The urinary stones history is as ancient as the civilization itself. Urinary stones are an ancient health problem that have plagued human beings since the dawn of humanity. In 1901, in El Amrah, Egypt, the English archeologist E. Smith discovered a bladder stone from a mummy who was 4,500 to 5,000 years old. Kidney and bladder stone replacement were one of his best known surgical techniques. Stone therapy was reported in ancient Egyptian medical writings dating back to 1500 BC. The earliest mentions of bladder stone surgical diagnosis can be found in both Hindu and Greek texts. Sushruta, a physician who lived about 600 BC in ancient India, gave a thorough explanation of the surgical removal of the bladder stone from the perineum (the region between genitals and anus).
Nephrolithiasis is a serious condition with an occurrence approaching 1 case per 1000 patients annually. The prevalence in developed nations is around 6 percent in women and 12 percent in men, which appears to increase with time. Its frequency peaks as patients are in their thirties and forties. With age the frequency grows in around the seventh decade of adulthood. Stones may consist, alone or in combination, of calcium oxalate, calcium phosphate, uric acid, magnesium ammonium phosphate (struvite), or cystine. The type of stone being formed is determined by a number of pathogenic mechanisms. Symptomatic stones tend to localize and accumulate in the renal tubules but are often often located inside the ureters and bladder. The recurrence rate of calcium oxalate stones is about 50% at 5 to 10 years and higher for cystine, uric acid, and struvite stones.
Mechanism of Kidney Stone Formation
Physiology
Kidney stones form when urine is over-saturated with the specific components of the stone. Saturation is dependent on the chemical-free ion behaviors of the stone constituents. Chemical free ion behavior is influenced by factors such as urinary ion aggregation, pH, and the association of the constituent ion with other compounds. Raising the concentration of urinary calcium or decreasing the volume of urine, for example, will increase the free ion content of calcium ions in the urine. Urine pH may also influence chemical free ion activity.
A low urinary pH raises the concentration of uric acid ions on free ions. A high urinary pH, on the other hand, promotes calcium complexation with phosphorus, raising the free ion content of both calcium and phosphorus. Citrate combines with calcium ions to form soluble complexes, which reduces unbound citrate and calcium free ion activity. As the concentration of chemical free ions reduces, the urine becomes supersaturated (also called oversaturated). In this setting, new stones will form, and existing stones will rise. As free ion activity decreases, urine becomes undersaturated, and stones do not enlarge and can also dissolve. The chemical-free action of the stone materials in a solution where the stone does not expand or dissolve is the product of equilibrium solubility.
Most clinicians calculate the volume of excretion of the major stone-forming ingredients in mass per unit time to determine the lithogenic potential of urine from stone formers (e.g., milligrams or millimoles per 24 hours). The lithogenic potential of the urine, on the other hand, clearly determines the degree of supersaturation. There are computer programs available that calculate saturation based on the amounts of different elements in urine and the pH of the urine, allowing for a more accurate assessment of the risk of stone formation. Any calculation of mean saturation understates the normal supersaturation, which, due to hourly variations in water and solvent excretion throughout the day, will drive stone forming.
Diet
Dietary influences have a significant impact on excreted ion concentration. Simply instructing patients to maximize fluid consumption tends to have a substantial effect in minimizing development and forming of stones. Renal calcium excretion is increased by decreased sodium excretion, and hypercalciuric patients appear to have a stronger calciuric reaction to a sodium load than control subjects.34 Dietary sodium restriction with the consequent reduction in urinary sodium excretion increases calcium excretion and decreases supersaturation with respect to calcium-containing kidney stones. To avoid hypercalciuria, patients are recommended to restrict their daily consumption of sodium to a maximum of 3000 mg (~130 mEq).
- In patients with nephrolithiasis, the small drop in animal protein (~1.0 mg / kg a day) is considered to be helpful.
- Although it is unclear that fructose is the only carbon that can increase the production of uric acid, and metabolism of fructose can increase the formation of stone.
- The age and gender of equitable calcium intake should be maintained in patients.
Pathogenesis of Idiopathic Hypercalciuria Idiopathic hypercalciuria (IH) is characterized in the setting of normalcalcemia as excessive urinary calcium excretion and the absence of secondary causes of hypercalciuria; IH is the most common cause of kidney stones which contain calcium. The disease is familial; it was originally thought to display an inheritance-dominant autosomal pattern but is almost definitely polygenic. New clinical findings also indicate that IH could be a chronic calcium homeostasis condition with calcium transportation dysregulation. Dysregulation of calcium transport can lead to hypercalciuria in the intestine, kidney or bone.
Bartter Syndrome
Bartter syndrome is caused by at least five genetic mutations, primarily autosomal recessive, which result in the loss of sodium chloride at the Henle loop TAL. Deficiencies that exist in NKCC2 (sodium potassium chloride cotransporter), ROMK (renal outer medullary potassium channel), CLC-Kb (basolateral chloride channel), or in a chloride subunit known as barttin. Such genes, both expressed in the TAL, induce a sodium transport defect that leads to a reduction in the gap in transtubular potential, resulting in a decline in the TAL’s reabsorption of paracellular calcium. The consequent decrease in intravascular volume also causes metabolic alkalosis that is mediated by aldosterone. Therefore, Bartter syndrome parallels high-dose administration of furosemide (which inhibits NKCC2) and differs from Gitelman syndrome in that hypercalciuria, nephrocalcinosis, and nephrolithiasis are seen with Bartter but not with Gitelman. In renal tubular cells, an autosomal dominant type of Bartter syndrome results from a gain-of-function mutation in the calciumsensing receptor. This mutation contributes to decreased reabsorption of calcium and hypocalcemia caused by low levels of PTH. Vitamin D therapy and treatment of calcium can trigger stone disease in this condition.
Causes of Calcium Stone Formation
- Hypercalciuria
- Cushing syndrome
- Granulomatous diseases
- Hypercalcemic disorders
- Idiopathic hypercalciuria
- Immobilization
- Malignancy
- Milk-alkali syndrome
- Primary hyperparathyroidism
- Sarcoid
- Thyrotoxicosis
- Medications
- Acetazolamide
- Amphotericin B
- Antacids (calcium and noncalcium antacids)
- Calcium supplements
- Glucocorticoids
- Loop diuretics
- Theophylline
- Vitamin C?
- Vitamin D
- Allopurinol (associated with xanthene stones)
- Probenecid
- Salicylates
- Acyclovir (when infused rapidly intravenously)
- Indinavir
- Nelfinavir
- Sulfonamides
- Triamterene
- Hyperoxaluria
- Biliary obstruction
- Chronic pancreatitis
- Crohn disease
- Dietary hyperoxaluria (urine oxalate secretion 40-60 mg/day)
- Enteric oxaluria (urine oxalate 60-100 mg/day)
- Jejunoileal bypass
- Malabsorptive disorders
- Primary hyperoxaluria types 1 and 2 (oxalate 80-300 mg/day)
- Sprue (celiac disease)
- Hyperuricosuria
- Hypocitraturia
- Androgens
- Exercise
- Hypokalemia
- Hypomagnesemia
- Infection
- Metabolic acidosis
- Starvation
- Renal tubular acidosis (distal, type 1)
- Anatomic genitourinary tract abnormalities
- Congenital megacalyx
- Medullary sponge kidney
- Tubular ectasia
Non-Calcium Stone Formation
- Uric Acid Stones
- Cushing syndrome
- Diarrhea
- Diet high in animal protein
- Excessive dietary purine
- Excessive insensible losses
- Genetic predisposition
- Glucose-6-phosphatase deficiency
- Gout
- Hemolytic anemia
- Hyperuricemia
- Hyperuricosuria
- Inadequate fluid intake
- Inborn errors of metabolism
- Insulin resistance
- Intracellular to extracellular uric acid shift
- Lesch-Nyhan syndrome
- Low urine pH (<5.5)
- Low urine volume
- Malabsorptive disorders
- Medications (see Table 30-4)
- Metabolic syndrome
- Myeloproliferative disorders
- Obesity
- Tumor lysis
- Struvite Stones
- Urease-producing bacteria
- Proteus, Pseudomonas, Haemophilus, Yersinia, Ureaplasma, Klebsiella,
- Corynebacterium, Serratia, Citrobacter, Staphylococcus, and others
- Never Escherichia coli—not a urease producer
- High urine pH (~6.5)
- Indwelling urinary catheter
- Neurogenic bladder
- Cystine Stones
- Autosomal recessive trait
- Excessive excretion of cystine, ornithine, lysine, and arginine
- Low solubility of cystine (<250 mg/L)
References:
- Williams Textbook of Endocrinology. Elsevier