Low Urine Citrate Excretion as Main Risk Factor for Recurrent Calcium Oxalate Nephrolithiasis in Males

Abstract

To better define the relative role of metabolic factors in the recurrence of stone formation, we studied the 24-hour urinary excretion of calcium (uCa), citrate (uCit), oxalic acid (uOx) and uric acid (uUa) in 73 male patients with primary calcium oxalate urolithiasis. According to the episodes of stone formation per year, we identified 51 recurrent stone formers (RSF) and 22 single stone formers (SSF). 20 normal adult males constituted the control group (C). uCa and uOx were higher in RSF than in C, but quite similar in SSF and RSF. The only difference between RSF and SSF was uCit, significantly lower (2.06 ± 1.04 mmol/24 h) in RSF than in SSF (3.22 ± 1.18 mmol/24 h, p < 0.001) and in C (3.42 ± 1.33 mmol/24 h, p < 0.001). Hypocitraturia (uCit < 1.5 mmol/24 h) was found in 16 of 51 RSF (31.4%) and in 1 of 22 SSF (4.5%). These data confirm that high levels of uCa and uOx represent a risk factor for lithogenesis, but also strongly indicate the low uCit excretion as the most important urinary abnormality accounting for the recurrence of calcium oxalate stones.

Stone Composition, Metabolic Profile and the Presence of the Gut-Inhabiting Bacterium <i>Oxalobacter formigenes</i> as Risk Factors for Renal Stone Formation

“…In this study, we also observed a high incidence of calcium oxalate stone: 70.8% in FSF patients and 59.4% in RSF patients. Hypocitraturia was the most common abnormality in this study in both groups, consistent with previous reports [5,17]. Although our data indicate that on the basis of urinary citrate levels, patients with recurrent stone formation cannot be distinguished from patients with 1 episode only, we can assume that urinary citrate is an important risk factor for stone disease.…”

“…Despite the introduction of non-invasive techniques for the removal of stones and the identification of several metabolic factors responsible for stone formation [4][5][6], stone recurrence continues to be a significant clinical problem [16]. About 80% of urolithiasis patients have been reported to have calcium oxalate stones [11].…”

“…The disease, which has a high incidence of recurrence following treatment, is one of the biggest challenges facing urologists today, partly due to the fact that the pathogenesis of the stone formation is not clearly understood [2,3]. Urolithiasis is a complex process influenced by several factors, including hyperoxaluria, hypercalciuria, hypocitraturia, hyperuricosuria, low urinary volume [4][5][6], anatomical malformations [7], and urinary stasis as well as dietary habits [8]. Recently, detection of Oxalobacter formigenes, a specific oxalate-degrading anaerobic bacterium inhabiting the gastrointestinal tracts of humans, has attracted attention because the absence of this bacterium appears to be a risk factor for development of hyperoxaluria and/or recurrent kidney stone disease [9].…”

Urine Calcium/Citrate Ratio in Children With Hypercalciuric Stones

“…Thus, it may not be the absolute urinary calcium or citrate concentrations that determine the risk of stone formation but rather the relative excess of calcium over citrate. Similarly, Cupisti et al (26) found that stone formers had higher urinary calcium excretion and low citrate excretion, which was more marked in recurrent stone formers. As early as 1976, Welshman and McGeown (14) had found urinary calcium/citrate ratio to be different in normal adult subjects and stone formers but found a difference between the two genders.…”

An Update and Practical Guide to Renal Stone Management

“…Urinary citrate is an inhibitor of crystallization of calcium salts in urine, and studies have linked lower levels of urinary citrate excretion to increased calcium oxalate stone risk [30]. Urinary citrate levels of <2.0 mmol/day in males and <2.5 mmol/day in females are considered abnormal.…”