Nona Casey D.

Baring, Group 7

NEPHROLITHIASIS

Incidence Pathogenesis
• Calcium Oxalate (most common) - 75%
• Calcium Phosphate - 15% • Supersaturation - the point at which the concentration product exceeds the
solubility product
• Struvite - 1%
• Presence of inhibitors of crystallization prevents majority from continuously
• Cysteine – <1%
forming stones
• Rarely, composed of medications: acyclovir, atazanavir, triamterene
• Urine Citrate - most clinically important inhibitor of calcium-containing
stones
• Calcium phosphate
Associated Medical Conditions
o found in the renal interstitium
• Nephrolithiasis is a systemic disorder o deposits at the thin limb of the loop of Henle, and then extends down to the
• Conditions predisposing to stone formation: papilla and erodes through the papillary epithelium, where it provides a site
o GI malabsorption (Crohn’s disease, gastric bypass) for deposition of calcium oxalate and calcium phosphate crystals
o Primary hyperparathyroidism • Calcium oxalate stones may grow on calcium phosphate at the tip of the renal
o Obesity papilla (Randall’s plaque)
o Type 2 DM • Tubular plugs of calcium phosphate may be the initiating event in calcium
o Distal Renal Tubular Acidosis phosphate stone development
• Conditions most likely present in patients with a history of nephrolithiasis: • Process of stone formation may begin years before a clinically detectable stone is
o HPN identified
o Gout
RISK FACTORS
o Cardiovascular Disease
o Cholelithiasis
o Reduced bone mineral density DIETARY
o CKD
• Does not directly cause Upper UTI → UTI in the setting of an obstructing stone • INCREASE RISK - animal protein, oxalate, sodium, sucrose, and
→ urologic emergency “pus under pressure” fructose

Reference:
1. Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, L. J., & Loscalzo, J. (2019). Harrisons Principles of Medicine, 20th Edition (20th ed.). McGraw-Hill Education/Medical
Nona Casey D. Baring, Group 7
• DECREASE RISK - calcium, potassium, and phytate
CALCIUM
• Higher dietary Ca = lower risk of stone formation
• may be due to a reduction in intestinal absorption of dietary
oxalate that results in lower urine oxalate
• Low calcium intake is contraindicated as it increases the risk of
stone formation and may contribute to lower bone density in stone
formers
• Supplemental calcium may increase the risk of stone formation
• Discrepancy between the risks from dietary calcium and calcium
supplements → due to timing of supplemental calcium intake or
higher total calcium consumption leading to higher urinary
calcium
OXALATE
• Absorption may be higher in stone formers
• Dietary oxalate is only a weak risk factor for stone formation
• Urinary oxalate is a strong risk factor for calcium oxalate stone
formation, and efforts to avoid high oxalate intake are beneficial
OTHER NUTRIENTS
• Higher intake of animal protein → increased excretion of calcium
and uric acid and decreased urinary excretion of citrate → increase
the risk of stone formation
• Higher sodium and sucrose intake increase calcium excretion
Reference:
1. Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, L. J., & Loscalzo, J. (2019). Harrisons Principles of Medicine, 20th Edition (20th ed.). McGraw-Hill Education/Medical
• Higher potassium intake decreases calcium excretion, and many
potassium-rich foods increase urinary citrate excretion due to
their alkali content
• May be associated with lower stone risk: magnesium and phytate
• Vitamin C supplements → increased risk of calcium oxalate stone
formation in men, possibly because of raised levels of oxalate in
urine → avoid Vitamin C supplements
FLUID AND BEVERAGES
• Risk of stone formation increases as urine volume decreases
• When the urine output is <1 L/d, the risk of stone formation more
than doubles
• Fluid intake: main determinant of urine volume
• Reduced risk of stone formation: coffee, tea, beer, wine, and orange
juice
• Increased risk: sugar-sweetened beverages
NON-DIETARY
• Age, race, body size, and environment → important risk factors
for nephrolithiasis
• incidence of stone disease is highest in middle-aged white men
• Weight gain → increases the risk of stone formation
• Environmental and occupational influences that may lead to
lower urine volume → working in a hot environment or lack of
ready access to water or a bathroom
URINARY
Nona Casey D. Baring, Group 7

URINE VOLUME • Higher urine levels of uric acid → risk factor for uric acid
stone formation → due to excess purine consumption and
• lower urine volume → higher concentrations of lithogenic factors rare genetic conditions that lead to overproduction of uric
acid
URINE CALCIUM
URINE pH
• Higher urine calcium excretion increases likelihood of formation
of calcium oxalate and calcium phosphate stones • Uric acid stones form only when the urine pH is consistently
• Greater gastrointestinal calcium absorption and greater bone ≤5.5 or lower
turnover (with a resultant reduction in bone mineral density) are • Calcium phosphate stones → more likely to form when the
important contributors urine pH is ≥6.5 or higher
• Cystine → more soluble at higher urine pH
URINE OXALATE • Calcium oxalate stones → not influenced by urine pH

• Higher urine oxalate excretion→ increases likelihood of calcium GENETIC

oxalate stone formation
• Higher dietary calcium intake → reduces gastrointestinal oxalate • The risk is >2-fold greater in individuals with a family history
absorption and thereby reduces urine oxalate of stone disease
• Primary hyperoxaluria and cystinuria: two most common
URINE CITRATE monogenic disorders that lead to stone formation
• Primary hyperoxaluria
• Urine citrate → natural inhibitor of calcium-containing stones o an autosomal recessive disorder that causes excessive
• Lower urine citrate excretion → increases risk of stone formation endogenous oxalate generation by the liver, with
• Citrate reabsorption is influenced by intracellular pH of proximal consequent calcium oxalate stone formation and crystal
tubular cells deposition in organs
• Metabolic acidosis due to higher animal flesh intake → reduces o Intraparenchymal calcium oxalate deposition in the
citrate excretion by increasing reabsorption of filtered citrate kidney can eventually lead to renal failure
• Cystinuria
URINE URIC ACID o an autosomal recessive disorder that causes abnormal
reabsorption of filtered basic amino acids

Reference:
1. Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, L. J., & Loscalzo, J. (2019). Harrisons Principles of Medicine, 20th Edition (20th ed.). McGraw-Hill Education/Medical
Nona Casey D. Baring, Group 7

o The excessive urinary excretion of cystine → cystine stone LABORATORY EVALUATION

formation
o Cystine stones are visible on plain radiographs → manifest as
staghorn calculi or multiple bilateral stones
CLINICAL PRESENTATION
• Two common presentations for individuals with an acute stone event: renal
colic and painless gross hematuria
• Discomfort often begins with a sudden onset of unilateral flank pain →
when a stone moves into the ureter
• The intensity of the pain can increase rapidly, and there are no alleviating
factors
• Pain often accompanied by nausea and occasionally by vomiting, may radiate,
depending on the location of the stone
• If the stone lodges in the upper part of the ureter, pain may radiate
anteriorly; if the stone is in the lower part of the ureter, pain can radiate
to the ipsilateral testicle in men or the ipsilateral labium in women
• Occasionally, a patient has gross hematuria without pain
DIAGNOSIS
• The diagnosis is often made on the basis of the history, physical
examination, and urinalysis
• Thus, it may not be necessary to wait for radiographic confirmation before
treating the symptoms
• Electrolytes (to uncover hypokalemia or renal tubular acidosis),
creatinine, calcium, and uric acid should be determined
• PTH level → indicated by high-normal or elevated serum and urine
calcium concentrations
• 25-hydroxy vitamin D → measured in concert with PTH to investigate the
possible role of secondarily elevated PTH levels in the setting of vitamin D
insufficiency
• WBC count may be elevated
• Examination of the urine sediment → reveal red and white blood cells and
occasionally crystals which may help identify the stone type and provide
prognostic information; crystalluria → strong risk factor for new stone
formation.
• Urine culture → if with concern for possibility of infection
• 24-h urine collections → serve as the cornerstone on which therapeutic
recommendations are based
o Recommendations on lifestyle modification should be deferred
until urine collection is complete
o As a baseline assessment, patients should collect at least two 24-h
urine samples while consuming their usual diet and usual volume
of fluid
o Total volume, calcium, oxalate, citrate, uric acid, sodium,
potassium, phosphorus, pH, and creatinine are measured
• Stone composition analysis → essential if a stone or fragment is available
o Patients should be encouraged to retrieve passed stones
• Pure uric acid stones → identified by low Hounsfield units on CT

Reference:
1. Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, L. J., & Loscalzo, J. (2019). Harrisons Principles of Medicine, 20th Edition (20th ed.). McGraw-Hill Education/Medical
Nona Casey D. Baring, Group 7

IMAGING CALCIUM PHOSPHATE

• Helical CT without contrast → gold standard
o highly sensitive, allows visualization of uric acid stones • Thiazide diuretics (with sodium restriction)
(traditionally considered “radiolucent”), and does not require • Alkali supplements (potassium citrate or bicarbonate)
radiocontrast • Reduction of dietary phosphate
o detects stones as small as 1 mm that may be missed by other
imaging modalities. URIC ACID
o Typically reveals a ureteral stone or evidence of recent passage
(e.g., perinephric stranding or hydronephrosis) • Increase intake of foods rich in alkali (fruits and vegetables)
• Abdominal ultrasound • Reduce intake of foods that produce acid (animal flesh)
o offers the advantage of avoiding radiation and provides • Supplementation with bicarbonate or citrate salts (pH goal of 6.5)
information on hydronephrosis • Xanthine oxidase inhibitor (allopurinol or febuxostat)
o not as sensitive as CT and images only the kidney and possibly the
proximal segment of the ureter CYSTINE
o most ureteral stones are not detectable by ultrasound
• Fluids to maintain high urine volume
RECOMMENDATIONS FOR SPECIFIC STONE TYPES • Alkalinize urine to pH 7.5 by potassium citrate or bicarbonates
• Tiopronin or Penicillamine
CALCIUM OXALATE
STRUVITE
• Avoid excessive calcium intake (>1200mg/day)
• Thiazide diuretics (chlorthalidone) may reduce calcium oxalate
• Complete removal by a urologist
stone formation
• Prevention of UTIs
• Dietary sodium restriction(<2.5g/day)
• Urease inhibitors (acetohydroxamic acid) for those with
• Avoiding high-dose Vitamin C supplements
recurrent upper UTIs
• Avoid foods with high amount of oxalate → spinach, rhubarb,
almonds and potatoes
• Restriction of non-dairy animal protein

Reference:
1. Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, L. J., & Loscalzo, J. (2019). Harrisons Principles of Medicine, 20th Edition (20th ed.). McGraw-Hill Education/Medical
Nona Casey D. Baring, Group 7

LONG TERM FOLLOW-UP • If with recurrent episodes of renal colic → repeat CT

▪ Minimize radiation exposure
• Followed up for the patient’s lifetime
• Repeat 24-hr urine collections
• Imaging

Reference:
1. Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, L. J., & Loscalzo, J. (2019). Harrisons Principles of Medicine, 20th Edition (20th ed.). McGraw-Hill Education/Medical
Nona Casey D. Baring, Group 7

APPROACH TO THE PATIENT

Reference:
1. Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, L. J., & Loscalzo, J. (2019). Harrisons Principles of Medicine, 20th Edition (20th ed.). McGraw-Hill Education/Medical