Incomplete dRTA in kidney stone formers: diagnostic performance of furosemide/fludrocortisone testing and non-provocative clinical parameters

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. Due to the lack of rigorous comparative studies, the validity of the furosemide/fludrocortisone test in stone formers remains unknown. In addition, the performance of conventional, non-provocative parameters in predicting incomplete distal renal tubular acidosis has not been studied. Design, setting, participants, and 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 7.78 %. Sensitivity and specificity of the furosemide/fludrocortisone test FF test were 77 % and 85 %, respectively, yielding a positive predictive value of 30 % and a negative predictive value of 98 %. Testing of several non-provocative 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 mmolmEq/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 non-provocative clinical parameters.