Our systematic review of randomized controlled trials (RCTs) found that high water intake lowered long-term risk of nephrolithiasis recurrence by approximately 60% and that among men with high baseline soft drink intake, reduced soft drink consumption modestly lowered risk of recurrent renal colic. Results from one trial suggested that when added to increased water intake, a diet including higher calcium, lower animal protein, and lower sodium reduced stone risk compared with a low-calcium diet. Results from other multicomponent diet intervention trials also suggested that diets including regular calcium may lower recurrence risk but did not provide further support for the efficacy of diets including low sodium, and these results suggested the possibility that lower animal protein may increase risk of stone recurrence. Furthermore, we found no trials that examined the independent effect of altering dietary intake of calcium, sodium, animal protein, fruit and fiber, purine, oxalate, or any other individual dietary element on risk of stone recurrence. There was no evidence for benefit of specific dietary supplements for prevention of stone recurrence. Adverse event reporting was poor.
Our finding that increased water or fluid intake is protective against recurrent nephrolithiasis is consistent with observational data [6
] and with research demonstrating that urinary dilution in vitro and in vivo reduces urinary supersaturation of calcium phosphate, calcium oxalate, and monosodium urate [21
]. Increased fluid intake also may help prevent nephrolithiasis by increasing crystalline-product transit through the nephron, thus decreasing contact time with potential adsorptive surfaces [22
]. Given the consistent findings of benefit, albeit from only two trials, there appears to be sufficient evidence to recommend increased fluid intake in patients with a history of nephrolithiasis, either by daily water intake of >2 liters or by daily urine output of >2.5 liters.
Trial findings that reduction in soft drink intake significantly lowered risk of recurrent renal colic in men with high baseline levels of soft drink consumption, particularly those whose drinks were acidified solely by phosphoric acid, did not appear to be explained by a compensatory increase in consumption of other liquids. Two large prospective cohort studies reported no increased risk of nephrolithiasis associated with any type of soft drink consumption after adjusting results for total fluid intake and other factors [23
]. Based on trial results, nephrolithiasis patients with high intake of phosphoric acid (via acidified soft drinks) may be advised to minimize their soft drink consumption while maintaining adequate total fluid intake.
In prior observational data, an inverse association has been reported between dietary calcium intake and risk of nephrolithiasis [5
]. The proposed mechanism for this effect is that adequate dietary calcium intake leads to binding of oxalate in the intestine, leading to a lower risk of hyperoxaluria; however, no trial studied the independent effect of regular dietary calcium on stone recurrence. One trial that compared a multicomponent diet including 1200 mg/d of calcium with a low-calcium diet reported a substantial reduction in stone recurrence. While a second trial that included regular or increased dietary calcium as part of a multicomponent diet reported reduced stone recurrence risk compared with a group that received general diet recommendations, the general diet recommendations included 750–1000 mg/d of dietary calcium, so that both treatment groups were assigned diets with daily calcium intake greater than their average baseline intake. Furthermore, actual dietary calcium intake during treatment was not reported [15
]. Therefore, it is possible that results in this second trial were not attributable to dietary calcium intake or, conversely, that observed outcome differences underestimated the benefit of regular dietary calcium intake relative to that of lower calcium intake. Although trial evidence for the beneficial effect of dietary calcium is limited and indirect, it seems reasonable for patients with a history of nephrolithiasis to maintain at least regular dietary calcium intake. Because the individual elements composing the different multicomponent dietary intervention trials were heterogeneous, and their results were conflicting in some aspects, conclusions about their efficacy for reducing risk of stone recurrence should be drawn cautiously. In one trial, for example, risk of stone recurrence was lower in participants assigned to regular dietary calcium, low sodium, and low animal protein versus a low-calcium diet. Because both groups were advised to increase water and to decrease oxalate intake, the observed treatment benefit appeared to be additional to any from these cointerventions; however, the specific impact of lowering sodium and/or animal protein intake on these results was uncertain. Although high sodium intake increases urine pH and urinary calcium excretion and reduces urinary citrate [25
], associations with increased risk of stones in observational studies are inconsistent [5
], and no other trials have examined the effect of lowering dietary sodium on risk of stone recurrence, even in combination with other diet changes. Therefore, at this time, no conclusion can be drawn regarding the efficacy of dietary sodium restriction for prevention of stone recurrence. A second multicomponent diet trial, in which both treatment groups were assigned increased fluid intake and dietary calcium, showed a lower risk of recurrence in the control group and a much greater risk of stone recurrence in participants assigned to lower animal protein, increased fruit, whole grains, and bran, and lower purines. Despite data indicating favorable effects of lower animal protein on urinary constituents [26
], associations between animal protein intake and stone risk in observational studies are inconsistent [5
]. Based on results from randomized trials, it is unclear whether a diet low in animal protein will, when combined with high water intake and regular dietary calcium intake, decrease, have no effect on, or will even increase risk of stone recurrence. It cannot be determined whether addition of increased fruit, whole grains, bran, and decreased purines increased stone-recurrence risk in the second trial, but at this time there is insufficient evidence to support their inclusion in a diet to reduce risk of stone recurrence. For a third multicomponent diet trial, because it reported only overall results from a comparison between groups assigned to a comprehensive metabolic evaluation and tailored diet versus a limited evaluation and general diet, it is not possible to separate out the beneficial or adverse effects of any specific dietary element or multicomponent diet, overall or in any metabolic subgroup. Inconsistent results from other trials suggest that not all components of the comprehensive metabolic evaluation and tailored diet were likely to be contributing to a reduction in recurrent stone risk.
There are few RCT data on the efficacy of supplements, with neither of two eligible trials suggesting benefit. Although mixed results from observational studies have suggested that calcium supplements may increase stone recurrence risk [5
], we identified no RCTs that randomized nephrolithiasis participants to calcium supplements compared with control for prevention of recurrent stones. A systematic review of RCTs of calcium supplementation, mostly performed in older women to prevent fractures or bone loss, reported no increased rate of stone events among those allocated to calcium supplementation [29
The current review is limited by the available evidence. First, heterogeneity in patient populations, treatment interventions, and methods of recurrent stone ascertainment hindered our ability to compare efficacy outcomes among trials and to explain apparently mixed results for specific individual dietary elements and multicomponent diets. Second, though one trial tested a general strategy of extensive metabolic evaluation and tailored diet versus limited evaluation and a general diet, there were no trials that evaluated the efficacy of a diet, fluid, or supplement intervention versus control within any specific metabolic subgroups, such as in patients with hyperoxaluria, hyperuricosuria or hyperuricemia, or hypercalcuria. Third, the small size of most trials limits the confidence that can be placed in efficacy estimates. Fourth, few adverse effects data were reported, though the relatively low withdrawal rates suggested that the interventions were tolerated. Finally, trials were predominately performed in younger men with calcium stones, so the generalizability of results to other patient populations is not certain.
In conclusion, evidence from this systematic review of RCTs indicates that high water intake reduces risk of recurrent nephrolithiasis and that reduction of soft drink intake may prevent recurrent colic in men with high baseline level of soft drink consumption. Limited data suggest that regular dietary calcium may provide additional benefit. Data on other diet interventions are inconclusive. Future trials are needed to better clarify whether there is additional benefit from reducing dietary intake of animal protein, sodium, or oxalate, and from increasing dietary calcium, potassium, or intake of fruit and/or fiber. Consensus should be sought regarding the definition of clinically meaningful end points, so that efficacy outcomes are standardized across trials. Adverse effects and patient compliance should be better tracked to provide additional insight regarding potential implementation of therapies shown to be effective.