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To learn more, please view our Kidney Stone educational video series here: https://www.uclahealth.org/core-kidney/genetic-causes-of-kidney-stones
Medical Director of the UCLA Kidney Stone Program | Ray Reza Goshtaseb, MD, FASN
Member of the Bruin Beans Health Club | Josh Ooka, UCLA Undergrad
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.
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:
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).
Kidney stones are the result of the build-up of electrolytes and chemicals in the urine.
The four main types of stones are:
Kidney stones are commonly diagnosed in the following ways:
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.
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:
Stones that are too large or cause severe symptoms need more extensive therapy such as:
Although a urologist may be seen for acute kidney stone needs, a nephrologist should be seen for long term management.
Please consult your healthcare provider before making any dietary changes.
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.
One of the major genetic causes of kidney stones is due to Primary Hyperoxaluria 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.
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.
Initial signs of primary hyperoxaluria disease are the manifestation of kidney stones. Common symptoms of kidneys stones include:
Primary hyperoxaluria disease can be diagnosed through various methods that include:
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.
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).
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.
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: