Protocol: Rat Renal Clearance Study v1 (protocols.io.bawaifae)

protocols.io ◽  
2019 ◽  
Author(s):  
John Maesaka
Keyword(s):  
Renal Clearance ◽  
Clearance Study

scholarly journals Pharmacokinetics of Boldine in Control and Mrp2-Deficient Rats

2016 ◽  
pp. S489-S497 ◽  
Author(s):  
J. CERMANOVA ◽  
A. PRASNICKA ◽  
E. DOLEZELOVA ◽  
L. ROZKYDALOVA ◽  
M. HROCH ◽  
...  
Keyword(s):  
Renal Clearance ◽  
Intravenous Administration ◽  
Half Life ◽  
Bolus Dose ◽  
Volume Of Distribution ◽  
Total Clearance ◽  
Lewis Rats ◽  
Biliary Clearance ◽  
Dose Study ◽  
Clearance Study

The aim of the present study was to describe the currently poorly understood pharmacokinetics (PK) of boldine in control rats (LW, Lewis rats), and Mrp2 transporter-deficient rats (TR-). Animals from the LW and TR- groups underwent a bolus dose study with 10 mg/kg of boldine applied either orally or intravenously in order to evaluate the major PK parameters. The TR- rats demonstrated significantly reduced total clearance with prolonged biological half-life (LW 12±4.6 versus TR- 20±4.4 min), decreased volume of distribution (LW 3.2±0.4 l/kg versus TR- 2.4±0.4 l/kg) and reduced bioavailability (LW 7 % versus TR- 4.5 %). Another set of LW and TR- rats were used for a clearance study with continuous intravenous administration of boldine. The LW rats showed that biliary and renal clearance formed less than 2 % of the total clearance of boldine. The treatment of samples with β glucuronidase showed at least a 38 % contribution of conjugation reactions to the overall clearance of boldine. The TR- rats demonstrated reduced biliary clearance of boldine and its conjugates, which was partly compensated by their increased renal clearance. In conclusion, this study presents the PK parameters of boldine and shows the importance of the Mrp2 transporter and conjugation reactions in the elimination of the compound.

scholarly journals Role of WNK4 and kidney-specific WNK1 in mediating the effect of high dietary K+ intake on ROMK channel in the distal convoluted tubule

2018 ◽  
Vol 315 (2) ◽  
pp. F223-F230 ◽  
Author(s):  
Peng Wu ◽  
Zhong-Xiuzi Gao ◽  
Xiao-Tong Su ◽  
David H. Ellison ◽  
Juliette Hadchouel ◽  
...  
Keyword(s):  
Renal Clearance ◽  
Collecting Duct ◽  
Distal Convoluted Tubule ◽  
Cortical Collecting Duct ◽  
Cell Models ◽  
High K ◽  
Cell Recording ◽  
Clearance Study ◽  
Stimulation Of

With-no-lysine kinase 4 (WNK4) and kidney-specific (KS)-WNK1 regulate ROMK (Kir1.1) channels in a variety of cell models. We now explore the role of WNK4 and KS-WNK1 in regulating ROMK in the native distal convoluted tubule (DCT)/connecting tubule (CNT) by measuring tertiapin-Q (TPNQ; ROMK inhibitor)-sensitive K+ currents with whole cell recording. TPNQ-sensitive K+ currents in DCT2/CNT of KS- WNK1−/− and WNK4−/− mice were significantly smaller than that of WT mice. In contrast, the basolateral K+ channels (a Kir4.1/5.1 heterotetramer) in the DCT were not inhibited. Moreover, WNK4−/− mice were hypokalemic, while KS- WNK1−/− mice had normal plasma K+ levels. High K+ (HK) intake significantly increased TPNQ-sensitive K+ currents in DCT2/CNT of WT and WNK4−/− mice but not in KS- WNK1−/− mice. However, TPNQ-sensitive K+ currents in the cortical collecting duct (CCD) were normal not only under control conditions but also significantly increased in response to HK in KS- WNK1−/− mice. This suggests that the deletion of KS-WNK1-induced inhibition of ROMK occurs only in the DCT2/CNT. Renal clearance study further demonstrated that the deletion of KS-WNK1 did not affect the renal ability of K+ excretion under control conditions and during increasing K+ intake. Also, HK intake did not cause hyperkalemia in KS- WNK1−/− mice. We conclude that KS-WNK1 but not WNK4 is required for HK intake-induced stimulation of ROMK activity in DCT2/CNT. However, KS-WNK1 is not essential for HK-induced stimulation of ROMK in the CCD, and the lack of KS-WNK1 does not affect net renal K+ excretion.

scholarly journals Cardiorenal Effects of Long‐Term Phosphodiesterase V Inhibition in Pre–Heart Failure

2022 ◽  
Author(s):  
Scott A. Hubers ◽  
Siu‐Hin Wan ◽  
Fadi W. Adel ◽  
Sherry L. Benike ◽  
John C. Burnett ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Clearance ◽  
Filtration Rate ◽  
Urinary Sodium ◽  
Short Term ◽  
Renal Response ◽  
Clearance Study

Background Phosphodiesterase V (PDEV) is upregulated in heart failure, leading to increased degradation of cGMP and impaired natriuresis. PDEV inhibition improves the renal response to B‐type natriuretic peptide in animal models. We tested the hypothesis that long‐term PDEV inhibition would improve renal function and cardiorenal response after short‐term volume load in subjects with pre–heart failure. Methods and Results A total of 20 subjects with pre–heart failure (defined as an ejection fraction ≤45% without previous diagnosis of heart failure) and renal impairment were randomized in a 2:1 manner to tadalafil or placebo. Baseline echocardiography and renal clearance study were performed, followed by a short‐term saline load and repeated echocardiography and renal clearance study. Subjects then received either tadalafil at a goal dose of 20 mg daily or placebo, and the study day was repeated after 12 weeks. Long‐term tadalafil did not improve glomerular filtration rate (median increase of 2.0 mL/min in the tadalafil group versus 13.5 mL/min in the placebo group; P =0.54). There was no difference in urinary sodium or cGMP excretion with PDEV inhibition following short‐term saline loading. Conclusions Glomerular filtration rate and urinary sodium/cGMP excretion were not significantly different after 12 weeks of tadalafil compared with placebo. These results do not support the use of PDEV inhibition to improve renal response in patients with pre–heart failure. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01970176.

Possible discrimination of Gitelman's syndrome from Bartter's syndrome by renal clearance study: Report of two cases

1995 ◽  
Vol 25 (4) ◽  
pp. 637-641 ◽  
Author(s):  
Tatsuo Tsukamoto ◽  
Tatsuya Kobayashi ◽  
Kunihiko Kawamoto ◽  
Masaaki Fukase ◽  
Kazuo Chihara
Keyword(s):  
Renal Clearance ◽  
Bartter’S Syndrome ◽  
Bartter's Syndrome ◽  
Gitelman's Syndrome ◽  
Study Report ◽  
Clearance Study

scholarly journals Inhibition of AT2R and Bradykinin Type II Receptor (BK2R) Compromises High K + Intake-Induced Renal K + Excretion

Hypertension ◽  
2020 ◽  
Vol 75 (2) ◽  
pp. 439-448
Author(s):  
Li Gu ◽  
JunLin Wang ◽  
Dan-Dan Zhang ◽  
XinXin Meng ◽  
YunHong Zhang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Clearance ◽  
Type Ii ◽  
Angiotensin Ii Receptor ◽  
Male And Female ◽  
Synergistic Activation ◽  
High K ◽  
Expression Activity ◽  
Clearance Study

The inhibition of Type II angiotensin II receptor (AT2R) or BK2R (bradykinin type II receptor) stimulates basolateral Kir4.1/Kir5.1 in the distal convoluted tubule (DCT) and activates thiazide-sensitive NCC (Na-Cl cotransporter). The aim of the present study is to examine the role of AT2R and BK2R in mediating the effect of HK (high dietary K + ) intake on the basolateral K + channels, NCC, and renal K + excretion. Feeding mice (male and female) with HK diet for overnight significantly decreased the basolateral K + conductance, depolarized the DCT membrane, diminished the expression of pNCC (phosphorylated NCC) and tNCC (total NCC), and decreased thiazide-sensitive natriuresis. Overnight HK intake also increased the expression of cleaved ENaC-α and -γ subunits but had no effect on NKCC2 expression. Pretreatment of the mice (male and female) with PD123319 and HOE140 stimulated the expression of tNCC and pNCC, augmented hydrochlorothiazide-induced natriuresis, and increased the negativity of the DCT membrane. The deletion of Kir4.1 not only decreased the NCC activity but also abolished the stimulatory effect of PD123319 and HOE140 perfusion on NCC activity. Moreover, the effect of overnight HK loading on Kir4.1/Kir5.1 in the DCT and NCC expression/activity was compromised in the mice treated with AT2R/BK2R antagonists. Renal clearance study showed that inhibition of AT2R and BK2R impairs renal K + excretion in response to overnight HK loading, and the mice pretreated with PD123319 and HOE140 were hyperkalemic during HK intake. We conclude that synergistic activation of AT2R and BK2R is required for the effect of overnight HK diet on Kir4.1/Kir5.1 in the DCT and NCC activity.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (03) ◽  
pp. 100-103 ◽  
Author(s):  
C. Schümichen ◽  
J. Waiden ◽  
G. Hoffmann
Keyword(s):  
Glomerular Filtration ◽  
Renal Clearance ◽  
Plasma Protein ◽  
Kinetic Data ◽  
Adult Rats ◽  
Compound A ◽  
Extravascular Space ◽  
Tubular Cells ◽  
Glomerular Filtrate ◽  
Kinetics Of

SummaryThe kinetic data of two different 99mTc-Sn-pyrophosphate compounds (compound A and B) were evaluated in non-adult rats. Only compound A concentrated in bone. Both compounds dispersed rapidly in the intravascular as well as the extravascular space. The plasma protein bond of both compounds increased with time after injection and impaired both the renal clearance of both compounds and the bone clearance of compound A. The renal clearance of both compounds was somewhat above that of 5 1Cr-EDTA. It is concluded that compound A and B is mainly excreted by glomerular filtration. About one fourth of the glomerular filtrate of compound B is reabsorbed and accumulated by the tubular cells.

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