Ch 13 Medical Management Of Stones

Front 1

Goals of medical management of stones

Back 1

1. Prevent new stones
2. Stabilize existing urolithiasis
3. Prevent urologic complications of urolithiasis
4. Prevent non-urologic complications
5. Identify non-urologic conditions predisposing to urolithiasis

Front 2

Prevent urologic complications of urolithiasis

Back 2

1. Urinary tract obstruction
2. Urinary tract infection
3. Renal compromise/ESRD
- Primary hyperoxaluria
- Hyperuricemia
- Staghorn renal calculi

Front 3

Prevent non-urologic complications

Back 3

1. Osteodystrophy
- absorptive hypercalciuria
- renal tubular acidosis
- primary hyperoxaluria
2. Cardiomyopathy
- primary hyperoxluria
3. Retinopathy
- primary hyperoxluria
4. Gouty arthritis
- hyperuricosemia

Front 4

Identify non-urologic conditions predisposing to urolithiasis

Back 4

1. Hyperparathyroidism
2. Gout
3. Sarcoidosis
4. GI malabsorptive conditions
5. Crohn's disease/Ulcerative colitis
6. Biliary disease
7. Pancreatitis
8. Bariatric surgery

Front 5

Calcium-based stones

Back 5

1. Calcium oxalate monohydrate
2. Calcium oxalate dihydrate
3. Calcium phosphate

Front 6

Non-calcium based stones

Back 6

1. Uric Acid
2. Ammonium acid urate
3. Cystine
4. Struvite
5. Sodium urate
6. Dihydroadenine
7. Xanthine
8. Drug induced (indinavir, ephedrine, triamterene)

Front 7

Possible associations with calcium oxalate stones

Back 7

1. Hypercalciuria
2. Hypercalcemia
3. Hyperoxaluria
4. Hypocitraturia
5. Gouty diathesis
6. Low urine volumes

Front 8

Possible associations with Ca Phos stones

Back 8

1. Distal renal tubular acidosis
2. Hyperparathyroidism
3. Low urine volumes
4. UTI's

Front 9

Possible associations with cystine stones

Back 9

Cystinuria

Front 10

Possible associations with struvite stones

Back 10

UTI

Front 11

Possible associations with uric acid, ammonium acid urate, sodium urate, dihydroadenine, and xanthine stones

Back 11

1. Gouty diathesis
2. Gouty arthritis
3. Gouty nephropathy
4. Gouty tophi
5. Hyperuricosuria
6. Hyperuricosemia
7. Obesity
8. Inborn errors of metabolism (Lesch-Nyhan dz)
9. Myloproliferative disorders
10. Tumor lysis syndrome
11. EtOH abuse

Front 12

Contributors to urolithiasis

Back 12

1. anatomic
2. functional

Front 13

Anatomic contributors to urolithiasis

Back 13

1. Obstruction (UPJ, stricture, BPH)
2. renal anatomy (medullary sponge kidney)
3. Foreign body (suture, staple, stent)
4. Diverticulum (calyceal, bladder)
5. Hydronephrosis
6. Urinary diversion/intestinal substitution

Front 14

Functional contributors to urolithiasis

Back 14

voiding dysfunction (neurogenic)

Front 15

Overall approach to classification of urolithiasis

Back 15

1. Type of stones
- Calcium based
- Non-calcium based
2. Predisposing factors
- Promoter excess
- Inhibitor deficiency
- General urine parameters

Front 16

Calcium-based stones

Back 16

1. Promoter excess
- Hypercalciuria
- Hyperuricosuria
- Hyperoxaluria
2. Inhibitor deficiency
- Hypocitraturia
- hypomagnesuria
3. General urine parameters
- Urine acidity ("Gouty diathesis")
- Low urine volumes

Front 17

Non-calcium based stones

Back 17

1. Promoter excess
- Hyperuricosuria
- Cystinuria
- Medications
2. Inhibitor deficiency
- Hypocitraturia
3. General urine parameters
- Urine acidity ("Gouty diathesis")
- Low urine volumes
- Urinary tract infection

Front 18

Classification of hypercalciuria

Back 18

1. Hypercalcemic
2. Normocalcemic

Front 19

Pathophysiology of hypercalcemic

Back 19

Increased serum calcium -> increased filtered calcium -> hypercalciuria

Front 20

Most common cause of hypercalcemic

Back 20

primary hyperparathyroidism

Front 21

Most common cause of normocalcemic

Back 21

absorptive hypercalciuria

Front 22

Most common cause of primary hyperparathyroidism

Back 22

1. Parathyroid adenoma
2. Parathyroid hyperplasia

Front 23

Effects of increased PTH

Back 23

1. Increase in Ca absorption from GI tract
2. Increase in Ca absorption from kidney
3. Increase in Ca absorption from bone
4. Increase in 1,25-OH-Vit D production from kidney--> increased Ca absorption from GI tract
5. Decreased phophate resorption from kidney

Front 24

Types of normocalcemic hypercalciuria

Back 24

1. Absorptive (types I,II,and III)
- Increased absorption/reabsorption of Ca from GI tract/bone/kidney -> increased filtered calcium to keep serum Ca near normal
2. Renal
- distal renal tubule "leaks" Ca into urine -> hypercalciuria
3. Resorptive
- Increased bone demineralization -> increased filtered Ca to keep serum Ca near normal -> hypercalciuria
4. Idiopathic

Front 25

Pathophys of Type I absorptive hypercalciuria

Back 25

1. Increased absorption for Ca from GI tract
2. Independent of dietary Ca content
3. Decreased dietary Ca -> negligible effect on urine Ca so fasting urinary Ca will cont to be elevated
4. Increased absorption -> negative feedback -> ***decreased serum PTH***

Front 26

Pathophys of Type II absorptive hypercalciuria

Back 26

1. Increased absorption of Ca from GI tract
2. Dependent on dietary Ca content***
3. Decreased dietary Ca -> normalizes urine Ca
4. Less severe from of AH type I
5. Because of the increased absorption of Ca -> negative feedback -> decreased serum PTH

Front 27

Pathophys of renal hypercalciuria

Back 27

1. Increased loss of Ca from kidney from distal tubule
2. Loss of Ca leads to increased serum PTH
3. Increased PTH leads to increased GI Ca absorption and increased bone Ca resorption to keep serum Ca near normal
4. Net effect is normal serum Ca and increased urine Ca
5. ***This is the mos common form of hypercalciuria in pediatric population

Front 28

Pathophys of resorptive hypercalciuria

Back 28

1. Mildly increased serum PTH leads to GI Ca absorption and increased bone Ca resorption
2. PTH levels not high enough to cause hypercalcemia***
3. Most of the increased Ca in the serum is filtered into the urine to keep serum Ca near normal

Front 29

How does high urinary uric acid contribute to calcium-based urolithiasis

Back 29

1. Formation of small uric acid crystals acts as nidus for calcium-based stones: heterogenous nucleation
2. Sodium acid urate may inhibit the effectiveness of naturally occurring inhibitors of stone formation, eg glycosaminoglycans

Front 30

Classification of hyperuricosuria

Back 30

1. hyperuricosemic hyperuricosuria -> serum uric acid increased
2. normouricosemic hyperuricosuria -> serum uric acid normal

Front 31

Properties of uric acid

Back 31

1. byproduct of purine metabolism
2. precursors are hypoxanthine and xanthine which are more soluble than uric acid
3. Xanthine oxidase is the enzyme that breaks hypoxanthine -> xanthine -> uric acid (both steps)
4. pKa uric acid = 5.5: so tx by increasing urine pH

Front 32

Risk factors for hyperuricosuria

Back 32

1. High dietary purine intake (eg red meat)
2. Heritable disorders of purine synthesis
- Lesch-Nyhan dz
- Overactivity of PRPP (phosphoribosyl pyrophosphate synthetase)
- Adenosine phospho-ribosyl transferase (APRT) deficiency
3. Myeloproliferative disorders - secondary to high cellular turnover leading to increased purine metabolism
4. Tymor lysis syndrome - significant tumor cell death during therapy, usually chemotherapy as well as high cellular turnover leading to purine metabolism
5. Medications (Probenicid, sulfinpyrazone)

Front 33

Classification of hyperoxaluria

Back 33

1. Primary
2. Secondary
3. Enteric
4. Idiopathic

Front 34

Pathophys of primary hyperoxaluria

Back 34

Increased hepatic production of oxalate leads to increased serum oxalate which leads to increased filtered oxalate which leads to hyperoxaluria

Front 35

How many types of primary hyperoxaluria

Back 35

Types I and II

Front 36

Properties of Type I primary hyperoxaluria

Back 36

1. More common
2. Excess glyoxylate oxidized to oxalate,
3. Enzyme defect - AGT (alalnine-glyoxylate amino-transferase)
4. Co-factor of AGT enzyme: Pyridoxine (Vit B6); one of the limiting factors of the reaction
5. Autosomal recessive; Chromosome 2 or 19
6. Presents early in life (mean age is 5 years old)

Front 37

Properties of Type II primary hyperoxaluria

Back 37

1. VERY rare
2. 2 enzyme deficiencies causes increased urine oxalate and glyceric acid
3. Condition also called L-glyceric aciduria
4. Enzyme defect: glyoxalate reductase and D-glycerate dehydrogenase
5. Pyridoxine is NOT a cofactor

Front 38

Classic findings of primary hyperoxaluria

Back 38

urinary oxalate > 100mg/day on 24-hour urine collection

Front 39

Urologic clinical manifestations of primary hyperoxaluria

Back 39

1. Early onset and recurrent urolithiasis
2. Renal insufficiency (Can be silent in 33%)
3. ESRD

Front 40

Non-urologic clinical manifestations of primary hyperoxaluria

Back 40

1. Pathophys: due to oxalate deposition in tissues
2. Heart: Cardiomyopathy, Arrhythima
3. Bones: Osteodystrophy, Joint pain
4. Eyes: Retinopathy, Maculopathy

Front 41

Pathophys of secondary hyperoxaluria (metabolic hyperoxaluria)

Back 41

1. Increased hepatic conversion of metabolites to oxalate leads to increased serum oxalate which leads to increased filtered oxalate which leads to hyperoxaluria
2. Hepatic enzymes normal

Front 42

Risk factors for secondary hyperoxaluria

Back 42

1. Pyridoxine/Vit B6 deficiency - almost like a secondary cause of primary hyperoxaluria type I
2. Excessive intake of high oxalate-containing food: spinach, tea, chocolate, nuts
3. Ethylene glycol ingestion - rare cause of recurrent urolithiasis

Front 43

Pathophys of enteric hyperoxaluria

Back 43

1. Increased GI absorption of oxalate leads to increased filtered oxalate which leads to hyperoxaluria
2. Small bowel pathology (esp ileum) leads to decreased bile salt reabsorption which leads to increased chelation of Ca in GI tract which leads to increased free oxalate which leads to increased GI absorption of oxalate
3. Increased bile salts in colon leads to increased permeability of colon to oxalate
4. Diarrhea leads to loss of Mg which leads to hypomagesuria
5. Decrease in oxalobacter formigines***- this bacterium metabolizes oxalate in GI tract

Front 44

Common conditions associated with enteric hyperoxaluria

Back 44

1. Inflammatory bowel disease (Crohn's/UC)
2. BIliary disease
3. Chronic diarrheal syndromes
4. Pancreatitis/pancreatectomy
5. Small bowel resection
6. Short gut syndrome
7. Small bowel bypass procedures (bariatric surgery)
8. Bacterial overgrowth syndromes

Front 45

Classic 24-hr urine collection findings associated with enteric hyperoxaluria

Back 45

1. Increased urine oxalate
2. Decreased urine Ca: Significant Ca loss in GI tract leads to less available for renal excretion (<100mg/day)
3. Decreased urine pH secondary to HCO3 loss in GI tract

Front 46

Pathophys of Idiopathic hyperoxaluria

Back 46

1. Abnormal GI tract receptor which binds and increases oxalate absorption
2. Decreased intestinal bacteria that metabolizes oxalate leads to increased oxalate absorption

Front 47

Pathophys/properties of Cystinuria

Back 47

1. Inborn error of metabolism
2. Defect in proximal convoluted tubule in transport system for 4 dibasic amino acids (COLA - cystine, ornithine, lysine, arginine) which leads to excretion of these in urine
3. Why cystine stones rather tan other dibasic amino acid stones? Cystine 9pKa 8.3) is relatively insoluble at typical urine pH (5-7)
4. Autosomal recessive
5. heterogenous nucleation can occur
6. Very few significant non-urinary tract manifestations

Front 48

Pathophys of drug-induced calculi

Back 48

1. Drug itself or a metabolite is filtered in the kidney and precipitates out of solution in the urine
2. Usually requires long-term use of drug

Front 49

Stone types of drug induced calculi

Back 49

1. Indinavir - protease inhibitor used in tx for HIV
2. Triamterence - K+-sparing diuretic
3. Ephedrine - synthetic alph-adrenergic agonist

Front 50

Pathophys of hypocitraturia

Back 50

1. Decreased citrate leads to decreased chelation of Ca in urine which leads to increased chelation of Ca in urine with other components to make stones
2. Intestinal citrate malabsorption
3. UTI (formation of enzyme citrate lyase)

Front 51

Pathophys of metabolic acidosis that leads to hypocitraturia

Back 51

1. Acidosis leads to increased chelation of H+ with citrate in mitochondria which leads to decreased citrate secretion into urine
2. Acidosis leads to increased absorption of citrate into renal tubular cells which leads to decreased citrate secretion into urine

Front 52

Conditions that lead to metabolic acidosis

Back 52

1. Distal renal tubular acidosis = RTA type 1***
2. Chronic diarrheal states
3. Medications: thiazides causes intracellular acidosis
4. High dietary protein intake = increased acid-ash load
5. Excessive exercise (lactic acidosis)
6. Idiopathic

Front 53

Pathophys of RTA type 1

Back 53

1. Inability of distal nephron to secrete H+
- Complete is the more severe form and will see systemic acidosis with high urinary pH
- Incomplete is less severe form which you do not see systemic acidosis. Urine pH may be normal but cannot acidify urine with acid load

Front 54

Associations with primary RTA type I

Back 54

1. AE1 gene
- AD form seen in caucasians
- AR form seen in southeast asians
- encodes for basolateral Cl-/HCO3- exchange on distal tubule's type I intercalated cells
2. H+/ATPase transporter mutation
- Autosomal recessive
- Transporter has multiple subunits different mutations can involve different subunits
- Sensorineural deafness
3. Carbonic anhydrase II mutation
- Autosomal recessive (often in consanguineous marriages)
- Mixed form of distal (Type i) and proximal (Type II) RTA
- Osteopetrosis and conductive deafness

Front 55

Associations with Secondary RTA type I

Back 55

1. Pyelonephritis
2. Urinary tract obstruction
3. Sarcoidosis
4. Renal transplant
5. ATN
6. Analgesic nephropathy
7. Primary hyperparathyroidism
8. Idiopathic hypercalciuria

Front 56

Findings with RTA type I

Back 56

1. Systemic acidosis
2. Hypocitraturia
- Severe (<200mg/day)
- Acidosis leads to increased chelation of H+ with citrate in mitochondria and decreased citrate secretion into urine
- Acidosis leads to increased absorption of citrate into renal tubular cells which leased to decreased citrate secretion into urine
- Sequelae of hypocitraturia: Urolithiasis, nephrocalcinosis, and bone disease
3. Hypercalciuria
- Acidosis leads to increased dissociation of Ca from serum proteins which leads to increased Ca available for renal filtration
- Acidosis leads to increased demineralization of bone which leads to increased Ca available for renal filtration
- Sequelae: urolithiasis, nephrocalcinosis
4. Hyperchloremia
- Dehydration leads to increased serum aldosterone which leads to reabsorption of H2O via Na+ resorption and concominant Cl reabsorption
- Sequelae: Can be early sign of metabolic acidosis
5. Hypokalemia
- Dehydration leads to increased serum aldosterone which leads ot reabsorption of H2) via Na+ reabsorption and concominante K+ secretion into urine
- Dehydration leads to increased serum aldosterone which leads to renalK+/H+ antiporter activity which leads to more loss of K+ in urine
- Sequelae: Cardiac - arrhythmia, msculoskeletal - weakness, and GI - ileus
6. Hyperphosphaturia
- Acidosis leads to increased demineralization of bone which leads to increased Phos available for renal filtration
- Sequelae: osteomalacia, growth retardation

Front 57

Concepts of incomplete distal renal tubular acidosis

Back 57

1. Previously known as RTA type III
2. Mild/absent acidosis
3. Normal/near-normal serum potassium

Front 58

Pathophys of hypomagnesuria

Back 58

1. Decreased Mg leads to decreased chelation of oxalate in urine to form soluble Mg-oxalate complex which leads to increased free oxalate in urine which leads to Ca chelation with oxalate
2. Etiology
- often associated with hypocitraturia
- GI malabsorptive conditions (Crohn's/UC)
- UTI's

Front 59

Mechanisms for stone formation - General urine parameters

Back 59

1. Low urine volume
2. Gouty diathesis
3. Infection based

Front 60

Mechanisms for stone formation - Low urine volume

Back 60

1. Important to all forms of urolithiasis
2. Can contribute to urine acidity - dehydration leads to increased renal Na+ reabsorption which leads to increased Na+/H+ exchanger activity and increased secretion of H+

Front 61

Mechanisms for stone formation - Gouty diathesis

Back 61

1. Definition: urine pH <5.5
2. Risk factors:
- High dietary purine intake which leads to metabolism of purines and increased uric acid production which leads to increased filtered uric acid
- High dietary protein intake which leads to amino acid load = acid-ash load
- Obesity which is associated with low urine pH
- Heritable disorders of purine synthesis (Lesch-Nyhan Disease, Overacitivty of PRPP, and ARPT deficiency
- Myeloproliferative disorders secondary to high cellular turnover and increased purine metabolism
- Tumor lysis syndrome due to high cellular turnover and increased purine metabolism (usually durin chemotx)
- Medications (Probenecid, sulfinpyrazone)
- EtOH abuse leads to metabolism to organic acids

Front 62

Clinical associations with Gouty diathesis

Back 62

1. Gout -Abnormality of purine metabolism associated with raised but variable serum uric acid levels secondary arthritis
2. Gouty arthritis - Often used as a synonym for gout; secondary to deposition of sodium urate crystals in joints
3. Gouty nephropathy - interstitial nephropathy secondary to uric acid crystal deposition
4. Gouty tophi - Subcutaneous depositions of uric acid in the periarticular tissues giving rise to raised painless subcutaneous lesions

Front 63

Mechanisms for stone formation - Infection-based

Back 63

1. UTI leads to urinary alkalination which leads to urolithiasis
2. Alkalinizing effect more significant if bacteria contains urease
3. E.coli does not produce urease
4. Urease metabolizes urea to ammonia and carbon dioxide. Ammonia leads to urinary alkalinization which leads to precipitation of urinary calculi with high pKA values (struvite/mag ammonium phos and calcium phos stones)
5. Bacteria resde in the interstices of the calculus which makes it difficult if not impossible to truly sterilize urine with antibiotic tx alone. Also necessitates removal of all stone material
6. Other possible contributors include factors which increased the risk of UTI
- urinary tract obstruction
- chronic non-obstructive hydronpehrosis
- neurogenic voiding dysfunction
- urinary diversion/intestinal subsitution

Front 64

When to complete an abbreviate metabolic evaluation for stone work-up

Back 64

1. Perform if low suspicion of significant metabolic abnormality or contributing pathyphys or if there are few/no obvious risk factors for recurrence
2. Indications (all should be true):
- First stone episode
- Single urinary calculus
- Calcium oxalate calculus
- Non-staghorn calculus
- Uncomplicated clinical course
- No anatomic GU anomalies
- Struvite stones - if pure struvite

Front 65

When to complete a comprehensive metabolic evaluation for stone work-up

Back 65

1. Perform if high suspicion of significant metabolic abnormality or risk factors for recurrence present
2. Indications for extensive metabolic eval:
- Uric acid, cystine, or Ca Phos stones
- Medical conditions with increased risk (gout, metabolic disorders, etc)
- Myeloproliferative disease
- Tymor lysis syndrome
- EtOH abuse
- GI malabsorptive/diarrheal states
- h/o GI surgery
- Type I RTA
- Hypercalcemia
- Urinary diversion/intestinal substitution
- High risk populations (hx of recurrent stones, fam hx of stones, pediatrics, nephrocalcinosis, solitary kidney)

Front 66

Parts of Abbrevieated metabolic evaluation

Back 66

1. History
2. Physical
3. Urine tests
4. Stone analysis
5. Bloodwork
6. Radiologic imaging

Front 67

Parts of extensive metabolic evaluation

Back 67

Same as abbreviated but also 24-hour urine collection and Pak test (calcium fast and loading test)

Front 68

Abbrevieated/Extensive metabolic evaluation: History

Back 68

1. Dietary excesses
a. Purine
b. Protein
c. Oxalate
d. Sodium
2.Medical conditions which might contribute to urolithiasis
3. Identification of high-risk populations
a. History of recurrent urolithiasis
b. Family history of stones
c. Pediatrics
d. Nephrocalcinosis
e. Solitary kidney
4.Medications
a. Indinavir
b. Triamterene
c. Ephedrine
d. Probenecid
e. Sulfapyrazole
f. Chemotherapy

Front 69

Abbrevieated/Extensive metabolic evaluation: Physical Exam

Back 69

1. Head and neck
a. Palpablemass
i. Parathyroid adenoma
ii. Parathyroid hyperplasia
2. Abdomen
a. Palpable kidney (Hydronephrosis or Palpable bladder)
b. Voiding dysfunction
3.Musculoskeletal
a. Lumbosacral abnormality
i. Neural tube defect→voiding dysfunction
b. Painful jointmovements
i. Gouty arthritis
ii. Primary hyperoxaluriarelated
4. Neurologic
a. Risk of voiding dysfunction
5. Cardiovascular
a. Arrhythmia
i. Hypokalemia→distal RTA
ii. Hyperoxaluria
6. Skin
a. Gouty tophi

Front 70

Abbrevieated/Extensive metabolic evaluation: Urine tests

Back 70

1. Urinalysis
a. pH <5.5 = Gouty diathesis
b. pH >7.5 = UTI
2. Urine culture
3. Urine microscopy - look for crystals

Front 71

Abbrevieated/Extensive metabolic evaluation: Stone analysis

Back 71

If not calcium oxalate, proceed with extensive metabolic evaluation

Front 72

Abbrevieated/Extensive metabolic evaluation: Bloodwork

Back 72

1. Electrolytes
a. Decreased HCO3 = Acidosis, eg, distal RTA
b. Decreased K = Distal RTA or medications
c. Increased Cl = Metabolic acidosis, eg, distal RTA
2. Ca
a. High = Hyperparathyroidism→check PTH
3. Phos
a. Low = Renal hypercalciuria
b. High = Resorptive hypercalciuria
4. Uric acid
a. High = Gout

Front 73

Abbrevieated/Extensive metabolic evaluation: Radiologic imaging

Back 73

1. KUB: Low sensitivity but Tomograms help to increase
sensitivity
2. IVP: Functional component to study
3. U/S: No radiation but less sensitive for ureteral calculi and may overestimate stone size. Can assess bladder emptying
4. CT: High sensitivity and specificity. Consider low-dose CT to reduce radiation exposure
5. Nuclear renogram: If obstruction in absence of calculus suspected

Front 74

Addtional tests for Extensive metabolic evaluation: 24-hr urine

Back 74

1. Do 2 separate collections initially
a. > 1 collection helps to correct for daily variations in
diet and fluid intake
2.Components measured (goal values)
b. Volume (>2–3L/day)
c. pH (5.5–7.0)
d. Ca (<250mg/day)
e.Mg (>60mg/day)
f. Phos (<1,100mg/day)
g. Na (<200mEq/day)
h. K (19–135mEq/day)
i. Citrate: Allows assessment of compliance
on potassium citrate therapy (value should
increase from baseline)
j. Creatinine (600–1,800 mg/day)
i. Value depends on patient characteristics
(weight, renal function)
ii. Allows for assessment of completeness of collection
iii. If too low (<500mg/day), consider incomplete collection or dilution with fluid
k. Uric acid (<700mg/day)
l. Oxalate (<45mg/day)
m. Citrate (>320mg/day)
n. SO4 (<30mmol/day)
o. Cystine (<250mg/L/day): Have to ask SPECIFICALLY
for cystine in some labs
3. Method of collection
a. Discard first voided urine on day of collection
b. Collect all urine for that day and the first voided urine of the NEXT day
c. Most containers do not need to be refrigerated/cooled (if preservatives are included
in the collection containers

Front 75

Addtional tests for Extensive metabolic evaluation: Stone analysis

Back 75

1. Calciumoxalate – Dihydrate or Monohydrate
2. Calcium phosphate – Brushite or Apatite
3. Uric acid
4. Cystine
5. Struvite

Front 76

Addtional tests for Extensive metabolic evaluation: Pak test (calciumfast and loading test)

Back 76

a. Allows differentiation of the different types of hypercalciuria
b. Rarely used because absorptive and renal
hypercalciuria are currently managed with thiazides and other tests can be used to determine presence of
resorptive hypercalciuria (serum phosphorus)
c. Uses calciumfasting and loading to exacerbate the differences between the types of hypercalciuria
d. Urine cAMP used as surrogate marker of serum PTH because it changesmore quickly and reliably with changes in serum Ca.
e. Procedure
i. 7 days low-Ca and low-Na diet
ii. Fast from 9 PM prior to day of test
iii.Distilled water between 9PM and midnight
iv. At 7 AM, empty bladder and discard urine
v. Collect urine from 7AM–9AM= fasting sample
vi. 1 gmCa PO
vii. Collect urine from 9AM–1PM= post-load sample
viii. Each sample checked for Ca, cAMP and creatinine

Front 77

Pak test results: Absorptive hypercalciuria Type I

Back 77

1. Fasting urine Ca: high: Remember – diet independent***
2. Fasting urine cAMP = fasting serum PTH: Low. The increased Ca absorption suppresses serum PTH
3. Post-load urine Ca: high. GI absorption of Ca still high and independent of diet
4. Post-load urine cAMP = post-load serum PTH: low. GI absorption of Ca still high and independent of diet

Front 78

Pak test results: Absorptive hypercalciuria Type II

Back 78

1. Fasting urine Ca: low. Remember – diet dependent***
2. Fasting urine cAMP = fasting serum PTH: normal. Because now Ca absorption is normal
3. Post-load urine Ca: high. Dietary dependent increase in Ca absorption
4. Post-load urine cAMP = post-load serum PTH: low. 2° to the increased dietary Ca

Front 79

Pak test results: Renal hypercalciuria

Back 79

1. Fasting urine Ca: high. Not related to diet but to distal renal tubule abnormality***
2. Fasting urine cAMP = fasting serumPTH: high. 2° to the Ca loss in urine
3. Post-load urine Ca: higher. More Ca available for renal filtration
4. Post-load urine cAMP = post-load serum PTH: normal. The increased Ca available from GI tract normalizes the serum PTH

Front 80

Pak test results: Resorptive hypercalciuria

Back 80

1. Fasting urine Ca: high. Not related to diet***
2. Fasting urine cAMP = fasting serum PTH: high. Primary problem is decreased Phos causing increased
serum PTH
3. Post-load urine Ca: high. Not related to diet
4. Post-load urine cAMP = post-load serum PTH: high. Again, not related to diet.

Front 81

Addtional results for Extensive metabolic evaluation: Distal RTA

Back 81

a. Blood gases: if Acidosis then consider distal RTA
b. Ammonium chloride loading test
i. Allows diagnosis of incomplete distal RTA (mild/absent systemic acidosis, normal/near normal
serum K)
ii. Premise: Primary problem is decreased ability to
renally eliminate excess acid→urine pH remains high even when significant acid load delivered
iii. Procedure
1. Baseline venous pH and bicarbonate level are drawn
2 .Ammonium chloride capsules (5mg or 0.1
mg/kg) PO given and 100ml of water given every hour
3. Urine collected over 6-hour period and pH
measured
4. Venous pH and bicarbonate levels measured
to confirm systemic acidosis
iv. Results: if Urine pH >5.5 after acid load: incomplete distal RTA

Front 82

Addtional results for Extensive metabolic evaluation: Cystinuria

Back 82

a. Sodium nitroprusside colorimetric test
i. Qualitative rather than quantitative test
ii. Results
1.Urine turns magenta color at urine cystine values >75mg/L

Front 83

Management Strategies: Absorptive hypercalciuria type I

Back 83

i. Decrease renal filtration of Ca
1. Decreased dietary sodium
2. Thiazides (chlorthalidone, indapamide, hydrochlorothiazide)
ii. Increase urine inhibitors of stone formation
1. Potassium citrate
iii. Change general urine parameters
1. Increased urine output
2. Urinary alkalization
a. Potassium citrate
b. Diet
i. Moderate calcium intake
ii. Decreased purine intake
iii. Decreased animal protein intake
iv. Increased fiber intake

Front 84

Management Strategies: Absorptive hypercalciuria type II

Back 84

i. Decreased renal filtration of Ca
1. Decreased dietary sodium
2. Thiazides
ii. Decreased GI absorption of Ca
1. Sodium cellulose phosphate (no longer available)
2. Orthophosphates
iii. Increased urine inhibitors of stone formation
1. Potassium citrate
iv. Change general urine parameters
1. Increased urine output
2. Urinary alkalinization
a. Potassium citrate
b. Diet
i.Moderate calcium intake
ii. Decreased purine intake
iii. Decreased animal protein intake
iv. Increased fiber intake

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Management Strategies for Absorptive hypercalciuria: Specifics

Back 85

i. Decreased dietary sodium: Renal sodium excretion correlates with renal Ca excretion

ii. Thiazide diuretics (chlorthalidone, indapamide): Inhibits distal tubular Na secretion→ concomitant decreased renal Ca excretion
1. Side effects
a. Lassitude/sleepiness
b. Hypokalemia: Often administered with K citrate or utilize K-sparing diuretic (eg,moduretic = HCTZ + amiloride)
c. Acidosis (mild): Secondary to mild hyperuricemia. Often administered with K citrate to address this issue
d. Can unmask subtle hyperparathyroidism
e. Glucose intolerance
f. Erectile dysfunction

iii. Sodium cellulose phosphate (no longer available): Binds Ca in GI tract
1. Side effects: nausea, diarrhea, hypomagnesuria, hyperoxaluria, and negative calcium balance
i. Hypomagnesuria: binds Mg in GI tract→ decreased GIMg absorption → decreased renal Mg filtration
ii. Hyperoxaluria: binds Ca and Mg in GI tract → increased free oxalate in GI tract→increased GI oxalate absorption → increased renal oxalate filtration
iii. Negative calcium balance: secondary increased PTH → bone resorption

iv. Orthophosphates: Bind Ca in GI tract (K-Phos neutral, Neutra-Phos K, Uro-KP-neutral)
i. Side Effects
1. GI: nausea, diarrhea
2. Hypomagnesuria: Binds Mg in GI tract→decreased GI Mg absorption →decreased renal Mg filtration
3. Hyperoxaluria: Binds Ca and Mg in GI tract→
increased free oxalate in GI tract →increased GI oxalate absorption →increased renal oxalate filtration

v. Potassium citrate: Increases urinary citrate and causes urinary alkalization (Citrate binds to H+). Also, counteracts the K-wasting and acidotic effects of thiazides
1. Side effects: GI intolerance - Reduced when taken with food/meals

vi. Diet
1. Decreased purine intake: Decreased purine load→
decreased purine metabolism → decreased uric acid production → decreased renal filtration of uric acid → decreased urine acidity → decreased risk of calciumoxalate urolithiasis
a. What to avoid: Excessive animal protein intake (high purine levels)
2. Decreased animal protein intake:
a. Decreased amino acid load → decreased serum acid load → decreased urine acidity
b. Decreased amino acid load → decreased serumacid
load → decreased consumption of cellular citrate → more citrate available for filtration into urine →
decreased hypocitraturia
c. Decreased amino acid load → decreased metabolism to oxalate→decreased risk of associated calcium oxalate urolithiasis
3. Decreased Sodium Intake: Renal sodium excretion correlates with renal Ca excretion. Reduction of urinary
sodium by 100mEq/day reduces urinary calcium by 50mg/day
4. Increased fiber intake: Binds Ca in GI tract
5. Increased urine output: Increased fluid intake to keep urine output >2,000mL/day
6. Neutral phosphates: Increased GI absorption of phosphate → increased serum phosphate → negative feedback → decreased vitamin D → decreased GI absorption of Ca. Side Effects include nausea, diarrhea

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Management Strategies for Renal hypercalciuria

Back 86

Goals
i. Decreased Renal Excretion of Ca
1. Thiazides (chlorthalidone, indapamide, HCTZ)
2. Decreased dietary sodium

ii. Increased stone inhibitors: Potassium citrate

iii. Change general urine parameters: Increased urine output

Specifics
i. Thiazides
1. Mainstay of therapy of renal hypercalciuria
2. Will correct renal leak of Ca
3. Will maintain positive calcium balance

ii. Decreased sodium intake
1. Renal sodium excretion correlates with renal Ca excretion

iii. Potassium citrate: Used in combination with thiazides to prevent hypokalemia with subsequent
hypocitraturia

iv. Increased urine output: Increased fluid intake to keep urine output >2,000mL/day

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Management Strategies for Resorptive hypercalciuria

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Goals
i. Decreased Ca resorption from bone
1. Bisphosphonates
2. Surgical removal of parathyroid adenoma or parathyroid hyperplasia

ii. Increased stone inhibitors: Potassium citrate

iii. Change general urine parameters: Increased urine output and Potassium citrate

Specifics

i. Surgical removal of parathyroid adenoma or hyperplastic parathyroid tissue best treatment

ii. Orthophosphate
1.Mechanismof action
a. Inhibition of osteoclast activity → counters effect of increased PTH → Decreased bone resorption
b. Possible augmentation of tubular Ca reabsorption → decreased hypercalciuria
c. This may result in negative feedback on PTH production → decreased PTH → decreased bone resorption of Ca
d. Increased urinary citrate excretion: Likely secondary to the alkaline nature of orthophosphate (sequesters H+)
e. Increases urinary pyrophosphate excretion → increased urine stone inhibitor: Likely from metabolism of the drug. Side effects include nausea, diarrhea

iii. Potassium citrate: Especially if hypercalciuria not well controlled on orthophosphate therapy

iv. Increased urine output: Increased fluid intake to keep urine output >2,000mL/day

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Management Strategies for Hyperuricosuria

Back 88

Goals:
i. Decreased stone promoters
1. Diet
a. Decrease dietary purine intake
b. Decrease dietary animal protein intake
c. Decrease dietary sodium intake
2. Allopurinol
ii. Increase stone inhibitors: Potassium citrate
iii. Change general urine parameters
1. Increase urine output
2. Urinary alkalization: Potassium citrate

Specifics:
i. Diet
1. Decrease purine intake: Decreased purine load → decreased purine metabolism → decreased uric acid production. Also, Decrease uric acid production → decreased renal filtration of uric acid → decreased urine acidity
2. Decrease animal protein intake:
i. Decreased amino acid load → decreased serum acid load → decreased urine acidity.
ii. Decreased amino acid load → decreased serum acid load → decreased consumption
of cellular citrate → more citrate available for filtration into urine → decreased hypocitraturia
iii. Decreased amino acid load → decreased metabolism to oxalate → decreased risk of associated calcium oxalate urolithiasis
3. Decrease sodium intake: Renal sodium excretion correlates with renal Ca excretion

ii. Allopurinol
1. Mechanismof action a. Inhibitor of xanthine oxidase → decreased uric acid, increased xanthine (more soluble)
2. Side effects
a. Rash: Can progress to an exfoliative
hemorrhagic dermatitis with systemic vasculitis
(rare)
b. Flare of gouty arthritis
c. Xanthine urolithiasis (rare)

iii. Febuxostat
1. Xanthine oxidase inhibitor
2. Approved for pts with gout
3. Studies on application for hyperuricosuria are pending

iv. Potassium citrate: Leads to urinary alkalinization =
Increased urinary citrate → increased chelation of urine Ca → decreased chance of associated Ca-oxalate
urolithiasis

v. Increase urine output: Increased fluid intake to keep urine output >2,000mL/day

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Management Strategies for Primary hyperoxaluria

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Goals
i. Increased conversion ofmetabolic intermediates to nonoxalate end products
1. Pyridoxine (= vitamin B6)

ii. Decreased GI oxalate absorption
1. Low oxalate diet
2. Neutral phosphates

iii. Decreased renal oxalate excretion
1. Thiazide
2. Avoid excessive vitamin C

iv. Increased stone inhibitors
1. Potassium citrate

v. Change general urine parameters
1. Increase urine output
2. Urinary alkalization: Potassium citrate

vi. Fix the primary problem
1. Liver transplant ± renal transplant

Specifics

i. Pyridoxine (= vitamin B6): Cofactor for AGT→maximizes the effect of the enzyme. Even if the enzyme is not defective (ie, type 2 primary hyperoxaluria), it can help tomaximize enzyme activity → minimize oxalate production

ii. Low oxalate diet
1. Avoid foods with high oxalate content
a. Spinach
b. Nuts
c. Chocolate
d. Beets
e. Tea
f. Soy

iii. Neutral phosphates: Bind oxalate in GI tract

iv. Thiazide:.Hypocalciuric effect → decreased Ca available for stone formation

v. Avoid excessive vitamin C: Excess ascorbic acid → converted to oxalate

vi. Potassium citrate: Urinary alkalinization and decreased chance of associated calcium xalate urolithiasis

vii. Increased urine output: Increased fluid intake to keep urine output >2,000mL/day

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Management Strategies for Enteric hyperoxaluria

Back 90

Goals
i. Decrease GI oxalate absorption
1. Increased GI chelation of oxalate
a. Low-fat diet
b. Bile salt resins
c. Oral calcium supplementation
d. Low-oxalate diet
e. Reversal of GI bypass if possible

ii. Increase stone inhibitors: Potassium citrate

iii. Change general urine parameters
1. Increase urine output
2. Urinary alkalinization: Potassium citrate or Sodium bicarbonate

Specifics

i. Low-fat diet: Decreases the chelation of Ca by fats → increased chelation of oxalate by Ca in GI tract

ii. Bile salt resins: Decreases the bile salts in GI tract → decreased chelation of Ca with bile salts → increased chelation of oxalate by Ca

iii. Low-oxalate diet
1. Avoid foods with high oxalate content
a. Spinach
b. Nuts
c. Chocolate
d. Beets
e. Soy
f. Tea

iv. Oral calcium supplementation
1. Usually as calcium citrate
2. Increased chelation of oxalate in GI tract with extra Ca
3. The extra Ca does not significantly increase the risk of stone formation since these patients have low urine
Ca 2° to Ca loss in GI tract

v. Potassium citrate: Alkalinizes urine and decreases chance of associated Ca-based urolithiasis

vi. Sodium bicarbonate: Many of these conditions associated with increased HCO3 loss in GI tract

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Management Strategies for Hypocitrauria

Back 91

Goals
i. Increase stone inhibitors: Potassium citrate

ii. Change general urine parameters
1. Increase urine output
2. Urinary alkalinization
a. Potassium citrate
b. Sodium bicarbonate
c. Citrus juice
1. Lemon juice
2. Orange juice – higher calories than lemonade

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Management Strategies for Hypomagnesuria

Back 92

Goals
i. Increase stone inhibitors
1.Magnesium citrate
2 .Magnesium gluconate
3. Potassium magnesium citrate (not yet FDA-approved)

Change general urine parameters
i. Increased urine output

ii. Treat concomitant hypocitraturia
1. Potassium citrate

Front 93

Management Strategies for Low urine volume

Back 93

Goals
i. Change general urine parameters
1. Increase urine output
i. Ideally >3,000mL/day
ii. Realistically >2,000mL/day
iii. Usually requires >100 oz fluid/day
iv. Need to be cognizant of situations where increased fluids required: Exercise, Heat, Illness

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Management Strategies for Gouty Diathesis

Back 94

Goals
i. Change general urine parameters
1. Increase urine output
2. Urinary alkalization: Potassium citrate or sodium bicarbonate
3.Citrus juices will not work for gouty diathesis (no significant change in urine pH)
a. Decrease acid load
i. Low-purine diet
ii. Low-sodium diet
iii. Low-sugar diet
iv. High-fiber diet
v. Allopurinol

Specifics
i. Potassium citrate
1. Urinary alkalization
2. Decreased acid load
3. Goal is urine pH 6.5–7.0

ii. Sodium bicarbonate
1. Urinary alkalization
2. Decreased acid load
3. Goal is urine pH 6.5–7.0
4. Problemis increase sodium load

iii. Low-purine diet: Decreased acid (especially uric acid)

iv. Low-sodium diet: Decreased urine Ca

v. Low-sugar diet: Decreased ketoacidosis

vi. High-fiber diet
1. Binds Ca in GI tract→decreased Ca absorption
2. Decreased intestinal transit time → decreased Ca absorption

vii. Allopurinol
1. Indications
a. Profound hyperuricosuria (urine uric acid >900–1,200 g/day)
b. Hyperuricosemia

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Management Strategies for Cystinuria

Back 95

Goals
i. Decreased stone promoters
1. Low methionine diet (rarely effective)

ii. Increase urinary inhibitors
1. Urinary cystine-chelating agents
a. Penicillamine
b. Thiola (alpha-mercaptopropionylglycine)
c. Bucillamine (investigational)
d. Captopril

iii. Change general urine parameters
1. Increase urine output
2. Urinary alkalization
a. Potassium citrate
b. Sodiumbicarbonate
c. Acetazolamide

Specifics

i. Low-methionine diet
1.Methionine: Essential amino acidmetabolized
to cystine. Fairly unpalatable → low compliance

ii. Thiola
1. = alpha-methyl-propionyl-glycine = alpha-MPG
2. Better side effect profile than penicillamine
3. Usually first-line treatment for cystinuria

iii. Penicillamine (specifically d-penicillamine)
1. Forms penicillamine-cystine disulfide: 50xmore soluble than cystine
2. Side effects
a.Hematologic: agranulocytosis, thrombocytopenia
b. Dermatologic: pemphigus
c. Renal: nephrotic syndrome
d. Rheumatologic: polymyositis
e. B6 Deficiency→usually add pyridoxine 50mg PO QD
3. Cheaper than thiola

iv. Bucillamine
1. Better side effect profile than penicillamine
2.Medication is still investigational

v. Captopril
1. Captopril-cysteine 200 xmore soluble than cystine
2. Effect not as reliable as other therapies
3. Rarely used

vi. Potassium citrate
1. Urinary alkalization
2. Goal: urine pH approximately 7.0 (Greater than this → paradoxical increased risk of CaPhos stone formation)

vii. Sodium bicarbonate
1. Urinary alkalization
2.Usually added when K-citrate maximized

viii. Increased urine output
1. Solubility of cystine approximately 250mg/Lof urine
a. Thus the goal for urinary cystine levels on therapy is <250mg cystine/L urine

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Management Strategies for Infection-based urolithiasis

Back 96

Goals
i. Decrease stone promoters
1. Surgical removal of as much stone material as possible. Ideally, complete stone removal
2. Correct anatomic/functional abnormalities
a. UPJO
b. UVJO
c. Calyceal diverticulum
d. Voiding dysfunction
3. Suppressive antibiotics
a. Especially where contributing factors difficult to control, eg, neurogenic voiding dysfunction

ii. Increase stone inhibitors
1. Urease inhibitors: Acetohydroxamic acid

iii. Change general urine parameters: Increase urine output

iv. Treat associated metabolic abnormalities
1.Metabolic evaluation warranted if stone is “mixed” (ie, struvite + calcium)
2. Metabolic abnormalities rarely found if stone composition is pure infection

Specifics

i. Surgical removal of asmuch stone material as possible
1. Decreased bacterial load
2. Decreased urine stasis

ii. Suppressive antibiotics
1. Especially where contributing factors difficult to control
a. Neurogenic voiding dysfunction
b. Chronic nonobstructive hydronephrosis

iii. Acetohydroxamic acid: Urease inhibitor.
1. Use especially where contributing factors difficult to control
a. Neurogenic voiding dysfunction
b. Chronic, nonobstructive hydronephrosis
2. Side effects
a.Hematologic: anemia, reticulocytosis
b. Dermatologic: rash
c. GI: hepatotoxicity, diarrhea, abdominal pain, nausea, vomiting
d. Teratogenic (avoid use in women of childbearing age)
e.Other: palpitations, H/A, deep venous thrombosis

iv. Treat associated metabolic abnormalities: approximately 50% will have additional metabolic
abnormalities

Front 97

Management Strategies for Medication based urolithiasis

Back 97

Goals
i. Decrease stone promoters
1. Stop/changemedication

ii. Change general urine parameters
1. Increase urine output

Front 98

Pitfalls of Medical Stone Management

Back 98

A. Ensure complete 24-hour urine collection
a. 24-hour creatinine asmeasure of “completeness” of collection

B.New stones/stone growth with 24-hour urine collection volumes → 2,000 mL and “normal” parameters
a. Check 24-hour creatinine to ensure patient is not adding water/fluid to 24-hour urine collections

C. Increased 24-hour uric acid after initiating K-citrate therapy
a. Decreased urine acidity →increased solubility of uric acid →more uric acid analyzed

D. Citrate level not responding to K-citrate therapy
a. 24-hour urine K should increase with K-citrate therapy
b. Is patient compliant?

E. Urinary diversions/intestinal substitutions often absorb some urinary components
a. 24-hour urine collections often unreliable
b. Often treat presumptively with K-citrate

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Ovals or Dumbells

Back 99

Calcium oxalate monohydrate (Whewellite)

Front 100

Envelopes octahedrons

Back 100

Calcium oxalate dihydrate (Weddellite)

Front 101

Parallelograms, double headed arrows, some in rosettes

Back 101

Uric acid

Front 102

Coffin lids

Back 102

Magnesium ammonium phosphate (Struvite)

Front 103

Pointing fingers, some in rosettes

Back 103

Calcium hydrogen phosphate (Brushite)

Front 104

Powder-like

Back 104

Calcium phosphate (Apatite)

Front 105

Hexagons

Back 105

Cystine