Reduced nephron endowment due to fetal uninephrectomy impairs renal sodium handling in male sheep

2010 ◽  
Vol 118 (11) ◽  
pp. 669-680 ◽  
Author(s):  
Reetu R. Singh ◽  
Kate M. Denton ◽  
John F. Bertram ◽  
Andrew J. Jefferies ◽  
Karen M. Moritz
Keyword(s):  
Cardiovascular Disease ◽  
Sodium Excretion ◽  
Kidney Weight ◽  
Salt Loading ◽  
Α Subunit ◽  
Nephron Endowment ◽  
Renal Sodium Handling ◽  
Nephron Deficit ◽  
Sodium Handling ◽  
Male Sheep

Reduced nephron endowment is associated with development of renal and cardiovascular disease. We hypothesized this may be attributable to impaired sodium homoeostasis by the remaining nephrons. The present study investigated whether a nephron deficit, induced by fetal uninephrectomy at 100 days gestation (term=150 days), resulted in (i) altered renal sodium handling both under basal conditions and in response to an acute 0.9% saline load (50 ml·kg−1 of body weight·30 min−1); (ii) hypertension and (iii) altered expression of renal channels/transporters in male sheep at 6 months of age. Uninephrectomized animals had significantly elevated arterial pressure (90.1±1.6 compared with 77.8±2.9 mmHg; P<0.001), while glomerular filtration rate and renal blood flow (per g of kidney weight) were 30% lower than that of the sham animals. Total kidney weight was similar between the groups. Renal gene expression of apical NHE3 (type 3 Na+/H+ exchanger), ENaC (epithelium Na+ channel) β and γ subunits and basolateral Na+/K+ ATPase β and γ subunits were significantly elevated in uninephrectomized animals, while ENaC α subunit expression was reduced. Urine flow rate and sodium excretion increased in both groups in response to salt loading, but this increase in sodium excretion was delayed by approximately 90 min in the uninephrectomized animals, while total sodium output was 12% in excess of the infused load (P<0.05). In conclusion, the present study shows that animals with a congenital nephron deficit have alterations in tubular sodium channels/transporters and cannot rapidly correct for variations in sodium intake probably contributing to the development of hypertension. This suggests that people born with a nephron deficit should be monitored for early signs of renal and cardiovascular disease.

Renal sodium handling in acute and chronic salt loading/depletion protocols

2000 ◽  
Vol 18 (11) ◽  
pp. 1657-1664 ◽  
Author(s):  
Michel Burnier ◽  
Marie-Laure Monod ◽  
Arnaud Chioléro ◽  
Marc Maillard ◽  
Jurg Nussberger ◽  
...  
Keyword(s):  
Salt Loading ◽  
Renal Sodium Handling ◽  
Sodium Handling

[PP.30.05] BLOOD PRESSURE IN RELATION TO 24-HOUR URINARY SODIUM EXCRETION AND RENAL SODIUM HANDLING

2016 ◽  
Vol 34 ◽  
pp. e308
Author(s):  
K. Stolarz-Skrzypek ◽  
A. Bednarski ◽  
A. Franczyk ◽  
M. Folta ◽  
H. Barton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Renal Sodium Handling ◽  
Sodium Handling

Fibroblast growth factor 23 is associated with fractional excretion of sodium in patients with chronic kidney disease

2018 ◽  
Vol 34 (12) ◽  
pp. 2051-2057 ◽  
Author(s):  
Hong Xu ◽  
Ali Hashem ◽  
Anna Witasp ◽  
Rik Mencke ◽  
David Goldsmith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Growth Factor ◽  
Sodium Excretion ◽  
Fibroblast Growth Factor 23 ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Fibroblast Growth ◽  
Fractional Excretion Of Sodium ◽  
Renal Sodium Handling ◽  
Sodium Handling

Abstract Background Recent studies suggest that the phosphaturic hormone fibroblast growth factor 23 (FGF23) is involved in regulation of renal sodium excretion and blood pressure. There is evidence of both direct effects via regulation of the sodium-chloride symporter (NCC) in the distal tubule, and indirect effects through interactions with the renin–angiotensin–aldosterone system. However, clinical data on the association between FGF23 and renal sodium regulation is lacking. Herein, we investigated the associations of FGF23 with renal sodium handling and blood pressure in non-dialysis CKD patients. Methods This was a cross-sectional study encompassing 180 CKD patients Stage 1–5, undergoing renal biopsy. Plasma intact FGF23, 24-h urinary sodium excretion, fractional excretion of sodium (FENa) and blood pressure were measured at baseline. The association between FGF23 and renal sodium handling was explored by multivariate regression analysis. Results The median age was 52.8 years, 60.6% were men and the median estimated glomerular filtration rate (eGFR) was 50.6 mL/min/1.73 m2. In univariate analysis, FGF23 was positively associated with FENa (Spearman’s rho = 0.47; P < 0.001) and systolic blood pressure (rho = 0.17, P < 0.05), but not with plasma sodium, 24-h urinary sodium excretion or mean arterial blood pressure. The association between FGF23 and FENa remained significant after adjustment for potential confounders (multivariable adjusted β coefficient 0.60, P < 0.001). This association was stronger among the 107 individuals with eGFR <60 mL/min/1.73 m2 (β = 0.47, P = 0.04) and in the 73 individuals on any diuretics (β = 0.88, P < 0.001). Adjustment for measured GFR instead of eGFR did not alter the relationship. Conclusions FGF23 is independently associated with increased FENa in non-dialysis CKD patients. These data do not support the notion that FGF23 causes clinically significant sodium retention. Further studies are warranted to explore the mechanism underlying this association.

Effects of insulin and atrial natriuretic peptide on renal tubular sodium handling in sickle cell disease

2000 ◽  
Vol 278 (3) ◽  
pp. F499-F505 ◽  
Author(s):  
Jan C. ter Maaten ◽  
Erik H. Serné ◽  
Wim Statius van Eps ◽  
Pieter M. ter Wee ◽  
Ab J. M. Donker ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Low Dose ◽  
High Dose ◽  
Cell Disease ◽  
Control Subjects ◽  
Renal Sodium Handling ◽  
Sodium Handling

We assessed the effect of insulin and atrial natriuretic peptide (ANP) on renal sodium handling in eight patients with sickle cell disease (SCD), who are characterized by loss of vasa recta and long loops of Henle, and matched control subjects. During insulin infusion (50 mU ⋅ kg− 1 ⋅ h− 1), fractional sodium excretion decreased by 0.44 ± 0.72% ( P = 0.13) in patients with SCD and by 0.57 ± 0.34% ( P = 0.002) in control subjects, whereas fractional distal sodium reabsorption increased by 4.1 ± 1.5% ( P < 0.001) and 3.0 ± 1.5% ( P < 0.001), respectively. Low-dose (0.3 pmol ⋅ kg− 1 ⋅ h− 1) ANP infusion did not affect renal sodium handling in patients with SCD but increased fractional sodium excretion by 0.34 ± 0.22% ( P= 0.003) in control subjects. High-dose (2 μg/min) ANP increased natriuresis to a similar extent in both groups. Insulin's antinatriuretic effects predominated over the natriuretic effects of low-dose, but not high-dose, ANP. These data suggest that insulin's antinatriuretic effect is localized at a distal tubular site other than the long loops of Henle and that the long loops are involved in the natriuretic effect of low-dose ANP, possibly mediated by changes in medullary blood flow.

scholarly journals Adenosine Activates Aromatic L-Amino Acid Decarboxylase Activity in the Kidney and Increases Dopamine

2001 ◽  
Vol 12 (1) ◽  
pp. 29-36
Author(s):  
TAKANOBU TAKEZAKO ◽  
KEITA NODA ◽  
EMIKO TSUJI ◽  
MANABU KOGA ◽  
MANABU SASAGURI ◽  
...  
Keyword(s):  
Amino Acid ◽  
Sodium Excretion ◽  
Left Kidney ◽  
D1 Receptor ◽  
Acid Decarboxylase ◽  
Decarboxylase Activity ◽  
Amino Acid Decarboxylase ◽  
Renal Sodium Handling ◽  
Renal Dopamine ◽  
Sodium Handling

Abstract. Renal sodium handling is important for regulating BP, and renal dopamine and adenosine play an important role in renal sodium handling, however the interaction of these hormones in the kidney was not clarified. In in vivo experiments, adenosine significantly increased water and sodium excretion by 50% compared with vehicle when infused into the left renal artery, accompanied by an increase in urinary dopamine excretion in the left kidney. Neither water-sodium excretion nor dopamine excretion changed in the vehicle-infused kidney. Aromatic L-amino acid decarboxylase activity in the left kidney was significantly higher than that in the noninfused right kidney. The increase in water-sodium excretion induced by adenosine was significantly inhibited by SCH23390, a selective D1 receptor antagonist. In in vitro experiments, porcine renal proximal tubular cells were incubated with 250 μM L-dopa and N6-cyclohexyladenosine, an adenosine type 1 receptor agonist, after treatment with adenosine deaminase. N6-cyclohexyladenosine significantly increased dopamine formation at a concentration of 10-9 to 10-7 M, and this was completely inhibited by 1,3-dipropyl-8-cyclopentylxanthin, an adenosine A1 antagonist. These results show that renal dopamine synthesis is stimulated by adenosine through the activation of aromatic L-amino acid decarboxylase and suggest that adenosine leads to an increase in renal dopamine and natriuresis.

Effect of Arterial Pressure and Inheritance on the Sodium Excretory Capacity of Normal Young Men

1978 ◽  
Vol 54 (6) ◽  
pp. 639-647 ◽  
Author(s):  
R. C. Wiggins ◽  
I. Basar ◽  
J. D. H. Slater
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Sodium Excretion ◽  
Adult Sons ◽  
Isotonic Fluid ◽  
Renal Sodium Excretion ◽  
Fluid Load ◽  
Renal Sodium Handling ◽  
Highly Correlated ◽  
Sodium Handling

1. In normal young adult sons of normotensive parents the rate of renal sodium excretion is highly correlated with mean arterial pressure after a large intravenous isotonic fluid load. The correlation appeared to strengthen with time and was improved when the rate of sodium excretion was corrected for variations in the rate of glomerular filtration. 2. There was no such correlation in normal, age-matched sons of hypertensive parents. 3. In eight of the 20 normotensive sons of hypertensive parents studied, the rate of renal sodium excretion per unit of mean arterial pressure was significantly higher than in the sons of normotensive parents. 4. Because the sons of hypertensive parents are much more likely to become hypertensive than those of normotensive parents, we suggest that an abnormality of renal sodium handling precedes the development of demonstrable hypertension.

scholarly journals Sex and Body Mass Index Modify the Association Between Leptin and Sodium Excretion: A Cross-sectional Study in an African Population

2019 ◽  
Vol 32 (11) ◽  
pp. 1101-1108
Author(s):  
Nora Schwotzer ◽  
Michel Burnier ◽  
Marc Maillard ◽  
Pascal Bovet ◽  
Fred Paccaud ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Cross Sectional Study ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Sectional Study ◽  
Cross Sectional ◽  
Renal Sodium Handling ◽  
Sodium Handling

Abstract BACKGROUND Renal sodium handling could be a potential mediator linking adipokines to hypertension. The aim of the study was to assess the relationship of leptin with urinary sodium excretion and proximal sodium reabsorption in humans. METHODS This cross-sectional study was conducted on participants of hypertensive families from the Seychelles Island. A split urine (daytime and nighttime) collection and plasma leptin were measured. Endogenous lithium clearance was used to assess proximal sodium reabsorption. Mixed multiple linear regression tests adjusted for confounding factors were used. RESULTS Three hundred and sixty-five participants (57% women) were included in this analysis. Leptin and adiponectin were higher in women (P < 0.001). Leptin was associated positively with daytime (coefficient [c]: 0.16, standard deviation (SD): 0.03, P < 0.001), nighttime urinary sodium excretion (c: 0.17, SD: 0.04), P < 0.01), daytime lithium clearance (c: 0.40, SD: 0.08, P < 0.001), and nighttime lithium clearance (c: 0.39, SD: 0.10, P < 0.001) after adjusting for sex. The association was lost or mitigated only when BMI was introduced in the model. When BMI was categorized in normal vs. overweight participant, leptin was associated with daytime and nighttime sodium excretion rates (c: 0.14, SD: 0.05, P = 0.011 and c: 0.22, SD: 0.07, P = 0.002, respectively) only in overweight participants. CONCLUSION Leptin is associated positively with daytime and nighttime sodium excretion and lithium clearance suggesting a natriuretic rather than a sodium retaining effect of leptin. Sex and body mass index (BMI) are major confounders in this association. These results highlight the importance of sex and obesity in our understanding of the relationships between leptin, blood pressure, and renal sodium handling.

Renal Sodium Handling in Relation to Environmental and Genetic Factors in Untreated Chinese

2020 ◽  
Author(s):  
Yuan-Yuan Kang ◽  
Yi-Bang Cheng ◽  
Qian-Hui Guo ◽  
Chang-Sheng Sheng ◽  
Qi-Fang Huang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Multiple Testing ◽  
Genetic Factors ◽  
Blood Pressure Monitoring ◽  
Lithium Concentration ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Renal Sodium Handling ◽  
Renal Tubular ◽  
Sodium Handling

Abstract Background We investigated proximal and distal renal tubular sodium handling, as assessed by fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa), in relation to environmental and genetic factors in untreated patients. Methods Our study participants were suspected hypertensive patients being off antihypertensive medication for ≥2 weeks and referred for 24-hour ambulatory blood pressure monitoring. We collected serum and 24-hour urine for measurement of sodium, creatinine and lithium concentration, and calculated FELi and FDRNa. We genotyped 19 SNPs associated with renal sodium handling or blood pressure using the ABI SNapShot method. Results The 1409 participants (664 men, 47.1%) had a mean (±SD) age of 51.0±10.5 years. After adjustment for host factors, both FELi and FDRNa were significantly (P≤0.01) associated with season and humidity, explaining ~1.3% and ~3.5% of the variance, respectively. FELi was highest in autumn and lowest in summer and intermediate in spring and winter (P=0.007). FDRNa was also highest in autumn but lowest in winter and intermediate in spring and summer (P&lt;0.001). Neither FELi nor FDRNa was associated with outdoor temperature or atmospheric pressure (P≥0.13). After adjustment for host and environmental factors and Bonferroni multiple testing, among the 19 studied genetic variants, only rs12513375 was significantly associated with FELi and FDRNa (P≤0.004) and explained about 1.7% of the variance. Conclusions Renal sodium handling as measured by endogenous lithium clearance was sensitive to major environmental and genetic factors. Our finding is towards the use of these indexes for the definition of renal tubular dysfunction.

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