Effect of Acute Metabolic Acidosis on the Levels of some Metabolic Intermediates in the Rat Kidney

Franklyn I. Bennett; George A.O. Alleyne

doi:10.1159/000172677

Ammoniagenesis by the Isolated Perfused Rat Kidney: The Critical Role of Urinary Acidification

Clinical Science ◽

10.1042/cs0560353 ◽

1979 ◽

Vol 56 (4) ◽

pp. 353-364 ◽

Cited By ~ 32

Author(s):

R. L. Tannen ◽

B. D. Ross

Keyword(s):

Metabolic Acidosis ◽

Rat Kidney ◽

Critical Role ◽

Sodium Reabsorption ◽

Ammonia Production ◽

Bicarbonate Concentration ◽

Urine Ph ◽

Average Value ◽

Acute Metabolic Acidosis

1. The effect of metabolic acidosis simulated in vitro on ammoniagenesis was investigated by using the isolated kidney of the rat perfused with an albumin Krebs—Henseleit medium containing glutamine and glucose. 2. Addition of HCl to a perfusate of normal bicarbonate concentration resulted in a prompt increase in urine flow rate, decrease in fractional sodium reabsorption and decrease in urine pH. 3. A minimum urine pH as low as 5·15 was achieved, with an average value of 5·92, indicating that this preparation has the capacity to acidify normally. 4. In contrast with studies in vitro with other preparations, with the functional perfused kidney a diminution in perfusate bicarbonate concentration resulted in a prompt increase in ammonia production, which was strikingly correlated with the decrease in urine pH. 5. The increase in ammonia production was diminished in studies carried out with a non-urinating kidney, in comparison with those that exhibited significant urine acidification. 6. These data suggest that a decrease in urine pH with trapping of ammonia in the urine may be a critical stimulus for increased ammonia production in acute metabolic acidosis.

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Effect of Acute Metabolic Acidosis on Vasopressin-Dependent Cyclic AMP in Rat Kidney

Endocrinology ◽

10.1210/endo-96-6-1552 ◽

1975 ◽

Vol 96 (6) ◽

pp. 1552-1558 ◽

Cited By ~ 10

Author(s):

NAMA BECK ◽

HEI-PAIK KIM

Keyword(s):

Metabolic Acidosis ◽

Cyclic Amp ◽

Rat Kidney ◽

Acute Metabolic Acidosis

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Effect of altered acid-base balance and of various agonists on levels of renal glutamate dehydrogenase mRNA

AJP Renal Physiology ◽

10.1152/ajprenal.1992.262.3.f507 ◽

1992 ◽

Vol 262 (3) ◽

pp. F507-F512 ◽

Cited By ~ 8

Author(s):

S. Kaiser ◽

J. J. Hwang ◽

H. Smith ◽

C. Banner ◽

T. C. Welbourne ◽

...

Keyword(s):

Metabolic Acidosis ◽

Glutamate Dehydrogenase ◽

Rat Kidney ◽

Acid Base Balance ◽

Normal Medium ◽

Rapid Induction ◽

F Cells ◽

Base Balance ◽

Acute Metabolic Acidosis

Rat kidney contains 3.5-kb and 2.8-kb mRNAs that encode for glutamate dehydrogenase (GDH). The levels of both mRNAs are increased gradually after onset of chronic metabolic acidosis and reach a maximum induction of 2.5-fold after 7 days. In contrast, during recovery from chronic acidosis, the levels of the GDH mRNAs are returned to normal within 1 day. The development of an acute metabolic acidosis causes a more rapid induction of GDH mRNA. This increase occurs after a 7-h lag and plateaus after 18 h at a level that is threefold greater than normal. A very similar profile was observed after the transfer of LLC-PK-F+ cells from normal medium to an acidic medium containing 10 mM bicarbonate and adjusted to pH 6.9. However, the transfer of cells from acidic to normal medium caused an immediate and rapid [half-life (t) = 1 h] decrease in GDH mRNA. The apparent half-lives of GDH mRNA were measured by treating cells grown in normal (t = 4 h) and acidic media (t = 12 h) with actinomycin D. Thus, increased stability may account for the induction of GDH mRNA that occurs during growth in response to acidosis. The levels of GDH mRNA are independently affected by changes in medium pH or bicarbonate concentration. The levels of GDH mRNA are also increased by treating cells with adenosine 3',5'-cyclic monophosphate, epinephrine, triiodothyronine, or retinoic acid, whereas treatment with angiotensin II, vasopressin, phorbol 12-myristate 13-acetate, or cycloheximide did not produce an increase. The inductive effect of dexamethasone, which is observed in vivo, is not reproduced in the LLC-PK-F+ cells.

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Effect of acute metabolic acidosis on ammonia metabolism in kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1989.256.2.f321 ◽

1989 ◽

Vol 256 (2) ◽

pp. F321-F328

Author(s):

R. T. Bogusky ◽

R. L. Dietrich

Keyword(s):

Metabolic Acidosis ◽

Glutamate Dehydrogenase ◽

Rat Kidney ◽

Methionine Sulfoximine ◽

Amide Nitrogen ◽

Ammonia Metabolism ◽

Perfused Rat Kidney ◽

Purine Nucleotide Cycle ◽

Acute Metabolic Acidosis ◽

Ammonia Formation

To understand the mechanisms that initiate the increase in ammonia formation during acute acidosis in kidney [amino-15N]- and [amino-15N]glutamine were used as substrates in isolated perfused rat kidney experiments. Perfused kidneys from methionine sulfoximine-treated rats take up glutamine nitrogen at the rate of 1.50 +/- 0.08 mumol.g kidney-1.min-1 while forming ammonia at a rate of 0.65 +/- 0.09 mumol.g.kidney-1.min-1. Mass spectrometer analysis of the perfusate and urine reveals that ammonia is formed from the amide nitrogen of glutamine at the rate of 0.32 +/- 0.06 mumol.g kidney-1.min-1 and ammonia is formed from glutamate derived from glutamine at the rate of 0.21 +/- 0.04 mumol.g kidney-1.min-1. The balance of the ammonia formed is from unidentified endogenous sources. Addition of HCl to the perfusate to lower perfusate pH increases ammonia formation to 1.09 +/- 0.10 mumol.g kidney-1.min-1. The results exclude a role for the purine nucleotide cycle during acute acidosis and confirm that ammonia formation from glutamate derived from glutamine is via glutamate dehydrogenase. Lowering perfusate pH increases the rate of glutamine deamidation significantly by 0.33 +/- 0.06 mumol.g kidney-1.min-1 and increases the rate of ammonia formation via glutamate dehydrogenase insignificantly by only 0.08 +/- 0.04 mumol.g kidney-1.min-1, whereas ammonia formation from endogenous sources remains unchanged. The results demonstrate that regulation of glutamine deamidation is an important controlling step in ammonia formation during acute metabolic acidosis in kidney.

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Effect of Decrease in Bicarbonate Concentration on Metabolism of the Isolated Perfused Rat Kidney

Clinical Science ◽

10.1042/cs0570103 ◽

1979 ◽

Vol 57 (1) ◽

pp. 103-111 ◽

Cited By ~ 15

Author(s):

B. D. Ross ◽

R. L. Tannen

Keyword(s):

Metabolic Acidosis ◽

Metabolic Regulation ◽

Phosphoenolpyruvate Carboxykinase ◽

Rat Kidney ◽

Ammonia Production ◽

Perfusion Medium ◽

Isolated Perfused Rat Kidney ◽

Acid Urine ◽

Perfused Rat Kidney ◽

Acute Metabolic Acidosis

1. An isolated perfused rat kidney preparation which responds to acidification of the perfusion medium with the production of an acid urine and increased ammonia production was used to study the metabolic regulation of ammonia production from glutamine. 2. An inhibitor of gluconeogenesis at phosphoenolpyruvate carboxykinase(GTP), mercaptopicolinate, completely prevented the increase in ammoniagenesis, without preventing acidification of the urine. 3. Acidification of the perfusion medium from pH 7·4 to 7·0 reduced the renal concentrations of malate and 2-oxoglutarate. 4. Malate concentration was restored by inhibition of phosphoenolpyruvate carboxykinase(GTP), but 2-oxoglutarate content remained low. This indicates that accelerated gluconeogenesis in acute acidosis cannot be the explanation for the fall in 2-oxoglutarate concentration. 5. The fall in 2-oxoglutarate content is taken to indicate an important fall in tissue pH or in the redox ratio (NAD+/NADH) or both during acute metabolic acidosis. 6. From these studies with lowered bicarbonate two separate stimuli to ammoniagenesis in acute metabolic acidosis are postulated: urinary trapping of ammonia and increased disposal of glutamine carbon atoms via the pathway of glucose synthesis.

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ACUTE METABOLIC ACIDOSIS: EFFECTS ON ARGININE IN VASOPRESSIN(AVP) RELEASE IN FETAL SHEEP

Pediatric Research ◽

10.1203/00006450-198404001-00264 ◽

1984 ◽

Vol 18 ◽

pp. 137A-137A

Author(s):

Daniel J Faucher ◽

Tom Lowe ◽

About Laptook ◽

John C Porter ◽

Charles R Rosenfeld

Keyword(s):

Metabolic Acidosis ◽

Fetal Sheep ◽

Acute Metabolic Acidosis

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Regulation of AE1 anion exchanger and H + -ATPase in rat cortex by acute metabolic acidosis and alkalosis

Kidney International ◽

10.1038/ki.1997.16 ◽

1997 ◽

Vol 51 (1) ◽

pp. 125-137 ◽

Cited By ~ 95

Author(s):

Ivan Sabolić ◽

Dennis Brown ◽

Stephen L. Gluck ◽

Seth L. Alper

Keyword(s):

Metabolic Acidosis ◽

Anion Exchanger ◽

Rat Cortex ◽

Acute Metabolic Acidosis

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Concentrations of Metabolic Intermediates in Kidneys of Rats with Metabolic Acidosis

Nature ◽

10.1038/217847a0 ◽

1968 ◽

Vol 217 (5131) ◽

pp. 847-848 ◽

Cited By ~ 32

Author(s):

G. A. O. ALLEYNE

Keyword(s):

Metabolic Acidosis ◽

Metabolic Intermediates

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Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

The Scientific World JOURNAL ◽

10.1155/2014/627673 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 37

Author(s):

María M. Adeva-Andany ◽

Carlos Fernández-Fernández ◽

David Mouriño-Bayolo ◽

Elvira Castro-Quintela ◽

Alberto Domínguez-Montero

Keyword(s):

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Sodium Bicarbonate ◽

Negative Impact ◽

Qtc Interval ◽

Bicarbonate Therapy ◽

Proximal Tubular ◽

Acute Metabolic Acidosis ◽

Renal Proximal Tubular

Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated.

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