Porth's Essentials of Pathophysiology, 4e

633

Disorders of Renal Function

C h a p t e r 2 5

surgical treatment of structural defects may be indicated. Treatment of complicating urinary tract infections due to urinary stasis is also important.

In addition to supersaturated urine, kidney stone for- mation requires a nidus or nucleus that facilitates crystal aggregation. In supersaturated urine, stone formation begins with small clusters of crystals such as calcium oxalate. Most small clusters tend to disperse because the internal forces that hold them together are too weak to overcome the random tendency of ions to move apart. Larger ion clusters form nuclei and remain sta- ble because the attraction forces balance surface losses. Once they are stable, nuclei can grow at levels of super- saturation below that needed for their creation. Organic materials, such as mucopolysaccharides derived from the epithelial cells that line the tubules, are also thought to act as nuclei for stone formation by lowering the level of supersaturation required for crystal aggregation. The fact that many people experience supersatura- tion of their urine without developing kidney stones is believed to be due to the presence of natural stone inhibitors, including magnesium, citrate, and the Tamm- Horsfall mucoprotein. To date, the measurement and manipulation of stone inhibitors has not been part of clinical practice, with the exception of citrate. 28,29 Urine citrate reduces supersaturation by binding calcium and inhibiting nucleation and growth of calcium crystals. Citrate is a normal by-product of the citric acid cycle in renal cells. Metabolic stimuli that consume this product (as with metabolic acidosis due to fasting or hypokale- mia) reduce the urinary concentration of citrate. Citrate supplementation (potassium citrate) may be used in the treatment of some forms of hypocitraturic kidney stones. Types of Stones There are four basic types of kidney stones: calcium (i.e., oxalate or phosphate), magnesium ammonium phosphate, uric acid, and cystine stones. 4,5,28–30 The causes and treatment measures for each of these types of renal stones are described in Table 25-2. Most kidney

Kidney Stones The most common cause of upper urinary tract obstruc- tion is urinary calculi. Although stones can form in any part of the urinary tract, most develop in the kidneys. Kidney stones, also known as nephrolithiasis or renal calculi , are the third most common disorder of the uri- nary tract, exceeded only by urinary tract infections and prostate disorders. 28 Kidney stones are polycrystalline aggregates composed of materials that the kidneys normally excrete in the urine. 4,5,28–31 The etiology of urinary stone formation is complex. It is thought to encompass a number of factors, including increases in blood and urinary levels of stone- forming components and interactions among the com- ponents; anatomic changes in urinary tract structures; metabolic and endocrine influences; dietary and intestinal absorption factors; and urinary tract infections. Added to the mystery of stone formation is the fact that although both kidneys are exposed to the same urinary constitu- ents, kidney stones tend to form in only one kidney. Two factors implicated in kidney stone formation are a supersaturated urine and an environment that allows the stone to grow. The risk for stone formation is increased when the urine is supersaturated with stone components (e.g., calcium salts, uric acid, magnesium ammonium phosphate, and cystine). Supersaturation depends on uri- nary pH, solute concentration, ionic strength, and com- plexation. The greater the concentration of two ions, the more likely they are to precipitate. Complexation influ- ences the availability of specific ions. For example, oxa- late complexes with sodium and decreases the availability of free sodium ions to participate in stone formation.

TABLE 25-2 Composition, Contributing Factors, andTreatment of Kidney Stones Type of Stone Contributing Factors Treatment

Calcium (oxalate and phosphate)

Hypercalcemia and hypercalciuria

Treatment of underlying conditions

Immobilization

Increased fluid intake Thiazide diuretics

Hyperparathyroidism Vitamin D intoxication Diffuse bone disease Milk-alkali syndrome Renal tubular acidosis Hyperoxaluria Intestinal bypass surgery

Dietary restriction of foods high in oxalate Treatment of urinary tract infection Acidification of the urine Increased fluid intake

Magnesium ammonium phosphate (struvite)

Urea-splitting urinary tract infections

Uric acid (urate)

Formed in acid urine with pH of approximately 5.5

Increased fluid intake

Gout

Allopurinol for hyperuricosuria

High-purine diet

Alkalinization of urine Increased fluid intake

Cystine

Cystinuria (inherited disorder of amino acid metabolism)

Alkalinization of urine