What causes calcium oxalate stones?

Causes of Calcium Oxalate Stones

Calcium oxalate stones form when urine becomes supersaturated with calcium and oxalate, driven by multiple dietary and metabolic factors that increase urinary excretion of these substances or reduce protective inhibitors like citrate. 1, 2

Primary Metabolic Abnormalities

Hypercalciuria

• Idiopathic hypercalciuria is the most common metabolic cause of calcium oxalate stones, characterized by excessive urinary calcium excretion (>200 mg/24 hours) despite normal serum calcium levels 3
• Approximately 20% of ingested calcium is normally absorbed, but this proportion increases significantly in individuals with idiopathic hypercalciuria 1
• Hypercalciuria accounts for a substantial proportion of the approximately 80% of kidney stones that contain calcium 1, 2

Hyperoxaluria

• Hyperoxaluria has a disproportionate effect on calcium oxalate solubility, with up to one-third of calcium oxalate stone formers experiencing increased intestinal absorption of dietary oxalate 2
• In normal individuals, approximately half of urinary oxalate derives from diet and half from endogenous synthesis 4
• Urinary oxalate excretion is a continuous variable when indexed to stone risk, with individuals excreting >25 mg/day benefiting from reduction strategies 4
• The only consistent difference identified between normal individuals and stone formers is enhanced intestinal oxalate absorption 5

Hypocitraturia

• Low urinary citrate is a critical risk factor because citrate normally inhibits calcium oxalate crystal nucleation, aggregation, and growth 2, 3
• Citrate complexes with calcium in urine, decreasing calcium ion activity and thus the saturation of calcium oxalate 6
• Hypocitraturia reduces the natural inhibition of calcium crystal formation 7

Hyperuricosuria

• Elevated urinary uric acid promotes calcium oxalate stone formation through heterogeneous nucleation 7
• High uric acid excretion is associated with both uric acid stones and calcium oxalate stones 7

Dietary Promoters

High Oxalate Intake

• Dietary oxalate is plant-derived from vegetables, nuts, fruits, and grains, contributing 10-50% of urinary oxalate 2
• High-oxalate foods include certain nuts, vegetables, wheat bran, rice bran, chocolate, tea, and strawberries 8
• However, dietary oxalate restriction should only be recommended for patients with documented hyperoxaluria, not all stone formers 1, 2

Excessive Sodium Intake

• High sodium intake reduces renal tubular calcium reabsorption, directly increasing urinary calcium excretion 1, 2
• Sodium restriction has been shown to reduce urinary calcium excretion in randomized trials 8
• The mechanism involves decreased proximal tubular calcium reabsorption when sodium delivery to the distal nephron increases 2

High Animal Protein Consumption

• Animal protein metabolism generates sulfuric acid, which increases urinary calcium and uric acid excretion while simultaneously reducing urinary citrate excretion 1, 2
• A positive association between animal protein consumption and kidney stone formation has been demonstrated in men 8
• This triple effect (increased calcium, increased uric acid, decreased citrate) makes animal protein particularly lithogenic 1

Vitamin C Supplementation

• Vitamin C is metabolized to oxalate in the body, leading to increased oxalate generation and excretion 1, 8
• Vitamin C supplementation can significantly increase urinary oxalate levels, particularly at doses exceeding 1000 mg/day 8

Low Dietary Calcium Intake (Paradoxical)

• Contrary to intuition, low dietary calcium intake paradoxically increases stone risk by reducing gastrointestinal binding of oxalate, thereby increasing oxalate absorption and urinary excretion 2, 9
• Higher calcium intake binds dietary oxalate in the gut, reducing oxalate absorption 1
• Multiple large prospective studies show individuals in the highest quintile of dietary calcium intake have more than 30% lower risk of stone formation compared to the lowest quintile 1

Inadequate Fluid Intake

• Low urine volume (<2 liters/day) concentrates stone-forming substances, increasing supersaturation 2, 7
• Dehydration is a fundamental driver of stone formation by concentrating all lithogenic factors 8

Other Dietary Factors

• High carbohydrate intake increases urinary calcium excretion 1
• Sugar-sweetened beverages, particularly colas acidified with phosphoric acid, increase stone recurrence risk 8

Endogenous Production Factors

• Hyperoxaluria predominantly results from increased endogenous production rather than dietary intake alone 9
• Vitamin B6 deficiency may increase endogenous oxalate production and oxaluria 1
• Intestinal hyperabsorption of oxalate can occur when insufficient calcium is available for complexation with oxalate in the intestinal lumen 9

Common Pitfalls to Avoid

• Never restrict dietary calcium in stone formers—this paradoxically increases stone risk by increasing urinary oxalate absorption 2
• Avoid calcium supplements taken between meals, as they do not bind dietary oxalate effectively; calcium should be consumed with meals 8, 2
• Do not assume all calcium oxalate stone formers require oxalate restriction—only those with documented hyperoxaluria benefit from limiting high-oxalate foods 1, 2
• Recognize that 24-hour urine assessment may miss transient surges in urinary oxalate excretion, which can promote stone growth 4