A diagnosis of nephrolithiasis may be suspected based on the clinical history, physical exam findings, and laboratory test results, and is confirmed with imaging studies.
Obstructed renal and ureteric stones can cause renal colic: severe, acute flank pain that may radiate to the ipsilateral groin, commonly associated with nausea and vomiting. Rarely, this is accompanied by macroscopic hematuria. As stones pass and get lodged in the distal ureter or intramural tunnel, this can lead to bladder irritation manifested as urinary frequency or urgency. Ipsilateral testicular and groin pain may occur rarely in men with obstructive stones. However, in the absence of obstruction, calculi may be asymptomatic.
In patients with renal colic, costovertebral angle and ipsilateral flank tenderness may be pronounced. Signs of sepsis, including fever, tachycardia, and hypotension, might indicate an obstructing stone with infection, warranting urgent urology referral.
Initial laboratory tests in all patients with suspected nephrolithiasis are urinalysis, CBC, and serum chemistry to include electrolytes, BUN/creatinine (to assess renal function), calcium, phosphorus, and uric acid. Urinalysis is helpful in confirming a diagnosis of renal stones as microscopic hematuria is present in the majority of patients. However, the absence of hematuria does not exclude nephrolithiasis.  Presence of more than 5 to 10 WBCs per high-powered field in urine or pyuria could indicate presence of urinary tract infection or be secondary to inflammation. Urinary crystals of calcium oxalate, uric acid, or cystine may indicate the nature of the calculus, although only cystine crystals are pathognomonic for the underlying type of stones. 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 5.5 suggests uric acid stones.
An elevated WBC count may indicate infection (pyelonephritis or urinary tract infection). Hypercalcemia may suggest hyperparathyroidism as an underlying etiology; hyperuricemia may indicate gout. In women of childbearing age, a pregnancy test should be done prior to imaging with ionizing radiation and to rule out ectopic pregnancy as a cause of symptoms.
Twenty-four-hour urine sampling is not always necessary in a first-time stone former without significant risk for recurrence. However, it is indicated in recurrent stone formers; those with bilateral or multiple stones, history of inflammatory bowel disease, chronic diarrhea, bowel surgery or malabsorption; those with primary hyperparathyroidism, gout or renal tubular acidosis, nephrocalcinosis or stones formed of cystine, uric acid or calcium phosphate; in children; and in interested first-time stone-formers. Basic measurements should include volume, pH, creatinine, calcium, sodium, oxalate, uric acid, and citrate. Analysis of stone composition provides information on chemical composition and etiology. Stones are analyzed after they are extracted during surgery or when patients expel and collect them for analysis. A urine screen for cystine, if the diagnosis of cystinuria is not excluded by stone analysis, should be considered. Serum parathyroid hormone is only measured in cases of high or high-normal serum calcium results.
If there is suspicion for nephrolithiasis based on the history, physical exam, and laboratory tests, then imaging is indicated.
Noncontrast helical computed tomography (NCCT) scan is the preferred imaging modality due to its high sensitivity and specificity. Computed tomography (CT) accurately determines presence, size, and location of stones; if it is negative, nephrolithiasis can be ruled out with high likelihood. A low-dose noncontrast CT (<4 mSv) is preferred for patients with a body mass index (BMI) ≤30 kg/m², as this limits the potential radiation exposure while maintaining both sensitivity and specificity at 90% or higher.  However, low-dose CT is not recommended for those with a BMI >30 kg/m², owing to lower sensitivity and specificity in these patients. Patients with indinavir and ritonavir stones from anti-HIV medication may have radiolucent stones on CT scan. However, this makes up only a tiny fraction of patients. CT scans are also used when patients with known stones have new onset of renal colic because stones commonly change location or new ones are formed. However, there is a risk of significant radiation exposure with repeated CT scans, and a physician should use his or her judgment.
Plain abdominal radiography (KUB) can determine whether stones are radiopaque and can be used to monitor disease activity. Calcium oxalate and calcium phosphate stones are radiopaque, whereas pure uric acid and indinavir stones are radiolucent and cystine stones are partially radiolucent. The KUB radiograph can suggest the fluoroscopic appearance of a stone, which determines whether it can be targeted with extracorporeal shock wave lithotripsy (ESWL).
Renal ultrasound can be used to diagnose renal stones, particularly in pregnancy or other situations where avoiding radiation exposure is advised, although it can be operator dependent and has low sensitivity for diagnosing mid and distal ureteric stones. The combination of renal ultrasonography with KUB has been proposed as a reasonable initial evaluation protocol when a CT scan cannot be performed or is unavailable. For a known stone-former who has previously had radiopaque stones, it has been suggested that a combination of renal ultrasonography and KUB are a viable option for follow-up imaging; sensitivities of 58% to 100% and specificities of 37% to 100% have been reported for this combination of modalities.   
Renal ultrasound and CT have been investigated for their safety and efficacy as an initial diagnostic test for patients who present to the emergency department with suspected nephrolithiasis. The results of a large, multicenter study showed no significant difference in high-risk diagnoses, serious adverse events, subsequent emergency room visits, or hospitalizations in those undergoing CT or renal ultrasound in this setting. However, some patients who had an ultrasound did go on to need CT imaging, but it is not clear from this study what factors predicted the need for CT. Further study in this regard would help determine in which patients to use renal ultrasound as an initial diagnostic tool. 
An intravenous pyelogram (IVP) can provide both anatomic and functional information on stones and the urinary tract and, before NCCT, was the traditional imaging modality. However, IVP is now less commonly used due to the improved sensitivity of CT scans. Disadvantages include the need for intravenous contrast material, which may provoke an allergic response or renal failure, and the need for multiple delayed films in certain cases and concerns for radiation exposure.
Renal ultrasound is the first-line imaging modality for pregnant patients. For pregnant patients when renal ultrasound is nondiagnostic, transvaginal ultrasound can assist with diagnosis by determining if ureteral dilation extends beyond the pelvic brim; it can also diagnose stones in the distal ureter. Magnetic resonance imaging (MRI), which confers no radiation to the patient, is a second-line imaging modality because stones are not directly visible on MRI and only seen as a filling defect in the collecting system. Radiation doses of <50 mGy have not been associated with increased risk of fetal anomalies or loss; therefore, low-dose protocol CT (<4 mGy) can be used as a last-line option in pregnant women after the first trimester to aid in difficult-to-diagnose cases.   
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