What is nephrolithiasis?
Nephrolithiasis or urolithiasis is most commonly known as kidney stone disease. Kidney stones (a.k.a. renal calculi) are solid crystals that form in the urinary tract and are a common health issue; statistics vary among countries and in the US the lifetime risk of developing kidney stones is around 7% for females and 12% for males. The incidence of this disease has been steadily increasing over the past decades with most stones developing in persons aged 20-49 with a recurrence rate after the first episode that can be as high as 94% depending on many factors.
Stones form in the upper urinary tract, but when they move into the ureter, the small tube between the kidney and the bladder, they can cause a renal colic which is often described by patients as the worse pain they ever experienced.
Causes of nephrolithiasis
There is no definite single cause for kidney stone formation, several factors are involved in the process. Kidney stones form due to supersaturation of urine: urine is a solution containing minerals and other substances that have the potential to crystalize; when the amount of these substances is higher than what can be dissolved in the liquid portion of urine, crystals starts to form leading eventually to kidney stones.
Risk Factors for Kidney Stones
Many factors play a role to increase the risk of suffering from nephrolithiasis, including:
- Low fluid intake. Not drinking enough causes a low volume of urine production; this means urine will be more concentrated and saturated, with higher risk for crystal formation.
- Diet. Eating too much salt, sugars, animal proteins and foods high in oxalate increases the risk of some types of kidney stones.
- Obesity and sedentary lifestyle.
- Genetics. A family history of kidney stone disease significantly increases the risk of developing it.
- Supplements. Vitamin C has been linked to higher risk of stone formation because it increases the oxalate output in urine.
- Medications. Sulfonamide drugs (large family of medications that includes many antibiotics, antivirals, diuretics, anticonvulsants, anti-inflammatories, and more), antiacids containing magnesium silicate, and other drugs can increase the risk of kidney stone formation.
- Previous surgeries. Gastric bypass surgery and other bariatric procedures that lead to malabsorption of nutrients may increase the risk of nephrolithiasis.
- Other medical conditions. Hyperparathyroidism, recurrent urinary tract infections, cystinuria, renal tubular acidosis, inflammatory bowel disease, Chron’s disease, gout are among the conditions that increase the risk of developing kidney stone disease.
Types of kidney stones
Not all kidney stones are the same. They can be composed of different chemicals which are associated with a different cause or underlying condition. Stones commonly contain a mixture of different chemicals and may also contain proteins.
Calcium stones – Calcium oxalate and calcium phosphate
Calcium stones are the most common type of kidney stone representing 70-90% of all renal calculi and can be made of two different chemicals:
- Calcium Oxalate stones. They represent 80% of calcium stones.
- Calcium phosphate or calcium hydroxyapatite.
Calcium stones may be caused by elevated calcium excretion in the urine (hypercalciuria), low citrate excretion (hypocitraturia), elevated oxalate excretion (hyperoxaluria), low urine volume, alkaline urine pH, or by conditions such as hyperparathyroidism, small bowel malabsorption, small bowel resection or gastric bypass surgery, distal renal tubular acidosis.
Uric acid stones
Uric acid stones represent 6-8% of all renal calculi. They can form due to low urine volume, low urine pH, gout disease, diabetes, obesity, bowel disease, high protein diet, metabolic syndrome.
Struvite stones account for 1-15% of all renal calculi depending on the source. Struvite is a mineral that forms when magnesium, ammonia and phosphates combine together. This happens when a bacterial infection occurs in the upper urinary tract, due to some bacteria that are able to convert the urea into ammonia and elevate the pH of urine including Pseudomonas, Proteus, Klebsiella and Staphylococcus.
A particular type of struvite stone is the Staghorn calculus, which is a coral shaped stone filling the renal pelvis and/or the renal calyces. Most patients will require surgical treatment to avoid loss of kidney function and sepsis.
Cystine stones are rare and represent just 1-2% of all renal calculi. They are caused by a genetic defect that leads to increased levels of cystine, an amino acid, in urine.
Symptoms of nephrolithiasis
Kidney stones in general don’t cause pain until they start moving through the kidney or into the ureters. Stones take weeks, months or even years to grow to a detectable size. They may take even longer to become symptomatic, due to their movement, with pain or blood in the urine (hematuria)
Small stones may cause no symptoms at all or just minimal pain or discomfort.
Larger stones cause symptoms such as:
- Sudden onset of pain. Also known as renal colic, this is due to ureteral spasm and is of increasing intensity. Such pain is often described as the worse ever experienced by the patient. Pain may be on one side of the back or abdomen and may radiate to the inguinal or groin area on the same side. There may be pain or a burning sensation also while urinating.
- Hematuria. Blood in the urine is another common sign of kidney stone disease.
- Nausea and vomiting.
- Difficulty urinating and persistent need to urinate may also be present.
Diagnosis of Nephrolithiasis
Kidney stones may be suspected based on the history of the patient, symptoms and physical examination. Blood test may show elevated white blood cell count when a urinary tract infection (UTI) is present. Urine analysis may show white and/or red blood cells and sometimes crystals, but their absence doesn’t rule out the presence of a kidney stone.
Confirmation of the diagnosis requires an imaging study such as the computed tomography (CT-Scan), magnetic resonance (MRI) or ultrasound scan.
How are Kidney Stones treated?
Treatment of nephrolithiasis varies depending on the type of stone, the size and the location, whether there is an infection or obstruction or not, and the symptoms experienced by the patient.
Small stones less than 5mm usually don’t require treatment and will pass through causing no symptoms, or just some discomfort or limited pain depending on the individual case.
Treatment of larger stones may include:
- Drinking plenty of water. Drinking more than 2-3 liters of water helps both with passing the stone and with preventing their formation and recurrence.
- Pain relievers. Depending on the intensity NSAIDs, acetaminophen, up to opioid drugs may be prescribed.
- Antiemetic drugs, when nausea is present.
- Antibiotics, when there is an infection.
- Alpha-blocker medications, such as tamsulosin that help relax the ureter aiding in relieving the pain from its spasm and allowing for easier passage.
- Calcium channel blockers medication, such as nifedipine which helps relaxing the ureteral smooth muscles acting as the alpha-blockers.
- Extracorporeal Shockwave Lithotripsy (ESWL). A non-invasive medical procedure that uses high-energy sound waves that target the kidney stones to break them into smaller pieces which will be able to pass through. To target the stone and monitor the progress, X-rays or an ultrasound machine are used.
- Ureteroscopy with laser or electrohydraulic stone fragmentation.
- Percutaneous nephrostomy or double J stent.
- Open Surgery.
How to prevent nephrolithiasis
The following are measures to help prevent kidney stone formation. They consist mainly of lifestyle and dietary changes and are easily adoptable by patients. Specific stone types, test results or specific conditions affecting patients may require different interventions, for this reason always refer to your treating physician for advice.
Increase water intake and urine volume
The main factor promoting kidney stone formation is supersaturation of the urine. Supersaturation of urine is caused by low urinary volume, which is the result of low fluid intake. For this reason, drinking plenty of water is a very easy and effective way of preventing kidney stone formation. Patients should aim at 2-2,5 L of urine every 24-hour which means drinking at least 2,5-3 liters of water every day. Those who live in warmer climates or who exercise more may have to drink larger amounts of fluids in order to achieve the target urine output.
Some drinks such as orange juice may be helpful in the prevention of kidney stones by increasing the levels of urinary citrate, while others such as cola may increase the risk of nephrolithiasis due to its phosphoric acid content.
Calcium and sodium dietary intake
Although calcium is a main component of most kidney stones, a limited calcium intake doesn’t appear to be beneficial: low calcium intake is linked with higher oxalate levels in urine and increased risk of stone formation, as well as high calcium intake through diet and/or supplementation is also linked with higher risk of nephrolithiasis.
1,000-1,200 mg of calcium per day, which is the calcium RDA, is associated with lower risk of stone formation.
Reduced sodium intake reduces the excretion of calcium in the urine, lowering the risk of calcium stone formation. High sodium intake also increases the risk of sodium urate crystals formation. Sodium intake should be limited to a maximum of 3g per day.
Animal proteins may increase the risk of stone formation by decreasing urine pH, lowering urinary citrate and increasing oxalate and uric acid levels in urine. Daily consumption of animal proteins should be limited to 0.8-1.0 g/kg body weight.
Fruits, Vegetables and Fibers
Fibers seem to have beneficial effects on nephrolithiasis and fruits and vegetables in general increase the pH of urine and citrate concentration lowering the risk of kidney stone formation.
Excessive intake of oxalate-rich products leads to high oxalate concentration in urine, with higher risk of oxalate stone formation. Oxalate rich products include rhubarb, beets, spinach, cocoa and chocolate, wheat bran, tea leaves and nuts. Vitamin C is a precursor of oxalate and should be limited to a maximum of 1,000 mg per day.
Specific therapies for specific metabolic causes of nephrolithiasis
Specific medical intervention to prevent kidney stone formation based on test results or metabolic abnormalities include:
- Urine alkalinization with potassium citrate or sodium bicarbonate. Effective against calcium oxalate, uric acid and cystine stone formation and in nephrolithiasis with hypocitraturia.
- Allopurinol. A medication effective against uric acid stones by reducing uric acid levels in urine.
- Hydrochlorothiazide. A diuretic medication that reduces calcium excretion in urine lowering the risk of developing calcium stones. It requires a low sodium diet to be effective.
- Tiopronin. A medication that lowers the excretion of cystine in urine and the risk of developing cystine stones.
- Oxalate chelation with calcium or magnesium, in those with high levels of oxalate (hyperoxaluria) in urine to lower the risk of calcium oxalate stone formation.
- Pyridoxine (Vitamin B6) in primary hyperoxaluria to lower the risk of calcium oxalate stone formation.
- Predictors of symptomatic kidney stone recurrence after the first and subsequent episodes.
LE Vaughan – Mayo Clinic Proceedings, Feb 2019
J Antonelli, N Maalouf – British Medical Journal Best Practice, Sep 2018
- Harrison’s Principles of Internal Medicine – 20th Ed.
JL Jameson et al. – McGraw-Hill, 2018
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M Lipkin, O Shah – Reviews in Urology, 2006
- Acute Renal Colic.
L Patti, SW Leslie – StatPearls, Jun 2020
- American Urological Association – Management of Kidney Stones Guidelines, 2019
- European Association of Urology (EAU) – Urolithiasis Guidelines, 2020
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