Acute Renal Colic

Renal colic is caused by dilation of the renal pelvis and ureteral segments. While usually colic is from an acute obstruction such as a ureteral calculus, it may also be due to a variety of other problems and disorders such as from ureteral spasms immediately after double J stent removal or ureteroscopy. Similar ureteral blockages from chronic sources (such as ureteropelvic junction obstructions, prostate, cervical or pelvic cancer, scarring and retroperitoneal fibrosis among others), do not generally cause acute pain or colic.

Flank pain can be caused by multiple etiologies. These include:

• Abdominal Aortic Aneurysm
• Angiomyolipoma
• Costochondritis (rib pain)
• Dermatological (skin) disorders (Herpes Zoster)
• Dietl's crisis
• Double J stent placement or recent removal
• Endometriosis
• Extrinsic ureteral compression (surgical clips, staples, cancers)
• Local mass or growth
• Neurological disorders and neuropathic pain
• Musculoskeletal conditions
• Papillary necrosis
• Pleural pain
• Pyelonephritis
• Referred pain from back or thoracic pathologies (radiculitis)
• Renal abscess, infarction or venous thrombosis
• Retroperitoneal fibrosis
• Retroperitoneal pathology (abscess, hematoma)
• Subcapsular spontaneous renal hematoma (Wunderlich syndrome)
• Ureteral stricture
• Ureteropelvic junction obstruction
• Ureteroscopy

Ureteral calculi are a common cause of the most acute and severe level of flank pain. The bulk of this review will therefore focus on renal colic from obstruction by a ureteral stone.

There are multiple predictors and risk factors for kidney stone formation. The following are the most common:[6][7]

1. Inadequate urinary volume: Patients with extremely low urine volumes (usually less than 1 liter per day) increase the concentration of solutes (indicated by urine with an osmolarity greater than 600 mOsm/kg) and promote urinary stasis, which can cause supersaturation of solutes and lead to stone formation. Optimal daily urine volumes for stone formers is 2,500 ml with a minimum acceptable level of 2,000 ml.
2. Hypercalciuria: Most often, this is an idiopathic finding. It can be secondary to increased intestinal absorption of calcium, higher circulating serum calcium, reduced renal calcium reabsorption (renal calcium leak), hypervitaminosis D, hyperparathyroidism, high protein load, or systemic acidosis. Hypercalciuria increases the urinary saturation of calcium salts like oxalate and phosphate, causing the formation of crystals and calculi. Calcium containing stones form approximately 80% of all renal calculi. Hypercalciuria is usually defined as urinary calcium of 250 mg or more per 24 hours. Treatment involves minimizing excessive daily oral calcium intake, correcting phosphate deficiencies that lead to increased Vitamin D activity, and the use of thiazides to increase calcium reabsorption in the nephron.
3. Hyperoxaluria: Oxalate naturally occurs in plants where it binds tightly to calcium in the plant's tissue fluid. Ingestion of vegetable material results in intestinal oxalate absorption and urinary excretion. As oxalate has no nutritional or beneficial role in human physiology, it is excreted in the urine where it can form crystals and stones with calcium. Oxalate is considered the strongest chemical promotor of stones. Normal urinary oxalate is up to about 40 mg per day but optimal 24-hour urine levels are generally at 25 mg/day or less. Green leafy vegetables like spinach, rhubarb, and collard greens are particularly high in oxalate.
4. Hyperuricosuria: High urinary uric acid levels can promote both calcium oxalate and uric acid stone formation. Uric acid stones account for 5% to 10% of all renal calculi. Hyperuricosuria can be secondary to a high animal protein diet or a genetic defect causing increased uric acid excretion. Most pure uric acid stones are caused by high total urinary acid levels and not by elevated urinary uric acid levels. Allopurinol or febuxostat (Uloric) can be used to reduce uric acid production and potassium citrate is used for aciduria. Goal of therapy is to achieve a pH of approximately 6.5 or more. Sodium bicarbonate can also be used to increase urinary pH. 
5. Infection stones: These are caused by urea-splitting organisms (Proteus or Klebsiella spp but not Escherichia coli) that break down urea in the urine, increasing concentrations of ammonia and pH which promote struvite stone formation and growth. Infection stones are also called struvite or triple (Magnesium, Ammonium, Calcium) phosphate calculi. Treatment includes control of infection with total surgical removal of all stones which are considered infected. A specific urease inhibitor, acetohydroxamic acid, may be useful in selected cases.[8]
6. Hypocitraturia: Inadequate urinary citrate levels can contribute to new nephrolithiasis formation. Citrate is the urinary equivalent of serum bicarbonate. It increases urinary pH, but it also acts as a specific inhibitor of crystal aggregation and stone formation by forming soluble complexes with calcium and magnesium. Optimal levels are approximately 300 mg (or more)/L of urine. Potassium citrate supplements are also recommended to optimize urine pH in cases of uric acid stones and aciduria.

Approximately 5% to 15% of the population will be affected by a kidney stone, and of those, 50% will have a recurrent stone within five to seven years of the initial presentation if preventive measures are not taken. Over 70% of stones occur in people 20 to 50 years old, and they are more common in men than women by a factor of about 2:1. Patients with obesity, hypertension, a positive family history of nephrolithiasis, irritable bowel syndrome and/or diabetes are at increased risk for kidney stone formation.[9][10][11]

As a stone moves from the renal collecting system, it can significantly affect the genitourinary tract. It can cause constant or intermittent obstruction and hydronephrosis of the ureter, causing urine to back up into the kidney. Intermittent obstruction often causes longer-lasting discomfort and pain than a constant blockage where compensatory mechanisms can offset the increased ureteral intraluminal pressure to some degree. An acute ureteral obstruction causes a decrease in the glomerular filtration rate of the affected kidney and increases urine excretion by the unaffected renal unit as well as very severe, excruciating pain. Complete obstruction of the ureter can lead to the eventual loss of renal function, with damage becoming irreversible, possibly starting at just one to two weeks. Additionally, there is a risk of rupture of a renal calyx with the development of a urinoma. Of even more concern is the possibility that an obstructed renal unit might become infected, causing obstructive pyelonephritis or pyonephrosis. This condition can be life-threatening and requires immediate surgical drainage as antibiotics alone will be ineffective.

Renal calculi can become impacted, most commonly at one of three locations: 1) at the ureteropelvic junction, as the renal pelvis narrows abruptly to meet the ureter, 2) near the pelvic brim, where the ureter takes a posterior turn, or 3) at the ureterovesical junction which is the narrowest portion of the ureter.

Pain is the result of a combination of ureteral muscle spasms, increased proximal peristalsis from activation of intrinsic ureteral pacemakers, stone-induced localized inflammatory changes, renal swelling with capsular stretching, edema, and irritation. These processes stimulate submucosal stretch receptors in the ureter, renal pelvis, and capsule which are a direct cause of pain. Of all the various factors that can contribute to flank pain and renal colic, stimulation of the renal pelvis, peripelvic renal capsule, and calices from stretching most closely mimics typical renal colic. 

Unfortunately, the severity of the pain does not reliably predict stone size or likelihood of spontaneous expulsion.[12]

Various parameters have been looked at to help predict which patients are more likely to fail conservative management of their acute renal colic and require surgery.  A previous history of renal colic weakly correlated with a failure of conservative treatment, but neither gender, degree of hydronephrosis, initial degree of pain, stone size, shape or location could reliably predict which patients would ultimately require surgical intervention.[13]

The immediate effect of a newly obstructing ureteral stone is to increase proximal intraluminal pressure which initially distends the renal pelvis and increases ureteral peristalsis.  Peak renal pelvic pressure from a high-grade obstruction is usually obtained within two to five hours of a complete ureteric obstruction. Other changes in the kidneys after a complete ureteral blockage include pyelolymphatic and pyelovenous backflow. Interstitial renal edema develops which significantly increases lymphatic drainage from the affected kidney and stretches the renal capsule leading directly to painful stimuli from capsular stretch receptors. 

Often, a state of equilibrium will be achieved as the increasing proximal ureteral dilation allows some urine to pass around the obstruction which is enough, along with the other compensatory measures, to relieve the pain and achieve stability.

Pain fibers are primarily through the preganglionic sympathetic nerves and the ascending spinothalamic tracts.  When the stone approaches the intramural ureter, the nervi erigentes can become involved which can cause various bladder symptoms including frequency, urgency, dysuria, hesitancy and difficulty in voiding. 

Renal blood flow increases for the first 90 minutes after initial ureteral blockage before diminishing. This is caused by vasodilation of the afferent preglomerular arterial blood supply. By five hours after the ureteral obstruction, renal blood flow and ureteral intraluminal pressures have decreased back to normal or below.  Over time, renal blood flow tends to slowly diminish.  After three days, renal blood flow has dropped to about half from the normal baseline and this continues to slowly diminish over time. By eight weeks, renal blood flow is only 12% of its prior, normal baseline value. Even then, the dilation and hydroureteronephrosis usually remains but ureteral peristalsis has almost disappeared. Renal blood flow in teh contralateral kidney has increased at this point.

Nausea and vomiting is associated with classic renal colic in about half or more of patients with acute obstructing calculi. This is due to a common innervation pathway between the kidneys and the GI tract embryologically through afferents of the vagus nerve and celiac axis. This effect can be exacerbated by NSAIDs and opioid medications that have GI side effects. 

History and Physical

Patients with renal colic typically present with sudden onset of flank pain radiating laterally to the abdomen and/or to the groin. Patients often report a dull constant level of pain with colicky episodes of increased pain. The constant pain is often due to stretching of the renal capsule due to obstruction, whereas colicky pain can be caused by peristalsis of the ureteral smooth muscle. Many patients report associated nausea or vomiting, and some may report gross hematuria. As the stone migrates distally and approaches the bladder, the patient may experience dysuria, urinary frequency, urgency, or difficulty in urination.

Patients experiencing renal colic may present in very severe pain. Classically, these patients are unable to find a comfortable position and are often writhing or constantly pacing around the examination table. The exam may reveal flank pain more commonly than abdominal pain, and the skin may be cool or diaphoretic. There is often a prior personal or family history history of stones, recent ureteroscopic surgery, or just after removal of a double J stent. 

In the case of recent ureteroscopy or immediately after removal of a double J stent, the history alone can provide the diagnosis. In these cases, the renal colic is due to ureteral spasm which effectively causes an obstruction with resultant proximal ureteral and renal dilation even without a stone. The pain can be just as intense as from an obstructing ureteral stone.

Evaluation

Diagnosis is made through a combination of history and physical exam, laboratory testing, and imaging studies. Urinalysis shows some degree of microscopic or gross hematuria in 85% of stone patients, but should also be evaluated for signs of infection (e.g., white blood cells, bacteria). Urinary pH greater than 7.5 may be suggestive of a urease producing bacterial infection, while pH values less than 5.5 may indicate the presence of uric acid calculi.

A basic metabolic panel (BMP) should be obtained to assess for renal function, dehydration, acid-base status, and electrolyte balance. Serum calcium should be checked. A complete blood count (CBC) can be considered to evaluate for leukocytosis if there is a concern for infection although a mild elevation of WBCs is common secondary to white blood cell demargination.

Hematuria is present in 85% of acute renal colic cases caused by calculi. While the presence of hematuria is suggestive of a stone, it is not definitive and neither does the absence of hematuria conclusively prove that a stone is not present. 

Consider obtaining a parathyroid hormone (PTH) level if hypercalcemia is present and therefore primary hyperparathyroidism is suspected. If possible, urine should be strained to capture stones for chemical analysis to help determine optimal preventive prophylactic measures. Further metabolic testing, such as a 24-hour urine collection for volume, pH, calcium, oxalate, uric acid, citrate, sodium, magnesium and potassium concentrations, should be considered in high-risk first-time stone formers, pediatric patients or recurrent stone formers. It is highly recommended in nephrolithiasis patients with solitary kidneys, renal failure, renal transplants, gastrointestinal (GI) bypass, and any patient with high or increased anesthesia risk.

Renal ultrasonography can be used to establish hydronephrosis and measure resistive index and track larger renal stones (especially uric acid), but it will often miss stones smaller than 5 mm in size and is not a reliable imaging modality for visualizing ureteral calculi. The degree of perinephric fluid can be a predictor of the degree of obstruction.[3] Resistive index can be useful in diagnosing ureteral obstructions. It is defined as (peak systolic velocity - end diastolic velocity)/ peak systolic velocity) where normal is typically 0.7 or less. Higher levels indicate either obstruction or intrinsic renal disease.[14][15]  

Unenhanced (or helical) CT is the gold standard for the initial diagnosis of suspected renal colic; with a sensitivity of 98%, the specificity of 100%, and negative predictive value of 97%. This modality allows rapid identification of stone, provides information as to the location and size of the stone, and any associated hydroureter, hydronephrosis, or ureteral edema, and can give information regarding potential other etiologies of pain (e.g., abdominal aortic aneurysm, malignancy). In those patients with no previous history of nephrolithiasis, CT should be performed to guide management. CT scans may underestimate stone size in comparison with an intravenous pyelogram or abdominal x-ray. 

However, CT scans expose patients to a significant radiation burden and they can be costly. In some patients with a history of renal colic that present with pain similar to previous obstructing urolithiasis, it may be sufficient to perform ultrasonography (US). While US is less sensitive (60% to 76%) than CT for detecting calculi less than 5 mm, it can reliably detect hydronephrosis and evidence of obstruction (increased resistive index in the affected kidney). It is also the modality of choice for evaluating a pregnant patient with concern for renal colic. Studies have shown that using ultrasonography as a primary imaging modality does not lead to an increase in complications in comparison to CT. Ultrasound is also a good way to follow a patient known to have uric acid urinary stones.

A plain abdominal x-ray (KUB) can identify many stones, but 10% to 20% of renal calculi are radiolucent and provide little information regarding hydronephrosis, obstruction, or the renal anatomy. Additionally, bowel gas, the bony pelvis, and abdominal organs may obstruct stone visualization. The KUB is recommended in kidney stone cases when the CT scan is positive, and the exact location of the stone is known. This helps in clearly identifying those stones that can be tracked by follow-up KUB and those that might be amenable to lithotripsy.

Combining renal ultrasound (which can easily demonstrate hydronephrosis but is less reliable in detecting stones) with a KUB (which has good sensitivity for imaging calculi but not dilation), can be very cost effective as an alternative to CT scans with lower cost and reduced radiation. Symptomatic stones are likely to produce hydronephrosis or obstruction (visible on ultrasound) or will be seen directly on the KUB. The combination of KUB radiography with renal ultrasonography provides a reported diagnostic accuracy for an obstructing stone of 90%, specificity of 93%, and a sensitivity of 88%.[16]

If the stone should pass before imaging can be performed, some evidence of residual inflammation may remain, such as hydronephrosis or pain, even if no stone is specifically or definitively identified. 

The degree of hydronephrosis does not always correlate well with the intensity of pain or the likelihood of spontaneous passage. In general, the presence of minimal to moderate hydronephrosis from a stone does not appear to significantly affect spontaneous stone passage rate, but severe hydronephrosis suggests a reduced passage rate and earlier surgical intervention may be warranted.[17]

Other factors associated with earlier surgical intervention for stones and acute renal colic include:[18]

• Ureteral stone length of 9 mm or more
• Higher stone density (>700 Hounsfield units)
• Stone volume of 0.2 cc or more
• Ureteral wall thickness >2 mm
• Extrarenal pelvis
• Anterior-posterior diameter of the renal pelvis of >18 mm.

Treatment / Management

Treatment includes the following:

1. Immediate intervention with analgesia and antiemetics. NSAIDs and opiates are first-line therapies for analgesia. NSAIDs work in two ways in renal colic. First, NSAIDs decrease the production of arachidonic acid metabolites, which mediate pain receptors, alleviating pain caused by distension of the renal capsule. Additionally, they cause contraction of the efferent arterioles to the glomerulus, causing a reduction in glomerular filtration, and reducing hydrostatic pressure across the glomerulus. Because patients are frequently unable to tolerate oral medications, parenteral NSAIDs such as ketorolac (15 mg to 30 mg intravenously (IV) or intramuscularly (IM)) or diclofenac (37.5 mg IV) are most commonly used.[6][7][19]
2. Successful use of intravenous lidocaine for renal colic has been reported. The protocol is to inject lidocaine 120 mg in 100 mL normal saline intravenously over 10 minutes for pain management. It has been quite effective for intractable renal colic unresponsive to standard therapy and typically starts to work in 3-5 minutes. No adverse events have been reported.[20]
3. Opiate pain medication, such as morphine sulfate (0.1 mg/kg IV or IM) or hydromorphone (0.02 mg/kg IV or IM), can also be used effectively for analgesia, especially when other measures have failed. However, opiates are associated with respiratory depression and sedation, and there is a risk of dependence associated with prolonged opiate use. 
4. Fluid hydration. Although there is no evidence to support that empiric fluid will help “flush out” a stone, many patients are dehydrated secondary to decreased oral intake or vomiting and can benefit from adequate hydration.
5. Medical expulsive therapy. Alpha 1 adrenergic receptors exist in increasing concentration in the distal ureter. The use of alpha blockade medications (for example, tamsulosin or nifedipine) is theorized to facilitate stone passage by decreasing intra-ureteral pressure and dilating the distal ureter. However, data from randomized control trials are somewhat mixed as to whether these medications improved stone passage. The consensus opinion is they may be helpful in smaller stones in the lower or distal ureter.  They are probably of little use in larger stones in the proximal ureter. Silodosin (Rapaflo) 4 and 8 mg was compared to standard tamsulosin 0.4 mg.  The higher dose silodosin (8 mg) was comparable to the tamsulosin, but the lower dose of 4 mg was clearly inferior with reduced expulsion rates and increased pain reported.[21] Mirabegron may have a beneficial effect on hastening spontaneous stone passage in patients with distal ureteral stones that are less than 6 mm in size.[22]Definitive management of impacted stones. There are several invasive methods to improve stone passage. These include shock wave lithotripsy, in which high energy shock waves are used to fragment stones, ureteroscopy with either laser or electrohydraulic stone fragmentation, or in rare cases, open surgery.  In the presence of infection, a double J stent or percutaneous nephrostomy may be used to help with urinary drainage of the affected renal unit with definitive stone therapy postponed until the patient is stable.
6. Optimal timing of intervention for renal colic depends on the underlying etiology. For an obstructing stone, intervention is suggested even in asymptomatic patients after 30 days due to the increased risk of scarring and other complications. 
7. Behavior modification and preventative management. Increase fluid intake to optimize urine output with a goal of 2 L to 2.5 L of urine daily. Patients with calcium stones and high urine calcium concentrations should limit sodium intake and have a goal of moderate calcium intake of 1000 mg to 1200 mg dietary calcium daily. Those with calcium stones and low urinary citrate or those with uric acid stones and high urinary uric acid should increase intake of fruits and vegetables and decrease non-dairy animal protein. They may benefit from potassium citrate supplementation. Uric acid stone formers are usually best treated with potassium citrate (urinary alkalinizer) to a pH of 6.5.  Hyperuricosuric calcium stone formers can benefit from allopurinol. Thiazide diuretics are indicated in those with high urinary calcium and recurrent calcium stones to reduce the amount of urinary calcium. Patients with hyperoxaluria should be encouraged to lower their oxalate intake (spinach, nuts, chocolate, green leafy vegetables). [20][23][24]
8. Nerve blocks can often be helpful, especially in chronic cases of flank pain. An anesthetic injection is typically injection proximal to the area of the 11th or 12th intercostal nerve. Good efficacy of a nerve block suggests a musculoskeletal or neuropathic etiology. Paraveterbral, splanchnic and intercostal nerve blocks have all shown varying degrees of efficacy in relief from flank pain.[25][26][27]
9. 24-hour urine testing for kidney stone prophylaxis is now recommended for all high risk and recurrent stone formers.  The American Urological Association Guidelines recommends informing even first time stone formers about 24-hour urine testing and prophylactic therapy. Good guidelines for interpretation of 24 hour urine tests and optimal treatment selection have been published and are now available for free download.[28]

Differential Diagnosis

• Angiomyolipomas
• Aortic aneurysms
• Biliary colic
• Iliac aneurysms
• Endometriosis
• Ovarian torsion
• Peritonitis
• Pyelonephritis
• Renal cancer
• Renovascular compromise
• Wunderlich syndrome (rare condition with spontaneous renal subcapsular and/or retroperitoneal bleeding and hematoma formation)