Continuing Education Activity

Ureterolithiasis is a painful condition that affects millions of Americans each year. To avoid the high morbidity and mortality associated with this condition, it must be promptly diagnosed and treated. This activity reviews the evaluation and treatment of ureterolithiasis and highlights the role of the interprofessional team in evaluating and treating patients with this condition. This article reviews the etiology, the typical history and physical of, evaluation, management, treatment, of nephrolithiasis.

Objectives:

• Identify the etiology of nephrolithiasis.
• Outline the appropriate evaluation of renal calculi.
• Summarize the differential diagnoses for nephro/ureterolithiasis.
• Describe the complications of nephro/ureterolithiasis.

Introduction

Ureterolithiasis is a worldwide disease that affects millions of people and places a large financial burden. Thus, this disease places a significant burden on the healthcare system. There is also an increasing incidence and prevalence of this disease. Moreover, there is upcoming evidence that nephrolithiasis is associated with other systemic diseases, specifically cardiovascular disease, diabetes mellitus, and obesity.[1] 

This condition is often very painful, presents suddenly without warning, and symptoms require many days to resolve. Usually, the course of this condition is benign, but sometimes it may require urological intervention and hospitalization. Urosepsis, renal abscess, infected stones, chronic kidney disease (CKD), obstruction, ureteral scarring, and stenosis are all complications of ureterolithiasis. This article will discuss the etiology, epidemiology, pathophysiology, evaluation, treatment, and management of ureterolithiasis.

Etiology

Often the etiology of a patient's kidney stone is unknown. Unless a patient passes a stone, is able to retrieve the stone, and sends it for analysis, the components of the stone usually remain unknown. In the past, there have been many theories as to what increases a patient's risk to form a stone. It used to be thought that dietary calcium contributed to the formation of renal calculi; however,  studies now prove this to be untrue.

Studies show the relative risk is lower with higher dietary calcium intake compared to lower dietary calcium intake. Another etiology of renal calculi in a minority of patients have inherited forms such as cystine based stones. 

Epidemiology

Many Americans in their lifetime will, at some point, experience the painful condition known as nephrolithiasis. This condition affects about 1 in 11 in the U.S.A.[2] Studies estimate the prevalence of renal calculi in the United States of America to be 10.6% for men and 7.1% for women. Furthermore, the prevalence is expected to be rising as well. There is also a difference in prevalence among different racial groups. In descending order of prevalence of racial groups, it is White/nonhispanic, Hispanic, and Black. Moreover, nephrolithiasis is generally diagnosed in patients in their 40s.

Based on a cohort study, the average age of diagnosis for symptomatic nephrolithiasis is 44.8 years in men and 40.9 years in women. Interestingly enough, the geographic location appears to affect the prevalence of this condition. Based on a Cancer Prevention Study, both men and women had a higher prevalence of nephrolithiasis in the southernmost latitude compared to the northernmost latitude.[1] Furthermore, it appears that those who experience renal stones are more likely to have a reoccurrence. For example, a cohort study from 1984 to 2003 researched the risk of stone recurrence to be 11% at year 2, 20% at year 5, and 39% at year 15.[3] 

Pathophysiology

Urine composition predicts stone composition. Renal calculi can form when the urine composition has higher concentrations of calcium, and/or oxalate, and/or uric acid. Hypercalcinuria results in calcium stones, hyperuricosuria results in uric acid stones, hyperoxaluria results in oxalate stones.[2] 

Calcium oxalate makes up 74% of all renal calculi types. Calcium phosphate makes up 20%, and uric acid makes up 4% of stone types. Cystine and magnesium ammonium phosphate (struvite) stones make up the rest of the stone types.  Usually, renal calculi are able to pass on their own. However, as the stone size increases to 7 mm and greater, they often do not pass without urologic intervention. Renal calculi 5 mm and smaller tend to pass on their own; however, since everyone's anatomy varies, some patients may be unable to pass what is considered a small stone. 

History and Physical

The typical presentation of nephrolithiasis is a patient in their 40s, possibly already with a history of renal calculi. Patients describe these episodes of pain as sudden, severe, colicky one-sided flank pain that may become constant as time progresses. They may have difficulty laying still and may be seen pacing around the room. The pain may wake up a patient in the middle of the night. Usually, the patient will remember the exact moment when symptoms began. The patient may experience nausea, vomiting, dysuria, gross hematuria, as well as urinary frequency.[2] 

The physical exam will often demonstrate a patient in moderate to severe distress, unable to stay still. Patients may be tachycardic, but unless septic, they will be afebrile and normotensive. The patients normally will have a normal abdominal exam. The patient may have costovertebral angle (CVA) tenderness on the side of the stone. Otherwise, the physical exam may be normal. Abdominal tenderness should raise concerns in a clinician as it can indicate another serious condition such as appendicitis, diverticulitis, small bowel obstruction (SBO) that may be occurring. Additionally, it is important to be aware of nonclassical symptoms of renal calculi such as low back pain, diarrhea, recurrent urinary tract infection, and isolate microscopic hematuria.[2]

Evaluation

The diagnosis of ureterolithiasis can usually be made by a thorough history and physical exam. Additional testing may be utilized to rule out serious complications of renal calculi such as an infected or obstructing stone, or pyelonephritis. Testing may be utilized to "rule out" ureterolithiasis mimics such as a renal abscess, mass, abdominal aortic aneurysm (AAA). However, the diagnosis may be aided by one or more of the following tests: complete blood count (CBC), basic metabolic panel (BMP), urinalysis, renal ultrasound, radiographs, and/or CT scan of the abdomen and pelvis. On urinalysis,  RBCs will often be present. However, when WBCs, leukocyte esterase, and/or bacteria are present, this may indicate a more serious condition specifically infected renal calculus. If possible, an evaluation of the stone composition may be performed in the outpatient or inpatient setting.

A 24-hour urine collection may be collected to evaluate urea, creatinine, uric acid, oxalate, citrate, calcium, phosphate, urine pH, urine volume, cultures. A comprehensive metabolic panel may be performed to check for renal function abnormalities, which may indicate an obstructing renal calculus. CT abdomen and pelvis without contrast imaging is the gold standard to diagnose ureterolithiasis and can characterize the size and location of the stone and thus its likelihood to pass on its own.

Treatment / Management

Ureterolithiasis management often involves the management of acute pain and medications to promote stone passage like tamsulosin. Tamsulosin is an alpha-adrenergic blocker. However, a double-blind placebo-controlled trial showed that tamsulosin did not show a statistically significant increase in stone passage compared to placebo.[4] Another study (prospective, randomized, double-blinded study) also supports this conclusion that tamsulosin did not improve stone passage at day 7.[5]

In addition to medication therapy, active interventions to remove a stone are required, especially in the setting of obstructing or large stones. Two main active interventions exist shockwave lithotripsy (SWL) or ureteroscopy (URS). In a meta-analysis comparing resolution rates for proximal stones with shock wave lithotripsy vs. ureteroscopy saw no statistical difference between the two. However, for distal stones, ureteroscopy was found to be superior to shock wave therapy.[6] 

Comparing procedure-related complication rates, shock wave therapy has a lower complication rate and shorter hospital lengths, compared to ureteroscopy. However, overall, shock wave therapy has lower stone-free rates compared to ureteroscopy.[7] Moreover, a meta-analysis of randomized controlled trial and prospective controlled studies showed that ureteroscopy lithotripsy with holmium laser was more efficient because it took less amount of time and was more successful compared to extracorporeal shock wave lithotripsy.[8]

Additionally, other factors besides stone location affect the efficacies of interventions. These include stone composition, density, and skin to stone distance. For example, shock wave therapy has a higher failure rate for higher density stones (>1000 HU)[9] or stones with a long skin to stone distance more than 10 cm.[10] For shock wave lithotripsy, stents do not appear to improve stone-free rates, decrease infection rates, and may affect the flow of stone fragments.[11] 

Staghorn renal calculi or infected stones usually require surgical intervention. In untreated staghorn calculi nephrectomy is needed in about half of all cases.[2]

Treatments to prevent stone formation target urinary abnormalities and include dietary changes and/or medication management. Specific treatments or dietary modifications depend on calculi composition. Studies show that increasing fluid intake and calcium intake decreases the reoccurrence of renal calculi. In a randomized controlled trial (RCT) that randomized 199 patients who form calcium oxalate stones into either a high fluid regimen with a goal of 2 liters of urine output or more vs. a control group, the 5 years recurrence rate were less than half compared to the control group. Some cohort studies show that certain beverages such as orange juice, coffee, tea, wine, beer are associated with decreased renal calculi formation. Other beverages that were high in sugar contact are associated with increased renal calculi formation. Beverages high in citrate are thought to decrease stone formation, but study results are mixed.[12]

Thiazide diuretics appear to be efficacious in reducing renal calculi formation, and this may not be limited to only the patients with hypercalciuria. In a meta-analysis study of 28 RCTs thiazides (RR 0.52), citrates (RR 0.25), and allopurinol (RR 0.59) reduced renal calculi reoccurrence.[13][14]

Also, a 2009 prospective study shows the DASH diet may be associated with a decreased stone risk.[15] Citrate therapy may also be considered. Three randomized studies showed reduced stone recurrence with citrate therapy. Also, for the treatment of oxalate stones, calcium 1200 mg/day may be considered as it binds oxalate in the intestines, thereby reducing urine oxalate.[16]

Reoccuring uric acid stones can be prevented with potassium citrate for urine alkalization as well as allopurinol.[17]

Cystinuria is an inherited disorder causing reoccurring kidney stones starting in childhood. The long term management includes increasing fluid intake and restricting sodium intake.[18] 

Differential Diagnosis

Sudden, colicky, flank pain, should not be assumed by the diagnostician to automatically be a renal calculus, even in a patient with a past medical history of nephrolithiasis. Other causes of this presentation must be considered to avoid missing another possibly life-threatening diagnosis. Other diagnoses that must be considered are a ruptured abdominal aortic aneurysm, renal cell carcinoma, pyelonephritis, pelvic inflammatory disease, small bowel obstruction, cholelithiasis, cholecystitis, diverticulitis, renal vein thrombosis. If a clinician misses or delays their diagnoses of a ruptured abdominal aortic aneurysm, which may present similarly to the classic presentation of nephrolithiasis, poor outcomes including death may occur. Thus it is prudent for a clinician to consider other causes to a patient's symptoms actively.

Prognosis

The prognosis for ureterolithiasis is generally favorable; however, there is evidence that it is associated with other systemic conditions such as diabetes, cardiovascular disease, and obesity. As mentioned above, reoccurrence rates are very high at an estimated 39% at 15 years. In patients with recurrent stones, it is prudent to do a full evaluation to try to identify the etiology; thus, lifestyle changes and medication management can be instituted to reduce reoccurrence. There is a large financial burden due to loss of work and emergency department visits due to recurrent nephrolithiasis as well as the complications of end-stage renal disease (ESRD), and thus prevention of recurrence is key.

Complications

Nephrolithiasis and ureterolithiasis do not always have a benign course. Infected kidney stones, sepsis, ureteral scarring, perforation, renal abscess formation, bleeding, impaired renal function, and obstruction are just some of its complications. Chronic kidney disease (CKD) can result from a urologic procedure or due to obstruction or due to the inherent cause of the stone formation. However, generally, the risk from ESRD is low from nephrolithiasis even in recurrent cases. Nephrolithiasis in pregnancy presents with additional complications and are associated with abortions, preeclampsia, gestational diabetes.[2]

Deterrence and Patient Education

Patients who present with a first time renal calculi must be educated on the high rate of recurrence. The patient should be educated that additional outpatient testing, such as calculi composition analysis may be needed to identify the cause of the stone, especially in recurrent cases. A patient can also be educated on the use of a sifter to retrieve a renal stone for analysis. Patients who present to the emergency department and are diagnosed with uncomplicated nephrolithiasis should be advised to look out for warning symptoms such a fever/chills, lethargy, difficulty urinating that would warrant additional evaluation. Otherwise, in uncomplicated nephrolithiasis, patients should be educated that this condition generally includes mainly symptomatic treatment only with NSAIDs such as ibuprofen or ketorolac. Appropriate outpatient follow up with a patient's primary care provider (PCP) and/or urologist should be given.

Enhancing Healthcare Team Outcomes

The treatment of ureterolithiasis is a team effort. Many patients present with symptoms in the emergency department or at their primary care physician (PCP). Patients should be referred to a urologist, especially if the patient has had multiple reoccurring episodes, a large stone, or difficulty passing calculus; this care can be coordinated by the physician. Physicians, nurses, and pharmacists should all be involved in educating the patient on this disease, including possible dietary modifications, increasing fluid intake, and how to correctly take the prescribed medications.