Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone Formers

Clin J Am Soc Nephrol. 2017 Sep 7;12(9):1507-1517. doi: 10.2215/CJN.01320217. Epub 2017 Aug 3.


Background and objectives: Incomplete distal renal tubular acidosis is a well known cause of calcareous nephrolithiasis but the prevalence is unknown, mostly due to lack of accepted diagnostic tests and criteria. The ammonium chloride test is considered as gold standard for the diagnosis of incomplete distal renal tubular acidosis, but the furosemide/fludrocortisone test was recently proposed as an alternative. Because of the lack of rigorous comparative studies, the validity of the furosemide/fludrocortisone test in stone formers remains unknown. In addition, the performance of conventional, nonprovocative parameters in predicting incomplete distal renal tubular acidosis has not been studied.

Design, setting, participants, & measurements: We conducted a prospective study in an unselected cohort of 170 stone formers that underwent sequential ammonium chloride and furosemide/fludrocortisone testing.

Results: Using the ammonium chloride test as gold standard, the prevalence of incomplete distal renal tubular acidosis was 8%. Sensitivity and specificity of the furosemide/fludrocortisone test were 77% and 85%, respectively, yielding a positive predictive value of 30% and a negative predictive value of 98%. Testing of several nonprovocative clinical parameters in the prediction of incomplete distal renal tubular acidosis revealed fasting morning urinary pH and plasma potassium as the most discriminative parameters. The combination of a fasting morning urinary threshold pH <5.3 with a plasma potassium threshold >3.8 mEq/L yielded a negative predictive value of 98% with a sensitivity of 85% and a specificity of 77% for the diagnosis of incomplete distal renal tubular acidosis.

Conclusions: The furosemide/fludrocortisone test can be used for incomplete distal renal tubular acidosis screening in stone formers, but an abnormal furosemide/fludrocortisone test result needs confirmation by ammonium chloride testing. Our data furthermore indicate that incomplete distal renal tubular acidosis can reliably be excluded in stone formers by use of nonprovocative clinical parameters.

Keywords: Acidosis, Renal Tubular; Ammonium Chloride; Ammonium Compounds; Diagnostic Tests, Routine; Fasting; Fludrocortisone; Furosemide; Kidney Calculi; Potassium; Prevalence; Prospective Studies; Sensitivity and Specificity; clinical nephrology; kidney stones; mineral metabolism; renal tubular acidosis.

Publication types

  • Comparative Study

MeSH terms

  • Acidosis, Renal Tubular / complications
  • Acidosis, Renal Tubular / diagnosis*
  • Acidosis, Renal Tubular / epidemiology
  • Adult
  • Ammonium Chloride / administration & dosage*
  • Female
  • Fludrocortisone / administration & dosage*
  • Furosemide / administration & dosage*
  • Humans
  • Kidney Calculi / diagnosis*
  • Kidney Calculi / epidemiology
  • Kidney Function Tests*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prevalence
  • Prospective Studies
  • Reproducibility of Results
  • Sodium Potassium Chloride Symporter Inhibitors / administration & dosage*
  • Switzerland / epidemiology


  • Sodium Potassium Chloride Symporter Inhibitors
  • Ammonium Chloride
  • Furosemide
  • Fludrocortisone