Radioimmunoassay Measurement of Urinary Ligandin Excretion in Nephrotoxin-Treated Rats

1979 ◽  
Vol 56 (5) ◽  
pp. 419-426 ◽  
Author(s):  
N. M. Bass ◽  
R. E. Kirsch ◽  
S. A. Tuff ◽  
J. A. Campbell ◽  
J. S. Saunders
Keyword(s):  
Proximal Tubule ◽  
Time Course ◽  
Potassium Dichromate ◽  
Tubular Damage ◽  
Moderate Increase ◽  
Normal Range ◽  
Pars Recta ◽  
Normal Urine ◽  
Renal Tubular ◽  
Pars Convoluta

1. A radioimmunoassay was used to establish normal urine excretion of ligandin, a renal tubular protein, in rats, and to study the pattern of ligandin excretion after nephrotoxin administration. 2. Validation of radioimmunoassay measurement of ligandin in urine is described. A normal range of 2–46 ng/h was obtained for ligandin excretion in rats (n = 24). 3. Mercuric chloride (HgCl2; 10 mg/kg) administration resulted in a significant increase in ligandin excretion within 6 h, preceding the onset of significant azotaemia. Serum ligandin concentrations were raised after 12 h, while renal ligandin concentration fell to 30% of control values by 24 h. 4. Rats given HgCl2 (5 mg/kg) developed massive ligandinuria between 6 and 12 h, which declined to normal values by 72 h. Potassium dichromate (K2Cr2O7; 7 mg/kg) administration produced a comparatively moderate increase in ligandin excretion after 24 h. 5. The time course of ligandin excretion in HgCl2- and K2Cr2O7-treated rats correlated with the histological sequence of damage to the pars recta and pars convoluta of the proximal tubule respectively. 6. The results of this study confirm that renal ligandin is confined mainly to the pars recta of the proximal tubule, and small quantities of this protein are present in the pars convoluta. Radioimmunoassay provides a sensitive and specific means for measuring ligandin in urine and provides a valuable tool for the detection and study of renal tubular damage.

scholarly journals 5-Azacytidine and renal tubular dysfunction

Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 182-185 ◽  
Author(s):  
BA Peterson ◽  
AJ Collins ◽  
NJ Vogelzang ◽  
CD Bloomfield
Keyword(s):  
Renal Toxicity ◽  
Tubular Damage ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Normal Range ◽  
Acid Base ◽  
Salt Wasting ◽  
Renal Tubular ◽  
Renal Abnormalities ◽  
Electrolyte Abnormalities

Abstract During initial trials of 5-azacytidine in adults with advanced acute leukemia, we unexpectedly observed acid-base, fluid, and electrolyte abnormalities that contributed directly to the deaths of two early patients. To evaluate this toxicity further, we studied 22 patients who received a total of 33 courses of combination chemotherapy that included 5-azacytidine. During 29 courses (88%) of treatment, polyuria, glucosuria, and/or transient changes in the serum concentrations of bicarbonate or phosphorus were detected. Spontaneous polyuria with demonstrable salt wasting and orthostatic hypotension occurred during seven courses (21%) of treatment. Inappropriate glucosuria was observed in nine courses (27%). In 24 courses (73%) the serum bicarbonate fell below the normal range. The urine became alkaline during 12 of these instances; the anion gap was not increased during the acidosis. Hypophosphatemia with serum phosphorus concentrations as low as 0.3 mg/dl occurred in 21 of 32 evaluable courses (66%). In the three patients studied the tubular reabsorption of phosphorus was 10%-18%. The renal abnormalities that were observed suggest both proximal and distal tubular damage from 5-azacytidine. Patients receiving 5- azacytidine should be monitored closely for manifestations of renal toxicity.

Induction of ornithine decarboxylase immunoreactivity in the male mouse kidney following testosterone treatment: an axial heterogeneity in the proximal tubule

1993 ◽  
Vol 136 (1) ◽  
pp. 85-NP ◽  
Author(s):  
N. Koibuchi ◽  
S. Matsuzaki ◽  
H.-T. Ma ◽  
M. Sakai ◽  
S. Yamaoka
Keyword(s):  
Proximal Tubule ◽  
Ornithine Decarboxylase ◽  
Protein Level ◽  
Male Mouse ◽  
Subcutaneous Injection ◽  
Mouse Kidney ◽  
Luminal Surface ◽  
Testosterone Treatment ◽  
Pars Recta ◽  
Pars Convoluta

ABSTRACT The effect of testosterone on the activity of ornithine decarboxylase (ODC), its protein level and immunocytochemical distribution were examined in the mouse kidney. Male BALB C mice at 8 weeks of age were used throughout. Fourteen hours before death, they received a subcutaneous injection of testosterone (1 mg/animal) or solvent to measure renal ODC activity or to detect the distribution of ODC immunoreactivity in the kidney. Renal ODC activity and the content of the enzyme were markedly increased after testosterone treatment. Histologically, few cells that were obviously immunoreactive to ODC were observed in the control animals and in the testosterone-treated animals a marked increase in ODC immunoreactivity was observed only in the cortex. ODC immunoreactive cells were located diffusely in the proximal tubule. In the pars recta, cells were stained weakly and homogeneously, while in the pars convoluta, the luminal surface of the cells showed stronger immunoreactivity. Moreover, many granule-like particles that were strongly ODC immunoreactive were observed inside the lumen of the pars convoluta. These results show that testosterone treatment induces an increase in ODC content in certain cells located in the proximal tubule of the cortex. Journal of Endocrinology (1993) 136, 85–89

Micropuncture study of tubular transport of urate and PAH in the pig kidney

1980 ◽  
Vol 239 (2) ◽  
pp. F107-F112 ◽  
Author(s):  
F. Roch-Ramel ◽  
F. White ◽  
L. Vowles ◽  
H. A. Simmonds ◽  
J. S. Cameron
Keyword(s):  
Proximal Tubule ◽  
Transport Mechanism ◽  
Fractional Excretion ◽  
Competitive Inhibitor ◽  
Pig Kidney ◽  
Tubular Transport ◽  
Pars Recta ◽  
Micropuncture Study ◽  
Plasma Urate ◽  
Pars Convoluta

At physiological plasma urate concentration (Purate) (0.05 mg/dl), net secretion of urate occurred in the convoluted part of the proximal tubule of micropunctured anesthetized pigs. The fraction of filtered urate delivered to the point of micropuncture ((TF/P)urate/(TF/P)polyfructosan) was 4.8 +/- 0.5 (mean +/- SE, n =10). Urate was reabsorbed from lower tubular segments, since the fractional excretion of urate (FEurate) was only 2.1. Saturation of secretion as well as reabsorption occurred at Purate of 1.6 mg/dl. p-Aminohippurate (PAH) secretion also occurred mainly in the pars convoluta of the proximal tubule: (TF/P)PAH/(TF/P)polyfructosan was 4.0 +/- 0.4 (n = 11), whereas the FEPAH was 4.5 +/- 0.5 (n = 5). Thus, the pars recta does not contribute significantly to the net secretion of either urate or PAH. PAH was a competitive inhibitor of urate secretion. At a PPAH of 60 mg/dl there was overall net reabsorption of urate. Accordingly, in the pig PAH and urate seem to be secreted by the same transport mechanism.

Time Course of Renal Proximal Tubule Injury, Reversal, and Related Biomarker Changes in Rats Following Cisplatin Administration

2013 ◽  
Vol 32 (4) ◽  
pp. 251-260 ◽  
Author(s):  
James Eric McDuffie ◽  
Jing Ying Ma ◽  
Marciano Sablad ◽  
Manisha Sonee ◽  
Lynn Varacallo ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Time Course ◽  
Intraperitoneal Administration ◽  
Spatial Relationship ◽  
Kidney Injury ◽  
Renal Proximal Tubule ◽  
Serum Biomarkers ◽  
Tubular Damage ◽  
Renal Biomarkers ◽  
Kidney Injury Molecule 1

Cisplatin (CDDP) is known to produce renal proximal tubule injury. Various renal biomarkers have been related to CDDP nephrotoxicity in previous research, but the temporal and spatial relationship of these biomarkers to injury reversal has not been well defined. In this study, the progression and reversal of renal histopathology findings relative to serum and urinary biomarker changes were examined during a 4-week postdose period following single intraperitoneal administration of CDDP (1 mg/kg) or 0.9% saline. Degeneration, vacuolation, inflammation, and regeneration of the S3 segment of proximal tubules were evident 72 hours following CDDP administration. Tubular degeneration and regeneration were also observed at 1 and 1.5 weeks but at lower incidences and/or severity indicating partial reversal. Complete histologic reversal was observed by 2 weeks following CDDP administration. Urinary kidney injury molecule 1 (KIM-1), α-glutathione-S-transferase (α-GST), and albumin levels increased at 72 hours postdosing, concurrently with the earliest histologic evidence of tubule injury. Changes in urinary KIM-1 correlated with KIM-1 immunostaining in the proximal tubular epithelial cells. No significant changes in serum biomarkers occurred except for a minimal increase in urea nitrogen at 1.5 weeks postdosing. Of the novel renal biomarkers examined, urinary KIM-1, α-GST, and albumin showed excellent concordance with CDDP-induced renal injury progression and reversal; and these biomarkers were more sensitive than traditional serum biomarkers in detecting early, acute renal tubular damage confirmed by histopathology. Furthermore, urinary KIM-1, α-GST, and albumin outperformed other biomarkers in correlating with the time of maximum histologic injury.

scholarly journals l-tryptophan uptake by segment-specific membrane vesicles from the proximal tubule of rabbit kidney

1992 ◽  
Vol 286 (1) ◽  
pp. 103-110 ◽  
Author(s):  
H Jessen ◽  
M I Sheikh
Keyword(s):  
Proximal Tubule ◽  
Basolateral Membrane ◽  
Membrane Vesicles ◽  
Rabbit Kidney ◽  
Basolateral Membrane Vesicles ◽  
Luminal Membrane ◽  
Transport Component ◽  
Pars Recta ◽  
Dependent Transport ◽  
Pars Convoluta

1. The mechanism of the renal transport of L-tryptophan by basolateral and luminal membrane vesicles prepared from either the pars convoluta or the pars recta of the rabbit proximal tubule was studied. The uptake of L-tryptophan by basolateral membrane vesicles from the pars convoluta was found to be an Na(+)-dependent transport event. The Na(+)-conditional influx of the amino acid was stimulated in the presence of an inwardly directed H+ gradient. Lowering the pH without an H+ gradient had no effect, indicating that L-tryptophan is co-transported with H+. 3. On the other hand, no transient accumulation of L-tryptophan was observed in the presence or absence of Na+ in basolateral membrane vesicles from the pars recta. 4. In luminal membrane vesicles from the pars recta, the transient Na(+)-dependent accumulation of L-tryptophan occurred via a dual transport system. In addition, an inwardly directed H+ gradient could drive the uphill transport of L-tryptophan into these vesicles in both the presence and the absence of an Na+ gradient. 5. By contrast, the uptake of L-tryptophan by luminal membrane vesicles from the pars convoluta was a strictly Na(+)-dependent and electrogenic transport process, mediated by a single transport component. 6. Investigation of the coupling ratio in luminal membrane vesicles suggested that 1 Na+:1 L-tryptophan are co-transported in the pars convoluta. In the pars recta, examination of the stoichiometry indicated that approx. 1 H+ and 2 Na+ (high affinity) or 1 Na+ (low affinity) are involved in the uptake of L-tryptophan.

scholarly journals Renal transport of monocarboxylic acids. Heterogeneity of lactate-transport systems along the proximal tubule

1984 ◽  
Vol 223 (3) ◽  
pp. 803-807 ◽  
Author(s):  
K E Jørgensen ◽  
M I Sheikh
Keyword(s):  
Proximal Tubule ◽  
Transport System ◽  
Membrane Vesicles ◽  
Transport Systems ◽  
Rabbit Kidney ◽  
Lactate Transport ◽  
Physiological Importance ◽  
High Affinity ◽  
Pars Recta ◽  
Pars Convoluta

The characteristics of D- and L-lactate transport in luminal-membrane vesicles derived from whole cortex, from the pars convoluta and from the pars recta of rabbit kidney proximal tubule were studied. It was found that uptake of both isomers in vesicles from whole cortex occurred by means of dual electrogenic transport systems, namely a low-affinity system and a high-affinity system. Uptake of both isomers in vesicles from the pars recta was strictly Na+-dependent and is mediated via a single high-affinity common transport system. Vesicles from the pars convoluta contained a cation-dependent but Na+-unspecific low-affinity common transport system for these compounds. The physiological importance of this system is briefly discussed.

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