Advanced microscope technology and cutting-edge geological science are giving new perspectives to an old medical mystery: How do kidney stones form, why are some people more susceptible to them and can they be prevented?
In a new paper published in the journal Nature Reviews Urology, researchers from the University of Illinois Urbana-Champaign, Mayo Clinic and other collaborators described the geological nature of kidney stones, outlined the arc of their formation, established a new classification scheme and suggested possible clinical interventions.
“We are bringing together geology, biology and medicine to map the entire process of kidney stone formation, step by step. With this road map in hand, more effective and targeted clinical interventions and therapies can now be developed.”
Kidney stones are a painful problem that will strike one in 10 adults in their lifetime and send half a million people in the United States to emergency rooms each year, according to the National Kidney Foundation. Yet little is understood about the geology behind how kidney stones form, Fouke said.
Previous work from Fouke’s group found that kidney stones form in the same way as geological stones in nature: Rather than crystalizing all at once, they partially dissolve and re-form multiple times, contrary to doctors’ belief that they form suddenly and intact.
In the new work, the research teamù – brought together by the Mayo Clinic and Illinois Alliance for Technology-Based Healthcare – describes in detail the multiple phases kidney stones go through in forming, dissolving and re-forming, documented through high-resolution imaging technologies.
The findings defy the typical classification schemes doctors use, which are based on bulk analyses of the type of mineral and the presumed location of formation in the kidney. Instead, the researchers developed a new classification scheme based on which phase of formation the stone is in and which chemical processes it is undergoing.
“If we can identify these phase transformations, what makes one step to go to another and how it progresses, then perhaps we can intervene in that progression and break the chain of chemical reactions happening inside the kidney tissues before a stone becomes problematic,” said Mayandi Sivaguru, the lead author of the study and assistant director of core facilities at the Carl R. Woese Institute for Genomic Biology at Illinois.
One particularly revelatory finding was in the very beginnings of kidney stone formation: Stones start as microspherules, or tiny droplets of mineral, which merge to form larger crystals throughout kidney tissues. Normally they are flushed out, but when they coalesce together to form larger stones that continue to grow, they can become excruciatingly painful and even deadly in some cases, Fouke said.
“But then there is a tipping point when those same mineral deposits start to grow together too rapidly and are physically unable to leave the kidney.”
As the stone goes through the formation process, more microspherules merge, lose their rounded shape and transform into much larger, perfectly geometric crystals. Stones go through multiple cycles of partially dissolving – shedding up to 50% of their volume, the researchers found – and then growing again, creating a signature pattern of layered crystals much like those of agates, coral skeletons and hot-spring deposits seen around the world.
“Looking at a cross-section of a kidney stone, you would never guess that each of the layers was originally a bunch of little balls that lined up and coalesced. These are revolutionary new ways for us to understand how these minerals grow within the kidney and provide specific targets for stone growth prevention,” Fouke said.
The study authors outlined several possible clinical interventions and treatment targets based on this expanded knowledge of kidney stone formation. They hope that researchers and clinicians can explore and test these options, from drug targets to changes in diet or supplements that could disrupt the chemical and biological cascade driving kidney stone formation, Sivaguru said.
To aid in this testing, Fouke’s group developed the GeoBioCell, a microfluidic cartridge designed to mimic the intricate internal structures of the kidney. The group hopes the device can accelerate not only research, but also clinical diagnostic testing and the evaluation of potential therapies, especially for the more than 70% of kidney stone patients with recurring stones.
“Ultimately, our vision is that every operating room would have a small geology lab attached. In that lab, you could do a very rapid diagnostic on a stone or stone fragment in a matter of minutes, and have informed and individualized treatment targets,” Fouke said.
Renal calculi; Nephrolithiasis; Stones – kidney; Calcium oxalate – stones; Cystine – stones; Struvite – stones; Uric acid – stones; Urinary lithiasis
A kidney stone is a solid mass made up of tiny crystals. One or more stones can be in the kidney or ureter at the same time.
f you ever have severe pain in your belly or one side of your back that comes and goes suddenly, you may be passing a kidney stone. Let’s talk about the painful condition of kidney stones. A kidney stone is a mass of tiny crystals in your kidney or urinary tract. Stones are quite common, and tend to run in families.
They can form in weeks or months when your urine contains too much of certain substances. There are several kinds of kidney stones. Calcium stones are by far the most common kind. They often form in men between the ages of 20 to 30. Calcium can combine with other substances found in your food, like oxalate, phosphate, or carbonate, to form stones. Cystine stones can form in people who have cystinuria, a condition passed down through families in which stones are made from an amino acid called cystine. Struvite stones are found mostly in women who have urinary tract infections.
These stones can grow very large and can block the kidney, ureter, or bladder. Uric acid stones are more common in men than in women.
They can occur in people who have a history of gout or are going through chemotherapy. So, how do you know if you have kidney stones?
Well, you may not have symptoms until the stone move down the ureter tubes through which urine empties into your bladder. When this happens, the stones can block the flow of urine out of your kidneys. The main symptom is severe sharp pain that starts suddenly, usually in your belly or one side of your back, and it may go away just as quickly. Other symptoms can include abnormal urine color, blood in your urine, fever, chills, nausea, and vomiting.
So, what do you do about kidney stones? Well, your health care provider will perform a physical exam. You may need blood tests, kidney function tests, and tests that look for crystals in your urine. Several imaging tests, like a CT scan, can see stones or a blockage in your urinary tract. Treatment will depend on the type of stone you have, and how bad your symptoms are. Small kidney stones that are less than 5 mm in diameter will usually pass on their own.
You should drink at least 6 to 8 glasses of water per day to produce a large enough amount of urine to help bring the stone out. Pain can be pretty bad when you pass a kidney stone, so your doctor may prescribe pain medicines to help as well as medications that will help the stone pass.
Other medicines can decrease stone formation or help break down and remove the material that is causing you to make stones. You may need surgery if the stone is too large to pass, the stone is growing, or the stone is blocking your urine flow. Kidney stones are painful, but you can usually pass them without causing permanent harm. However, kidney stones often come back, so you and your doctor will need to work on finding the cause of your stone. Lastly, delaying treatment can lead to serious complications, so if you think that you have kidney stones see your doctor right away.
Kidney stones are common. Some types run in families. They often occur in premature infants.
There are different types of kidney stones. The cause of the problem depends on the type of stone.
Stones can form when urine contains too much of certain substances that form crystals. These crystals can develop into stones over weeks or months.
- Calcium stones are most common. They are most likely to occur in men between ages 20 to 30. Calcium can combine with other substances to form the stone.
- Oxalate is the most common of these. Oxalate is present in certain foods such as spinach. It is also found in vitamin C supplements. Diseases of the small intestine increase your risk for these stones.
Calcium stones can also form from combining with phosphate or carbonate.
Other types of stones include:
- Cystine stones can form in people who have cystinuria. This disorder runs in families. It affects both men and women.
- Struvite stones are mostly found in men or women who have repeated urinary tract infections. These stones can grow very large and can block the kidney, ureter, or bladder.
- Uric acid stones are more common in men than in women. They can occur with gout or chemotherapy.
- Other substances, such as certain medicines, also can form stones.
The biggest risk factor for kidney stones is not drinking enough fluids. Kidney stones are more likely to occur if you make less than 1 liter (32 ounces) of urine a day.
You may not have symptoms until the stones move down the tubes (ureters) through which urine empties into your bladder. When this happens, the stones can block the flow of urine out of the kidneys.
The main symptom is severe pain that starts and stops suddenly:
- Pain may be felt in the belly area or side of the back.
- Pain may move to the groin area (groin pain), testicles (testicle pain) in men, and labia (vaginal pain) in women.
Other symptoms can include:
- Abnormal urine color
- Blood in the urine
- Nausea and vomiting
Exams and Tests
The health care provider will perform a physical exam. The belly area (abdomen) or back might feel sore.
Tests that may be done include:
- Blood tests to check calcium, phosphorus, uric acid, and electrolyte levels
- Kidney function tests
- Urinalysis to see crystals and look for red blood cells in urine
- Examination of the stone to determine the type
Stones or a blockage can be seen on:
- Abdominal CT scan
- Abdominal x-rays
- Intravenous pyelogram (IVP)
- Kidney ultrasound
- Retrograde pyelogram
Treatment depends on the type of stone and the severity of your symptoms.
Kidney stones that are small most often pass through your system on their own.
- Your urine should be strained so the stone can be saved and tested.
- Drink at least 6 to 8 glasses of water per day to produce a large amount of urine. This will help the stone pass.
- Pain can be very bad. Over-the-counter pain medicines (for example, ibuprofen and naproxen), either alone or along with narcotics, can be very effective.
Some people with severe pain from kidney stones need to stay in the hospital. You may need to get fluids through an IV into your vein.
For some types of stones, your provider may prescribe medicine to prevent stones from forming or help break down and remove the material that is causing the stone. These medicines can include:
- Allopurinol (for uric acid stones)
- Antibiotics (for struvite stones)
- Diuretics (water pills)
- Phosphate solutions
- Sodium bicarbonate or sodium citrate
- Water pills (thiazide diuretics)
- Tamsulosin to relax the ureter and help the stone pass
Surgery is often needed if:
- The stone is too large to pass on its own.
- The stone is growing.
- The stone is blocking urine flow and causing an infection or kidney damage.
- The pain cannot be controlled.
Today, most treatments are much less invasive than in the past.
- Lithotripsy is used to remove stones slightly smaller than one half an inch (1.25 centimeters) that are located in the kidney or ureter. It uses sound or shock waves to break up stones into tiny fragments. Then, the stone fragments leave the body in the urine. It is also called extracorporeal shock-wave lithotripsy or ESWL.
- Procedures performed by passing a special instrument through a small surgical cut in your skin on your back and into your kidney or ureters are used for large stones, or when the kidneys or surrounding areas are incorrectly formed. The stone is removed with a tube (endoscope).
- Ureteroscopy may be used for stones in the lower urinary tract. A laser is used to break up the stone.
- Rarely, open surgery (nephrolithotomy) may be needed if other methods do not work or are not possible.
Talk to your provider about what treatment options may work for you.
You will need to take self-care steps. Which steps you take depend on the type of stone you have, but they may include:
- Drinking extra water and other liquids
- Eating more of some foods and cutting back on other foods
- Taking medicines to help prevent stones
- Taking medicines to help you pass a stone (anti-inflammatory drugs, alpha-blockers)
Kidney stones are painful, but most of the time can be removed from the body without causing lasting damage.
Kidney stones often come back. This occurs more often if the cause is not found and treated.
You are at risk for:
- Urinary tract infection
- Kidney damage or scarring if treatment is delayed for too long
Complication of kidney stones may include the obstruction of the ureter (acute unilateral obstructive uropathy).
When to Contact a Medical Professional
Call your provider if you have symptoms of a kidney stone:
- Severe pain in your back or side that will not go away
- Blood in your urine
- Fever and chills
- Urine that smells bad or looks cloudy
- A burning feeling when you urinate
If you have been diagnosed with blockage from a stone, passage must be confirmed either by capture in a strainer during urination or by follow-up x-ray. Being pain free does not confirm that the stone has passed.
If you have a history of stones:
- Drink plenty of fluids (6 to 8 glasses of water per day) to produce enough urine.
- You may need to take medicine or make changes to your diet for some types of stones.
- Your provider may want to do blood and urine tests to help determine the proper prevention steps.
reference link: https://www.mountsinai.org/health-library/diseases-conditions/kidney-stones
More information: Mayandi Sivaguru et al, Human kidney stones: a natural record of universal biomineralization, Nature Reviews Urology (2021). DOI: 10.1038/s41585-021-00469-x