The Renal Response to Blood Volume Expansion in the Rat: Proximal Tubular Function and Urinary Excretion

1971 ◽  
Vol 49 (6) ◽  
pp. 525-535 ◽  
Author(s):  
H. Sonnenberg
Keyword(s):  
Blood Volume ◽  
Filtration Rate ◽  
Renal Excretion ◽  
Tubular Function ◽  
Volume Increase ◽  
Blood Volume Expansion ◽  
Single Nephron ◽  
Proximal Tubular ◽  
Proximal Tubular Function ◽  
Proximal Convolution

Chronically salt- and deoxycorticosterone-acetate-loaded (DOCA) rats and chronically salt-deficient (NaD) rats were infused with blood, and consequent changes in renal excretion of water and electrolytes were compared with simultaneous alterations in proximal tubular function. During the period of intravascular expansion maintained by reinfusion of urine, diuresis and natriuresis, significant compared to control excretion, were seen in both groups. Although absolute levels of diuresis were not statistically different, DOCA rats excreted more sodium and less potassium than NaD rats; total cation excretion (Na+K) was comparable. A 10% reduction in proximal fractional reabsorption occurred in both series, associated, however, with large similar increases in single nephron filtration rate, so that absolute rates of proximal fluid reabsorption were actually increased. No correlation was found between changes in fractional or absolute reabsorption and renal excretion. Since vascular expansion results in similar alterations of filtration rate and proximal transport in both groups, the different ratios of excretion of sodium and potassium must be due to differences in tubular function at sites distal to the proximal convolution. The lack of direct correlation between proximal function and magnitude of renal excretion in these experiments further suggests that the excretory response to blood volume increase is determined ultimately by tubular mechanisms located in the distal part of the nephron.

Proximal tubular function in transgenic mice overexpressing atrial natriuretic factor

1994 ◽  
Vol 72 (10) ◽  
pp. 1168-1170 ◽  
Author(s):  
H. Sonnenberg ◽  
U. Honrath ◽  
C. K. Chong ◽  
L. J. Field ◽  
A. T. Veress
Keyword(s):  
Atrial Natriuretic Factor ◽  
Filtration Rate ◽  
Tubular Function ◽  
Nephron Filtration Rate ◽  
Natriuretic Factor ◽  
Single Nephron Filtration Rate ◽  
Single Nephron ◽  
Proximal Tubular ◽  
Proximal Tubular Function ◽  
Atrial Natriuretic

A transgenic mouse model in which atrial natriuretic factor (ANF) expression is targeted to the liver was used to study intrarenal adjustments to the chronically elevated hormone level. Such animals, designated TTR-ANF, are characterized by reduced arterial blood pressure but similar sodium excretion compared with nontransgenic siblings. Proximal tubular micro-puncture gave the following results: single-nephron filtration rate = 12.7 ± 1.1 vs. 15.6 ± 1.9 nL/min (TTR-ANF versus nontransgenic, ns); end-proximal tubular fluid/plasma concentration ratio of inulin = 1.93 ± 0.09 vs. 1.97 ± 0.15 (ns); fractional reabsorption of sodium = 45.5 ± 2.8 vs. 46.0 ± 3.8% (ns); fractional reabsorption of chloride = 33.6 ± 3.3 vs. 32.4 ± 4.1% (ns). These data indicate that life-long elevation of plasma ANF concentration was not associated with significant alteration in single-nephron filtration rate and proximal tubular function. We conclude that compensatory anti-natriuretic mechanisms, localized downstream from the proximal tubule, can prevent ANF natriuresis.Key words: micropuncture, single-nephron filtration rate, sodium chloride reabsorption.

Effect of substance P on proximal tubular reabsorption in the rat

1976 ◽  
Vol 230 (6) ◽  
pp. 1662-1667 ◽  
Author(s):  
WJ Arendshorst ◽  
MA Cook ◽  
IH Mills
Keyword(s):  
Substance P ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Sodium Concentration ◽  
Control Series ◽  
Time Period ◽  
Single Nephron ◽  
Proximal Tubular ◽  
Proximal Convolution

Micropuncture and clearance techniques were used simultaneously to determine the effect of substance P on proximal tubular and overall renal function in anesthetized rats. This polypeptide, infused in saline at 50 pg/min into the abdominal aorta above the renal arteries, produced increases in urine flow, 2.7-3.7 mul/min.g kidney wt (P is less than 0.005); urinary sodium concentration, 32-61 meq/liter (P is less than 0.01); and sodium excretion, 89-223 neq/min (P is less than 0.005). Tubular fluid to plasma inulin concentration ratio measured in the last accessible proximal convolution fell from 2.21 to 1.80 (P is less than 0.001), and thus fractional reabsorption was reduced from 54 to 44% (P is less than 0.001). Absolute reabsorption by the proximal convoluted tubule was also reduced 15.5-12.5 nl/min (P is less than 0.025). In a control series of animals, saline alone infused at the same rate did not produce any statistically significant changes in the measured parameters over the same time period. The intrerenal mechanism responsible for the reduction in proximal reabsorption appears to be a tubular one since no consistent or significant changes were observed in kidney or single nephron glomerular filtration rate, renal plasma flow, or intrarenal hydrostatic pressures. No evidence was found to indicate redistribution of filtration rate, or plasma flow, or a reduction in filtration fraction.

scholarly journals Renal effects of the serine protease inhibitor aprotinin in healthy conscious mice

2021 ◽  
Author(s):  
Stefan Wörner ◽  
Bernhard N. Bohnert ◽  
Matthias Wörn ◽  
Mengyun Xiao ◽  
Andrea Janessa ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Kidney Injury ◽  
Serine Protease Inhibitor ◽  
Tubular Function ◽  
Proteolytic Activation ◽  
Salt Diet ◽  
Low Salt ◽  
Proximal Tubular ◽  
Proximal Tubular Function

AbstractTreatment with aprotinin, a broad-spectrum serine protease inhibitor with a molecular weight of 6512 Da, was associated with acute kidney injury, which was one of the reasons for withdrawal from the market in 2007. Inhibition of renal serine proteases regulating the epithelial sodium channel ENaC could be a possible mechanism. Herein, we studied the effect of aprotinin in wild-type 129S1/SvImJ mice on sodium handling, tubular function, and integrity under a control and low-salt diet. Mice were studied in metabolic cages, and aprotinin was delivered by subcutaneously implanted sustained release pellets (2 mg/day over 10 days). Mean urinary aprotinin concentration ranged between 642 ± 135 (day 2) and 127 ± 16 (day 8) µg/mL . Aprotinin caused impaired sodium preservation under a low-salt diet while stimulating excessive hyperaldosteronism and unexpectedly, proteolytic activation of ENaC. Aprotinin inhibited proximal tubular function leading to glucosuria and proteinuria. Plasma urea and cystatin C concentration increased significantly under aprotinin treatment. Kidney tissues from aprotinin-treated mice showed accumulation of intracellular aprotinin and expression of the kidney injury molecule 1 (KIM-1). In electron microscopy, electron-dense deposits were observed. There was no evidence for kidney injury in mice treated with a lower aprotinin dose (0.5 mg/day). In conclusion, high doses of aprotinin exert nephrotoxic effects by accumulation in the tubular system of healthy mice, leading to inhibition of proximal tubular function and counterregulatory stimulation of ENaC-mediated sodium transport.

scholarly journals Detailed investigations of proximal tubular function in Imerslund-Gräsbeck syndrome

2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Tina Storm ◽  
Christina Zeitz ◽  
Olivier Cases ◽  
Sabine Amsellem ◽  
Pierre J Verroust ◽  
...  
Keyword(s):  
Tubular Function ◽  
Proximal Tubular ◽  
Proximal Tubular Function

Cardiac output, GFR, and renal excretion rates during maintained volume load in rats

1978 ◽  
Vol 235 (6) ◽  
pp. H670-H676 ◽  
Author(s):  
U. Ackermann
Keyword(s):  
Cardiac Output ◽  
Blood Volume ◽  
Renal Excretion ◽  
Venous Pressure ◽  
Circulating Blood Volume ◽  
Reservoir Volume ◽  
Volume Load ◽  
Blood Volume Expansion ◽  
Highly Correlated ◽  
Excretion Rates

The correlation among cardiac output (CO), glomerular filtration rate (GFR), fractional tubular sodium rejection (TFRNa), and renal excretion rates of water and salt was investigated during ischemic blood volume expansion in rats. Initially circulating blood volume was equilibrated isovolemically with a reservoir volume of 6% albumin solution equal to one-third the estimated blood volume. Later the equilibrated reservoir contents were infused intravenously. CO was measured by thermodilution, GFR by inulin clearance. Significant linear correlations existed between GFR and the rates of urine flow (r = 0.90), sodium excretion (r = 0.75) and potassium excretion (r = 0.76) that prevailed 5--10 min after a given GFR change. The increased GFR was highly correlated with CO (r = 0.94), probably correlated with mean central venous pressure (r = 0.45), but not correlated with mean abdominal aortic blood pressure. The correlation between CO and time-delayed (5--10 min) TRFNa was also highly significant (r = 0.98). The saluresis appears to have been caused initially by increased tubular load and subsequently by decreased absolute tubular reabsorption.

Feedback mediation of SNGFR autoregulation in hydropenic and DOCA- and salt-loaded rats

1979 ◽  
Vol 237 (1) ◽  
pp. F63-F74 ◽  
Author(s):  
L. C. Moore ◽  
J. Schnermann ◽  
S. Yarimizu
Keyword(s):  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Tubuloglomerular Feedback ◽  
Single Nephron ◽  
Proximal Tubular

Tubuloglomerular feedback (TGF) mediation of autoregulation was investigated by measuring the response of single nephron glomerular filtration rate (SNGFR) to changes in arterial pressure (AP) following acute or chronic TGF inhibition. In hydropenic rats with intact TGF, distal SNGFR was 25.0 +/- 1.2 (SE) and 23.9 +/- 1.4 nl/min at AP of 111 and 135 mmHg, respectively. In the same 20 nephrons during proximal tubular microinfusion of furosemide, distal SNGFR was 23.6 +/- 1.4 (n = 16) and 29.7 +/- 1.4 nl/min (n = 20) (P less than 0.001, n = 16) at 112 and 133 mmHg. When determined proximally, SNGFR was 25.6 +/- 1.0 and 29.5 +/- 0.9 nl/min (P less than 0.001, n = 31) at 112 and 157 mmHg; kidney GFR increased similarly. These data and the predictions of a GFR model were then used to estimate autoregulatory efficiency. This analysis indicated that partial autoregulation occurred during TGF inhibition. Therefore, TGF is an essential, but probably not the only, mechanism mediating SNGFR autoregulation.

scholarly journals 1962. Renal Outcomes for Participants Taking F/TAF vs. F/TDF for HIV PrEP in the DISCOVER Trial

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S64-S64
Author(s):  
Anthony Mills ◽  
Kimberly Workowski ◽  
Thomas Campbell ◽  
Paul Benson ◽  
Gordon Crofoot ◽  
...  
Keyword(s):  
Renal Function ◽  
Study Drug ◽  
Tubular Function ◽  
Full Cohort ◽  
Renal Outcomes ◽  
Proximal Tubular ◽  
Renal Biomarker ◽  
Proximal Tubular Function ◽  
Tenofovir Alafenamide ◽  
Sex With Men

Abstract Background In the DISCOVER PrEP trial, emtricitabine/tenofovir alafenamide (F/TAF) was noninferior to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV prevention. Here, we report on the renal outcomes of F/TAF and F/TDF among all DISCOVER participants and in those on baseline F/TDF PrEP who were randomized to F/TAF. Methods In total, 5387 men who have sex with men (MSM) and transgender women (TGW) at risk for HIV were randomized 1:1 to receive blinded F/TDF or F/TAF taken once daily (full cohort). Of these, 905 were on F/TDF PrEP at enrollment; of whom, 465 were randomized to F/TAF. Renal function and safety assessments included urinalysis (UA), estimated glomerular filtration rate (eGFRCG), urine protein:creatinine (Cr) ratio (UPCR), markers of proximal tubular function (β2-microglobulin:Cr ratio [β2M:Cr] and retinol-binding protein:Cr ratio [RBP:Cr]) and investigator-reported renal adverse events (AEs). Week 48 data are presented. Results In the full cohort, F/TAF was associated with more favorable changes in eGFRCG, β2M:Cr, and RBP:Cr compared with F/TDF (Table 1). Treatment-emergent proteinuria by UA was more common with F/TDF than F/TAF (24.3% vs. 21.3% P = 0.009), as were treatment-emergent elevations in UPCR >200 mg/g (35 [1.5%] vs. 16 [0.7%], P = 0.005). Compared with F/TDF, participants taking F/TAF had numerically fewer study drug-related renal AEs, severe study drug-related renal AEs, and discontinuations due to renal AEs (Table 2). Proximal renal tubulopathy (Fanconi syndrome) was reported in one participant in the F/TDF arm and none in the F/TAF arm. In participants on F/TDF PrEP at enrollment who were randomized to F/TAF, statistically significant increases in eGFRCG were apparent as early as week 4 (Table 1 and Figure 1), as were decreases in tubular proteinuria (Table 1). Renal biomarker changes in PrEP-naïve participants mirrored those in the full cohort. Conclusion Through 48 weeks, MSM and TGW taking F/TAF for PrEP had significantly better measures of renal function and fewer study-drug-related renal AEs compared with those taking F/TDF; switching from F/TDF to F/TAF was associated with improvements in eGFRCG and tubular function biomarkers. F/TAF for PrEP is effective and has a superior renal safety profile compared with F/TDF. Disclosures All Authors: No reported Disclosures.

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