Effects of non-pharmacological interventions on urinary citrate levels: a systematic review and meta-analysis

Hypocitraturia is a known risk factor for nephrolithiasis, present in 20-60% of stone-forming patients. The administration of citrate or other alkali preparations has been demonstrated to benefit hypocitraturic stone formers. Dietary modifications that include citrate-containing fluids can be an alternative option to pharmacological agents. We aimed to systematically review, summarize and quantify available evidence on the effects of non-pharmacological interventions on urinary citrate and nephrolithiasis.

Manual and electronic database searches (MEDLINE/PubMed, Embase, Cochrane Library, Scopus, Scielo, LILACS) were performed for studies published up to July 2014. Two reviewers independently identified studies for inclusion and extracted data on study characteristics, outcomes and quality assessments. We included controlled studies with non-pharmacological interventions that assessed urinary citrate levels or nephrolithiasis pre- and post-intervention. Meta-analysis was performed by random effects and subgrouped by the type of intervention, and heterogeneity was analysed by I(2).

Of the 427 studies identified, 13 studies were included (18 samples), involving 358 participants with a mean age of 43 ± 11.0 years across the studies. Interventions were grouped as commercial fruit juices, soft drinks, calcium-/magnesium-rich mineral water, high-fiber diet, low-animal-protein diet and plant extract. Almost half of the studies (6/13; 8/18 samples) reported effects in non-stone formers. Two studies included stone formers and non-stone formers. Commercial fruit juice interventions showed high I(2) (88.1%, P = 0.000) and an increase in citraturia levels ( 95% confidence interval) of 167.2 (65.4; 269) mg/day. Other types of intervention did not show important heterogeneity; however, pooled estimates were not significant.

Our review indicates that further larger scale trials are required to analyze whether non-pharmacological interventions can increase urinary citrate levels and act in kidney stone prevention.