Urinary Calculi

STONE FORMATION

The genesis of urinary stones requires both crystal formation and aggregation. Crystal formation occurs when concentrations of the stone components reach supersaturation within the urine at a specific temperature and pH. Intermittent supersaturation occurs frequently, e.g., after meals or during periods of dehydration. These crystals must then aggregate to form stones and be retained within the kidney. Normal urine contains inhibitors of crystal formation and aggregation. Citrate and magnesium are inhibitors of crystal formation. Tamm-Horsfall protein and nephrocalcin are potent inhibitors of crystal aggregation.

TYPES AND CAUSES OF STONES

Calcium Stones (75%)

Calcium oxalate, as either a monohydrate or dihydrate (less dense), is a major component of most urinary stones. Calcium phosphate (apatite) is the second most common component of stones and is usually found in association with calcium oxalate. Both are highly insoluble salts in urine. Factors that are significant in calcium stone formation are discussed below. Hypercalciuria is the direct antecedent of most calcium stones.

▪ Causes of Hypercalciuria

Increased intestinal absorption—the mechanism of excessive intestinal calcium absorption that occurs in patients with idiopathic hypercalciuria is unknown; however, it is believed to be the most common etiology, accounting for approximately 50% of cases. Serum calcium is usually normal in the idiopathic group. Excessive vitamin D intake will also produce increased intestinal absorption resulting in hypercalcemia and hypercalciuria.
Decreased renal reabsorption—the second major cause of idiopathic hypercalciuria is thought to be a “renal leak” mechanism.
The loss of calcium in the urine leads to increased parathyroid hormone (PTH), which in turn causes elevated 1,25-vitamin D₃ and increased intestinal absorption to maintain normal serum levels of calcium.
Increased bone resorption—the most common etiology of increased bone resorption is hyperparathyroidism; however, it accounts for <5% of stone patients. Parathyroid hyperplasia or adenomas secrete excessive amounts of PTH. PTH causes (1) increased calcium reabsorption in the proximal convoluted tubule, (2) increased 1,25-vitamin D₃, and (3) increased bone demineralization and calcium release from the bone. Patients will have both elevated PTH and serum calcium levels. Other less frequent causes of resorptive hypercalciuria include chronic immobilization, metastatic cancer to bone, multiple myeloma, and vitamin D intoxication.

▪ Hyperoxaluria

Oxalate is a major component of most calcium stones and has an effect on crystallization that is ten times greater than that of calcium. Eighty percent of urinary oxalate comes from endogenous production in the liver (40% from ascorbic acid and 40% from glycine) and 20% from dietary sources. Foods high in oxalate are tea, coffee, beer, rhubarb, cocoa, spinach, and other green leafy vegetables. The primary site of oxalate absorption is the distal bowel (colon). Patients with small bowel resection (or bypass) or inflammatory bowel disease can have increased oxalate absorption.

▪ Hyperuricosuria

Uric acid promotes calcium oxalate crystal formation. Hyperuricosuria with normal urine pH (>5.5) is frequently associated with calcium stones.

▪ Hypocitraturia

Citrate in the urine has an inhibitory effect on stone formation by binding with calcium in the urine and thereby decreasing calcium oxalate and calcium phosphate crystal formation. A low urinary citrate level is associated with calcium nephrolithiasis in 20% to 60% of patients with stone formation. Conditions that can result in hypocitraturia are renal tubular acidosis (RTA), strenuous exercise, enteric hyperoxaluria, and diets high in animal protein.

▪ Type I (Distal) Renal Tubular Acidosis

Type I RTA is caused by an inability of the distal nephron to establish and maintain a hydrogen ion gradient between the
tubular fluid and the blood (see Chapter 28). It causes primarily calcium phosphate stone formation in up to 70% of adults with the disorder because of hypocitraturia and hypercalciuria. The diagnosis of type I RTA is made by finding hypokalemia, hyperchloremia, metabolic acidosis, and a urine pH ≥ 5.5. Giving potassium citrate corrects the hypocitraturia, hypokalemia, and metabolic acidosis.

Infection Stones (Struvite) (15%)

Magnesium ammonium phosphate (MgNH4PO4-6H2O) or “triple phosphate” stones occur in the setting of persistently high urinary pH caused by urea-splitting bacteria, resulting in high ammonia production. Alkaline pH > 7.2 markedly reduces the solubility of magnesium ammonium phosphate in urine, resulting in its precipitation. The major urea-splitting organisms include Proteus species, Pseudomonas, and Klebsiella. Neurogenic bladder and foreign bodies in the urinary tract (e.g., catheters and sutures—even chromic catgut) have a high association with the formation of struvite calculi. Struvite stones have been shown to contain numerous infective bacteria within their structure where antibiotics cannot penetrate; therefore, they must be removed if infection is to be cured. Prophylaxis against recurring magnesium ammonium phosphate stones requires maintenance of sterile urine (long-term suppressive antibiotics), high urine volumes, and decreased urinary phosphate levels (limit dietary phosphate ingestion and intestinal absorption by administering phosphate-binding aluminum hydroxide gels). Struvite calculi account for most staghorn stones.

Uric Acid Stones (5%-10%)

Uric acid is a product of purine metabolism and is excreted in the urine. Stones form in the setting of low urine volume, low pH (acid urine), and high levels of urinary uric acid (hyperuricosuria). They are the only radiolucent urinary calculi. Uric acid stone formers can be categorized into two major groups: those with high blood levels of uric acid and those with normal levels.

▪ Hyperuricosuria without Hyperuricemia

Causes of isolated uric acid stones include a consistently abnormal low pH (e.g., patients with chronic diarrheal states or those taking acidifying medications), excessive water loss (especially
from the gastrointestinal tract), uricosuric drugs (e.g., salicylates and thiazides), and high protein diets. Management of these patients consists of increasing urinary volume to 2 L/day (or 1 L urine output for every 300 mg uric acid in a 24-hour urine collection), limiting dietary proteins to <90 g/day, and alkalinizing urine (to a level between pH 6.5 and 7.0).

▪ Hyperuricosuria with Hyperuricemia

Elevated serum uric acid levels can be caused by gout, myeloproliferative disorders (acute leukemia), or neoplastic disease and the Lesch-Nyhan syndrome (an inborn error of metabolism owing to a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase). These patients will usually require treatment with allopurinol 300 mg/day, in addition to the above measures.

Cystine Stones (1%)

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