• Title/Summary/Keyword: Kidney tubules, proximal

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CUBN mutation: a benign genetic cause of proteinuria?

  • Hyun Kyung Lee
    • Childhood Kidney Diseases
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    • v.27 no.1
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    • pp.19-25
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    • 2023
  • Proteinuria is an important risk factor for renal and cardiovascular disease. It is associated with a risk for glomerulonephritis, chronic kidney disease, and end-stage renal disease. Therefore, if persistent proteinuria is detected, kidney biopsy is considered to diagnose and treat the underlying disease. Recently, variants in the cubilin (CUBN) gene, which is associated with albuminuria, have been reported. This gene encodes cubilin, a membrane glycoprotein receptor expressed in the renal proximal tubules. Cubilin is a component of the megalin and cubilin-amnionless complex that mediates albumin reabsorption into the proximal tubules through endocytosis. A defect in cubilin leads to a reduction in albumin reuptake, resulting in albumin-dominant proteinuria. Although numerous controversies exist, several reports suggest that cubilin defects lead to proteinuria with a high portion of albuminuria but may not impair renal filtration function. If albuminuria due to reduced cubilin function is confirmed as a benign condition, we can consider using genetic studies to detect CUBN mutations in patients with proteinuria and they may not require any treatment or kidney biopsy. Here, we review recent papers on CUBN mutations and discuss the prognosis and management of individuals with this mutation.

The Effects of Kami-bangpungtongseong-san Extracts on the Mouse Liver and Kidney Toxicated by Mercuric Chloride Subcutaneous Injection (가미방풍통성산(加味防風通聖散)이 수은의 피하 주입으로 중독된 마우스의 간 및 신기능에 미치는 영향)

  • Yang, Joon-Hyoung;Hong, Seong-Ug
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.2
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    • pp.1-12
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    • 2010
  • Objective : For this study, mice on mercurial toxication were given mercuric subcutaneous injection to their abdomen factitiously. After delivering Kami- bangpungtongseong-san(KBT) extracts to the mice by oral administration, we observed changes from liver and kidney of mice. Method : The BALB/c mice were distributed into three groups: No treated group(Normal group), Mercuric chloride subcutaneous injection group(Control group), Kami-bangpungtongseong-san-treated group (Sample group). KBT Extracts were delivered orally in 7 days. We observed involution of liver, necrosis of liver and cell plate loss of liver, lipid peroxidation CYP1A1 expression. We observed involution of proximal convoluted tubules, hypertrophy of Bowman's capsule, periodic acid-Schiff(PAS)'s positive reaction of proximal convoluted tubules, heat shock protein(HSP)700's positive reaction in glomerulus. For the charting the results, image analysis was taken. The result of image analysis was verified significance by Sigmaplot 2000(P<0.05). Result : The mice' liver on mercurial toxication were relieved involution of liver, necrosis of liver, and cell plate loss of liver and also declined lipid peroxidation and CYP1A1 expression. The mice' kidney on mercurial toxication were relieved involution of proximal convoluted tubules, hypertrophy of Bowman's capsule and increasing PAS's positive reaction of proximal convoluted tubules. On the other hand it was declined HSP700's positive reaction in glomerulus. Conclusion : According to the result of study, we think that we can expect to the effect of KBT extracts' therapeutic action to tissue injuries of the mice' liver and kidney on acute mercurial toxication.

Glycoconjugates Properties of the Kidney in the Hibernating Chipmunks (동면 중 한국산 다람쥐 신장의 복합당질 변화)

  • Gil, Young-Gi
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1239-1243
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    • 2008
  • Though relatively little is known of the physiology involved, there is reduced kidney activity during hibernation. In this experimental study, male Korean chipmunks (Tamias sibiricus barberi) were maintained in cold conditions ($6^{\circ}C$) for 9 months, in an attempt to mimic conditions occurring during seasonal hibernation. The examination was made to determine changes of glycoconjugates on the kidney after hibernation by lectin histochemistry. The changes of lectin affinities in the kidney categorize into three groups: a) increase ones only in the early hibernation stage b) increase ones during hibernation and c) decrease ones during hibernation. The transient increase of Con A affinity in the proximal convoluted tubules were demonstrated only in the early cold-treated stage, and PNA and Con A in the distal convoluted tubules and DBA and sWGA in the collecting tubules. SBA affinity tended to increase with hibernation in the proximal convoluted tubules, but sWGA affinities were significantly decreased in the all tubule examined with hibernation. The present results suggest that the glycosylation pattern of the kidney undergoes profound changes during hibernation, and is probably associated with transiently reduced renal function.

Effects of High Glucose on Na,K-ATPase and Na/glucose Cotransporter Activity in Primary Rabbit Kidney Proximal Tubule Cells

  • Han, Ho-Jae
    • The Korean Journal of Physiology
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    • v.29 no.1
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    • pp.69-80
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    • 1995
  • Renal proximal tubular hypertrophy and hyperfunction are known to be early manifestations of experimental and human diabetes. As the hypertrophy and hyperfunction have been suggested to be central components in the progression to renal failure, an understanding of their underlying causes is potentially important for the development of therapy. A primary rabbit kidney proximal tubule cell culture system was utilized to evaluate the possibility that the renal proximal tubular hypertrophy and hyperfunction observed in vivo in diabetes mellitus, can be attributed to effects of elevated glucose levels on membrane transport systems. Primary cultures of rabbit proximal tubules, which achieved confluence at 10 days, exhibited brush-border characteristics typical of proximal tubular cells. Northern analysis indicated $2.2{\sim}2.3$ and 2.0 kb Na/glucose cotransporter RNA species appeared in fresh and cultured proximal tubule cells after confluence, repectively. The cultured cells showed reduced Na/glucose cotransporter activity compared to fresh proximal tubules. Primary cultured proximal tubule cells incubated in medium containing 20 mM glucose have reduced ${\alpha}-MG$ transport compared to cells grown in 5 mM glucose. In the proximal tubule cultures incubated in medium containing 5 mM or 20 mM glucose, phlorizin at 0.5 mM inhibited 0.5 mM ${\alpha}-MG$ uptake by 84.35% or 91.85%, respectively. The uptake of 0.5 mM ${\alpha}-MG$ was similarly inhibited by 0.1 mM ouabain (41.97% or 48.03% inhibition was observed, respectively). In addition, ${\alpha}-MG$ uptake was inhibited to a greater extent when $Na^{+}$ was omitted from the uptake buffer (81.86% or 86.73% inhibition was observed, respectively). In cell homogenates derived from the primary cells grown in 5 mM glucose medium, the specific activity of the Na/K-ATPase $(6.17{\pm}1.27\;{\mu}mole\;Pi/mg\;protein/hr)$ was 1.56 fold lower than the values in cell homogenates treated with 360 mg/dl D-glucose, 20 mM $(9.67{\pm}1.22\;{\mu}mole\;Pi/mg\;protein/hr)$. Total $Rb^{+}$ uptake occurred at a significantly higher rate (1.60 fold increase) in primary cultured rabbit kidney proximal tubule cell monolayers incubated in 20 mM glucose medium $(10.48{\pm}2.45\;nM/mg\;protein/min)$ as compared with parallel cultures in 5 mM glucose medium. $Rb^{+}$ uptake rate in 5 mM glucose medium was reduced by 28% when the cultures were incubated with 1 mM ouabain. The increase of the $Rb^{+}$ uptake by rabbit kidney proximal tubule cells in 20 mM glucose could be attributed primarily to an increase in the rate of ouabain-sensitive $Rb^{+}$ uptake $(5\;mM\;to\;20\;mM;\;4.68{\pm}0.85\;to\;8.38{\pm}1.37\;nM/mg\;protein/min)$. In conclusion, the activity of the renal proximal tubular Na,K-ATPase is elevated in high glucose concentration. In contrast, the activity of the Nafglucose cotransport system is inhibited.

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Influence of Bradykinin on the tubular function of the dog kidney (신세뇨관기능(腎細尿管機能)에 미치는 Bradykinin의 영향(影響))

  • Sub, Byoung-Chul
    • The Korean Journal of Pharmacology
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    • v.2 no.1 s.2
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    • pp.5-12
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    • 1966
  • In this study the influence of Bradykinin, a biogenic polypeptide, on the excretory function of the dog kidney was investigated, utilizing the clearance and stop-flow method. The results are summarized as follows; 1) Bradykinin administered intravenously elicited a marked antidiuresis. 2) When given into the renal artery, however, prompt increase of the urine flow, sodium excretion and free water clearance without significant change in the glomerular filtration rate ensued. 3) It was also effective during an osmotic diuresis with 10% Mannitol infusion, though the response was not so marked. 4) The stop-flow experiment showed that sodium reabsorption in the proximal tubules is inhibited by the infusion of bradykinin into the renal artery. It was thus concluded that the diuretic effect of bradykinin given intra-arterially results from the inhibition of sodium transport in the proximal tubules.

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A Study on the Effect of Thiamine on the Toxicity of Phenylmercuric Acetate in Albino Rats (Thiamine이 水銀中毒 白鼠의 各臟器에 미치는 影響)

  • Rhim, Kook Hwan
    • Journal of Environmental Health Sciences
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    • v.12 no.2
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    • pp.1-9
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    • 1986
  • The purpose of this study is to determine the antidotal effects of thiamine in phenylmercury poisoning rats. Sixty-six rats were divided into six groups the control group, the $40{\gamma}$ thiamine-only-dosed group, the 6 ppm phenylmercury-only-dosed group, the simultaneously-dosed-group with 6 ppm mercury & $20{\gamma}$ thiamine, and with 6 ppm mercury & $40{\gamma}$ thiamine, and with 6 ppm mercury & $80{\gamma}$ thiamine. The thiamine was put into pellet by various concentrations, and phenylmercury was mixed in drinking water by 6 ppm concentration. The rats were sacrificed for observing the histopathological changes of brain, liver and kidney. The remits summarized are as follows 1. In the group dosed with only $40{\gamma}$ thiamine, the tissues of brain, liver and kidney did not show any abnormal architecture. 2. The phenyhnercury-only-dosed group and the simultaneoulsy-dosed group with mercury and $20{\gamma}$ thiamine showed remarkable degenerative or necrotic hepatic cells. In addition, a remarkable swelling and necrosis on epithelium of proximal tubules in kidney were found. 3. The simultaneously-dosed group with mercury and $40{\gamma}$ thiamine showed moderate degeneration and necrosis of Purkinje cells in cerebellum. A moderate necrosis and swelling on epithelium of proximal tubules and a large amount of tubular casts were found as well. 4. The simultaneously-dosed group with mercury and $80{\gamma}$ thiamine showed a slight degenerative change of Purkinje cells. A slight degenerative change on epithelium of proximal tubules and a small amount of tubular casts were also found.

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Studies on Gentamicin-induced Nephrotoxicity in Rats (랫트에서의 Gentamicin신장독성(腎臟毒性)에 관한 연구(硏究))

  • Cho, In-soo;Kim, Tae-jong;Yoon, Hwa-joong
    • Korean Journal of Veterinary Research
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    • v.26 no.1
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    • pp.125-137
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    • 1986
  • Sprague-Dawley rats received subcutaneous injections of gentamicin sulfate, 50 and 100mg/kg for 3, 7 and 10 days. The hematological and blood chemical values were determined. Kidneys were examined histologically and ultrastructurally. The results obtained were summarized as follows; 1. The serum values of aspartate transaminase, blood urea nitrogen and creatinine in the rats administered gentamicin, 50 and 100mg/kg/day were significantly increased than those in the control. 2. The ratio of kidney weight to body weight was significantly increased in the rats injected gentamicin, 100mg/kg for 10 days than those in the control. 3. The brush borders of proximal convoluted tubules in the kindneys received gentamicin, 50 and 100mg/kg/day were decreased or absent in periodic acid-Schiff staining. 4. The necrosis of proximal convoluted tubules was shown in the rats given gentamicin, 50 and 100mg/kg for 7 and 10 days. 5. The regeneration of the proximal tubular epithelia was observed in the rats treated gentamicin, 100mg/kg for 10 days. 6. The number and size of lysosomes were increased in the proximal convoluted tubules of the rats injected gentamicin, 50mg/kg for 7 days, many of which contained myeloid bodies.

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Chitosan Increases the Release of Renal Dipeptidase from Porcine Renal Proximal Tubule Cells

  • Hyun Joong, Yoon;Kim, Young-Ho;Park, Sung-Wook;Lee, Hwanghee-Blaise;Park, Haeng-Soon
    • Animal cells and systems
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    • v.7 no.4
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    • pp.309-315
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    • 2003
  • Renal dipeptidase (RDPase, membrane dipeptidase, dehydropeptidase 1, EC 3.4.13.19) has been widely studied since it was first purified from porcine kidney brush border membrane. It was reported that RDPase activity in urine samples of acute and chronic renal failure patients decreases. Nitric oxide (NO) is a highly reactive free radical involved in a number of physiological and pathological processes. NO is able to act in a dual mode, leading either to induction of apoptosis or to blunted execution of programmed cell death. NO inhibited the RDPase release from porcine renal proximal tubules, which could be blocked by L-NAME. Chitosan, the linear polymer of D-glucosamine in $\beta$(1\longrightarrow4) linkage, not only reversed the decreased RDPase release by NO but also increased NO production in the proximal tubule cells. The stimulatory effect of NO on RDPase release from proximal tubules in the presence of chitosan must be different from the previously proposed mechanism of RDPase release via NO signaling pathway. Chitosan stimulated the RDPase release in the proximal tubules and increased RDPase activity to 220% and 250% at 0.1% and 1%, respectively. RDPase release was decreased to about 40% in the injured proximal tubules and was recovered in proportion to the increase of chitosan. Chitosan may be useful in recovery of renal function from $HgCl_2$injury.

Detection of Mercury in Kidney, Liver, Spleen and Cerebellum of the Mouse by Autometallography (오토메탈로그라피에 의한 마우스의 신장, 간장, 비장, 및 소뇌에 축적된 수은의 검출)

  • 조현욱;김명훈;황규영;이성태
    • Toxicological Research
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    • v.13 no.4
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    • pp.401-408
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    • 1997
  • Adult male ICR mice were exposed to methylmercuric chloride (CH$_3$HgCI) through drinking water for 80 days. The distribution of mercury in the kidney, liver, spleen and cerebellum of the mouse was examined according to a autometallographic silver-enhancement technique based on a physical development process which renders mercury deposit visible. Grains of mercury traces were located in the proximal convoluted tubules. Lesser staining of the grains was seen in the collecting tubules of medulla. The glomerular basement membrane was void. In the liver, mercury accumulations were present primarily in the hepatocytes around portal area containing interlobular bile duct, artery and portal vein. Also grains of mercury traces were accumulated in the white pulp of the spleen and Purkinje cell layer of the cerebellum.

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Experimental Studies on the Excretion of Uric acid in Rabbit (가토의 요산배설에 관한 실험적연구)

  • Hong, Yoon-Pyo
    • The Korean Journal of Pharmacology
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    • v.7 no.1
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    • pp.67-76
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    • 1971
  • The excretion of uric acid in man has been of great interest because of its importance as an end product in purine metabolism as well as of its role in causing gout. There are many differences in the modes of renal handling of urate among various species of animals. Uric acid actively secreted by the renal tubules of most vertebrate including amphibians, reptiles, and birds. On the other hand, in most mammals net tubular reabsorption of urate appears to be occurred with some exception, such, as Dalmatian dog. In the rabbits, however, the mechanism of renal excretion of uric acid has long been a subject of controversial results. Within a given group it was possible to find individuals with either net secretion or net reabsorption of urate depend on the experimental conditions. Excretion of urate can be depressed or enhanced by a variety of drugs belonging mainly to the aromatic acid group. Diodrast, probenecid, cinchophen and salicylates have been reported as uricosuric agents, on the other hand, lactate, benzoate, pyrazinoic acid, acetazolamide and chlorothiazide are known to be contraindicated to use for the patient with gout since these agents depress the excretion of uric acid from the kidney. However, complex and sometimes the paradoxical effects on the urate excretion by those above mentioned drugs are not uncommon. The experiments were designed to investigate the mechanisms of renal handling of urate as well as the effects of variety of drugs on the tubular transport of uric acid in the rabbits. Male or female white rabbits, from 1.5 to 2.5 kg in weight, were used. The experimental methods used in these studies were clearance, stop-flow, and retrograde injection techniques. The effects of saline, salicylate, chlorothiazide and probenecid were investigated in each experimental conditions. Results of the experiments were summarized as follows; 1. In the rabbits, the rate of urate clearance was always lower than the rate of inulin clearance. The filtration fraction of the urate was one third on an average, therefore, it is estimated that approximately two thirds of filtered urate was reabsorbed. 2. In the kidneys of rabbits, the urate clearance was increased significantly by administration of chlorothiazide and decreased by probenecid. The administration of salicylate had no effect on the rate of urate clearance. The filtration fraction of urate was increased by chlorothiazide and decreased by probenecid. 3. In the stop-flow studies, the U/P ratio of urate was higher than the U/P ratio of inulin in the proximal region, indicating the secretion of uric acid in the proximal tubules. The proximal peak was increased by chlorothiazide and inhibited by probenecid.4. In the retrograde injection studies, the reabsorption of urate in the proximal region was observed, and these reabsorptive transport of urate was depressed by either probenecid or by chlorothiazide. 5. No distal tubular activity was observed under any of these experimental conditions concerning urate transport. The results of these experiments show that probenecid inhibits both secretory and reabsorptive transport of uric acid in the kidney of the rabbits. The enhancement of secretory transport of urate by chlorothiazide in the clearance study was due to the secondary action of chlorothiazide which inhibits the reabsorptive transport of urate in the proximal tubules. It is evident that the urate transport in the kidneys of rabbits is bidirectional nondiffusive flux both secretory and reabsorptive directions in the proximal tubules.

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