Medical School · Year 2 · Renal · includes a quiz and discussion video

Lecture 12: Nephrolithiasis

Unit 2.1: Renal System

Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the epidemiology and types of kidney stones
2. Explain the pathophysiology of stone formation
3. Describe the clinical presentation and diagnosis of nephrolithiasis
4. Differentiate stone types by composition and etiology
5. Explain acute management of renal colic
6. Describe prevention strategies for recurrent stone disease

Epidemiology and Overview

Kidney stones represent one of the most common and painful urologic conditions encountered in clinical practice. The lifetime prevalence reaches 10-15% in developed countries, with men affected two to three times more frequently than women. Peak incidence occurs between ages 40 and 60, though stones can develop at any age. Without preventive measures, recurrence affects approximately 50% of patients within five years of their first stone episode, emphasizing the importance of metabolic evaluation and targeted prevention strategies.

Multiple risk factors contribute to stone formation. Dietary factors include low fluid intake (concentrated urine), high sodium consumption (increases urinary calcium), high animal protein intake (acidifies urine and increases uric acid and calcium), and paradoxically, low dietary calcium (increases oxalate absorption). Medical conditions predisposing to stones include obesity, diabetes mellitus, gout, and primary hyperparathyroidism. Anatomic abnormalities such as medullary sponge kidney, horseshoe kidney, and ureteropelvic junction obstruction promote stone formation through urinary stasis. Certain medications including topiramate (carbonic anhydrase inhibition causes alkaline, hypocitraturic urine), excessive vitamin C supplementation (converted to oxalate), and calcium supplements taken without food increase stone risk. Hot climates promote dehydration and concentrated urine.

Stone composition varies, with calcium-containing stones predominating. Calcium oxalate stones account for 70-80% of all stones and appear radiopaque on plain radiographs. Pure calcium phosphate stones constitute 5-10% and are also radiopaque. Uric acid stones represent 5-10% but are radiolucent, invisible on plain X-ray though readily detected on CT. Struvite (magnesium ammonium phosphate) stones account for 5-10% and form only in the presence of urease-producing bacteria. Cystine stones, though rare at 1-2%, cause significant morbidity due to their high recurrence rate and association with inherited cystinuria.

<image>Panel A: Prevalence statistics showing 10-15% lifetime risk with male-to-female ratio of 2-3:1, age distribution curve peaking at 40-60 years, and 50% recurrence at 5 years without preventive measures. Panel B: Risk factors by category including dietary (low fluid, high sodium, high protein, low calcium), medical conditions (obesity, diabetes, gout, hyperparathyroidism), anatomic (medullary sponge kidney, horseshoe kidney), and medications (topiramate, vitamin C, calcium supplements). Panel C: Pie chart of stone composition showing calcium oxalate (70-80%), calcium phosphate (5-10%), uric acid (5-10%), struvite (5-10%), and cystine (1-2%). Panel D: Radiographic appearance by stone type showing calcium stones as radiopaque, uric acid as radiolucent (invisible on KUB but visible on CT), struvite as radiopaque, and cystine as faintly radiopaque.</image>

Pathophysiology of Stone Formation

Stone formation requires supersaturation of urine with stone-forming constituents. Supersaturation occurs when the concentration of a solute exceeds its solubility in that solution, creating thermodynamic conditions favoring crystal precipitation. The urine exists in one of three states: undersaturated (crystals dissolve), metastable (between solubility and nucleation thresholds, where crystals neither form spontaneously nor dissolve), or supersaturated above the nucleation threshold (crystals form and grow). Most stone formers have urine in the metastable range much of the time, with intermittent excursions into the supersaturated zone.

Multiple factors influence whether supersaturation leads to clinical stone formation. Increased urinary solute excretion provides more substrate for crystallization—hypercalciuria, hyperoxaluria, hyperuricosuria, and cystinuria all increase respective stone risks. Low urine volume concentrates all solutes, raising concentrations toward supersaturation. Urinary pH dramatically affects solubility of certain stone components: uric acid is markedly less soluble below pH 5.5, while calcium phosphate precipitates in alkaline urine above pH 7.0. Reduced inhibitor concentrations remove natural protection against crystallization.

The urine contains multiple crystal inhibitors that normally prevent stone formation despite supersaturation. Citrate is the most clinically important inhibitor, binding calcium to form soluble complexes and directly inhibiting crystal growth and aggregation. Hypocitraturia therefore represents a major modifiable risk factor. Magnesium binds oxalate, reducing free oxalate available for calcium oxalate crystallization. Pyrophosphate, Tamm-Horsfall protein, nephrocalcin, and other macromolecules inhibit various stages of crystal nucleation and growth.

Randall's plaques provide the nidus for most calcium oxalate stones. These interstitial calcium phosphate deposits form at the tips of renal papillae, in the basement membrane of the thin loops of Henle. When plaques erode through the urothelium, they become exposed to supersaturated urine, serving as heterogeneous nucleation sites where calcium oxalate crystals preferentially deposit and grow.

<image>Panel A: Supersaturation concept showing concentration gradient from undersaturated (crystals dissolve) through metastable zone (neither form nor dissolve) to supersaturated above nucleation threshold (crystal formation and growth). Panel B: Factors promoting stone formation including increased solute excretion (calcium, oxalate, uric acid, cystine), decreased urine volume concentrating all solutes, and pH effects with uric acid precipitating below pH 5.5 and calcium phosphate above pH 7.0. Panel C: Urinary crystal inhibitors showing citrate binding calcium to form soluble complexes, magnesium binding oxalate, and macromolecular inhibitors (pyrophosphate, Tamm-Horsfall protein, nephrocalcin) coating crystals to prevent growth. Panel D: Randall's plaque mechanism showing interstitial calcium phosphate deposits at papillary tips in the thin loop of Henle basement membrane, erosion through urothelium, and heterogeneous nucleation of calcium oxalate crystals on exposed surface.</image>

Calcium Stones

Calcium oxalate stones predominate among all stone types, appearing as either monohydrate (whewellite) or dihydrate (weddellite) forms. Under microscopy, calcium oxalate monohydrate crystals appear as dumbbell or oval shapes, while dihydrate forms have characteristic envelope or bipyramidal morphology. The major metabolic abnormalities driving calcium oxalate stone formation include hypercalciuria, hyperoxaluria, and hypocitraturia, often in combination.

Hypercalciuria, defined as urinary calcium excretion exceeding 250 mg/day in women or 300 mg/day in men (or >4 mg/kg/day), occurs through several mechanisms. Absorptive hypercalciuria, the most common type, results from increased intestinal calcium absorption, particularly after meals. Renal leak hypercalciuria occurs when tubular calcium reabsorption is impaired, causing obligate urinary calcium loss that triggers secondary hyperparathyroidism to maintain serum calcium. Resorptive hypercalciuria results from primary hyperparathyroidism, where PTH-driven bone resorption releases calcium that overwhelms tubular reabsorptive capacity. Idiopathic hypercalciuria, likely representing a spectrum of these mechanisms, accounts for most cases.

Hyperoxaluria results from dietary excess, enteric hyperabsorption, or rare primary hyperoxalurias. Dietary hyperoxaluria follows consumption of oxalate-rich foods including spinach, rhubarb, chocolate, nuts, and tea. Enteric hyperoxaluria occurs in malabsorptive conditions (Crohn's disease, post-bariatric surgery, chronic pancreatitis) where unabsorbed fatty acids bind intestinal calcium, leaving oxalate free for absorption. Primary hyperoxaluria encompasses rare inherited enzyme deficiencies causing massive oxalate overproduction.

Calcium phosphate stones form preferentially in alkaline urine above pH 7.0. Conditions promoting alkaline urine and calcium phosphate stones include distal renal tubular acidosis (impaired acid secretion causes alkaline urine with hypocitraturia) and primary hyperparathyroidism (which may produce mixed calcium oxalate and phosphate stones).

<image>Panel A: Calcium oxalate crystal morphology showing monohydrate (whewellite) as dumbbell or oval shapes and dihydrate (weddellite) as characteristic envelope or bipyramidal shapes under microscopy. Panel B: Hypercalciuria types including absorptive (increased intestinal calcium absorption), renal leak (impaired tubular reabsorption triggering secondary hyperparathyroidism), resorptive (primary hyperparathyroidism with bone resorption), and idiopathic. Panel C: Hyperoxaluria sources showing dietary (spinach, chocolate, nuts), enteric mechanism (fat malabsorption with fatty acids binding calcium leaving free oxalate for absorption), and primary hyperoxaluria (rare inherited enzyme deficiencies). Panel D: Calcium phosphate stone formation showing pH-solubility curve with precipitation above pH 7.0, association with distal RTA (alkaline urine plus hypocitraturia), and primary hyperparathyroidism producing mixed stones.</image>

Uric Acid Stones

Uric acid stones possess unique characteristics that distinguish them from calcium-containing stones. They are radiolucent on plain radiographs, appearing invisible on KUB X-ray but readily detected on CT scan where they demonstrate lower Hounsfield units (<400) than calcium stones. This radiolucency allows uric acid stones to masquerade as soft tissue or be missed entirely if only plain radiography is obtained.

The pathophysiology of uric acid stones centers on urinary pH rather than serum uric acid levels. Uric acid has a pKa of 5.5, meaning it exists predominantly in the poorly soluble undissociated form below this pH and in the more soluble urate form above it. At pH 5.0, uric acid solubility is only about 100 mg/L, while at pH 6.5 it exceeds 1000 mg/L. This tenfold difference explains why acidic urine is the primary risk factor for uric acid stone formation, even more important than hyperuricosuria.

Multiple conditions promote acidic urine and uric acid stone formation. Metabolic syndrome and insulin resistance impair renal ammoniagenesis, reducing urinary buffer capacity and producing persistently acidic urine—explaining the association between obesity, diabetes, and uric acid stones. Chronic diarrhea causes bicarbonate loss, resulting in metabolic acidosis and compensatory acidic urine. Gout and myeloproliferative disorders increase uric acid production and excretion. High purine diets contribute additional uric acid load.

Treatment and prevention strategies exploit the pH-dependent solubility. Uric acid stones can be dissolved with urinary alkalinization, a property unique among common stone types. Potassium citrate or sodium bicarbonate raises urine pH to the target range of 6.0-6.5, converting undissociated uric acid to soluble urate. Adequate hydration dilutes urinary uric acid concentration. Allopurinol or febuxostat reduce uric acid production when hyperuricosuria persists despite alkalinization.

<image>Panel A: Stone appearance showing radiolucent on KUB X-ray (invisible) versus visible on CT with lower Hounsfield units (below 400 HU) compared to calcium stones. Panel B: pH-solubility relationship curve showing pKa at 5.5 with dramatic solubility increase, approximately 100 mg/L at pH 5.0 versus 1000 mg/L at pH 6.5, explaining why acidic urine is the primary risk factor. Panel C: Risk factors showing metabolic syndrome pathway (insulin resistance causing impaired ammoniagenesis and persistently acidic urine), chronic diarrhea (bicarbonate loss), gout and myeloproliferative disorders (increased uric acid production), and high purine diet. Panel D: Treatment and dissolution protocol showing potassium citrate or sodium bicarbonate alkalinizing urine to target pH 6.0-6.5, adequate hydration, and allopurinol or febuxostat for persistent hyperuricosuria.</image>

Struvite Stones

Struvite stones, composed of magnesium ammonium phosphate (MgNH₄PO₄), form exclusively in the presence of urease-producing bacteria and are therefore also called infection stones. Their tendency to grow rapidly and fill the renal collecting system produces the characteristic staghorn calculus appearance, with branches extending into multiple calyces. These large stones can occupy the entire renal pelvis and cause significant morbidity if not completely removed.

The pathogenesis requires urease, a bacterial enzyme that hydrolyzes urea into ammonia and carbon dioxide. The ammonia alkalinizes the urine, often raising pH above 7.2, which favors precipitation of magnesium ammonium phosphate. Simultaneously, the ammonia provides the ammonium component of the struvite crystal. Bacteria become incorporated into the growing stone, creating a nidus for persistent infection that cannot be eradicated with antibiotics alone.

Urease-producing organisms include Proteus species (most common), Klebsiella, Pseudomonas, and certain Staphylococcus species (particularly S. saprophyticus). Notably, Escherichia coli, the most common urinary pathogen overall, does not produce urease and does not cause struvite stones. This distinction helps identify which patients with recurrent UTIs are at risk for struvite stone formation.

Management requires complete stone removal because residual fragments harbor bacteria and serve as nidus for rapid regrowth. Antibiotics are essential before and after surgical intervention to reduce sepsis risk, but cannot sterilize the stone without removal. Percutaneous nephrolithotomy (PCNL) is typically required for these large stones. Acetohydroxamic acid, a urease inhibitor, serves as adjunctive therapy when complete stone removal is not possible, though side effects limit its use. Prevention focuses on treating and preventing urinary tract infections, particularly in patients with anatomic abnormalities predisposing to infection.

<image>Panel A: Staghorn calculus appearance on KUB X-ray showing branching radiopaque stone filling the renal pelvis and extending into multiple calyces, with anatomic correlate labeled. Panel B: Pathogenesis cascade showing urease-producing bacteria (Proteus most common, Klebsiella, Pseudomonas; E. coli shown with X indicating no urease), urease reaction hydrolyzing urea to ammonia and CO2, and ammonia alkalinizing urine above pH 7.2 while providing ammonium for crystal formation. Panel C: Struvite precipitation (MgNH4PO4) with bacteria incorporated into the growing stone matrix creating a nidus for persistent infection that antibiotics alone cannot eradicate. Panel D: Management algorithm showing complete surgical removal by PCNL (residual fragments cause regrowth), perioperative antibiotics, acetohydroxamic acid as adjunctive urease inhibitor, and prevention through treating and preventing UTIs.</image>

Cystine Stones

Cystine stones result from cystinuria, an inherited defect in the renal and intestinal transport of dibasic amino acids. The autosomal recessive condition affects the SLC3A1 or SLC7A9 genes encoding subunits of the amino acid transporter responsible for reabsorbing cystine, ornithine, lysine, and arginine (remembered by the mnemonic COLA). While all four amino acids are lost in urine, only cystine causes clinical problems because of its poor solubility.

Cystine is the least soluble of the naturally occurring amino acids, with solubility of only about 300 mg/L at physiologic pH. Patients with cystinuria excrete 400-1000 mg or more of cystine daily, far exceeding the solubility threshold and ensuring supersaturation. Stone formation typically begins in childhood or adolescence, and recurrence rates are extremely high without aggressive prevention.

The characteristic hexagonal crystals visible on urine microscopy are pathognomonic for cystinuria and may be seen even in the absence of clinical stone disease. Cyanide-nitroprusside testing provides a rapid qualitative screen, producing a purple color with elevated cystine. Quantitative 24-hour urine cystine measurement confirms the diagnosis and guides treatment intensity.

Prevention requires extraordinary measures given the inherent insolubility of cystine. Massive fluid intake targeting urine output of 3 liters or more daily dilutes cystine below the supersaturation threshold. Urinary alkalinization to pH above 7.0 improves cystine solubility, though higher targets (pH 7.5) provide even greater benefit. Dietary sodium and protein restriction reduces cystine excretion. When these measures prove insufficient, thiol-binding drugs (D-penicillamine, tiopronin/alpha-mercaptopropionylglycine) bind cystine to form more soluble disulfide compounds. These medications carry significant side effects including proteinuria and bone marrow suppression, limiting their use to patients with refractory disease.

<image>Panel A: Genetics and transport defect showing autosomal recessive inheritance, SLC3A1/SLC7A9 gene mutations, and transporter at proximal tubule and intestine failing to reabsorb COLA amino acids (Cystine, Ornithine, Lysine, Arginine) with cystine highlighted as the insoluble culprit. Panel B: Diagnosis showing pathognomonic hexagonal crystals on urine microscopy, cyanide-nitroprusside qualitative screen (purple color reaction), and quantitative 24-hour urine cystine measurement, with typical childhood or adolescence onset. Panel C: Cystine solubility of approximately 300 mg/L at physiologic pH versus excretion of 400-1000 mg/day ensuring supersaturation, with improved solubility above pH 7.0-7.5. Panel D: Prevention pyramid from base to apex showing massive hydration (greater than 3 L urine output daily), urinary alkalinization (target pH above 7.0), dietary sodium and protein restriction, and thiol-binding drugs (D-penicillamine, tiopronin) for refractory disease with their cystine-binding mechanism.</image>

Clinical Presentation

Renal colic represents the classic presentation of symptomatic nephrolithiasis and ranks among the most severe pains patients experience. The pain results from acute urinary tract obstruction, with distension of the renal capsule and ureter triggering visceral afferent stimulation. The character is typically colicky, waxing and waning in intensity as ureteral peristalsis attempts to propel the stone distally. Patients are classically unable to find a comfortable position, writhing in distress—a presentation that distinguishes renal colic from peritoneal irritation, where patients remain still.

Pain location correlates with stone position along the urinary tract. Stones at the ureteropelvic junction (UPJ) or proximal ureter cause flank pain. As stones migrate to the mid-ureter, pain radiates to the lower abdomen and flank. Distal ureteral stones near the ureterovesical junction (UVJ) produce groin pain and may radiate to the ipsilateral scrotum or labia. Stones at the UVJ additionally cause urinary urgency and frequency from bladder irritation.

Associated symptoms include nausea and vomiting, occurring in the majority of patients and reflecting autonomic responses to visceral pain. Hematuria is present in about 90% of cases microscopically and 30% grossly, though absence of hematuria does not exclude the diagnosis.

Red flags requiring urgent attention include fever with an obstructing stone, which suggests infected hydronephrosis (pyonephrosis)—a urologic emergency requiring immediate drainage. Anuria indicates complete obstruction, either bilateral or in a solitary kidney. Uncontrolled pain despite appropriate analgesics suggests need for intervention. Significant acute kidney injury may indicate obstruction of a functionally significant kidney.

Differential diagnosis includes other causes of acute flank or abdominal pain: appendicitis (RLQ pain, fever, no hematuria), acute pyelonephritis (fever, CVA tenderness, pyuria), abdominal aortic aneurysm rupture (older patient, pulsatile mass, hypotension), ovarian torsion (female, adnexal mass, acute onset), and ectopic pregnancy (female of reproductive age, positive pregnancy test).

<image>Panel A: Pain pattern by stone location showing UPJ/proximal ureter causing flank pain, mid-ureter causing flank-to-lower-abdomen radiation, and distal ureter/UVJ causing groin pain with radiation to ipsilateral scrotum or labia plus urgency and frequency. Panel B: Associated symptoms including nausea and vomiting from autonomic visceral pain response, hematuria (microscopic in 90%, gross in 30%), and characteristic writhing inability to find a comfortable position. Panel C: Red flags requiring urgent attention including fever with obstructing stone (pyonephrosis as a urologic emergency), anuria (complete obstruction), uncontrolled pain despite adequate analgesia, and significant AKI. Panel D: Differential diagnosis with distinguishing features showing appendicitis (RLQ pain, fever, no hematuria), pyelonephritis (fever, pyuria, CVA tenderness), AAA rupture (elderly, pulsatile mass, hypotension), ovarian torsion (adnexal mass), and ectopic pregnancy (positive beta-hCG).</image>

Diagnosis

Initial evaluation of suspected nephrolithiasis includes urinalysis, basic metabolic panel, and imaging. Urinalysis typically reveals hematuria, which supports the diagnosis though its absence does not exclude stones. Crystal identification may suggest stone composition—envelope-shaped crystals indicate calcium oxalate, hexagonal crystals are pathognomonic for cystine. Signs of infection (pyuria, bacteriuria) warrant urine culture. The basic metabolic panel assesses renal function (obstruction may cause AKI) and screens for electrolyte abnormalities suggesting underlying metabolic disorders.

Non-contrast computed tomography of the abdomen and pelvis has become the gold standard imaging modality, with sensitivity exceeding 95% for detecting stones. CT identifies stones regardless of composition, including radiolucent uric acid stones that are invisible on plain radiographs. Stone size, location, and degree of obstruction (hydronephrosis) are readily assessed. Hounsfield units help predict stone composition: calcium stones typically exceed 400 HU, while uric acid stones measure below 400 HU. CT also identifies alternative diagnoses when stones are absent.

Ultrasound serves as first-line imaging in pregnancy and may be appropriate in other settings to avoid radiation. Ultrasound detects hydronephrosis indicating obstruction and can visualize larger stones, though sensitivity for small stones and ureteral stones is limited. Plain abdominal radiography (KUB) remains useful for following known radiopaque stones but cannot detect radiolucent stones and has limited sensitivity overall.

Metabolic evaluation is recommended after the first stone episode to identify treatable abnormalities and guide prevention. Stone analysis, when a stone is captured, determines composition and directs subsequent workup. Twenty-four-hour urine collection measures volume, calcium, oxalate, citrate, uric acid, sodium, and creatinine. Serum calcium screens for hyperparathyroidism. Serum uric acid assesses for hyperuricemia. The metabolic evaluation ideally occurs after acute resolution, when the patient has resumed their normal diet and fluid intake.

<image>Panel A: Initial workup showing urinalysis (hematuria, crystal identification with envelope shapes for calcium oxalate and hexagons for cystine, infection signs), BMP (creatinine and electrolytes), and urine culture if pyuria present. Panel B: Imaging modalities showing non-contrast CT as gold standard (sensitivity greater than 95%, identifies all stone compositions) with Hounsfield unit characterization (calcium greater than 400 HU, uric acid below 400 HU), ultrasound as first-line in pregnancy, and KUB for follow-up of known radiopaque stones. Panel C: Metabolic evaluation components including stone analysis from captured specimen, 24-hour urine collection measuring volume, calcium, oxalate, citrate, uric acid, sodium, and creatinine, and serum calcium and uric acid screening. Panel D: Timeline note indicating metabolic workup should occur after acute resolution when the patient has resumed normal diet and fluid intake.</image>

Acute Management

Pain control takes priority in acute renal colic. NSAIDs represent first-line therapy, with ketorolac commonly used intravenously in the emergency setting and ibuprofen or naproxen appropriate for outpatient management. NSAIDs provide effective analgesia through inhibition of prostaglandin synthesis, reducing ureteral spasm and renal pelvic pressure. When NSAIDs prove insufficient or are contraindicated, opioid analgesics provide alternative pain relief. Intravenous fluids provide comfort but evidence does not support aggressive hydration to "flush" stones, and forced diuresis may increase intrapelvic pressure and pain.

Medical expulsive therapy (MET) with alpha-adrenergic blockers such as tamsulosin aims to facilitate stone passage by relaxing ureteral smooth muscle. Evidence supporting MET remains controversial, with some studies showing modest benefit particularly for distal ureteral stones 5-10 mm in size while others show no significant effect. Current guidelines suggest MET as an option for patients with stones likely to pass spontaneously when pain is controlled.

Spontaneous passage rates depend primarily on stone size. Stones smaller than 5 mm pass spontaneously in over 90% of cases. Stones 5-10 mm pass approximately 50% of the time. Stones larger than 10 mm rarely pass without intervention. Stone location also affects passage probability, with distal ureteral stones more likely to pass than proximal ones. Expectant management is appropriate for 4-6 weeks when stones are likely to pass, no complicating factors exist, and pain is controlled.

Indications for urgent intervention include infected obstructed kidney (pyonephrosis), which constitutes a urologic emergency requiring immediate drainage by ureteral stent or percutaneous nephrostomy. Uncontrolled pain despite adequate analgesia, acute kidney injury from obstruction, obstruction of a solitary kidney, and stones larger than 10 mm that are unlikely to pass all warrant timely intervention.

<image>Panel A: Pain control showing first-line NSAIDs (ketorolac IV, ibuprofen or naproxen PO) and second-line opioids, with IV fluids for comfort but no evidence for forced diuresis. Panel B: Medical expulsive therapy with tamsulosin (alpha-blocker relaxing ureteral smooth muscle), controversial evidence, best for distal ureteral stones 5-10 mm, and expectant management for 4-6 weeks. Panel C: Spontaneous passage rates by stone size showing less than 5 mm (greater than 90%), 5-10 mm (approximately 50%), and greater than 10 mm (less than 10%), with distal location improving passage probability. Panel D: Urgent intervention indications including infected obstructed kidney (pyonephrosis as urologic emergency requiring ureteral stent or percutaneous nephrostomy), uncontrolled pain, AKI, solitary kidney obstruction, and stones greater than 10 mm.</image>

Surgical Management and Prevention

When intervention is required, multiple surgical options exist with selection based on stone size, location, and composition. Shock wave lithotripsy (SWL) uses focused acoustic waves to fragment stones, which then pass spontaneously. SWL works best for stones smaller than 2 cm in the kidney or upper ureter and is least effective for lower pole stones (difficult fragment passage), very hard stones (calcium oxalate monohydrate, brushite), and cystine stones. Ureteroscopy (URS) involves passage of a small scope through the urethra, bladder, and ureter to directly visualize and fragment stones with laser energy. URS has become the dominant approach for ureteral stones and is increasingly used for renal stones as well. Percutaneous nephrolithotomy (PCNL) involves creating a tract through the flank into the kidney, allowing direct removal of large stone burdens. PCNL is preferred for stones larger than 2 cm, staghorn calculi, and lower pole stones where SWL fails.

General prevention strategies apply to all stone formers. Adequate fluid intake represents the single most important intervention, with the goal of producing urine output exceeding 2.5 liters daily. Dietary sodium restriction below 2300 mg daily reduces urinary calcium excretion. Moderate animal protein intake reduces acid load, uric acid production, and calcium excretion. Importantly, dietary calcium should not be restricted—in fact, normal calcium intake (1000-1200 mg daily with meals) reduces oxalate absorption and stone risk, while calcium restriction paradoxically increases stone risk.

Stone type-specific prevention targets the underlying metabolic abnormality. For calcium oxalate stones, thiazide diuretics reduce urinary calcium excretion in patients with hypercalciuria, while potassium citrate increases urinary citrate and inhibits crystallization. Dietary oxalate restriction helps patients with hyperoxaluria. For uric acid stones, urinary alkalinization with potassium citrate represents first-line therapy, with allopurinol added if hyperuricosuria persists. Struvite stone prevention requires complete stone removal and prevention of recurrent urinary tract infections. Cystine stone prevention demands aggressive fluid intake, alkalinization, dietary sodium and protein restriction, and thiol-binding drugs when necessary.

<image>Panel A: Surgical options showing SWL (best for stones below 2 cm in kidney or upper ureter, limited for lower pole and very hard stones), ureteroscopy (dominant approach for ureteral stones with laser fragmentation, increasingly used for renal stones), and PCNL (preferred for stones greater than 2 cm, staghorn calculi, and lower pole stones). Panel B: General prevention pyramid with fluid intake at base (target greater than 2.5 L urine output daily), dietary sodium restriction below 2300 mg, moderate animal protein, and normal dietary calcium (1000-1200 mg with meals, as restriction paradoxically increases stone risk). Panel C: Calcium stone-specific prevention showing thiazide diuretics reducing urinary calcium in hypercalciuria, potassium citrate increasing urinary inhibition, and dietary oxalate restriction for hyperoxaluria. Panel D: Other stone-specific prevention showing uric acid (alkalinization to pH 6.0-6.5 with allopurinol for hyperuricosuria), struvite (complete removal plus UTI prevention), and cystine (hydration greater than 3 L, pH above 7.0, low sodium/protein diet, thiol drugs for refractory disease).</image>

Summary

Nephrolithiasis affects 10-15% of the population with 50% recurrence at 5 years without prevention. Calcium oxalate stones predominate (70-80%), with hypercalciuria, hyperoxaluria, and hypocitraturia as major risk factors. Uric acid stones are radiolucent and form in acidic urine below pH 5.5; they can be dissolved with urinary alkalinization. Struvite stones form only with urease-producing bacteria (Proteus, Klebsiella, Pseudomonas—not E. coli), often appearing as staghorn calculi requiring complete surgical removal. Cystine stones result from inherited cystinuria and produce pathognomonic hexagonal crystals with high recurrence rates.

Diagnosis relies on non-contrast CT as the gold standard, with ultrasound preferred in pregnancy. Stone analysis determines composition and guides prevention. Acute management prioritizes pain control with NSAIDs, medical expulsive therapy with alpha-blockers for stones 5-10 mm, and expectant management for 4-6 weeks if stones are likely to pass (<5 mm pass >90%). Urgent intervention is required for infected obstructed kidney, uncontrolled pain, AKI, or solitary kidney obstruction.

Prevention centers on adequate fluid intake (>2.5 L urine output), sodium restriction, and stone type-specific therapy including thiazides and citrate for calcium stones, alkalinization for uric acid stones, complete removal and UTI prevention for struvite, and intensive measures for cystine stones.

Key Terms

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