Urinary acidification and net acid excretion in  adult rats treated neonatally with enalapril

Neonatal blockade of the renin-angiotensin system in rats induces irreversible renal histological abnormalities, including papillary atrophy and an impaired urinary concentrating ability. The aim was to investigate urinary acidification and net acid excretion in adult Wistar rats treated neonatally with enalapril (10 mg ⋅ kg−1 ⋅ day−1) or vehicle from 5 to 24 days of age. Analyses were performed in both metabolic balance studies and renal clearance experiments performed under pentobarbital sodium anesthesia. There were no differences between groups in urine pH or urinary excretion rates of bicarbonate, titratable acid, or ammonium, neither during control conditions nor after chronic NH4Cl loading (assessed before and after Na2SO4infusion). Glomerular filtration rate, maximal tubular bicarbonate reabsorption, and the urine-to-blood[Formula: see text] gradient in alkaline urine during NaHCO3 infusion did not differ between groups. Neonatally enalapril-treated rats showed a urine concentration defect and papillary damage. In conclusion, neonatal enalapril treatment produces a differentiated abnormality in tubular function in which urine concentration is impaired but urinary acidification and net acid excretion are intact.

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Role of organic anions in renal response to dietary acid and base loads

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.2.f170 ◽

1989 ◽

Vol 257 (2) ◽

pp. F170-F176 ◽

Cited By ~ 11

Author(s):

J. C. Brown ◽

R. K. Packer ◽

M. A. Knepper

Keyword(s):

Organic Anion ◽

Organic Anions ◽

Acid Excretion ◽

Acid Base Balance ◽

Acid Base ◽

Urine Ph ◽

Renal Response ◽

Base Balance ◽

Net Acid Excretion

Bicarbonate is formed when organic anions are oxidized systemically. Therefore, changes in organic anion excretion can affect systemic acid-base balance. To assess the role of organic anions in urinary acid-base excretion, we measured urinary excretion in control rats, NaHCO3-loaded rats, and NH4Cl-loaded rats. Total organic anions were measured by the titration method of Van Slyke. As expected, NaHCO3 loading increased urine pH and decreased net acid excretion (NH4+ + titratable acid - HCO3-), whereas NH4Cl loading had the opposite effect. Organic anion excretion was increased in response to NaHCO3 loading and decreased in response to NH4Cl loading. We quantified the overall effect of organic ion plus inorganic buffer ion excretion on acid-base balance. The amounts of organic anions excreted by all animals in this study were greater than the amounts of NH4+, HCO3-, or titratable acidity excreted. In addition, in response to acid and alkali loading, changes in urinary organic anion excretion were 40-50% as large as changes in net acid excretion. We conclude that, in rats, regulation of organic anion excretion can contribute importantly to the overall renal response to acid-base disturbances.

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Acid excretion by bicarbonate-free perfused rat kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1981.240.4.f306 ◽

1981 ◽

Vol 240 (4) ◽

pp. F306-F310

Author(s):

M. H. Garvey ◽

D. L. Maude

Keyword(s):

Carbonic Anhydrase ◽

Rat Kidney ◽

Acid Excretion ◽

Total Acid ◽

Urine Ph ◽

Titratable Acid ◽

Perfused Rat Kidney ◽

Reduced Rate ◽

Isolated Rat

We measured titratable acid (TA) and NH4 excretion by isolated rat kidneys perfused either with conventional bicarbonate-containing solutions or with solutions in which bicarbonate was replaced by propionate. Rates of TA excretion by bicarbonate-perfused kidneys were similar to in vivo values, 0.27 +/- 0.04 mueq.ml GF-1 (0.21 mueq.min-1.g-1), and increased significantly under bicarbonate-free conditions to 0.70 +/- 0.12 mueq.ml GF-1 (0.42 mueq.min-1.g-1). At the same time the perfusate/urine pH difference (delta pH) increased significantly, from 0.63 +/- 0.06 to 0.92 +/- 0.06. Carbonic anhydrase inhibition by 5 X 10(-4) M acetazolamide alkalinized the urine of bicarbonate-perfused kidneys, while in the bicarbonate-free preparation the urine remained acid (delta pH = 0.27 +/- 0.04) and titratable acid continued to be excreted, though at a reduced rate, 0.19 +/- 0.04 mueq.ml GF-1. Under these same bicarbonate-free carbonic anhydrase-inhibited conditions, lowering the perfusate pH from 7.4 to 7.1 increased delta pH to 0.36 +/- 0.02 and caused total acid excretion (TA + NH4) to rise from 0.29 +/- 0.04 to 0.45 +/- 0.06 mueq.ml GF-1, and increasing the perfusate [HPO4] from 2.4 to 9.6 mM increased TA to 0.80 +/- 0.09 mueq.ml GF-1.

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Pendrin in the mouse kidney is primarily regulated by Cl− excretion but also by systemic metabolic acidosis

AJP Cell Physiology ◽

10.1152/ajpcell.00419.2008 ◽

2008 ◽

Vol 295 (6) ◽

pp. C1658-C1667 ◽

Cited By ~ 41

Author(s):

Patricia Hafner ◽

Rosa Grimaldi ◽

Paola Capuano ◽

Giovambattista Capasso ◽

Carsten A. Wagner

Keyword(s):

Metabolic Acidosis ◽

Collecting Duct ◽

Relative Number ◽

High Protein ◽

Acid Excretion ◽

Acid Base ◽

Urinary Acidification ◽

Apical Side ◽

Acid Base Status ◽

Net Acid Excretion

The Cl−/anion exchanger pendrin (SLC26A4) is expressed on the apical side of renal non-type A intercalated cells. The abundance of pendrin is reduced during metabolic acidosis induced by oral NH4Cl loading. More recently, it has been shown that pendrin expression is increased during conditions associated with decreased urinary Cl− excretion and decreased upon Cl− loading. Hence, it is unclear if pendrin regulation during NH4Cl-induced acidosis is primarily due the Cl− load or acidosis. Therefore, we treated mice to increase urinary acidification, induce metabolic acidosis, or provide an oral Cl− load and examined the systemic acid-base status, urinary acidification, urinary Cl− excretion, and pendrin abundance in the kidney. NaCl or NH4Cl increased urinary Cl− excretion, whereas (NH4)2SO4, Na2SO4, and acetazolamide treatments decreased urinary Cl− excretion. NH4Cl, (NH4)2SO4, and acetazolamide caused metabolic acidosis and stimulated urinary net acid excretion. Pendrin expression was reduced under NaCl, NH4Cl, and (NH4)2SO4 loading and increased with the other treatments. (NH4)2SO4 and acetazolamide treatments reduced the relative number of pendrin-expressing cells in the collecting duct. In a second series, animals were kept for 1 and 2 wk on a low-protein (20%) diet or a high-protein (50%) diet. The high-protein diet slightly increased urinary Cl− excretion and strongly stimulated net acid excretion but did not alter pendrin expression. Thus, pendrin expression is primarily correlated with urinary Cl− excretion but not blood Cl−. However, metabolic acidosis caused by acetazolamide or (NH4)2SO4 loading prevented the increase or even reduced pendrin expression despite low urinary Cl− excretion, suggesting an independent regulation by acid-base status.

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Comparison of estimated renal net acid excretion from dietary intake and body size with urine pH

Journal of the American Dietetic Association ◽

10.1016/s0002-8223(03)00469-3 ◽

2003 ◽

Vol 103 (8) ◽

pp. 1001-1007 ◽

Cited By ~ 26

Author(s):

Dominique S. Michaud ◽

Richard P. Troiano ◽

Amy F. Subar ◽

Shirley Runswick ◽

Sheila Bingham ◽

...

Keyword(s):

Body Size ◽

Dietary Intake ◽

Acid Excretion ◽

Urine Ph ◽

Renal Net Acid Excretion ◽

Net Acid Excretion

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Effects of glucocorticoid steroids on renal and systemic acid-base metabolism

AJP Renal Physiology ◽

10.1152/ajprenal.1980.239.1.f30 ◽

1980 ◽

Vol 239 (1) ◽

pp. F30-F43 ◽

Cited By ~ 5

Author(s):

H. N. Hulter ◽

J. H. Licht ◽

E. L. Bonner ◽

R. D. Glynn ◽

A. Sebastian

Keyword(s):

Steady State ◽

Acid Production ◽

Chronic Administration ◽

Acid Excretion ◽

Acid Base ◽

Unmeasured Anion ◽

Urine Ph ◽

Group I ◽

Potassium Clearance ◽

Net Acid Excretion

Clinical states of hyperglucocorticoidism are associated with renal metabolic alkalosis, yet the systemic and renal acid-base response to chronic administration of glucocorticoid steroids (dexamethasone, triamcinolone) possessing little or no mineralocorticoid activity has not been investigated. In balance studies studies in dogs administration of triamcinolone (Tcn), 1.0 mg. kg-1. day-1 for 6–9 days (group I, n = 5), resulted in a persistent reduction in urine pH and increase in net acid excretion (NAE), and in the excretion of urinary unmeasured anions (C+NH4,Na;K minus A-Cl,HCO3,Pi), which were identified as organic anions and sulfate. A significant degree of metabolic acidosis occurred initially (delta [HCO3-]p, -3.4 meq/liter, P less than 0.05, day 1). As Tcn administration was continued, the cumulative increment in net acid excreted exceeded the cumulative increment in urinary unmeasured anion excreted and [HCO-3]p returned to pre-Tcn control values and remained stable thereafter. In the steady state of Tcn administration plasma potassium concentration and renal potassium clearance were not significantly different from pre-Tcn control, in contrast to the findings of hypokalemia and increased renal potassium clearance during chronic administration of deoxycorticosterone (DOC). Triamcinolone did not result in antinatriuresis or antichloruresis. Chronic administration of a 10–fold smaller dose of Tcn (0.1 mg . kg-1 . day-1) in an additional group (group III) also resulted in a persisting reduction in urine pH and an increase in net acid excretion that exceeded unmeasured anion excretion and resulted in a small increase in steady-state plasma bicarbonate concentration. These results suggest that chronic administration of potent glucocorticoid steroids results in 1) a persisting increase in endogenous acid production, and 2) stimulation of renal hydrogen ion secretion that was of greater degree than accounted for by the increment in endogenous acid production and that was not accompanied by renal mineralocorticoid effects on sodium and potassium transport.

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Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs

AJP Renal Physiology ◽

10.1152/ajprenal.1977.232.2.f136 ◽

1977 ◽

Vol 232 (2) ◽

pp. F136-F146 ◽

Cited By ~ 4

Author(s):

H. N. Hulter ◽

L. P. Ilnicki ◽

J. A. Harbottle ◽

A. Sebastian

Keyword(s):

Hydrogen Ion ◽

Ion Concentration ◽

Ammonium Excretion ◽

Acid Excretion ◽

Concentration Gradients ◽

Urine Ph ◽

Hydrogen Ion Concentration ◽

Titratable Acid ◽

Potassium Restriction ◽

Potassium Retention

When the administration of exogenous mineralocorticoid hormones was discontinued in adrenalectomized dogs maintained on glucocorticoid, net acid excretion decreased due largely to a reduction in urinary ammonium excretion (UNH4+V), and hyperchloremic hyperkalemic metabolic acidosis occurred and persisted. The reduction in UNH4+V was not associated with an increase in urine pH (UpH) or a decrease in urine flow, but correlated with the severity of hyperkalemia and was mitigated by dietary potassium restriction. UpH decreased to values as low as 5.3. During acidosis, UpH varied directly with UNH4+V, but in relation to UNH4+V, UpH exceeded that in acid-fed mineralocorticoid-replete dogs. Extrapolated to UNH4+V=0, however, UpH was not significantly different in the two groups (5.27 vs. 5.44). When distal delivery of sodium was increased by infusion of sodium phosphate, titratable acid excretion increased in both groups but pateaued at lower rates in the mineralocorticoid-deficient dogs. These results suggest that in mineralocorticoid-deficient dogs, renal ammonia production is diminished, in part due to potassium retention and hyperkalemia; renal hydrogen ion secretory capacity is reduced even when sodium and buffer delivery to the distal nephron is not reduced; and the ability of the kidney to generate normally steep urine-to-blood hydrogen ion concentration gradients is unimpaired.

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Estimated Net Acid Excretion Inversely Correlates With Urine pH in Vegans, Lacto-Ovo Vegetarians, and Omnivores

Journal of Renal Nutrition ◽

10.1053/j.jrn.2008.04.007 ◽

2008 ◽

Vol 18 (5) ◽

pp. 456-465 ◽

Cited By ~ 22

Author(s):

Lynne M. Ausman ◽

Lauren M. Oliver ◽

Barry R. Goldin ◽

Margo N. Woods ◽

Sherwood L. Gorbach ◽

...

Keyword(s):

Acid Excretion ◽

Urine Ph ◽

Net Acid Excretion

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Inner medullary collecting duct function during rebound alkalemia

AJP Renal Physiology ◽

10.1152/ajprenal.1987.252.4.f712 ◽

1987 ◽

Vol 252 (4) ◽

pp. F712-F716

Author(s):

H. H. Bengele ◽

E. R. McNamara ◽

J. H. Schwartz ◽

E. A. Alexander

Keyword(s):

Collecting Duct ◽

Acid Excretion ◽

Acid Base ◽

Proton Secretion ◽

Inner Medullary Collecting Duct ◽

Titratable Acid ◽

Base Parameters ◽

Arterial Ph ◽

Medullary Collecting Duct ◽

Net Acid Excretion

Rats, made acidemic when fed NH4Cl, become alkalemic with discontinuation of the NH4Cl. This phenomenon has been called rebound metabolic alkalemia (RMA). This study examines the function of the inner medullary collecting duct (IMCD) during RMA. Rats drank only 1.5% NH4Cl for 5 days and then water for 16 h prior to study, yielding an arterial pH = 7.50 +/- 0.01, PCO2 = 39 +/- 1 mmHg, and bicarbonate = 29.5 +/- 1.0 mM. The IMCD data were obtained by microcatheterization from deep (1.5-3.0 mm) and tip (0.2-0.5 mm) samples. Equilibrium pH decreased from 5.92 +/- 0.09 (n = 20) to 5.38 +/- 0.04 (n = 20) and PCO2 increased from 32 +/- 1 to 38 +/- 1 mmHg between deep and tip samples. Bicarbonate delivery decreased from 37 +/- 8 to 7 +/- 1 nmol/min. Titratable acid and ammonium delivery increased from 284 +/- 52 to 347 +/- 62 nmol/min and from 549 +/- 38 to 685 +/- 40 nmol/min, respectively. Calculated net acid excretion increased from 796 +/- 88 to 1,026 +/- 95 nmol/min. Thus during RMA, proton secretion continues along the IMCD, although there is a systemic alkalemia. It appears that factors in addition to systemic acid-base parameters are important in the regulation of proton secretion by the IMCD.

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Net Acid Excretion and Urinary Organic Anions in Idiopathic Uric Acid Nephrolithiasis

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.10420818 ◽

2019 ◽

Vol 14 (3) ◽

pp. 411-420 ◽

Cited By ~ 8

Author(s):

I. Alexandru Bobulescu ◽

Sun K. Park ◽

L.H. Richie Xu ◽

Francisco Blanco ◽

John Poindexter ◽

...

Keyword(s):

Body Mass Index ◽

Uric Acid ◽

Organic Acids ◽

Body Mass ◽

Organic Anions ◽

Acid Excretion ◽

Urine Ph ◽

Control Subjects ◽

Uric Acid Nephrolithiasis ◽

Net Acid Excretion

Background and objectivesIdiopathic uric acid nephrolithiasis, which is closely associated with obesity and the metabolic syndrome, is increasing in prevalence. Unduly acidic urine pH, the quintessential pathophysiologic feature of this disease, is in part explained by inadequate excretion of the principal urinary buffer ammonium. The role of net acid excretion in the pathogenesis of uric acid nephrolithiasis is incompletely understood.Design, setting, participants, & measurementsWe compared acid-base parameters of patients with idiopathic uric acid nephrolithiasis with matched control subjects under controlled diets in an inpatient metabolic unit. Measurements included fasting blood and 24-hour urine chemistries and 24-hour urine metabolomic analysis. Comparisons between groups included analysis of covariance models controlling for urine pH or body mass index.ResultsSubjects with idiopathic uric acid nephrolithiasis had lower urine pH (5.5 versus 5.9; P<0.001) and higher net acid excretion (60 versus 43 mEq/24 h; P<0.001), with the excess H+ carried by nonammonium buffers. In all subjects, there was a positive relationship of net acid excretion with higher body mass index in spite of strictly controlled equivalent dietary acid intake. This relationship was most evident among control subjects (r=0.36; P=0.03). It was attenuated in patients with idiopathic uric acid nephrolithiasis whose net acid excretion remained fixedly high and ammonium excretion remained low relative to net acid excretion, resulting in low urine pH over a wide body mass index range. Urinary metabolomics was performed to attempt to identify excess organic acids presented to the kidney in idiopathic uric acid nephrolithiasis. Among the tricarboxylic acid cycle intermediates and amino acid and lipid metabolites analyzed, 26 organic anions with acid dissociation constants values in the range of urine pH showed greater protonation. However, protons carried by the identified organic acids did not entirely account for the higher titratable acidity seen in idiopathic uric acid nephrolithiasis.ConclusionsHigher acid load to the kidney, resulting in higher urinary net acid excretion, is an important factor in the pathogenesis of idiopathic uric acid nephrolithiasis.

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