Transcript Urinalysis - Caribbean Institute of Nephrology

Diet and Nephrolithiasis
Fasika Tedla, MD, MSc
Medical Director of Transplantation
Assistant Professor of Medicine
SUNY Downstate Medical Center
9th Annual Conference on Nephrology & HTN
January 2017, Kingston, Jamaica
Outline
• Epidemiology
– Prevalence/incidence: Global, US
– Risk factors
• Pathogenesis
– Supersaturation
• Diagnosis and Mx
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Approach to patient
Indications for metabolic work up
Acute Rx
Longterm Mx
Case
A 52-years old obese man presented with acute
excruciating left flank pain, radiating to the left groin.
No relief by acetaminophen. No tenderness.
•Urinalysis: many RBC and 2-3 WBC under HPF trace
protein, no glucose, and pH 5.
•Abdominal XR: No stone;
•Non-contrast CT: obstructive stone in left ureter.
Pain suddenly disappeared. The next morning, a 10 mm
stone recovered after straining the urine. Lost to follow
up
Course
• 5 years later – Ca Oxalate stone
• Treatment with potassium citrate,
allopurinol and hydrochlorothiazide
• 7 years later – Brushite stone
Epidemiology – Geographic Variation
H4hinitiative.com
Epidemiology – Geographic Variation
Brikowski et al. Proc Natl Acad Sci U S A. 2008;105(28):9841-6.
Epidemiology – Risk Factors
Stamatelou et al. Kidney Int. 2003;63(5):1817-23..
Risk Factors – Role of Genetics
• Stone disease more common in
those with family history
– (McGeown, Clin Sci, 1960;
Resnick. NEJM 1968; Coe, NEJM,
1979; Curhan, JASN, 1997)
• Increased risk in part genetic
– Higher concordance in monozygotic
than dizygotic twins (Goldfarb, KI,
2005)
– Stone disease and urine
biochemical traits exhibit heritability
(McGeown, Clin Sci, 1960;
Resnick, NEJM, 1968; Mong, J
Urol, 2006; Lieske, CJASN, 2014)
• Heritability (H2) range
– ~46 – 63% stone disease
– ~20 – 95% urinary traits
– Rare monogenic disorders
associated with stones
• 15% of stone formers had identifiable
single gene mutations (Halbritter,
JASN, 2015)
Risk Factors – Diet, Obesity and Metabolic
Syndrome
• Dietary habits (Health Professionals Study)1
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Fluid intake < ~ 2000/d
Calcium intake < ~ 600 mg/d
Magnesium > 360 mg/d (protective)
Potassium > ~ 2900 mg/d (protective)
? Vitamin C > 500 mg/d
?high sodium, protein intake
• Obese2,3
– Higher risk of stone disease
– Lithogenic urine metabolic profile (low pH, citrate; higher uric
acid, Ca, oxalate, phosphate, sodium)
• Diabetes and Metabolic syndrome4,5
– Associated with stones – both Ca and UA
1.Taylor et al. J Am Soc Nephrol. 2004 ;15(12):3225-32.
2.Taylor et al. JAMA. 2005 ;293(4):455-62.
3.Taylor & Curhan. Am J Kidney Dis. 2006;48(6):905-15
4.West et al. Am J Kidney Dis. 2008;51(5):741-7.
5.Taylor et al. Kidney Int. 2005 ;68(3):1230-5.
Risk Factors - Summary
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Family history
Demographic: Older age, white, men
Hot, humid climate
Obesity, diabetes, metabolic syndrome
Dietary habits
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Fluid intake < ~ 2000/d
Calcium intake < ~ 600 mg/d
Magnesium > 360 mg/d (protective)
Potassium > ~ 2900 mg/d (protective)
?high sodium, protein intake
?high dose vitamin C
Types of Stones
• Stone centers1
– Calcium stones (~ 80%)
• Ca oxalate
• Ca phosphate (apatite or brushite)
– Uric acid (~ 5-9%)
– Struvite (infection) (10%)
– Rest (~ 1%)
• Cystine, Xanthine, dihydroxyadenine
• Medications (triamterene, indinavir)
• Community prevalence (Olmsted County)2
– ~ 95% Calcium stones, ~ 20% ca phosphate
– Struvite ~ 1%
– Uric acid ~ 5%
1.Coe et al. J Clin Invest. 2005;115(10):2598-608.
2.Singh et al. Mayo Clin Proc. 2015;90(10):1356-65.
Pathogenesis
• Solubility
– Maximum amount of solute dissolved in a unit volume
of solvent
• Factors for solids
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Nature of solute and solvent
Temperature
For weak acids or bases: pH
Effect of other chemicals
• Supersaturation
– Metastable state
– Solute concentration exceeds solubility
– Disturbance (e.g. addition of crystal, agitation) 
crystals
Pathogenesis
• Too much stone forming chemicals:
– Ca, Oxalate, HPO4=, Uric acid, PO4=
• Too little stone inhibitors:
– Citrate, Mg, pyrophosphate, Tamm Horsfall
Protein.
Pathogenesis
Supersaturation
Nucleation
Epitaxial
Growth
Aggregation
Moe O. Lancet. 2006;367(9507):333-44
Diet and Kidney Stones – Role of Citrate
• Acidosis
– Increased reabsorption
– Reduced excretion
– Increased metabolism
with chronic acidosis
– Same effect with
hypokalemia (= proximal
tubule intracellular
acidosis)
• Alkalosis
– Reverse
– Effect on
• NaDC-1 (citrate-3 is an
inhibitor)
• m-Aconitase
Zuckerman. Rev Urol. 2009;11(3):134-44.
Calcium Oxalate Stones
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pK of oxalic acid
1.2 & 4.2
normal urine pH is
higher than 4.2
most oxalate in urine
remains as a divalent
anion
calcium oxalate stone
is unaffected by urine
pH
COOH
COO-
COOH
COO-
Causes Of Hypercalciuria
• Primary hyperparathyroidism.
• Vitamin D intoxication.
– Endogenous (e.g. sarcoidosis, Hodgkins)
– Exogenous (supplements, iatrogenic)
• Idiopathic hypercalciuria
– Absorptive hypercalciuria
– Renal hypercalciuria
Causes Of Hyperoxaluria
1. Excess ingestion
2. Enteric hyperoxaluria
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ingested oxalate bound to Ca and excreted in stool.
in fat malabsorption, bacteria in colon convert fat to free fatty
acids
Free fatty acids bind ca++ and displace oxalate
oxalate absorbed into the blood and is excreted in urine
causing kidney stone.
Conditions associated: IBD, bariatric surgery
3. Primary hyperoxaluria
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Inborn error of metabolism of increased oxalate
production.
Oxalate deposits in many organs (e.g. heart,
kidney)
Liver transplant curative
Maltese Cross
Appearance
Envelope-shaped
Calcium Oxalate Crystals
Ca++HPO4= (Brushite) Stone
• pH = 6.8 (pK) + Log (HPO4=/H2PO4-)
• Alkaline urine increases the ratio of
HPO4=/H2PO4-.
• CaHPO4 is more likely to form in:
– Type I RTA
– Treatment with carbonic anhydrase inhibitors
(topiramate, acetazolamide)
Netter Collection
Coe et al. Clin J Am Soc Nephrol. 2011;6(8):2083-92.
Coe et al. Clin J Am Soc Nephrol. 2011;6(8):2083-92.
Uric acid and Sodium Urate
Crystals
Uric Acid
Sodium Urate
Urine pH and Uric Acid
Concentration
pH = 5.5 + Log (Urate / Uric Acid)
Effect of pH (cont’d)
• At pH 5.5: 1 to 1
• At pH 4.5: Urate/UA is 1 to 10 (mostly uric
acid)
• At pH 6.5: Urate/UA is 10 to 1 (mostly
urate)
Approach to Patient
• History
– Renal: asymptomatic
– Pain
• Varies by site in ureter where stone impacted
• dysuria, frequency if at bladder-ureter junction
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Hematuria
Vomiting
Thorough medication and family history
Complication: obstruction, infection
• Exam
– In distress (from pain)
• Lab/Imaging
– U/A: pH, microscopy (hematuria, crystals [DHA, cystine])
– non-contrast CT (Rarely, IVP; Plain X-ray for follow up)
– Metabolic evaluation
• Serum electrolytes including phosphorus, BUN, creatinine, iPTH, 1,25 (OH) 2 Vit D
• 24-hr Urine chemistry (volume, pH, creatinine, citrate, calcium, oxalate, uric acid,
phosphate, cystine, chloride, sulfate, ammonium)
– Stone analysis
Indication for Metabolic Work Up
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Family history
Childhood onset
Multiple or recurrent stones
Nephrocalcinosis or chronic kidney
disease
• High-risk clinical conditions
– Gastric bypass, IBD, malapsorption, chronic
diarrhea, hyperparathyroidism
• Stones other than calcium oxalate
Radiologic Characteristics
• Radio-opaque stones:
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Ca oxalate,
Ca phosphate,
struvite
cystine (slightly)
• Radio-lucent stones:
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uric acid
xanthine
Cystine
indinavir
Treatment Of Kidney Stone
• Acute treatment (colic)
– Volume expansion, analgesia
– α1- adrenergic blockers
– With obstruction: Urologic intervention
• Longterm
– General
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Increase fluid intake
Low salt, normal/high calcium diet
Avoid high protein diet
Supplement citrate (usu K citrate)
Calcium stones: thiazide diuretic
Uric acid stones: Alkalinize urine (K citrate), allopurinol
Struvite stones: eradicate infection
Cystine stones: if general measures fail: D-penicillamine, tiopronin
Brushite stones: thiazides
• Removal of stones
– Lithotripsy (Extracoroporeal or endoscopic)
– Endoscopic retrieval
– Open surgery
Endoscopic Approach
Case
A 52-years old obese man presented with acute
excruciating left flank pain, radiating to the left groin.
No relief by acetaminophen. No tenderness.
•Urinalysis: many RBC and 2-3 WBC under HPF trace
protein, no glucose, and pH 5.
•Abdominal XR: No stone;
•Non-contrast CT: obstructive stone in left ureter.
Pain suddenly disappeared. The next morning, a 10 mm
stone recovered after straining the urine. Lost to follow
up
Course
• 5 years later – Ca Oxalate stone
• Treatment with potassium citrate,
allopurinol and hydrochlorothiazide
• 7 years later – Brushite stone