Use of pyrazinamide to assess renal uric acid transport in the rat: a micropuncture study

1976 ◽  
Vol 230 (5) ◽  
pp. 1276-1283 ◽  
Author(s):  
RG Abramson ◽  
MF Levitt
Keyword(s):  
Uric Acid ◽  
Proximal Tubule ◽  
Volume Expansion ◽  
Acid Transport ◽  
Sodium Dependent ◽  
Micropuncture Study ◽  
Bidirectional Transport ◽  
Fluid Collections ◽  
Uniform Reduction ◽  
Column Chromatographic

Free-flow micropuncture studies were performed to evaluate renal uric acid transport in control and pyrazinamide-treated rats. In all studies [2-14C]uric acid and [methoxy-3H]inulin were administered. [2-14C]uric acid was determined after column chromatographic separation from its labeled oxidation product in tubular fluid, plasma, and urine. Tubular fluid collections were obtained from the early and late proximal tubule under hydropenic conditions and from the early proximal tubule during volume expansion induced with 0.9% sodium chloride. These studies indicate that pyrazinamide, in the dose employed, provokes a uniform reduction in fractional uric acid excretion but simultaneously inhibits both net uric acid reabsorption and secretion in the early and late proximal tubule, respectively. In addition, these experiments unmasked uric acid reabsorption within the late proximal tubule and bidirectional transport beyond this nephron site. These studies also suggest at least two mechanisms for uric acid reabsorption; one sodium dependent, the other independent of sodium and water transport.

Micropuncture study of uric acid transport in rat kidney

1975 ◽  
Vol 228 (5) ◽  
pp. 1597-1605 ◽  
Author(s):  
RG Abramson ◽  
MF Levitt
Keyword(s):  
Uric Acid ◽  
Proximal Tubule ◽  
Rat Kidney ◽  
Chromatographic Technique ◽  
Acid Transport ◽  
Cent Sodium ◽  
Micropuncture Study ◽  
Nephron Segment ◽  
Fluid Collections ◽  
Column Chromatographic

Free-flow micropuncture studies were perfromed to evaluated uric acid transport in the rat kidney. In all studies (a-minus 14C) uric acid and (methoxy-3H) inulin wereadministered. A simple two-step, column-chromatographic technique was utilized to separate (2-minus 14C) uric acid from its labeled oxidation product in plasma, urine, and tubular fluid. Tubular fluid collections were obtained from the early-and late-proximal tubule under control conditions and during subsequent volume expansion induced with 0.9 per-cent sodium chloride. These studies indicate bidirectional, possible active, uric acidtransport in the proximal tubule undr control conditions, with net reabsorption evident early and net decretion apparent late in this nephron segment. In association with volumeexpansion net uric acid reabsorption and secretion both decreased. No significant nettransport was evident beyond the accessible portion of the late-proximal tubule in either experimental state.

Renal excretion of allantoin in rats: a micropuncture and clearance study

1977 ◽  
Vol 233 (5) ◽  
pp. F373-F381 ◽  
Author(s):  
J. P. Briggs ◽  
M. F. Levitt ◽  
R. G. Abramson
Keyword(s):  
Uric Acid ◽  
Renal Excretion ◽  
Rat Kidney ◽  
Chromatographic Technique ◽  
Experimental Conditions ◽  
Clearance Studies ◽  
Fluid Collections ◽  
And Control ◽  
Clearance Study ◽  
Column Chromatographic

Free-flow micropuncture and clearance studies were performed to evaluate the transport of allantoin inthe rat kidney. Inn all studies [2-14C]uric acid and [methoxy-3H]inulin were administered. With a two-step column chromatographic technique, radiolabeled uric acid and allantoin were separated in plasma, urine, and tubular fluid, and the [2-14C]allantoin concentration was determined. Tubular fluid collections were obtained under hydropenic and control coneated animals in the control and volume-expanded states. Clearance data were obtained in oxonic acid-treated animals under the same experimental conditions. These studies indicate that allantoin is not bound to plasma protein and is, therefore, freely filterable. Neither net reabsorption nor net secretion of allantoin was evident along the length of the nephron. The bubular handling of allantoin was demonstrated to be dissociated from that of uric acid in all experimental states. No significant intrarenal production of allantoin from uric acid was observed.

scholarly journals A model of uric acid transport in the rat proximal tubule

2019 ◽  
Vol 316 (5) ◽  
pp. F934-F947 ◽  
Author(s):  
Aurélie Edwards ◽  
Muriel Auberson ◽  
Suresh K. Ramakrishnan ◽  
Olivier Bonny
Keyword(s):  
Uric Acid ◽  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Glucose Transporter ◽  
Transport Model ◽  
Ang Ii ◽  
Acid Transport ◽  
Secretion Pathways ◽  
Experimental Findings ◽  
Urate Reabsorption

The objective of the present study was to theoretically investigate the mechanisms underlying uric acid transport in the proximal tubule (PT) of rat kidneys, and their modulation by factors, including Na+, parathyroid hormone, ANG II, and Na+-glucose cotransporter-2 inhibitors. To that end, we incorporated the transport of uric acid and its conjugate anion urate in our mathematical model of water and solute transport in the rat PT. The model accounts for parallel urate reabsorption and secretion pathways on apical and basolateral membranes and their coupling to lactate and α-ketoglutarate transport. Model results agree with experimental findings at the segment level. Net reabsorption of urate by the rat PT is predicted to be ~70% of the filtered load, with a rate of urate removal from the lumen that is 50% higher than the rate of urate secretion. The model suggests that apical URAT1 deletion significantly reduces net urate reabsorption across the PT, whereas ATP-binding cassette subfamily G member 2 dysfunction affects it only slightly. Inactivation of basolateral glucose transporter-9 raises fractional urate excretion above 100%, as observed in patients with renal familial hypouricemia. Furthermore, our results suggest that reducing Na+ reabsorption across Na+/H+ exchangers or Na+-glucose cotransporters augments net urate reabsorption. The model predicts that parathyroid hormone reduces urate excretion, whereas ANG II increases it. In conclusion, we have developed the first model of uric acid transport in the rat PT; this model provides a framework to gain greater insight into the numerous solutes and coupling mechanisms that affect the renal handing of uric acid.

Placental uric acid transport system and its impact on fetal development

2018 ◽  
Author(s):  
B Lüscher ◽  
D Surbek ◽  
P Schneider ◽  
M Baumann
Keyword(s):  
Uric Acid ◽  
Transport System ◽  
Fetal Development ◽  
Acid Transport

scholarly journals Serum uric acid, disease severity and outcomes in COVID-19

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Inès Dufour ◽  
Alexis Werion ◽  
Leila Belkhir ◽  
Anastazja Wisniewska ◽  
Marie Perrot ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Uric Acid ◽  
Respiratory Failure ◽  
Confidence Interval ◽  
Proximal Tubule ◽  
Disease Severity ◽  
Serum Levels ◽  
Kidney Proximal Tubule ◽  
Urate Transporter ◽  
Low Serum

Abstract Background The severity of coronavirus disease 2019 (COVID-19) is highly variable between individuals, ranging from asymptomatic infection to critical disease with acute respiratory distress syndrome requiring mechanical ventilation. Such variability stresses the need for novel biomarkers associated with disease outcome. As SARS-CoV-2 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid, we hypothesized that low serum levels of uric acid (hypouricemia) may be associated with severity and outcome of COVID-19. Methods In a retrospective study using two independent cohorts, we investigated and validated the prevalence, kinetics and clinical correlates of hypouricemia among patients hospitalized with COVID-19 to a large academic hospital in Brussels, Belgium. Survival analyses using Cox regression and a competing risk approach assessed the time to mechanical ventilation and/or death. Confocal microscopy assessed the expression of urate transporter URAT1 in kidney proximal tubule cells from patients who died from COVID-19. Results The discovery and validation cohorts included 192 and 325 patients hospitalized with COVID-19, respectively. Out of the 517 patients, 274 (53%) had severe and 92 (18%) critical COVID-19. In both cohorts, the prevalence of hypouricemia increased from 6% upon admission to 20% within the first days of hospitalization for COVID-19, contrasting with a very rare occurrence (< 1%) before hospitalization for COVID-19. During a median (interquartile range) follow-up of 148 days (50–168), 61 (12%) patients required mechanical ventilation and 93 (18%) died. In both cohorts considered separately and in pooled analyses, low serum levels of uric acid were strongly associated with disease severity (linear trend, P < 0.001) and with progression to death and respiratory failure requiring mechanical ventilation in Cox (adjusted hazard ratio 5.3, 95% confidence interval 3.6–7.8, P < 0.001) or competing risks (adjusted hazard ratio 20.8, 95% confidence interval 10.4–41.4, P < 0.001) models. At the structural level, kidneys from patients with COVID-19 showed a major reduction in urate transporter URAT1 expression in the brush border of proximal tubules. Conclusions Among patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation.

Electrolyte handling by the superficial nephron of the rabbit

1986 ◽  
Vol 250 (4) ◽  
pp. F590-F595 ◽  
Author(s):  
N. L. Wong ◽  
S. J. Whiting ◽  
C. L. Mizgala ◽  
G. A. Quamme
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Concentration Ratio ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Mean Value ◽  
Loop Of Henle ◽  
Collection Site ◽  
Micropuncture Study ◽  
The Mean

A micropuncture study of the rabbit was performed to evaluate the function of the superficial nephron. The mean glomerular filtration rate of the left micropunctured kidney was 4.0 +/- 0.8 ml/min. The concentration profile of electrolytes within the proximal tubule was similar to that of species previously investigated except for potassium. The mean tubular fluid (TF)-ultrafilterable (UF) concentration ratios were as follows: sodium, 1.01 +/- 0.03; chloride, 1.14 +/- 0.04; calcium, 1.12 +/- 0.04; magnesium, 1.47 +/- 0.08; and phosphate, 0.94 +/- 0.09, with a mean TF-plasma (P) inulin concentration ratio of 1.78 +/- 0.14 (n = 32). The TF/UF potassium value significantly increased in association with TF/P inulin to a mean value of 1.26 +/- 0.06. Accordingly, 29% of the filtered potassium was reabsorbed in the superficial proximal tubule compared with 43% of the filtered sodium. The loop of Henle reabsorbed 55-60% of the filtered sodium, chloride, and calcium, whereas considerably less magnesium (33%) was reabsorbed. Segments beyond the distal tubule collection site reabsorbed little of the delivered magnesium, which supports the notion that the loop of Henle is the principal segment accounting for adjustments in magnesium balance. These studies indicate that the superficial nephron of the rabbit performs similar to other species reported, except potassium reabsorption is significantly less in the proximal convoluted tubule.

Micropuncture study of ammonia excretion in the rat

1963 ◽  
Vol 205 (1) ◽  
pp. 127-132 ◽  
Author(s):  
Sheldon Glabman ◽  
R. M. Klose ◽  
Gerhard Giebisch
Keyword(s):  
Proximal Tubule ◽  
Ammonium Chloride ◽  
Ammonia Excretion ◽  
The Other ◽  
Water Reabsorption ◽  
Micropuncture Study

Ammonia has been determined in blood and in samples of tubular fluid obtained by micropuncture at various sites along the nephron from two groups of rats, one untreated and the other pretreated with ammonium chloride. Ammonia has been found in tubular fluid from all segments of the nephron, the concentrations being generally higher in those animals which were pretreated with ammonium chloride. In addition, there is a tendency for the concentration of ammonia to increase as the site of micropuncture progresses along the nephron. In the proximal tubule, concentrations of ammonia have been found which are greater than can be accounted for solely by the extraction of water in this segment. This is taken to indicate tubular addition of ammonia at this site. Since the increments of ammonia along the nephron generally exceed that which could be due to water reabsorption, it is concluded that all parts of the nephron contribute to urinary ammonia excretion.

Common gene variants interactions related to uric acid transport are associated with knee osteoarthritis susceptibility

2018 ◽  
Vol 60 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Javier Fernández-Torres ◽  
Gabriela Angélica Martínez-Nava ◽  
Francesca Oliviero ◽  
Alberto Gabriel López-Reyes ◽  
Karina Martínez-Flores ◽  
...  
Keyword(s):  
Uric Acid ◽  
Knee Osteoarthritis ◽  
Gene Variants ◽  
Acid Transport ◽  
Common Gene
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