Liddle's-like syndrome associated with nephrotic syndrome secondary to membranous nephropathy: the first case report

BMC Nephrol. 2018 May 23;19(1):122. doi: 10.1186/s12882-018-0916-3.


Background: Liddle's syndrome is a rare monogenic form of hypertension caused by truncating or missense mutations in the C termini of the epithelial sodium channel (ENaC) β or γ subunits. Patients with this syndrome present with early onset of hypertension, hypokalemia, metabolic alkalosis, hyporeninemia and hypoaldosteronism, and a potassium-sparing diuretics (triamterene or amiloride) can drastically improves the disease condition. Although elderly patients having these characteristics were considered to have Liddle's syndrome or Liddle's-like syndrome, no previous report has indicated that Liddle's-like syndrome could be caused by nephrotic syndrome of primary glomerular disease, which is characterized by urinary excretion of > 3 g of protein/day plus edema and hypoalbuminemia, or has explained how the activity function of ENaC could be affected in the setting of high proteinuria.

Case presentation: A 65-year-old Japanese man presented with nephrotic syndrome. He had no remarkable family history, but had a medical history of hypertension and hyperlipidemia. On admission, hypertension, spironolactone-resistant hypokalemia (2.43 mEq/l), hyporeninemic hypoaldosteronism, and metabolic alkalosis, which suggested Liddle's syndrome, were observed. Treatment with triamterene together with a steroid for nephrotic syndrome resulted in rapid and remarkable effective on improvements of hypertension, hypokalemia, and edema of the lower extremities. Renal biopsy revealed membranous nephropathy (MN) as the cause of nephrotic syndrome, and advanced gastric cancer was identified on screening examination for cancers that could be associated with the development of MN. After total gastrectomy, triamterene was not required and proteinuria decreased. A mutation in the β or γ subunits of the ENaC gene was not identified.

Conclusion: We reported for the first time a case of Liddle's-like syndrome associated with nephrotic syndrome secondary to MN. Aberrant activation of ENaC was suggested transient during the period of high proteinuria, and the activation was reversible with a decrease in proteinuria.

Keywords: Epithelial sodium channel; Liddle’s syndrome; Membranous nephropathy; Nephrotic syndrome; Urinary plasmin.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Glomerulonephritis, Membranous / complications
  • Glomerulonephritis, Membranous / diagnosis*
  • Glomerulonephritis, Membranous / genetics
  • Humans
  • Liddle Syndrome / diagnosis*
  • Liddle Syndrome / etiology
  • Liddle Syndrome / genetics
  • Male
  • Nephrotic Syndrome / diagnosis*
  • Nephrotic Syndrome / etiology
  • Nephrotic Syndrome / genetics