Urinary stone (Kidney stone) prevalence is estimated at 3% in all individuals, and it affects up to 12% of the population during their lifetime. Urinary stone recurrence rates approach 50% at 10 years and males have the highest incidence. Prior to the development of modern urologic techniques for treatment, mortality from untreated staghorn calculi was 27%. Currently mortality from stone disease is rare, although there is still a significant rate (28%) of renal deterioration with certain stone types.

Urinary calculi may have various compositions which include, in order of decreasing frequency: calcium oxalate (monohydrate or dihydrate), uric acid, struvite (magnesium ammonium phosphate), calcium phosphate, and cystine. There are other less common stones, including xanthine and drug-related stones as well. Stones are solutes that occur in amounts too high tostay dissolved (supersaturated) in urine. As a result of supersaturation, the solutes precipitate and aggregate to form concretions or stones.

It is thought that the majority of calcium oxalate stones form from an initial calcium phosphate concretion that originates near the renal calyx epithelium in the highly concentrated environment of the terminal collecting duct. The calcium phosphate concretion (called a Randall’s plaque) erodes through the urothelium, is exposed to urine, and forms a nidus for calcium oxalate deposition with time.

The calcium oxalate deposition grows until the stone becomes large enough to break free of its urothelial “anchor” and then may pass through the collecting system. Factors that promote calcium oxalate supersaturation (and calcium oxalate deposition) are dehydration, hypercalciuria, hyperoxaluria, hypernatrituria, and hyperuricosuria. Urinary citrate is an important inhibitor of calcium oxalate formation so hypocitraturia is a risk factor for stone formation.

Uric acid is a product of purine metabolism. Uric acid is 100 times more soluble at a pH > 6 compared to a pH Less than 5.5. Other than dehydration, the most common risk factor for uric acid lithiasis is persistently acidic urine including the lack of a normal postprandial alkaline tide. Likewise, patients with persistent acidosis (e.g., distal renal tubular acidosis) are also at risk for developing uric acid stones. Less commonly, gout (hyperuricemia) is associated in approximately 20% of cases with hyperuricosuria and uric acid lithiasis. Hyperuricosuria is also associated diseases such as lymphoma or leukemia that are treated with chemotherapy. With such treatment, the sudden lysis of millions of cells releases a large quantity of purines into the circulation and urine that may precipitate in the renal tubules and cause uric acid stones.

Struvite stones are caused by urinary infections with urease producing organisms, the most common being Proteus mirabilis. Less common pathogens include Klebsiella, Enterobacter, or Pseudomonas. (E. Coli is not a urease producing organism.) Urease cleaves each mole of (soluble) urea into two moles of (relatively insoluble) ammonium. As this cleavage occurs, free H+ is bound to NH3 to produce NH4, yielding OH- from water, making urine more alkaline.

Phosphate is less soluble at alkaline versus acidic pH, so phosphate precipitates onto the insoluble ammonium products, yielding magnesium ammonium phosphate. As the bacteria that produce urease remain in urine and within the stone, they continue to produce urease, and continue to cleave urea, and so large (staghorn shaped) stones may develop quite rapidly and fill the calyceal spaces of the kidney (Figure 2).

Cystine stones are produced in patients with a homozygous recessive gene defect affecting cystine transport, resulting in excessive urinary cystine. Cystine is an amino acid composed of cysteine-S-S-cysteine. The four dibasic amino acids are cystine, ornithine, lysine, and arginine, remembered by the mnemonic COLA. Normal individuals generally excrete less than 100 mg of cystine per day in the urine, whereas the majority of homozygous cystinuric patients excrete more than 200 mg per day. There are no known inhibitors of cystine.

Cystine is more soluble at a pH of 9.6 and higher compared to lower pH’s, but it is practically impossible to achieve such a high urine pH by oral alkali agents (and not without risk of calcium phosphate stone formation).