Aldosterone-dependent and -independent regulation of Na+ and K+ excretion and ENaC in mouse kidneys

We investigated the regulation of Na+ and K+ excretion and the epithelial Na+ channel (ENaC) in mice lacking the gene for aldosterone synthase (AS) using clearance methods to assess excretion and electrophysiology and Western blot analysis to test for ENaC activity and processing. After 1 day of dietary Na+ restriction, AS−/− mice lost more Na+ in the urine than AS+/+ mice did. After 1 wk on this diet, both genotypes strongly reduced urinary Na+ excretion, but creatinine clearance decreased only in AS−/− mice. Only AS+/+ animals exhibited increased ENaC function, assessed as amiloride-sensitive whole cell currents in collecting ducts or cleavage of αENaC and γENaC in Western blots. To assess the role of aldosterone in the excretion of a K+ load, animals were fasted overnight and refed with high-K+ or low-K+ diets for 5 h. Both AS+/+ and AS−/− mice excreted a large amount of K+ during this period. In both phenotypes the excretion was benzamil sensitive, indicating increased K+ secretion coupled to ENaC-dependent Na+ reabsorption. However, the increase in plasma K+ under these conditions was much larger in AS−/− animals than in AS+/+ animals. In both groups, cleavage of αENaC and γENaC increased. However, Na+ current measured ex vivo in connecting tubules was enhanced only in AS+/+ mice. We conclude that in the absence of aldosterone, mice can conserve Na+ without ENaC activation but at the expense of diminished glomerular filtration rate. Excretion of a K+ load can be accomplished through aldosterone-independent upregulation of ENaC, but aldosterone is required to excrete the excess K+ without hyperkalemia.

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Serum cystatin is not a marker of glomerular filtration rate in pregnancy

Obstetric Medicine ◽

10.1258/om.2009.090019 ◽

2009 ◽

Vol 2 (3) ◽

pp. 121-122 ◽

Cited By ~ 2

Author(s):

Kate Bramham ◽

David Makanjuola ◽

Wael Hussein ◽

Debra Cafful ◽

Hassan Shehata

Keyword(s):

Glomerular Filtration Rate ◽

Observational Study ◽

Glomerular Filtration ◽

Filtration Rate ◽

Prospective Observational Study ◽

Second Trimester ◽

Third Trimester ◽

Serum Cystatin ◽

In Pregnancy

The role of cystatin C (Cys-C) as a marker of glomerular filtration rate (GFR) in pregnancy is undetermined. Measurements of Cys-C and creatinine (Cr) were taken at 14–17+6, 18–23+6, 27–31+6 weeks' gestation, at delivery and 2–6 weeks postpartum in a prospective observational study of 27 women. There was no difference between Cys-C levels in early and late second trimester, but they were significantly higher in early third trimester ( P < 0.001) than second trimester, despite no concurrent increase in Cr. Cys-C was also significantly higher at delivery than at all other times in pregnancy ( P < 0.001) and fell to postpartum values higher than second trimester measurements ( P < 0.01), but lower than delivery ( P<0.001). In conclusion, changes in Cys-C may be influenced by pregnancy-related changes in glomerular filtration and therefore we would advise against their use as a marker of GFR in pregnancy.

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MO190NORMATIVE DATA FOR GLOMERULAR FILTRATION RATE IN HEALTHY KIDNEY DONOR POPULATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.0068 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Ashish Bhoyar ◽

Vinant Bhargava ◽

Ashwani Gupta ◽

Anurag Gupta ◽

Vaibhav Tiwari ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Serum Creatinine ◽

Creatinine Clearance ◽

Filtration Rate ◽

Age Groups ◽

Kidney Donor ◽

Urinary Creatinine ◽

Donor Population ◽

Sample Method ◽

Clearance Methods

Abstract Background and Aims Glomerular filtration rate (GFR) is estimated traditionally from 24-hour urinary creatinine clearance. Creatinine is mainly filtered by glomerulus. The collection of 24-hour urinary sample is a difficult task with many patients fail to collect all the urine samples. As measuring GFR is cumbersome, expensive, and not easily available in all centers, various equations are developed for estimating GFR from creatinine like MDRD, CKD EPI creatinine. GFR obtained from serum creatinine shows wide variation as muscle mass and dietary protein intake are important determinants of serum creatinine concentration. Literature shows very few studies with GFR estimation with reference to age in Indian population. Hence, this study is planned to develop age specific nomogram for GFR in healthy kidney donor population as well as to study agreement between GFR obtained by 99m Tc DTPA three sample method and GFR estimated by 24-hour urinary creatinine. The aim of this stidy was to develop age-specific nomogram GFR in healthy kidney donor population and to study the agreement between the GFR measured by Technetium-99m diethylene triamine pentaacetic acid (99m Tc DTPA) and 24-hour urinary creatinine method. Method This study was conducted at Sir Ganga Ram hospital, New Delhi. All healthy individuals aged more than 20 years and less than 65 years, undergoing evaluation as prospective kidney donor at our hospital were the part of this study. GFR was measured by 99m Tc DTPA clearance using 3 sample method. GFR measured by DTPA method was used to develop nomogram. Creatinine Clearance was calculated from 24-hour urinary creatinine by formula U x V/P where, U is urinary creatinine level, P is plasma creatinine level and V is total volume of urine. Nomogram was developed with respect to these 3 Age groups; namely, 20 to 40 years, 40 to 50 years and 50 to 65 years Results Total 100 kidney donors were included in this study. Enrolled subjects were divided into 3 age groups; 20 to 40 years (n=28), 40 to 50 years (n=46) and 50 to 65 years (n=26). Majority of the donors were females (n=80). The agreement between GFR obtained by 99m Tc DTPA and 24-hour urinary creatinine clearance methods was 92.6 vs. 94 ml/min, 80.4 vs. 76 ml/min and 76.3 vs. 70 ml/min in respective age groups. Conclusion In the younger age group (20 to 40 years), there is better agreement in GFR measured by 99m Tc DTPA method and 24-hour urinary creatinine clearance methods.

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Increased tubuloglomerular feedback activity in Milan hypertensive rats

AJP Renal Physiology ◽

10.1152/ajprenal.1986.250.6.f967 ◽

1986 ◽

Vol 250 (6) ◽

pp. F967-F974 ◽

Cited By ~ 5

Author(s):

U. Boberg ◽

A. E. Persson

Keyword(s):

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Tubuloglomerular Feedback ◽

Spontaneously Hypertensive ◽

Arterial Blood ◽

Single Nephron ◽

Flow Pressure ◽

Normotensive Strain

Studies of whole-kidney function and micropuncture measurements in superficial nephrons were performed to investigate the role of the tubuloglomerular feedback (TGF) in the excretion of salt and water in hydropenic and volume-expanded rats of the spontaneously hypertensive Milan strain (MHS). The rats were 3.5-5 and 5-7 wk old, and age-matched animals from the Milan normotensive strain (MNS) served as controls. There was no difference in mean arterial blood pressure (Pa) between the 3.5- to 5-wk-old prehypertensive MHS (MHSp) and MNS rats, but the glomerular filtration rate (GFR) was higher in MHSp than in MNS [1.35 vs. 0.80 ml X min-1 X g kidney wt (KW)-1, P less than 0.01]. The distal single-nephron glomerular filtration rate (SNGFR) was also higher in MHSp than in MNS (28.6 vs. 20.2 nl X min-1 X g KW-1, P less than 0.05). TGF was determined from both stop-flow pressure response and proximal and distal SNGFR. It was found that MHSp exhibited essentially no TGF response. During development of hypertension 5- to 7-wk-old MHS (MHSd) had a higher Pa than MNS (120 vs. 98 mmHg, P less than 0.01). Normally GFR and SNGFR increase with age, and such was the case with MNS (0.8 to 1.02 ml X min-1 X g KW-1 and 20.2 to 23.4 nl X min-1 X g KW-1), but in MHSd there was a decrease in both GFR and SNGFR with age (1.35 to 1.10 ml X min-1 X g KW-1 and 28.3 to 18.3 nl X min-1 X g KW-1).(ABSTRACT TRUNCATED AT 250 WORDS)

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Renal nerves and cation excretion after acute reduction in functioning renal mass in the rat

AJP Renal Physiology ◽

10.1152/ajprenal.1984.246.3.f260 ◽

1984 ◽

Vol 246 (3) ◽

pp. F260-F265 ◽

Cited By ~ 4

Author(s):

J. Ribstein ◽

M. H. Humphreys

Keyword(s):

Glomerular Filtration Rate ◽

Mean Arterial Pressure ◽

Renal Mass ◽

Filtration Rate ◽

Renal Nerves ◽

Potassium Excretion ◽

Contralateral Kidney ◽

Efferent Limb ◽

Ureteral Occlusion

We evaluated the role of the renal nerves in the increased cation excretion by the contralateral kidney after acute unilateral nephrectomy (AUN) or unilateral ureteral occlusion (UUO) in anesthetized rats. Both AUN and UUO caused large increases in sodium (UNaV) and potassium excretion (UKV) by the control kidney without change in glomerular filtration rate or mean arterial pressure. Prior denervation of either the ipsilateral (experimental) kidney or the control kidney completely prevented the increase in UNaV and UKV after UUO. Prior denervation of either kidney also prevented the increase in UNaV after AUN. However, a significant kaliuresis persisted after AUN despite unilateral denervation although reduced in magnitude when compared with the increase in UKV after AUN with both kidneys innervated. These results indicate that the renal nerves play a major role in the excretory response of the control kidney after acute reduction in functioning renal mass. This role of the renal nerves may be through the activation of a renorenal reflex. The reflex is activated by afferents from the ipsilateral kidney; the efferent limb is composed of the renal nerves to the control kidney. This reflex can entirely account for the compensatory increase in cation excretion after UUO. However, a separate mechanism, not dependent on the renal nerves, contributes to UKV after AUN.

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The potential role of the eGFR in differentiating between true and pseudohyperkalaemia

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563220966858 ◽

2020 ◽

Vol 57 (6) ◽

pp. 444-455

Author(s):

Thomas G Morris ◽

Sushmita Lamba ◽

Thomas Fitzgerald ◽

Gary Roulston ◽

Helen Johnstone ◽

...

Keyword(s):

Renal Function ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Blood Count ◽

Potential Role ◽

Estimated Glomerular Filtration Rate ◽

Full Blood Count ◽

Cut Points

Background Differentiating between true and pseudohyperkalaemia is essential for patient management. The common causes of pseudohyperkalaemia include haemolysis, blood cell dyscrasias and EDTA contamination. One approach to differentiate between them is by checking the renal function, as it is believed that true hyperkalaemia is rare with normal function. This is logical, but there is limited published evidence to support it. The aim of this study was to investigate the potential role of the estimated glomerular filtration rate in differentiating true from pseudohyperkalaemia. Methods GP serum potassium results >6.0 mmol/L from 1 January 2017 to 31 December 2017, with a repeat within seven days, were included. Entries were retrospectively classified as true or pseudohyperkalaemia based on the potassium reference change value and reference interval. If the initial sample had a full blood count, it was classified as normal/abnormal to remove blood cell dyscrasias. Different estimated glomerular filtration rate cut-points were used to determine the potential in differentiating true from pseudohyperkalaemia. Results A total of 272 patients were included with potassium results >6.0 mmol/L, with 145 classified as pseudohyperkalaemia. At an estimated glomerular filtration rate of 90 ml/min/1.73 m2, the negative predictive value was 81% (95% CI: 67–90%); this increased to 86% (95% CI: 66–95%) by removing patients with abnormal full blood counts. When only patients with an initial potassium ≥6.5 mmol/L were included (regardless of full blood count), at an estimated glomerular filtration rate of 90 ml/min/1.73 m2, the negative predictive value was 100%. Lower negative predictive values were seen with decreasing estimated glomerular filtration rate cut-points. Conclusion Normal renal function was not associated with true hyperkalaemia, making the estimated glomerular filtration rate a useful tool in predicting true from pseudohyperkalaemia, especially for potassium results ≥6.5 mmol/L.

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Acute Effect of Passive Heymann Nephritis on Renal Blood Flow and Glomerular Filtration Rate in the Rat: Role of the Anaphylatoxin C5a and the Alpha-Adrenergic Nervous System

Nephron ◽

10.1159/000186808 ◽

1992 ◽

Vol 60 (4) ◽

pp. 453-459 ◽

Cited By ~ 8

Author(s):

Ingegjerd Sekse ◽

Bjarne M. Iversen ◽

Mohamed R. Daha ◽

Jarle Ofstad

Keyword(s):

Blood Flow ◽

Nervous System ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Acute Effect ◽

Heymann Nephritis ◽

Anaphylatoxin C5a ◽

Adrenergic Nervous System

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FP307IMPROVEMENT OF RENAL FUNCTION EVALUATION IN LIVING KIDNEY DONORS: ROLE OF RADIOISOTOPIC GLOMERULAR FILTRATION RATE AND OF RENAL FUNCTIONAL RESERVE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz106.fp307 ◽

2019 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Gabriele Guglielmetti ◽

Angelo Nappo ◽

Umberto Maria Morosini ◽

Gian Mauro Sacchetti ◽

Ronco Claudio ◽

...

Keyword(s):

Renal Function ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Function Evaluation ◽

Functional Reserve ◽

Kidney Donors ◽

Living Kidney Donors ◽

Renal Functional Reserve

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Maintenance of renal autoregulation during infusion of aminophylline or adenosine

AJP Renal Physiology ◽

10.1152/ajprenal.1985.248.3.f366 ◽

1985 ◽

Vol 248 (3) ◽

pp. F366-F373 ◽

Cited By ~ 11

Author(s):

A. J. Premen ◽

J. E. Hall ◽

H. L. Mizelle ◽

J. E. Cornell

Keyword(s):

Blood Flow ◽

Glomerular Filtration Rate ◽

Filtration Rate ◽

Plasma Renin ◽

Receptor Blockade ◽

Renal Metabolism ◽

Renal Autoregulation ◽

Before And After ◽

Anesthetized Dogs

Adenosine has been postulated to link control of glomerular filtration rate (GFR) and renal blood flow (RBF) with changes in renal metabolism. In the present study, we examined the role of adenosine in renal autoregulation by comparing the responses of normal anesthetized dogs to step decreases in renal artery pressure (RAP) to the response obtained after receptor blockade of adenosine with aminophylline or by flooding the kidney with exogenous adenosine. In six dogs at normal RAP, intrarenal infusion of aminophylline (10 mumol/min) did not alter renal hemodynamics. GFR and RBF were well autoregulated (greater than 90% of control) at RAP values equal to or greater than 85 mmHg before and after aminophylline. At RAP equal to 75 mmHg, GFR and RBF decreased by 27 +/- 10 and 20 +/- 8%, respectively, before aminophylline and by 25 +/- 7 and 13 +/- 6% after aminophylline. In a different group of six dogs, intrarenal infusion of adenosine (6 mumol/min) significantly increased RBF (32 +/- 9%) and decreased GFR (38 +/- 10%) at normal RAP. However, GFR and RBF were both well autoregulated (greater than 90% of control) at RAP values equal to or greater than 85 mmHg before and after adenosine. At RAP equal to 75 mmHg, GFR and RBF decreased by 10 +/- 5 and 7 +/- 3%, respectively, before adenosine and by 12 +/- 6 and 17 +/- 5% after adenosine. Neither aminophylline nor adenosine attenuated the elevations in plasma renin activity associated with reductions in RAP. These data fail to provide evidence that adenosine is an important factor in autoregulation of GFR and RBF during acute reductions in RAP within the autoregulatory range.

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