II. Epidemiology
- Nephrolithiasis prevelance is increasing in U.S.
- Prevalence 1994: 5%
- Prevalence 2010: 9%
- Ureterolithiasis Incidence
- Accounts for 2% of U.S. Emergency Department visits
- Life-time risk
- Males: 10-13%
- Females: 3-7%
- Recurrence of Nephrolithiasis
- One recurrence in 50% of patients
- More than 3 recurrences in 10% of patients
- Peak age 20-50 years
- Peak Incidence in midlife
- However childhood stone Incidence is increasing (pediatric diabetes, Obesity, Hypertension)
- Gender associations: Overall Male:Female ratio 4:1
- Males: Calcium oxalate
- Females: Struvite
- Both: Urate Stones and Cystine Stones
- Pregnancy: Calcium Phosphate (75% of cases)
III. Pathophysiology
- Stone formation is inhibited by Citrate
- Women have much higher levels of citrate than men
- Low citrate levels are related to most stone forms
IV. Risk Factors
V. Types: Stones
-
Calcium Nephrolithiasis (75%)
- Calcium oxalate (70%)
- Calcium Phosphate (5-10%)
- Approaches 75% in pregnant women
- Also more common in children
-
Struvite Nephrolithiasis (15-20%)
- Chronic infection (e.g. Proteus, Pseudomonas) that forms staghorn calculi
-
Uric Acid Nephrolithiasis (10-15%)
- Radiolucent stones that may be associated with gout and low Urine pH
-
Cysteine Nephrolithiasis (1%)
- Typically due to inborn error of metabolism
- Like Struvute, forms staghorn calculi
- Drug-Induced (1%)
- Indinavir (Protease Inhibitor in HIV)
- Triamterene
VI. Symptoms: Renal Colic
- Severe Abdominal Pain of sudden onset
- Onset is often at night
- Severe pain, with difficulty finding a comfortable position
- Episodic pain, each lasting 20 to 60 minutes
- Distribution (see Stone Location related pain below)
- Unilateral Flank Pain
- Lower, unilateral Abdominal Pain
- Ipsilateral inguinal or Groin Pain
- Associated symptoms
- Nausea and Vomiting
- Renal capsule related pain via splanchnic innervation (shared with intestinal innervation), triggers Vomiting
- Gross Hematuria (30%)
- Most common on the first day of Ureteral Colic
- Gross Hematuria is neither sensitive nor specific for Ureteral Stones
- Dysuria, urine frequency and fever may be present
- Exclude Urinary Tract Infection and Pyelonephritis associated with stone (requires emergent management)
- Fever is atypical in Ureterolithiasis outside of infection
- Nausea and Vomiting
VII. Symptoms: By stone location
-
Kidney Calyx (typically asymptomatic other than Hematuria)
- Vague Flank Pain
- Hematuria
- Ureteropelvic junction or UPJ (Proximal ureter where ureter meets renal Pelvis)
- Flank Pain
- Upper Abdominal Pain
- Renal Colic
- Pelvic Brim (Low-Mid Ureter, where ureter crosses over iliac crest and iliac artery, iliac vein)
- Flank Pain
- Anterior Abdominal Pain
- Renal Colic
- Distal ureter: Ureterovesicular junction or UVJ (most common impaction site)
- Dysuria
- Urinary Frequency
- Anterior Abdominal Pain
- Flank Pain
- Renal Colic
VIII. Differential Diagnosis
- See Flank Pain
- See Hematuria
- See Dysuria
- See Urinary Frequency
- See Acute Abdominal Pain Causes in Adults
- See Acute Pelvic Pain Causes
- Acute onset of symptoms
- Urinary Tract Infection (esp. Pyelonephritis)
- Acute Prostatitis
- Musculoskeletal spasm
- Acute Constipation or other acute bowel disorder
- Ectopic Pregnancy
- Ovarian Torsion
- Testicular Torsion
- Appendicitis
- Incarcerated Hernia
- Biliary Colic
- Diverticulitis
- Acute Bowel Ischemia
- Aortic Dissection
- Abdominal Aortic Aneurysm rupture
- Consider in new onset Ureterolithiasis symptoms in age over 50 years old (especially if Tobacco use)
- May present with Flank Pain and Hematuria
- Ureterolithaisis is the most common mis-diagnosis of Abdominal Aortic Aneurysm presentations
- Chronic intermittent or insidious onset of symptoms
- Bowel disease
- Interstitial Cystitis
- Inguinal Hernia
- Testicular Mass
- Urothelial or Renal Mass
- Benign prostatitic hyperplasia
IX. Imaging: General
- Indications
- Stone size and location
- Exclude alternative diagnosis
- Imaging Selection
X. Imaging: Sample approach for suspected uncomplicated Nephrolithiasis (emergency department)
- Background
- Intention
- Reduce ionizing radiation exposure in the evaluation of Nephrolithiasis
- Avoid delaying intervention (when indicated)
- Bedside renal Ultrasound can reliably identify stones >5mm based on Hydronephrosis
- Bedside Ultrasound is a safe evaluation strategy without serious missed conditions
- Relies on appropriate patient selection (Ureteral Colic most likely, no significant comorbidity)
- Moore (2019) Ann Emerg Med 74(3): 391-9 [PubMed]
- Smith-Bindman (2014) N Engl J Med 371(12):1100-10 +PMID:25229916 [PubMed]
- Consider scoring system (e.g. STONE Score) approach to imaging
- See STONE Score
- Bedside Ultrasound with Hydronephrosis present after hydration increases STONE Score Specificity
- High risk STONE Score (10-13) is associated with a 87% Test Specificity for Ureteral Stone
- Consider expectant management in otherwise healthy patients at low risk for alternative diagnosis
- Consider low dose CT if needed for stone localization or size
- Moderate risk STONE Score (6-9) is associated with a 51% Test Specificity for Ureteral Stone
- Bedside Ultrasound with Hydronephrosis increases likelihood of Ureteral Stone and may be sufficient for diagnosis
- Low risk STONE Score (0 to 5) suggests alternative diagnosis
- Intention
- Step 1: Suspicion for uncomplicated Ureterolithiasis
- Hematuria and abdominal, pelvic or Flank Pain AND
- No Urinary Tract Infection AND
- No serious comorbidity (e.g. cancer, AAA risk) or other confounding factor (e.g. single Kidney)
- Step 2: Bedside renal Ultrasound (bilateral for comparison) and Bladder (for obstruction, distal stone shadowing at UVJ)
- Ultrasound offers best accuracy for Hydronephrosis
- Hydronephrosis on side of pain
- Consider empiric treatment of Ureterolithiasis with expectant management
- Consider other causes of Hydronephrosis (e.g. Abdominal Aortic Aneurysm)
- Consider non-contrast CT as indicated (see Step 3 below)
- No Hydronephrosis
- Extend Bedside Ultrasound to explore other diagnoses (e.g. AAA, Urinary Retention, Cholecystitis)
- Consider imaging with discussion of risks (e.g. CT-associated Radiation Exposure)
- Strongly consider CT if UTI by Urinalysis (exclude infected stone)
- False NegativeUltrasound for Hydronephrosis
- Alternative intraabdominal diagnosis (e.g. Appendicitis, Diverticulitis)
- May treat empirically as small, non-obstructing stone (likely to pass without intervention)
- Close interval follow-up
- Consider alternative diagnoses
- Step 3: Consider Helical, Non-Contrast CT Abdomen and Pelvis for Ureterolithiasis
- Non-Contrast CT indications
- First stone suspected (no prior imaging or Ureterolithiasis history), esp. if over age 50 years old
- Persistent Ureterolithiasis symptoms at 14 weeks without prior imaging
- Infected stone suspected
- Urology consulted for intervention (see indications as below)
- IV Contrast Enhanced CT Indications
- Alternative intraabdominal diagnosis (e.g. Appendicitis, Diverticulitis, Abdominal Aortic Aneurysm)
- Intravenous Contrast does not significantly reduce Test Sensitivity for Ureterolithiasis
- Consider KUB Abdominal XRay if CT positive for Ureteral Stone of 5 mm or greater
- Helical CT will localize the stone and ease simultaneous identification on KUB XRay
- KUB XRay allows for serial XRays for monitoring progression without significant radiation exposure
- KUB XRay is preferred over CT scout film due to better resolution and for easier comparison on future films
- Non-Contrast CT indications
XI. Labs: Initial Diagnostics
- Precautions
- Absent gross and Microscopic Hematuria does not exclude Nephrolithiasis (may miss up 10-40% of cases)
- Infected Ureteral Stone is a urologic emergency
-
Urinalysis with reflex to Urine Culture
- Microscopic or Gross Hematuria in 90% of Nephrolithiasis cases
- Evaluate for Urinary Tract Infection
- Send urine for Urine Culture in all cases of suspected UTI and Ureteral Stone
- Nephrolithiasis with Urinary Tract Infection is high risk and requires immediate urologic Consultation (and urgent intervention)
- Factors most suggestive or higher risk of Urinary Tract Infection complicating Nephrolithiasis
- Fever (associated Likelihood Ratio of 10)
- Female (associated Likelihood Ratio of 27)
- Positive Urine Nitrite (associated Likelihood Ratio of 36)
- White Blood Cells in urine has Test Specificity of 25%
- However, risk of infection increases with WBC concentration
- Abrahamian (2013) Ann Emerg Med 62(5): 526-33 [PubMed]
XII. Labs: Evaluation of single stone former without risk (labs to consider)
- Chemistry panel
- Serum Electrolytes
- Serum Calcium
- Renal Function tests
- Serum Uric Acid
- Stone Analysis (nidus and outer layer)
- Stone analysis is important to direct preventive strategies, esp. if Ureterolithiasis Risk Factors
- However, stone analysis is often not performed for the initial stone
- Microscopic Crystal Analysis
- Stone analysis is important to direct preventive strategies, esp. if Ureterolithiasis Risk Factors
XIII. Labs: Evaluation of recurrent stone formation
- See those labs listed above
-
Parathyroid Hormone level
- Obtain if Urine Calcium >10 mg/dl
-
24 hour Urine Collection
-
Urine pH
- Acidic urine predisposes to Uric Acid stones, Cystine Stones and Calcium Oxalate Stones
- Alkaline urine predisposes to Struvite Stones and Calcium Phosphate Stones
- Urine Sodium
- Urine Creatinine
- Urine Calcium (Hypercalciuria >300 mg/day)
- Urine Uric Acid (Hyperuricosuria >750 mg/day)
- Urine Oxalate (Hyperoxaluria >40 mg/day)
- Urine Citrate (Hypocitraturia <320 mg/day)
- Urine Magnesium (Hypomagnesuria <50 mg/day)
- Other urine labs to consider
- Urine Phosphorus
- Urine Calcium Oxalate (Supersaturation)
- Urine Calcium Phosphate
-
Urine pH
XIV. Precautions
- Do not miss concurrent Urinary Tract Infection and Ureterolithiasis (requires emergent stone management)
- Do not miss Abdominal Aortic Aneurysm (which may also cause Hydronephrosis or otherwise mimic Renal Colic)
- Post-Renal Transplant obstructive uropathy
- Struvite Stones are more common with corynebacterium urealyticum infections (seen in transplant patients)
- Consult urology
- Corynebacterium Antibiotic coverage
- References
XV. Management: Indications for Urology Consultation
- Failure to pass stone
- Unpassed stone after 14 days (may be followed without intervention up to 4-6 weeks)
- Overall, 86% of Kidney Stones pass spontaneously
- Large calculus >5 mm (esp. >10 mm)
- Calculi <5 mm pass spontaneously in 90% of cases
- Calculi 5 mm pass spontaneously in 50% of cases
- Calculi >6 mm pass spontaneously in 10% of cases
- Calculi 10 mm rarely pass spontaneously
- Persistent proximal stones
- Stones distal to the sacroiliac joint pass in 84% of cases
- Stones proximal to the sacroiliac joint pass in 52% of cases
- Jendeberg (2017) Eur Radiol 27(11): 4775-85 [PubMed]
- Ureterolithiasis and Urinary Tract Infection
- Emergent management for stone removal required
- May quickly progress to Sepsis
- Struvite Stones or Staghorn calculi (Magnesium ammonium phosphate stones) are high risk for infection
- Significant Hydronephrosis or renal dysfunction
- Even significant Hydronephrosis alone does not drive urgent management
- In otherwise healthy patient with normal Renal Function (and 2 Kidneys) and no Urinary Tract Infection
- However significant persistent Hydronephrosis may result in permanent renal damage
- Urgent management indications for significant Hydronephrosis
- Persistent severe Hydronephrosis
- Single Kidney with obstruction
- Impaired Renal Function
- Even significant Hydronephrosis alone does not drive urgent management
- Intractable pain and Vomiting
- High grade ureteral obstruction
- Severe pain requiring Opioids >2 days
- Multiple stones (esp. bilateral obstruction)
- Recurrent stone formation
-
Struvite Stones or Staghorn calculi (Magnesium ammonium phosphate stones)
- High risk of infection and typically do not pass without intervention
- Pregnancy with failed expectant management
- Occupation (unable to return to work until clear)
- Police officer
- Firefighter
- Train engineer
- Airline pilot
XVI. Management: Indications for Hospitalization and Urgent Urology Evaluation
- Ureterolithiasis with Urinary Tract Infection (infected stone)
- Acute Renal Failure
- Solitary Kidney with complete obstruction
- Intractable pain and Vomiting
XVII. Management: Emergency Department
- Exclude Urinary Tract Infection complicating Ureterolithiasis
- Obstructive uropathy with a Urinary Tract Infection requires emergent urologic management
- Empiric Antibiotics in suspected concurrent Urinary Tract Infection (for Escherichia coli, Klebsiella, Proteus)
- Antibiotic selection is influenced by local Antibiotic Resistance rates
- Fluoroquinolones (Ciprofloxacin, Levofloxacin) IV
- Ceftriaxone IV
- Oral agents in inconclusive cases in non-toxic, afebrile patients (consider with one dose Ceftriaxone before discharge)
- Fluoroquinolones (Ciprofloxacin, Levofloxacin) orally
- Trimethoprim-Sulfamethoxazole (Septra, Bactrim)
- Amoxicillin-Clavulanate (Augmentin)
- Cefpodoxime (Vantin)
- Cefdinir (Omnicef)
- Empiric Antibiotics in suspected Urinary Tract Infection after urologic instrumentation (Pseudomonas coverage)
- Consider crystalloid (NS, LR) in emergency department (consider D5 1/2NS if calciuria)
- IV fluid hydration as of 2012 is limited to those patients with signs, symptoms of Dehydration
- May worsen pain, and does not offer significant benefit in a well-hydrated patient
- May allow for Emergency Department Nephrolithiasis management without Intravenous Access
- Patient could be discharged after Urinary Tract Infection was excluded and analgesia administered
- No evidence that high volume IV fluids improves stone passage, pain control or avoids intervention
- IV fluid hydration as of 2012 is limited to those patients with signs, symptoms of Dehydration
-
Analgesics
- Ketorolac (Toradol) 15-30 mg IV
- Hydromorphone (Dilaudid) or Morphine Sulfate IV
- Ketamine 0.15 mg/kg IV (as adjunct to Ketorolac and Opioids)
- Antiemetics
- Disposition
- See below for Outpatient Management including Medical Expulsive Therapy
XVIII. Management: Outpatient
- See Prevention below
- Fluid and dietary measures apply to both acute management and prevention
- Maintain >2-2.5 liters of oral fluid daily
- See Specific Types
- Adequate Analgesics
- Example Protocol
- Ibuprofen 600 mg every 6 hours scheduled AND
- Acetaminophen 1000 mg orally every 6 hours scheduled AND
- Oxycodone 5 mg orally every 4-6 hours for breakthrough pain esp. at night (avoid use if possible)
- NSAIDs
- Avoid NSAIDS in significant renal disease (e.g. congenital cysteine Ureterolithiasis) or otherwise containdicated
- Highly effective in Renal Colic (which is in part Prostaglandin mediated)
- NSAIDs compared with Opioids
- Equal to or more effective than Opioids
- Less Vomiting than with Opioids
- Holdgate (2004) BMJ 328:1401-4 [PubMed]
- ParenteralNSAIDs given intramuscularly
- Ketorolac (Toradol) 30-60 mg IM (or 15-30 mg IV) or
- Diclofenac (Voltaren) 75 mg IM
- Opioids may be required as adjuncts to NSAIDs and Acetaminophen for adequate analgesia
- If Morphine or Oxycodone are used, then Acetaminophen may be used separately
- Example Protocol
- Medical Expulsive Therapy
- Efficacy - mixed data (may be allow moderate stones >=5 mm to pass without intervention)
- Some studies have shown benefit in stone expulsion with alpha Antagonists
- Tamsulosin may facilitate more distal stones >5 mm to pass spontaneously without intervention
- Tamsulosin increased chance of passing Ureteral Stone to >80%
- Most studies have shown no benefit (particularly for small stones <5 mm)
- Tamsulosin and Nifedipine are ineffective at four weeks to facilitate stone passage
- Preparations
- Tamsulosin (Flomax)
- Preferred over Nifedipine or Doxazosin (Tamsulosin has no effect on Blood Pressure)
- Dose: 0.4 mg orally daily for 14 days
- Other alpha blockers are probably effective
- Doxazosin (Cardura)
- Dose: 4 mg orally daily for 14 days
- Nifedipine (Procardia)
- Not recommended, as may be no better than Placebo
- Less effective than Tamsulosin and Doxazosin
- Dose: 30 mg orally daily for 14 days
- Hollingsworth (2006) Lancet 368:1171-9 [PubMed]
- Wang (2016) Drug Des Devel Ther 10:1257-65 [PubMed]
- Tamsulosin (Flomax)
- Efficacy - mixed data (may be allow moderate stones >=5 mm to pass without intervention)
- Disposition
- Re-evaluation and repeat imaging (e.g. renal Ultrasound) every 2 weeks
- May continue to observe if only partial obstruction, pain controlled and no Urinary Tract Infection
- Refer to Urology if indicated (see indications above)
- Consider non-contrast CT Abdomen by 2 weeks for persistent pain (if not already obtained)
- Return precautions
- Re-evaluation and repeat imaging (e.g. renal Ultrasound) every 2 weeks
XIX. Management: Specific Stone Therapy
- See Urate Stones
- See Calcium Stones
- See Struvite Stones
- See Cystine Stones (Cystinuria)
XX. Management: Interventions
- Anatomic directed stone therapy
- Stone above Illiac crest
- Extracorporeal Shock Wave Lithotripsy (ESWL)
- Pushback and Extracorporeal Shock Wave Lithotripsy
- Antegrade or retrograde Ureteroscopy
- Percutaneous Nephrostomy tube
- Open surgery (See Below)
- Stone below Illiac Crest
- Pushback and Extracorporeal Shock Wave Lithotripsy
- Cystoscopy and stent placement
- Ureteroscopy and Stone Manipulation (Loop, basket)
- Open surgery (See Below)
- Stone above Illiac crest
- Available Interventions
- Ureteroscopy
- Ureteral Stone
- Ureterorenoscopy
- Renal stones <2 cm
- Extracorporeal Shock Wave Lithotripsy (ESWL)
- Radiolucent calculi
- Renal stones <2 cm
- Ureteral Stones <1 cm
- Percutaneous Nephrolithotomy
- Renal stones >2 cm
- Proximal Ureteral Stones >1 cm
- Open Surgery Procedures in refractory cases
- Anatomic nephrolithotomy
- Partial nephrectomy
- Illeal ureter
- Ureteroscopy
XXI. Management: Asymptomatic Renal Stones
- Incidental asymptomatic Kidney Stones are commonly found on abdominal imaging (10-25% annual risk of symptoms)
- Repeat imaging in 6 months, then each year
- Intervention indications for stone removal
- Symptomatic stone
- Obstruction
- Recurrent Urinary Tract Infection
- Increasing stone size
- Future conception desired
- Calyceal Diverticular stones
- Stones >10 mm
- Renal pathology
XXII. Prevention
- See stone types for specific prevention
- Eliminate modifiable predisposing factors (responsible for 50% of Ureteral Stones)
- Prevention can be more finely directed by stone type
- See Calcium Oxalate Nephrolithiasis for prevention of the most common type
- Maintain fluid intake >2.5 to 3 Liters per day
- Most important single measure
- Ingest 8 to 12 ounces fluid on awakening and at bedtime
- Avoid soft drinks (esp. colas which contain phosphoric acid, predisposing to stone formation)
- Recommended fluids
- Water
- Citrus juice
- Maintain Urine Volume > 2 Liters per day
- Periodically measure Urine Output in a 2 liter bottle
- Urine should be clear in appearance with minimal color
- Dietary restrictions
- Limit animal Protein to 8 ounces per day (or <1 gram/kg/day)
- Limit Sodium intake to <4 grams per day (target 2.3 grams)
- Limit Oxalate Containing Foods (e.g. tea, tomatoes, cashews, almonds, potatoes, spinach)
- Decreases urinary oxalate excretion
- Limit high sugar or fat content (Obesity predisposes to stone formation)
- Avoid excessive Vitamin C (target <1 g/day)
- Lifestyle
- Move toward target BMI, Ideal Weight
- Encourage daily physical Exercise
- Dietary increases or no restriction
- Consider DASH Diet
- Diet high in vegetables and fruits, low animal Protein, moderate no-fat dairy
- Increase vegetable Dietary Fiber
- Maintain Calcium intake at at least 1000 to 1200 mg/day (if Calcium Oxalate Stone)
- No Dietary Calcium restriction (unless absorptive Hypercalciuria)
- Calcium binds oxalate in the Intestine and decreases oxalate absorption
- Take Calcium with meals
- Consider DASH Diet
XXIII. Complications
- Renal Scarring
- Urinary Tract Infection (emergent intervention required)
- Renal Forniceal Rupture or Calyceal Rupture (emergent Ureteral Stenting required)
- Rare complication of ureteral obstruction and increased renal Pelvis pressure
- Results in urine leakage into the Retroperitoneum
XXIV. References
- Mobley (Feb 1999) Hospital Medicine, p. 21-38
- Herbert (2012) EM:Rap 2(8): 7-8
- Spangler and Varghese (2022) Crit Dec Emerg Med 36(11): 4-10
- Swaminathan in Herbert (2014) EM:Rap 14(12): 11-2
- Goldfarb (1999) Am Fam Physician 60(8): 2269-76 [PubMed]
- Houshiar (1996) Postgrad Med 100(4): 131-8 [PubMed]
- Fontenelle (2019) Am Fam Physician 99(8): 490-6 [PubMed]
- Frassetto (2011) Am Fam Physician 84(11): 1234-42 [PubMed]
- Pietrow (2006) Am fam Physician 74(1): 86-94 [PubMed]
- Preminger (2007) J Urol 178(6): 2418-34 [PubMed]
- Portis (2001) Am Fam Physician 63(7):1329-38 [PubMed]
- Segura (1997) J Urol 158:1915-21 [PubMed]
- Teichman (2004) N Engl J Med 350:684-93 [PubMed]
- Trivedi (1996) Postgrad Med, 100(6): 63-78 [PubMed]