Nephrolithiasis

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Nephrolithiasis

• Adnan Alsaka M.D.
• Nephrology Fellow

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• Nephrolithiasis is estimated to produce medical
  costs of 2.1 billion per year in the US
• Incidence is 0.5
• Prevalence is 5.2

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• More common in Asians and whites than in Native
  Americans, Africans, African Americans
• male-to-female ratio of 31
• Stones due to infection (struvite) are more
  common in women

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• Most urinary calculi develop in persons aged
  20-49 years
• An initial stone attack after age 50 years is
  relatively uncommon

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• Pathophysiology

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• 1- supersaturation of the urine by stone-forming
  constituents
• Crystals or foreign bodies can act as nidi,
  upon which ions from the supersaturated urine
  form microscopic crystalline structures

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Randall plaque

• is deposition of stone material on a renal
  papillary calcium phosphate nidus
• Calcium phosphate precipitates in the basement
  membrane of the thin loops of Henle, erodes into
  the interstitium, and then accumulates in the
  subepithelial space of the renal papilla
• The subepithelial deposits, eventually erode
  through the papillary urothelium

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• Causes of Nephrolithiasis

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Hypercalciuria

• most common metabolic abnormality
• can be subdivided into absorptive, resorptive,
  and renal-leak categories

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Absorptive Hypercalciuria

• related to increased intestinal absorption of
  calcium (associated with excess dietary calcium
  and/or overactive calcium absorption mechanisms)
• the treatment may include modest dietary calcium
  restriction, thiazide diuretics, oral calcium
  binders

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Resorptive hypercalciuria

• related to excess resorption of calcium from bone
  (i.e., hyperparathyroidism)
• Treatment requires parathyroidectomy

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Renal-leak hypercalciuria

• less common than absorptive hypercalciuria
• related to an inability of the renal tubules to
  properly reclaim calcium in the glomerular
  filtrate
• Usually associated with secondary
  hyperparathyroidism and is best managed with
  thiazide diuretics

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• Indiscriminate dietary calcium restriction is not
  advantageous
• The reduced dietary calcium reduces the
  oxalate-binding sites in the gastrointestinal
  tract, increasing the free dietary oxalate and
  leading to increased oxalate absorption

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Hyperoxaluria

• Primary ( rare genetic disease)
• Enteric
• Dietary

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Primary hyperoxaluria

• Type I mutation of AGXT gene on chromosome 2 that
  codes for alanine glyoxylate aminotransferase
• Type II mutation of GRHPR gene on chromosome 9
  that codes for glyoxylate reductase and
  hydroxypyruvate reductase.

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Enteric

• Due to malabsorption
• Associated with chronic diarrhea or short bowel
  syndrome
• Normally, calcium binds to intestinal oxalate
  reducing its absorption

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• Ingestion of large amount of Vitamin C
• (gt 2 gram/day) increase the risk of Oxalate stone

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• Calcium citrate is the recommended supplement
  because it tends to further reduce stone
  formation
• Calcium carbonate supplementation is less
  expensive but does not provide citrate's added
  benefit

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• Calcium therapy works as an oxalate binder,
  reducing oxalate absorption from the intestinal
  tract.
• Calcium should be administered with meals,
  especially those that contain high-oxalate foods.

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• The supplement should not contain added vitamin D
  because this increases calcium absorption
• The optimal 24-hour urine oxalate level is 20
  mg/d or less

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Hyperuricosuria

• predisposes to the formation of
  calcium-containing calculi because sodium urate
  can produce malabsorption of macromolecular
  inhibitors
• can serve as a nidus for the heterogeneous growth
  of calcium oxalate crystals
• Therapy involves potassium citrate
  supplementation, allopurinol, or both

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Uric acid stones

• Exists in equilibrium with urate at a pK of 5.5
• As pH falls below 5.5, concentration of
  undissociated uric acid greatly exceeds that of
  urate
• High BMI, glucose intolerance and overt DM 2 are
  common in uric acid stone formers

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• The optimal 24-hour urine uric acid level is 600
  mg/d or less

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Sodium and phosphorus

• Elevated urinary sodium levels are almost always
  associated with dietary indiscretions
• Decreasing the oral sodium (lt2.5 gm/day) intake
  can decrease calcium excretion by increasing
  proximal calcium absorption

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Hyperphophaturia

• Renal phosphate leak high urinary phosphate
  levels, low serum phosphate levels, high serum
  1,25 vitamin D-3 (calcitriol) levels, and
  hypercalciuria.
• This type of hypercalciuria is uncommon and does
  not respond well to standard therapies

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• Phosphate supplements are used to correct the low
  serum phosphate level, which then decreases the
  inappropriate activation of vitamin D originally
  caused by the hypophosphatemia

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Citrate and magnesium

• are important chemical inhibitors of stone
  formation
• Hypocitraturia is one of the most common
  metabolic defects that predispose to stone
  formation
• 24-hour urine citrate levels of 320 mg/d is the
  normal threshold

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• Magnesium is a more recently recognized inhibitor
  of stone formation, and the clinical role of
  magnesium replacement therapy is less well
  defined than that of citrate

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High Protein diet

• The institution of a high protein diet (2 g/kg
  per day) adversely effects the metabolic
  parameters determining the risk of calcium stone
  formation

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Protein restriction reduce Ca oxalate formation
by

• less acidic urine reduces the formation of UA
  stones
• less acidic urine favors the trivalent form of
  the citrate anion, which is less able to bind the
  Na/citrate cotransporter in PT
• Reduction of daily acid load reduces bone
  buffering (calcium resorption) to reduce ca
  excretion

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Struvite Stones

• form in chronic upper urinary tract infection due
  to a urease-producing organism
• are composed of magnesium ammonium phosphate
  (struvite) and calcium carbonate-apatite
• Normal urine is undersaturated with ammonium
  phosphate, and struvite stone occurs only when
  ammonia production is increased and the urine pH
  is elevated to decrease the solubility of
  phosphate

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Struvite Stones

• may grow rapidly over a period of weeks to months
  can develop into a staghorn calculus involving
  the entire renal collecting system

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Cystine stones

• only develop in patients with cystinuria (an
  autosomal recessive disorder)
• due to the poor solubility of cystine in the
  urine
• Autosomal recessive or dominant
• Increased excretion of COAL (cystine, ornithine,
  arginine, lysine)

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• Cystine superstauration occurs at cystine
  concentration gt 250 mg/L
• its solubility will gradually increase as pH
  increases from 6.5 to 7.5
• The hallmark of treatment is water, water and
  more water.

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Cystine crystals
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Phosphate crystals
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Uric acid crystals
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Calcium oxalate
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• Obstructive Uropathy

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• refers to obstruction of the urinary tract at any
  point from the renal pelvis to the distal urethra
• The acute or chronic loss of kidney function
  resulting from obstruction is termed obstructive
  nephropathy

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The likelihood of functional impairment depends
on

• The duration of the obstruction
• Whether it is partial or complete
• Whether it involves one or both functioning
  kidneys

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Dilated urinary tract without obstruction

• 1- Pregnancy is the most common cause
• occurring in 50 of women in 3rd trimester
• due to reduced peristalsis movement and ureteral
  relaxation due to progesterone
• It is not a cause of renal failure

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Dilated urinary tract without obstruction

• 2- Vesicoureteral reflux
• 3- high urine flow rate
• 4- Acute pyelonephritis

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• Effects on glomerular filtration

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The first 2-3 hours

• the release of Prostaglandin from Macula densa
  in response to distal tubular flow will lead to
  vasodilation
• GFR is maintained because the increase in tubular
  pressure is offset by increase in tubular blood
  flow

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After 4-5 hours

• Intra-tubular pressure falls as sodium and water
  are reabsorbed
• The release of Angiotensin II from Macula densa
• in response to decreased distal sodium delivery
  and promotes vasoconstriction
• Renal blood flow and GFR both fall in the
  subsequent 12-24 hours

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Tubular functions during obstruction

• Early on, urine indices are suggestive of a
  pre-renal insult due to enhanced absorption of
  sodium and water in response to decreased distal
  delivery
• With more prolonged obstruction, FENA gt1 as
  sodium reabsorption falls

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Natriuresis follows the release of obstruction

• down-regulation in the number and activity of
  sodium transport proteins throughout the nephron
• reduced activity of NA/K ATPase
• Release of prostaglandin by inflammatory cells

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Question 1

• In industrialized countries, what is the most
  common type of urinary stone?
• A- Calcium phosphate
• B- Calcium oxalate
• C- Ammonio magnesium phosphate (struvite)
• D- Uric acid
• E- Cystine

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Question 1

• In industrialized countries, what is the most
  common type of urinary stone?
• A- Calcium phosphate
• B- Calcium oxalate
• C- Ammonio magnesium phosphate (struvite)
• D- Uric acid
• E- Cystine

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Question 2

• A 48-year-old woman is admitted to the hospital
  for intravenous hydration and analgesics after
  experiencing her third bout of renal colic in the
  past year. Previous intravenous pyelograms
  revealed recurrent right- and left-sided 3-mm
  caliceal stones. A current sonogram shows a 3-mm
  right caliceal stone and a 2-mm distal ureteral
  stone. Physical examination of the heart and
  lungs is unremarkable. Abdominal examination
  reveals right flank tenderness. Which of the
  following is the LEAST likely diagnosis?
• Hyperparathyroidism
• Gout
• Rheumatoid arthritis
• Sarcoidosis
• Renal tubular acidosis

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Question 2

• 3. A 48-year-old woman is admitted to the
  hospital for intravenous hydration and analgesics
  after experiencing her third bout of renal colic
  in the past year. Previous intravenous pyelograms
  revealed recurrent right- and left-sided 3-mm
  caliceal stones. A current sonogram shows a 3-mm
  right caliceal stone and a 2-mm distal ureteral
  stone. Physical examination of the heart and
  lungs is unremarkable. Abdominal examination
  reveals right flank tenderness. Which of the
  following is the LEAST likely diagnosis?
• Hyperparathyroidism
• Gout
• Rheumatoid arthritis
• Sarcoidosis
• Renal tubular acidosis

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Question 3

• A 44-year-old male patient has passed his second
  Ca Oxalate urinary stone. He was told to increase
  his fluid intake and referred to your evaluation.
  A 24-hour urine collection reveals the following
• Volume 2500 ml
• Sodium 250 mEq
• Calcium 240 mg
• Uric Acid 700 mg
• Oxalate 25 mg
• Citrate 350 mg

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• What treatment do you recommend?
• A- Increase fluid intake
• B- Thiazide diuretic
• C- Reduce sodium intake
• D- Allopurinol
• E- Urocit-K

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• Thank you