Nephrolithiasis (Kidney Stones) - Harrison's Principles of Internal Medicine, 22nd Edition

Overview

• Harrison's Principles of Internal Medicine 22E, p.2464

Stone Types

• Harrison's, p.2468

Epidemiology

• Prevalence is increasing, likely due to Westernization (dietary changes, rising BMI).
• Up to 20% of men and 10% of women will develop at least one stone in their lifetime (NHANES 2007-2016).
• Prevalence is ~50% lower in Black individuals vs. whites.
• Peak annual incidence in white men: ~3.5 cases/1000 at age 40.
• Substantial economic impact as those affected are often of working age.
• Harrison's, p.2473

Associated Medical Conditions

• GI malabsorption (Crohn's disease, gastric bypass surgery)
• Primary hyperparathyroidism
• Obesity and type 2 diabetes mellitus
• Distal renal tubular acidosis

• Harrison's, p.2478

Risk Factors

Dietary Risk Factors

• Low fluid intake / low urine volume - the single most important modifiable risk factor
• High sodium intake - increases urine calcium
• High animal protein intake - increases urine uric acid and calcium, decreases citrate
• High oxalate intake - increases urine oxalate
• Low calcium intake - paradoxically increases risk (dietary calcium binds intestinal oxalate)
• High fructose intake - increases urine oxalate, calcium, and uric acid

Non-dietary Risk Factors

• Highest incidence in middle-aged white men
• Obesity, high BMI
• Hot climate / geographic "stone belt" regions
• Anatomic abnormalities (e.g., medullary sponge kidney, horseshoe kidney)
• Genetic factors - monogenic disorders cause nephrolithiasis; GWAS studies reveal polygenic contributors

Urinary Risk Factors (the proximate determinants)

• Hypercalciuria - most common urinary abnormality
• Hyperoxaluria
• Hypocitraturia - citrate is the main natural inhibitor of crystallization
• Hyperuricosuria
• Low urine volume
• High or low urine pH (depending on stone type)
• Harrison's, p.2494-2534

Clinical Presentation

• Renal colic: Sudden onset severe flank pain radiating to the groin; classically colicky but often constant; nausea and vomiting common
• Hematuria (gross or microscopic) in ~90% of cases
• Urinary urgency/frequency when stone is near the ureterovesical junction
• Stones <5 mm usually pass spontaneously; >10 mm unlikely to pass without intervention

Diagnosis

• Non-contrast CT (CT-KUB): Gold standard - detects virtually all stone types, determines size and location
• Plain X-ray (KUB): Calcium-containing stones are radiopaque; uric acid stones are radiolucent
• Renal ultrasound: Useful to detect hydronephrosis; avoids radiation (preferred in pregnancy)
• Urinalysis: Hematuria; crystal type may suggest stone composition; pH helps (low pH - uric acid; high pH - struvite)
• 24-hour urine collection: Essential for metabolic evaluation in recurrent stone formers - measures calcium, oxalate, uric acid, citrate, sodium, creatinine, pH, volume

Prevention by Stone Type

Calcium Oxalate

• Increase fluid intake (goal urine volume >2 L/day)
• Reduce sodium and animal protein
• Maintain adequate dietary calcium (~1200 mg/day with meals)
• Thiazide diuretics (e.g., hydrochlorothiazide, indapamide, chlorthalidone) - reduce urine calcium
• Potassium citrate - increases urine citrate, reduces crystallization
• DASH diet or Mediterranean diet - strong observational data for reduced stone risk

Calcium Phosphate

• Same as above for calcium oxalate
• Monitor urine pH (supplemental alkali can worsen by raising pH - since these patients already have high pH)
• Reduce dietary phosphate
• Harrison's, p.2665-2667

Uric Acid

• Urine pH is the key factor - uric acid stones form at persistently low pH
• Alkali supplementation (potassium citrate/bicarbonate) - goal urine pH 6.5 throughout day and night
• Reduce purine-containing foods (animal flesh)
• Increase fruits and vegetables
• If above measures fail: xanthine oxidase inhibitor (allopurinol or febuxostat) reduces urine uric acid by 40-50%
• Note: serum uric acid does NOT reliably predict urine uric acid excretion
• Harrison's, p.2669-2671

Cystine

• High fluid intake is essential (highest priority)
• Tiopronin (preferred) or D-penicillamine - bind cystine covalently to increase solubility
• Potassium citrate/bicarbonate to alkalinize urine (goal pH 7.5)
• Avoid sodium salts (sodium increases cystine excretion)
• Harrison's, p.2673

Struvite (Infection Stones)

• Form only when the upper urinary tract is infected with urease-producing bacteria (e.g., Proteus mirabilis, Klebsiella)
• Urease splits urea into ammonium, raising urine pH to 7.2-8.0 - an alkaline environment that precipitates magnesium ammonium phosphate
• Also called "infection stones" or "triple-phosphate stones"
• Can form staghorn calculi that fill the renal pelvis and calyces
• Require complete surgical removal + eradication of the infection; stone fragments harbor bacteria and lead to recurrence
• Harrison's, p.2675

Summary Table