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Evidence for cystic fibrosis transmembrane conductance regulator-dependent sodium reabsorption in kidney, using
J D Kibble1, A M Neal, W H Colledge
1Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK. j.kibble@sheffield.ac.uk
Abstract:
The aims of this study were to investigate (a) if renal Na(+) handling was normal in Cftr(tm2cam) delta F508 cystic fibrosis mice, (b) whether adaptation to dietary salt depletion was preserved and (c) whether Cftr(tm2cam) delta F508 mice exhibited enhanced amiloride-sensitive Na(+) absorption. In Na(+)-replete animals (maintained on a 0.32 % NaCl diet) given a 150 mM NaCl i.v. maintenance infusion, there was no difference in fractional Na(+) excretion (FE(Na)) between wild-type (0. 42 +/- 0.06 %, n = 12) and Cftr(tm2cam) delta F508 mice (0.47 +/- 0.13 %, n = 7). Amiloride infusion significantly increased FE(Na) in both wild-type (3.14 +/- 0.83 %, n = 6) and Cftr(tm2cam) delta F508 mice (3. 47 +/- 0.63 %, n = 9), though with no significant difference between genotypes. A 14 day dietary salt restriction (animals maintained on a 0.03 % NaCl diet) and maintenance infusion with a 15 mM NaCl vehicle caused a reduction in FE(Na) to 0.14 +/- 0.05 %, n = 8 in wild-type mice and 0.14 +/- 0.04 %, n = 8 in Cftr(tm2cam) delta F508 mice. No significant difference in the ability to adapt to low salt conditions was apparent comparing the two genotypes. Treatment of salt-restricted mice with amiloride resulted in a blunted natriuresis in both wild-type mice (FE(Na) = 1.10 +/- 0.16 %, n = 7) and Cftr(tm2cam) delta F508 mice (FE(Na) = 1.97 +/- 0.29 %, n = 9). The natriuresis induced by amiloride was significantly greater in Cftr(tm2cam) delta F508 mice than in wild-type controls. In conclusion, Cftr(tm2cam) delta F508 mice exhibit normal renal salt excretion when either salt replete or salt restricted. Enhanced amiloride-sensitive FE(Na) is consistent with increased Na(+) absorption via the amiloride-sensitive sodium channel ENaC, in cystic fibrosis kidney, but this was only observed during salt restriction.
Insights
Cystic fibrosis mice (Cftr(tm2cam) delta F508) show normal renal sodium handling and salt adaptation. However, they exhibit increased amiloride-sensitive sodium absorption during salt restriction, suggesting altered ENaC activity in the kidney.
Area of Science:
- Nephrology
- Physiology
- Genetics
Background:
- Cystic fibrosis (CF) is a genetic disorder affecting ion transport.
- The role of CF transmembrane conductance regulator (CFTR) in renal sodium handling is not fully understood.
- CFTR dysfunction may impact kidney function and salt balance.
Purpose of the Study:
- To investigate renal sodium handling in Cftr(tm2cam) delta F508 cystic fibrosis mice.
- To determine if these mice can adapt to dietary salt restriction.
- To assess amiloride-sensitive sodium (Na+) absorption in CF mice.
Main Methods:
- Comparison of fractional sodium excretion (FE(Na)) between wild-type and Cftr(tm2cam) delta F508 mice under normal and salt-restricted conditions.
- Administration of amiloride to assess its effect on FE(Na).
- Analysis of renal adaptation to low-salt diets.
Main Results:
- No significant difference in FE(Na) between genotypes when salt-replete or salt-restricted.
- Both genotypes adapted to salt restriction by reducing FE(Na).
- Amiloride administration induced a greater increase in FE(Na) in CF mice compared to wild-type mice, but only during salt restriction.
Conclusions:
- Cftr(tm2cam) delta F508 mice maintain normal renal salt excretion under varying salt conditions.
- Enhanced amiloride-sensitive sodium absorption in CF mice during salt restriction suggests increased epithelial sodium channel (ENaC) activity.
- These findings indicate a potential role for CFTR in regulating renal sodium balance, particularly under conditions of salt depletion.