Abstract
PurposeProspective evaluation of the prevalence of incomplete distal renal tubular acidosis (idRTA) in idiopathic calcium stone formers (ICSF) diagnosed by half-dose ammonium chloride loading (NH4Cl, 0.05 g/kg body weight/day) and impact of alkali treatment of idRTA.MethodsEvaluation of 386 consecutive idiopathic calcium stone formers (ICSF) (280 males, 106 females) for idRTA. If screening fasting urine pH was > 5.80, 1-day NH4Cl loading was performed without severe adverse effects. Normally, urine pH falls below 5.45.ResultsSixty-four idiopathic calcium stone formers exhibited idRTA, one complete dRTA. Prevalence was higher in women (25.4%) than in men (13.6%). Thus, for more equilibrated comparisons, we formed pairs of 62 idiopathic calcium stone formers (ICSF) with and 62 without idRTA, matched for gender, age, BMI and serum creatinine. Idiopathic calcium stone formers with idRTA more often had hypercalciuria (p < 0.025) and urine citrate < 2 mmol/d (p < 0.05), formed calcium phosphate stones more frequently, exhibited higher numbers of stones/year (1.4 ± 1.5 vs. 0.9 ± 0.8, p = 0.034) and 2.5 times more intrarenal calcifications (4.6 ± 5.9 vs. 1.8 ± 3.6, p = 0.002). All idiopathic calcium stone formers with idRTA were recommended chronic alkali therapy. After 4–15 years of follow-up, stone events /years follow-up (stone passage or urologic intervention) were higher in patients non-adherent to alkali therapy (0.61 ± 0.92) than in patients adherent to treatment (0.11 ± 0.21, p = 0.006).Conclusion Incomplete distal renal tubular acidosis is 1.8-fold more prevalent among female idiopathic calcium stone formers, predicts more stone recurrences, predisposes to calcium phosphate stones and is associated with 2.5 times more intrarenal calcifications vs. non-idRTA patients. Chronic alkali treatment reduces clinical stone recurrences by 5.5 times.Graphical abstract
Highlights
On a diet rich in animal proteins, the kidneys have to excrete up to 100 mmol of hydrogen ions per day [1]
Four key findings emerge: first, N H4Cl loading at half the “classic” dose can be performed at home with results equal to those originally published [9]; second, incomplete incomplete distal renal tubular acidosis (idRTA) is highly prevalent, especially in women; third, idRTA patients exhibit more active stone disease and more marked nephrocalcinosis; and fourth, alkali therapy reduces clinical stone recurrences in idRTA patients
In the 10 normals of the original test, average urine pH had fallen by 0.7 units, from about 5.5 to 4.81
Summary
On a diet rich in animal proteins, the kidneys have to excrete up to 100 mmol of hydrogen ions per day [1]. Reduced H+ secretion by collecting tubules causes distal renal tubular acidosis (dRTA) [2,3,4], either complete (overt metabolic acidosis, elevated urine pH) or more frequently incomplete (idRTA, no systemic acidosis, elevated urine pH) [2, 4, 5]. In both forms, chronic H+ retention predisposes to calcium nephrolithiasis [2,3,4] and low bone mass [6,7,8]. Administration of furosemide and fludrocortisone with subsequent urine pH measurements produces equal results with better tolerance [5, 10]
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