scholarly journals The intrinsic circadian clock in podocytes controls glomerular filtration rate

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Camille Ansermet ◽  
Gabriel Centeno ◽  
Svetlana Nikolaeva ◽  
Marc P. Maillard ◽  
Sylvain Pradervand ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Circadian Clock ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Transcriptome Profiling ◽  
Circadian Rhythmicity ◽  
Water Excretion ◽  
Key Indicator ◽  
Genes Encoding ◽  
Urine Formation

Abstract Glomerular filtration rate (GFR), or the rate of primary urine formation, is the key indicator of renal function. Studies have demonstrated that GFR exhibits significant circadian rhythmicity and, that these rhythms are disrupted in a number of pathologies. Here, we tested a hypothesis that the circadian rhythm of GFR is driven by intrinsic glomerular circadian clocks. We used mice lacking the circadian clock protein BMAL1 specifically in podocytes, highly specialized glomerular cells critically involved in the process of glomerular filtration (Bmal1lox/lox/Nphs2-rtTA/LC1 or, cKO mice). Circadian transcriptome profiling performed on isolated glomeruli from control and cKO mice revealed that the circadian clock controls expression of multiple genes encoding proteins essential for normal podocyte function. Direct assessment of glomerular filtration by inulin clearance demonstrated that circadian rhythmicity in GFR was lost in cKO mice that displayed an ultradian rhythm of GFR with 12-h periodicity. The disruption of circadian rhythmicity in GFR was paralleled by significant changes in circadian patterns of urinary creatinine, sodium, potassium and water excretion and by alteration in the diurnal pattern of plasma aldosterone levels. Collectively, these results indicate that the intrinsic circadian clock in podocytes participate in circadian rhythmicity of GFR.

Sodium and Water Excretion in Nephrotic Patients: Effects of Changes in Renal Haemodynamics

1990 ◽  
Vol 79 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Michael Allon ◽  
Charles B. Pasque ◽  
Mariano Rodriguez
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Sodium Reabsorption ◽  
Plasma Volume Expansion ◽  
Water Excretion ◽  
Significant Change

1. Eight nephrotic patients were studied in order to evaluate the effects of acute changes in renal plasma flow and glomerular filtration rate on renal solute and water handling, in the absence of plasma volume expansion. 2. The subjects were studied first after the administration of captopril, a manoeuvre that increased renal plasma flow without a significant change in glomerular filtration rate, and a second time after receiving combined therapy with captopril and ibuprofen, a manoeuvre that decreased glomerular filtration rate without a significant change in renal plasma flow. 3. After captopril therapy, despite the increase in renal plasma flow, there was no significant change in proximal sodium reabsorption (as estimated from fractional lithium reabsorption), urine volume or urine osmolality. 4. The decrease in glomerular filtration rate observed after the administration of captopril plus ibuprofen was associated with decreases in fractional excretion of sodium and urine volume, and an increase in urine osmolality. The changes in these parameters of tubular function were proportionate to the changes in glomerular filtration rate. Fractional proximal sodium reabsorption increased substantially. 5. These observations suggest that, in the absence of plasma volume expansion, an increase in renal plasma flow does not increase sodium or water excretion by the nephrotic kidney. Moreover, during acute decreases in glomerular filtration rate, glomerulotubular balance appears to be disrupted, resulting in disproportionately high rates of proximal tubule sodium reabsorption.

The Effect of Glucagon on Glomerular Filtration Rate in Dogs During Reduction of Renal Blood Flow

1975 ◽  
Vol 53 (4) ◽  
pp. 660-668 ◽  
Author(s):  
Mortimer Levy
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Acute Tubular Necrosis ◽  
Filtration Rate ◽  
Renal Perfusion ◽  
Beneficial Effects ◽  
Tubular Necrosis ◽  
Arterial Blood ◽  
Urine Formation

Glucagon in small intravenous (i.v.) doses markedly increases glomerular filtration rate (GFR) in normal anesthetized dogs. In this study, the effects of glucagon 5 μg/min (i.v.) on renal hemodynamics was tested in four canine models of acute pre-renal failure (hemorrhage, barbiturate overdose; renal arterial clamping and renal arterial infusions of noradrenaline) and in a model of unilateral acute tubular necrosis at 4 h and 6–7 days following completion of the ischemic insult. Following hemorrhage and barbiturate excess, with arterial blood pressure maintained at 65–70 mm Hg, whole-kidney GFR and clearance rate of p-aminohippurate decreased by 50–70%. During this reduction of perfusion pressure, the subsequent infusion of glucagon increased GFR by 90–130%. In models where arterial pressure was normal during the period of ischemia (clamping and noradrenaline infusion), not only did glucagon significantly increase renal perfusion, but the ischemic kidney proved to be far more sensitive to the hemodynamic effects of glucagon (ΔGFR = 120–160%) than the contralateral control (ΔGFR = 30–40%). In three dogs completely anuric following renal arterial clamping, glucagon was able to improve blood flow and restart urine formation. Glucagon, but not dopamine, was able to simulate the beneficial effects of hypertonic mannitol on renal function in dogs with hemorrhagic hypotension. Glucagon was without effect in established acute tubular necrosis. This study, therefore, indicates that, during renal ischemia, glucagon may be quite effective in preserving urine output and perfusion of the kidneys.

Localization of alpha 2-adrenoceptor-mediated increase in renal Na+, K+, and water excretion

1987 ◽  
Vol 252 (6) ◽  
pp. F1016-F1021 ◽  
Author(s):  
B. Stanton ◽  
E. Puglisi ◽  
M. Gellai
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Water Transport ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Urine Osmolality ◽  
Water Excretion ◽  
Arterial Blood ◽  
Adrenoceptor Agonist

Free-flow micropuncture and clearance studies were conducted in male Sprague-Dawley rats to investigate the effects of alpha 2-adrenoceptor stimulation on Na+, K+, and water transport along the nephron. Intravenous infusion of the selective alpha 2-adrenoceptor agonist B-HT 933 at 1 mg X kg-1 X h-1 increased urinary flow rate from 16.2 +/- 3.6 to 84.8 +/- 11.9 microliter/min, fractional excretion of Na+ from 1.36 +/- 0.31 to 3.57 +/- 0.52%, and fractional excretion of K+ from 26.9 +/- 3.0 to 42.3 +/- 2.2%, The diuresis, saluresis, and kaliuresis were not the result of increases in glomerular filtration rate or mean arterial blood pressure. Urine osmolality decreased from 1,126 +/- 177 to 325 +/- 33 mosmol/kg water and in 8 of the 11 animals studied B-HT 933 decreased urine osmolality to hyposmotic levels, suggesting a possible interaction between the alpha 2-adrenoceptor agonist and vasopressin. The alpha 2-adrenoceptor antagonist yohimbine (0.25/mg bolus, iv) inhibited the diuresis, saliuresis, and kaliuresis. In micropuncture studies, B-HT 933 was without effect on single-nephron glomerular filtration rate or on Na+, K+, and water transport along the superficial proximal tubule, loop of Henle, or distal tubule. Thus stimulation of alpha 2-adrenoceptors increases Na+, K+, and water excretion by inhibiting tubule reabsorption of these substances at nephron sites beyond the superficial distal tubule, most likely by the collecting tubule.

Abstract 386: A Novel Aquaretic and Glomerular Filtration Rate Enhancing Peptide Without Vascular Vasodilatory Actions in Experimental CHF.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Horng H Chen ◽  
ShuChong Pan ◽  
John C Burnett ◽  
Robert D Simari
Keyword(s):  
Blood Pressure ◽  
Amino Acids ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Urinary Sodium Excretion ◽  
Sodium Concentration ◽  
Water Excretion ◽  
Arterial Blood ◽  
Change In Mean

BACKGROUND: BNP is a cardiac peptide with vasodilatory, natriuretic and diuretic properties. Recent studies have suggested that its vasodilatory hypotensive properties may limit the renal actions of BNP, especially in patients with borderline low blood pressure. We have recently identified an alternatively spliced transcript for BNP (ASBNP) that includes a unique and distinct longer carboxyl-terminus consisting of 34 amino acids. Based upon preliminary studies, we generated a truncated form (ASBNP2.1) that contains the first 16 amino acids of the C-terminal of ASBNP. METHODS: We determined the cardiorenal and humoral actions of intravenous infusion of ASBNP2.1 at 2 pmol/Kg/min, 10 pmol/Kg/min and 100 pmol/Kg /min in 10 dogs with rapid ventricular pacing induced overt CHF (240 bpm for 10 days). * p<0.05 RESULTS: IV infusion of ASBNP 2.1 increased aquaresis (from 0.19±0.04 to 0.32±0.07, 0.46±0.11 and 0.39±0.09 ml/min*) without a significant change in urinary sodium excretion. Importantly, ASBNP 2.1 enhanced glomerular filtration rate (GFR), from 31±4 to 47±8, 69±10 and 56±9 ml/min*. These renal actions were associated with increases in urinary BNP*, ANP* and cGMP* excretion. BNP 2.1 did not have any systemic vasodilatory action resulting in no change in mean arterial blood pressure or cardiac-filling pressures even at the highest dose. There was not change in serum sodium concentration. CONCLUSION: We report for the first time that this novel peptide based upon ASBNP has potent aquaretic and GFR enhancing actions without the vasodilatory hypotensive properties in an experimental model of overt CHF. The lack of vasodilatation but with renal actions also suggest that the C-terminus plays a key role in the vascular actions of this peptide offering new insights into vascular-renal structure function of BNP and related peptides. This renal specific peptide may have potential therapeutic benefit in states of renal dysfunction with volume overload to enhance GFR and water excretion without the detrimental side effect of hypotension.

Acute effect of changes in renal arterial pressure and sympathetic blockade on kidney function

1959 ◽  
Vol 197 (3) ◽  
pp. 595-600 ◽  
Author(s):  
Jimmy B. Langston ◽  
Arthur C. Guyton ◽  
William J. Gillespie
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Spinal Anesthesia ◽  
Renal Blood Flow ◽  
Kidney Function ◽  
Filtration Rate ◽  
Sympathetic Blockade ◽  
Urine Formation

The effect of varying the renal arterial pressure on kidney function has been studied before and after complete spinal anesthesia. It is concluded that an increase in renal arterial pressure between 60 and 300 mm Hg always results in an increase in renal blood flow, glomerular filtration rate and urine formation, and that filtration rate and urinary output are related to renal arterial pressure in a linear fashion at pressures above 120 mm Hg. Sympathetic blockade, accomplished by complete spinal anesthesia, resulted in a higher rate of urine formation and renal blood flow but not of glomerular filtration rate at each level of arterial pressure than before the spinal anesthesia was administered. Since the sympathetic blockade was not followed by an increase in glomerular filtration rate, it is concluded that the diuresis which followed this blockade resulted from a decrease in reabsorption of glomerular filtrate.

Effects of glucagon on glomerular filtration rate and urea and water excretion

1992 ◽  
Vol 263 (1) ◽  
pp. F24-F36 ◽  
Author(s):  
M. Ahloulay ◽  
N. Bouby ◽  
F. Machet ◽  
M. Kubrusly ◽  
C. Coutaud ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Flow Rate ◽  
Filtration Rate ◽  
Urine Flow ◽  
Urine Flow Rate ◽  
Urea Synthesis ◽  
Physiological Level ◽  
Water Excretion ◽  
Urea Excretion

Clearance experiments were performed in anesthetized male Wistar rats to reevaluate the renal effects of glucagon (Gluc) on glomerular filtration rate (GFR) and solute and water excretion. After an 80-min control period, these effects were evaluated in the last 80 min of a 2-h intravenous Gluc infusion. Gluc induced significant increases in GFR (+20%), urine flow rate (+150%), free water reabsorption (+50%), urea synthesis and urea excretion (+66%), and nonurea solute excretion (+67%). In addition, fractional urea excretion (FEurea) increased by 43% (P less than 0.01). Additional experiments showed that increases in either urea excretion or urine flow rate (induced by appropriate infusion of urea or half-dilute saline), similar to those seen after Gluc, could not account for the increased FEurea. All significant effects of Gluc were also observed during infusion of antidiuretic hormone or during water diuresis. The tubular effects of Gluc could be explained by a reduction in proximal reabsorption. The dose of Gluc required to induce all the effects described above was 12 ng.min-1.100 g body wt-1, a dose producing an approximately 10-fold supraphysiological peripheral plasma concentration but a “physiological” level for the liver. Infusion of 1.2 ng induced almost no change in renal function, and infusion of 120 ng induced no greater effects than 12 ng. These results suggest 1) that Gluc, a hormone liberated after protein ingestion, exerts coordinated effects on liver and kidney to increase simultaneously urea synthesis and excretion and to promote water conservation and 2) that these effects could, at least in part, be indirect and depend on the Gluc-induced stimulation of hepatocyte metabolism.

Changes in inorganic phosphate excretion induced by renal arterial infusion of calcium

1963 ◽  
Vol 205 (5) ◽  
pp. 1025-1032 ◽  
Author(s):  
A. R. Lavender ◽  
Theodore N. Pullman
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Tubular Reabsorption ◽  
Water Excretion ◽  
Phosphate Excretion ◽  
Constant Rate ◽  
Calcium Infusion ◽  
Inorganic Phosphate Excretion

Calcium chloride in varying concentrations was infused at a slow and constant rate into the renal artery of one kidney in the dog. The opposite kidney served as a control. In 20 experiments, the mean glomerular filtration rate and effective renal plasma flow diminished in the infused relative to the noninfused kidneys. Mean phosphate excretion was decreased in the infused relative to the control kidneys by both a fall in filtered phosphate and a rise in the net tubular reabsorption of phosphate. Mean calcium, sodium, and water excretion did not change in the infused relative to the control kidneys during calcium infusion. The data indicate that hypercalcemia acts directly on the kidney to decrease phosphate excretion by decreasing glomerular filtration rate and increasing net tubular reabsorption of phosphate.

scholarly journals The Intrinsic Circadian Clock in Podocytes Controls the Glomerular Filtration Rate

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Camille Ansermet ◽  
Gabriel Centeno ◽  
Sylvain Pradervand ◽  
Marc Maillard ◽  
Dmitri Firsov
Keyword(s):  
Glomerular Filtration Rate ◽  
Circadian Clock ◽  
Glomerular Filtration ◽  
Filtration Rate
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