Nephrolithiasis

Adnan Alsaka M.D.

Nephrology Fellow
 Nephrolithiasis is estimated to produce
medical costs of $2.1 billion per year in the
US
Incidence is 0.5%
Prevalence is 5.2%
 More common in Asians and whites than
in Native Americans, Africans, African
Americans
male-to-female ratio of 3:1
Stones due to infection (struvite) are
more common in women
 Most urinary calculi develop in persons
aged 20-49 years
An initial stone attack after age 50 years is
relatively uncommon
Pathophysiology
 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
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
Causes of Nephrolithiasis
Hypercalciuria
most common metabolic abnormality
can be subdivided into absorptive,
resorptive, and renal-leak categories
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
Resorptive hypercalciuria
related to excess resorption of calcium
from bone (i.e., hyperparathyroidism)
Treatment requires parathyroidectomy
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
 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
Hyperoxaluria
Primary ( rare genetic disease)

Enteric

Dietary
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.
Enteric
Due to malabsorption
Associated with chronic diarrhea or short
bowel syndrome
Normally, calcium binds to intestinal
oxalate reducing its absorption
 Ingestion of large amount of Vitamin C
(> 2 gram/day) increase the risk of Oxalate
stone
 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
 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.
 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
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
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
 The optimal 24-hour urine uric acid level is
600 mg/d or less
Sodium and phosphorus
Elevated urinary sodium levels are almost
always associated with dietary
indiscretions
Decreasing the oral sodium (<2.5 gm/day)
intake can decrease calcium excretion by
increasing proximal calcium absorption
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
 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
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
 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
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
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
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
Struvite Stones
may grow rapidly over a period of weeks
to months can develop into a staghorn
calculus involving the entire renal
collecting system
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)
 Cystine superstauration occurs at cystine
concentration > 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.
Cystine crystals
Phosphate crystals
Uric acid crystals
Calcium oxalate
Obstructive Uropathy
 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
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
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
Dilated urinary tract without
obstruction

2- Vesicoureteral reflux
3- high urine flow rate
4- Acute pyelonephritis
Effects on glomerular filtration
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
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
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
>1 as sodium reabsorption falls
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
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
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
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
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
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
What treatment do you recommend?
A- Increase fluid intake
B- Thiazide diuretic
C- Reduce sodium intake
D- Allopurinol
E- Urocit-K
Thank you