Etiology

Renal stones are crystalline mineral depositions that form from microscopic crystals in the loop of Henle, distal tubules, or the collecting duct. This is usually in response to elevated levels of urinary solutes, such as calcium, uric acid, oxalate, and sodium, as well as decreased levels of stone inhibitors, such as citrate and magnesium. Low urinary volume and abnormally low or high urinary pH also contribute to this process. All of these can lead to urine supersaturation with stone-forming salts and subsequent stone formation.[19] Supersaturation depends on urine pH, ionic strength, solute concentration, and solute chemical interaction. The higher the concentration of 2 ions, the more likely they are to precipitate out of solution and form crystals. As ion concentrations increase, their activity product reaches the solubility product (Ksp). Concentrations above this point can initiate crystal growth.[1] Once crystals are formed, they either pass out with the urine or become retained in the kidney, where they can grow and stones can form. In urine, even when the concentration of calcium oxalate exceeds the solubility product, crystallization may not occur because of prevention from urinary inhibitors. Both urinary calcium and oxalate are important and equal contributors to calcium oxalate stone formation.[20] Several factors increase calcium oxalate supersaturation in urine. These include low urine volume and low citrate, and increased calcium, oxalate, and uric acid.[20]

Pathophysiology

There are differing theories as to the exact pathophysiology of stone formation. Free and fixed particle theories of stone formation are still being debated. Therefore, it is not known whether stones form by deposition of microscopic crystals in the loop of Henle, distal tubules, or the collecting duct. In one study, renal papillary plaques were examined in idiopathic calcium oxalate stone formers.[21] Plaques were composed of calcium phosphate/apatite deposits, localized to the basement membrane of the thin loop of Henle and extending into the papillary interstitium. Once these plaques form, they erode through the urothelium and constitute a stable, anchored surface on which calcium oxalate crystals can nucleate and grow as attached stones. Plaque lesions though reached the basement membrane of collecting ducts, but did not affect the ductal cells. The papillary surfaces of nonstone formers did not show any plaques. In the same study papillary areas of patients with stones due to obesity-related bypass procedures did not have such plaques, but instead had intratubular hydroxyapatite crystals in collecting ducts, with dilation and damage to lining cells proximal to obstruction,[21] hence indicating that stone formation is a heterogeneous process.

Renal colic from nephrolithiasis is secondary to obstruction of the collecting system by the stone. The stretching of the collecting system or ureter is due to an increase in intraluminal pressure. This causes nerve endings to stretch and therefore the sensation of renal colic.[1] Pain from urinary calculi can also be due to local inflammatory mediators, edema, hyperperistalsis, and mucosal irritation.[1]

Classification

Chemical composition of renal calculi

There is no formal classification system for renal stones, but they can be classified by composition. For patients with recurrent nephrolithiasis, 24-hour urine measurements allow risk factors to be identified and corrected, which may direct ongoing medical management. A working classification is:

  • Calcium stones: 80% of renal calculi[2]

  • Calcium oxalate: 80% of all calcium stones; risk factors include low urine volume, hypercalciuria, hyperuricosuria, hyperoxaluria, and hypocitraturia

  • Calcium phosphate (hydroxy apatite or brushite): 20% of all calcium stones; risk factors include low urine volume, hypercalciuria, hypocitraturia, high urine pH, and associated conditions include primary hyperparathyroidism and renal tubular acidosis

  • Uric acid stones: 10% to 20% of renal calculi; most commonly due to urinary pH <5.5, although hyperuricosuria can also contribute[3]

  • Cystine stones: 1% of renal calculi; caused by an inborn error of metabolism, cystinuria, an autosomal-recessive disorder that results in abnormal renal tubular reabsorption of the amino acids cystine, ornithine, lysine, and arginine[2]

  • Struvite stones: 1% to 5% of renal calculi, also known as infection stones; composed of magnesium, ammonium, and phosphate. They frequently present as staghorn calculi and may be associated with urea-splitting organisms, such as Proteus, Pseudomonas,and Klebsiella species. E coli is not a urease-producing organism.[4]

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