What are the causes and risk factors for developing kidney stones in individuals of any age, particularly those with a family history, dehydration, or underlying medical conditions such as gout or inflammatory bowel disease?

Causes of Kidney Stones

Kidney stones form when urine becomes supersaturated with minerals due to metabolic abnormalities, inadequate fluid intake, dietary factors, genetic predisposition, and underlying medical conditions, with low fluid intake being the single most important modifiable cause. 1

Primary Metabolic Abnormalities

The following metabolic disorders directly cause stone formation:

• Hypercalciuria (elevated urinary calcium excretion) is the most common metabolic abnormality in recurrent stone formers 2
• Hyperoxaluria (elevated urinary oxalate) increases calcium oxalate supersaturation and stone risk 2
• Hypocitraturia (low urinary citrate, which normally inhibits stone formation) predisposes to calcium stones 2
• Hyperuricosuria can promote calcium oxalate stone formation even without forming uric acid stones 2
• Low urine volume increases supersaturation of all stone-forming salts 2
• Abnormal urine pH determines stone type: acidic urine (pH <5.5) promotes uric acid stones, while alkaline urine promotes calcium phosphate stones 2

Dietary and Fluid Factors

Inadequate fluid intake resulting in urine output below 2 liters daily is the most critical modifiable risk factor. 2

Additional dietary causes include:

• High sodium intake (>2,300 mg/day) reduces renal tubular calcium reabsorption and increases urinary calcium excretion 1, 2
• Excessive animal protein consumption generates sulfuric acid, increasing urinary calcium and reducing protective urinary citrate 2
• Low dietary calcium intake paradoxically increases stone risk by reducing gastrointestinal oxalate binding, leading to increased oxalate absorption 2
• Sugar-sweetened beverages, particularly colas acidified with phosphoric acid, increase stone recurrence risk 2
• High oxalate foods (spinach, nuts, chocolate) increase stone risk in susceptible individuals 2
• Excessive vitamin C supplementation increases oxalate generation through metabolism 2

Genetic and Familial Factors

Family history substantially increases kidney stone risk, with a relative risk of 2.57 for incident stone formation compared to those without family history. 3

• Genetic factors account for approximately 45% of heritability in kidney stone disease 4, 1
• Monogenic forms occur in 12-21% of children/young adults and 1-11% of adults 4, 1
• Genetic testing should be considered for: children, adults aged <25 years, those with recurrent stones (≥2 episodes), bilateral disease, or strong family history 4, 1

Specific genetic disorders include:

• Primary hyperoxaluria causes severe hyperoxaluria exceeding 75 mg/day 2
• Cystinuria results in cystine stone formation 2

Underlying Medical Conditions

Endocrine and Metabolic Disorders

• Primary hyperparathyroidism causes hypercalciuria and hypercalcemia, identified when serum calcium is high or high-normal 2
• Renal tubular acidosis type 1 leads to persistently alkaline urine, hypocitraturia, and nephrocalcinosis 2
• Obesity is one of the strongest modifiable risk factors, with impact being greater in women than men 5, 1
• Type 2 diabetes, hypertension, and dyslipidemia are commonly associated with stone disease as part of metabolic syndrome 2

Gastrointestinal Disorders

Inflammatory bowel disease significantly increases stone risk through multiple mechanisms. 6, 7

• Chronic bowel disease increases oxalate absorption due to fat malabsorption and increased colonic permeability 2, 6
• Patients with small bowel resection develop hyperoxaluria when the colon is present, as fatty acids increase colonic oxalate permeability 6
• Patients with colon resection and ileostomy form uric acid stones due to bicarbonate loss in ileostomy effluent, leading to acidic urine 6
• IBD patients show decreased urinary citrate, magnesium, volume, and pH—all promoting stone formation 7

Anatomic Abnormalities

• Medullary sponge kidney predisposes to stone formation through urinary stasis 2
• Nephrocalcinosis implies underlying metabolic disorders 2
• Urinary stasis from any anatomic obstruction increases stone risk 2

Infectious Causes

• Recurrent urinary tract infections with urea-splitting organisms (Proteus, Klebsiella) produce struvite (magnesium ammonium phosphate) stones 2

Medication-Induced Stone Formation

• Topiramate and other carbonic anhydrase inhibitors increase calcium phosphate stone risk 2
• Loop diuretics can cause hypercalciuria 2
• Calcium supplements may increase stone risk 2
• Protease inhibitors, certain antibiotics, and some diuretics increase risk of specific stone types 8

Demographic Risk Factors

• Male sex: men are affected more frequently than women (10.6% versus 7.1%), though the gender gap is closing 1, 9
• Age: men over 40 years represent a particularly high-risk group, with incidence increasing until age 60 1
• Hypertension is independently associated with increased stone formation 1

Stone Composition and Underlying Causes

Understanding stone composition guides identification of underlying causes:

• Calcium oxalate (61% of stones) typically indicates hypercalciuria, hyperoxaluria, or hypocitraturia 1, 9
• Calcium phosphate (15%) suggests alkaline urine or renal tubular acidosis 9
• Uric acid (12%) indicates acidic urine, often associated with obesity, gout, or high animal protein intake 9
• Calcium oxalate monohydrate stones with peculiar morphology (white or pale yellow with disorganized internal structure) suggest primary hyperoxaluria 4

Critical Clinical Pitfall

The recurrence rate among first-time stone formers is 26% within 5 years, and approximately 50% of recurrent stone formers experience another episode, emphasizing the importance of identifying and addressing underlying causes rather than treating stones as isolated events. 4, 1