Prevalence of Hypocitraturia and Hypopyrophosphaturia in Recurrent Calcium Stone Formers: As Isolated Defects or Associated with Other Metabolic Abnormalities

Abstract

Several underlying metabolic abnormalities may be present in patients with recurrent calcium calculus disease (RCCD). The aim of this study was to determine the prevalence of deficiencies of 2 well-known potent inhibitors of crystal formation and growth, citrate and pyrophosphate, in the various metabolic subgroups and as single defects. In 107 patients with RCCD, urinary citrate was significantly decreased in all metabolic subgroups with 49% of patients having hypocitraturia (2.53 ± 1.19 mmol/24 h) versus controls (3.44 ± 0.96 mmol/24 h; p < 0.001). Reduced pyrophosphate: creatinine ratios were present in all the patient subgroups, and 48% of all patients had reduced ratios (1.68 ± 1.68 vs. 3.10 ± 2.66 in controls; p < 0.01). There was no correlation between citrate and pyrophosphate concentration. Isolated hypocitraturia was found in 11.2%, reduced pyrophosphate: creatinine ratios as the single defect in 11.2% and a combination of both in 12.1% of patients. Thus inhibitor defects play an important role in patients with RCCD and frequently occur as isolated biochemical defects.

Inhibitors of Stone Formation in Hypercalciuric Children with and without Stone Disease

“…Hypocitraturia is a well-recognized inhibitor defect and has been mainly investigated in adult patients with IH, hyperoxaluria or hyperuricosuria [11,20,21], Our data demonstrated that both SF and NSF had a significant lower citrate/calcium ratio than controls (p < 0.001); in addition, it was also lower in SF than in NSF (p < 0.05; table 4). Other investigators reported a significantly low citrate/Ca ratio in SF, especially in recur rent SF [22,23], Our study showed no difference in citrate excretion between patients and controls.…”

“…Some other substances (e.g. magnesium, citrate, glycosaminoglycans, pyrophosphate, zinc) can modify the ability of inorganic microcrystals to grow and form stones [6][7][8][9][10][11].…”

“…[10] in27.5%andLaminski et al [11] in 44% of patients with renal hypercalciuria and urinary stones. In a recent work by Esen et al [25], hypocitraturia and hypomagnesuria were found to be the most frequent abnormality associated with urolithiasis with a 44.9 and 24.8% incidence, respectively.…”

Expression and Localisation of the Pyrophosphate Transporter, ANK, in Murine Kidney Cells

“…Taken together with the demonstration of renal epithelial cell expression of ANK and PP export to apical/basal bathing media in vitro, we postulate that pyrophosphate transport to either interstitium or tubular lumen comprises an important mechanism that protects against nephrocalcinosis/nephrolithiasis. Indeed hypopyrophosphaturia has been documented in a group of recurrent stone-forming patients [20]. Ho et al mention that ank-/-animals show renal calcification [9].…”

Genetic basis of renal cellular dysfunction and the formation of kidney stones

“…If it is equally efficient in urine it can contribute 50% crystal COM growth inhibition in the collecting ducts (5 times dilution) and up to 80% in the urine. Hypopyrophosphaturia is postulated to be a metabolic risk factor for recurrent kidney stone formers [90]. Mutations in pyrophosphate transporter, ANKH , are associated with defects of calcification such as craniometaphyseal dysplasia and chodrocalcinosis.…”