Kidney Stones

What are kidney stones?

Kidney stones (also known as nephrolithiasis), are one of the most common causes of urgent care, emergency room, and primary care visits. Nephrolithiasis is prevalent in approximately 10.6% of men and 7.1% of women in the United States and the rate of people affected by this disease is rising (PubMed). This rising trend is likely attributed to the average diet, lifestyle, and increasing obesity rate of the U.S. population. It is estimated that more than one in eleven people will have a kidney stone at some point in their lives (PubMed). Kidney Stones may cause extreme pain, severe infection, and kidney function decline if left untreated. These hard masses, created from a build-up of minerals and salts that occur as a result of biochemical abnormalities in the blood and/or urine, are caused by genetic, dietary, and/or environmental factors. Evaluation by a nephrologist (a kidney specialist) can help prevent the recurrence of kidney stones.

What causes kidney stones?

Kidney stones are the result of an abnormal amount of electrolytes or chemicals in the urine. Since urine volume is not constant, these substances are measured by their concentration.

The higher the urinary concentration of certain chemicals, the higher the likelihood of the formation of kidney stones. Any process that increases the concentration of calcium, oxalate, or other chemicals in the urine to a critical point (called supersaturation) makes it more likely that stones will form. Once a stone forms, chemicals will continue to deposit on the initial stone causing the stone to grow.

Factors that increase the risk of developing kidney stones include:

• Dehydration or drinking too little water
• Eating a diet high in protein, sodium, and sugar (fructose)
• Excessive exercise
• Obesity: high body mass index (BMI) have been linked to an increased risk of stone formation
• Genetics: if someone in your family has kidney stones, you are more likely to develop a stone

How do you recognize a kidney stone?

The classical symptom of a kidney stone is pain on the side (flank) of the body that can radiate down to the groin. This pain can be severe, cramping, and constant.

Some kidney stones are as small as a grain of sand while others are larger. In general, the larger the stone, the more noticeable the symptoms. You may start to experience symptoms when the stone moves through the ureter (the tube that connects the kidney to the bladder).

Symptoms include:

• Flank pain
• Additional vague pain or stomach discomfort that does not go away
• Persistent need to urinate
• Pain with urination
• Abnormal urination (urinating either more than usual or urinating a smaller amount)
• Urine that smells bad or looks cloudy
• Hematuria (blood in the urine)
• Nausea and vomiting
• Fever
• Chills
  

What are the most common types of kidney stones?

Kidney stones are the result of the build-up of electrolytes and chemicals in the urine.

The four main types of stones are:

• Calcium Oxalate: The most common type of kidney stone. Oxalate is a naturally occurring substance in fruits, vegetables, nuts, and chocolate. When bound with calcium, hard clumps of mineral can form. These crystals usually form when there is a high concentration of oxalate or too little urine in the body.
• Uric Acid: These stones can be caused by foods with high concentrations of natural purines, such as meats. High purine intake leads to a higher production of uric acid (also known as monosodium urate) which causes the urine to become acidic. If not enough water is consumed while the urine is highly acidic, the urine can become too concentrated making stones more likely to form.
• Struvite Stones: These stones are less common and are caused by an infection. During a bacterial infection, such as a urinary tract infection (UTI), ammonium levels rise turning urine, which is normally slightly acidic, to become alkaline. These stones are built up of ammonium, magnesium, and phosphate mineral which do not dissolve in alkaline urine. Struvite crystals can grow quickly and become quite large.
• Cystine Stones: These stones are rare and tend to be caused by genetics. They are commonly produced with patients who are homozygous for the recessive cystine transport gene causing a disorder called cystinuria causing elevated levels of cystine in the urine which make stones more likely to form.

How are kidney stones diagnosed?

Kidney stones are commonly diagnosed in the following ways:

• Medical history and physical examination
• Blood testing (may reveal elevated levels of calcium or uric acid in the urine)
• Imaging tests such as a CT scan, ultrasound, or KUB (kidney-ureter-bladder) x-ray. In some cases, an intravenous pyelogram (IVP), a type of x-ray taken after injecting a dye is required. 

After the removal of the stone, your doctor will analyze it to determine the cause of the formation. Not everyone needs to see a doctor about kidney stones, but it is necessary in some cases, such as with young children and patients with only one kidney or recurrent stone formers.

If you had one stone, you are at an approximated 50% increased risk of having another stone within 5 to 7 years.

How are kidney stones treated?

Kidney stones are treated based on several factors including the severity of pain, the location of the stone, and the presence of infection. Most stones less than 5 mm in diameter are easily passed on their own while those that are larger than 10 mm require further treatment. Most patients can be treated at home while others require admission to the hospital. If a stone is too large to pass on its own, is extremely painful, or is obstructing, a surgical procedure or another procedural attempt to dislodge/break up the stone may be indicated. These procedures are performed by urologists who are surgeons of the kidneys, ureters, and bladder.

Most stones do not require an invasive procedure. You can pass a small stone by:

• Drinking as much as 2-3 liters of water a day to flush your kidneys
• Medication for pain and nausea
• Intravenous fluids
• Medical therapy to relax the muscles of the ureter

Stones that are too large or cause severe symptoms need more extensive therapy such as:

• Shock wave lithotripsy (SWL) to break down stones
• Scopes to remove stones
• Surgery

Although a urologist may be seen for acute kidney stone needs, a nephrologist should be seen for long term management.

How do you prevent kidney stones?

• Drinking enough non-sugary fluid will help to keep your urine less concentrated with waste products. It is recommended to drink 2-3 liters of fluid per day (mostly water and some lemonade). Urine should appear very light yellow to clear if you are well hydrated.
• Diets low in sodium and protein by eating less processed, fast food, and restaurant meals
• Restricting foods rich in oxalates (nuts, tea, chocolate, soy, beets, okra, etc.)
• Eating more fruits and vegetables which make the urine less acidic.
• Maintaining a healthy weight

Please consult your healthcare provider before making any dietary changes.

Genetic Causes of Kidney Stones

It is estimated that 40% of patients with kidney stones are caused by inherited genetics. Listed below are a few rare genetic causes of kidney stones.

• Cystinuria: This rare condition affecting the kidneys causes an elevated level of cystine, an amino acid, to be excreted in the urine that make cystine stones more likely to form
• Hypocitraturia: Citrate naturally metabolizes kidney stones, but patients that inherit hypocitraturia have a decreased level of citrate in the urine, therefore, increasing the risk factor of harmful kidney stones developing
• Hypercalciuria: This genetic condition promotes elevated levels of calcium in the urine that increase the risk of developing calcium oxalate stones along with various other medical conditions.
• Enteric Hyperoxaluria: When there is an elevated level of oxalate excreted in the urine as a result of several intestinal diseases. This excess oxalate when combined with calcium can form calcium oxalate stones.

One of the major genetic causes of kidney stones is due to Primary Hyperoxaluria disease.
 

Primary Hyperoxaluria Disease

Overview of Disease

Primary Hyperoxaluria (PH) is distinguished by high levels of oxalate in the urine caused by rare inherited disorders of the liver. Elevated levels of oxalate, a product of metabolism that is also found in certain types of foods, are toxic because the body is unable to break it down and greatly increases the risk of kidney stones which may cause kidney failure.

There are three types of Primary Hyperoxaluria disease: type 1 (PH1), type 2 (PH2), and type 3 (PH3). PH1 is the most prevalent and severe form affecting 70-80% of PH patients which is approximately 4 individuals per million in the United States and Europe. Type 1 is currently treated with combined liver and kidney transplants while type 2 is a milder where kidney failure is not as apparent.

Early diagnosis and proper treatment of hyperoxaluria are essential to maintain the long-term health of your kidneys.

Causes of Primary Hyperoxaluria disease

PH is an inherited disease in which the liver does not create enough functional enzymes to prevent elevated levels of oxalate in the blood and urine. Since PH is a condition present from birth, kidney stones may form as early as during childhood or adolescence and may progress to kidney failure by adulthood if not properly treated.

In the body, glyoxylate is metabolized into glycine in the presence of an AGT enzyme in healthy individuals. However, in patients with PH1, the absence of the AGT enzyme converts glyoxylate into oxalate. This, in turn, results in elevated levels of oxalate that increases the risk of kidney stone formation that can cause kidney failure. If oxalate is unable to be excreted from the kidneys through urine, it may deposit in vital organs such as the eyes, bones, skin, and heart. This is a condition called oxalosis. 

Symptoms

Initial signs of primary hyperoxaluria disease are the manifestation of kidney stones. Common symptoms of kidneys stones include:

• Flank pain
• Additional vague pain or stomach discomfort that does not go away
• Persistent need to urinate
• Pain with urination
• Abnormal urination (urinating either more than usual or urinating a smaller amount)
• Urine that smells bad or looks cloudy
• Hematuria (blood in the urine)
• Nausea and vomiting
• Fever
• Chills

Diagnosis

Primary hyperoxaluria disease can be diagnosed through various methods that include:

• Urine and Blood tests to measure oxalate levels
• Stone analysis to examine the composition of the stone
• X-ray, ultrasound, or computed tomography (CT) scan to locate kidney stones and calcium oxalate deposits
• DNA testing to investigate genetic causes
• Kidney biopsy to locate oxalate deposits in the kidney
• Echocardiogram to locate oxalate deposits in the heart
• Eye examination to locate oxalate deposits in the eyes
• Bone Marrow biopsy to locate oxalate deposits in the bone
• Liver Biopsy to determine enzyme deficiencies in rare cases that genetic testing does not indicate hyperoxaluria disease

Treatment

For patients with PH, currently the only curative treatment is a liver transplant, and if kidney failure is apparent, a dual liver/kidney transplant is required. However, treatments to reduce calcium oxalate formation can be effective in kidney stone management.

• Medications: Doses of vitamin B-12 and prescription phosphate and citrate can be effective in preventing the formation of calcium oxalate stones.
• High fluid intake to flush the kidneys
• Dietary Changes: Your doctor may recommend changes in your diet that may include limiting foods high in oxalate and salt and restricting animal proteins and processed sugars.
• Dialysis may be necessary if there is a significant decline in kidney function

Recently there have been significant advancements in PH1 treatment and a novel treatment is on the horizon. Lumasiran is an investigational, subcutaneously administered (under the skin) RNA interference (RNAi) therapeutic targeting hydroxyacid oxidase 1 (HAO1) gene in development for the treatment of primary hyperoxaluria type 1 (PH1). HAO1 encodes the glycolate oxidase (GO) enzyme. Thus, by silencing HAO1 and depleting the GO enzyme, lumasiran inhibits the production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1. Lumasiran has received both U.S. and EU Orphan Drug Designations, a Breakthrough Therapy Designation, and pediatric rare disease designation from the U.S. Food and Drug Administration (FDA).

Complications of Disease Progression

Although PH1 is a genetically inherited disease and patients may experience symptoms during childhood, many patients are not diagnosed immediately since kidney stones are not common in children. As a result, patients with PH1 may not be diagnosed until they are adults or presented with severe kidney disease. PH1 can progress and result in end-stage renal disease (ESRD) in which the kidneys are unable to filter fluids and waste from the body. Oxalate buildup can also be deposited in the eyes, skin, heart, and nervous system which may cause blurred vision, ulcers, heart failure, bone fractures, and other complications.

Disclaimer: The information on this website is for informational purposes only and is not intended to serve as a substitute for consultation, diagnosis, or medical treatment from a qualified healthcare provider. Readers should consult with their physician or healthcare provider before making any changes. The UCLA Health System cannot guarantee the accuracy of such information.

Kidney Stones

Contributors:

Medical Director of the UCLA Kidney Stone Program | Ray Reza Goshtaseb, MD, FASN

Member of the Bruin Beans Health Club | Josh Ooka, UCLA Undergrad

References:

Edvardsson, Vidar O, et al. “Hereditary Causes of Kidney Stones and Chronic Kidney Disease.” Pediatric Nephrology (Berlin, Germany), U.S. National Library of Medicine, 20 Jan. 2013, pubmed.ncbi.nlm.nih.gov/23334384/.

“Hyperoxaluria and Oxalosis.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 16 Mar. 2019, www.mayoclinic.org/diseases-conditions/hyperoxaluria/symptoms-causes/syc-20352254.

“Kidney Stones.” National Kidney Foundation, 2 Oct. 2020, www.kidney.org/atoz/content/kidneystones.

Scales, Charles D, et al. “Prevalence of Kidney Stones in the United States.” European Urology, U.S. National Library of Medicine, 31 Mar. 2012, pubmed.ncbi.nlm.nih.gov/22498635/.

“Understanding Primary Hyperoxaluria-Symptoms and Causes: Alnylam®.” Alnylam, www.alnylam.com/patients/primary-hyperoxaluria/.

For additional information, please contact our UCLA CORE Kidney Stone Program experts:

Ray Reza Goshtaseb MD, FASN

Medical Director | Kidney Stone Center

Clinical Instructor 

UCLA CORE Kidney Program

Division of Nephrology | Department of Medicine

DGSOM and UCLA Health 

1245 16th Street Ste. #307 Santa Monica, CA 900404

Ph: 310-481-4228

Matthew D. Dunn, MD

Associate Clinical Professor of Urology

Division Chief of Endourology and Stone Disease 

1260 15th Stre. #1200 Santa Monica, CA 90404

Ph: 310-794-7700

Kymora B. Scotland MD, PhD

Assistant Professor

Department of Urology

UCLA