The cystic fibrosis transmembrane regulator (CFTR) in the kidney.

Marcelo M Morales,Aníbal Gil Lopes,Doris Falkenstein

doi:10.1590/s0001-37652000000300013

Abstract

The cystic fibrosis transmembrane regulator (CFTR) is a Cl - channel. Mutations of this transporter lead to a defect of chloride secretion by epithelial cells causing the Cystic Fibrosis disease (CF). In spite of the high expression of CFTR in the kidney, patients with CF do not show major renal dysfunction, but it is known that both the urinary excretion of drugs and the renal capacity to concentrate and dilute urine is deficient. CFTR mRNA is expressed in all nephron segments and its protein is involved with chloride secretion in the distal tubule, and the principal cells of the cortical (CCD) and medullary (IMCD) collecting ducts. Several studies have demonstrated that CFTR does not only transport Cl - but also secretes ATP and, thus, controls other conductances such as Na+ (ENaC) and K+ (ROMK2) channels, especially in CCD. In the polycystic kidney the secretion of chloride through CFTR contributes to the cyst enlargement. This review is focused on the role of CFTR in the kidney and the implications of extracellular volume regulators, such as hormones, on its function and expression.

Highlights

In mammalians, the kidneys are responsible for the maintenance of the extracellular sodium chloride (NaCl) concentration that regulate the extracellular fluid volume (ECFV) and blood pressure
The function of cystic fibrosis transmembrane regulator (CFTR) in proximal tubules is uncertain because the reabsorption of NaCl in this segment of the nephron is increased in Cystic Fibrosis disease (CF), rather than decreased as would be expected if CFTR mediates Cl− absorption (Bates et al 1997, Stenvinkle et al 1991)
CFTR expression and chloride channel function is normal in polycystic kidney disease (PKD), an autosomal dominant genetic disease (Hanaoka et al 1996, Sullivan et al 1998)

Summary

Introduction

The kidneys are responsible for the maintenance of the extracellular sodium chloride (NaCl) concentration that regulate the extracellular fluid volume (ECFV) and blood pressure. The function of CFTR in proximal tubules is uncertain because the reabsorption of NaCl in this segment of the nephron is increased in CF, rather than decreased as would be expected if CFTR mediates Cl− absorption (Bates et al 1997, Stenvinkle et al 1991). The mRNA for CFTR was found in the thin ascending limbs of Henle’s loop, but no protein was indentified in this nephron segment by immunolocalization or patch clamp studies (Crawford et al 1991, Devuyst et al 1996).

Results

Conclusion