Nephrolithiasis for the
Internist
Rajiv Kumar
Divisions of Nephrology and Endocrinology
Departments of Medicine, Biochemistry and Molecular
Biology
Mayo Clinic, Rochester
Meira and Shaul G. Massry Visiting Professorship
Dr. Massry has had an exceptionally distinguished
career. He has received honorary doctorates from
universities across Europe and has been the recipient
of numerous awards from universities and societies
throughout the world. Dr. Massry was the Editor-inChief of the American Journal of Nephrology, and
of Mineral and Electrolyte Metabolism. He is the coEditor of the Textbook of Nephrology.
Shaul G. Massry, M.D. , Professor
Emeritus of Medicine and Physiology
& Biophysics at the Keck School of
Medicine, University of Southern
California and Emeritus Chief of the
Division of Nephrology (1974-2000).
Dr. Massry is a past President of the National Kidney
Foundation, American Society of Renal Biochemistry
and Metabolism, International Society of Nutrition and
Metabolism in Renal Diseases, International Society of
Uremia Research and Toxicity, and International
Association of the History of Nephrology. Dr. Massry
has been a frequent guest speaker at national and
international meetings and a visiting professor at many
universities across the globe. He has published over
600 scientific papers, 111 chapters in books and edited
32 books.
Mayo Clinic Rochester
Disclosures
• None
Objectives
• Familiarize you with recent trends in kidney
stone prevalence
• Discuss the pathogenesis of kidney stones
• Review diagnostic tests required to assess
kidney stones
• Review medical therapeutic interventions
which will reduce stone recurrence
Case 1
• You are asked to evaluate an 85 yo female with a history of
Crohn's disease with multiple ileal resections and an ileal
transverse colostomy. 122 cm of the ileum have been
resected. At the present time the patient does not have
any diarrhea, but she has had frequent loose stools in the
past.
• She was evaluated in the ED for left-sided ureteric colic
three weeks ago. She underwent a cystoscopy, left
retrograde pyelogram, left flexible ureteroscopy, laser
lithotripsy and basket extraction of stones from her left
ureter. A ureteral stent was placed. Since then, she has
been asymptomatic. Chemical analysis of her stones has
been performed.
• The patient does take vitamin D and calcium for treatment
of osteoporosis, but she has not been hypercalcemic or
hypercalciuric per report. There is also a history of vitamin
C use. Oral fluid intake is low.
Case 1
• VITAL SIGNS. Height 15.0 cm; weight 58.0 kg;
BMI 24.2 kg/m2; temp 36.8 C; BP 99/55 mmHg; P
56 bpm, regular.
• PHYSICAL EXAMINATION. Negative except for
colostomy and multiple abdominal surgical
scars.
Case 1 contd.
Stone analysis is likely to reveal:
•
•
•
•
•
Ca oxalate monohydrate and Ca oxalate dihydrate
100% uric acid
Struvite (Ca-Mg-NH4) stone
Brushite (Ca phosphate)
Hydroxyapaptite
Case 1 contd.
You would recommend treatment with which of the
following?
•
•
•
•
•
A high fluid intake – 2.5 L/day or more
A low oxalate diet
Calcium carbonate 1gm po tid
All of the above
None of the above
Case 2
• You are asked to evaluate an 80 yo female with a history of
recurrent kidney stones. Recently, she underwent a
cystoscopy and laser lithotripsy for a L ureteral stone. Two
and four years prior to seeing you, she had extracorporeal
shock wave lithotripsy for stones in the left and right renal
pelvis, respectively.
• With respect to risk factors for stones, she has a two-year
history of intermittent hypercalcemia with serum Ca values
as high as 11.1 mg/dL and a non-suppressed PTH. She
also has a history of gout dating back twenty years, for
which she takes colchicine when she has an acute attack,
and for which she is on chronic allopurinol. She has not
had any recent gouty attacks. With respect to
medications, she takes no vitamin D, calcium, or vitamin C.
She has taken prednisone in the past for a short period of
time.
Case 2
• There is no history of ulcerative colitis, regional
ileitis, malabsorption, or diarrhea.
• Her diet does not reveal a high oxalate or purine
precursor intake. She is on treatment at the
present time with Urocit-K 20 mEq PO t.i.d. as
well as allopurinol.
Case 2 contd.
• VITAL SIGNS: Height: 167.3 cm. Weight: 97.60 kg. BSA(G): 2.16 M2.
BMI: 34.870 KG/M2. Temperature: 36.8 °C. Blood Pressure: 141/68
mmHg. Pulse Rate: 78/minute, regular. PHYSICAL EXAMINATION: There
was a left parotid mass approximately 3 cm in diameter. No nodes were
felt. No other neck masses noted. The rest of the exam was normal. Labs:
PTH
120
Case 2 contd.
Case 2 contd.
Chest x-ray; 2 views: Prominent fat pad right
cardiophrenic angle. Slight scarring or atelectasis in
the right middle lobe. Calcified granuloma left lower
lobe. Mild thoracolumbar curve.
ECG normal.
Case 2 contd.
ACE – 71 U/L (nl 8-53); PTH-RP < 0.2 pmol/L (nl - < 2.0 pmol/L); whole
molecule PTH – 120 pg/mL (nl 5-65 pg/mL); serum monoclonal protein
by immunofixation small IgG l.
Parathyroid scan performed with technetium 99m sestamibi and
I-123 including SPECT imaging. Subtraction imaging showed a
discordant area of increased sestimibi uptake test posterior to the
inferior pole of the right thyroid lobe consistent with an abnormal
parathyroid gland. In addition there was increased sestamibi localization
posterior to the left inferior lobe of the thyroid that is less certain but
worrisome for a second abnormal parathyroid gland. No additional foci
of discordant sestimibi uptake.
Ultrasound of the neck demonstrated a 6 mm by 8mm x 9 mm hypoechoic
nodule posterior to the lower right thyroid lobe which could be a
parathyroid adenoma. There was also a 6 mm x 7 mm hypoechoic nodule in
the posterior portion of the inferior left thyroid lobe which is
likely a benign thyroid nodule. Small area of calcification in the mid
left thyroid lobe which was not associated with a focal nodule. No
cervical adenopathy.
Case 2 contd.
• An endocrine surgeon performed a two gland
parathyroidectomy with resolution of
hypercalcemia and subsequent stone activity.
Intra-operative Neck Vein PTH, pg/mL
Baseline
PTH
10 minutes
15 minutes
254
48
40
Post-op Ca 9.0 mg/dL.
Pathology of parathyroid glands: A. Parathyroid, left
superior, parathyroidectomy: Normocellular parathyroid
gland (50.0 milligrams). B. Parathyroid, left inferior,
biopsy: Normocellular parathyroid tissue. C. Parathyroid,
right superior, parathyroidectomy: Hypercellular
parathyroid (230.0 milligrams). D. Parathyroid, right
inferior, parathyroidectomy: Hypercellular parathyroid
(240.0 milligrams).
Case 2 contd.
Stone analysis is likely to reveal:
•
•
•
•
•
Ca oxalate monohydrate and Ca oxalate dihydrate
100% uric acid
Struvite (Ca-Mg-NH4) stone
Brushite (Ca phosphate)
Hydroxyapaptite
Nephrolithiasis is Common, Costly
and Preventable
• Nephrolithiasis is a common disorder (yearly
incidence of nephrolithiasis in the US is ~ 0.5%)
that is associated with considerable morbidity
and economic cost.
• In the USA the economic cost is estimated at
between $2.1 and $5.3 billion billion per year,
with the vast majority ($4.5 billion) attributed to
direct medical/urological costs.
• Strategies to accurately diagnose the type of
stones and institute measures to prevent stone
recurrence will have a great impact on reducing
costs associated with this illness.
The Prevalence of Nephrolithiasis has
Increased
• The prevalence of nephrolithiasis in the United
States and Europe has increased in the two
decades between 1970-1990 from about 3% to
about 5%.
Percent Prevalence of History of
Kidney Stones 1976-1980 and 1988-1994
Statmatelou, Kidney International 63: 2003
Incidence of Kidney Stones
1950-1974 and 1970-2000 in Rochester, MN
Lieske et al, Kidney International (2006) 69, 760–764.
Why the “Stone Boom”?
• Better diagnostic tools
• Life style
• Dietary habits
• Obesity
Life Style Risk Factors
for Stone Formation
• Low water intake : low volume and infrequent
intake  increased urine supersaturation
• Consumption of food rich in calories and salt, and
low in fiber and alkali  hypercalciuria,
deficiency in urinary stone inhibitors
• Sedentary lifestyle  obesity
Stone Episodes and Obesity
Siener R, Obesity Res, 12: 106-113, 2004
BMI and Relative Risk of
Symptomatic Stones
Taylor E, JAMA, 293(4), 455-462 2005
Urine Composition with Obesity
• Decreased Urine pH
• Elevated urinary excretion of
 Sodium
 Calcium (men > women)
 Phosphate, sulfate
 Uric acid
 Oxalate (women)
Siener R, Obesity Research 12:106-113, 2004
Nephrolithiasis is Associated with an
Increase in the Incidence of CKD
Rule et al, Clin J Am Soc Nephrol, 6:2069-2075, 2011.
Nephrolithiasis is Associated with an
Increased Incidence of Myocardial
Infarction
Rule et al, J Am Soc Nephrol. 2010 Oct;21(10):1641-4.
Composition of Kidney Stones
Percentage of stones
Characteristics
Calcium oxalate
monohydrate
40-60%
Radio-opaque, wellcircumscribed
Calcium oxalate dihydrate
40 to 60%
Radio-opaque
Calcium phosphate, apatite,
Ca10[PO4]6[OH]2
20-60%
Radio-opaque
Calcium phosphate,
Brushite, CaHPO4.2H2O
2-4%
Radio-opaque
Uric Acid
5-10%
Radiolucent
Struvite (magnesium
ammonium phosphate)
5-15%
Can be staghorn
Cystine
1.0-2.5%
Mildly radio-opaque
Ammonium urate
0.5-1 .0%
Crystal type
Mixed stones
Calcium oxalate-phosphate
35-40%
Radio-opaque
Mixed uric acid-calcium
oxalate
5%
Radio-opaque
Herring et al, J. Urol, 88:545, 1962; Mandel et al, J. Urol, 142-1513, 1989; Mandel et al, J. Urol, 142:1516,1989
Pathophysiology of Stones
A number of metabolic abnormalities are
associated with the occurrence of renal calculi.
• Increased urinary concentration of solutes
due to a reduction in fluid intake and urine
volume.
• Metabolic abnormalities: Hypercalciuria,
hypocitraturia, hyperoxaluria,
hyperuricosuria, and altered urinary pH.
Individuals at Increased Risk for Stone
Formation
•
•
•
•
•
Hypercalciuria
Hypocitraturia
Hyperparathyroidism
Hyperoxaluria
GI diseases (Colitis,
Crohn’s,
malabsorption)
• Surgery for obesity
• Family History
• Gout/hyperuricosuria/
Uric acid
• Infected stones
• Genetically
determined
•Cystinuria
•Primary
Hyperoxaluria
•RTA Type I
•2,8
Dihydroxyadenine
•Xanthine
Pathophysiology of Renal Stones
Cause
Pathophysiology
Stone
Composition
Clinical Clues
All Stones
Low urine volume
(raises
concentration of
solutes)
Reduced intake
or increased
loss of water
Renal water conservation
All stones
Urine volume less
than 1 L per day and
osmolality greater
than 600 mOsm/Kg
Absorptive
hypercalciuria
Increased absorption in
intestine
Calcium oxalate
or calcium
phosphate
Urine Ca >6
mmol/liter (240 mg)
per day
Renal leak
Loss of Ca in via kidney
Urine Ca >6
mmol/liter (240 mg)
per day
HPT
Increased absorption in the
intestine and increased
bone resorption
High PTH
concentrations and
high 1, 25(OH)2D
concentrations.
Immobilization
Increased bone resorption
High U Ca
Excess sodium
in diet
Sodium induced
hypercalciuria
Increased urine Na
Excess protein
or acid in diet
Protein induced bone loss
and renal leak
Urine NH4
increased, high
urine sulfate, low
urine pH
Range of
monogenic
disorders
Bone loss, gut hyperabsorption and various
combinations
Calcium stones
Hypercalciuria
(raises saturation of
calcium salts)
Pathophysiology of Renal Stones
Cause
Pathophysiology
Stone
Composition
Clinical Clues
Calcium stones
Hypocitraturia
(increases urinary
ionized Ca, reduces
inhibitor activity
against Ca salts)
Renal tubular acidosis
(distal type)
Abnormal renal
defense of acid-base
balance
Calcium
phosphate
Urine citrate
concentrations less
than 1.7 mmol/day.
High urine pH
High acid load
(absence of detectable
acidemia)
Physiological
hypocitraturia
Calcium
phosphate and
calcium oxalate
Urine citrate
concentrations less
than 1.7 mmol/day.
High urine pH
Hyperoxaluria
(raises saturation of
calcium oxalate)
Hyperuricosuria (Na
urate precipitation
causes nidation of
Ca salts)
Excess of dietary
oxalate
Increased delivery of
luminal oxalate
Calcium oxalate
Urine oxalate greater
than 0.4 mmol/day
Bowel disease
(malabsorption, gastric
bypass procedures)
Reduced formation of
luminal/intestinal Caoxalate complexes
Calcium oxalate
Urine oxalate greater
than 0.4 mmol/day
Increased endogenous
production of oxalate
Primary hyperoxaluria,
type I and 2
High purine intake
High purine intake
Raised
production &
excretion of
sodium urate
Urinary uric acid
excretion of greater
than 600 mg/day
Gout, Myeloproliferative
disease, enzymatic
defect, uricosuric
drugs, renal leak
Increased excretion of
uric acid
Hyperuricosuria,
serum uric acid may
be decreased
Pathophysiology of Renal Stones
Cause
Pathophysiology
Stone
Composition
Clinical Clues
Uric acid stones
Low urine pH or
hyperuricosuria
High acid load,
metabolic syndrome,
other causes of
hyperuricosuria
Urate salts are
converted to uric acid
which is insoluble and
low urinary pH
Uric acid
Low urine pH, less
than 5.5
Congenital mutations of
di-basic amino acid
transportersubunits
Increased urinary
cystine and other of
basic amino acids
Cystine
Urine cystine greater
than 150 μmol/mmol
creatinine
Urea-splitting
organisms
Production of
ammonium and
bicarbonate ions from
urea
Magnesium
ammonium
phosphate,
carbonate
apatite
High urinary pH,
pyuria, positive
cultures for
organism producing
urease
Cystine stones
Cystinuria
Infection-related
stones
Urinary tract
infection
Kidney Stone Management
Recognize Risks
Manage risks
Monitor
Evaluation of the First Stone
First Stone Episode
Diet
Fluid
3-6 month follow-up
Determine Metabolic Activity
Dual Energy CT
Urinalysis
Urine chemistries
No growth
Monitor every 1-2 years
Metabolic activity
Treatment options
Chemical Evaluation of Stones
• Serum
•Ca, Pi
•PTH
•Vitamin D
Metabolites
•Uric Acid
•Na, K, Cl, HCO3
• Urine
•pH
•Sediment
•Osmolality
•Gram’s stain
•Culture
• 24hr urinary profile
•Volume
•Calcium
•Citrate
•Oxalate
•Phosphorus
•Sodium
•Magnesium
•Urinary
supersaturation
• Radiological Studies
•Dual energy CT
•CT Urogram
Renal Stone Characterization Using DECT
Uric acid calculus
Non-uric acid/
Calcium calculus
Hartman et al. Radiologic Clinics of North America 2012 vol:50 iss:2 pg:191 -205
Renal Stone Characterization Using DECT
Ca oxalate
calculus
Hydroxyapaptite
calculus
Liu et al, Academic Radiology, 20, 1521–1525, 2013
General Measures for the Treatment
of Renal Stones: Lifestyle changes
These interventions are applicable to all stones
•
•
•
•
BMI 18-25 kg/m2
Balancing excess fluid loss
Dietary changes
Physical activity
General Measures: Dietary
Prevention of Stone Formation
These interventions are applicable to all stones
• Fluid
•
•
•
•
Total intake: 2.5-3.0 L/day
Urine output: 2.0-2.5 L/day
Intake balanced throughout the day
Neutral beverages
General Measures: Dietary Prevention
of Stone Formation
These interventions are applicable to all stones
• Limit animal protein: 0.8-1.0 grams/Kg/day
• Limit sugar and fat content
• Limit sodium: 4-5 grams/day Calcium: 1,000•
•
•
1,200 mg/day (not with absorptive
hypercalciuria)
Limit oxalate intake
Rich in vegetable fiber
Rich in alkaline potassium
General Measures: Restriction of
Dietary Animal Protein and Sodium
A high intake of animal proteins/purine precursors
•
•
•
•
Increases urinary uric acid excretion
Decreases urinary pH
Decreases urinary citrate excretion
Increases urinary calcium excretion
A high intake of sodium chloride
• High salt diet – increases urinary calcium
excretion
Dietary Animal Proteins
and Salt:
Risks for Stone
Formation
Kok D at al. J Clin Endocrinol Metab. 71:661. 1990
A High Calcium Intake is Associated with Reduced
Urinary Oxalate Excretion
Von Unruh G, et al, JASN 15(6), 1567-73, 2004
Specific Measures for the Treatment
of Nephrolithiasis
Lifestyle or Dietary
Modification
Pharmacological
Treatment
Low urine volume
Increase fluid intake to
2.5-3 liters per day
Increased Fluid Intake
Hypercalciuria
Sodium moderation less
than 150 mmol per 24
hours
Hydrochlorothiazide or
indapamide + potassium
alkali (potassium citrate
5-10 mEq p.o. t.i.d.)
Protein moderation
Hyperoxaluria
Restriction of dietary
oxalate
Avoidance of calcium
restriction
Calcium
supplementation in
malabsorption
syndrome or following
bypass surgery
Low-fat intake in
malabsorption
syndrome
Pyridoxine for primary
hyperoxaluria; liver
kidney transplantation
Specific Measures for the Treatment
of Nephrolithiasis
Lifestyle or Dietary
Modification
Hyperuricosuria
Purine restriction
Pharmacological
Treatment
Potassium citrate, other
alkalinizing agents such
as Bicitra
Allopurinol
Low urinary pH
Protein restriction
Potassium citrate
Cystinuria
High fluid intake
Potassium citrate, Dpenicillamine, bmercaptopropionyl
glycine
Urinary Tract Infection
Antibiotics
Specific Measures For Calcium
Oxalate Stones
•
•
•
•
•
Assessment of Risk factors
Hypercalciuria, Hyperoxaluria,
Hyperuricosuria, Hypocitraturia
Low urine volume
Diet: Low fluids, High salt, High protein, High
sugar
Family History
Sex
Measures Which Decrease the Risk of
Recurrent Calcium Oxalate Stone Disease
•
•
•
•
Low animal protein diet
Low salt diet
Increased fluids 2.5-3 L/day
Normal Ca intake (1 g/day)
A High Calcium Intake is Associated with Reduced
Urinary Oxalate Excretion
Von Unruh G, et al, JASN 15(6), 1567-73, 2004
Management of Calcium Oxalate Stones:
Urinary Profiles, Risks and Interventions
• Hypercalciuria –
• Hydrochlorothiazide 25-50 mg/d
• Indapamide 1.25 mg/d
• Chlorthalidone 50 mg/d
• Potassium citrate 5-10 mEq p.o. t.i.d.
• Hypocitraturia –
• Lower dietary animal protein
• Potassium citrate 5-10 mEq p.o. t.i.d.
Management of Calcium Oxalate Stones:
Urinary Profiles, Risks and Interventions
• Hyperoxaluria –
• Calcium 500 mg/day with meals
• Magnesium 200 - 400 mg/day
• Hyperuricosuria –
• Potassium citrate 5-10 mEq p.o. t.i.d.
• Allopurinol 100 mg/day
• Hypomagnesiuria –
• Magnesium 200 - 400 mg/day
Nephrolithiasis and Hyperoxaluria are
Complications of Bariatric Surgery
• Although there is a decrease in overall mortality and
an improvement in lipid and carbohydrate
metabolism in patients after RYGB surgery, the
incidence of nephrolithiasis and hyperoxaluria
increases post-RYGB surgery.
• In a recent study of 4,639 RYGB patients who had
undergone bariatric surgery and 4,639 obese control
patients, Matlaga et al noted that 7.65% (355 of
4,639) of RYGB patients developed urolithiasis
compared to 4.63% (215 of 4,639) of the obese
control patients in the control group (Matlaga et al J.
Urol, 2009).
Kidney Stones Associated with
Malabsorption and Gastric Bypass Surgery:
Hyperoxaluric Stone Disease
• Increased oxalate absorption from the colon
• Excess free fatty acids – fat malabsorption
• Bind calcium and magnesium
• Leave free oxalate to be absorbed
• Fatty acids and bile salts increase colonic oxalate
absorption
Kidney Stones Associated with
Malabsorption and Gastric Bypass Surgery:
Hyperoxaluric Stone Disease
• Increase in Urinary supersaturation
• Decreased water absorption – low urine volumes
• Decreased absorption of crystallization inhibitors:
• Magnesium, phosphate, pyrophosphate
Kidney Stones Associated with
Malabsorption and Gastric Bypass Surgery:
Hyperoxaluric Stone Disease
• Urinary Profile
•Hypocalciuria
•Hypomagnesiuria
•Hypocitraturia
•Hyperoxaluria
•Low urine volumes
•Acidic urine
• Treatment
•Correct underlying
malabsorption
•Dietary calcium
•Magnesium sup.
•Citrate
•Low oxalate diet
•Increase fluids
•Decrease dietary
fat
•Cholestyramine
Kidney Stones Associated with Bowel
Disease: Uric Acid Stones
• Etiology: low urine output and acidic urine
• Colectomy with ileostomy – loss of fluid and alkali
• Treatment
• Alkalinize the urine
• Fluids
• Allopurinol
Stones Associated with an Acidic
Urine: Uric Acid Stones
• 5-10% of all stones
• With gout, 25% form uric acid stones
• Etiology:
• Low urine volume
• Acidic urine
• Chronic diarrhea – colectomy and ileostomy
• Excess protein intake
Stones Associated with an Acidic
Urine: Uric Acid Stones
• Treatment: dissolve and prevent
• Increase fluid intake and decrease protein
intake
• Alkalinize the urine – citrate
• Allopurinol
Stones with an Acidic Urine:
Cystine Stones
• 1% of Kidney stones formers
• Autosomal recessive : homozygotes – stones
• Defect in intestinal and renal absorption of
cystine, ornithine, lysine, and arginine (COLA)
• Diagnosis:
• Crystalluria on UA – hexagonal
• Cystinuria ( 400mg/day)
• Family History
Stones with an Acidic Urine
Cystine Stones
• Treatment
• Alkalinize urine to > 7.0
• Chelators: tiopronin or penicillamine
(+ pyridoxine)
Stones Associated with an Alkaline
Urine :Calcium Phosphate Stones
• RTA type I
• Hyperparathyroidism
• Use of absorbable alkali (Tums, Rolaids, AlkaSeltzer)
• Medullary Sponge Kidney
Stones Associated with an Alkaline
Urine: RTA Type I
• Hyperchloremic Hyperkalemic Metabolic Acidosis
• Nephrocalcinosis
• Urinary Profile
• Hypercalciuria
• Hypocitraturia
• Urine pH always > 5.3
Stones Associated with an Alkaline
Urine: RTA Type I
• Treatment
• High fluid intake
• Correct acidosis: K citrate
Stones Associated with an
Alkaline Urine: Struvite Stones
• Magnesium ammonium phosphate stones
• All are infected
Proteus, other gram-negative organisms
• 10% of all kidney stones / 50% are bilateral
• Urine Profile : pH 8.0
• Treatment:
• Preoperative antibiotics
• Surgical removal of all stone material
• Post-op bacterialcidal antibiotics for 6-12
months
Hyperparathyroidism and Kidney Stones
The association is well-recognized – “stone, bones, groans”
etc. The association first recognized in the case of Captain
Martell by Dr. Eugene F. DuBois in 1926. Captain Martell
had become disabled by demineralization of the skeleton in
association with hypercalcemia over many years. He had
several episodes of flank pain, kidney calcification and
stones. He was extensively studied at the MGH and
eventually, a parathyroid adenoma was removed from the
mediastinum at his seventh operation in 1932 with
correction of his serum calcium.
Interestingly, in 1925 in Europe, Felix Mandl, had removed a
parathyroid tumor from a patient with kidney stones and a
bony disorder, with marked clinical improvement.
Hyperparathyroidism and Nephrolithiasis
• Only 15-20% of patients with HPT develop stones.
• The reason for this might be that patients with
stones have a concomitant increase in their
1,25(OH)2D concentrations and increase in
intestinal Ca absorption.
Broadus et al , N Engl J Med 1980; 302:421-426.
Treatment of Stone with HPT
• Identify aberrant gland
• Parathroidectomy
Primary Hyperoxaluria
Oxalate Metabolism
•Oxalate is poorly absorbed from the alimentary tract.
About 10-20 percent of the oxalate excreted in the
urine is dietary in origin, the vast majority being
endogenously derived.
•About 40 percent of oxalate production appears to be
derived from glycine metabolism.
•Most oxalate precursors are metabolized via
glyoxylate and/or glycolate the oxidation of which is
the main regulatory step in the metabolism of
carbohydrates to oxalate.
Metabolism of Oxalate
Aronson PS, Kidney International 2006
Oxalate Metabolism
C. J. Danpure
•PH1 is caused by a functional deficiency of the liver-specific
peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT)
•PH2 by a deficiency of the cytosolic enzyme glyoxylate
reductase (GR) and hydroxypyruvate reductase (HPR).
•One-third of PH1 patients have significant levels of AGT catalytic
activity due to a unique intracellular protein trafficking defects in
which AGT is erroneously localized to the mitochondria.
Treatment Stones and PH
• Pyridoxine
• Hepatic or hepatic/renal
transplantation
Surgical Therapy
• Obstruction
• Persistent severe hematuria
• Persistent metabolic activity despite
maximal medical therapy
Case 1
• Patient with long standing Crohn’s disease and
an intact colon.
Case 1 contd.
Stone analysis is likely to reveal:
•
•
•
•
•
Ca oxalate monohydrate and Ca oxalate dihydrate
100% uric acid
Struvite (Ca-Mg-NH4) stone
Brushite (Ca phosphate)
Hydroxyapaptite
Case 1 contd.
On a 24 hour urine you would expect to see which of the
following:
•
•
•
•
•
•
Hyperoxaluria
Hyper-uricosuria
Hypercalciuria
Hypo-citraturia
All of the above
None of the above
Case 1 contd.
You would recommend treatment with:
•
•
•
•
•
A high fluid intake – 2.5 L/day or more
A low oxalate diet
Calcium carbonate 1gm po bid or tid
All of the above
None of the above
Case 2
• Patient with primary HPT
Case 2 contd.
Stone analysis is likely to reveal:
•
•
•
•
•
Ca oxalate monohydrate and Ca oxalate dihydrate
100% uric acid
Struvite (Ca-Mg-NH4) stone
Brushite (Ca phosphate)
Hydroxyapaptite
Summary
• Nephrolithiasis is increasing in frequency
• Metabolic abnormalities can and should
be identified in the urine and serum to guide
therapy
• A treatment program can be designed based
on findings
• Serial follow-up is necessary