Evidence for a secretory component in the handling of unconjugated bilirubin by the isolated perfused rat kidney

1985 ◽  
Vol 63 (12) ◽  
pp. 1581-1585 ◽  
Author(s):  
María M. Elías ◽  
Elbio J. Comin ◽  
Elena J. Ochoa ◽  
Emilio A. Rodríguez Garay
Keyword(s):  
Urinary Excretion ◽  
Glomerular Filtration ◽  
Excretion Rate ◽  
Rat Kidney ◽  
Renal Tissue ◽  
Secretory Component ◽  
Tubular Secretion ◽  
Unconjugated Bilirubin ◽  
Clearance Ratio ◽  
Virtual Absence

Previous studies in rats have suggested that the urinary excretion of unconjugated bilirubin (UB) comprises only a small fraction of the pigment that reaches the tubular lumen by glomerular filtration and escapes from tubular cell reabsorption. However, additional data also indicated that UB interacts with renal peritubular cell membranes impairing the secretion of p-aminohippurate (PAH). In this study we examined the possibility of a secretory step which could also be involved in the renal excretory mechanism for UB. An isolated rat kidney preparation was used, and the uptake of UB by renal tissue, the UB appearance in the urine, and the secretion of PAH were analyzed throughout the perfusion. The results indicated that the UB urinary excretion rate changed independently of UB filtered load. The latter remained almost unchanged during the perfusion, whereas the excretion rate of UB and the UB-to-creatinine (Cr) clearance ratio increased significantly. Furthermore, a relationship between the uptake of UB by the kidney, the UB-to-Cr clearance ratio, and the decrease in PAH secretion rate, was proved. In addition, when probenecid was added to the perfusate solution the cumulative uptake of UB by the kidney and the rate of excretion of UB in the urine were diminished. We conclude that the mechanism of UB excretion by the kidney may be considered as the result of a process involving glomerular filtration plus tubular secretion followed by a back diffusion step from the lumen in a similar way to other endogenous compounds, thus explaining the virtual absence of UB from the normal urine.

scholarly journals Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration

2021 ◽  
Vol 22 (15) ◽  
pp. 7867
Author(s):  
Marlena Typiak ◽  
Tomasz Kulesza ◽  
Patrycja Rachubik ◽  
Dorota Rogacka ◽  
Irena Audzeyenka ◽  
...  
Keyword(s):  
Growth Factor ◽  
Urinary Excretion ◽  
Glomerular Filtration ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptors ◽  
Renal Tissue ◽  
Proper Function ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors ◽  
Plasma Filtration

Hyperglycemic conditions (HG), at early stages of diabetic nephropathy (DN), cause a decrease in podocyte numbers and an aberration of their function as key cells for glomerular plasma filtration. Klotho protein was shown to overcome some negative effects of hyperglycemia. Klotho is also a coreceptor for fibroblast growth factor receptors (FGFRs), the signaling of which, together with a proper rate of glycolysis in podocytes, is needed for a proper function of the glomerular filtration barrier. Therefore, we measured levels of Klotho in renal tissue, serum, and urine shortly after DN induction. We investigated whether it influences levels of FGFRs, rates of glycolysis in podocytes, and albumin permeability. During hyperglycemia, the level of membrane-bound Klotho in renal tissue decreased, with an increase in the shedding of soluble Klotho, its higher presence in serum, and lower urinary excretion. The addition of Klotho increased FGFR levels, especially FGFR1/FGFR2, after their HG-induced decrease. Klotho also increased levels of glycolytic parameters of podocytes, and decreased podocytic and glomerular albumin permeability in HG. Thus, we found that the decrease in the urinary excretion of Klotho might be an early biomarker of DN and that Klotho administration may have several beneficial effects on renal function in DN.

Fate of Vasopressin Perfused into Nephrons of Wistar and Brattleboro (Diabetes Insipidus) Rats

1980 ◽  
Vol 58 (2) ◽  
pp. 139-144 ◽  
Author(s):  
M. D. Lindheimer ◽  
A. Reinharz ◽  
A. Grandchamp ◽  
M. B. Vallotton
Keyword(s):  
Diabetes Insipidus ◽  
Wistar Rats ◽  
Rat Kidney ◽  
Renal Tissue ◽  
Tubular Secretion ◽  
Urinary Recovery ◽  
Contralateral Kidney ◽  
Linear Peptide ◽  
Lissamine Green ◽  
Distal Tubules

1. Iodinated vasopressin was microinjected into early proximal or distal tubules of Wistar and Brattleboro (diabetes insipidus) rats. Sites of infusion were determined by the lissamine green transit time method. 2. Urinary recovery of 125I after proximal and distal injections was 89 ± se 1·7% and 94 ± 1·0% in Wistar rats (corrected for inulin) and 81 ± 20 and 92 ± 2·0% in Brattleboro rats (uncorrected); injection of hormone into vascular stars resulted in similar 125I recoveries from punctured and contralateral kidneys. 3. Radioactive substances excreted after perfusing proximal and distal sites in Brattleboro animals, and 125I-labelled hormone added to urine from the contralateral kidney, bound similarly to a specific arginine vasopressin antiserum and demonstrated similar radioactive elution profiles after passage through Sephadex G25 columns. 4. Incubation of labelled and unlabelled vasopressin with rat kidney homogenates resulted in similar and complete degradation of the hormone. 5. Results indicate that most of the vasopressin injected into either proximal or distal nephrons enters the urine intact, and no evidence of tubular secretion was found when perfusing vascular stars. Enzymes in rat renal tissue degrade labelled vasopressin, but the ability of the proximal tubule to hydrolyse the 125I-labelled vasopressin is limited, especially when compared with that reported for several linear peptide hormones.

Enalaprilat handling by the kidney: barrier-limited cell entry

1992 ◽  
Vol 263 (5) ◽  
pp. F858-F869
Author(s):  
A. J. Schwab ◽  
I. A. de Lannoy ◽  
C. A. Goresky ◽  
K. Poon ◽  
K. S. Pang
Keyword(s):  
Red Blood Cells ◽  
Glomerular Filtration ◽  
Blood Cells ◽  
Enzyme Inhibitor ◽  
Rat Kidney ◽  
Tubular Secretion ◽  
Distributed Model ◽  
Renal Elimination ◽  
Tubular Cells ◽  
Time Space

The angiotensin-converting enzyme inhibitor enalaprilat is formed in vivo in liver and kidney by esterolysis of the antihypertensive drug enalapril. To gain insight into the renal elimination of enalaprilat, we carried out multiple-indicator dilution experiments in the isolated perfused rat kidney. Kidneys were perfused single pass with an amino acid-supplemented Krebs-Henseleit buffer containing 20% bovine red blood cells and 4% bovine serum albumin, at a flow rate of 0.11 +/- 0.02 (SD) ml.s-1 x g-1. A bolus of 51Cr-labeled red blood cells (vascular red blood cell indicator), 125I-labeled albumin (vascular plasma indicator), L-[14C]glucose (interstitial space indicator), and [3H]-enalaprilat was injected into the renal artery, and timed samples of venous blood (up to 1 min) and urine (up to 10 min) were collected. The data were analyzed using a variable-transit-time, space-distributed model with modifications accounting for glomerular filtration and the observed 14% protein binding of enalaprilat; the glomerular filtration rate (GFR) estimated from L-glucose clearance was 9.0 +/- 2.9% of total plasma flow. The ratio of renal clearance of unbound enalaprilat to GFR was 1.56 +/- 0.29, indicating both glomerular filtration and net tubular secretion of enalaprilat. Unidirectional influx from plasma to tubular cells exceeded tubular secretion by a factor of 2.2 +/- 0.5. Thus only about one-half of the enalaprilat taken up by the tubular cells was excreted into urine, with the remainder refluxing into the capillary blood stream, indicating bidirectional permeation of enalaprilat across the basolateral tubular membrane.

Complexing activity and excretion of 2,3-dimercapto-1-propane sulfonate in rat kidney

1988 ◽  
Vol 254 (6) ◽  
pp. F871-F878 ◽  
Author(s):  
J. M. Klotzbach ◽  
G. L. Diamond
Keyword(s):  
Urinary Excretion ◽  
Rat Kidney ◽  
Inorganic Mercury ◽  
Mercury Content ◽  
Tubular Secretion ◽  
Complexing Agent ◽  
Renal Handling ◽  
Carrier Mediated Transport ◽  
Dose Dependent Decrease ◽  
Dose Dependent

The renal handling of the heavy metal complexing agent, 2,3-dimercapto-1-propane sulfonate (DMPS), was examined in the isolated perfused rat kidney (IPRK). Net tubular secretion of DMPS was saturable and blocked by p-aminohippuric acid (PAH) and probenecid (PRB), indicating involvement of carrier-mediated transport in the excretion of DMPS. DMPS was oxidized to a disulfide form (DMPSS) in perfusate and reduced to a sulfhydryl form (DMPSH) in kidney. In kidneys isolated from rats pretreated with HgCl2, DMPS produced a dose-dependent decrease in retention of inorganic mercury, an increase in urinary excretion of mercury, and an increase in the amount of mercury transferred from kidney into venous perfusate. At a maximally effective dose, 40% of the renal mercury content was excreted in urine during 30 min of perfusion. Urinary excretion of mercury induced by DMPS was completely blocked by concentrations of PRB that blocked tubular secretion of DMPS and decreased uptake of DMPS in kidney. Thus tubular secretion of DMPS and reduction of DMPSS to DMPSH are important in the renal handling of DMPS and may contribute to the activity of DMPS as a complexing agent for renal mercury.

Urinary excretion rate of C-peptide in fed and fasted obese humans

1988 ◽  
Vol 118 (1) ◽  
pp. 38-44 ◽  
Author(s):  
R. Pasquali ◽  
P. Buratti ◽  
F. Casimirri ◽  
D. Patrono ◽  
M. Capelli ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
B Cell ◽  
Cell Function ◽  
Excretion Rate ◽  
Secretion Rate ◽  
Urinary Excretion Rate ◽  
Serum Samples ◽  
Clearance Ratio ◽  
Renal Metabolism ◽  
C Peptide

Abstract. The aim of the study was to evaluate the reliability of urinary excretion rate of C-peptide as a marker of B-cell function during fasting. Ten obese subjects of both sexes fasted for 5 days. Diurnal serum C-peptide was collected before and on the 5th day; morning serum samples (for glucose, insulin and C-peptide) and 12-h urine samples (7.00 to 19.00 h) were collected daily. Body weight decreased from 138.7 ± 15.9 to 132.9 ± 15.6 kg. Morning glucose, insulin (–40%) and C-peptide (–50%) fell significantly throughout the study. Mean diurnal C-peptide values were 2.19 ±0.69 nmol/l before and 0.60 ±0.19 nmol/l after fasting (P < 0.0001) and its secretion rate was 909.4 ± 297.9 and 244.4 ± 83.9 nmol/12 h (P < 0.005), respectively. Excretion rate of C-peptide fell progressively from basal (11.2 ± 4.2 nmol/12 h) to a nadir value of 1.3 ± 0.8 nmol/12 h (P < 0.0005); similarly, the C-peptide to creatinine clearance ratio fell from 0.062 ± 0.035 to 0.028 ± 0.015 (P < 0.05). These results indicate that fasting modifies renal metabolism of C-peptide thus creating several complications in the quantitative interpretation of urinary levels as an index of its secretion rate from the B-cell.

Renal transport of NAP-taurine

1981 ◽  
Vol 241 (1) ◽  
pp. F9-F13
Author(s):  
M. F. Stokols ◽  
F. J. Koschier ◽  
J. M. Goldinger ◽  
S. K. Hong
Keyword(s):  
Rat Kidney ◽  
Organic Anion ◽  
Kinetic Studies ◽  
Tubular Secretion ◽  
Metabolic Inhibitors ◽  
Renal Transport ◽  
Dependent Manner ◽  
Clearance Ratio ◽  
Photoaffinity Label ◽  
Anion Transport System

The renal transport of N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate (NAP-taurine), a potential photoaffinity label, was studied using the rabbit renal cortical slice and the isolated perfused rat kidney. NAP-taurine inhibited the slice accumulation of PAH in a dose-dependent manner (ID50 = 2.5 X 10(-5) M). It accumulated to a steady-state slice-to-medium concentration ratio of 14. However, NAP-taurine was not toxic to the tissue, as it did not influence the accumulation of the organic cation tetraethylammonium. NAP-taurine transport was saturable and its accumulation was inhibited by the metabolic inhibitors PAH, probenecid, 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS), ouabain, and the absence of sodium. Kinetic studies showed that the Km for NAP-taurine is 3.5 X 10(-5) M, and also that PAH competitively inhibits NAP-taurine influx with a Ki of 1.2 X 10(-3) M. Experiments with the rat isolated perfused kidney gave the NAP-taurine-to-inulin clearance ratio of approximately 5, indicating net tubular secretion. DIDS significantly reduced this clearance ratio to 0.8. The results suggest NAP-taurine is handled by the kidney in a manner analogous to PAH and may thus be useful as a photoaffinity label for the renal organic anion transport system.

Evidence for bidirectional net movement of creatinine in the rat kidney

1983 ◽  
Vol 244 (6) ◽  
pp. F719-F723 ◽  
Author(s):  
P. Namnum ◽  
K. Insogna ◽  
D. Baggish ◽  
J. P. Hayslett
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Rat Kidney ◽  
Plasma Creatinine ◽  
Test Substance ◽  
Clearance Ratio ◽  
Conscious Rats ◽  
Plasma Creatinine Level ◽  
Basal Plasma

Although the clearance of endogenous creatinine is used in many physiologic and metabolic studies in the rat as an index of glomerular filtration rate, there is no evidence that creatinine is a reliable test substance. Studies were therefore performed in anesthetized and conscious rats to determine the creatinine-to-inulin clearance ratio (CCr/CIn). In anesthetized animals the CCr/CIn ratio was 0.5 and in conscious rats it was 0.7 at normal basal plasma creatinine levels. After an increase in plasma creatinine to 1.9 mg/dl induced by the intravenous infusion of creatinine, the CCr/CIn ratio was 1.2. Accordingly, these data indicate that net creatinine transport across the renal tubule is bidirectional and that transport is influenced by the plasma creatinine level. At normal plasma levels creatinine is extensively reabsorbed along the nephron, whereas net secretion is associated with elevated plasma creatinine. The results demonstrate that creatinine is not a reliable marker of glomerular filtration rate in the rat.

Direct Proportionality of Urinary Excretion Rate and Serum Level of Tetracycline in Human Subjects

Nature ◽  
1963 ◽  
Vol 198 (4879) ◽  
pp. 450-453 ◽  
Author(s):  
T. CHULSKI ◽  
R. H. JOHNSON ◽  
C. A. SCHLAGEL ◽  
J. G. WAGNER
Keyword(s):  
Serum Level ◽  
Urinary Excretion ◽  
Excretion Rate ◽  
Human Subjects ◽  
Urinary Excretion Rate ◽  
Direct Proportionality

Compartmental transfer of mercury released from amalgam

1997 ◽  
Vol 16 (11) ◽  
pp. 667-672 ◽  
Author(s):  
S. Halbach ◽  
L. Kremers ◽  
H. Willruth ◽  
A. Mehl ◽  
G. Welzl ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Urinary Excretion ◽  
Total Mercury ◽  
Excretion Rate ◽  
Absorbed Dose ◽  
Correlation Coefficients ◽  
Urinary Excretion Rate ◽  
Amalgam Fillings

The number of amalgam-covered surfaces and the occlusal area of the fillings, the concentrations of total mercury in plasma, erythrocytes and urine, the urinary excretion rate, and the absorbed daily doses estimated by two separate methods from intra-oral Hg emission were determined in 29 volunteers with a low amalgam load. The transfer ofHg from the fillings via the oral cavity and blood to urinary excretion was evaluated by multiple correla tions between these variables. In addition, the combina tion of variables most representative of the entire compartmental transfer of amalgam Hg was determined. Urinary excretion (1), Hg concentration in plasma (2) and absorbed dose (3) were most closely correlated to each other, followed by correlations with the variables of the fillings (4). Correlation coefficients were 0.75 for variables 1 vs 2 and 2 vs 3, and 0.49 for variables 3 vs 4. It was concluded that variables 1-3 best reflected the transfer of mercury from amalgam fillings throughout the organism and that they were relatively insensitive to dietary mercury. The determination of total mercury in plasma and of its urinary excretion rate appears, under practical aspects, most suitable for the investigation of Hg uptake from amalgam.

Net urate reabsorption in the Dalmatian coach hound with a note on automated measurement of urate in species with low plasma urate

1982 ◽  
Vol 60 (12) ◽  
pp. 1499-1504 ◽  
Author(s):  
B. Moulin ◽  
P. Vinay ◽  
N. Duong ◽  
A. Gougoux ◽  
G. Lemieux
Keyword(s):  
Glomerular Filtration Rate ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Progressive Reduction ◽  
Clearance Ratio ◽  
Plasma Urate ◽  
Urate Reabsorption ◽  
Dalmatian Dog ◽  
Pyrazinoic Acid

A progressive reduction of renal blood flow and glomerular filtration rate induced by the stepwise clamping of a Goldblatt clamp increases the urate over creatinine clearance ratio from 1.2 to 1.9 in normal urate-secreting Dalmatian dogs. These clearance data support the existence of a predominant postreabsorptive secretory flux of urate in the normal Dalmatian dog. In contrast, in Dalmatians loaded with pyrazinoic acid which suppresses urate secretion, net reabsorption of urate is unmasked and the urate over creatinine clearance ratio decreases with the progressive reduction in glomerular filtration rate (down to 0.44). It is concluded that the net reabsorption of urate measured by conventional clearance techniques after pharmacologic depression of the urate secretory flux probably reflects true urate reabsorption in the nephron of this species.

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