• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.601-610
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• 2024

Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CL_NR) and renal clearance (CL_R) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CL_NR, and CL_R) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance. Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.

• Journal of Pharmaceutical Investigation
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• v.17 no.4
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• pp.205-211
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• 1987

Renal dysfunction can have pronounced effects on the pharmacokinetic and pharmacodynamic characteristics of drugs. Because the exploration of these effects in patients may be limited by ethical and practical considerations, it often become necessary to perform studies on animals with experimental renal failure(ERF). ERF was produced in rats by the administration of uranyl nitrate, glycerol, salicylate, gentamicin and folate in this study. Changes in glomerular filtration rate(GFR) and renal secretion clearance of tetraethylammonium bromide$(CL^{scn}_{TEA})$, together with morphological changes of kidney cortex were evaluated and compared among ERF models. GFR(or glomeruli) and $CL^{scn}_{TEA}$(or renal tubules) were not damaged parallelly in some ERF model rats. Therefore, it seemed to be necessary to adjust dosage regimen of some basic drugs like TEA in renal dysfunction considering the functional changes of renal secretion in addition to glomerular filtration.

• YAKHAK HOEJI
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• v.20 no.1
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• pp.97-106
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• 1976

The actions of Atractylodes rhizoma alba on renal function of dog were investigated with water and methanol extract of it, utilizing clearance technique. Water extract elicited diuresis while methanol extract induced antidiuresis in the dog when they were given intravenously. The diuresis induced by the intravenous water extract seemed to be closely related to the decrement of reabsorption of electrolytes in renal tubules. On the contrary, the antidiuresis by intravenous methanol extract appeared to be related to the increment of renal reabsorption of sodium. Water and methanol extract, when infused into a renal artery, exhibited identical resposes to the intravenous actions confined only to the infused kidney, inferring that renal actions of water and methanol extract are not mediated by any endognous humoral extract are not mediated by any endogenous humoral agents. From these observations it is concluded that diuretic action of water extract and antidiuretic action of methanol extract were brought about by direct action in the renal tubules.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.413-417
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• 2002

Gitelman's syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria that has recently been reported to be linked to thiazide- sensitive Na-Cl cotransporter gene mutation. In this study, we performed renal clearance studies to differentiate Gitelman's from Bartter's syndrome and to confirm the diagnosis in two patients clinically diagnosed with Gitelman's syndrome. Each patient was hydrated by 20 mL/kg body weight of oral water within 30 minutes, which was followed by intravenous half saline. When urinary flow reached 10 mL/min, samples of urine and serum were obtained to calculate the osmolar clearance, free water clearance, chloride clearance, and distal fractional chloride reabsorption. Subsequently, furosemide or hydrochlorothiazide was administered. Samples were collected and the same parameters were calculated. In our patients, chloride clearance was increased more than 10 times after furosemide administration(2.1 : 25.7 and 2.2 : 27.4 mL/min/100 mL GFR), but not increased after hydrochlorothiazide treatment(2.1 : 1.6 and 2.2 : 2.6 mL/min/100 mL GFR). And the distal fractional chloride reabsorption was significantly decreased by furosemide injection (73% : 15% and 75% : 4.6%), whereas hydrochlorothiazide had no effect on it(73% : 63% and 75% : 78%). These findings indicate that our patients have a defect in thiazide-sensitive Na-Cl cotransporter in the distal tubule, which is compatible with the pathophysiology of Gitelman's syndrome.

• Clinical and Experimental Pediatrics
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• v.52 no.9
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• pp.999-1004
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• 2009

Purpose : Glomerular filtration rate (GFR) is a fundamental parameter in assessing renal function and predicting the progression of chronic renal disease. Because the use of serum creatinine has several disadvantages, many studies have investigated the use of cystatin C for estimating GFR. We compared creatinine clearance and GFR with formulas using serum creatinine and cystatin C. Methods : We retrospectively analyzed 211 patients with various renal diseases and classified them into two groups according to creatinine clearance (Group 1: CrCl >$90mL/min/1.73m^2$, Group 2: CrCl <$90mL/min/1.73m^2$). We measured serum creatinine, cystatin C, and creatinine clearance. We calculated GFR using the Schwartz, Counahan, Filler and Lepage, Bokencamp et al, and Grubb et al formulas. Results : GFR determined by the Schwartz formula had the highest correlation to creatinine clearance (r=0.415, P=0.00). GFR determined by various formulas using cystatin C had lower correlation to creatinine clearance (r=0.187, r=0.187, r=0.291). The Schwartz and Counahan formulas showed greater diagnostic accuracy in detecting decreased GFR than cystatin C in group 2 (areas under the curve: Schwartz, 0.596; Counahan, 0.572; Filler, 0.512; Bokencamp, 0.508; and Grubb, 0.514). Conclusion : GFR determined by the Schwartz and Counahan formulas using serum creatinine showed higher correlation coefficient than that determined by formulas using cystatin C. The formulas using cystatin C were not superior to those using serum creatinine in detecting decreased GFR. Cystatin C measurement was not satisfactory for assessing GFR in patients whose renal function was not severely decreased.

• YAKHAK HOEJI
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• v.38 no.5
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• pp.568-578
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• 1994

This study was performed in order to investigate the effect of diltiazem, which is a $Ca^{2+}$ channel blocker of benzothiazepine derivatives, on renal function in the dog. Diltiazem, when infused into the vein or carotid artery, produced the antidiuresis accompanied with the decreased excretion rates of sodium and potassium in urine$(E_{Na},\;E_K)$ and the increased reabsorption rates of sodium and potassium in renal tubules$(R_{Na},\;R_K)$. Diltiazem, when infused into a renal artery, exhibited the diuresis along with the increased renal plasma flow(RPF), osmolar clearance$(C_{osm})$, $E_{Na}$ and $E_K$, and decreased $R_{Na}$ and $R_K$ in only infused kidney. Above results suggest that diltiazem possess both antidiuretic action through central action and diuretic action by direct inhibition of electrolytes reabsorption rates in renal tubules, mainly distal tubule.

• YAKHAK HOEJI
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• v.41 no.4
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• pp.498-511
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• 1997

The effects of UK 14,304, an ${\alpha}_2$-adrenergic agonist, on renal function were investigated in dogs. UK 14,304, when given intravenousely($15.0{\mu}g/kg,\;50{\mu}g/kg$), produced the increase of urine flow accompanied with the marked augmentation of free water clearance ($C_{H_2O}$) and reabsorption rates of sodium in renal tubules ($R_{Na}$), and the remarkable decrease of osmolar clearance ($C_{osm}$) and the amounts of sodium excreted in urine ($E_{Na}$). UK 14,304 given into a renal artery($1.5{\mu}g/kg,\;5.0{\mu}g/kg$) elicited the increase of urine flow with the augmentation of $C_{H_2O}$ in both kidney. UK 14,304, when administered into carotid artery($3.0{\mu}g/kg,\;10.0{\mu}g/kg$). exhibited the same aspect as shown in intravenous UK 14.304 at smaller dose than the intravenous dose. Diuretic action of intravenous UK 14,304 were produced together with increase of $C_{H_2O}$ in situation of water diuresis too, changes of renal function in this state were the increase of $C_{osm},\;E_{Na},\;and\;E_K$ (excreted amounts of potassium in urine), and the decrease of $R_{Na}\;and\;R_K$, these were different appearances from situation of saline diuresis. Diuretic action of intravenous UK 14,304 were blocked completely by post or pretreatment of yohim-bine, ${\alpha}_2$-adrenergic blocking agents, and inhibited by pretreatment of vasopressin, antidiuretic hormone. Above results suggest that UK 14,304 produces the diuretic action by the inhibition of vasopressin secretion and suppression of electrolytes reabsorption of electrolytes in renal tubules mediated with central ${\alpha}_2$-adrenoceptor in dog.

• Childhood Kidney Diseases
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• v.11 no.2
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• pp.161-167
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• 2007

Purpose : GFR(glomerular filtration rate) is a fundamental parameter in detecting renal impairment and predicts the progression of renal disease. Because serum creatinine has several disadvantages, serum cystatin C has been recently proposed as a new endogenous marker for GFR. We compared serum cystatin C with creatinine and creatinine clearance to investigate the clinical usefulness of cystatin C. Methods : We retrospectively analyzed 46 patients(60 case numbers) who had various renal diseases and classified them into 3 groups according to creatinine clearance(Group 1 : CrCl <40 mL/min/$1.73m^2$, Group 2 : CrCl 40-60 mL/min/$1.73m^2$, Group 3 CrCl >60 mL/min/$1.73m^2$). We measured serum creatinine, cystatin C and creatinine clearance and also analyzed the correlations among them. Results : Serum cystatin C and creatinine showed a similar correlation to creatinine clearance (r=0.685, r=0.640, respectively) and showed similar diagnostic accuracy in detecting decreased GFR(AUC, cystatin C 0.829 vs. creatinine 0.826, P=0.848). Serum cystatin C showed a greater sensitivity for detecting a decreased GFR than creatinine in Group 2 and 3(Group 1 : 100% vs. 100%, Group 2 : 70% vs. 35%, Group 3 : 46% vs. 15%). Conclusions : Serum cystatin C could be a useful endogenous marker for GFR and would be superior to serum creatinine in early detection of renal impairment in pediatric patients with renal diseases.

• 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.

• Korean Journal of Pharmacognosy
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• v.6 no.2
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• pp.101-110
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• 1975

In this study attempts were made to explore effects of the water and alcohol extracts of Junci Herba on the renal function of dogs. The water extract (in a dose 15 mg/kg, i.v.) and alcohol extract (in a dose 1.5 mg/kg, i.v.) elicited a diuretic response and produced a marked diuresis during bicarbonate infusion whereas no diuresis ensues during infusion of hydrochloric acid. The ratios of potassium and sodium excreted in urine $(K^+/Na^+)$, pH of urine, Cosm (osmolar clearance) and $C_{H_2O}$ (free water clearance) increased but hemodynamic states changed little with both extracts. All the observed facts can be best explained on the assumption that Junci Herba inhibits the carbonic anhydrase in the tubule. Thus it produces the effect by increasing urinary potassium and sodium.