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

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.

Download Full-text

Faculty Opinions recommendation of FGF23 regulates renal sodium handling and blood pressure.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718376319.793499116 ◽

2014 ◽

Author(s):

Christie Thomas

Keyword(s):

Blood Pressure ◽

Renal Sodium Handling ◽

Sodium Handling

Download Full-text

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

American Journal of Hypertension ◽

10.1093/ajh/hpaa160 ◽

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<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.

Download Full-text