Renal excretion of uric acid in the rat: a micropuncture and microperfusion study

1976 ◽  
Vol 230 (3) ◽  
pp. 768-776 ◽  
Author(s):  
F Roch-Ramel ◽  
F Diezi-Chomety ◽  
D De Rougemont ◽  
M Tellier ◽  
J Widmer ◽  
...  

Free-flow micropuncture experiments were done in rats of three strains infused with small amounts of urate [plasma urate (P urate) = 95 +/- 8 muM]. Urate concentrations in tubular fluid were measured by an accurate chemical fluorometric ultramicromethod. In fluid from surface glomeruli, the glomerular fluid-to-plasma urate ratio [GF/P) urate] was 0.99 +/- 0.03 (n=11), i.e., lower than expected for total ultrafiltrability of plasma urate. Along proximal convolutions, net reabsorption of 55% of filtered urate was demonstrated. Small amounts of urate may have been reabsorbed between late proximal and early distal sites. Net transepithelial movements of urate did not occur in distal tubules or collecting ducts. In microperfusion experiments on proximal tubules, both a reabsorptive flow of urate (loss of perfused [2-14C]urate) and a secretory flow (entrance of cold urate into perfusate) of the same order of magnitude were demonstrated. Neither flow was influenced by simultaneous water movements. Microperfusion of Henle's loops indicated a significant but very small net reabsorption.

1975 ◽  
Vol 228 (6) ◽  
pp. 1641-1645 ◽  
Author(s):  
CR Ross ◽  
F Diezi-Chomety ◽  
F Roch-Ramel

The renal excretion of N'1-methylnicotinamide (NMN) was studied in the rat. Renal clearance experiments clearly demonstrated that: 1) NMN is secreted; 2)a tubularmaximum (Tm), 7 mumol/min per kg, could be reached; and 3)NMN secretion is inhibitedby a competitive inhibitor, mepiperphenidol. In free-flow micropuncture experiments, animals were infused with plasma concentrations of NMN ABOVE Tm; the TF/P NMNto TF/P inblin ratio for proximal and distal samples was 2.34 and 2.28, respectively, indicating that NMN is secreted in the proximal tubules and is not secreted orreabsorbed in the distal tubules. This finding was further confirmed by intratubularmicroinjections of ['14C]NMN into rats. In diuretic animals approxiamately 10%of the NMN injected into early proximal tubules was reabsorbed, but no reabsorption could be detected after distal injections. The nondiuretic animals showed no significant reabsorption of NMN. It was concluded that NMN transport is a carrier-mediated process and that reabsorption, if it occurs, plays only a minor role.


1977 ◽  
Vol 14 (3) ◽  
pp. 261-272 ◽  
Author(s):  
D. N. Kitchen ◽  
W. W. Carlton ◽  
J. Tuite

Beagle dogs were given ochratoxin A (0.1 and 0.2 mg/kg) and citrinin (5 and 10 mg/kg) alone and in two dose combinations for 14 days. The gross lesions included focal peritonitis and intestinal intussusceptions in dogs given citrinin. Changes in the kidneys of dogs given ochratoxin A were degeneration and necrosis with desquamation of tubular epithelial cells, primarily in the straight segment of the proximal tubules. Dogs given 10 mg/kg citrinin had similar changes in the distal tubules and collecting ducts. Dogs given combined doses of citrinin and ochratoxin A had degeneration and necrosis in proximal and distal tubules, and in thin segments and the collecting ducts; there were desquamated cells and granular casts in the lumina. Dogs given ochratoxin A had necrosis of lymphoid tissues in the spleen, tonsil, thymus, peripheral lymph nodes and lymph nodules of the ileum, colon and rectum. There was ulceration of the mucosa of the intestine in dogs given large combined doses of ochratoxin A and citrinin.


2021 ◽  
Author(s):  
Kave Esfandiari ◽  
Mohammad Babaei ◽  
Mina Amiri-Farahani ◽  
Ali Kalantari-Hesari ◽  
Hassan Morovvati

Abstract Kidneys play an important role in regulating the balance of water and ions in freshwater and seawater fish. However, complex kidney structures impair a comprehensive understanding of kidney function. In this study, in addition to renal histology, Na+/K+/ATPase ion transporter proteins and Na+/K+/2Cl− and NHE3 cotransporters were located in Priophthalmus waltoni kidney tissue to evaluate the ion regulation abilities of epithelial cells in various parts of nephrons. The renal tubules are composed of proximal tubules and distal tubules, followed by collecting tubes and finally collecting ducts. Light microscope immunohistochemistry was utilized to locate Na+/ K+-ATPase along renal tubules and collecting ducts. However, the distribution of the Na+/K+-ATPase immune response varies in different sections. Na+/K+/CL− cotransporter positioning was reported only in collecting tubes and collecting ducts, and proximal tubes and distal tubes did not respond to Na+/K+/Cl− cotransporter immunolocalization. Immunohistochemical response for NHE3 localization was detected only at the apex of epithelial cells of proximal tubules and collecting tubes. The distal tubes showed negative reaction and the collecting ducts showed a weak response to NHE3 safety immunolocalization.


2009 ◽  
Vol 53 (8) ◽  
pp. 3302-3307 ◽  
Author(s):  
Kunio Fujiwara ◽  
Masashi Shin ◽  
Hayato Matsunaga ◽  
Tetsuya Saita ◽  
Lars-Inge Larsson

ABSTRACT Gentamicin (GM) is a widely used antibiotic but shows renal toxicity. We produced a serum against GM (anti-GM) conjugated to bovine serum albumin with N-(gamma-maleimidobutyryloxy)succinimide. The antiserum was monospecific for GM and did not cross-react with the analog streptomycin, tobramycin, kanamycin, or amikacin. The antiserum also detected glutaraldehyde-fixed GM, and this enabled us to develop an immunocytochemical method for detecting the uptake of GM in rat kidney. Twelve hours after a single intravenous administration of GM, immunocytochemistry revealed that GM accumulated in the S1, S2, and S3 segments of the proximal tubules, as well as in the distal tubules and collecting ducts. By 12 h after injection, the drug was detected in cytoplasmic granules of the proximal tubule cells. However, early (1 h) after injection, drug accumulation was detected in the microvilli of these cells. The distal tubules and collecting ducts contained scattered swollen cells, reminiscent of necrotic cells, in which both the nuclei and the cytoplasm reacted strongly with GM. No staining occurred in the kidneys of saline-injected control rats. These results agree with previous studies showing that GM is endocytosed in the proximal tubules and accumulates in lysosomes. Additionally, our results show that GM also accumulates in the distal tubules and collecting ducts. This was achieved by systematically varying the pretreatment conditions—an approach necessary for detecting GM in different subcellular compartments. This approach should be useful for accurately detecting the uptake and toxicity of the antibiotic in different tissues.


2007 ◽  
Vol 19 (5) ◽  
pp. 525-531 ◽  
Author(s):  
Cathy A. Brown ◽  
Kyu-Shik Jeong ◽  
Robert H. Poppenga ◽  
Birgit Puschner ◽  
Doris M. Miller ◽  
...  

Sixteen animals affected in 2 outbreaks of pet food-associated renal failure (2 dogs in 2004; 10 cats and 4 dogs in 2007) were evaluated for histopathologic, toxicologic, and clinicopathologic changes. All 16 animals had clinical and laboratory evidence of uremia, including anorexia, vomiting, lethargy, polyuria, azotemia, and hyperphosphatemia. Where measured, serum hepatic enzyme concentrations were normal in animals from both outbreaks. All animals died or were euthanized because of severe uremia. Distal tubular lesions were present in all 16 animals, and unique polarizable crystals with striations were present in distal tubules or collecting ducts in all animals. The proximal tubules were largely unaffected. Crystals and histologic appearance were identical in both outbreaks. A chronic pattern of histologic change, characterized by interstitial fibrosis and inflammation, was observed in some affected animals. Melamine and cyanuric acid were present in renal tissue from both outbreaks. These results indicate that the pet food-associated renal failure outbreaks in 2004 and 2007 share identical clinical, histologic, and toxicologic findings, providing compelling evidence that they share the same causation.


1986 ◽  
Vol 70 (4) ◽  
pp. 379-387 ◽  
Author(s):  
S. J. Walter ◽  
D. G. Shirley

1. Hydrochlorothiazide was administered at two doses to Long-Evans rats for 7–10 days. Both doses resulted in an initial natriuresis and diuresis. After 1 day of treatment the natriuresis abated, but the diuresis persisted. 2. The mechanisms responsible for these chronic effects were investigated by performing clearance and micropuncture studies on all animals; collections were made from late proximal tubules and from early and late regions of distal tubules. 3. Values for total glomerular filtration rate and single-nephron filtration rate in thiazide-treated rats were not significantly different from those in control animals. 4. The delivery of sodium to the end of the proximal convoluted tubule was considerably reduced in each group of thiazide-treated rats. Although sodium delivery to the early distal tubule was also significantly lower than in control animals, the difference had disappeared by the late distal tubule. 5. It is concluded that the return of sodium excretion to control levels during chronic hyrochlorothiazide administration is a consequence of increased fractional reabsorption by the proximal tubules, secondary to a thiazide-induced sodium depletion. This results in less sodium being delivered to the nephron site at which thiazides exert their major inhibitory effect. 6. Fluid delivery to the end of the proximal convoluted tubule and to the early distal tubule was significantly reduced in thiazide-treated rats; in animals given the higher dose of diuretic it was also significantly reduced at the end of the distal tubule. Nevertheless, in both thiazide-treated groups urine flow rate was elevated, suggesting that reabsorption of water from the collecting ducts is reduced during chronic thiazide administration.


2008 ◽  
Vol 68 (3) ◽  
pp. 561-569 ◽  
Author(s):  
MF. Izaguirre ◽  
MN. García-Sancho ◽  
LA. Miranda ◽  
J. Tomas ◽  
VH. Casco

Cell adhesion molecules act as signal transducers from the extracellular environment to the cytoskeleton and the nucleus and consequently induce changes in the expression pattern of structural proteins. In this study, we showed the effect of thyroid hormone (TH) inhibition and arrest of metamorphosis on the expression of E-cadherin, β-and α-catenin in the developing kidney of Bufo arenarum. Cell adhesion molecules have selective temporal and spatial expression during development suggesting a specific role in nephrogenesis. In order to study mechanisms controlling the expression of adhesion molecules during renal development, we blocked the B. arenarum metamorphosis with a goitrogenic substance that blocks TH synthesis. E-cadherin expression in the proximal tubules is independent of thyroid control. However, the blockage of TH synthesis causes up-regulation of E-cadherin in the collecting ducts, the distal tubules and the glomeruli. The expression of β-and α-catenin in the collecting ducts, the distal tubules, the glomeruli and the mesonephric mesenchyme is independent of TH. TH blockage causes up-regulation of β-and α-catenin in the proximal tubules. In contrast to E-cadherin, the expression of the desmosomal cadherin desmoglein 1 (Dsg-1) is absent in the control of the larvae kidney during metamorphosis and is expressed in some interstitial cells in the KClO4 treated larvae. According to this work, the Dsg-1 expression is down-regulated by TH. We demonstrated that the expression of E-cadherin, Dsg-1, β-catenin and α-catenin are differentially affected by TH levels, suggesting a hormone-dependent role of these proteins in the B. arenarum renal metamorphosis.


1976 ◽  
Vol 231 (2) ◽  
pp. 387-392 ◽  
Author(s):  
D De Rougemont ◽  
M Henchoz ◽  
F Roch-Ramel

Free-flow micropuncture experiments were performed in male Sprague-Dawley rats undergoing moderate mannitol diuresis and infused with urate-containing solutions. The resulting plasma urate concentrations ranged from 37.5 +/- 2.4 to 601.2 +/- 23.8 muM. With urate loading, the fraction of filtered urate excreted in pelvic urine increased from 0.32 +/- 0.02 to 0.92 +/- 0.05 mu M, but net secretion was not observed. At normal urate levels net reabsorption occurred along superficial proximal tubules, whereas net secretion could be demonstrated at the highest plasma urate levels. Net movements of urate did not appear to occur across the walls of the lower segments of nephrons.


2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S152-S153
Author(s):  
M Deebajah ◽  
Z Qu ◽  
P Zhang

Abstract Introduction/Objective GATA3 is found in glomerular mesangial cells, and the distal tubules & collecting ducts in metanephros and eventual kidneys, but not associated with the proximal tubules and loops of Henle. We hypothesize that GATA3 can be used as a marker to identify the origin of tubular differentiation in most renal tumors. Methods/Case Report Ten negative controls and 43 renal mass lesions (RCC, papillary, clear cell papillary, and chromophobe carcinomas, oncocytoma, and polycystic kidney disease). GATA3 nuclear stain was graded as negative (absent stain), equivocal and positive (< 5 and > 5% cells, respectively). Details of their GATA3 nuclear expression was analyzed for identifying their tubular segmental origins. Results (if a Case Study enter NA) In 10 normal renal parenchyma, GATA3 was positive in mesangial cells, distal tubules, and collecting ducts, but was negative in the proximal tubules and loop of Henle. The cystic lining of glomerulocystic renal disease was stained negatively for GATA3 (proximal tubular origin), whereas pediatric and adult variants of polycystic kidney diseases was positive for GATA3 staining (distal tubular origin). 1/10 ten clear cell RCC and papillary RCC showed focal positive GATA3 stain. GATA3 showed weakly positive staining in some oncocytomas (4/11) and some chromophobe RCC (4/11), indicating that they might be derived from the junctional segment between the loop of Henle and the distal tubules. By contrast, all clear cell papillary RCC (distal tubule origin) were diffusely positive. Conclusion Our results indicate that GATA3 is a useful immunohistochemical marker to determine the developmental origin in the specific renal tubular segment for the majority of renal mass lesions. Thus, it may be useful for routine differential diagnosis of these lesions.


1998 ◽  
Vol 1 (1) ◽  
pp. 49-55 ◽  
Author(s):  
T. Nadasdy ◽  
G. Lajoie ◽  
Z. Laszik ◽  
K.E. Blick ◽  
G. Molnar-Nadasdy ◽  
...  

In a previous study, utilizing antibodies to proliferating cell nuclear antigen (PCNA), we determined the proliferation index (PI) (percentage of PCNA-positive cells) of intrinsic renal cell populations in the normal adult and pediatric kidney. We have found that the PI in both adult and pediatric kidneys was very low (below 0.5 in all examined cell populations). In our present study, we investigated cell proliferation in the developing human kidney with an antibody to PCNA. Histologically normal kidneys were collected from 25 fetuses (spontaneous abortions and stillborns) ranging from 10 wk of gestation to term. Immature mesenchyme (blastema), immature early tubules, ampulla of ureteric bud, proximal tubules, Tamm-Horsfall protein (THP)-positive tubules, distal tubules, collecting ducts, and glomeruli were evaluated separately. The PI for each cell population was calculated. The PI of immature early tubules remains high (33–43) throughout embryonic life. The PI of blastemal cells is initially similarly high, but gradually decreases starting from the second trimester. The PI of THP-positive tubules, distal tubules, collecting ducts, and glomeruli starts out relatively high (5.9, 8.6, 6.0, and 12.4, respectively) and decreases gradually as term approaches (1.8, 1.3, 1.2, and 1.4, respectively). Interestingly, as soon as proximal tubules become differentiated (appearance of light microscopic features of proximal tubular epithelium with TP lectin positive brush border), their PI becomes very low (below 1) irrespective of the age of the kidney. This is the first quantitative study to show changes of the PI in various renal cell populations during human nephrogenesis. These changes in the PI relate to the stage of differentiation of the developing nephron segments.


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