scholarly journals THE ROLE OF ACIDURIA IN THE DEVELOPMENT OF HEMOGLOBINURIC NEPHROSIS IN DEHYDRATED RABBITS

1950 ◽  
Vol 92 (1) ◽  
pp. 11-23 ◽  
Author(s):  
Joseph J. Lalich ◽  
Seymour I. Schwartz
Keyword(s):  
Tubular Damage ◽  
Urine Ph ◽  
Kidney Weight ◽  
Collecting Tubules

The effect of acid diets, fasting, and dehydration on the urine pH and the kidneys was determined in 11 control animals. Hyaline casts in the collecting tubules and interstitial medullary edema were observed in the 8 that survived. The test rabbits were subjected to the same treatment as the controls but, in addition, received 1.8 gm./kilo of intravenous homologous hemoglobin. Eleven of 18 animals died of hemoglobinuric nephrosis. The rabbits which died of hemoglobinuric nephrosis exhibited significant alterations in two or more of the following: kidney weight, pigment cast accumulation, and elevations of NPN. The theories which have been advanced to explain the pathogenesis of hemoglobinuric nephrosis are evaluated in the light of the present observations. It is proposed on the basis of them that antecedent tubular damage is of primary importance in the pathogenesis of hemoglobinuric nephrosis.

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

1989 ◽  
Vol 257 (2) ◽  
pp. F170-F176 ◽  
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.

Ammonia metabolism

1978 ◽  
Vol 235 (4) ◽  
pp. F265-F277 ◽  
Author(s):  
R. L. Tannen
Keyword(s):  
Critical Role ◽  
Tca Cycle ◽  
Gamma Glutamyl Transferase ◽  
Urine Ph ◽  
Ammonia Metabolism ◽  
Adaptive Process ◽  
Purine Nucleotide Cycle ◽  
Tca Cycle Intermediates ◽  
Glutamyl Transferase

The pathways responsible for an the mechanisms underlying the adaptive increase in ammonia production in response to acidosis are considered. It seems unlikely that the cytosolic pathways (glutamine synthetase, glutaminase II, phosphate-independent glutaminase, and gamma-glutamyl transferase) are of primary importance in the adaptive process, but the role of the purine nucleotide cycle has not been resolved. The intramitochondrially located phosphate-dependent glutaminase pathway is generally believed to be of primary importance. Adaptation involved either enhanced glutamine entry into the mitrochondria and/or activation of phosphate-dependent glutaminase, but the relative importance of each has not been resolved definitively. The overall adaptive response is probably modulated by factors regulating alpha-ketoglutarate metabolism to phosphoenolpyruvate, and possibly also by metabolism of TCA cycle intermediates. It seems unlikely that a decrease in systemic pH is the direct effector for the acidosis-induced increase in ammonia formation; however, the resulting decrease in urine pH may play a critical role. Other potential messengers, including potassium, glucocorticoids, mineralocorticoids, cyclic AMP, and calcium probably do not serve a primary function, but the importance of other circulating factor(s) is unclear.

Collecting tubule adaptation to respiratory acidosis induced in vivo

1990 ◽  
Vol 258 (1) ◽  
pp. F15-F20 ◽  
Author(s):  
M. E. Laski ◽  
N. A. Kurtzman
Keyword(s):  
Respiratory Acidosis ◽  
In Vitro Study ◽  
Co2 Flux ◽  
Urine Ph ◽  
Collecting Tubule ◽  
Bicarbonate Solutions ◽  
Animal Exposure ◽  
Collecting Tubules

To examine the effects of respiratory acidosis in vivo on the adaptation of acidification in the collecting tubule, New Zealand White rabbits were exposed to a 6.7% CO2-93.3% O2 gas mixture in an environmental chamber for 0, 6, 24, or 48 h before obtaining collecting tubules for in vitro study. These collecting tubules were then perfused and bathed in vitro in identical Krebs-Ringer bicarbonate solutions. After 1 h equilibration total CO2 flux (JtCO2) was measured. The urine pH of the rabbits fell, whereas the blood bicarbonate rose as CO2 exposure time increased. In cortical collecting tubules, JtCO2 in vitro correlated with length of animal exposure to hypercarbia (y = 1.14174 + 0.1437x, r = 0.57, P = 0.002), and with the blood bicarbonate of the animal (y = 26.8471 + 0.0858x, r = 0.59, P less than 0.05). In vitro JtCO2 in medullary collecting tubules from rabbits that had been in hypercarbic atmosphere for 48 h (23.2 +/- 4.9 pmol.mm-1.min-1) did not differ from JtCO2 in control tubules (25.0 +/- 3.2 pmol.mm-1.min-1, not significant). Thus the cortical collecting tubule exhibits an adaptive increase in JtCO2 in response to hypercarbia, whereas the medullary collecting tubule does not.

Effect of basolateral or apical hyposmolarity on apical maxi K channels of everted rat collecting tubule

1995 ◽  
Vol 268 (4) ◽  
pp. F569-F580 ◽  
Author(s):  
L. C. Stoner ◽  
G. E. Morley
Keyword(s):  
Apical Membrane ◽  
Physiological Role ◽  
Reversal Potential ◽  
K Channel ◽  
Apical Surface ◽  
Open Probability ◽  
Volume Regulatory Decrease ◽  
Collecting Tubules ◽  
High Conductance

We are able to evert and perfuse rat cortical collecting tubules (CCT) at 37 degrees C. Patch-clamp techniques were used to study high-conductance potassium channels (maxi K) on the apical membrane. Under control conditions (150 mM Na+ and 5 mM K+ in pipette and bathing solutions), the slope conductance averaged 109.8 +/- 6.6 pS (12 channels), and reversal potential (expressed as pipette voltage) was +26.3 +/- 2.4 mV. The percent of time the channel spends in the open state and unitary current when voltage was clamped to 0 mV were 1.4 +/- 0.7% and 3.12 +/- 0.42 pA, respectively. In six patches voltage clamped to 0 mV, the isosmotic solution perfused through the everted tubule (basolateral surface) was exchanged for one made 70 mosmol/kgH2O hyposmotic to the control saline. Open probability increased from 0.019 to 0.258, an increase of 0.239 +/- 0.065 (P ' 0.005). In four patches where a maxi K channel was evident, no increase in open probability was observed when a hyposmotic saline was placed on the apical surface. However, when vasopressin was present on the basolateral surface, apical application of hyposmotic saline resulted in a series of bursts of channel activity. The average increase in open probability during bursts was (0.055 +/- 0.017, P < 0.005). We conclude that one function of the maxi K channel located in the apical membrane of the rat CCT may be to release intracellular solute (potassium) during a volume regulatory decrease induced by placing a dilute solution on the basolateral surface or when the apical osmolarity is reduced in the presence of vasopressin. These data are consistent with the hypothesis that the physiological role of the channel is to regulate cell volume during water reabsorption.

Role of arginine vasopressin in medullary thick ascending limb on maximal urinary concentration

1986 ◽  
Vol 251 (2) ◽  
pp. F266-F270 ◽  
Author(s):  
J. K. Kim ◽  
S. N. Summer ◽  
A. E. Erickson ◽  
R. W. Schrier
Keyword(s):  
Adenylate Cyclase ◽  
Arginine Vasopressin ◽  
Urinary Concentration ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Urinary Osmolality ◽  
Medullary Thick Ascending Limb ◽  
Sprague Dawley Rats ◽  
Collecting Tubules

Two groups of Sprague-Dawley rats, Harlan (H) and Charles River (CR), were discovered in that the medullary thick ascending limb (MAL) had a profoundly different adenylate cyclase response to arginine vasopressin (AVP). Using these two groups of rats, we studied the correlation between AVP action on the MAL and maximal urinary concentration. AVP (10(-6) M) significantly stimulated adenylate cyclase in MAL of H rats (7.4 +/- 0.9 to 43.8 +/- 4.6 fmol cAMP formed X 30 min-1 X mm-1, P less than 0.001) but not in CR rats (10.3 +/- 1.4 to 12.7 +/- 2.0 fmol cAMP formed X 30 min-1 X mm-1, NS). In contrast, AVP significantly stimulated adenylate cyclase of cortical, outer and inner medullary collecting tubules from both H and CR rats. Glucagon (10(-6) M) significantly stimulated adenylate cyclase of MAL from both H and CR rats. After 48 h of fluid deprivation, urinary osmolality was significantly higher (P less than 0.001) in the H (4,504 +/- 399 mosmol/kg H2O, n = 14) than CR (2,840 +/- 176 mosmol/kg H2O, n = rats. This observation was not attributable to differences in creatinine clearance (CR, 1.30 +/- 0.24; H, 1.24 +/- 0.03 ml/min, NS, n = 4) or plasma AVP (CR, 12.75 +/- 1.44; H, 12.38 +/- 1.17 pg/ml, NS, n = 6) levels. These results therefore suggest that the action of AVP on the MAL, in addition to the effect on collecting tubules, is involved in maximal urinary concentration in rats.

Two automated procedures for N-acetyl-beta-D-glucosaminidase determination evaluated for detection of drug-induced tubular nephrotoxicity.

1986 ◽  
Vol 32 (11) ◽  
pp. 2052-2055 ◽  
Author(s):  
M P Goren ◽  
R K Wright ◽  
S Osborne
Keyword(s):  
Enzymatic Activity ◽  
Methotrexate Therapy ◽  
Tubular Damage ◽  
Sample Treatment ◽  
Urine Ph ◽  
Drug Induced ◽  
Alkaline Urine ◽  
Automated Procedures ◽  
Drugs And Metabolites

Abstract We automated two procedures for determination of urinary N-acetyl-beta-D-glucosaminidase (NAG; EC 3.2.1.30) concentrations and evaluated their reliability for detecting drug-induced tubular damage in children receiving cisplatin, methotrexate, or ifosfamide. Results for 174 patient specimens correlated well (r = 0.98), but NAG concentrations determined by the m-cresolsulfonphthaleinyl (MCP) procedure were about 40% lower than those obtained with p-nitrophenyl-N-acetyl-beta-D-glucosaminide substrate. Dialysis and assay of 50 specimens disclosed no evidence of activators or inhibitors of enzymatic activity. Drugs and metabolites added to urine had negligible effect on NAG determinations; however, NAG was unstable in alkaline urine (pH greater than 8) associated with methotrexate therapy. Both procedures detect tubular damage equally well and neither requires laborious sample treatment. The MCP procedure, being more sensitive and not requiring a sample blank, is better suited for rapid automated assays. Comparisons of clinical data obtained by the two procedures require standardization against human NAG.

Association of mitochondrial SOD deficiency with salt-sensitive hypertension and accelerated renal senescence

2007 ◽  
Vol 102 (1) ◽  
pp. 255-260 ◽  
Author(s):  
Bernardo Rodriguez-Iturbe ◽  
Lili Sepassi ◽  
Yasmir Quiroz ◽  
Zhenmin Ni ◽  
Nosratola D. Vaziri
Keyword(s):  
Oxidative Stress ◽  
Glomerular Sclerosis ◽  
Tubular Damage ◽  
Wild Type ◽  
Mitochondrial Superoxide ◽  
Show Evidence ◽  
Blood Pressures ◽  
Renal Senescence ◽  
Salt Sensitive Hypertension

Mitochondria are the major source of superoxide (O2−) in the aerobic organisms. O2− produced by the mitochondria is converted to hydrogen peroxide by mitochondrial superoxide dismutase (SOD2). Mice with complete SOD2 deficiency (SOD2−/−) exhibit dilated cardiomyopathy and fatty liver leading to neonatal mortality, whereas mice with partial SOD2 deficiency (SOD2+/−) show evidence of O2−-induced mitochondrial damage resembling cell senescence. Since earlier studies have provided compelling evidence for the role of oxidative stress and tubulointerstitial inflammation in the pathogenesis of hypertension, we tested the hypothesis that partial SOD2 deficiency may result in hypertension. Wild-type (SOD2+/+) and partial SOD2-deficient (SOD2+/−) mice had similar blood pressures at 6–7 mo of age, but at 2 yr SOD2+/− mice had higher blood pressure. Oxidative stress, renal interstitial T-cell and macrophage infiltration, tubular damage, and glomerular sclerosis were all significantly increased in 2-yr-old SOD2+/− mice. High-salt diet induced hypertension in 6-mo-old SOD2-deficient mice but not in wild-type mice. In conclusion, partial SOD2 deficiency results in oxidative stress and renal interstitial inflammation, changes compatible with accelerated renal senescence and salt-sensitive hypertension. These findings are consistent with the pattern described in numerous other models of salt-sensitive hypertension and resemble that commonly seen in elderly humans.

Distal acidification in the rabbit: role of diet and blood pH

1982 ◽  
Vol 243 (4) ◽  
pp. F364-F371
Author(s):  
M. Cruz-Soto ◽  
D. Batlle ◽  
S. Sabatini ◽  
J. A. Arruda ◽  
N. A. Kurtzman
Keyword(s):  
Sodium Bicarbonate ◽  
Ammonium Chloride ◽  
Sodium Phosphate ◽  
Blood Ph ◽  
Normal Urine ◽  
Collecting Tubules ◽  
Bicarbonate Infusion ◽  
Neutral Sodium ◽  
Sodium Bicarbonate Infusion

A distal acidification defect is said to exist in rabbits because this species does not achieve a normal urine minus blood (U-B) PCO2 gradient in response to sodium bicarbonate infusion. This observation contrasts with data derived from studies in isolated rabbit cortical collecting tubules that have shown an acidifying capacity when the tubules were obtained from acidotic animals. The present study was designed to examine the role of diet and blood pH on distal acidification in the rabbit. Maximal alkalinization of the urine by acute sodium bicarbonate infusion was associated with a low U-B PCO2 gradient (0.7 +/- 2.1 mmHg). Rabbits made acidotic by ammonium chloride administration for 1 wk achieved a substantial U-B PCO2 gradient (29 +/- 5 mmHg) in response to neutral sodium phosphate infusion. To further evaluate the role of blood pH on the ability to raise U-B PCO2 gradient, rabbits and rats made acidotic by chronic ammonium chloride administration were studied. Neutral sodium phosphate was then infused to stimulate distal acidification. At comparable levels of urinary phosphate concentration and blood pH, acidotic rabbits were able to achieve a U-B PCO2 (50 +/- 7 mmHg) comparable with that of acidotic rats (48 +/- 8.3 mmHg). These data show that the failure of rabbits to raise U-B PCO2 gradient can be partially corrected by prior exposure to acid in the diet and further corrected by maintaining the blood pH within the acidotic range.

FGF21 prevents low protein diet-induced renal inflammation in aged mice

2021 ◽  
Author(s):  
Han Fang ◽  
Sujoy Ghosh ◽  
Landon Sims ◽  
Kirsten P. Stone ◽  
Cristal M Hill ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Renal Damage ◽  
Protective Role ◽  
Wild Type ◽  
Kidney Weight ◽  
Albumin Creatinine Ratio ◽  
Low Protein ◽  
The Impact ◽  
Protein Diets

Low protein diets extend lifespan through a comprehensive improvement in metabolic health across multiple tissues and organs. Many of these metabolic responses to protein restriction are secondary to transcriptional activation and release of FGF21 from the liver. However, the effects of a low protein (LP) diet on the kidney in the context of aging has not been examined. Therefore, the goal of the current study was to investigate the impact of chronic consumption of a LP diet on the kidney in aging mice lacking FGF21. Wild type (WT, C57BL/6J) and FGF21 KO mice were fed a normal protein (NP, 20% casein) or a LP (5% casein) diet ad libitum from 3 to19 months of age. The LP diet led to a decrease in kidney weight and urinary albumin/creatinine ratio in both WT and FGF21 KO mice. Although the LP diet produced only mild fibrosis and infiltration of leukocytes in WT kidneys, the effects were significantly exacerbated by the absence of FGF21. Accordingly, transcriptomic analysis showed that inflammation-related pathways were significantly enriched and upregulated in response to LP diet in FGF21 KO but not WT mice. Collectively, these data demonstrate that the LP diet negatively affected the kidney during aging, but in the absence of FGF21, the LP diet-induced renal damage and inflammation were significantly worse, indicating a protective role of FGF21 in the kidney.

scholarly journals Interrelationship of dipeptidyl peptidase IV (DPP4) with the development of diabetes, dyslipidaemia and nephropathy: a streptozotocin-induced model using wild-type and DPP4-deficient rats

2008 ◽  
Vol 200 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Yasushi Kirino ◽  
Youichi Sato ◽  
Takayuki Kamimoto ◽  
Kazuyoshi Kawazoe ◽  
Kazuo Minakuchi ◽  
...  
Keyword(s):  
Renal Function ◽  
Blood Glucose ◽  
Serum Creatinine ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Wild Type ◽  
Rat Strains ◽  
Kidney Weight ◽  
Kidney Liver

We examined the role of dipeptidyl peptidase IV (DPP4) in the development of diabetes, dyslipidaemia and renal dysfunction induced by streptozotocin (STZ). F344/DuCrlCrlj rats, which lack DPP4 activity, and wild-type rats were treated with STZ. Plasma DPP4 activity and biochemical parameters were measured until 42 days after STZ treatment. At the end of the experiment, renal function and DPP4 expressions of the kidney, liver, pancreas and adipose tissues were determined. Increases in blood glucose, cholesterol and triglycerides were evoked by STZ in both rat strains; however, the onset of hyperglycaemia was delayed in DPP4-deficient rats as compared with wild-type rats. By contrast, more severe dyslipidaemia was observed in DPP4-deficient rats than in wild-type rats after STZ treatment. Plasma DPP4 activity increased progressively with time after STZ treatment in wild-type rats. The kidney of wild-type rats showed decreased DPP4 activity with increased Dpp4 mRNA after STZ treatment. In addition, kidney weight, serum creatinine and excreted amounts of urinary protein, glucose and DPP4 enzyme were enhanced by STZ. DPP4-deficient rats showed increased serum creatinine in accordance with decreased creatinine clearance as compared with wild-type rats after STZ treatment. In conclusion, plasma DPP4 activity increased after STZ treatment, positively correlating to blood glucose. DPP4-deficient rats were resistant to developing diabetes, while susceptible to dyslipidaemia and reduction of glomerular filtration rate by STZ. DPP4 activation may be responsible for hyperglycaemia, lipid metabolism and preservation of renal function.

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