UrologySchool.com

Stones: Evaluation and Medical Management: Difference between revisions

← Older edit
Visual
 
(44 intermediate revisions by the same user not shown)
Line 5: Line 5:
=== Plain Abdominal Film ===
=== Plain Abdominal Film ===
*'''Findings'''
*'''Findings'''
**Can identify nephrocalcinosis, suggestive of RTA
**'''<span style="color:#ff0000">Radiolucent stones (6):</span>'''
** '''<span style="color:#ff0000">Radiolucent stones (6):</span>'''
*** '''<span style="color:#ff0000">Uric acid</span>'''
*** '''<span style="color:#ff0000">Uric acid</span>'''
*** '''<span style="color:#ff0000">Matrix</span>'''
*** '''<span style="color:#ff0000">Matrix</span>'''
Line 21: Line 20:
****'''<span style="color:#ff0000">Cystine stones</span>'''
****'''<span style="color:#ff0000">Cystine stones</span>'''
***** '''Although magnesium ammonium phosphate and cystine stones are often radioopaque, they are not as dense as calcium oxalate or calcium phosphate stones'''
***** '''Although magnesium ammonium phosphate and cystine stones are often radioopaque, they are not as dense as calcium oxalate or calcium phosphate stones'''
**'''Nephrocalcinosis'''
***'''Formation of diffuse deposits of calcium throughout the kidneys'''
****'''Usually occurs within the renal medulla''' but occasionally it has been found in the cortex or within both the medulla and the cortex
****Minute calcifications seen in early stages may not be visible
***'''Can give rise to renal colic and hydronephrosis from dislodged calcific foci'''
***[[File:Nephrocalcinosis.jpg|alt=Nephrocalcinosis. Source: Wikipedia|thumb|Plain film x-ray demonstrating bilateral diffuse calcium deposits in the kidneys. Source: [[commons:File:Nephrocalcinosis.jpg|Wikipedia]]|400x400px]]'''Causes[https://radiopaedia.org/articles/medullary-nephrocalcinosis §]'''
****'''Medulla'''
*****'''Type 1 (distal) RTA'''
*****'''Hyperparathyroidism'''
*****'''Medullary sponge kidney'''
*****'''Hypervitaminosis D'''
*****'''Milk-alkali syndrome'''
*****'''Sarcoidosis'''
*****'''Hyper/hypothyroidism'''
*****'''Other pathological hypercalcemic or hypercalciuric states'''
******'''Cushing syndrome'''
******'''Multiple myeloma'''
******'''Bartter syndrome'''
******'''Bone metastases'''
****'''Pyramids'''
*****'''Hyperuricemia'''
***** '''Infection (particularly renal tuberculosis)'''
*****'''Sickle cell disease (leading to infarction and subsequent dystrophic calcification)'''
*****'''Renal papillary necrosis'''
*****'''Drugs'''
*****'''Furosemide abuse'''
****'''Corticol COAG'''
*****'''Corticol necrosis'''
*****'''Oxalosis (Primary hyperoxaluria)'''
*****'''Alport syndrome'''
*****'''Glomerulonephritis (chronic)'''
*Test characteristics[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443345/ §]
*Test characteristics[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443345/ §]
**Sensitivity: 57%
**Sensitivity: 57%
Line 80: Line 110:
** Cost (most expensive, 30x cost of KUB)[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443345/ §]
** Cost (most expensive, 30x cost of KUB)[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443345/ §]


== Acute management ==
== Acute Diagnosis and Management ==


* Renal colic pain management[https://smhs.gwu.edu/urgentmatters/content/alternatives-opioids-pain-management-ed]
=== Diagnosis and Evaluation ===
** Toradol 30 mg IV
*'''History and Physical Exam'''
** Cardiac Lidocaine 1.5 mg/kg IV in 100 mL NS over 10 minutes (MAX 200 mg)
** History
** Acetaminophen 1000 mg PO
*** New-onset urgency and frequency may indicate a stone at the UVJ irritating the bladder
** 1 L 0.9% NS bolus
*** Sudden relief of flank pain may indicate either passage or forniceal rupture as the pressure in the collecting system dramatically decreases.
** Physical Exam
*** Abdomen
*** Costovertebral angle tenderness
*'''Labs'''
**'''Urinalysis +/- culture'''
**'''CBC'''
**'''Serum creatinine'''
*'''Imaging'''
 
=== Management ===
*'''Renal colic pain management[https://smhs.gwu.edu/urgentmatters/content/alternatives-opioids-pain-management-ed]'''
** '''Toradol 30 mg IV'''
** '''Acetaminophen 1000 mg PO'''
** '''1 L 0.9% NS bolus'''
**Cardiac Lidocaine 1.5 mg/kg IV in 100 mL NS over 10 minutes (MAX 200 mg)
*'''<span style="color:#ff0000">Urologic Emergency: If obstructing stones with suspected infection, must urgently drain the collecting system with a stent or nephrostomy tube and delay stone treatment</span>[https://pubmed.ncbi.nlm.nih.gov/27238616/ ★]'''
**Definitive management of the stone should not be undertaken until sepsis has resolved and the infection has been treated with an appropriate course of antibiotic therapy.


== Diagnosis and Evaluation of Metabolic Stone Disease ==
== Diagnosis and Evaluation of Metabolic Stone Disease ==
Line 102: Line 149:
**#'''<span style="color:#ff0000">Serum creatinine</span>'''
**#'''<span style="color:#ff0000">Serum creatinine</span>'''
**#'''<span style="color:#ff0000">Serum uric acid</span>'''
**#'''<span style="color:#ff0000">Serum uric acid</span>'''
**'''<span style="color:#ff0000">Imaging</span>'''
***'''<span style="color:#ff0000">Obtain or review available imaging studies to quantify stone burden.</span>'''
* '''<span style="color:#ff0000">Extended evaluation</span>'''
* '''<span style="color:#ff0000">Extended evaluation</span>'''
** '''<span style="color:#ff0000">One or two 24-hour urine collections</span>'''
** '''<span style="color:#ff0000">One or two 24-hour urine collections</span>'''
Line 142: Line 191:
**#'''<span style="color:#ff0000">Primary hyperparathyroidism</span>'''
**#'''<span style="color:#ff0000">Primary hyperparathyroidism</span>'''
**#'''<span style="color:#ff0000">Malabsorptive gastrointestinal states</span>''' due to bowel resection, bariatric surgery or bowel or pancreatic disease
**#'''<span style="color:#ff0000">Malabsorptive gastrointestinal states</span>''' due to bowel resection, bariatric surgery or bowel or pancreatic disease
**##Chronic diarrhea that could be caused by inflammatory bowel disease (Crohn disease, ulcerative colitis) or irritable bowel syndrome
**##'''Chronic diarrhea that could be caused by inflammatory bowel disease (Crohn disease, ulcerative colitis) or irritable bowel syndrome'''
**## Gout may predispose the patient to hyperuricosuria or gouty diathesis with either uric acid calculi or calcium oxalate stone formers
**## Gout may predispose the patient to hyperuricosuria or gouty diathesis with either uric acid calculi or calcium oxalate stone formers
**## Surgical history should be obtained focusing particularly on bariatric surgery and surgeries of the intestinal tract.  
**## '''Surgical history should be obtained focusing particularly on bariatric surgery and surgeries of the intestinal tract.'''
**###Roux-en-Y-gastric bypass surgery may significantly increase the overall risk for stone formation
**###'''Roux-en-Y-gastric bypass surgery may significantly increase the overall risk for stone formation'''
**###'''In contrast to gastric bypass surgery, restrictive bariatric surgeries such as gastric sleeve or gastric band do not seem to increase the risk for kidney stones'''
**###'''In contrast to gastric bypass surgery, restrictive bariatric surgeries such as gastric sleeve or gastric band do not seem to increase the risk for kidney stones'''
**'''<span style="color:#ff0000">Dietary history</span>'''
**'''<span style="color:#ff0000">Dietary history</span>'''
Line 175: Line 224:


=== Laboratory ===
=== Laboratory ===
* '''Urinalysis +/- culture +/- microscopy'''
 
** '''Urinalysis should include pH'''
==== <span style="color:#ff0000">Urinalysis +/- culture +/- microscopy</span> ====
*** '''pH > 7.0 is suggestive of infection lithiasis or RTA'''
* '''<span style="color:#ff0000">Urinalysis should include pH</span>'''
*** '''pH < 5.5 suggests uric acid lithiasis secondary to gouty diathesis'''
** '''<span style="color:#ff0000">pH > 7.0 is suggestive of infection lithiasis or RTA</span>'''
** '''Urine culture'''
** '''<span style="color:#ff0000">pH < 5.5 suggests uric acid lithiasis secondary to gouty diathesis</span>'''
*** Should be obtained in patients with a urinalysis suggestive of UTI.
* '''Urine culture'''
***Presence of urea-splitting organisms, such as Proteus species, raises the possibility of struvite stones
** '''Should be obtained in patients with a urinalysis suggestive of UTI.'''
***Many infected calculi will harbour bacteria even after treatment with broad-spectrum antibiotics
**'''Presence of urea-splitting organisms, such as Proteus species, raises the possibility of struvite stones'''
*** Half of infected calculi grow bacterial cultures that are different from the preoperative urine specimen
**Many infected calculi will harbor bacteria even after treatment with broad-spectrum antibiotics
**'''Urine microscopy'''
** Half of infected calculi grow bacterial cultures that are different from the preoperative urine specimen
***'''Identify crystals pathognomonic of stone type.'''
*'''Urine microscopy'''
*'''<span style="color:#ff0000">Serum chemistries (electrolytes (Na, K, Cl, HCO3), calcium, creatinine and uric acid)</span>'''
**'''Identify crystals pathognomonic of stone type.'''
** May suggest underlying medical conditions associated with stone disease (e.g., primary hyperparathyroidism, gout, RTA type 1 or other metabolic derangements)
 
** '''Assessment of underlying renal function is necessary'''
==== <span style="color:#ff0000">Serum chemistries</span> ====
*'''<span style="color:#ff0000">Parathyroid hormone (PTH)</span>'''
 
**'''<span style="color:#ff0000">Indicated as part of the screening evaluation if primary hyperparathyroidism is suspected</span>'''
*'''<span style="color:#ff0000">Includes</span>'''  
***'''<span style="color:#ff0000">Primary hyperparathyroidism should be suspected when (3):</span>'''
*#'''<span style="color:#ff0000">Electrolytes (Na, K, Cl, HCO3)</span>'''
***#Mid-range PTH despite '''<span style="color:#ff0000">high or high normal serum calcium</span>'''
*#'''<span style="color:#ff0000">Calcium</span>'''
***#'''<span style="color:#ff0000">Increased urinary calcium</span>'''
*#'''<span style="color:#ff0000">Uric acid</span>'''
***#'''<span style="color:#ff0000">Predominantly calcium phosphate stone composition</span>'''
*#'''<span style="color:#ff0000">Creatinine</span>'''
**'''Measurement of vitamin D levels may be helpful as''' '''low vitamin D levels may mask primary hyperparathyroidism, or contribute to secondary hyperparathyroidism.'''
* May suggest underlying medical conditions associated with stone disease (e.g., primary hyperparathyroidism, gout, RTA type 1 or other metabolic derangements)
**A high or high normal intact PTH in these settings should prompt further endocrine evaluation, imaging or referral for consideration of parathyroidectomy.
* '''Assessment of underlying renal function is necessary'''
*'''Stone composition, if available'''
 
**'''When a stone is available, a stone analysis should be obtained at least once.'''
==== <span style="color:#ff0000">Parathyroid hormone (PTH)</span> ====
**Can direct metabolic investigation or potentially obviate the need for a complete metabolic evaluation
*'''<span style="color:#ff0000">Indicated as part of the screening evaluation if primary hyperparathyroidism is suspected</span>'''
**'''<span style="color:#ff0000">Calcium phosphate stone composition associated with:</span>'''
**'''<span style="color:#ff0000">Primary hyperparathyroidism should be suspected when (3):</span>'''
**#'''<span style="color:#ff0000">RTA Type 1</span>'''
**#Mid-range PTH despite '''<span style="color:#ff0000">high or high normal serum calcium</span>'''
**#'''<span style="color:#ff0000">Primary hyperparathyroidism</span>'''
**#'''<span style="color:#ff0000">Increased urinary calcium</span>'''
**#'''<span style="color:#ff0000">Medullary sponge kidney</span>'''
**#'''<span style="color:#ff0000">Predominantly calcium phosphate stone composition</span>'''
**#'''<span style="color:#ff0000">Use of carbonic anhydrase inhibitors</span>'''
*'''Measurement of vitamin D levels may be helpful as''' '''low vitamin D levels may mask primary hyperparathyroidism, or contribute to secondary hyperparathyroidism.'''
*A high or high normal intact PTH in these settings should prompt further endocrine evaluation, imaging or referral for consideration of parathyroidectomy.
 
==== Stone composition, if available ====
*'''When a stone is available, a stone analysis should be obtained at least once.'''
*Can direct metabolic investigation or potentially obviate the need for a complete metabolic evaluation
*'''<span style="color:#ff0000">Calcium phosphate stone composition associated with:</span>'''
*#'''<span style="color:#ff0000">RTA Type 1</span>'''
*#'''<span style="color:#ff0000">Primary hyperparathyroidism</span>'''
*#'''<span style="color:#ff0000">Medullary sponge kidney</span>'''
*#'''<span style="color:#ff0000">Use of carbonic anhydrase inhibitors</span>'''
 
=== Imaging ===
 
* '''Obtain or review available imaging studies to quantify stone burden.''' '''<span style="color:#ff0000">[https://pubmed.ncbi.nlm.nih.gov/24857648/ ★]</span>'''


=== Metabolic/Extended Diagnostic Evaluation ===
=== Metabolic/Extended Diagnostic Evaluation ===
Line 226: Line 289:
*# Children should generally be evaluated because of concerns about renal damage and long-term sequelae of stone recurrence
*# Children should generally be evaluated because of concerns about renal damage and long-term sequelae of stone recurrence


==== <span style="color:#ff0000">24-hour urine collections</span> ====
==== 24-hour urine collections</span> ====


*Can be used to inform and monitor treatment protocols
*Can be used to inform and monitor treatment protocols
Line 242: Line 305:
*#Sulfate can be added to assess the volume of protein loading from animal meat
*#Sulfate can be added to assess the volume of protein loading from animal meat


* The accuracy of a 24-hour urine collection should be assessed prior to interpretation of results.
* '''<span style="color:#ff0000">Assess adequacy of 24-hour urine collection, prior to interpretation of results'''
**'''To assess the adequacy of collection, 24-hour urinary creatinine excretion, taking into account patient gender and body weight,''' as well as patient recall of the start and end times of his or her collection, '''should be considered'''
**'''<span style="color:#ff0000">To assess the adequacy of collection, 24-hour urinary creatinine excretion should be considered</span>, taking into account patient gender and body weight (males 20-25mg/kg and females 15-20mg/kg in 24 hours),''' as well as patient recall of the start and end times of his or her collection
***'''Significant aberrations in total creatinine excretion from estimated volumes (males 20-25mg/kg and females 15-20mg/kg in 24 hours) imply incomplete collection, overcollection, greater than expected muscle mass, or less than expected muscle mass'''
***'''Significant aberrations in total creatinine excretion from estimated volumes imply incomplete collection, overcollection, greater than expected muscle mass, or less than expected muscle mass'''
**** For abnormally collected 24 hour urine collections, can divide metabolite excretion by creatinine excretion to compare collections
**** For abnormally collected 24 hour urine collections, can divide metabolite excretion by creatinine excretion to compare collections
*'''Markers of protein intake, such as urine urea nitrogen or urinary sulfate, are reflective of animal protein intake and can be used to assess dietary adherence'''.
*'''Markers of protein intake, such as urine urea nitrogen or urinary sulfate, are reflective of animal protein intake and can be used to assess dietary adherence'''.
Line 252: Line 315:
*If a patient with calcium urolithiasis uses calcium supplements, 24-hour urine samples should be collected on and off the supplement.
*If a patient with calcium urolithiasis uses calcium supplements, 24-hour urine samples should be collected on and off the supplement.
**If urinary supersaturation of the calcium salt in question increases during the period of supplement use, the supplement should be discontinued.
**If urinary supersaturation of the calcium salt in question increases during the period of supplement use, the supplement should be discontinued.
== Diet Therapies ==
== Diet Therapies ==
* '''General diet therapies to reduce risk of stone recurrence (6)'''
* '''<span style="color:#ff0000">General diet therapies to reduce risk of stone recurrence (6)'''
*# '''Increase fluid intake'''
*# '''<span style="color:#ff0000">Increase fluid intake (urine volume of > 2.5 liters daily)'''
*# '''Limit sodium intake'''
*# '''<span style="color:#ff0000">Limit sodium intake (≤100 mEq (2,300 mg) per day)'''
*# '''Moderate calcium intake'''
*# '''<span style="color:#ff0000">Moderate calcium intake (1,000-1,200 mg per day)'''
*# '''Limit intake of oxalate-rich foods'''
*# '''<span style="color:#ff0000">Limit intake of oxalate-rich foods'''
*# '''Increase intake of fruits and vegetables'''
*# '''<span style="color:#ff0000">Increase intake of fruits and vegetables'''
*# '''Limit intake of non-dairy animal protein'''
*# '''<span style="color:#ff0000">Limit intake of non-dairy animal protein'''


=== Increase fluid intake ===
=== Increase fluid intake ===
Line 344: Line 408:
** '''Controversy exists over the role of vitamin D supplementation and kidney stone formation'''
** '''Controversy exists over the role of vitamin D supplementation and kidney stone formation'''
** '''Patients who undergo vitamin D repletion should have their 24-hour urine calcium monitored'''
** '''Patients who undergo vitamin D repletion should have their 24-hour urine calcium monitored'''
=== Follow-up of diet therapies ===
* If the patient’s metabolic or environmental abnormalities have been corrected, the conservative therapy can be continued and the patient followed every 6-12 months with repeat 24-hour urine testing as indicated.
** Follow-up is essential not only to monitor the efficiency of treatment but also to encourage patient compliance. If, however, a metabolic defect persists, a more selective medical therapy may be instituted.


== Pharmacologic Therapies ==
== Pharmacologic Therapies ==
===Calcium or calcium phosphate stones===
===Calcium or calcium phosphate stones===
*'''<span style="color:#ff0000">Thiazide diuretics should be offered to patients with recurrent calcium or calcium phosphate stones and hypercalcuria</span>'''
 
**'''Thiazides'''
==== <span style="color:#ff0000">Thiazide diuretics</span> ====
*** '''MOA'''
 
***# '''Directly stimulate calcium reabsorption in the distal nephron'''
*'''<span style="color:#ff0000">Indications</span>'''
***# '''Promotes excretion of sodium causing extracellular volume depletion'''
**'''<span style="color:#ff0000">Should be offered to patients with (2):</span>'''
***#* '''Long-term thiazide therapy results in volume depletion, extracellular volume contraction, and proximal tubular resorption of sodium and calcium.'''
***'''<span style="color:#ff0000">Hypercalcuria AND</span>'''
*** Specific drugs and dosages associated with a hypocalciuric effect:
***'''<span style="color:#ff0000">Recurrent calcium or calcium phosphate stones</span>'''
****'''Hydrochlorothiazide (25mg orally, twice daily; 50mg orally, once daily)'''
* '''Mechanism of Action'''
****'''Chlorthalidone (25mg orally, once daily)'''
*# '''Directly stimulate calcium reabsorption in the distal nephron''' (hypocalcuric effect)
****Indapamide (2.5mg orally, once daily).
*# '''Promotes excretion of sodium causing extracellular volume depletion'''
****Chlorthalidone (25-50 mg/day) or indapamide (2.5 mg/day) are preferred to hydrochlorothiazide since they are long-acting and are once a day dosing.
*#* '''Long-term thiazide therapy results in volume depletion, extracellular volume contraction, and proximal tubular resorption of sodium and calcium.'''
***** Indapamide is technically not a thiazide but does share a successful hypocalciuric effect with the other agents.
* '''<span style="color:#ff0000">Drugs and dosages'''
*** '''Patients placed on thiazide diuretics for management of hypercalciuria should also be placed on dietary sodium restriction'''
*#'''<span style="color:#ff0000">Hydrochlorothiazide</span> (50mg orally, once daily;''' 25mg orally, twice daily''')'''
**** An excess sodium load will inhibit reabsorption of calcium in the proximal tubule, thereby causing hypercalciuria.
*#'''<span style="color:#ff0000">Chlorthalidone</span>''' (25mg orally, once daily)
*** '''Adverse events'''
*#'''<span style="color:#ff0000">Indapamide</span> (2.5mg orally, once daily)'''
**** '''Lassitude and sleepiness'''
*#*Chlorthalidone or indapamide are preferred to hydrochlorothiazide since they are long-acting and are once a day dosing.
***** '''Most common side effects of thiazides'''
*#* Indapamide is technically not a thiazide but does share a successful hypocalciuric effect with the other agents.
***** Can occur in the absence of hypokalemia
* '''<span style="color:#ff0000">Patients placed on thiazide diuretics for management of hypercalciuria should also be placed on dietary sodium restriction'''
***** Usually seen on initiation of treatment but resolves with continued therapy.
** '''An excess sodium load will inhibit reabsorption of calcium in the proximal tubule, thereby causing hypercalciuria.'''
**** '''Metabolic/electrolyte abnormalities''' ('''3 hypers, 3 hypos + metabolic alkalosis''')
* '''<span style="color:#ff0000">Adverse events'''
****# '''Hyperglycemia'''
** '''<span style="color:#ff0000">Sleepiness and lassitude'''
****# '''Hyperlipidemia'''
*** '''<span style="color:#ff0000">Most common side effects of thiazides'''
****# '''Hyperuricemia'''
*** Can occur in the absence of hypokalemia
****# '''Hypokalemia'''
*** Usually seen on initiation of treatment but resolves with continued therapy.
****# '''Hypomagnesemia'''
** '''<span style="color:#ff0000">Metabolic/electrolyte abnormalities''' ('''3 hypers, 3 hypos + metabolic alkalosis''')
****# '''Hypocitraturia'''
**# '''<span style="color:#ff0000">Hyperglycemia'''
****# '''Metabolic alkalosis'''
**# '''<span style="color:#ff0000">Hyperlipidemia'''
****'''Hypocitraturia'''
**# '''<span style="color:#ff0000">Hyperuricemia'''
*****'''Result of hypokalemia with intracellular acidosis'''
**# '''<span style="color:#ff0000">Hypokalemia'''
****'''Hypokalemia and hyperglycemia'''
**# '''<span style="color:#ff0000">Hypomagnesemia'''
***** '''The degree of diuretic-induced hypokalemia correlates with level of hyperglycemia.'''
**# '''<span style="color:#ff0000">Hypocitraturia'''
****** Mechanism: hypokalemia impairs insulin secretion, thereby increasing plasma glucose.
**# '''<span style="color:#ff0000">Metabolic alkalosis'''
*****'''<span style="color:#ff0000">Potassium supplementation (either potassium citrate or potassium chloride)</span>'''  
**'''<span style="color:#ff0000">Hypokalemia and glucose intolerance'''
******'''<span style="color:#ff0000">May be needed when thiazide therapy is employed because of the hypokalemic effects of these medications</span>'''
*** '''The degree of diuretic-induced hypokalemia correlates with level of hyperglycemia.'''
******'''Should always be considered at either the onset of thiazide therapy or upon the discovery of glucose intolerance'''
**** Mechanism: hypokalemia impairs insulin secretion, thereby increasing plasma glucose.
******* '''Can prevent or significantly lessens the degree of hypokalemia or glucose intolerance'''
***'''<span style="color:#ff0000">Potassium supplementation (either potassium citrate or potassium chloride)</span>'''  
******* '''Can be administered as potassium citrate or with dietary supplements such as a banana per day'''
****'''<span style="color:#ff0000">May be needed when thiazide therapy is employed because of the hypokalemic effects of these medications</span>'''
******** '''Citrates are generally well tolerated, with only a small risk for GI upset'''
****'''<span style="color:#ff0000">Should always be considered at either the onset of thiazide therapy or upon the discovery of glucose intolerance'''
********* A liquid preparation of potassium citrate, rather than the slow-release tablet preparation, is recommended in patients with rapid intestinal transit time (i.e. chronic diarrhea); the slow-release medication may be poorly absorbed
***** '''Can prevent or significantly lessens the degree of hypokalemia or glucose intolerance'''
******** Conflicting evidence of an increased risk of calcium phosphate stone formation with the long-term use of potassium citrate therapy
***** '''Can be administered as potassium citrate or with dietary supplements such as a banana per day'''
******* Particularly important in patients with evident potassium deficiency, patients on digitalis therapy, and those individuals who develop hypocitraturia
****** '''Citrates are generally well tolerated, with only a small risk for GI upset'''
******'''The addition of amiloride or spironolactone may avoid the need for potassium supplementation'''.
******* A liquid preparation of potassium citrate, rather than the slow-release tablet preparation, is recommended in patients with rapid intestinal transit time (i.e. chronic diarrhea); the slow-release medication may be poorly absorbed
******Triamterene, although it is potassium-sparing, should be avoided as stones of this compound have been reported
****** Conflicting evidence of an increased risk of calcium phosphate stone formation with the long-term use of potassium citrate therapy
****'''Patients with undiagnosed primary hyperparathyroidism may develop hypercalcemia after initiation of thiazide therapy'''
***** Particularly important in patients with evident potassium deficiency, patients on digitalis therapy, and those individuals who develop hypocitraturia
***** Although most patients with primary hyperparathyroidism demonstrate hypercalcemia and hypercalciuria, a normal serum calcium level in the presence of an inappropriately high serum PTH value may be seen in some cases, making the diagnosis more difficult. Administration of a thiazide diuretic will enhance renal calcium reabsorption and exacerbate the hypercalcemia, thereby facilitating the diagnosis (“thiazide challenge”)
****'''The addition of amiloride or spironolactone may avoid the need for potassium supplementation'''.
****** In the thiazide challenge, cessation of thiazide should reduce PTH and serum calcium. However, in primary hyperparathyroidism, PTH and serum calcium remain persistently elevated with cessation of thiazide.
****Triamterene, although it is potassium-sparing, should be avoided as stones of this compound have been reported
**** '''Bisphosphonates combined with thiazide diuretics appear to reduce hypercalciuria while protecting the bone'''
**'''Hypocitraturia'''
*** '''Thiazide diuretics lose their effectiveness in the treatment of hypercalciuria in up to 25% of patients on long-term management.'''
***'''Result of hypokalemia with intracellular acidosis'''
**** '''Loss of effectiveness is due to increased serum calcium levels which stimulate the C cells in the thyroid to produce more calcitonin.''' Increased calcitonin leads to increased urinary calcium excretion.
**'''Patients with undiagnosed primary hyperparathyroidism may develop hypercalcemia after initiation of thiazide therapy'''
*'''<span style="color:#ff0000">Potassium citrate therapy should be offered to patients with recurrent calcium or calcium phosphate stones and hypocitraturia</span>'''**'''Citrates are first-line therapy for the management of RTA, thiazide-induced hypocitraturia, and idiopathic hypocitraturia'''
*** Although most patients with primary hyperparathyroidism demonstrate hypercalcemia and hypercalciuria, a normal serum calcium level in the presence of an inappropriately high serum PTH value may be seen in some cases, making the diagnosis more difficult. Administration of a thiazide diuretic will enhance renal calcium reabsorption and exacerbate the hypercalcemia, thereby facilitating the diagnosis (“thiazide challenge”)
*** Potassium citrate therapy is able to correct the metabolic acidosis and hypokalemia found in patients with distal RTA
**** In the thiazide challenge, cessation of thiazide should reduce PTH and serum calcium. However, in primary hyperparathyroidism, PTH and serum calcium remain persistently elevated with cessation of thiazide.
**'''Calcium stone-forming patients with normal citrate excretion but low urinary pH may also benefit from citrate therapy'''
** '''Bisphosphonates combined with thiazide diuretics appear to reduce hypercalciuria while protecting the bone'''
***There is also a risk that higher urine pH can promote calcium phosphate stone formation, or change calcium oxalate stone formers to calcium phosphate stone formers.
* '''Thiazide diuretics lose their effectiveness in the treatment of hypercalciuria in up to 25% of patients on long-term management.'''
** '''Potassium citrate is preferred over sodium citrate'''
** '''Loss of effectiveness is due to increased serum calcium levels which stimulate the C cells in the thyroid to produce more calcitonin.''' Increased calcitonin leads to increased urinary calcium excretion.
***'''Patient's treated with sodium alkali will occasionally begin forming calcium oxalate stones due to an excess sodium load that will inhibit reabsorption of calcium in the proximal tubule, thereby causing hypercalciuria'''
 
***'''If the patient is at risk for hyperkalemia, other agents such as sodium bicarbonate or sodium citrate should be considered.'''
==== <span style="color:#ff0000">Potassium citrate</span> ====
*'''<span style="color:#ff0000">Indications</span>'''
**'''<span style="color:#ff0000">Should be offered to patients with (2)</span>'''
**#'''<span style="color:#ff0000">Hypocitraturia AND</span>'''
**#'''<span style="color:#ff0000">Recurrent calcium or calcium phosphate stones</span>'''
**#*'''Citrates are first-line therapy for the management of RTA, thiazide-induced hypocitraturia, and idiopathic hypocitraturia'''
**#** Potassium citrate therapy is able to correct the metabolic acidosis and hypokalemia found in patients with distal RTA
**#*'''Calcium stone-forming patients with normal citrate excretion but low urinary pH may also benefit from citrate therapy'''
**#**There is also a risk that higher urine pH can promote calcium phosphate stone formation, or change calcium oxalate stone formers to calcium phosphate stone formers.
**#* '''Potassium citrate is preferred over sodium citrate'''
**#**'''Patient's treated with sodium alkali will occasionally begin forming calcium oxalate stones due to an excess sodium load that will inhibit reabsorption of calcium in the proximal tubule, thereby causing hypercalciuria'''
**#**'''If the patient is at risk for hyperkalemia, other agents such as sodium bicarbonate or sodium citrate should be considered.'''
*'''<span style="color:#ff0000">Adverse Events (2)</span>'''
**'''<span style="color:#ff0000">Hyperkalemia</span>'''
**'''<span style="color:#ff0000">GI upset</span>'''
 
===Recurrent calcium stones===
===Recurrent calcium stones===
*'''<span style="color:#ff0000">Allopurinol should be offered to patients with recurrent calcium oxalate stones who have hyperuricosuria and normal urinary calcium</span>'''
*'''<span style="color:#ff0000">Allopurinol should be offered to patients with recurrent calcium oxalate stones who have hyperuricosuria and normal urinary calcium</span>'''
Line 416: Line 491:
**'''For patients with no identified risk factors for nephrolithiasis, potassium citrate may be the preferred first-line therapy, given its relatively low side effect profile.'''
**'''For patients with no identified risk factors for nephrolithiasis, potassium citrate may be the preferred first-line therapy, given its relatively low side effect profile.'''
===Uric acid stones===
===Uric acid stones===
*'''<span style="color:#ff0000">First-line therapy for patients with uric acid stones is alkalinization of the urine with potassium citrate so that uric acid remains in a dissolved state.</span>'''
*'''<span style="color:#ff0000">First-line therapy for patients with uric acid stones is alkalinization of the urine with potassium citrate to raise urinary pH to an optimal level so that uric acid remains in a dissolved state.</span>'''
**'''<span style="color:#ff0000">Allopurinol should not be routinely offered as first-line therapy to patients with uric acid stones</span>'''
**'''<span style="color:#ff0000">Allopurinol should not be routinely offered as first-line therapy to patients with uric acid stones</span>'''
***'''Most patients with uric acid stones have low urinary pH rather than hyperuricosuria as the predominant risk factor'''
***'''Most patients with uric acid stones have low urinary pH rather than hyperuricosuria as the predominant risk factor'''
***'''Goal is to increase the urinary pH > 5.5, preferably between 6.0-6.5, through an alkalinizing agent such as potassium citrate'''
***'''<span style="color:#ff0000">Goal is to increase the urinary pH > 5.5 (AUA targets 6.0 and CUA targets 6.5), through an alkalinizing agent such as potassium citrate'''
**** With adequate alkali therapy, patient's can raise the urine pH above the dissociation constant of uric acid.
**** With adequate alkali therapy, patient's can raise the urine pH to an optimal level so that uric acid remains in a dissolved state.
***** '''Attempts at alkalinizing the urine to a pH > 7.0 should be avoided. At a higher pH, there is a danger of increasing the risk for calcium phosphate stone formation.'''
***** '''<span style="color:#ff0000">Attempts at alkalinizing the urine to a pH > 7.0 should be avoided. At a higher pH, there is a danger of increasing the risk for calcium phosphate stone formation.'''
***Patients may initially present with low/normal 24-hour urinary uric acid levels because the uric acid will precipitate out of solution in the acid urinary environment. Once the urine has been alkalized, all of the uric acid will come back into solution, causing a significant increase in the measured urinary uric acid.
***Patients may initially present with low/normal 24-hour urinary uric acid levels because the uric acid will precipitate out of solution in the acid urinary environment. Once the urine has been alkalized, all of the uric acid will come back into solution, causing a significant increase in the measured urinary uric acid.
*'''<span style="color:#ff0000">Allopurinol may be considered as an adjunct when alkalinization is not successful or for patients who continue to form uric acid stones despite adequate alkalinization of the urine.</span>'''
*'''<span style="color:#ff0000">Allopurinol may be considered as an adjunct when alkalinization is not successful or for patients who continue to form uric acid stones despite adequate alkalinization of the urine.</span>'''
Line 430: Line 505:
** Acetazolamide, a carbonic anhydrase inhibitor, leads to an increase in urinary bicarbonate and increased H+ reabsorption.
** Acetazolamide, a carbonic anhydrase inhibitor, leads to an increase in urinary bicarbonate and increased H+ reabsorption.
** Up to 50% of patients may discontinue acetazolamide due to adverse effects.
** Up to 50% of patients may discontinue acetazolamide due to adverse effects.
===Uric acid and cystine stones===
===Uric acid and cystine stones===
* '''<span style="color:#ff0000">Potassium citrate should be offered to patients with uric acid and cystine stones to raise urinary pH to an optimal level</span>'''
* '''<span style="color:#ff0000">Potassium citrate should be offered to patients with uric acid and cystine stones to raise urinary pH to an optimal level</span>'''
Line 436: Line 512:
===Cystine stones===
===Cystine stones===
*'''<span style="color:#ff0000">First-line therapy for patients with cystine stones:</span>'''
*'''<span style="color:#ff0000">First-line therapy for patients with cystine stones:</span>'''
**'''<span style="color:#ff0000">Increased fluid intake</span>'''
*#'''<span style="color:#ff0000">Increased fluid intake</span>'''
**'''<span style="color:#ff0000">Restriction of sodium and protein intake</span>'''
*#'''<span style="color:#ff0000">Urinary alkalinization</span>'''
**'''<span style="color:#ff0000">Urinary alkalinization</span>'''
*#'''<span style="color:#ff0000">Restriction of sodium and protein intake</span>'''
*##Excess dietary sodium can lead to increases in cystine excretion
*'''<span style="color:#ff0000">Potassium citrate should be offered to patients with cystine stones to raise urinary pH to an optimal level</span>'''
**'''AUA: Urine pH of 7.0 (CUA targets >7.0) should be achieved'''
*'''<span style="color:#ff0000">Cystine-binding thiol drugs, such as alpha-mercaptopropionylglycine (tiopronin), should be offered to patients with cystine stones who are unresponsive to dietary modifications and urinary alkalinization, or have large recurrent stone burdens.</span>'''
*'''<span style="color:#ff0000">Cystine-binding thiol drugs, such as alpha-mercaptopropionylglycine (tiopronin), should be offered to patients with cystine stones who are unresponsive to dietary modifications and urinary alkalinization, or have large recurrent stone burdens.</span>'''
** '''Tiopronin is possibly more effective and associated with fewer adverse events than d-penicillamine and should be considered first.'''
** '''MOA: increase cystine solubility in urine by formation of a more soluble mixed-disulfide bond (i.e., cystine to drug, rather than cystine to cystine).'''
**'''Captopril, another thiol agent, has not been shown to be effective for the prevention of recurrent cystine stones'''
** '''Options include α-mercaptopropionylglycine (tiopronin [Thiola]),''' D-penicillamine (Cuprimine), and captopril
===Struvite stones===
*** '''Tiopronin is possibly more effective and associated with fewer adverse events than d-penicillamine and should be considered first.'''
***'''Captopril, another thiol agent, has not been shown to be effective for the prevention of recurrent cystine stones'''
***d-Penicillamine and α-MPG are equally effective in their ability to decrease urinary cystine levels. However, α-mercaptopropionylglycine is significantly less toxic than d-penicillamine.
*** Side effects of '''D-penicillamine''' include gastrointestinal disturbances, fever and rash, arthralgia, leukopenia, thrombocytopenia, proteinuria with nephrotic syndrome, polymyositis, and '''pyridoxine (Vitamin B6) deficiency'''
**** '''Pyridoxine (vitamin B6) deficiency supplementation is recommended'''
===Infection/Struvite stones===
*'''<span style="color:#ff0000">The preferred management of struvite calculi involves aggressive surgical approaches'''
**'''The medical management of infection calculi centers on the prevention of recurrence, rather than medical dissolution.'''
*'''<span style="color:#ff0000">Acetohydroxamic acid (AHA) may be offered to patients with residual or recurrent struvite stones only after surgical options have been exhausted.</span>'''
*'''<span style="color:#ff0000">Acetohydroxamic acid (AHA) may be offered to patients with residual or recurrent struvite stones only after surgical options have been exhausted.</span>'''
** '''Patients treated for struvite stones may still be at risk for recurrent UTIs after stone removal, and in some patients surgical stone removal is not feasible.'''
** '''Patients treated for struvite stones may still be at risk for recurrent UTIs after stone removal, and in some patients surgical stone removal is not feasible.'''
**'''The use of a urease inhibitor, AHA, may be beneficial in these patients, although the extensive side effect profile may limit its use. In particular, patients taking this medication should be closely monitored for phlebitis and hypercoagulable phenomena'''
**'''The use of a urease inhibitor, AHA, may be beneficial in these patients, although the extensive side effect profile may limit its use. In particular, patients taking this medication should be closely monitored for phlebitis and hypercoagulable phenomena'''
**'''<span style="color:#ff0000">Acetohydroxamic acid (AHA)'''
*** '''MOA: urease inhibitor; may reduce the urinary saturation of struvite and therefore delay stone formation'''
*** '''<span style="color:#ff0000">Adverse effects'''
**** Minor side effects common (up to 30% of patients)
**** '''<span style="color:#ff0000">Deep venous thrombosis</span>''' (15%)
**** '''<span style="color:#ff0000">Hemolytic anemia'''
***** '''Most serious side effect'''
***** '''Occurs in up to 15% of the patients; more prevalent in patients with renal insufficiency'''
****'''<span style="color:#ff0000">Phlebitis'''
*** '''Frequently reserved for patients deemed too ill for surgical management.'''
*Long-standing effective control of infection with urea-splitting organisms should be achieved if at all possible with improved bladder health, adequate urinary drainage, and suppressive antibiotics
*'''Phosphate therapy is contraindicated in cases of infection calculi because this medication may promote further stone formation.'''


=== Other ===
=== Other ===
Line 451: Line 549:
** '''An effective, first-line therapy for mild-moderate hypercalciuria'''
** '''An effective, first-line therapy for mild-moderate hypercalciuria'''
*** Thought to have a protective role in preventing nephrolithiasis by decreasing urinary calcium and oxalate excretion through alteration of prostaglandin metabolism
*** Thought to have a protective role in preventing nephrolithiasis by decreasing urinary calcium and oxalate excretion through alteration of prostaglandin metabolism
* '''Hyperparathyroidism complicated by stone disease is best treated with surgical excision of the adenoma'''
* '''Hyperparathyroidism complicated by stone disease'''
**'''Best treated with surgical excision of the adenoma'''


* '''Enteric hyperoxaluria'''
* '''Enteric hyperoxaluria'''
Line 463: Line 562:
*** Potassium-magnesium may restore urinary magnesium and citrate levels with minimal GI side effects
*** Potassium-magnesium may restore urinary magnesium and citrate levels with minimal GI side effects


* '''Uric acid stones'''
=== Medical Management of Pediatric Calculi ===
***
 
* '''Cystinuria'''
** '''First-line: aggressive fluid intake, urinary alkalinization, and salt avoidance''' (excess dietary sodium can lead to increases in cystine excretion)
** '''Second line: cystine-binding agents'''
*** '''MOA: increase cystine solubility in urine by formation of a more soluble mixed-disulfide bond (i.e., cystine to drug, rather than cystine to cystine).'''
*** '''Options include α-mercaptopropionylglycine (tiopronin [Thiola]),''' D-penicillamine (Cuprimine), and captopril
**** d-Penicillamine and α-MPG are equally effective in their ability to decrease urinary cystine levels. However, α-mercaptopropionylglycine is significantly less toxic than d-penicillamine.
**** Side effects of '''D-penicillamine''' include gastrointestinal disturbances, fever and rash, arthralgia, leukopenia, thrombocytopenia, proteinuria with nephrotic syndrome, polymyositis, and '''pyridoxine (Vitamin B6) deficiency'''
***** '''Pyridoxine (vitamin B6) deficiency supplementation is recommended'''
 
* '''Infection stones'''
** '''The preferred management of struvite calculi involves aggressive surgical approaches'''
** '''The medical management of infection calculi centers on the prevention of recurrence, rather than medical dissolution.'''
*** Long-standing effective control of infection with urea-splitting organisms should be achieved if at all possible with improved bladder health, adequate urinary drainage, and suppressive antibiotics
*** '''Acetohydroxamic acid (AHA)'''
**** '''MOA: urease inhibitor; may reduce the urinary saturation of struvite and therefore delay stone formation'''
**** '''Adverse effects'''
***** Minor side effects common (up to 30% of patients)
***** '''Deep venous thrombosis''' (15%)
***** '''Hemolytic anemia'''
****** '''Most serious side effect'''
****** '''Occurs in up to 15% of the patients; more prevalent in patients with renal insufficiency'''
**** '''Frequently reserved for patients deemed too ill for surgical management.'''
*** '''Phosphate therapy is contraindicated in cases of infection calculi because this medication may promote further stone formation.'''
 
=== Medical management of pediatric calculi ===


* '''Neonates can develop furosemide-induced nephrolithiasis.'''
* '''Neonates can develop furosemide-induced nephrolithiasis.'''
Line 499: Line 571:
* There is a lack of consensus regarding normal laboratory values during 24-hour urine collections in children. Clinicians have relied on ratios to correct for the wide variation of weight
* There is a lack of consensus regarding normal laboratory values during 24-hour urine collections in children. Clinicians have relied on ratios to correct for the wide variation of weight
* '''The medical management of nephrolithiasis and the prevention of subsequent recurrences in children do not differ that dramatically from the approaches undertaken for adults'''
* '''The medical management of nephrolithiasis and the prevention of subsequent recurrences in children do not differ that dramatically from the approaches undertaken for adults'''
== Follow-up==
*'''<span style="color:#ff0000">Labs</span>'''
**'''<span style="color:#ff0000">Repeat 24-hour urine collection</span>'''
***'''<span style="color:#ff0000">A single 24-hour urine specimen for stone risk factors should be obtained within 6 months of the initiation of treatment to assess response to dietary and/or medical therapy</span>'''
***'''<span style="color:#ff0000">After the initial follow-up, a single 24-hour urine specimen should be obtained annually or with greater frequency, depending on stone activity, to assess patient adherence and metabolic response</span>'''
**'''<span style="color:#ff0000">Periodic blood testing should be obtained to assess for adverse effects in patients on pharmacological therapy.</span>'''
***'''<span style="color:#ff0000">Thiazide therapy may promote hypokalemia and glucose intolerance</span>'''
*** '''<span style="color:#ff0000">Allopurinol and tiopronin may cause an elevation in liver enzymes</span>'''
***'''<span style="color:#ff0000">AHA and tiopronin may induce anemia and other hematologic abnormalities</span>'''
***'''<span style="color:#ff0000">Potassium citrate may result in hyperkalemia</span>'''
***'''Patients with undiagnosed primary hyperparathyroidism may develop hypercalcemia after initiation of thiazide therapy'''
**Repeat stone analysis, when available, should be obtained especially in patients not responding to treatment
*'''<span style="color:#ff0000">Imaging'''
** '''<span style="color:#ff0000">Periodic imaging to assess for stone growth or new stone formation based on stone activity (plain abdominal imaging, renal ultrasonography or low dose CT).'''
*'''<span style="color:#ff0000">Patients with struvite stones should be monitored for reinfection with urease-producing organisms and utilize strategies to prevent such occurrences.'''
**Monitoring should include surveillance urine culture testing on a periodic basis. In some cases, recurrences may be reduced with long-term, prophylactic antibiotic therapy
*If patients remain stone free on their treatment regimen for an extended period of time, discontinuation of follow-up testing may be considered.
== Questions ==
== Questions ==


# What is the risk of stone recurrence at 10 years in first-time stone formers?
# What are lifestyle changes a patient could make to reduce risk of stone recurrence?
# What is the microscopic appearance of common urinary calculi?
#What are side effects related to thiazides?


== Answers ==
== Answers ==
1. 50%
 
#What are lifestyle changes a patient could make to reduce risk of stone recurrence?
#What are side effects related to thiazides?
 
== Next Chapter: [[Stones: Surgical Modalities for Management of Upper Urinary Tract Calculi|Surgical Modalities for Management of Upper Urinary Tract Calculi]] ==


== References ==
== References ==


* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 52
* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 52
*[https://pubmed.ncbi.nlm.nih.gov/24857648/ Pearle, Margaret S., et al. "Medical management of kidney stones: AUA guideline." ''The Journal of urology'' 192.2 (2014): 316-324.]
Retrieved from "https://urologyschool.com/wikiuro/index.php/Stones:_Evaluation_and_Medical_Management"