Nephrolithiasis

Aka: Nephrolithiasis, Urolithiasis, Ureterolithiasis, Kidney stone, Renal Calculi, Ureteral Calculus, Renal Colic, Medical Expulsive Therapy

1. See Also
   1. Nephrolithiasis Risk Factors
   2. Medication Causes of Nephrolithiasis
   3. Nephrolithiasis Imaging
   4. Calcium Nephrolithiasis
   5. Uric Acid Nephrolithiasis
   6. Struvite Nephrolithiasis
   7. Cystine Nephrolithiasis
2. Epidemiology
   1. Nephrolithiasis prevelance is increasing in U.S.
      1. Prevalence 1994: 5%
      2. Prevalence 2010: 9%
   2. Life-time risk
      1. Males: 10-12%
      2. Females: 3-5%
   3. Recurrence of Nephrolithiasis
      1. One recurrence in 50% of patients
      2. More than 3 recurrences in 10% of patients
   4. Peak age 20-50 years
      1. Peak Incidence in midlife
      2. However childhood stone Incidence is increasing (pediatric diabetes, Obesity, Hypertension)
   5. Gender associations: Overall Male:Female ratio 4:1
      1. Males: Calcium oxalate
      2. Females: Struvite
      3. Both: Urate Stones and Cystine Stones
      4. Pregnancy: Calcium Phosphate (75% of cases)
3. Pathophysiology
   1. Stone formation is inhibited by Citrate
   2. Women have much higher levels of citrate than men
   3. Low citrate levels are related to most stone forms
4. Risk Factors
   1. See Nephrolithiasis Risk Factors
5. Types: Stones
   1. Calcium Nephrolithiasis (75%)
      1. Calcium oxalate (70%)
      2. Calcium Phosphate (5-10%)
         1. Approaches 75% in pregnant women
         2. Also more common in children
   2. Struvite Nephrolithiasis (15-20%)
      1. Chronic infection (e.g. Proteus, pseudomonas) that forms staghorn calculi
   3. Uric Acid Nephrolithiasis (10-15%)
      1. Radiolucent stones that may be associated with gout and low Urine pH
   4. Cysteine Nephrolithiasis (1%)
      1. Typically due to inborn error of metabolism
      2. Like Struvute, forms staghorn calculi
   5. Drug-Induced (1%)
      1. Indinavir (Protease Inhibitor in HIV)
      2. Triamterene
6. Symptoms: Renal Colic
   1. Severe Abdominal Pain of sudden onset
      1. Unilateral Flank Pain
      2. Lower Abdominal Pain
   2. Associated symptoms
      1. Nausea and Vomiting
      2. Hematuria
      3. Fever may be present
         1. Consider Pyelonephritis associated with stone (requires emergent management)
7. Symptoms: By stone location
   1. Kidney Calyx (typically asymptomatic other than Hematuria)
      1. Vague Flank Pain
      2. Hematuria
   2. Ureteropelvic junction or UPJ (Proximal ureter where ureter meets renal Pelvis)
      1. Flank Pain
      2. Upper Abdominal Pain
      3. Renal Colic
   3. Pelvic Brim (Low-Mid Ureter, where ureter crosses over iliac crest and iliac artery, iliac vein)
      1. Flank Pain
      2. Anterior Abdominal Pain
      3. Renal Colic
   4. Distal ureter: Ureterovesicular junction or UVJ (most common impaction site)
      1. Dysuria
      2. Urinary Frequency
      3. Anterior Abdominal Pain
      4. Flank Pain
      5. Renal Colic
8. Differential Diagnosis
   1. See Flank Pain
   2. See Hematuria
   3. See Dysuria
   4. See Urinary Frequency
   5. See Acute Abdominal Pain Causes in Adults
   6. See Acute Pelvic Pain Causes
   7. Acute onset of symptoms
      1. Urinary Tract Infection
      2. Acute Prostatitis
      3. Musculoskeletal spasm
      4. Acute Constipation or other acute bowel disorder
      5. Ectopic Pregnancy
      6. Ovarian Torsion
      7. Testicular Torsion
      8. Appendicitis
      9. Incarcerated Hernia
      10. Biliary Colic
      11. Abdominal Aortic Aneurysm rupture
          1. Consider in new onset Ureterolithiasis symptoms in age over 50 years old (especially if Tobacco use)
          2. May present with Flank Pain and Hematuria
          3. Ureterolithaisis is the most common mis-diagnosis of Abdominal Aortic Aneurysm presentations
   8. Chronic intermittent or insidious onset of symptoms
      1. Bowel disease
      2. Interstitial Cystitis
      3. Inguinal Hernia
      4. Testicular mass
      5. Urothelial or Renal Mass
      6. Benign prostatitic hyperplasia
9. Imaging: General
   1. See Nephrolithiasis Imaging
10. Imaging: Sample approach for suspected uncomplicated Nephrolithiasis (emergency department)
    1. Background
       1. Intention
          1. Reduce ionizing radiation exposure in the evaluation of Nephrolithiasis
          2. Avoid delaying intervention (when indicated)
       2. Bedside renal Ultrasound can reliably identify stones >5mm based on Hydronephrosis
          1. Goertz (2010) Am J Emerg Med 28(7):813-6 [PubMed]
          2. Edmonds (2010) CJEM 12(3): 201-6 [PubMed]
       3. Bedside Ultrasound is a safe evaluation strategy without serious missed conditions
          1. Smith-Bindman (2014) N Engl J Med 371(12):1100-10 +PMID:25229916 [PubMed]
    2. Step 1: Suspicion for uncomplicated Nephrolithiasis
       1. Hematuria and abdominal, pelvic or Flank Pain AND
       2. No Urinary Tract Infection AND
       3. No serious comorbidity (e.g. cancer, AAA risk) or other confounding factor (e.g. single Kidney)
    3. Step 2: Bedside renal Ultrasound (bilateral for comparison) and Bladder (for obstruction, distal stone shadowing at UVJ)
       1. Hydronephrosis on side of pain
          1. Consider empiric treatment of Ureterolithiasis with expectant management
          2. Consider other causes of Hydronephrosis (e.g. Abdominal Aortic Aneurysm)
          3. Consider non-contrast CT as indicated (see Step 3 below)
       2. No Hydronephrosis
          1. Consider imaging with discussion of risks (e.g. CT-associated Radiation Exposure)
             1. Strongly consider CT if UTI by Urinalysis (exclude infected stone)
             2. False negative Ultrasound for Hydronephrosis
             3. Alternative intraabdominal diagnosis (e.g. Appendicitis, Diverticulitis)
          2. May treat empirically as small, non-obstructing stone (likely to pass without intervention)
          3. Close interval follow-up
          4. Consider alternative diagnoses
    4. Step 3: Consider Helical, Non-Contrast CT Abdomen and Pelvis for Ureterolithiasis
       1. Non-Contrast CT indications
          1. First stone suspected (no prior imaging or Ureterolithiasis history), esp. if over age 50 years old
          2. Persistent Ureterolithiasis symptoms at 14 weeks without prior imaging
          3. Infected stone suspected
          4. Urology consulted for intervention (see indications as below)
          5. Alternative intraabdominal diagnosis (e.g. Appendicitis, Diverticulitis)
       2. Consider KUB Abdominal XRay if CT positive for ureteral stone of 5 mm or greater
          1. Helical CT will localize the stone and ease simultaneous identification on KUB XRay
          2. KUB XRay allows for serial XRays for monitoring progression without significant radiation exposure
          3. KUB XRay is preferred over CT scout film due to better resolution and for easier comparison on future films
11. Labs: Initial diagnostics
    1. Precaution: Absent gross and Microscopic Hematuria does not exclude Nephrolithiasis (may miss up to 10% of cases)
    2. Urinalysis with reflex to Urine Culture
       1. Microscopic or Gross Hematuria in 90% of Nephrolithiasis cases
       2. Evaluate for Urinary Tract Infection
          1. Nephrolithiasis with Urinary Tract Infection is high risk and requires immediate urologic Consultation
          2. Factors most suggestive or higher risk of Urinary Tract Infection complicating Nephrolithiasis
             1. Fever (associated Likelihood Ratio of 10)
             2. Female (associated Likelihood Ratio of 27)
             3. Positive Urine Nitrite (associated Likelihood Ratio of 36)
             4. White Blood Cells in urine has Test Specificity of 25%
             5. Abrahamian (2013) Ann Emerg Med 62(5): 526-33 [PubMed]
12. Labs: Evaluation of single stone former without risk (labs to consider)
    1. Chemistry panel
       1. Serum electrolytes
       2. Serum Calcium
    2. Renal Function tests
       1. Blood Urea Nitrogen
       2. Serum Creatinine
    3. Serum Uric Acid
    4. Stone Analysis (nidus and outer layer)
       1. Stone analysis is important to direct preventive strategies, esp. if Ureterolithiasis Risk Factors
          1. However, stone analysis is often not performed for the initial stone
       2. Microscopic Crystal Analysis
          1. Envelope shape crystal: Calcium oxalate
          2. Diamond shape crystal: Uric Acid
          3. Coffin-lid shape crystal: Struvite
          4. Hexagon shape crystal: Cystine
13. Labs: Evaluation of recurrent stone formation
    1. See those labs listed above
    2. Parathyroid Hormone level
       1. Obtain if Urine Calcium >10 mg/dl
    3. 24 hour Urine Collection
       1. Urine pH
          1. Acidic urine predisposes to Uric Acid stones, Cystine Stones and Calcium Oxalate Stones
          2. Alkaline urine predisposes to Struvite Stones and Calcium Phosphate Stones
       2. Urine Sodium
       3. Urine Creatinine
       4. Urine Calcium (Hypercalciuria >300 mg/day)
       5. Urine Uric Acid (Hyperuricosuria >750 mg/day)
       6. Urine Oxalate (Hyperoxaluria >40 mg/day)
       7. Urine Citrate (Hypocitraturia <320 mg/day)
       8. Urine Magnesium (Hypomagnesuria <50 mg/day)
       9. Other urine labs to consider
          1. Urine pHosphorus
          2. Urine Calcium Oxalate (Supersaturation)
          3. Urine Calcium Phosphate
14. Precautions
    1. Do not miss concurrent Urinary Tract Infection and Ureterolithiasis
    2. Do not miss Abdominal Aortic Aneurysm (which may also cause Hydronephrosis)
15. Management: Indications for Urology Consultation
    1. Failure to pass stone
       1. Unpassed stone after 14 days (may be followed without intervention up to 4-6 weeks)
       2. Overall, 86% of Kidney stones pass spontaneously
          1. Tchey (2011) Korean J Urol 52(12): 847-51 [PubMed]
       3. Large calculus >5 mm (esp. >10 mm)
          1. Calculi <5 mm pass spontaneously in 90% of cases
          2. Calculi 5 mm pass spontaneously in 50% of cases
          3. Calculi >6 mm pass spontaneously in 10% of cases
          4. Calculi 10 mm rarely pass spontaneously
    2. Ureterolithiasis and Urinary Tract Infection
       1. Emergent management for stone removal required
    3. Significant Hydronephrosis or renal dysfunction
       1. Even significant Hydronephrosis alone does not drive urgent management
          1. In otherwise healthy patient with normal Renal Function (and 2 Kidneys) and no Urinary Tract Infection
          2. However significant persistent Hydronephrosis may result in permanent renal damage
       2. Urgent management indications for significant Hydronephrosis
          1. Persistent severe Hydronephrosis
          2. Single Kidney with obstruction
          3. Impaired Renal Function
    4. Intractable pain and Vomiting
    5. High grade ureteral obstruction
    6. Severe pain requiring Opioids >2 days
    7. Multiple stones (esp. bilateral obstruction)
    8. Recurrent stone formation
    9. Occupation (unable to return to work until clear)
       1. Police officer
       2. Firefighter
       3. Train engineer
       4. Airline pilot
16. Management: Hospitalization and urgent urology indications
    1. Ureterolithiasis with Urinary Tract Infection (infected stone)
    2. Acute Renal Failure
    3. Solitary Kidney with complete obstruction
    4. Intractable pain and Vomiting
17. Management: Emergency Department
    1. Exclude Nephrolithiasis with Urinary Tract Infection!
    2. Consider crystalloid (NS, LR) in emergency department (consider D5 1/2NS if calciuria)
       1. IV fluid hydration as of 2012 is limited to those patients with signs, symptoms of dehydration
          1. May worsen pain, and does not offer significant benefit in a well-hydrated patient
          2. May allow for Emergency Department Nephrolithiasis management without Intravenous Access
          3. Patient could be discharged after Urinary Tract Infection was excluded and analgesia administered
       2. No evidence that high volume IV fluids improves stone passage, pain control or avoids intervention
          1. Worster (2012) Cochrane Database Syst Rev 2: CD004926 [PubMed]
    3. Analgesics
       1. Ketorolac (Toradol) 15-30 mg IV
       2. Hydromorphone (Dilaudid) or Morphine Sulfate IV
       3. Ketamine 0.15 mg/kg IV (as adjunct to Ketorolac and Opioids)
          1. Abbasi (2017) Am J Emerg Med +PMID:28821365 [PubMed]
    4. Antiemetics
       1. Ondansetron
    5. Disposition
       1. See below for Outpatient Management including Medical Expulsive Therapy
18. Management: Outpatient
    1. See Prevention below
       1. Fluid and dietary measures apply to both acute management and prevention
       2. Maintain >2-2.5 liters of oral fluid daily
    2. See Specific Types
       1. Calcium Nephrolithiasis
       2. Uric Acid Nephrolithiasis
       3. Struvite Nephrolithiasis
       4. Cystine Nephrolithiasis
    3. Adequate Analgesics
       1. Example Protocol
          1. Ibuprofen 600 mg every 6 hours scheduled AND
          2. Acetaminophen 1000 mg orally every 6 hours scheduled AND
          3. Oxycodone 5 mg orally every 4-6 hours for breakthrough pain esp. at night (avoid use if possible)
       2. NSAIDs
          1. Avoid in significant renal disease (e.g. congenital cysteine Ureterolithiasis)
          2. Highly effective in Renal Colic
             1. Cordell (1994) Ann Emerg Med 23(2):262 [PubMed]
             2. Cordell (1996) Ann Emerg Med 28:151-8 [PubMed]
          3. NSAIDs compared with Opioids
             1. Equal to or more effective than Opioids
             2. Less Vomiting than with Opioids
             3. Holdgate (2004) BMJ 328:1401-4 [PubMed]
          4. Parenteral NSAIDs given intramuscularly
             1. Ketorolac (Toradol) 30-60 mg IM (or 15-30 mg IV) or
             2. Diclofenac (Voltaren) 75 mg IM
                1. Pathan (2016) Lancet 387(10032): 1999-2007 [PubMed]
       3. Opioids may be required as adjuncts to NSAIDs and Acetaminophen for adequate analgesia
          1. If Morphine or Oxycodone are used, then Acetaminophen may be used separately
    4. Medical Expulsive Therapy
       1. Efficacy - mixed data (may be allow moderate stones >=5 mm to pass without intervention)
          1. Some studies have shown benefit in stone expulsion with alpha antagonists
             1. Singh (2007) Ann Emerg Med 50(5): 552-63 [PubMed]
             2. Al-Ansari (2010) Urology 75(1): 4-7 [PubMed]
          2. Tamsulosin may facilitate more distal stones >5 mm to pass spontaneously without intervention
             1. Furyk (2015) Ann Emerg Med +PMID: 26194935 [PubMed]
          3. Tamsulosin increased chance of passing ureteral stone to >80%
             1. Porpiglia (2004) J Urol 172:568-71 [PubMed]
          4. Most studies have shown no benefit (particularly for small stones <5 mm)
             1. Vincendeau (2010) Arch Intern Med 170(22): 2021-7 [PubMed]
             2. Ferre (2009) Ann Emerg Med 54(3): 432-9 [PubMed]
             3. Hermanns (2009) Eur Urol 56(3): 407-12 [PubMed]
          5. Tamsulosin and Nifedipine are ineffective at four weeks to facilitate stone passage
             1. Pickard (2015) Lancet 386: 341-9 [PubMed]
       2. Preparations
          1. Tamsulosin (Flomax)
             1. Preferred over Nifedipine or Doxazosin (Tamsulosin has no effect on Blood Pressure)
             2. Dose: 0.4 mg orally daily for 14 days
             3. Other alpha blockers are probably effective
          2. Doxazosin (Cardura)
             1. Dose: 4 mg orally daily for 14 days
          3. Nifedipine (Procardia)
             1. Not recommended, as may be no better than Placebo
             2. Less effective than Tamsulosin and Doxazosin
             3. Dose: 30 mg orally daily for 14 days
             4. Hollingsworth (2006) Lancet 368:1171-9 [PubMed]
             5. Wang (2016) Drug Des Devel Ther 10:1257-65 [PubMed]
    5. Disposition
       1. Re-evaluation and repeat imaging (e.g. renal Ultrasound) every 2 weeks
          1. May continue to observe if only partial obstruction, pain controlled and no Urinary Tract Infection
       2. Refer to Urology if indicated (see indications above)
       3. Consider non-contrast CT Abdomen by 2 weeks for persistent pain (if not already obtained)
19. Management: Specific Stone Therapy
    1. See Urate Stones
    2. See Calcium Stones
    3. See Struvite Stones
    4. See Cystine Stones (Cystinuria)
20. Management: Interventions
    1. Anatomic directed stone therapy
       1. Stone above Illiac crest
          1. Extracorporeal Shock Wave Lithotripsy (ESWL)
          2. Pushback and Extracorporeal Shock Wave Lithotripsy
          3. Antegrade or retrograde Ureteroscopy
          4. Percutaneous nephrostomy tube
          5. Open surgery (See Below)
       2. Stone below Illiac Crest
          1. Pushback and Extracorporeal Shock Wave Lithotripsy
          2. Cystoscopy and stent placement
          3. Ureteroscopy and Stone Manipulation (Loop, basket)
          4. Open surgery (See Below)
    2. Available Interventions
       1. Ureteroscopy
          1. Ureteral stone
       2. Ureterorenoscopy
          1. Renal stones <2 cm
       3. Extracorporeal Shock Wave Lithotripsy (ESWL)
          1. Radiolucent calculi
          2. Renal stones <2 cm
          3. Ureteral stones <1 cm
       4. Percutaneous Nephrolithotomy
          1. Renal stones >2 cm
          2. Proximal ureteral stones >1 cm
       5. Open Surgery Procedures in refractory cases
          1. Anatomic nephrolithotomy
          2. Partial nephrectomy
          3. Illeal ureter
21. Management: Asymptomatic Renal Stones
    1. Incidental asymptomatic Kidney stones are commonly found on abdominal imaging (10-25% annual risk of symptoms)
    2. Repeat imaging in 6 months, then each year
    3. Intervention indications for stone removal
       1. Symptomatic stone
       2. Obstruction
       3. Recurrent Urinary Tract Infection
       4. Increasing stone size
       5. Future conception desired
       6. Calyceal Diverticular stones
       7. Stones >10 mm
       8. Renal pathology
22. Prevention
    1. See stone types for specific prevention
    2. Eliminate modifiable predisposing factors
       1. See Nephrolithiasis Risk Factors
       2. See Medication Causes of Nephrolithiasis
    3. Prevention can be more finely directed by stone type
       1. See Calcium Oxalate Nephrolithiasis for prevention of the most common type
    4. Maintain fluid intake >2.5 Liters per day
       1. Most important single measure
       2. Ingest 8 to 12 ounces fluid on awakening and at bedtime
       3. Avoid soft drinks (esp. colas which contain phosphoric acid, predisposing to stone formation)
       4. Recommended fluids
          1. Water
          2. Citrus juice
    5. Maintain Urine Volume > 2 Liters per day
       1. Periodically measure Urine Output in a 2 liter bottle
       2. Urine should be clear in appearance with minimal color
    6. Dietary restrictions
       1. Limit animal protein to 8 ounces per day (or <1 gram/kg/day)
          1. Animal protein increases urinary calcium and Uric Acid excretion
          2. Animal protein decreases urinary pH and urinary citrate excretion
       2. Limit Sodium intake to 4-5 grams per day
       3. Limit Oxalate Containing Foods (e.g. tea, tomatoes, cashews)
       4. Limit high sugar or fat content (Obesity predisposes to stone formation)
       5. Avoid excessive Vitamin C
    7. Lifestyle
       1. Move toward target BMI, Ideal Weight
       2. Encourage daily physical Exercise
    8. Dietary increases or no restriction
       1. Increase vegetable Dietary Fiber
       2. Maintain calcium intake at at least 1000 mg/day (if Calcium Oxalate Stone)
          1. No Dietary Calcium restriction (unless absorptive Hypercalciuria)
          2. Calcium binds oxalate in the Intestine and decreases oxalate absorption
          3. Take calcium with meals
23. Complications
    1. Renal Scarring
    2. Urinary Tract Infection (emergent intervention required)
    3. Ruptured renal capsule
24. References
    1. Mobley (Feb 1999) Hospital Medicine, p. 21-38
    2. Herbert (2012) EM:Rap 2(8): 7-8
    3. Swaminathan in Herbert (2014) EM:Rap 14(12): 11-2
    4. Goldfarb (1999) Am Fam Physician 60(8): 2269-76 [PubMed]
    5. Houshiar (1996) Postgrad Med 100(4): 131-8 [PubMed]
    6. Fontenelle (2019) Am Fam Physician 99(8): 490-6 [PubMed]
    7. Frassetto (2011) Am Fam Physician 84(11): 1234-42 [PubMed]
    8. Pietrow (2006) Am fam Physician 74(1): 86-94 [PubMed]
    9. Preminger (2007) J Urol 178(6): 2418-34 [PubMed]
    10. Portis (2001) Am Fam Physician 63(7):1329-38 [PubMed]
    11. Segura (1997) J Urol 158:1915-21 [PubMed]
    12. Teichman (2004) N Engl J Med 350:684-93 [PubMed]
    13. Trivedi (1996) Postgrad Med, 100(6): 63-78 [PubMed]