What are the causes and risk factors for developing kidney stones in individuals, particularly those with a family history, who are overweight, or men over 40?

Causes and Risk Factors for Kidney Stones

Kidney stones form when urine becomes supersaturated with minerals, primarily due to a combination of metabolic abnormalities, dietary factors, genetic predisposition, and systemic conditions—with obesity, male sex, and family history being particularly strong risk factors. 1

Epidemiology and High-Risk Demographics

The prevalence of kidney stones has increased dramatically, reaching 8.8% overall in the United States, with men affected more frequently than women (10.6% versus 7.1%). 1, 2 However, the gender gap is closing, with a 70% increase in prevalence observed across all age groups and both sexes over recent decades. 1 Men over 40 years of age represent a particularly high-risk group, with incidence increasing with age until 60 years. 1, 2

Genetic and Familial Factors

Family history substantially increases kidney stone risk, with a relative risk of 2.57 for incident stone formation in individuals with a positive family history compared to those without. 3 Genetic factors account for approximately 45% of heritability in kidney stone disease. 1

• Monogenic forms occur in 12-21% of children and young adults, and 1-11% of adults. 1
• Genetic testing should be considered for children, adults aged <25 years, those with recurrent stones (≥2 episodes), bilateral disease, or strong family history. 1

Metabolic and Systemic Conditions

Obesity is one of the strongest modifiable risk factors, with impact being greater in women than men. 1 Stone disease has been increasingly linked to several systemic conditions: 1

• Overweight/obesity increases stone risk through multiple mechanisms including altered urinary composition 1
• Hypertension is independently associated with increased stone formation 1
• Diabetes and metabolic syndrome significantly elevate risk 1, 2, 4
• Gout increases the multivariate relative risk of incident kidney stones to 2.12 (95% CI 1.22-3.68) 5
• Primary hyperparathyroidism should be suspected when serum calcium is high or high-normal 1

Dietary and Nutritional Factors

The American Urological Association identifies specific nutritional factors that predispose to stone formation: 1

• Low fluid intake leading to concentrated urine (most important modifiable factor) 1
• High sodium intake (>2,300 mg/day) increases urinary calcium excretion 1
• Calcium intake below or significantly above the recommended dietary allowance (1,000-1,200 mg/day) 1
• High intake of animal-derived purines and excessive animal protein 1
• Limited intake of fruits and vegetables 1
• High oxalate-containing foods in susceptible individuals 1

Medication-Induced Stone Formation

Patients should be queried regarding regular use of stone-provoking medications or supplements. 1 Medications that increase stone risk include: 6

• Protease inhibitors 6
• Certain antibiotics 6
• Some diuretics 6
• Vitamin C supplements exceeding 1,000 mg/day (metabolized to oxalate) 7, 8
• Calcium supplements (increase stone risk by 20% compared to dietary calcium) 7, 8, 9
• Cranberry supplements (may increase urinary oxalate) 8

Underlying Metabolic Abnormalities

Specific metabolic disorders predispose to stone formation and should be identified through 24-hour urine testing: 1

• Hypercalciuria (high urinary calcium excretion) 1
• Hyperoxaluria (elevated urinary oxalate) 1
• Hypocitraturia (low urinary citrate, a stone inhibitor) 1
• Hyperuricosuria (elevated urinary uric acid) 1
• Renal tubular acidosis type 1 1
• Primary hyperoxaluria (genetic disorder) 1
• Cystinuria (genetic disorder) 1

Anatomic and Infectious Causes

• Recurrent urinary tract infections predispose to struvite (infection) stones 1, 2
• Renal and ureteral anatomic abnormalities increase stone risk 2
• Medullary sponge kidney predisposes to nephrocalcinosis and stone formation 1
• Nephrocalcinosis implies underlying metabolic or anatomic conditions 1

Stone Composition and Etiology

Understanding stone composition guides identification of underlying causes: 1

• Calcium oxalate (61% of stones): most common, associated with dietary and metabolic factors 2, 4
• Calcium phosphate (15%): often forms on Randall's plaques, associated with alkaline urine 2, 4
• Uric acid (12%): associated with acidic urine, gout, high purine intake 2
• Struvite (magnesium ammonium phosphate): infection stones 1, 6
• Cystine: genetic disorder requiring specific management 1, 6

Critical Clinical Pitfall

The recurrence rate among first-time stone formers is 26% within 5 years, and approximately 50% of recurrent stone formers experience recurrence within 5 years of the initial episode. 1, 4 This high recurrence rate underscores the importance of identifying and addressing underlying causes rather than treating stones as isolated events. Multiple or bilateral renal calculi at initial presentation place patients at even greater risk of recurrence and suggest underlying metabolic disorders requiring comprehensive evaluation. 1