbit, pigeon and rat liver: implications for lipogenesis.

Rabbit, pigeon and rat liver mitochondria convert exogenous phosphoenolpyruvate and acetylcarnitine to citrate at rates of 14, 74 and 8 nmol/15 min/mg protein. Citrate formation is dependent on exogenous HCO3-, is increased consistently by exogenous nucleotides (GDP, IDP, GTP, ADP, ATP) and inhibited strongly by 3-mercaptopicolinate and 1,2,3-benzenetricarboxylate. Citrate is not made from pyruvate alone or combined with acetylcarnitine. Pigeon and rat liver mitochondria make large amounts of citrate from exogenous succinate, suggesting the presence of an endogenous source of acetyl units or means of converting oxalacetate to acetyl units. Citrate synthesis from succinate by pigeon and rabbit mitochondria is increased significantly by exogenous acetylcarnitine. Pigeon and rat liver contain 80 and 15 times, respectively, more ATP:citrate lyase activity than does rabbit liver. Data suggest that mitochondrial phosphoenolpyruvate carboxykinase in vivo could convert glycolysis-derived phosphoenolpyruvate to oxalacetate that, with acetyl CoA, could form citrate for export to support cytosolic lipogenesis as an activator of acetyl CoA carboxylase, a carbon source via ATP:citrate lyase and NADPH via NADP:malate dehydrogenase or NADP:isocitrate dehydrogenase.

Acetylcarnitine↗
PubMed2000

Zinc causes a shift toward citrate at equilibrium of the m-aconitase reaction of prostate mitochondria.

Prostate secretory epithelial cells have the unique function and capability of accumulating and secreting extraordinarily high levels of citrate. To achieve this, these cells possess a uniquely limiting mitochondrial (m)-aconitase activity that minimizes the oxidation of citrate via the Krebs cycle. The steady-state citrate/isocitrate ratio of mammalian tissues is generally maintained at about 10-11/l, independent of the concentration of citrate, which is the result of the chemical equilibrium reached in the presence of m-aconitase. In contrast, the citrate/isocitrate ratio of prostate tissue is about 30-40/l. Zinc, which is also accumulated in prostate cells at much higher levels than in other cells, inhibits m-aconitase activity thereby minimizing citrate oxidation. This current report is concerned with an effect of zinc on the equilibrium of the reaction catalyzed by m-aconitase. Studies were conducted with mitochondrial extract preparations from rat ventral prostate epithelial cells. With citrate as the initial substrate, the addition of zinc (7-10 microM) to the prostate mitochondrial preparation resulted in a change in the citrate/isocitrate ratio at equilibrium from an average of 10.5/l to 13.5/l. In contrast, the identical treatment of kidney mitochondrial preparations resulted in no zinc-induced change in the citrate/isocitrate ratio. When either cis-aconitate or isocitrate was employed as the initial substrate, the addition of zinc did not alter the citrate/isocitrate ratio of prostate or kidney preparations. Partial purification of the prostate preparation revealed that the prostate mitochondrial extract contained a putative protein (which we have designated as 'citrate factor protein') that is required for the zinc-induced increase in the citrate/isocitrate ratio. This novel effect of zinc provides another mechanism by which it is assured that the accumulation of citrate is maximized in citrate-producing prostate epithelial cells.

Aconitate Hydratase↗
PubMed1997

Aluminum citrate is transported from brain into blood via the monocarboxylic acid transporter located at the blood-brain barrier.

Aluminum citrate transport across the blood-brain barrier was assessed in rats by in vivo microdialysis. Microdialysis probes were implanted in the jugular vein as well as the left and right frontal cortex. It was demonstrated previously (Allen et al., 1995), in this study, that the steady-state aluminum citrate brain-to-blood-ratio (BBr) is less than 1, suggesting the presence of a process other than diffusion. The addition of 2,4-dinitrophenol (10 microM) to the dialysate perfusing a microdialysis probe in the brain increased the steady-state aluminum citrate brain-to-blood-ratio to a value (1.14) not significantly different from 1, suggesting the presence of an active transporter that is blocked by the metabolic inhibitor. The addition of valproic and pyruvic acid, as putative and known substrates for the monocarboxylic acid transporter, respectively, to brain dialysate (10 and 100 mM) had different outcomes. Valproic acid was ineffective at either concentration, whereas pyruvic acid (100 mM) significantly increased the aluminum citrate brain-to-blood-ratio from 0.19 to 0.31. Pyruvic acid (1 M in the dialysate) increased the aluminum citrate brain-to-blood-ratio to a value not different from unity, suggesting competition between aluminum citrate and pyruvic acid for transport. The only energy-dependent, pyruvic acid-inhibitable transporter is the monocarboxylic acid transporter. Theoretical, pharmacokinetic modeling suggests that the transporter producing an aluminum citrate brain-to-blood-ratio less than 1 is predominantly located at the blood-brain barrier, rather than at neuronal or glial cell membranes. We propose that the monocarboxylic acid transporter at the blood-brain barrier maintains a steady-state aluminum citrate brain-to-blood-ratio much less than 1.

2,4-Dinitrophenol↗
PubMed2005

Genetic and dietary factors in urinary citrate excretion.

BACKGROUND AND PURPOSE: Hypocitraturia, an important risk factor for calcium oxalate nephrolithiasis, is the result of numerous factors. We studied citrate excretion by patients with and without stones consuming normal and controlled formula diets. SUBJECTS AND METHODS: Subjects with and without a history of calcium oxalate stones (N = 101 per group) provided two or three 24-hour urine specimens during consumption of self-selected diets. Data also were collected on subsets of subjects consuming formula (Ensure) diets. Citrate was determined using the citrate lyase method of Petrarulo and associates, and values for multiple specimens were averaged. The data were adjusted for creatinine excretion and examined on a per-day basis. RESULTS: The mean citrate excretion of the non-stone formers was slightly but not significantly higher than that of the stone formers (442 +/- 217 versus 378 +/- 153 mg/g of creatinine). All statistical analyses revealed highly significant differences between, but not within, individuals, a result compatible with a genetic influence. In the normal population, 5% of subjects had a citrate excretion <200 mg/g of creatinine, whereas this result was seen in 34% of the stone-forming subjects. When the subjects consumed a formula diet, women in both groups had much higher citrate excretion than when on a self-selected diet, but little difference was seen in the men. The patterns of citrate recovery suggest low, intermediate, and high excretors. In the normal population, 15% of subjects excreted <340 mg/g of creatinine, whereas this was true of 43% of the stone-forming subjects. Analysis of six families suggested three excretor phenotypes, with a codominant pattern of inheritance. CONCLUSION: These findings imply a genetic influence on citrate excretion, as has already been demonstrated for calcium excretion. Further studies of genetic influences on calcium oxalate stone formation are warranted.

Adult↗
PubMed1998

Minimum specimen volume requirements for routine coagulation testing: dependence on citrate concentration.

We evaluated the effect of sample volume and citrate concentration on results of routine coagulation assays (prothrombin time [PT] and activated partial thromboplastin time [APTT]). The study was performed on samples obtained from healthy persons and patients receiving oral anticoagulant therapy. Standard evacuated tubes (3.2% and 3.8% sodium citrate) were filled to varying total sample volumes ranging from 3.0 to 5.0 mL, and results of routine coagulation tests were compared. Underfilling may significantly affect the APTT and PT, resulting in artifactual prolongation of results. This effect is most pronounced in samples drawn into 3.8% citrate. By using 3.8% citrate, there is a statistically significant difference in the results of PT assays in the samples less than 80% filled compared with those that are 100% filled. For APTT assays performed on samples drawn into 3.8% citrate, a statistical difference occurred at less than 90% filled. This effect was less pronounced when samples were drawn into 3.2% sodium citrate. We found no statistically significant difference in PT results from a 3.2% citrate tube between fill volumes of 60% and 100% and none for APTT results between fill volumes of 70% and 100%. This study further supports the recommendation to use 3.2% sodium citrate concentration, because 60% of the optimum filled volume for PT and 70% of the optimum filled volume for APTT are acceptable.

Anticoagulants↗
PubMed2000

Citrate determines calcium oxalate crystallization kinetics and crystal morphology-studies in the presence of Tamm-Horsfall protein of a healthy subject and a severely recurrent calcium stone former.

BACKGROUND: The aim of this study was to measure the effects of normal (nTHP) and abnormal stone former Tamm-Horsfall protein (SF-THP) on calcium oxalate (CaOx) nucleation and aggregation as well as on crystal morphology, in presence or absence of citrate. METHODS: Nucleation and aggregation of CaOx crystals from a supersaturated, stirred solution (200 mM NaCl, 10 mM Na-acetate, pH 5.70, 5 mM Ca and 0.5 mM Ox) were studied by spectrophotometric time-course measurements of OD at 620 nm (OD(620)). Measured parameters were induction time t(I) (time to induce formation of detectable particles), S(N), (slope of increase of OD(620), mainly due to crystal nucleation), and S(A), (slope of decrease of OD(620) after equilibrium has been reached, due to crystal aggregation). Effects of citrate, nTHP and SF-THP on these parameters were measured, and scanning electron microscopy (SEM) was performed. RESULTS: At 1.5, 2.5 and 3.5 mM, citrate increased t(I) and inhibited crystal nucleation (by 78-87%) as well as aggregation (by 63-70%), and smaller CaOx crystals (length/width ratio 1.7+/-0.1) than under standard conditions (length/width 3.9+/-0.5) were visible (P<0.001). Normal THP at 30 and 40 mg/l inhibited crystal nucleation and, more strongly, aggregation (inhibition 76-81%). SEM revealed a decrease in length/width ratio to 2.6+/-0.4 (P=0.051 vs standard conditions) and less aggregation than without nTHP. At all concentrations tested, SF-THP reduced t(I) (P=0.0001 vs standard conditions) and promoted aggregation (inhibition -48 to -33%); crystals were elongated with a length/width ratio of 4.3+/-0.6 (P<0. 05 vs nTHP). When simultaneously present with nTHP, citrate enhanced the inhibitory effects of nTHP, producing the smallest (length/width 1.5+/-0.1) and least aggregated crystals. Finally, 3.5 mM citrate turned promotory SF-THP into a crystallization inhibitor with abundant small and clustered, but not aggregated crystals. CONCLUSION: Citrate appears to be the main determinant of CaOx crystallization rates and crystal morphology in the presence of nTHP as well as SF-THP. Its effects appear to predominate over those of THP, since even promotory SF-THP is turned into a crystallization inhibitor in the presence of citrate. This re-emphasizes at a morphological level what has been concluded from functional as well from clinical studies, namely that citrate is needed in urine at equimolar concentrations to calcium in order to prevent the formation of large crystal aggregates in presence of abnormal THP.

Adult↗
PubMed2001

The clinical relevance of the citrate effect on International Normalized Ratio determinations depends on the reagent and instrument combination used.

Multiple studies have shown that the two different citrate concentrations in common use as the anticoagulant in blood collection for haemostasis assays can affect the results obtained with the prothrombin time assay. It is clear from the literature that there is considerable variability in the results obtained using different instrument-reagents combinations, but the clinical relevance of these differences is unclear. Most of the studies have used an optical system for end-point detection. This study reports on the citrate sensitivity using mechanical end-point detection. Using two different reagents, one previously shown to be citrate sensitive on optical systems (Neoplastin CI plus) and a citrate-insensitive reagent (Neoplastin CI), we demonstrate that the effect of using different citrate concentrations (0.105 or 0.129 mol/l) has statistically significant but clinically irrelevant effects on the International Normalized Ratio using a mechanical instrument (STA)-reagent combination (mean percentage difference in results, 1.9 and 3.8% respectively). This demonstrates that the citrate effect is both instrument type and reagent dependent. Every reagent and instrument combination needs to be tested to see whether any citrate effect exists. In a secondary study, it was shown that the international reference rabbit thromboplastin (CRM 149(s)) was not citrate-concentration sensitive.

Animals↗