Preventive treatment of nephrolithiasis with alkali citrate—a critical review

Using the keywords “urolithiasis and citrate treatment”, “nephrolithaisis and citrate treatment”, “kidney stones and citrate treatment”, a Medline search revealed 635 articles published between 1 January 1966 and 1 December 2004. For the present analysis, only studies meeting all of the following criteria were included: (1) publications in English or German, (2) studies on preventive alkali citrate treatment in patients with calcium oxalate, uric acid and infection stone disease, (3) clinical studies including at least ten subjects, and (4) treatment phases of at least 1 week duration. A total of 43 studies met the inclusion criteria and were further subclassified according to intermediate or ultimate endpoints as well as to study design. With stone recurrence as the ultimate endpoint, 21 uncontrolled studies in almost 1,000 patients demonstrated a reduction in stone forming rate by 47–100%. In four randomized controlled trials including 227 patients, 53.5% on alkali citrate vs 35% on placebo remained stone-free after at least 1 year of treatment (P<0.0005). Similar values (66% vs 27.5% for alkali citrate vs placebo, P<0.0005) were obtained in 104 patients from two randomized trials with dissolution/clearance of residual stones as endpoint. Unfortunately, up to 48% of alkali citrate treated patients left the studies prematurely, primarily due to adverse effects such as eructation, bloating, gaseousness or frank diarrhea.