Nephrolithiasis, more commonly known as kidney stones, affects approximately 1 in 11 people at some point in their lives, causing intense pain and, without proper care, potentially recurring episodes. While painful, most stones can pass naturally or be managed with modern treatments, and understanding the options—both standard and emerging—helps patients navigate this common but challenging condition.

How Kidney Stone Treatment Works

When kidney stones form, the main goals of treatment are to relieve severe pain, help the stones pass out of the body, prevent complications like infection or blockage, and reduce the chance of new stones developing. The approach chosen depends on several factors: the size and location of the stone, the type of minerals it contains, whether infection is present, and the patient’s overall health and medical history.^[1][2]

Doctors today can choose from a range of treatments approved by medical organizations, from simple pain management and increased fluid intake to surgical removal procedures. At the same time, researchers are exploring new therapies in clinical trials that may offer better outcomes for people who have recurring stones or who don’t respond well to standard treatments. The field of kidney stone treatment continues to evolve, giving patients more options than ever before.^[7]

Standard Treatment Approaches

The majority of kidney stones—particularly those smaller than 4 millimeters—will pass through the urinary system on their own within a few weeks. During this time, doctors focus on making the patient as comfortable as possible while the stone moves from the kidney, down the tube connecting the kidney to the bladder (called the ureter), and eventually out of the body.^[9][10]

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or diclofenac, are typically the first choice for pain control. These medications not only relieve pain but also reduce inflammation in the urinary tract. For patients who cannot take NSAIDs, doctors may prescribe other pain medications, including acetaminophen or, in cases of severe pain, opioid medications like morphine. However, opioids are used cautiously due to their side effects and potential for dependence.^[7][9]

To help stones pass more easily and quickly, doctors often prescribe a class of medications called alpha blockers. These drugs, such as tamsulosin, work by relaxing the muscles in the ureter, making it easier for the stone to travel through. Studies show that alpha blockers can increase the rate of stone passage and reduce the time it takes, which means less pain and fewer emergency visits for patients. Treatment with alpha blockers typically continues until the stone passes or until imaging shows it has moved into the bladder.^[7][13]

Hydration plays a central role in treatment. Patients are encouraged to drink enough water to produce at least 2 to 2.5 liters of urine daily. This helps dilute the urine and may prevent new crystals from forming, though it doesn’t necessarily speed up the passage of an existing stone. Clear or pale yellow urine is a good sign of adequate hydration, while dark yellow urine suggests the person needs to drink more.^[7][13]

When Stones Can’t Pass on Their Own

Stones larger than 10 millimeters rarely pass without help, and those that become stuck can cause serious problems. In such cases, doctors use procedures to break up or remove the stone. The choice of procedure depends on the stone’s size, location, and composition, as well as the patient’s anatomy and preferences.^[8][10]

Shock wave lithotripsy (SWL) is a common non-invasive option for stones in the kidney or upper ureter. The patient lies on a special table while a machine uses ultrasound to locate the stone. The device then sends shock waves through the body to break the stone into smaller fragments that can pass more easily in the urine. While generally safe, some patients experience bruising, blood in the urine, or discomfort afterwards. The procedure is performed under sedation or pain medication and may need to be repeated if the stone doesn’t fully break apart.^[10][14]

Ureteroscopy involves passing a thin, flexible telescope (called a ureteroscope) through the urethra and bladder and up into the ureter or kidney. Once the stone is located, the doctor can either remove it whole using special tools or break it up using laser energy. This procedure is done under general anesthesia, meaning the patient is asleep and feels no pain during the operation. Most people go home the same day. Ureteroscopy is particularly useful for stones in the lower ureter or for those that cannot be broken with shock waves.^[10][14]

Percutaneous nephrolithotomy (PCNL) is reserved for very large stones or those with complex shapes, such as staghorn calculi that fill part of the kidney’s internal structure. The surgeon makes a small cut in the patient’s back and inserts a thin telescope directly into the kidney. The stone is then broken up and removed in pieces. This is a more invasive procedure requiring general anesthesia and usually a hospital stay of a few days. While it carries more risk than other methods, it’s often the most effective treatment for large, difficult stones.^[10][14]

After any of these procedures, doctors may place a temporary plastic tube called a ureteral stent inside the ureter. The stent helps urine drain from the kidney and keeps the ureter open as it heals. While stents prevent serious complications, they can cause discomfort, frequent urination, or a feeling of bladder fullness. They are typically removed within a few weeks.^[9][10]

Preventing Stone Recurrence with Medications

About half of people who develop a kidney stone will have another within 10 to 15 years if they don’t take preventive measures. Once a stone has passed or been removed, doctors focus on identifying why it formed and preventing future episodes. This involves analyzing the stone’s composition, performing blood and urine tests, and sometimes conducting a 24-hour urine collection to measure levels of substances that promote or inhibit stone formation.^[2][7]

Most kidney stones—75 to 85 percent—are made of calcium, usually combined with oxalate or phosphate. For patients with recurrent calcium stones, thiazide diuretics such as hydrochlorothiazide or chlorthalidone are often prescribed. These medications reduce the amount of calcium released in the urine, making it less likely that crystals will form. Thiazides are typically taken daily and can reduce stone recurrence by about 50 percent. Side effects may include increased urination, low potassium levels, and dizziness.^[7][13][15]

Potassium citrate is another important medication for stone prevention. Citrate binds to calcium in the urine, preventing it from forming crystals. It also makes urine less acidic, which helps prevent both calcium and uric acid stones. Patients usually take potassium citrate tablets two or three times daily. The medication is generally well tolerated, though some people experience stomach upset or nausea. Doctors monitor potassium levels in the blood to ensure they don’t become too high.^[7][13][15]

For patients with uric acid stones, which account for 3 to 16 percent of kidney stones in adults, the medication allopurinol is highly effective. Allopurinol blocks the production of uric acid in the body, reducing the amount that ends up in urine. It’s especially useful for people who have gout or who produce excessive uric acid due to diet or genetics. Combined with medications to make urine more alkaline (less acidic), allopurinol can actually dissolve existing uric acid stones and prevent new ones from forming. The typical dose is taken once daily.^[7][13][15]

Patients with rare cystine stones, which occur in people with an inherited condition called cystinuria, may be treated with medications called thiols, such as penicillamine or tiopronin. These drugs bind to cystine in the urine, making it more soluble and less likely to crystallize. Treatment usually continues for life, as cystinuria is a genetic condition. Thiol medications can have side effects including rash, loss of taste, and stomach problems, so patients need regular monitoring.^[15]

Bisphosphonates, medications typically used to treat osteoporosis, may be prescribed for patients with certain metabolic abnormalities that cause high calcium in the urine. These drugs help the body regulate calcium better and can reduce stone formation in selected cases. However, they are not routinely used for all stone patients.^[15]

Treatment in Clinical Trials

While standard treatments work well for many patients, researchers continue to explore new approaches for people with difficult-to-treat or frequently recurring stones. Clinical trials are research studies that test new medications, devices, or treatment strategies before they become widely available. Participating in a trial gives patients access to cutting-edge therapies while contributing to medical knowledge that may help others in the future.^[2]

Biological Therapies for Hyperoxaluria

One promising area of research involves using bacteria to break down oxalate, a substance that combines with calcium to form the most common type of kidney stone. A bacteria called Oxalobacter formigenes naturally lives in the human intestine and consumes oxalate before it can be absorbed into the bloodstream. Some people lack this helpful bacteria, which may increase their risk of calcium oxalate stones.^[15]

Clinical trials are testing whether giving patients Oxalobacter formigenes as a supplement can reduce oxalate levels in their urine and prevent stone formation. Early research suggests this approach might be particularly helpful for people with primary or secondary hyperoxaluria—conditions where the body produces too much oxalate or absorbs too much from food. The therapy would work by reestablishing the normal bacterial balance in the gut, essentially using biology to treat a metabolic problem. Studies are examining the safety, proper dosing, and effectiveness of this bacterial therapy in different patient populations.^[15]

Related to this concept, researchers are also studying probiotics—beneficial bacteria that support digestive health—to see if certain strains can help break down oxalate or reduce its absorption. This approach is still in relatively early phases of testing, but it represents an innovative way of thinking about stone prevention that focuses on the gut-kidney connection rather than just treating the kidneys directly.^[15]

Novel Medications for Prevention

Pharmaceutical researchers are investigating new chemical compounds that might prevent stones more effectively or with fewer side effects than current medications. Some trials are testing improved formulations of existing drugs, such as slow-release versions of potassium citrate that need to be taken less frequently and may cause less stomach upset. Others are examining entirely new molecules that target specific steps in crystal formation or growth.^[15]

Some experimental drugs work by changing the shape or structure of crystals as they form, making them less likely to stick together and grow into stones. Other compounds being studied aim to coat crystals with protective molecules that prevent them from attaching to the kidney tissue. These innovative mechanisms could offer alternatives for patients who don’t respond to or cannot tolerate standard preventive medications.^[15]

Understanding Clinical Trial Phases

Clinical trials typically progress through three main phases before a treatment can be approved for general use. Phase I trials focus primarily on safety. Researchers test the new treatment in a small group of people (usually 20 to 80) to determine safe dosing, identify side effects, and learn how the body processes the drug. These early studies provide essential information but don’t yet tell us whether the treatment actually works to prevent or treat kidney stones.^[2]

Phase II trials expand the research to a larger group (typically 100 to 300 participants) to begin evaluating effectiveness. Researchers measure whether the treatment reduces stone formation, lowers levels of stone-forming substances in urine, or improves other relevant outcomes. Phase II studies also continue to monitor safety and may compare different doses to find the optimal amount. If results are promising, the treatment moves forward to larger studies.^[2]

Phase III trials are large-scale studies involving hundreds or even thousands of patients. These trials compare the new treatment directly to the current standard of care or to a placebo (inactive treatment). They provide the strongest evidence about whether a new therapy is truly effective and safe enough to become a standard treatment option. Only after successful Phase III trials can pharmaceutical companies apply to regulatory agencies like the FDA for approval to market the drug.^[2]

Finding and Joining Clinical Trials

Clinical trials for kidney stone treatments are conducted at medical centers across the United States, Europe, and other regions around the world. Some trials focus on specific types of stones or particular patient groups, such as children with inherited stone-forming conditions or adults with recurrent stones despite preventive treatment. Others may be open to anyone who has had at least one kidney stone and wants to prevent future episodes.^[2]

Patients interested in clinical trials can discuss options with their urologist or nephrologist. Many major medical centers maintain lists of active trials recruiting participants. National resources also provide searchable databases of kidney stone studies, including information about locations, eligibility requirements, and how to enroll. Joining a trial typically involves additional monitoring visits and tests compared to routine care, but study-related expenses are often covered by the research sponsor.^[2]

Most Common Treatment Methods

• Pain Management
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or diclofenac are the first choice for controlling pain during stone passage
  • Acetaminophen can be used for mild to moderate pain, particularly in patients who cannot take NSAIDs
  • Opioid medications such as morphine may be prescribed for severe pain but are used cautiously due to side effects
• Medical Expulsive Therapy
  • Alpha blocker medications like tamsulosin relax ureter muscles to help stones pass more quickly and with less pain
  • This therapy is particularly effective for stones in the lower ureter
  • Treatment continues until the stone passes or imaging confirms it has moved into the bladder
• Surgical Stone Removal
  • Shock wave lithotripsy uses sound waves to break stones into passable fragments without surgery
  • Ureteroscopy involves passing a telescope through the urinary tract to remove or break up stones using laser energy
  • Percutaneous nephrolithotomy directly accesses the kidney through a small back incision to remove large or complex stones
• Preventive Medications
  • Thiazide diuretics reduce calcium in urine to prevent calcium stone recurrence
  • Potassium citrate binds calcium and makes urine less acidic, preventing both calcium and uric acid stones
  • Allopurinol reduces uric acid production in the body for patients with uric acid stones
  • Thiol medications help dissolve cystine for patients with cystinuria
• Hydration Therapy
  • Drinking enough water to produce 2 to 2.5 liters of urine daily is the foundation of stone prevention
  • Adding lemon juice to water provides citrate, which inhibits stone formation
  • Maintaining pale yellow or clear urine indicates adequate hydration
• Experimental Therapies
  • Oxalobacter formigenes bacteria supplements are being tested to reduce oxalate absorption in the intestines
  • Novel chemical compounds that modify crystal formation are in development and testing
  • Probiotic formulations are being studied for their potential to break down stone-forming substances