Factors limiting renal proximal tubular reabsorption at high glomerular filtration rate

1978 ◽  
Vol 38 (6) ◽  
pp. 573-579 ◽  
Author(s):  
Øystein Mathisen ◽  
Tom Monclair ◽  
Fredrik Kiil
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Tubular Reabsorption ◽  
Proximal Tubular ◽  
Renal Proximal Tubular ◽  
Proximal Tubular Reabsorption

A Micropuncture Study of Proximal Tubular Function after Acute Hydrochlorothiazide Administration to Brattleboro Rats with Diabetes Insipidus

1979 ◽  
Vol 57 (5) ◽  
pp. 427-434 ◽  
Author(s):  
S. J. Walter ◽  
J. F. Laycock ◽  
D. G. Shirley
Keyword(s):  
Glomerular Filtration Rate ◽  
Diabetes Insipidus ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Inhibitory Effect ◽  
Tubular Reabsorption ◽  
Brattleboro Rats ◽  
Fluid Reabsorption ◽  
Proximal Tubular ◽  
Proximal Tubular Reabsorption

1. Renal function in anaesthetized Brattleboro rats with hereditary hypothalamic diabetes insipidus was studied with micropuncture techniques before, and 1–3 h after, a single injection of hydrochlorothiazide. 2. In rats given hydrochlorothiazide and kept in sodium and water balance, total glomerular filtration rate and superficial nephron filtration rate were similar to values in control animals, whereas fractional fluid reabsorption in the proximal tubule (as evidenced by tubular fluid/plasma inulin concentration ratios) was slightly, but significantly, reduced. This suggests that hydrochlorothiazide may have a small direct inhibitory effect on proximal tubular reabsorption. 3. When rats were given hydrochlorothiazide and the resultant extra urinary sodium losses were not replaced, there was a marked antidiuresis. In these animals total glomerular filtration rate was reduced by 23% and superficial nephron filtration rate by 27% when compared with values in control rats. Fractional proximal tubular fluid reabsorption increased significantly whereas absolute proximal fluid reabsorption was unaffected. 4. It is concluded that the reduction in body sodium which follows acute hydrochlorothiazide administration over-rides any inhibitory effect of the drug on proximal tubular reabsorption, and leads instead to an increase in fractional fluid reabsorption at this site. This effect, combined with the fall in glomerular filtration rate, results in a greatly reduced delivery of fluid to the more distal nephron segments, and is probably largely responsible for the observed antidiuresis.

scholarly journals Extracellular microRNA signature in chronic kidney disease

2017 ◽  
Vol 312 (6) ◽  
pp. F982-F991 ◽  
Author(s):  
Jagdeesan Muralidharan ◽  
Ali Ramezani ◽  
Monica Hubal ◽  
Susan Knoblach ◽  
Shashi Shrivastav ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

MicroRNAs (miRNAs) are noncoding RNAs that regulate posttranscriptional gene expression. In this study we characterized the circulating and urinary miRNA pattern associated with reduced glomerular filtration rate, using Affymetrix GeneChip miR 4.0 in 28 patients with chronic kidney disease (CKD). Top miRNA discoveries from the human studies were validated in an Alb/TGFβ mouse model of CKD, and in rat renal proximal tubular cells (NRK52E) exposed to TGFβ1. Plasma and urinary levels of procollagen III N-terminal propeptide and collagen IV were elevated in patients with decreased estimated glomerular filtration rate (eGFR). Expression of 384 urinary and 266 circulatory miRNAs were significantly different between CKD patients with eGFR ≥30 vs. <30 ml·min−1·1.73 m−2. Pathway analysis mapped multiple miRNAs to TGFβ signaling-related mRNA targets. Specifically, Let-7a was significantly downregulated, and miR-130a was significantly upregulated, in urine of patients with eGFR <30; miR-1825 and miR-1281 were upregulated in both urine and plasma of patients with decreased eGFR; and miR-423 was significantly downregulated in plasma of patients with decreased eGFR. miRNA expression in urine and plasma of Alb/TGFβ mice generally resembled and confirmed most, although not all, of the observations from the human studies. In response to TGFβ1 exposure, rat renal proximal tubular cells overexpressed miR-1825 and downregulated miR-423. Thus, miRNA are associated with kidney fibrosis, and specific urinary and plasma miRNA profile may have diagnostic and prognostic utility in CKD.

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 P27 The juvenile pig as animal model for unraveling renal drug elimination processes in children

2019 ◽  
Vol 104 (6) ◽  
pp. e28.1-e28
Author(s):  
L Dhondt ◽  
S Croubels ◽  
P De Paepe ◽  
P De Cock ◽  
M Devreese
Keyword(s):  
Animal Model ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Tubular Secretion ◽  
Tubular Reabsorption ◽  
Drug Elimination ◽  
Renal Drug Elimination

BackgroundOver the years pigs were promoted as potential animal model for humans due to their high degree of anatomical and physiological similarities with humans. Gasthuys et al. demonstrated that the maturation of the kidney function in terms of the glomerular filtration rate (GFR) in growing pigs was comparable to humans, but no data are currently available on renal plasma flow, renal tubular secretion and reabsorption.1 The aim of this pilot study was to unravel the contribution of distinct renal elimination processes in juvenile pigs and to compare with reported human values.MethodsEight seven-week-old pigs were intravenously administered a single bolus of a cocktail of following renal markers: iohexol (64.7 mg/kg body weight (BW), GFR), para-aminohippuric acid (PAH, 10 mg/kg BW, effective renal plasma flow (ERPF) and anion secretion), pindolol (0.05 mg/kg BW, cation secretion) and fluconazole (0.5 mg/kg, tubular reabsorption). Plasma and urinary concentrations were determined for PAH, pindolol and fluconazole at several time points. Only plasma concentrations were assessed for iohexol. PK modelling was performed with Phoenix® WinNonlin®.ResultsThe clearance of iohexol was 97.9 ± 16.1 ml/min/m² (mean ± SD). The ERPF, calculated as the renal clearance of PAH, was 9.5 ± 2.1 ml/min/kg. These GFR and ERPF values are approximately a factor 1.3 higher than the values observed in humans, namely 63.5–75.0 mL/min/m² and 6.5 ± 2.0 mL/min/kg.2,3 The net tubular secretion of PAH was 5.4 ± 1.8 mL/min/kg, which was comparable with the values obtained in humans (5.0 ± 1.8 mL/min/kg).3 Results for cation secretion and tubular reabsorption are not yet available (to be presented at the congress).ConclusionThe net tubular secretion of PAH was comparable between the juvenile pigs and humans. The GFR and ERPF were generally a factor 1.3 higher in juvenile pigs compared to humans.ReferencesGasthuys E., et al., Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research. Frontiers in Pharmacology 2017. 8.Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatric Nephrology 2007;22(11):1839–1848.Gross AS, et al., Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol. British Journal of Clinical Pharmacology 2001. 51(6):547–555.Disclosure(s)This study was funded by the Special Research Fund of Ghent University (BOF16/DOC/285).

MAXIMUM TUBULAR REABSORPTION CAPACITY OF GLUCOSE IN DIABETES MELLITUS

1965 ◽  
Vol 50 (1) ◽  
pp. 79-94 ◽  
Author(s):  
A. Vitelli ◽  
C. Cattaneo ◽  
P. F. Martini
Keyword(s):  
Diabetes Mellitus ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Vascular Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Normal Subjects ◽  
Tubular Reabsorption ◽  
Functional Changes ◽  
Two Factors

ABSTRACT The glomerular filtration rate (GFR) and maximum tubular reabsorption of glucose (TmG) were measured in 24 cases of diabetes mellitus. The patients, who were of different ages, varied with regard to the severity and duration of the disease and 11 patients showed clinical and functional evidence of vascular disease. The GFR and TmG were diminished in almost 50 per cent of cases, and the diminution of the two factors was closely correlated. The incidence of these renal functional changes was almost the same in the group of diabetics with vascular disease as in the group without complications. The GFR and TmG were not correlated with the age of the patients or with the severity of diabetes, though these factors were to some extent correlated with the duration of the disease. No relationship was observed between the incidence of impairment of the renal function and sex. The examinations carried out in this series of cases as well as in a number of normal subjects suggest various considerations with regard to the value of the various techniques which have been proposed for the measurement of the TmG.

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