Urinary Citrate Excretion Research Articles

Hypocitricemic effect of surgical stress

Plasma citrate changes in response to surgical stress were studied in 30 patients. A marked hypocitricemia was apparent by 1 day postoperative and persisted over the recovery period (7–14 days in these studies). Plasma cortisol levels were markedly increased within 6 hr postoperatively, and by 1 day postoperatively the cortisol levels declined toward the preoperative level. Only a slight, transient decrease in plasma calcium was observed postoperatively, and the citrate changes were independent of any corresponding calcium effects. No increased urinary citrate excretion was observed which would account for the removal of citrate from circulation. Studies with dogs indicated that general anesthesia was not a contributing factor to hypocitricemic response to surgical stress.

Renal excretion of citrate in the dog. Enzymatic determination of citrate (author's transl)

Clearance measurements were made in 15 dogs in order to study the urinary citrate excretion. The citrate determination is performed in blood plasma and urine, with an enzymatic specific method. The authors find that more than 99% of the citrate filtered through the glomerulus is reabsorbed. The greater sensitivity, specificity and accuracy of the enzymatic method, which has been compared with the usual chemical methods, may explain the discrepancy between these data and the results published by other authors. These results are consistent with the hypothesis that citrate is filtered, reabsorbed and not secreted by the tubule in the dog.

Urinary excretion of citrate, succinate and ketone bodies by iron-deficient rats.

Urinary excretion of citrate, succinate and ketone bodies by iron-deficient rats.

Carbohydrate and Amino Acid Metabolism in Lambs Fed Purified Diets Containing Urea or Isolated Soy Protein

A purified basal diet was pair-fed to five sets of twin lambs for comparing the effects of soybean protein (SP) or urea (U) on liver, heart, kidney, plasma and urinary concentrations of amino acids, metabolic intermediates and other constituents. Feed was available from 8 to 10 am and 1 to 3 pm daily during the entire feeding period of 76 days. Blood samples were drawn at 10 am once each week except on day 34 when samples were taken immediately before the morning feeding and at frequent intervals thereafter. NH3-N in peripheral blood following the am feeding was higher and blood glucose was lower in the U-fed lambs with blood urea being the same in both groups. Plasma lactate and succinate declined and blood glucose increased following feeding in both treatment groups. Plasma citrate increased after feeding in the U-fed lambs. During 6 hours after the morning feeding total urinary excretion of citrate, α-ketoglutarate and malate increased by factors of 12.2, 3.5 and 1.9, respectively, for U-fed lambs while their cis-aconitate excretion decreased. Plasma glutamate was higher at 1 pm than at 9 am, 11 am or 3 pm for both treatment groups. Plasma alanine, threonine, valine, leucine, isoleucine, lysine, ornithine and arginine were significantly lower in U-fed lambs but serine and glutamate were higher. Liver threonine, valine, leucine, isoleucine, lysine, histidine and ornithine concentrations were lower in U-fed lambs. Concentrations of valine and leucine were lower in the kidney and heart, isoleucine was lower in the heart, and lysine was lower in the kidney of U-fed lambs. Plasma Ca2+, Mg2+ and phosphate were the same for both dietary treatments.

The relative importance of urinary pH and urinary content of citrate, magnesium and calcium in the production of nephro calcinosis by diet and acetazolamide in the rat.

1. The association of varying levels of urinary pH, urinary citrate and urinary calcium and magnesium excretion rates with kidney citrate, calcium and magnesium concentrations in experimental nephrocalcinosis was examined in twenty-four rats in a 3 × 2 multifactorial experiment with four replicates. All rats received the same synthetic diet for 6 weeks before being killed in the seventh week. In addition the rats received calcium supplements as calcium chloride (diet A), calcium carbonate (diet B), or as an equal mixture of calcium chloride and carbonate (diet N), the content of calcium being kept constant at 6·3 mg per g of diet for all rats. Half of the rats also received 2·5 mg of acetazolamide per g of diet. 2. Diet A produced a systemic acidosis and the most acid urinary pH. Diet B plus acetazolamide produced a more severe systemic acidosis and the most alkaline urinary pH. Urinary magnesium, citrate and calcium excretion rates were generally reduced below normal. Urinary excretion of magnesium and calcium were significantly higher in those rats on diet A than in those on diet B, while urinary citrate excretion was highest in the latter. Acetazolamide caused a further increase in urinary calcium excretion but a decrease in urinary magnesium and citrate excretions. 3. Acetazolamide significantly reduced plasma calcium but elevated plasma magnesium. The changes produced in plasma and urinary calcium and magnesium in the present study were consistent with an action through systemic acidosis for calcium and through urinary pH for magnesium, both being effected at a tubular site. 4. Variation in diet alone as well as acetazolamide administration were significantly associated with variation in the degree of nephrocalcinosis (P < 0·05 and P < 0·005 respectively). Acetazolamide increased nephrocalcinosis by a factor of at least 10. Analysis of covariance showed that acetazolamide was no longer associated with significant nephrocalcinosis when its effects on urinary pH and magnesium were removed from its effect on nephrocalcinosis. Removal of the effect of acetazolamide on urinary citrate excretion did not alter the effect of acetazolamide in producing nephrocalcinosis. Although urinary citrate was reduced to below 10% of normal whenever nephrocalcinosis was severe, it was also reduced to below 10% in rats on diet A which had normal kidney tissue calcium content, the most acid urinary pH and the highest urinary magnesium. 5. Elevation of urinary pH and reduction in urinary magnesium excretion were therefore considered to be of major importance in the causation of experimental nephrocalcinosis; reduction in urinary citrate excretion appeared to be only of secondary importance.

Excretion of citrate during the menstrual cycle, pregnancy and lactation.

Summary: The daily urinary excretion of citrate was followed through 10 menstrual cycles in 5 subjects (3 under balance conditions) and in 2 subjects at various times during pregnancy and lactation. There was considerable day‐to‐day variation in excretion of citrate, and a cyclic pattern of citrate excretion could only be made out in 4 menstrual cycles. Statistical analysis revealed few significant correlations of citrate excretion with the pH of the urine, or with the excretion of inorganic phosphate, or of potassium, and no correlation with the excretion of calcium.

Effect of Vitamin D Deficiency and the Role of Citrate in Kidney Calcification of Magnesium-deficient Rats

Weanling male albino rats were used in studies designed to investigate the relationship of vitamin D status and other parameters affecting citrate and mineral metabolism on renal calcification in magnesium deficiency. In experiment 1 the basal diet contained 0.5% calcium and 0.5% phosphorus, 90 ppm of magnesium and no known source of vitamin D. Magnesium (600 ppm), vitamin D (1.25 IU per gram) and galactose (15%) were included in diets to form a 23 factorial design. In experiment 2 the effect of L-thyroxine on citrate excretion was studied in magnesium-deficient and normal animals. Kidney calcification was produced only in the presence of vitamin D and was prevented by thyroxine treatment, although these treatments each increased urinary citrate excretion. Serum citrate levels were not influenced by magnesium but were increased by vitamin D and by galactose. Thus urine citrate was not correlated with either serum citrate or kidney calcification.

Renal tubular acidosis: A family with an autosomal dominant genetic defect in renal hydrogen ion transport, with proximal tubular and collecting duct dysfunction and increased metabolism of citrate and ammonia

Renal tubular acidosis with a dominant autosomal inheritance pattern was found in ten of thirteen members of a family investigated by the one day renal function test of Edwards et al. [1]. A significantly lower minimum urine pH was attained in affected members who were “asymptomatic” than in the four members who were “symptomatic” (because of renal stones and/or nephrocalcinosis and infection). The mean pH values were 6.11 and 6.64, respectively (p < 0.05), representing maximum urinary hydrogen ion concentrations one-twentieth and one-sixtieth of normal. The “asymptomatic” group also had a significantly increased phosphate excretion (25.6 μM per minute per 1.73 M 2.; p < 0.05) and this caused an increase in titratable acid excretion giving a measure of protection against systemic acidosis in addition to that due to a lower urine pH. A defect in proximal tubular function was also detected by the fifteen minute phenolsulfonphthalein excretion test, the mean values being 86 per cent in the “asymptomatic” group and 67 per cent of the expected value (derived from the glomerular filtration rate) in the “symptomatic” group (p < 0.05; normal control subjects 93 per cent). These findings were considered to represent variable expression of the primary genetic defect, which might well lead to the differences observed clinically. Hyperuricemia and a decreased clearance of urate were noted in some members, particularly in the “symptomatic” group. Urinary citrate excretion was greatly reduced in all members and was found to be inversely related to the degree of systemic acidosis rather than to the urine pH under both acid and alkali loading. A hypothesis has been put forward regarding the extramitochondrial role of circulating citrate (derived mainly from the tubular lumen) in energy production by tubular cells, especially the collecting duct cells which are poor in mitochondria and yet capable of producing maximum urinary acidification.

Urinary citrate excretion in primary aldosteronism.

Urinary citrate output was studied in 5 cases of primary aldosteronism, in 3 of Addison's disease and in 8 of normal subjects. The urinary citrate output was decreased in 4 of 5 cases of primary aldosteronism, and the citrate output could not be normalized by removal of adrenocortical adenoma. In patients with primary aldosteronism citrate excretion was somewhat increased by admini-stration of potassium chloride, but rather decreased by spironolactone. In these patients urinary citrate output could not be correlated with either plasma CO2 content or plasma potassium concentration. The low urinary citrate excretion in primary aldosteronism may not be satisfactorily explained either by direct action of aldosterone on the kidney or by intracellular acidosis.

Carbohydrate Metabolism and Physical Activity in Rats Fed Diets containing Purified Casein Versus a Mixture of Amino Acids Simulating Casein

The effects of varying energy intake levels on physical activity and glucose metabolism were studied in young growing rats. Male rats 28 days of age were fed for 31 days diets containing either casein or an amino acid mixture simulating casein at 2 levels of calorie intake. Physical activity was measured and 14C recovery from injected glucose-1-14C, -6-14C, and -U-14C was determined as percentage of dose in expired CO2, feces, and urine, from one to 24 hours after giving each rat his daily ration. The average revolutions per day run was higher for calorie-restricted animals, but there was no significant difference in activity due to substituting the mixture of amino acids for casein, although casein-fed rats tended to be more active. This increase in physical activity caused by calorie restriction was due to a significant difference in daytime activity, as all rats were equally active in the dark. There were no significant differences due to calorie level or nitrogen source in 14CO2 recovery from glucose-6-14C and glucose-U-14C, but amino acid-fed rats converted more glucose-1-14C to 14CO2 as measured cumulatively 6 and 23 hours after injection. Calorie-restricted rats expired less glucose-1-14C as 14CO2 during the first 6 hours after injection, but this effect was not evident after 23 hours. There was a trend toward lower 14C recovery from glucose-U-14C in urinary citrate of amino acid-fed rats, although urinary citrate excretion was unaltered by diet. These data indicate a greater utilization of alternative pathways to the glycolytic scheme and tricarboxylic acid cycle for metabolism of glucose in amino acid-fed rats and several possible explanations are discussed.

TISSUE CITRATE LEVELS AND CITRATE UTILIZATION AFTER SODIUM BICARBONATE ADMINISTRATION.

SummarySodium bicarbonate administration increased the excretion of C14-labeled citrate in the urine. It decreased the conversion of C14-labeled citrate to C14O2 to approximately the same extent as it increased the urinary excretion of radioactive citrate. Tissue levels of citrate in the kidney rose 3-fold after sodium bicarbonate administration; there was a significant but relatively small rise in liver citrate and no change in heart citrate after sodium bicarbonate. Thus sodium bicarbonate appears to affect citrate metabolism predominantly in the kidney.

Citrate Excretion in Renal Tubular Acidosis

Case Studies1 January 1963Citrate Excretion in Renal Tubular AcidosisJAMES F. MORRISSEY, M.D., MANUEL OCHOA JR., M.D., WILLIAM D. LOTSPEICH, M.D., CHRISTINE WATERHOUSE, M.D., F.A.C.P.JAMES F. MORRISSEY, M.D.Search for more papers by this author, MANUEL OCHOA JR., M.D.Search for more papers by this author, WILLIAM D. LOTSPEICH, M.D.Search for more papers by this author, CHRISTINE WATERHOUSE, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-1-159 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMetabolic and respiratory acidosis has been shown to decrease the urinary citrate excretion in man (1). Conversely, metabolic or respiratory alkalosis will increase this parameter, without associated increase in the plasma citrate level (2). In these situations, usually the urine pH varies directly with the pH of the blood which does not allow one to differentiate the significance of either factor in the renal excretion of citrate. Recently, Evans, Maclntyre, Macpherson, and Milne (2) have shown that potassium repletion in a patient with primary aldosteronism was associated with an increased urinary citrate excretion. In their case, this occurred in the...

Metabolism of acetate in scorbutic guinea pigs.

The effects of feeding acetate on the glucose tolerance, deposition of liver glycogen; urinary excretion of citric acid, malic acid and ketone bodies; total body lipid, phospholipid and cholesterol; and cholesterol content of different tissues were studied in normal and scorbutic guinea pigs. The effects of prolonged insulin treatment on the urinary excretion of citrate, malate and ketone bodies were also studied in normal and scorbutic guinea pigs fed acetate. It was observed that when normal guinea pigs were fed acetate, total body lipid and liver glycogen increased and there was no change in body cholesterol, tissue cholesterol and glucose tolerance. In scorbutic guinea pigs total body cholesterol and cholesterol contents of blood, small intestine and testes were increased and were further enhanced when the animals were fed acetate. Lowered glucose tolerance, diminished liver glycogen, total body lipid and phospholipid observed in scorbutic guinea pigs did not change after acetate feeding. The increased urinary excretions of ketone bodies, citric acid and malic acid by scorbutic guinea pigs came down to normal levels when they were injected with insulin. The increased cholesterogenesis in scurvy seems to be due to hypoinsulinism.

The Effect of Carbonic Anhydrase Inhibitors on Urinary Excretion of Citrate by Humans

The Effect of Carbonic Anhydrase Inhibitors on Urinary Excretion of Citrate by Humans

Urinary Excretion of Citrate in Humans Following Administration of Acetazolamide (Diamox)

Citrate is excreted in comparatively large amounts in human urine, and its excretion varies with age, diet, sex, and other factors from 100 to 1500 mg. per day. 1-4 It is lower in infants and children as compared with adults. 1-3,5-7 Citrate excretion is decreased by acidosis 7-12 (dietary, uremic, and diabetic) and by testosterone administration. 13 It is increased in alkalosis 7-12 and by the administration of estrogens, 14,15 parathyroid extract, 2,16,17 and vitamin D. 18-22 Previous experimental and clinical studies have suggested that urinary citrate aids in the chelation of calcium into a soluble complex. Low citrate levels in the presence of normal calcium-phosphorous ratios may play a role in the formation of renal calculi.2,23,24 In addition, citrate therapy has been reported to have induced an apparent improvement in a case of nephrocalcinosis. 25 In rats, acetazolamide administration has been observed to result in the deposition of calcium

Acute effects of acetazolamide (diamox) on plasma and urinary electrolytes of dogs with special reference to calcium.

Administration of Diamox by ingestion or injection to adult fasting female dogs consistently produced an acute increase of approximately 1 mg % in the plasma concentration of calcium. At the same time there was an increase in the plasma phosphate and chloride concentration and a decrease in total plasma content of carbon dioxide of Diamox-infused dogs. Diamox did not affect the plasma concentration of calcium, chloride or bicarbonate if renal excretory function was abolished prior to its administration. Infusion of Diamox produced a prompt rise in the urinary excretion of sodium, potassium, calcium, phosphate, citrate, chloride and water in fasting female dogs. The effect of Diamox on the fasting concentration of calcium rendered unsatisfactory the interpretation of data concerned with a study of its effect on the disappearance of injected calcium. However, intravenous injection of small amounts of sodium carbonate was found to produce a definite delay in the rate of disappearance of injected calcium.

Effect of acetazolamide on citrate excretion and formation of renal calculi.

ÖSTBERG,1 in 1931, suggested that the citric acid in urine functions to keep relatively insoluble calcium salts in solution. Since that time evidence has accumulated that in man the urinary citrate-calcium balance is an important mechanism for preventing the development of calcium calculi in the urinary tract.2 3 4 5 Additional evidence substantiating this concept has recently been provided by Harrison and Harrison.6 These investigators found that the urinary excretion of citrate was markedly reduced in rats that had been fed acetazolamide (Diamox). Furthermore, precipitation of calcium salts in the urinary tract of these animals was a striking finding.Recently, we have had . . .

The Influence of the Diet on Urinary Citrate Excretion

The Influence of the Diet on Urinary Citrate Excretion

Inhibition of urine citrate excretion and the production of renal calcinosis in the rat by acetazoleamide (diamox) administration.

Inhibition of urine citrate excretion and the production of renal calcinosis in the rat by acetazoleamide (diamox) administration.

THE URINARY EXCRETION OF CITRATE IN URANIUM-POISONED RATS

THE URINARY EXCRETION OF CITRATE IN URANIUM-POISONED RATS