• YAKHAK HOEJI
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• v.35 no.6
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• pp.504-508
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• 1991

In order to investigate whether the function of distal nephron is disturbed in adenine-induced renal failure rats, we measured the urinary kallikrein level in adenine-ingesting rats fed on 0.75% adenine diet for 1 to 10 days. Administration of 0.75% adenine to rats significantly increased blood urea nitrogen level and urine volume, while the level of kallikrein along with the urinary excretions of urea and inorganic phosphate were significantly decreased. From these results, it is suggested that adenine-induced renal failure is caused by early deterioration of distal nephron as well as proximal nephron.

• Journal of Genetic Medicine
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• v.10 no.2
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• pp.81-87
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• 2013

Pseudohypoaldosteronism (PHA), a rare syndrome of systemic or renal mineralocorticoid resistance, is clinically characterized by hyperkalemia, metabolic acidosis, and elevated plasma aldosterone levels with either renal salt wasting or hypertension. PHA is a heterogeneous disorder both clinically and genetically and can be divided into three subgroups; PHA type 1 (PHA1), type 2 (PHA2) and type 3 (PHA3). PHA1 and PHA2 are genetic disorders, and PHA3 is a secondary disease of transient mineralocorticoid resistance mostly associated with urinary tract infections and obstructive uropathies. PHA1 includes two different forms with different severity of the disease and phenotype: a systemic type of disease with autosomal recessive inheritance (caused by mutations of the amiloride-sensitive epithelial sodium channel, ENaC) and a renal form with autosomal dominant inheritance (caused by mutations of the mineralocorticoid receptor, MR). In the kidneys, the distal nephron takes charge of the fine regulation of water absorption and ion handling under the control of aldosterone. Two major intracellular actors necessary for the action of aldosterone are the MR and the ENaC. Impairment of the intracellular aldosterone signal transduction pathway results in resistance to the action of mineralocorticoids, which leads to PHA. Herein, ion handling the distal nephron and the clinico-genetic findings of PHA are reviewed with special emphasis on PHA type 1.

• Childhood Kidney Diseases
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• v.14 no.2
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• pp.120-131
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• 2010

Renal tubular acidosis (RTA) is a metabolic acidosis due to impaired excretion of hydrogen ion, or reabsorption of bicarbonate, or both by the kidney. These renal tubular abnormalities can occur as an inherited disease or can result from other disorders or toxins that affect the renal tubules. Disorders of bicarbonate reclamation by the proximal tubule are classified as proximal RTA, whereas disorders resulting from a primary defect in distal tubular net hydrogen secretion or from a reduced buffer trapping in the tubular lumen are called distal RTA. Hyperkalemic RTA may occur as a result of aldosterone deficiency or tubular insensitivity to its effects. The clinical classification of renal tubular acidosis has been correlated with our current physiological model of how the nephron excretes acid, and this has facilitated genetic studies that have identified mutations in several genes encoding acid and base ion transporters. Growth retardation is a consistent feature of RTA in infants. Identification and correction of acidosis are important in preventing symptoms and guide approved genetic counseling and testing.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.4
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• pp.403-411
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• 1997

To elucidate the mechanism of gentamicin induced renal dysfunction, renal functions and activities of various proximal tubular transport systems were studied in gentamicin-treated rats (Fisher 344). Gentamicin nephrotoxicity was induced by injecting gentamicin sulfate subcutaneously at a dose of 100 $mg/kg{\cdot}day$ for 7 days. The gentamicin injection resulted in a marked polyuria, hyposthenuria, proteinuria, glycosuria, aminoaciduria, phosphaturia, natriuresis, and kaliuresis, characteristics of aminoglycoside nephropathy. Such renal functional changes occurred in the face of reduced GFR, thus tubular transport functions appeared to be impaired. The polyuria and hyposthenuria were partly associated with a mild osmotic diuresis, but mostly attributed to a reduction in free water reabsorption. In renal cortical brush-border membrane vesicles isolated from gentamicin-treated rats, the $Na^+$ gradient dependent transport of glucose, alanine, phosphate and succinate was significantly attenuated with no changes in $Na^+-independent$ transport and the membrane permeability to $Na^+$. These results indicate that gentamicin treatment induces a defect in free water reabsorption in the distal nephron and impairs various $Na^+-cotransport$ systems in the proximal tubular brush-border membranes, leading to polyuria, hyposthenuria, and increased urinary excretion of $Na^+$ and other solutes.

• YAKHAK HOEJI
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• v.54 no.3
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• pp.180-186
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• 2010

Aldosterone, mineralocorticoid hormone, has important functions related to the regulation of blood pressure and balance of fluids and electrolytes in the distal region of the nephron. By genomic and non-genomic action of aldosterone, the physiological kidney functions are modulated. However, many of them except several kind of sodium channel have not been identified and analyzed yet. In this study, proteomic technologies with two-dimensional gel electrophoresis (2-DE) gel using aldosterone rat model were applied to analyze and identify the aldosterone dependently expressed proteins in rat kidney cortex. As a result, the established aldosterone rat model exhibited the normal physiological responses to aldosterone and modulated proteins were identified, which included 15 increased and 3 decreased proteins on 2-DE analysis. Among them, 11 proteins were identified as changed proteins by LC-MS/MS analysis. These proteins identified as aldosterone induced proteins were involved in several cellular pathways such as cytoskeleton remodeling, energy metabolism, amino acid metabolism, and chaperone process. In conclusion, our data could provide the insights into the new mechanism underlying regulation of kidney functions by aldosterone.

• Journal of Oriental Physiology
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• v.14 no.2 s.20
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• pp.189-198
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• 1999

Aminoglycosides, including gentamicin, have been used as antibiotics for the various infections by gram-negative bacteria. However, there are some restrictions for using these drugs. Gentamicin, a typical aminoglycoside, has the side effect of nephrotoxicity, including polyuria, glycosuria, proteinuria, glomerulonephritis, and uremia. The aims of this study were to examine the prevention or reduction effects of Jinmootang on the gentamicin-induced nephrotoxicity and to investigate the possible mechanisms on the effect of Jinmootang. The subcutaneous injections of 60mg of gentamicin per kg of boby weight to Sprague-Dawley rats for 8 days induced typical symptoms of nephrotoxicity by aminoglycosides. 0.6ml of water extract Jinmootang (100ml/chup) was orally treated in the experimental animal. 24-hour urine was collected with the metabolic cage and plasma was sampled from the abdominal aorta. The plasma concentration of sodium was significantly decreased by the treatment of gentamicin but it was not-significantly changed by the treatment of Jinmootang to the animal. The concentration of potassium was greatly decreased in the gentamicin-treated animals. However. it was returned to the normal level in the Jinmootang-treated animals. The concentrations of creatinine and urea were increased by gentamicin treatment. But, Jinmootang reduced these concentrations. Nevertheless, the osmolalities of plasma in both group were not different from each other. Even though the plasma concentration of aldosterone was not significantly changed, the mean value was increased by the gentamicin intoxication. The concentration of aldosterone was decreased by the treatment of Jinmootang. The reduction of aldosterone level in plasma could be a factor to improve the hypokalemia. The fractional excretion of potassium was much higher than normal by the treatment of gentamicin and it was decreased by 50% in the Jinmootang-treated rats. Therefore, the reabsorption of potassium was significantly increased by the treatment of Jinmootang, even though the filtered load of potassium in the experimental group was much highter than control. Even though the concentration of plasma aldosterone was decreased by the treatment of Jinmootang, the fractional excretion of sodium was not increased, slightly lower. These data suggested that Na reabsorption was increased in the proximal tubule by Jinmootang. The filtered load of glucose in the Jinmootang-treated group was greater than in control. Nevertheless, the fractional excretion of glucose in the experimental group was not different from that in control. These results indicate that glucose reabsorption was increase in the proximal tubule by Jinmootang treatment. The results of this study suggest that Jinmootang could improve the some nephrotoxic symptoms induced by gentramicin treatment. Hypokalemia, the reduced glomerular filtration rate, and dysfunctions of renal proximal tubule and distal nephron were significantly recovered to normal level. The increase of glomerular filtration rate by Jinmootang might contribute to eliminate the waste product, including creatinine and urea, and/or gentamicin through the kidney.