Nephrolithiasis Workup

Acute renal colic with resultant flank pain is a common and sometimes complex clinical problem. Whereas noncontrast abdominopelvic computed tomography (CT) scans have become the imaging modality of choice, in some situations, renal ultrasonography or a contrast study such as intravenous pyelography (IVP) may be preferred.

A kidneys-ureters-bladder (KUB) radiograph, in addition to the renal colic CT scan, facilitates the review and follow-up of stone patients. Alternatively, the “CT scout” (a digital reconstruction from the CT that has an appearance similar to a KUB) is almost as sensitive as a KUB and is a good substitute at the initial assessment if the stone seen on the CT scan is visible on the CT scout. Adding contrast to the CT scan study may sometimes help clarify a difficult or confusing case but in general, contrast obscures calcific densities and as such, contrast scans are usually only indicated during subsequent evaluation of patients with stones. The noncontrast CT is the cornerstone of initial radiographic assessment.

Most authors recommend diagnostic imaging to confirm the diagnosis in first-time episodes of ureterolithiasis, when the diagnosis is unclear, or if associated proximal urinary tract infection (UTI) is suspected. Lindqvist et al found that patients who are pain-free after receiving analgesics could be discharged from the emergency department (ED) and undergo radiologic imaging after 2-3 weeks without increasing morbidity. ^[25]

Initial stones in elderly people and in children are relatively uncommon; however, consider kidney stones whenever acute back or flank pain is encountered, regardless of patient age. When stones occur in persons in these uncommon age groups, a metabolic workup consisting of a 24-hour urine collection and appropriate serum laboratory testing is recommended. To minimize radiation exposure, Tasian and Copelovitch recommend ultrasound as the initial imaging study in children with suspected nephrolithiasis, with noncontrast CT reserved for those in whom ultrasound is nondiagnostic and the suspicion of nephrolithiasis remains high. ^[20]  In pregnant women, ultrasound is also the preferred diagnostic modality.

Guidelines from the European Association of Urology (EAU) recommend the following laboratory tests in all patients with an acute stone episode ^[1] :

• Urinary sediment/dipstick test for demonstration of blood cells, with a test for bacteriuria (nitrite), urinary pH, and urine culture in case of a positive reaction

• Serum creatinine level, as a measure of kidney function

• Serum uric acid, (ionized) calcium, sodium, and potassium

• Complete blood cell count (CBC)

• C-reactive protein (CRP)

• Coagulation testing, if intervention is likely or planned: Activated partial thromboplastin time (aPTT) and prothrombin time (PT) with International Normalized ratio (INR)

• If no intervention is planned, examination of sodium, potassium, CRP, and blood coagulation time can be omitted

• The 2023 EAU guideline recommends ultrasound for initial assessment when there is concern for an acute symptomatic stone, followed by non–contrast-enhanced computed tomography to confirm stone diagnosis. ^[1]

Microscopic examination of the urine for evidence of hematuria and infection is a critical part of the evaluation of a patient thought to have renal colic. Gross or microscopic hematuria is only present in approximately 85% of patients with urinary calculi. The lack of microscopic hematuria does not eliminate renal colic as a potential diagnosis. In addition to a dipstick evaluation, always perform a microscopic urinalysis in these patients.

One retrospective study found that 67% of patients with ureterolithiasis had more than 5 red blood cells (RBCs) per high-power field (hpf), and 89% of patients had more than 0 RBCs/hpf on urine microscopic examination. ^[26] In addition, 94.5% have hematuria if screened with microscopy plus urine dipstick testing. ^[27]

Degree of hematuria is not predictive of stone size or likelihood of passage. No literature exists to support the theory that ureterolithiasis without hematuria is indicative of complete ureteral obstruction.

Attention should also be paid to the presence or absence of leukocytes, crystals, and bacteria and to the urinary pH. In general, if the number of white blood cells (WBCs) in the urine is greater than 10 cells per high-power field or greater than the number of RBCs, suspect a UTI. Pyuria (>5 WBCs/hpf on a centrifuged specimen) in a patient with ureterolithiasis should prompt a careful search for signs of infected hydronephrosis.

Urinary crystals of calcium oxalate, uric acid, or cystine may occasionally be found upon urinalysis. When present, these crystals are very good clues to the underlying type and nature of any obstructing calculus.

Determining urinary pH also helps. A urine pH greater than 7 suggests presence of urea-splitting organisms, such as Proteus, Pseudomonas, or Klebsiella species, and struvite stones. A urine pH less than 5 suggests uric acid stones.

Complete blood count

Whereas mild leukocytosis often accompanies a renal colic attack, a high index of suspicion for a possible renal or systemic infection should accompany any serum WBC count of 15,000/µL or higher in a patient presenting with an apparent acute kidney stone attack, even if afebrile. A depressed RBC count suggests a chronic disease state or severe ongoing hematuria.

Serum electrolytes, creatinine, calcium, uric acid, parathyroid hormone, and phosphorus

Measurements of serum electrolyte, creatinine, calcium, uric acid, parathyroid hormone (PTH), and phosphorus are needed to assess a patient’s current renal function and to begin the assessment of metabolic risk for future stone formation.

A high serum uric acid level may indicate gouty diathesis or hyperuricosuria, while hypercalcemia suggests either renal-leak hypercalciuria (with secondary hyperparathyroidism) or primary hyperparathyroidism. If the serum calcium level is elevated, serum PTH levels should be obtained.

Serum creatinine level is the major predictor of contrast-induced nephrotoxicity. If the creatinine level is higher than 2 mg/dL, use diagnostic techniques that do not require an infusion of contrast, such as ultrasonography or helical CT scanning.

Hypokalemia and decreased serum bicarbonate level suggest underlying distal (type 1) renal tubular acidosis, which is associated with formation of calcium phosphate stones.

To identify urinary risk factors, a 24-hour urine profile, including appropriate serum tests of renal function, uric acid, and calcium, is needed. Such testing is available from various commercial laboratories. This study is designed to provide more information about the exact nature of the chemical problem that caused the stone. This information is useful not only to allow more specific and effective therapy for stone prevention but also to identify patients with renal calculi who might have other significant health problems.

Keep in mind that all of the 24-hour urine chemistry findings may be within the reference range in patients who actively form stones and who are at high risk for stones. In these cases, optimizing the levels is beneficial and certain pharmacologic interventions may be suggested to prevent further stone formation.

The following are objective indications for a metabolic evaluation with a 24-hour urinalysis:

• Residual calculi after surgical treatment
• Initial presentation with multiple calculi
• Initial presentation before age 30 years
• Renal failure
• Solitary kidney (including renal transplant)
• Family history of calculi
• More than 1 stone in the past year
• Bilateral calculi

Patient preference is also an important consideration in determining whether to perform a 24-hour urine study. If a patient is strongly motivated to follow a protracted stone-prevention treatment plan (involving diet, supplements, medications, or a combination), obtain the study. If a patient is unlikely or unwilling to follow a long-term treatment plan, a metabolic evaluation is probably unwarranted. Patients have to understand that stone disease is a chronic disease. If they do not commit to helping themselves in behavioral modification, dietary changes, or medical compliance, they are prone to more frequent calculi formation.

The most common findings on 24-hour urine studies include hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia, and low urinary volume. Other factors, such as high urinary sodium and low urinary magnesium concentrations, may also play a role. A finding of hypercalcemia should prompt follow-up with an intact parathyroid hormone study to evaluate for primary and secondary hyperparathyroidism.

Calcium, oxalate, and uric acid

Elevation of the 24-hour excretion rate of calcium, oxalate, or uric acid indicates a predisposition to form calculi.

Hypercalciuria can be subdivided into absorptive, resorptive, and renal-leak categories on the basis of the results of blood tests and 24-hour urinalysis on both regular and calcium-restricted diets. Depending on the specific subtype, the treatment of absorptive hypercalciuria may include modest dietary calcium restriction, thiazide diuretics, oral calcium binders, or phosphate supplementation.

Resorptive hypercalciuria is primary hyperparathyroidism and requires parathyroidectomy, when possible. If parathyroid surgery is not possible, phosphate supplementation is usually recommended. Renal-leak hypercalciuria, which is less common than absorptive hypercalciuria, is usually associated with secondary hyperparathyroidism and is best managed with thiazide diuretics.

Another clinical approach to hypercalciuria, when hyperparathyroidism has been excluded with appropriate blood tests, is avoidance of excessive dietary calcium (usual recommendation, 600-800 mg/d), modest limitation of oxalate intake, and thiazide therapy. If thiazide therapy fails, additional workup (eg, calcium-loading test, more thorough evaluation) may be needed.

Indiscriminate dietary calcium restriction is not advantageous and in fact may increase formation of calculi owing to a secondary increase in oxalate absorption. The reduced dietary calcium reduces the oxalate-binding sites in the gastrointestinal (GI) tract, increasing the free dietary oxalate and leading to increased oxalate absorption. The final product of this is a net increase in stone production.

Hyperoxaluria may be primary (a rare genetic disease), enteric (due to malabsorption and associated with chronic diarrhea or short-bowel syndrome), or idiopathic. Oxalate restriction and vitamin B-6 supplementation are somewhat helpful in patients with idiopathic hyperoxaluria. Enteric hyperoxaluria is the type that is most amenable to treatment; dietary calcium supplementation often produces dramatic results.

Calcium citrate is the recommended supplement because it tends to further reduce stone formation. Calcium carbonate supplementation is less expensive but lacks citrate’s added benefit. Calcium works as an oxalate binder, reducing oxalate absorption from the GI tract. It should be administered with meals, especially those that contain high-oxalate foods. The supplement should not contain added vitamin D, because this increases calcium absorption, leaving less calcium in the GI tract to bind to oxalate. The optimal 24-hour urine oxalate level is 20 mg/d or less.

Hyperuricosuria predisposes to the formation of calcium-containing calculi because sodium urate can produce malabsorption of macromolecular inhibitors or can serve as a nidus for the heterogeneous growth of calcium oxalate crystals. Gouty diathesis, a condition of increased stone production associated with high serum uric acid levels, is also possible.

Therapy involves potassium citrate supplementation, allopurinol, or both. In general, patients with pure uric acid stones and hyperuricemia are treated with allopurinol, and those with hyperuricosuric calcium stones are treated with citrate supplementation. The optimal 24-hour urine uric acid level is 600 mg/d or less.

Sodium and phosphorus

Excess sodium excretion can contribute to hypercalciuria by a phenomenon known as solute drag. Elevated urinary sodium levels are almost always associated with dietary indiscretions. Decreasing the oral sodium intake can decrease calcium excretion, thereby decreasing calcium saturation.

An elevated phosphorus level is useful as a marker for a subtype of absorptive hypercalciuria known as renal phosphate leak (absorptive hypercalciuria type III). Renal phosphate leak is identified by high urinary phosphate levels, low serum phosphate levels, high serum 1,25 vitamin D-3 (calcitriol) levels, and hypercalciuria. This type of hypercalciuria is uncommon and does not respond well to standard therapies.

The above laboratory tests are confirmatory but are performed only if the index of clinical suspicion is high. Any patient with hypercalciuria who has a low serum phosphorus level and a high-normal or high urinary phosphorus level may have this condition. Repeat laboratories along with a 1,25 vitamin D-3 level are confirmatory.

Phosphate supplements are used to correct the low serum phosphate level, which then decreases the inappropriate activation of vitamin D originally caused by the hypophosphatemia. This corrects the hypercalciuria, which is ultimately a vitamin D–dependent function in this condition. This therapy is not well tolerated, however.

Citrate and magnesium

Magnesium and, especially, citrate are important chemical inhibitors of stone formation. Hypocitraturia is one of the most common metabolic defects that predispose to stone formation, and some authorities have recommended citrate therapy as primary or adjunctive therapy to almost all patients who have formed recurrent calcium-containing stones.

Many laboratories use 24-hour urine citrate levels of 320 mg/d as the normal threshold, but optimal levels are probably closer to the median level (640 mg/d) in healthy individuals. Periodic monitoring of pH with pH test strips can be very useful to titrate and optimize citrate supplementation. A pH level of 6.5 is usually considered optimal. A pH level over 7.0 should be discouraged, as it prompts calcium phosphate precipitation.

Potassium citrate is the preferred type of pharmacologic citrate supplement, though a potassium/magnesium preparation is under investigation. Liquid or powder pharmacologic citrate preparations are recommended when absorption is a problem or in cases involving chronic diarrhea. Sustained-release tablets are available and may be more convenient for some patients. Lemon juice is an excellent source of citrate; alternatively, large quantities of lemonade can be ingested, and this, of course, has the added benefit of providing increased fluid intake.

Magnesium is a more recently recognized inhibitor of stone formation, and the clinical role of magnesium replacement therapy is less well defined than that of citrate.

Creatinine

Creatinine is the control that allows verification of a true 24-hour sample. Most individuals excrete 1-1.5 g of creatinine daily. Values at either extreme that are not explained by estimates of lean body weight should prompt consideration that the sample is inaccurate.

Total urine volume

Patients in whom stones form should strive to achieve a urine output of more than 2 L daily in order to reduce the risk of stone formation. Patients with cystine stones or those with resistant cases may need a daily urinary output of 3 L for adequate prophylaxis.

pH

Some stones, such as those composed of uric acid or cystine, are pH-dependent, meaning that they can form only in acidic conditions. Calcium phosphate and struvite only form when the urine pH is alkaline. Although the other parameters in the 24-hour urine usually identify patients at risk of forming these stones, pH studies can be important in monitoring these patients, in optimizing therapy with citrate supplementation, and in identifying occult stone disease in some patients.

Plain abdominal radiography (also referred to as flat plate or KUB radiography) is useful for assessing total stone burden, as well as the size, shape, composition, and location of urinary calculi in some patients. Calcium-containing stones (approximately 85% of all upper urinary tract calculi) are radiopaque, but pure uric acid, indinavir-induced, and cystine calculi are relatively radiolucent on plain radiography.

When used with other imaging studies, such as a renal ultrasonography or, particularly, CT scanning, the plain film helps provide a better understanding of the characteristics of urinary stones revealed with these other imaging studies. This may also be helpful in planning surgical therapy.

The flat plate radiograph uses the same orientation and anatomical presentation that is observed on fluoroscopy images and retrograde pyelograms or during endoscopic ureteral surgery, such as ureteroscopy or intracorporeal lithotripsy. Not all urinary calculi may be visible on the KUB radiograph, whether because of their small size, stone radiolucency, or overlying gas, stool, or bone. The stones that are observed can be correlated with opacities found on other studies for identification and tracking progress.

If a stone is not visible on a flat plate radiograph, it could be a radiolucent uric acid stone that can be dissolved with alkalinizing medication. Such a stone is more likely if the urine pH indicates very acidic urine. In practice, any patient with symptoms of acute renal colic who demonstrates a urine pH lower than 6.0 should be considered at risk for a possible uric acid stone. If a stone of adequate size is visible on a CT scan but not visible on KUB, then uric stones should be considered.

The flat plate radiograph is inexpensive, quick, and usually helpful even if no specific stone is observed. It is extremely useful in following the progress of previously documented radiopaque calculi and checking the position of any indwelling double-J stents. The KUB radiograph can suggest the fluoroscopic appearance of a stone, which determines whether it can be targeted with extracorporeal shockwave lithotripsy (ESWL).

The KUB radiograph is also quite accurate for helping determine the exact size and shape of a visible radiopaque stone and sometimes is more accurate than CT in this regard. Note that most stones will appear larger on KUB radiograph than on CT, with CT-based measurement of maximum stone dimension approximately 12% smaller than a corresponding KUB-based measurement. ^[28]

Many calcifications observed on the KUB radiograph are phleboliths, vascular calcifications, calcified lymph nodes, appendicoliths, granulomas, various calcified masses, or even bowel contents. All can be confused with urinary tract calculi.

The insoluble radiopaque carrier for osmotically controlled-release oral system (OROS) pharmaceuticals can sometimes be mistaken for urinary calculi on KUB radiographs.

Differentiation between a phlebolith and an obstructing calcific stone becomes easier when the KUB radiograph demonstrates a lucent center, identifying the calcification as a phlebolith. This central lucency may not be observed as often on CT scans. For these reasons, many urologists recommend the flat plate radiograph in addition to CT scan for any renal colic–type scenario.

A number of studies have suggested that the flat plate has a relatively low sensitivity (40-50%) and specificity for renal and ureteral calculi. Many patients have numerous pelvic calcifications that make pinpointing specific stones difficult. Any calcific density observed on a KUB radiograph that happens to overlie the course of the ureter is not guaranteed to be a stone.

A large clinical study from Johns Hopkins University by Jackman et al concluded that "plain abdominal radiograph is more sensitive than scout CT for detecting radiopaque nephrolithiasis. ^[29] Of the stones visible on plain abdominal radiograph, 51% were not seen on CT. To facilitate outpatient clinic follow-up of patients with calculi, plain abdominal radiographs should be performed."

Many urologists, including this author, recommend that in addition to other studies (eg, noncontrast helical or spiral CT scans), a KUB radiograph be obtained in all patients with a clinical presentation of acute flank pain suggestive of renal colic. Knowing the exact size and shape of a stone, its position, fluoroscopic appearance, surgical orientation, and relative radiolucency is an advantage.

In addition, the progress of the stone can be easily monitored with a follow-up KUB radiograph, which may prove helpful in determining the exact size and shape of the stone, in establishing a baseline for follow-up studies, and for visualization of the surgical orientation.

A reasonable practical compromise is to obtain a KUB film only in cases in which the stone is not visible on the digital CT scout radiograph.

Renal ultrasonography by itself is frequently adequate to determine the presence of a renal stone. The study is mainly used alone in pregnancy ^{[30, 21]} or in combination with plain abdominal radiography to determine hydronephrosis or ureteral dilation associated with an abnormal radiographic density believed to be a urinary tract calculus. A stone easily identified with renal ultrasonography but not visible on the plain radiograph may be a uric acid or cystine stone, which is potentially dissolvable with urinary alkalinization therapy.

For some stones, ultrasonography works quite well; however, it has been found to be less accurate than IVP or CT in diagnosis of ureteral stones, especially those in the distal ureter. Diagnostic criteria include direct visualization of the stone, hydroureter more than 6 mm in diameter, and perirenal urinoma suggesting calyceal rupture. ^[31]

In addition, ultrasonography is not reliable for small stones (ie, those smaller than 5 mm) and does not help in the evaluation of kidney function.

A urine-filled bladder provides an excellent acoustic window for ultrasound imaging; sonograms occasionally may demonstrate a stone at the ureterovesical junction that is not definitive on helical CT or IVP.

Ultrasonography requires no intravenous (IV) contrast and can easily detect any significant hydronephrosis, although this must be differentiated from ureteropelvic junction (UPJ) obstruction or an extrarenal pelvis. A large extrarenal pelvis or UPJ obstruction can easily be misread for hydronephrosis if ultrasonography alone is used.

Middleton et al reported perhaps the most successful use of ultrasonography for renal colic: a 91% stone detection rate. Most authors report rates of approximately 30%. The unusually high success rate achieved by Middleton et al is partly explained by the fact that a radiologist specializing in ultrasonography performed the studies, which typically required at least 15-20 minutes to complete. The success of diagnostic ultrasonography is very dependent on operator skill and experience, which is probably demonstrated by the unique setting of this study. ^[32]

Renal ultrasonography works best in the setting of relatively large stones within the renal pelvis or kidney and sometimes at the UPJ. Whether the stones are radiolucent or radio-opaque does not matter because an ultrasound image is based strictly on density, not on calcium content. Ultrasonography is a good way to monitor known stones after medical or surgical therapy if the stones are large enough to be detected by this modality and are in a suitable position.

Ultrasonography can also be used to check the abdomen for a possible abdominal aortic aneurysm (AAA) or cholelithiasis, which can sometimes be mistaken for acute renal colic. It is also useful in differentiating filling defects observed on contrast studies because stones are much more echogenic than tumors, clots, or tissue. It is the initial imaging modality of choice for pregnant patients with acute renal colic because it avoids all potentially hazardous ionizing radiation.

Ultrasonography relies on indirect visualization clues to identify stones. Differentiating an extrarenal pelvis from an obstructed one is sometimes difficult when using ultrasonography alone. Intermittent obstruction or mild hydronephrosis can be easily missed with ultrasonography, and, with the few exceptions mentioned above, it generally does not provide much information about most other disease processes capable of causing acute flank pain.

Sometimes, a KUB abdominal flat plate radiograph is used in addition to ultrasonography to help identify and monitor suspected stones, especially if renal dilation is detected. As with the KUB radiograph alone, any density detected along the expected course of the ureter is not guaranteed to be an actual stone within the collecting system.

The combination of renal ultrasonography with KUB radiography has been proposed as a reasonable initial evaluation protocol when a CT scan cannot be performed or is unavailable. When combined with KUB radiography, ultrasonography can quickly and inexpensively provide substantial information about the urinary tract without the risk of contrast nephrotoxicity or hypersensitivity. IVP is rarely used in most clinicial settings but is an option for patients for whom additional information is required for a diagnosis or for whom the etiology of the pain remains unclear.

The intrarenal resistive index, as measured on Doppler studies, has been proposed as one way to diagnose acute renal obstruction using ultrasound. Under normal conditions, renal vascular resistance is relatively low and renal blood flow is excellent throughout the cardiac cycle, with a reasonable flow continuing even during diastole. During conditions associated with increased vascular resistance (eg acute ureteric obstruction), the decrease in renal blood flow during diastole is proportionately of greater magnitude than that during systole.

The resistive index is calculated as peak systolic velocity minus end-diastolic velocity divided by peak systolic velocity. An elevated resistive index of 0.7 or more is considered indicative of an acute ureteral obstruction. A change in the resistive index between the affected and contralateral (healthy) kidney of 0.04 or more also suggests a ureteral obstruction. (The affected kidney has the higher resistive index value.)

This study may be particularly useful in pregnancy (when exposure to ionizing radiation must be minimized), severe contrast media allergy, and azotemia. For best results, measure the intrarenal resistive index during a pain attack but before any nonsteroidal anti-inflammatory drugs (NSAIDs) or other anti-inflammatory medications are administered.

However, the intrarenal resistive index does not identify partial or intermittent obstructions and is less helpful in the early phase of even complete ureteral blockage. It also does not provide any information about the radiolucency, size, shape, or position of any stone and cannot be used to differentiate between intrinsic and extrinsic urinary obstructions.

Pyelosinus extravasation or fornix rupture, which occurs in up to 20% of patients with acute ureteral obstructions, leads to a loss of dilation and may be responsible for false-negative findings from studies. Other nonobstructive renal problems, such as renal failure, diabetic nephropathy, and renal compression, can affect the readings.

Considering that up to perhaps 35% of patients with documented acute ureteral obstruction do not demonstrate any significant hydroureteronephrosis, the use of a noninvasive study such as Doppler ultrasonography and intrarenal resistive index, which does not depend on visual ureteral or renal pelvic dilation, may eventually prove very useful. For now, additional studies on this technique are needed before the intrarenal resistive index can be reliably used for diagnosing acute renal colic and ureteric obstruction.

Future studies may utilize 2-dimensional ultrasonography in combination with color Doppler analysis of the ureteral jets to enhance sensitivity of ultrasonography in patients with ureteral colic. ^[33]

Before the advent of helical CT, IVP, also known as intravenous urography (IVU), was the test of choice in diagnosing ureterolithiasis. IVP is widely available and fairly inexpensive but less sensitive than noncontrast helical CT. CT scanning with delayed contrast series and thin slices has reduced the need for IVP in the evaluation of problematic ureteral stones. European Association of Urology guidelines recommend non-contrast CT to confirm the diagnosis in patients with acute flank pain, as it is superior to IVP. ^[1]

The main advantage of IVP is the clear outline of the entire urinary system that it provides, making visualization of even mild hydronephrosis relatively easy. IVP is helpful in identifying the specific problematic stone among numerous pelvic calcifications, as well as in demonstrating renal function and establishing that the other kidney is functional. These determinations are particularly helpful if the degree of hydronephrosis is mild and the noncontrast CT scan findings are not definitive. IVP can also show nonopaque stones as filling defects.

Disadvantages include the need for IV contrast material, which may provoke an allergic response or renal failure, and the need for multiple delayed films, which can take up to 6 hours. Obtaining the IVP is also a relative labor-intensive process. In addition, IVP may fail to reveal alternative pathology if a stone is not discovered, delaying the final diagnosis. False-negative results usually occur with stones located at the ureterovesical junction.

The dose of IV contrast is usually about 1 mL/kg. Bolus administration is usually recommended for renal colic evaluations because it allows for a nephrogram-effect phase film. This normally occurs within the first minute after bolus contrast injection and cannot be obtained with slow-drip infusion.

Acute ureteral obstruction causes an intense persistent finding on nephrograms. This may take several hours or more to fully visualize, which necessarily delays completion of the study. The so-called delayed nephrogram on IVP is one of the hallmark signs of acute urinary tract obstruction. The relative delay in penetration of IV contrast passing through an obstructed kidney elicits this sign. The kidney appears to develop a whitish color, and contrast appearance within the collecting system of the affected renal unit is significantly delayed.

KUB radiographs are obtained immediately before contrast administration and at 1, 5, 10, and 15 minutes afterwards or until visible contrast material fills both ureters (see the image below). Prone films are sometimes obtained to enhance visualization of the ureters. When the bladder is full of contrast and the distal ureters contain sufficient contrast for visualization, the patient is asked to void; then a postvoid film is taken. Sometimes, oblique views are needed when bone or bowel contents overlie the area of interest.

Look for direct visualization of stone within the ureter, unilateral ureteral dilation, delayed appearance of the nephrogram phase, lack of normal peristalsis pattern of the ureter, or perirenal contrast extravasation. Degree of obstruction is graded based on delay in appearance of the nephrogram.

Typically, an IVP positive for a ureteral stone is one that shows a delayed nephrogram effect and columnization. The ureter is peristaltic, so the entire ureter is not usually visualized on a single film except when an obstruction is present, such as from a stone. Even without observing any specific stone, the presence of a nephrogram effect in one kidney with normal function of the opposite kidney is highly suggestive, but not diagnostic, of ureteral obstruction.

Extravasation of contrast around the collecting system may be a sign of a ruptured fornix, while pyelolymphatic backflow indicates that contrast has entered into the renal lymphatic drainage system. Both are considered signs of a more severe ureteric obstruction.

However, no published study has indicated that the clinical course, treatment outcome, or residual renal damage is altered in any way in these patients. In fact, this information about the radiological assessment of the relative severity of the obstruction rarely affects clinical treatment decisions, except perhaps in persons with solitary kidneys.

Contrast-induced nephropathy

Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure. A serum creatinine level of more than 2 mg/dL is a relative contraindication to the use of IV contrast agents. Patients with azotemia, multiple myeloma, pregnancy, or diabetes, especially if dehydrated, are particularly susceptible to acute CIN (25% or greater increase in serum creatinine within 2-3 days of IV contrast exposure). Ischemia, direct intracellular high–contrast-concentration toxicity, and free-radical injury are thought to be the causative mechanisms of CIN.

Low osmolarity or iso-osmolar contrast may help to reduce the risk of CIN. The renal vasodilator fenoldopam mesylate has been used to minimize renal complications in higher-risk patients requiring IV contrast studies who would otherwise be at high risk for azotemia. Fenoldopam is a dopamine type 1A agonist that has been shown to increase renal plasma flow and to help prevent contrast nephropathy.

Theophylline and N-acetylcysteine have also been used with some success, but the standard prophylactic therapy is IV saline at a rate of 1-3 mL/kg/h. Hemodialysis before and after IV contrast can also be used to minimize renal toxicity, but such a regimen is costly and too cumbersome for general use except in special high-risk situations.

A randomized study by Merten et al comparing standard IV saline hydration prophylaxis with a 154-mEq/L sodium bicarbonate solution found a substantial benefit with the latter. ^[34] Patients treated with saline were 8 times more likely to develop nephropathy after contrast exposure than those treated with sodium bicarbonate. Such a treatment plan is practical, inexpensive, simple, safe, and effective, and the author now recommend IV sodium bicarbonate hydration as the method of choice for prevention of CIN. ^[34]

Anaphylaxis to ionic contrast agents occurs in 1-2 patients per 1000 IVP studies. Risk of recurrence is approximately 15% if reexposed to ionic agents but falls to 5% when nonionic agents are used. Risk of anaphylaxis can be reduced further by pretreatment with a combination of H1- and H2-blockers and steroids, but studies showing the benefit of pretreatment began pretreatment more than 12 hours prior to study.

Nonionic contrast media is more expensive but less likely to provoke an allergic response than the older ionic media, especially if the patient has a history of mild or moderate allergic reactions to contrast or injected dye. Risk of nephrotoxicity is not clearly reduced with use of nonionic agents. Indications for use of nonionic contrast agents vary among institutions but consistently include history of prior mild to moderately severe reaction to ionic contrast, asthma, multiple allergies, or severe cardiac disease.

Many institutions currently use only nonionic agents for all IV contrast studies, despite the added cost, because of the increased safety. Glucophage should be discontinued at least 1 day before any IV contrast study, particularly in patients with proven or borderline azotemia, because of the risk of worsening renal function and the rare development of potentially life-threatening lactic acidosis. It can be resumed 48 hours after the contrast study if renal function has normalized.

Medullary sponge kidney

Medullary sponge kidney (MSK), also called tubular or ductal ectasia or cystic dilation of the collecting ducts, is a generally benign congenital condition that demonstrates dilation of the distal renal collecting tubules on IVP as the tubules fill with contrast. These normally invisible microscopic tubules show a whitish blush in the papilla in persons with MSK. In severe cases, stones, cysts, and diverticula can be present. The condition can be unilateral, or even limited to one calyceal system, but it is bilateral in 70% of patients. It is not usually discovered until the second or third decade of life, even though MSK is congenital.

MSK is the most common anatomical problem found in calcium nephrolithiasis patients, affecting approximately 2% overall. Most stones in patients who have MSK are composed of calcium oxalate with or without calcium phosphate. Stones tend to be small and are usually passed spontaneously.

In most cases, MSK is not hereditary, although rare autosomal inherited forms have been described. The exact cause is unknown, but it could be caused by tubular obstruction due to calcium oxalate calculi from infantile hypercalciuria or collecting duct dilation from blockage by fetal uric acid stones, embryonal remnants, or other material.

The most accurate way to demonstrate MSK is to employ high-quality excretory urography (ie, IVP) with serial renal tomography starting just before the injection of the contrast media and continuing every 4 minutes for the next 20 minutes.

Most patients with MSK are asymptomatic; unless they have an IVP for an unrelated reason, the condition may never be diagnosed. Of patients who are symptomatic, renal colic and calcium urinary stones are the most common problems. (UTIs and hematuria are the others.) Women are more likely to have MSK than men.

Some patients with MSK may report severe chronic renal pain without any evidence of infection, stones, or obstruction. The etiology of this pain is unclear. These patients may be treated best by physicians comfortable with the management of chronic pain disorders, although recent reports suggest that ureteroscopic laser papillotomy may provide temporary relief. ^[35]

Long-term management of MSK, as in any frequent stone former, is aimed toward identifying metabolic risk factors for continuing stone formation, with serum and 24-hour urine testing. The most common metabolic problems in MSK are hypercalciuria and hypocitraturia.

At most institutions that offer this examination, CT scanning has replaced IVP, the historic criterion standard, for the assessment of urinary tract stone disease, especially for acute renal colic. CT scans are readily available in most hospitals and can be performed and read in just a few minutes. Numerous studies have demonstrated that CT has a sensitivity of 95-100% and superior specificity and accuracy when compared with IVP. ^[31]

A renal colic study consists of a noncontrast or unenhanced CT scan of the abdomen and pelvis, including very narrow cuts taken through the kidneys and bladder areas, where symptomatic stones are most likely to be encountered.

Technically, a relatively high pitch of more than 1.5 with thin collimation of 2-3 mm is generally considered a good compromise between imaging quality and radiation dosage. No rectal, oral, or IV contrast is used, because contrast material obscures any calcium-containing stones; both the stone and the contrast material would appear bright on the scans. Optimally, the patient’s bladder is filled, which facilitates viewing the ureterovesical junction (see the image below).

In equivocal cases in which an indeterminate calcification is found along the course of the ureter or an abrupt change in ureteral caliber is found without a conclusively identified stone, an overlapping retrospective series can be performed to better evaluate this specific area and eliminate any sampling error.

An abdominal flat plate or KUB radiograph is sometimes automatically included in a renal colic study, depending on the institution and the preferences of the medical staff.

Advantages of CT scanning include the following:

• It can reveal other pathology (eg, abdominal aortic aneurysms, appendicitis, pancreatitis, cholecystis, ovarian disorders, diverticular disease, renal carcinoma). ^[36] If the patient’s true underlying pathology is something other than a kidney stone, the CT scan is more clinically useful than an IVP for examining the possibilities.

• It can be performed quickly (< 5 min acquisition time)

• It avoids the use of IV contrast materials.

• The density of the stone can assist in predicting stone composition and response to shockwave lithotripsy.

Disadvantages of CT scanning include the following:

• It cannot be used to assess individual kidney function or degree of obstruction.

• It can fail to reveal some unusual radiolucent stones, such as those caused by indinavir and atazanavir, which are typically invisible on the CT scan (though some serve as a nidus for deposition of calcium oxalate or calcium phosphate deposition and thus become radiopaque). Because of this possibility, IVP with contrast should be used for patients taking indinavir or atazanavir. Sulfadiazine stones are also difficult to visualize on CT because of relatively low attenuation. ^[37]

• It is relatively expensive.

• It exposes the patient to a relatively high radiation dose (and thus should not be performed on pregnant women).

• Precise identification of small distal stones is occasionally difficult.

• Although CT scans can be used to estimate the overall size, width, and location of a stone, they can only approximate its shape. ^[38] Stone location can be described in anatomical terms, but the CT scan lacks the surgical orientation that most urologists prefer.

• It is not suitable for tracking the progress of the stone over time, supporting the recommendation for KUB radiography along with the CT scan.

If a KUB or flat plate radiograph is performed at the same time as the CT scan, some of the above objections and problems disappear. However, obtaining the extra films involves some additional delay, the patient is exposed to more ionizing radiation, and the total cost for the workup increases.

The "scout" reconstruction of the CT scan, formatted to look like a plain radiograph, is a reasonable substitute for a formal KUB radiograph in some cases. Stones 3 mm and larger can be observed routinely on these studies. If the findings from a noncontrast CT scan are positive for a stone and the findings from the scout CT radiograph are negative, a separate KUB radiograph should be performed.

A digital scout CT radiograph is not nearly as sensitive as a good plain radiograph in detecting calculi; however, if the stone is visible on the "scout" reconstruction, only plain radiography may be needed later to determine if the stone has moved or passed.

Stone size as measured on CT KUB correlates poorly with actual size of the stone measured after spontaneous passage. ^[39] This has dictated the need for caution in counseling patients on the likelihood of spontaneous stone passage when stone size is determined using CT-based measurement. However, software programs have now been developed for estimating stone volume, which has proved more accurate than linear stone dimensions for predicting spontaneous passage, especially with larger and/or more proximal stones. ^[40] Software has also been developed that estimates stone volume and the expected duration of lithotripsy on the basis of non-enhanced-CT scans. ^[41]

Differentiation of phleboliths from urinary tract stones

Phleboliths are often confused with calcific ureteral stones. On a KUB radiograph, the characteristic lucent center of a phlebolith is often visible; this is not present in a true calculus. Unfortunately, CT scans usually fail to reveal this central lucency or a bifid peak if a central lucency cannot be identified. Why this finding of a central transparency is so uncommon with CT scanning is unclear, but it may involve the orientation of the veins that form the phleboliths.

The "rim sign," originally reported by Smith in 1995, is described as a rim, ring, or halo of soft tissue visible on CT scans that completely surrounds ureteral stones. ^[34] The effect is enhanced by the local inflammation a stone produces in the ureteral wall, with subsequent edema at the site of the calculus. The rim sign is generally missing or incomplete with phleboliths.

While not absolutely definitive, the rim sign is strong evidence that the calcific density it surrounds is a stone and not a phlebolith. In several studies, more than 75% of all ureteral stones demonstrated a rim sign, while only 2-8% of phleboliths demonstrated it. The rim sign is more likely to be present in small or medium stones up to 5 mm in diameter. Larger stones (>6 mm) tend to lose the rim sign, presumably from stretching and thinning of the ureteral wall around a relatively large calculus.

Another way to differentiate a phlebolith from a calculus is to find a comet’s tail or comet sign, which is the noncalcified portion of a pelvic vein that is contiguous with the phlebolith. It appears as a small linear area of soft tissue that seems to pass obliquely through the CT scan section and attaches to the calcific density at one end. This is not observed in ureteral stones, although a ureter can mimic this sign to some degree. The comet sign is found in less than 20% of phleboliths, so its absence helps little, and its reliability is still unproved.

Estimation of stone density, composition, and size

Currently, CT scans can be used to estimate the relative stone density and composition to some extent, although the results have not replaced the formal stone chemical composition analysis. However, this information can still help to plan therapy. Low-density stones are more amenable to shockwave lithotripsy, whereas higher-density stones may require ureteroscopy.

For example, a lucent stone that is not visible on the KUB radiograph that is clearly visible on the CT scan may indicate a uric acid calculus. This suggests a different diagnosis and therapy (urinary alkalinization) than for a calcium stone. For these reasons, many institutions routinely perform KUB radiography whenever renal colic noncontrast CT scanning is performed.

The Hounsfield unit density of the calculus on CT scanning can also be useful in predicting whether the stone is composed of uric acid. In a study of the unenhanced CT scans of 129 patients with renal stones, researchers from the University of Wisconsin concluded that the peak Hounsfield attenuation level of a kidney stone, used either by itself or divided by the size of the calculus in millimeters, may be a useful indicator of the stone’s chemical composition.

An attenuation-to-size ratio of 80 or greater was found to be highly suggestive of calcium oxalate stone material, especially in larger calculi. Uric acid stones have relatively low peak attenuation levels, and their attenuation-to-size ratios were generally below 80. In this Wisconsin study, uric acid stones averaged a mean peak Hounsfield reading of 344 HU, while the mean for calcium oxalate calculi was 652 HU.

Calculating the peak attenuation level and attenuation-to-size ratio adds no financial cost, patient morbidity, or time delay. While this study and similar reports are interesting and suggestive, the precise clinical role of CT scans in predicting stone fragility and chemical composition remains unclear.

Secondary signs of obstruction

Secondary signs of obstruction may be visible only on CT scans. In some cases, if a stone was passed shortly before the study, these signs may be the only evidence that the patient has or ever had a stone. These secondary signs include ureteral dilation with hydronephrosis, renal enlargement from interstitial edema (nephromegaly), and inflammatory changes, such as stranding or streaking in the perinephric fatty tissue.

In a 1996 study of 54 ureteral stone patients reported by Katz et al, hydronephrosis was present in 69%, proximal ureteral dilation was found in 67%, and perinephric stranding was detected in 65%. The other secondary signs had a similar frequency in adults and children. In the study, only 2 of the patients with ureteral calculi did not demonstrate any of the secondary signs of obstruction. The other secondary signs had a similar frequency in adults and children. ^[42]

A similar 1996 study by Smith et al involving 220 patients found an even higher correlation between these secondary signs of obstruction and the presence of a ureteral calculus. In particular, the combination of collecting system dilation and perinephric stranding had a positive predictive value of 98%, while the absence of both of these secondary signs had a negative predictive value of 91%. ^[43]

However, perinephric stranding was found less often in children with ureteral calculi than in adults in a 2001 study by Smergel and associates; therefore, this secondary sign, at least in the pediatric population, may be less reliable. ^[44]

An additional secondary sign of acute renal obstruction on noncontrast CT scans has been reported by investigators from Johns Hopkins University. This sign is defined as a reduction in renal parenchymal attenuation (radiologic density) on the nonenhanced CT scan of the acutely obstructed renal unit compared with the normal unobstructed contralateral kidney. The difference in density is at least 2 standard deviations. This sign was identified in 95% of patients with acute ureteral obstruction, which suggests it is a reliable indicator.

Rarely, in indeterminate cases in which the secondary signs are negative and a stone is strongly suspected clinically but not clearly visible on the unenhanced CT scan, IV contrast can be used to help visualize the ureter. Repeat scanning after contrast infusion allows for improved visualization of the ureters. This allows physicians to make direct comparisons with the earlier studies to help make the correct diagnosis. Flat abdominal radiograph films taken after the contrast provide information similar to IVP, but delayed films or scans are likely to be needed.

Current recommendations

In current clinical practice, the renal colic noncontrast CT scan is the standard of care in most EDs when a patient is thought to have renal colic or presents with acute flank pain. Guidelines from the American College of Radiology (ACR) recommend noncontrast CT as the most appropriate radiologic procedure for both suspected stone disease and recurrent symptoms of stone disease. Reduced-dose techniques are preferred. ^[45]

Because of the limitations of CT scans, some urologists request additional studies, such as KUB radiography or IVP, to help them make critical decisions about management, follow-up, and possible surgical interventions. In cases of suspected stone disease in pregnant patients and in patients allergic to iodinated contrast or when noncontrast CT is unavailable, the ACR considers ultrasonography of the kidney and bladder retroperitoneal with Doppler and KUB the preferred examination. ^[45]

As noted earlier, obtaining a KUB radiograph when a renal colic CT scan study is performed for acute flank pain provides more precise information about the size and shape of any stone and quickly reveals whether stones are nonopaque and radiolucent. Follow-up evaluations are easier because only a repeat KUB radiograph is needed for comparison. A KUB radiograph also helps the urologist determine if a stone will be visible on fluoroscopic images, which is useful for possible shockwave lithotripsy since for most lithotripters used in the United States, fluoroscopic visualization is needed for stone targeting and positioning.

While the addition of an abdominal flat plate study (KUB radiograph) adds to the overall financial cost and requires additional time, the extra information the study provides is often quite valuable and ultimately beneficial to the patient. If the stone is visible on the CT scout image, however, then this provides the same information as a KUB and thus the latter is not needed.

Comparison of CT with IVP

CT has largely supplanted IVP in a number of settings. However, a comparison of the pros and cons of the two modalities suggests IVP retains some advantages (see Table, below).

Table. Intravenous Pyelography Versus CT Scanning: Which Is Better? (Open Table in a new window)

The noncontrast or renal colic-type CT scan is good for the initial diagnosis of a stone, especially in unusual or atypical cases or when patients are unable to tolerate intravenous contrast because of allergy or azotemia. Without definite hydronephrosis, a CT scan may not be able to isolate a specific stone, although secondary signs, such as perinephric streaking and nephromegaly, may be present.

The CT scan can be performed quickly in most institutions, even with an additional KUB radiograph, but it usually costs more than the IVP. In one series of 397 consecutive emergency urolithiasis patients from several university centers, the average fee for a CT scan was $1407, compared with $445 for an IVP.

CT scans are generally preferred by most ED physicians for the initial evaluation of patients with acute flank pain, except for HIV-positive patients who may be on protease inhibitors, who require an IVP, and pregnant women, who require ultrasonography for their initial imaging modality.

The IVP is better for clearly outlining the entire urinary tract and determining relative renal function. This test clearly shows stones causing blockage, whether the stones are radiolucent or opaque. While an IVP can reliably help in the diagnosis of an MSK, the clinical importance of this diagnosis is limited. The IVP is sometimes preferred by urologists in certain situations because of its better orientation and superior value in predicting possible stone passage, although these advantages are mostly negated if a KUB radiograph routinely accompanies the CT scan.

Plain renal tomography requires moving the radiograph projector and film in such a way that a zone of photographic clarity is positioned at the stationary focus point of the radiograph beam. All other overlying material is eliminated. The focal point is adjusted along the anteroposterior axis a distance of 1 cm, and the radiograph procedure is repeated. Usually, a series of 4-6 films is needed to completely image both kidneys. If such a series of films is needed, it should be obtained before any IV contrast is administered; contrast obscures any stones present.

Although largely replaced by CT scanning without contrast, plain renal tomography has some uses and advantages. It does not require extensive preparation and can be performed quickly. In addition, the cost and radiation dosage to the patient are less than with CT scanning.

Plain renal tomography can be useful for monitoring a difficult-to-observe stone after therapy. Observing even a relatively large radiopaque stone located in the kidney or renal pelvis on a standard abdominal flat plate radiograph can be difficult or impossible if the patient has abundant gas or stool overlying the area, and plain renal tomography can often overcome this difficulty.

Plain renal tomography may be helpful for clarification of stones not clearly detected or identified with other studies (eg, differentiating intrarenal calcifications that are likely to be stones from extrarenal opacities that are clearly not renal calculi). It is often helpful in finding small stones in the kidneys, especially in patients who are large or obese whose bowel contents complicate observation of any renal calcifications.

Plain renal tomography is also useful for determining the number of stones present in the kidneys before a stone-prevention program is instituted. This information is used to better differentiate stones formed before therapy began from those formed later.

The most precise imaging method for determining the anatomy of the ureter and renal pelvis and for making a definitive diagnosis of any ureteral calculus is not IVP or renal colic CT scanning but retrograde pyelography.

In this study, the patient is taken to the operating room (OR) cystoscopy suite, and an endoscopic examination is performed with the patient under anesthesia. After a cystoscope is placed in the bladder, a thin ureteral catheter is inserted into the ureteral orifice on the affected side. A radiographic picture is taken while contrast material is injected through the ureteral catheter directly into the ureter. Any stone, even if radiolucent, and any ureteral kinks, strictures, or tortuousities that may not be visualized easily on other studies become clearly visible.

Urologists perform retrograde pyelograms when a precise diagnosis cannot be made by other means or when a need clearly exists for an endoscopic surgical procedure and the exact anatomical characteristics of the ureter must be clarified.

Retrograde pyelograms are rarely performed merely for diagnostic purposes, because other less invasive studies are usually sufficient. They are considered essential when surgery is deemed necessary because of uncontrollable pain, severe urinary infection or urosepsis with a blocked kidney, a solitary obstructed kidney, a stone that is considered unlikely to pass spontaneously because of its large size (generally ≥8 mm), or the presence of possible anatomical abnormalities (eg, ureteral strictures).

Retrograde pyelograms can be performed safely both in patients highly allergic to IV contrast media and in patients with renal failure because the contrast medium never enters the bloodstream and therefore requires no renal filtration or excretion and causes no anaphylaxis.

A nuclear renal scan can be used to objectively measure differential renal function, especially in a dilated system for which the degree of obstruction is in question. This is also a reasonable study in pregnant patients, in whom radiation exposure must be limited.

The intravenously injected radioisotope is eliminated via the nephron, with the rate of clearance from the renal unit providing an excellent estimate of the glomerular filtration rate and the relative rate of drainage or clearing from each kidney. A drainage half-time that is 20 minutes or longer indicates obstruction, while a drainage half-time of 10 minutes or less is considered unobstructed. If the drainage half-time is 10-20 minutes, the result is indeterminate.

Magnetic resonance imaging (MRI) has virtually no role in the current evaluation of acute renal colic in the typical patient. Direct detection of most stones is not possible with MRI, and MRI should not be used for that purpose in most instances. MRIs are generally more expensive than other studies, such as CT scans, which reveal stones much better.

On the other hand, MRI produces no dangerous radiation, the gadolinium contrast it uses has minimal nephrotoxicity, and it can readily reveal urinary obstruction even if the stones themselves are not easily visualized. These attributes make using MRI reasonable in selected cases in which other technologies are too toxic or potentially dangerous, such as in some children and in pregnant women (see below). Gadolinium contrast, however, is contraindicated if the estimated glomerular filtration rate is less than 30, owing to the risk of nephrogenic systemic fibrosis.

Use of MRI in pregnant patients is somewhat controversial. Long-term effects on the fetus are unknown, and MRI is not specifically indicated in pregnancy, although it is not specifically contraindicated either. Anecdotal reports suggest that MRI has no immediately detectable deleterious effects. When other imaging modalities cannot be used or are insufficient, magnetic resonance urographic imaging can be considered on a case-by-case basis when the benefits to the mother and fetus outweigh the potential risks.

Although MRI does not play a major role in the diagnosis of ureteral stones, it can be used for this purpose. One study of 40 consecutive patients with acute flank pain found sensitivity of 54-58% and specificity of 100% using breath-hold heavily T2-weighted sequences. ^[46] Sensitivity and specificity increased to 96.2-100% and 100%, respectively, using gadolinium-enhanced 3-D FLASH MR urography. Its lack of radiation makes MRI a good choice in this setting for pregnant women who have nondiagnostic findings from a sonogram.