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STONES: EPIDEMIOLOGY & PATHOGENESIS

Epidemiology of Urolithiasis

Lifetime prevalence of kidney stone disease: ≈1%-15%, varies by age, gender, race, geographic location, and BMI

Age: relatively uncommon age < 20 but peaks in incidence in the 40-60s
Gender: upper urinary tract stones occur more commonly in males than females, but gender gap is narrowing
Race: Whites have the highest incidence of upper tract stones compared with Asians, Hispanics, and African-Americans
Geographic location: In the US, highest prevalence in the Southeast
BMI, waist size, and weight gain are positively correlated with an increased risk for stone episodes

Incidence of asymptomatic renal stones is ≈10% of screened populations

Physicochemistry and pathogenesis

Urine must be supersaturated for stones to form; supersaturation alone is not sufficient for crystallization to occur in urine due to the presence of urinary inhibitors
- The state of saturation of the urine with respect to particular stone-forming salts indicates the stone-forming propensity of the urine. The state of saturation is determined by pH and the ionic strength of the major ions in solution.
- The solubility product refers to the point of saturation where dissolved and crystalline components in solution are in equilibrium. Addition of more crystals to the solution will result in precipitation of crystals. In this supersaturated urine (metastable state), crystallization can occur on preexisting crystals, but spontaneous crystallization occurs only when the concentration product exceeds the formation product. In the supersaturated state, the presence of inhibitors prevents or delays crystallization.
  - The process by which nuclei form in pure solutions is called homogeneous nucleation.
  - Heterogeneous nucleation occurs when microscopic impurities or other constituents in the urine promote nucleation by providing a surface on which the crystal components can grow.

Known inhibitors of calcium oxalate and calcium phosphate crystallization (6) No More Bad Colicky Torturous Urolithiasis:
1. Nephrocalcin
2. Magnesium
3. Bikunin
4. Citrate
5. Tamm-Horsfall mucoprotein
  - Most abundant protein in the urine
6. Uropontin
No known inhibitors affect uric acid crystallization

Renal calculi consist of 2 components: crystalline and non-crystalline (matrix) components

Crystalline
- Calcium is the most common component of urinary calculi
Non-crystalline (matrix)
- Typically accounts for 2.5% of the weight of the stone.
- Matrix is a heterogenous mixture consisting of ≈65% protein. Other components include mucoproteins, carbohydrates, and urinary inhibitor

In idiopathic calcium oxalate stone formers, Randall plaques, which are composed of calcium apatite, have been found to originate in the basement membrane of the thin loops of Henle. From there, they extend through the medullary interstitium to a subepithelial location, where they serve as an anchoring site for calcium oxalate stone formation.

Mineral metabolism

Calcium
- 30-40% of dietary calcium is absorbed from the intestine, with most being absorbed in the small intestine and only ≈10% absorbed in the colon
- Absorption of calcium varies with calcium intake by a process of intestinal adaptation - at times of low calcium intake, fractional calcium absorption is enhanced; during high calcium intake, fractional calcium absorption is reduced
- Substances that complex with calcium, such as oxalate, citrate, phosphate, sulfate, and fatty acids, reduce the availability of calcium for absorption
- Calcium homeostasis
  - PTH
    - Secreted in response to low serum calcium
    - Functions (3):
      1. Increases renal reabsorption of calcium and reduces reabsorption of phosphate from distal tubule (primary effect)
      2. Stimulates the enzyme 1α-hydroxylase in the proximal renal tubule which converts 25-hydroxyvitamin D3 (calcifediol/calcidiol) to 1,25(OH)2D3 (calcitriol)
        
        This enzyme is also stimulated by hypophosphatemia
        
        The first step to synthesis of calcitriol involves the conversion of 7-dehydrocholesterol in the skin to previtamin D3 and is promoted by sunlight. Previtamin D3 is hydroxylated in the liver, which is further hydroxylated in the proximal renal tubule to 1,25(OH)2D3.
      3. Increases calcium release from bone
    - A population-based study found that serum PTH levels were positively correlated with serum uric acid levels§
  - Calcitriol (1,25(OH)2D3)
    - Active form of Vitamin D
    - Functions (4):
      1. Most potent stimulator of intestinal calcium absorption
        
        Note PTH does not target intestine
      2. Increases renal reabsorption of calcium and phosphate
        
        Note PTH increases phosphate excretion
        
        Similar to PTH, vitamin D induces calcium reabsorption in the distal tubule
      3. Increases calcium release from bone
      4. Inhibits release of PTH
Oxalate
- Only 6-14% of ingested oxalate is absorbed (compared to 30-40% of ingested calcium is absorbed)
  - Oxalate absorption occurs throughout the intestinal tract, with about half or more occurring in the small intestine and half in the colon
  - Factors that influence oxalate absorption (2):
    1. Oxalate-degrading bacteria
    2. Presence of oxalate-binding cations such as calcium or magnesium
- Absorbed oxalate is nearly completely excreted in the urine
  - Urinary oxalate is derived from both endogenous production in the liver (from ascorbic acid and glycine) and dietary sources.
    - On average, half of urinary oxalate is derived from the diet, with the precise amount depending on the relative amount of ingested calcium and oxalate
  - It is estimated that between 86-98% of oxalate is ultrafilterable. However, renal tubular handling of oxalate has not been clearly defined, although both secretion and reabsorption have been suspected.

Classification of nephrolithiasis

Calcium-containing stones
1. Calcium oxalate (60%)
2. Hydroxyapatite (20%)
3. Brushite (2%)
Non-calcium containing stones
1. Uric acid (7%)
2. Struvite (7%)
3. Cystine (1-3%)
4. Triamterene (<1%)
5. Silica (<1%)
6. 2,8-dihydroxyadenine (<1%)

Calcium stones

Urinary calcium and oxalate are both important and equal contributors to calcium oxalate stone formation
Hypercalcuria

Most common abnormality identified in calcium stone formers
- Recall, hypercalcuria is the most common cause of microscopic hematuria in children
Classification:
1. Absorptive hypercalcuria
  - Characterized by
    1. Normal serum calcium
    2. Normal or suppressed PTH
    3. Hypercalcuria
  - Calcium fasting and load tests can discriminate between the various types of absorptive hypercalcuria; however, routine performance of these tests is not required
2. Renal (leak) hypercalcuria
  - Characterized by
    1. Normal serum calcium
    2. Elevated PTH
    3. High fasting urinary calcium levels
3. Resorptive hypercalcuria
  - Infrequent abnormality; most commonly associated with primary hyperparathyroidism
  - Characterized by:
    1. Elevated serum calcium
    2. Elevated PTH
    3. Hypercalcuria
    4. Hypophosphatemia
  - Recurrent calcium phosphate (100%) brushite stones are unusual and should raise suspicion for primary hyperparathyroidism (resorptive hypercalciuria)
    - Mechanism: elevated PTH increases phosphate excretion
  - Additional, rare causes of resorptive hypercalciuria include hypercalcemia of malignancy, sarcoidosis, thyrotoxicosis, and vitamin D toxicity. Many granulomatous diseases, including tuberculosis, histoplasmosis, leprosy, and silicosis, have been reported to produce hypercalcemia.
    - The hypercalcemia in sarcoidosis is due to the production of 1,25(OH)2D3 from 1α-hydroxylase present in macrophages of the sarcoid granuloma
4. Idiopathic (unclassified) hypercalcuria
  - Often refers to unevaluated or unknown cause
  - Patients may demonstrate hypercalcuria in all phases of the dietary calcium manipulation, but will not demonstrate serum abnormalities
5. Malignancy-associated hypercalemia
6. Glucocorticoid-induced hypercalemia

Hyperoxaluria

Classification (4):
1. Primary hyperoxaluria
2. Enteric hyperoxaluria
  - In patients with enteric hyperoxaluria, intestinal hyperabsorption of oxalate is the most significant risk factor leading to recurrent calculus formation
    - Fat malabsorption results in increased intestinal oxalate absorption
      - In fat malabsorption, saponification of fatty acids occurs with divalent cations such as calcium and magnesium, which reduces calcium available for complexation with oxalate thereby resulting in an increased amount of oxalate available for reabsorption.
      - The poorly absorbed fatty acids and bile salts may increase colonic permeability to oxalate, further enhancing intestinal oxalate absorption
      - Patients with enteric hyperoxaluria are more likely to form calcium oxalate stones, due to increased urinary excretion of oxalate and decreased inhibitory activity from hypocitraturia, secondary to chronic metabolic acidosis and hypomagnesuria.
    - Malabsorption of any cause (chronic diarrheal states, inflammatory bowel disease, celiac sprue, or intestinal resection) can lead to increased intestinal absorption of oxalate and hyperoxaluria; as a result of intestinal fluid loss, patients will often exhibit dehydration, bicarbonate losses, low urine volume
      - Hyperoxaluria has been described in both stone-forming and non-stone-forming patients who have undergone Roux-en-Y gastric bypass surgery, with urinary oxalate levels in some patients exceeding 100 mg/day
        
        Bariatric surgery patients typically develop enteric hyperoxaluria, which should be managed with calcium supplementation
        
        Iron deficiency is the most common cause of anemia following bariatric surgery, particularly in premenopausal women.
      - Chronic diarrheal syndromes promote intestinal loss of alkali and dehydration, resulting in metabolic acidosis and reduced urinary citrate levels.
        Chronic metabolic acidosis can lead to low urine pH, hypercalciuria, and hypocitraturia.
  - Restricting oxalate is generally insufficient as the cause is not an overabundance of oxalate
3. Dietary hyperoxaluria
  - Overindulgence in oxalate-rich foods such as (Oxalate Rich Chocolate, Pepper, Nuts): Okra, Rhubarb, Chocolate, Pepper, Nuts, Tea (black), cocoa, spinach, mustard greens, pokeweed, swiss chard, beets, berries, wheat germ, and soy crackers can result in hyperoxaluria in otherwise normal individuals.
    - Compliance is difficult for regimens intending to eliminate all oxalate sources
  - Severe calcium restriction may result in reduced intestinal binding of oxalate and increased intestinal oxalate absorption, hence calcium intake should be moderate, rather than restricted
    - Increasing calcium intake, which may include supplements, specifically timed with meals, may reduce hyperoxaluria
  - High substrate levels (vitamin C) can also cause hyperoxaluria; doses should be limited to 2 g/day
4. Idiopathic hyperoxaluria

Hyperuricosuria

May be associated with pure uric acid calculi or calcium oxalate calculi through heterogenous nucleation

Patients with hyperuricosuric calcium nephrolithiasis who form calcium oxalate stones present with normal urinary pH and hyperuricosuria, accompanied sometimes by hypercalciuria
In contrast, those with gouty diathesis, who can form either uric acid or calcium oxalate calculi, have a low fractional excretion of urate (that contributes to hyperuricemia) and low urinary pH (that leads to increased amount of undissociated uric acid)

Causes:
1. Increased dietary purine intake (most common cause)
2. Gout
3. Myeloproliferative and lymphoproliferative disorders
4. Multiple myeloma
5. Thalassemia
6. Hemolytic disorders
7. Pernicious anemia
8. Hemoglobinopathies
9. Secondary polycythemia
10. Complete or partial hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency
  - Lesch-Nyhan syndrome is an inherited deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase, which leads to the accumulation of hypoxanthine, which is ultimately converted to uric acid
11. Overactivity of phosphoribosylpyrophosphate synthetase
12. Hereditary renal hypouricemia

Renal tubular acidosis (RTA)

RTA is a clinical syndrome characterized by metabolic acidosis
Classified: acquired vs. inherited;

Causes of acquired RTA A CASH POT

Analgesic nephropathy
Idiopathic hyperCalciuria
Acute tubular necrosis (ATN)
Sarcoidosis
Hyperparathyroidism (primary)
Pyelonephritis, recurrent
Obstructive uropathy
Transplant (renal)

3 types: type 1 (distal), type 2 (proximal), and type 4 (distal)
1. Type 1 (distal) RTA
  - Most common form of RTA and most commonly associated with kidney stones (up to 70% of adults with type 1 RTA have kidney stones)
  - Characterized by (5):
  - Potassium citrate therapy is able to correct the metabolic acidosis and hypokalemia
  - Most common stone composition associated with distal RTA is calcium phosphate as a result of increased urinary pH, hypercalciuria, and hypocitraturia
2. Type 2 (proximal) RTA
3. Type 4 (distal) RTA

Usually seen in patients with chronic renal damage (obstructive uropathy, interstitial renal disease, diabetic nephropathy, multicystic dysplasia)
Pathophysiology results from impaired response to mineralocorticoid caused by damage to the cortical collecting duct
Associated with hyperkalemia
Nephrolithiasis is uncommon in this disorder

Nephrocalcinosis

Formation of diffuse deposits of calcium throughout the kidneys

Usually occurs within the renal medulla but occasionally it has been found in the cortex or within both the medulla and the cortex
Minute calcifications seen in early stages may not be visible

Can give rise to renal colic and hydronephrosis from dislodged calcific foci
Causes§

Medulla

Type 1 (distal) RTA
Hyperparathyroidism
Medullary sponge kidney
Hypervitaminosis D
Milk-alkali syndrome
Sarcoidosis
Hyper/hypothyroidism
Other pathological hypercalcemic or hypercalciuric states

Cushing syndrome
Multiple myeloma
Bartter syndrome
Bone metastases

Pyramids

Hyperuricemia
Infection (particularly renal tuberculosis)
Sickle cell disease (leading to infarction and subsequent dystrophic calcification)
Renal papillary necrosis
Drugs
Furosemide abuse

Corticol COAG

Corticol necrosis
Oxalosis
Alport syndrome
Glomerulonephritis (chronic)

Plain film x-ray demonstrating bilateral diffuse calcium deposits in the kidneys

Source: Wikipedia

Hypomagnesiuria

Rare cause of nephrolithiasis
Most common cause is inflammatory bowel disease associated with malabsorption
Frequently associated with chronic thiazide therapy
Magnesium complexes with oxalate and calcium salts, and therefore low magnesium levels result in reduced inhibitory activity. Low urinary magnesium is also associated with decreased urinary citrate levels

Hypocitraturia

Acid-base state is the primary determinant of urinary citrate excretion
- Metabolic acidosis reduces urinary citrate levels by augmenting citrate reabsorption and mitochondrial oxidation
- Metabolic alkalosis enhances citrate excretion
Causes (4) DIRT:
1. Chronic Diarrhea
2. Idiopathic
3. Type 1 (distal) RTA: laboratory hallmark is low urine citrate with an inappropriately high urine pH; Severe hypocitraturia should immediately raise suspicious for RTA.
4. Thiazide-induced (side effects of thiazide therapy)

Urine pH
- At low urine pH (<5.5), the undissociated form of uric acid predominates, leading to uric acid and/or calcium stone formation.
  - Any disorder leading to low urine pH may predispose to stone formation.
  - Calcium oxalate stones can form in low urine pH as a result of heterogeneous nucleation with uric acid crystals.
  - Chronic metabolic acidosis can lead to low urine pH, hypercalciuria, and hypocitraturia.

Uric acid stones

Determinants of uric acid stone formation (3):
1. Low urine pH (<5.5) (most important)
2. Low urine volume
3. Hyperuricosuria
Causes: congenital vs. acquired

Congenital

Disorders associated with uric acid stones involve renal tubular urate transport or uric acid metabolism, leading to hyperuricosuria

Acquired:
1. Diabetes
  - Diabetic stone formers have a lower urine pH compared with non-diabetic stone formers due to insulin resistance
    - In normal individuals, insulin stimulates ammoniagenesis in renal tubule cells by promoting gluconeogenesis from glutamine and by stimulating ammonium excretion by the proximal tubular sodium/hydrogen exchanger. Failure of the renal tubule cells to respond to insulin results in defective ammonia production and/or excretion, thereby leading to a reduction in urinary pH and uric acid stone formation.
  - Diabetic stone formers are approximately 6x more likely to develop a uric acid stone.
    - Uric acid stones are found in 34% of stone-forming patients with diabetes mellitus compared to 6% of non-diabetic stone formers
2. Obesity
3. Metabolic syndrome
4. Tumour lysis syndrome
5. Volume depletion
6. High animal protein intake
7. Chronic diarrhea
8. Uricosuric drugs
9. Idiopathic

All 11 conditions associated with hyperuricosuria listed above

Cystine stones

Cystinuria
- An inherited autosomal recessive disorder caused by mutations of SLC7A9 or SLC3A1
- Results in inadequate renal tubular reabsorption of the amino acids Cystine, Ornithine, Lysine, and Arginine (COLA), and also inadequate intestinal absorption of these amino acids
  - Several factors determine the solubility of cystine, including cystine concentration, pH, ionic strength, and urinary macromolecules
- May be accompanied by other metabolic abnormalities
- Stones are considered poorly radioopaque on imaging§
- Sodium nitroprusside spot test will turn urine purple in the presence of cystine.
  - Used for screening purposes to identify patients with cystine stone disease who are undergoing a 24 hour urine collection for evaluation.

Infection stones (magnesium ammonium phosphate)

Struvite stones occur only in association with urinary infection by urea-splitting organisms.
- Urease hydrolyzes urea, forming ammonium and carbon dioxide, which increases urinary pH.
  - Alkaline urine promotes supersaturation and precipitation of crystals of magnesium ammonium phosphate and carbonate apatite.
Most common urease-producing pathogens (4):
1. Proteus (most common)
2. Klebsiella
3. Pseudomonas
4. Staphylococcus aureus

Some yeasts and mycoplasma species have the capacity to synthesize urease
Although E. coli is a common cause of UTIs, only rare species of E. coli produce urease

Pathogenesis
- Occur more often in females than males by a ratio of 2:1 because infection stones occur most commonly in those prone to frequent UTIs.
  - Other populations at risk of recurrent infection include the diabetics, elderly, premature infants or congenital urinary tract malformation, urinary stasis as a result of urinary tract obstruction, urinary diversion, or neurologic disorders
- Spinal cord–injured patients are at particular risk for both infection and metabolic stones owing to neurogenic urinary tract dysfunction and hypercalciuria related to immobility
Commonly produce staghorn stones; however, other crystals, including cystine, calcium oxalate monohydrate, and uric acid, can assume a staghorn configuration
See Table 52-7

Other stones

Matrix stones
- Rare
- Predominately composed (65%) of organic proteins, sugars, and glucosaminses, unlike other stones that have minimal organic material (2.5%)
  - Among the proteins incorporated into the matrix substance are Tamm-Horsfall protein, nephrocalcin, a γ-carboxyglutamic acid–rich protein, renal lithostathine, albumin, glycosaminoglycans, free carbohydrates, and a mucoprotein called matrix substance A
- Most common predisposing factors: recurrent UTI by urea-splitting bacteria, previous stone formation, previous surgery due to urolithiasis and obstructive uropathy
- Challenging to diagnose preoperatively, as they can mimic upper tract collecting system soft-tissue masses and require a high index of suspicion
- Radiolucent on plain film x-ray
Xanthine stones
- Result of an inherited disorder in xanthine dehydrogenase (XDH) or xanthine oxidase.
- Allopurinol, which inhibits XDH and is consequently used to treat hyperuricemia and hyperuricosuria, can, at high levels, predispose to xanthine stones. This side effect is distinctly uncommon
- Radiolucent on plain film x-ray
2,8-dihydroxyadenine stone
- Results from adenine phosphoribosyltransferase deficiency, a rare autosomal recessive disorder
- Radiolucent on plain film x-ray
Ammonium acid urate stones
- Infrequently seen in industrialized nations
- Associated with laxative abuse, recurrent UTI, recurrent uric acid stone formation, inflammatory bowel disease, and children with low-protein, low-phosphate diet resulting in primary bladder calculus
  - Ammonium excretion is increased with starvation, dehydration, or consumption of acid-forming foods or toxins§
  - Subjects who abuse laxatives are chronically dehydrated, resulting in intracellular acidosis. In addition, urinary sodium is low from sodium loss as a result of the laxatives. In this environment, urate preferentially complexes with the abundant ammonium rather than sodium and produces ammonium acid urate stones.
Medication associated stones (12): Lotta Good Drugs Cause Calculi FIT TEST
1. Laxatives
2. Guaifenesin
3. Vitamin D
4. Vitamin C
5. Carbonic anhydrase inhibitors
6. Furosemide
  - Thiazides cause intracellular acidosis and subsequent hypocitraturia
7. Indinavir
  - MOA: protease inhibitor
  - Used in patients with HIV/AIDS.
  - Individuals taking indinavir on a regular basis are at high risk of producing indinavir stones because of the high urinary excretion and poor solubility of the drug at physiologic urinary pH.
  - Now infrequently used, replaced with newer generation agents. Kidney stone formation has been associated with a number of newer anti-retroviral agents.
  - Radiolucent on plain film and may not be seen on CT
8. Topiramate
9. Triamterene
  - MOA: potassium-sparing diuretic
  - Used for the treatment of hypertension
  - Radiolucent
10. Ephedrine
11. Silicates
12. TMP/SMX

Anatomic predisposition to stones

Ureteropelvic Junction Obstruction (UPJO)

Correction of the UPJO does not prevent recurrent stones in most patients, emphasizing the role of underlying metabolic abnormalities in the etiology of renal calculi in patients with UPJO

Horseshoe kidneys

Although urinary stasis likely contributes to a propensity toward stone formation in patients with horseshoe kidneys, an underlying metabolic abnormality is required for stone formation to occur

Caliceal Diverticula
Medullary Sponge Kidney

Congenital disorder
Characterized by cystic dilatation of the collecting tubules in one or both kidneys, resulting in stasis of urine and may eventually lead to calculi deposits
May independently cause both nephrocalcinosis (see above) and distal RTA with associated RTA metabolic abnormalities including hypercalciuria, hypocitraturia and defective urinary acidification
Increased risk for kidney stones and UTI
Imaging: hyperechoic papillae with clusters of small stones on ultrasound examination of the kidney or with an abdominal x-ray.

Questions

List inhibitors of calcium oxalate formation.
What are functions of PTH?
What stimulates release of PTH?
What are the functions of vitamin D?
What is the most common metabolic abnormality found in stone formers?
What are 4 different types of hypercalcuria and what would their blood work show?
What are the 4 different types of hyperoxaluria?
Why is intestinal malabsorption associated with hyperoxaluria?
List 5 oxalate rich foods
What is the most common cause of hyperuricosuria?
List 6 causes of hyperuricosuria
List 8 causes of acquired RTA
What are the 3 different types of RTA, metabolic abnormality, and which is associated most commonly with stones?
List 4 causes of hypocitraturia
What are 2 lithogenic metabolic derangements associated with thiazide use?
List 10 conditions associated with uric acid stones
What are the main determinants of uric acid stone formation?
What is the inheritance pattern associated with cysteine stones?
Impaired reabsorption of which amino acids occurs in cystinuria?
List 4 radiolucent stones
Which metabolic abnormality is associated with excess vitamin C intake?
Which type of stone is associated with laxative abuse?
List 5 stone types that are formed from medications?
List anatomic causes the predispose patients to stone formation

Answers

List inhibitors of calcium oxalate formation.
1. Nephrocalcin
2. Magnesium
3. Bikunin
4. Citrate
5. Tamms-Horsfall protein
6. Uropontin
What are functions of PTH?
1. Stimulates reabsorption of calcium and excretion of phosphate in kidney
2. Stimulates release of calcium from bone
3. Stimulates to 1-alpha-hydroxylase enzyme to produce activated vitamin D
What stimulates release of PTH?
- Hypocalcemia
What are the functions of vitamin D?
1. Increase intestinal calcium absorption (Note PTH does not target intestine)
2. Increases renal reabsorption of calcium and phosphate (Note PTH increases phosphate excretion)
3. Increases calcium release from bone
4. Inhibits release of PTH
What is the most common metabolic abnormality found in stone formers?
- Hypercalcuria
What are 4 different types of hypercalcuria and what would their blood work show?
1. Absorptive, normal serum calcium, normal/supressed PTH
2. Renal leak, normal serum calcium, elevated PTH
3. Resorptive, elevated serum calcium, elevated PTH
4. Idiopathic
What are the 4 different types of hyperoxaluria?
1. Primary
2. Enteric
3. Dietary
4. Idiopathic
Why is intestinal malabsorption associated with hyperoxaluria?
- Intestinal malabsorption of fat results in saponification of fatty acids with calcium and other substrates that would otherwise bind oxalate; this results in increased oxalate absorption
List 5 oxalate rich foods
- Okra, rhubarb, chocolate, pepper, nuts, beets, spinach
What is the most common cause of hyperuricosuria?
- Increased dietary intake of purine
List 6 causes of hyperuricosuria
1. Gout
2. Myeloproliferative disorder
3. Multiple myeloma
4. Thalassemia
5. Hemolytic disorders
6. Pernicious anemia
7. Hemoglobinopathies
8. Secondary polycythemia
9. Complete or partial hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency
10. Overactivity of phosphoribosylpyrophosphate synthetase
11. Hereditary renal hypouricemia
List 8 causes of acquired RTA
1. Analgesic abuse
2. Hypercalcemia
3. ATN
4. Sarcoidosis
5. Hyperparathyroidism, primary
6. Pyelonephritis, recurrent
7. Obstructive uropathy
8. Transplant, renal
What are the 3 different types of RTA, metabolic abnormality, and which is associated most commonly with stones?
1. Type 1: impaired H+ secretion, associated with stones
2. Type 2: impaired bicarb reabsorption
3. Type 4: renal failure
List 4 causes of hypocitraturia
1. Idiopathic
2. Type 1 RTA
3. Thiazide diuretics
4. Chronic diarrhea
What are 2 lithogenic metabolic derangements associated with thiazide use?
- Hypomagnesuria and hypocitraturia
List 10 conditions associated with uric acid stones
1. Chronic diarrhea
2. Diabetes
3. Obesity
4. Metabolic syndrome
5. Tumour lysis syndrome
6. Volume depletion
7. High animal protein intake
8. Uricosuric drugs
9. All 11 conditions associated with hyperuricosuria listed above
10. Idiopathic
What are the main determinants of uric acid stone formation?
1. Low urine pH (<5.5)
2. Low urine volume
3. Hyperuricosuria
What is the inheritance pattern associated with cysteine stones?
- Autosomal dominant
Impaired reabsorption of which amino acids occurs in cystinuria?
- Cystine, Ornithine, Lysine, Arginine
List 4 radiolucent stones
1. Uric acid
2. Matrix
3. Cystine
4. Indinavir
5. Trimaterene
6. Xanthine
7. 2,8-dihydroxyadenine stone
Which metabolic abnormality is associated with excess vitamin C intake?
- Hyperoxaluria
Which type of stone is associated with laxative abuse?
- Ammonium acid urate stones
List 5 stone types that are formed from medications?
- Lotta Good Drugs Cause Calculi FIT TEST
1. Laxatives
2. Vitamin D
3. Vitamin C
4. Carbonic anhydrase inhibitors
5. Furosemide
6. Indinavir
7. Triamterene
8. TMP/SMX
9. Ephedrine
10. Silicates
11. Topiramate
List anatomic causes the predispose patients to stone formation
1. UPJO
2. Horseshoe kidney
3. Caliceal diverticula
4. Medullary sponge kidney

References

Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 51