Nephrolithiasis is the most common condition affecting the urinary system. Crystallization of chemical precipitates in the urine under certain conditions is the main pathophysiological feature of kidney stone formation.
Nephroliths can be classified according to their chemical makeup into calcium stones, struvite or magnesium ammonium phosphate stones, uric acid stones, and cystine stones.
Common clinical features include flank or lumbocostal pain, hematuria, dysuria, or the appearance of stones in the urine.
Diagnosis is based on laboratory studies and imaging. Renourinary ultrasound is the first choice study in most cases, followed by a low-dose CT scan, especially useful for differential diagnosis.
Treatment strategies include analgesics, hydration, medical expulsive therapy, and in selected cases, shock wave lithotripsy or surgery.
Nephrolithiasis in Adults – Introduction
Nephrolithiasis, also known as Kidney stones, is the most prevalent ailment affecting the urinary system, affecting roughly 12% of the global population and occurring in America on average at a rate of 600,000. A crystal or crystalline concretion that traveled from the kidney through the genitourinary system is what caused it . A higher risk of end-stage renal failure, cardiovascular disease, diabetes, and hypertension are associated with kidney stones .
Epidemiology of Nephrolithiasis [1-2]
Around 12% of people globally are affected by the prevalence and recurrence rates of nephrolithiasis, which has few effective treatment choices regarding medications and surgeries. In the United States, there are thought to be 600,000. Men are more likely than women to get kidney stones between the ages of 20 and 49. (2 to 1). Males have a higher lifetime recurrence rate than females. This fact is related to the rising prevalence of obesity brought on by unhealthy eating patterns and insufficient exercise.
Pathophysiology of Nephrolithiasis
Physical and chemical changes, as well as urine supersaturation, are involved in renal stone development. In a supersaturated environment, solutes precipitate in the urine and cause crystal concretions and nucleation. The conversion of a liquid to a solid is influenced by the PH and particular quantities of surplus chemicals. Supersaturation of stone-forming substances like calcium, phosphorus, uric acid, oxalate, and cystine, as well as inadequate urine volume, are risk factors for crystallization in nephrolithiasis. It is possible to prevent nephrolithiasis by avoiding supersaturation. 
Classifications of Kidney Stones (Nephrolithiasis).
The anomalies in urine’s chemical composition can affect kidney stones’ chemical makeup. The size, form, and chemical makeup of stones vary (mineralogy). Kidney stones are often divided into five kinds based on changes in mineral composition and pathophysiology. [5-7]
About 80% of all urinary calculi are calcium stones, which predominate among renal stones. Pure calcium oxalate (CaOx) (50%) and calcium phosphate (CaP, also known as apatite) (5%), as well as a combination of both (45%), may account for the group of calcium stones. Brushite (calcium hydrogen phosphate) or hydroxyapatite is the primary component of calcium stones. Most kidney stones contain calcium oxalate, which can take the forms of CaOx monohydrate (COM, also known as weddellite, CaC2O4-H2O), CaOx dihydrate (COD), or a combination of the two, which makes up more than 60%. Stone in COM is the most stable form in terms of thermodynamics. In clinical stones, COM is more frequently seen than COD.
Struvite or Magnesium Ammonium Phosphate Stones
Struvite stones, also referred to as infection stones and triple phosphate stones, are relatively common, occurring in 10-15% of cases. Patients with chronic urinary tract infections caused by urease-producing organisms, most frequently Proteus mirabilis, but also Klebsiella pneumonia, Pseudomonas Aeruginosa, and Enterobacter, are susceptible to it. Urease is required to break down urea into ammonia and CO2, which raises the pH of the urine to a higher level (usually > 7).
Since phosphate is less soluble at an alkaline pH than it is at an acidic pH, it precipitates on the insoluble ammonium compounds, creating a sizable staghorn stone. This form of stone develops more frequently in women than in men. Escherichia Coli cannot break down urea and is unrelated to struvite stones.
Urate or Uric Acid Stones
This stone makes up between 3 and 10% of all stone kinds. Purine-rich diets, particularly those heavy in animal protein like meat and fish, cause hyperuricosuria, low urine volume, and low urinary pH (pH 5.05), which worsens the development of uric acid stones. People with gouty arthritis may develop kidney stones. Idiopathic causes account for most cases of uric acid nephrolithiasis, and men are more likely than women to develop uric acid stones.
Less than 2% of all stone types are these stones. It is a hereditary condition that affects how an amino acid and cystine are transported. It leads to an overabundance of cystinuria, an autosomal recessive illness marked by decreased renal tubular uptake of cystine or cystine leakage into the urine, and is brought on by a genetic deficiency in the rBAT gene on chromosome 2. It does not dissolve in urine and causes the development of cystine stones. Cystinuria homozygotes excrete more than 600 millimoles of insoluble cystine each day. The only clinical sign of this cystine stone illness is the formation of urine cystine.
This stone represents 1% of all types. They are brought on by medications, including guaifenesin, triamterene, atazanavir, and sulfa medicines. For instance, those who use the HIV medicine indinavir sulfate, a protease inhibitor, increase the risk of kidney stones. Such lithogenic medications or their metabolites may deposit to create a nidus on already existing renal calculus. On the other hand, these medications may cause calculi to develop by their metabolic effect by interfering with the metabolism of calcium oxalate or purine.
Etiology of Nephrolithiasis
About 80% of patients with nephrolithiasis have calcium stones, most of which are predominantly made of calcium oxalate or calcium phosphate. Uric acid, struvite (magnesium ammonium phosphate), and cystine stones are prevalent, among other forms. It should be noted that a patient may have a stone that contains multiple crystal types.
The Risk Factors for Nephrolithiasis may be related to a certain medical condition, habits, or urine composition. 
- Personal and Family History: subjects are more likely to get kidney stones if someone in their family has had them. They have a higher risk of getting kidney stones if they already have one or more.
- Specific Diets: consuming a diet heavy in protein, sodium (salt), and sugar may increase the susceptibility to developing kidney stones. This particularly may occur when eating high amounts of sodium. The risk for kidney stones greatly increases when subjects consume significant amounts of salt because it increases the quantity of calcium their kidneys must filter.
- Obesity: a higher incidence of kidney stones has been linked with a high body mass index (BMI), a larger waist circumference, and increased weight.
- Dehydration: the risk of kidney stones can increase if subjects do not drink enough water every day. People who sweat heavily and live in dry, warm climates may have a higher incidence than others.
- Digestive Diseases and Surgeries: changes in the digestive system that impact calcium and water absorption can result from gastric bypass surgery, inflammatory bowel disease, or persistent diarrhea, which increases the levels of stone-producing chemicals in the urine.
- Medications and Supplements: the risk of kidney stones can be raised by substances including vitamin C, nutritional supplements, laxatives (when used excessively), calcium-based antacids, and some drugs for migraines or depression.
- Medical Disorders: the risk of kidney stones can also be increased by conditions like renal tubular acidosis, cystinuria, hyperparathyroidism, and frequent urinary tract infections.
If kidney stones can be removed with pee straining, urine microscopy can be used to analyze them. In general, each type of stone has the following crystal forms :
- Calcium Oxalate is formed like an envelope or a dumbbell.
In the majority of stones, calcium oxalate is the main ingredient. They frequently happen alongside conditions such as hypercalciuria, hyperoxaluria, hypomagnesuria, hypercystinuria, and hypocitraturia.
- Calcium Phosphate: wedge-shaped prisms that are amorphous and found in rosettes.
- Magnesium Ammonium Phosphate is formed like a coffin lid.
As observed in contagious stones, also known as struvite stones, when infections with urease-producing bacteria, such as Proteus mirabilis, Klebsiella pneumonia, Enterobacter, and Pseudomonas Aeruginosa, are present. Urine with a basic pH (>7) results from the urease’s production of ammonia and CO2.
- Rhomboid-Shaped Uric Acid
Usually idiopathic, these stones. They develop in people who consume much protein in their diets, which lowers the pH of their urine (to around 7), allowing uric acid stones to form.
- Cystine: Hexagon-Like
Hypercystinuria, a genetic abnormality in the transport of the amino acid cystine, leads to these stones.
Diagnosis and Tests
A basic or extensive metabolic panel can be utilized in laboratory testing to evaluate renal function. A urinalysis, urine electrolytes, and urine pH might also point to a particular kind of stone. Kidney stones evaluation can also be performed using the following tests: [10,11]
A medical practitioner tests the urine sample during a urinalysis. A medical professional will test a urine sample that the patient provides at a lab or a doctor’s office. A urine analysis can reveal whether the urine contains minerals that can cause kidney stones and bleeding. Patients might have a urinary tract infection if white blood cells and germs are in the urine.
Blood may be drawn by a medical professional, who will then submit it to a lab for analysis. A blood test can reveal if the patient has excessive levels of specific minerals in the blood that can cause kidney stones.
Medical practitioners use imaging tests to identify kidney stones. The tests may also reveal issues, such as an obstruction in the urinary tract or a birth condition, that led to the formation of a kidney stone. For these imaging studies, anesthesia is not required.
Abdominal or Kidney, Ureter, Bladder (KUB) X-ray
An abdominal X-ray is an image of the abdomen taken with low radiation levels and stored on film or a computer. NIH external link in a hospital or outpatient facility, an abdominal x-ray is taken, and a radiologist reviews the images. Patients can stand up or recline on a table for an abdominal X-ray. Patients could be asked to adjust their position so that the X-ray technician can take more images. The location of kidney stones in the urinary tract can be seen on abdominal X-rays. On an abdominal x-ray, some stones are not visible.
The first line of imaging study for nephrolithiasis is ultrasound. The technique is amenable to detecting urinary tract anomalies and hydronephrosis, a complication of urinary tract obstruction due to kidney stones. Although sensitive when stones are located in the renal pelvis or proximal ureters, it is less sensitive to detect stones located in the distal ureter.
Computed tomography (CT)
X-rays and computer technology are combined in CT scans to produce images of the urinary tract. Although a CT scan without contrast material is most frequently used to examine the urinary tract, a medical professional may administer a contrast material injection. A contrast medium is a dye or other material that facilitates imaging internal body structures.
A kidney stone’s size and position, whether it is obstructing the urinary tract, and any factors that may have contributed to the kidney stone’s formation can all be seen on a CT scan, as well as detecting differential diagnosis of nephrolithiasis.
Signs and Symptoms of Nephrolithiasis
The following are the most common signs and symptoms of a patient with kidney stones: 
|Signs and symptoms of kidney stone||n = 101 (%)|
|Pain in the back and side areas of the kidney||(71.28%)|
|Blood in urine||(23.76%)|
|Pain in the lower abdomen||(18.81%)|
The following conditions may mirror the flank pain brought on by nephrolithiasis:
- Pyelonephritis frequently manifests as flank discomfort, fever, chills, and pyuria.
- Torsion of an ovarian cyst.
- Ectopic conceptions.
- Digestive tract diseases, such as diverticulitis, appendicitis, and blockage.
- Biliary colic, hepatitis, and cholecystitis.
- Herpes zoster
- Renal cell cancers.
Treatment of Nephrolithiasis
Kidney stones cause excruciating discomfort. With NSAIDs, pain is controlled to the greatest extent possible by reducing smooth muscle activation and ureteral spasm. Additionally, increasing hydration intake is crucial. Tamsulosin may also help with stone passing and lessens stimulation of the smooth muscles. It is often helpful for those with diameters between 5 and 10 mm in the distal ureter.
Stones larger than 6mm likely need treatment, such as shock wave lithotripsy, rigid and flexible ureteroscopy, and percutaneous nephrolithotomy .
The Treatment depends on the etiology and type of stone, and many treatments are available for kidney stones.
Small Stones with Mild Symptoms
Most minor kidney stones can be treated non-invasively:
Drinking up to 1.9 to 3.6 liters of fluids each day can maintain the urine diluted and clear; this also helps to avert the formation of kidney stones. Drinking enough liquid, ideally and mainly water, until the urine is clear or almost clear unless there are contraindications to fluid intake.
Small stones may cause pain when passing. Therefore, physicians may prescribe ibuprofen (Trufen, Motrin IB, and other brands) or naproxen sodium and one of the Non-Steroid Anti-Inflammatory Drugs (NSAIDs) to treat minor pain.
To assist in passing kidney stones, physicians could prescribe alpha-blockers, which relax the smooth muscles in the ureter. Tamsulosin (Flomax), an example of an alpha-blocker, and the medication combination dutasteride and tamsulosin are also available (Jalyn).
The following Medications usage depends on the type of kidney stone and the underlying condition that has caused the stone formation :
|Name of Drug||Classification||Route of Administration||Dosage||Adverse Effects|
|Diclofenac||NSAIDs||Orally||50Mg/ 2-3times/day||Abdominal Pain, Diarrhea|
|Nifedipine||CCB||Orally||10Mg/ 3times/day||Headache, Flushing, Dizziness|
|Tamsulosin||Alpha-Blocker||Orally||0.4Mg/Once/daily (After Meal)||Dizziness, Headache, Nasal swelling|
|Allopurinol||Xanthine oxidase inhibitor||Orally||300Mg/Once/day||Allergic reactions, Skin rash, diarrhea|
|Penicillamine||Chelator||Orally||250Mg/Once/day||Abdominal Pain, Diarrhea, Ageusia|
|Hydrochlorothiazide||Diuretic||Orally||25Mg/Once/day||Low blood pressure, Headache, Dizziness|
Surgical Procedures for Nephrolithiasis
The main objectives of surgical kidney-stone management are to relieve pain for the patient, get rid of the infection, and restore kidney function that has been affected by large kidney or ureteral stones.
Surgical Approach for Nephrolithiasis
- Percutaneous Nephrolithotomy (PNL).
- Ureteroscopy (URS). Urgent decompression of the collecting system with ureteral stenting is suggested in patients who require emergency surgery for stone removal .
Reasons to perform emergency surgery – The collecting system should be decompressed immediately in the following clinical situations:
- Impeding stones and urinary tract infection (UTI) that is either suspected or proven.
- Acute Kidney injury and bilateral blockage.
- Single-working kidney and a unilateral blockage with AKI
Specific Recommendations Nephrolithotomy
The American Urological Association/Endourological Society guidelines recommend surgical management in the following clinical settings and provide specific indications for surgical stone treatment among adult patients who do not have an emergency indication for surgery .
- >10 mm ureteral stones.
- Simple distal ureteral stones less than 10 mm in size and have not passed after four to six weeks of observation, with or without medical expulsive therapy (MET).
- Symptomatic kidney stones in those with no other causes of pain.
- Pregnant individuals with kidney or ureteral stones which have not responded to the observation.
- Continuous renal blockage brought on by stones.
- Recurrent stone-related.
The two most frequently used surgical techniques to remove ureteral stones are ultrasound-guided ureteroscopy (URS) and shock wave lithotripsy (SWL).
The author does not report any conflict of interest.
This information is for educational purposes and is not intended to treat disease or supplant professional medical judgment. Physicians should follow local policy regarding the diagnosis and management of medical conditions.
- Alelign T, Petros B. Kidney Stone Disease: An Update on Current Concepts. Adv Urol. 2018;2018:3068365.
- López M, Hoppe B. History, epidemiology and regional diversities of urolithiasis. Pediatr Nephrol. 2010 Jan;25(1):49-59.
- Sigurjonsdottir VK, Runolfsdottir HL, Indridason OS, Palsson R, Edvardsson VO. Impact of nephrolithiasis on kidney function. BMC Nephrol. 2015 Aug 28;16:149.
- Aggarwal KP, Narula S, Kakkar M, Tandon C. Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators. Biomed Res Int. 2013;2013:292953.
- Chhiber N, Sharma M, Kaur T, Singla S. Mineralization in health and mechanism of kidney stone formation. International Journal of Pharmaceutical Science Invention. 2014;3:25–31.
- Barbasa C, Garciaa A, Saavedraa L, Muros M. Urinary analysis of nephrolithiasis markers. Journal of Chromatography B. 2002;781(1-2):433–455. doi: 10.1016/s1570-0232(02)00557-3.
- Alelign T, Petros B. Kidney Stone Disease: An Update on Current Concepts. Adv Urol. 2018;2018:3068365. Published 2018 Feb 4. doi:10.1155/2018/3068365
- Pruthi S, et al. 2022. Kidney stones.https://www.mayoclinic.org/diseases-conditions/kidney-stones/symptoms-causes/syc-20355755 [Accessed on 10/8/22]
- Coe FL, Evan A, Worcester E. Kidney stone disease. J Clin Invest. 2005 Oct;115(10):2598-608.
- expert, N., 2017. Diagnosis of Kidney Stones. https://www.niddk.nih.gov/health-information/urologic-diseases/kidney-stones/diagnosis. [Accessed on 10/8/22]
- Nojaba L, Guzman N. Nephrolithiasis. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. [Available from: https://www.ncbi.nlm.nih.gov/books/NBK559227/] [Accessed on 10/8/22]
- Jabbar F, Asif M, Dutani H, Hussain A, Malik A, Kamal MA, & Rasool, M. (2015). Assessment of the role of general, biochemical and family history characteristics in kidney stone formation. Saudi Journal of Biological Sciences, 22(1), 65-68
- Gnyawali D, Pradhan MM, Sigdel PR, Parajuli P, Chudal S, Poudyal S, Chapagain S, Luitel BR, Chalise PR, Sharma U, Gyawali PR. Efficacy of Tamsulosin plus Tadalafil versus Tamsulosin as Medical Expulsive Therapy for Lower Ureteric Stones: A Randomized Controlled Trial. Adv Urol. 2020;2020:4347598.
- Rehmam A. 2020. Kidney Stone Treatments and Medications. https://www.singlecare.com/conditions/kidney-stone-treatment-and-medications [Accessed on 10/8/22]
- Borofsky MS, Walter D, Shah O, Goldfarb DS, Mues AC, Makarov DV. Surgical decompression is associated with decreased mortality in patients with sepsis and ureteral calculi. J Urol. 2013;189(3):946-951. doi:10.1016/j.juro.2012.09.088.
- Assimos D, Krambeck A, Miller NL, et al. Surgical Management of Stones: American Urological Association/Endourological Society Guideline, PART II. J Urol. 2016;196(4):1161-1169. doi:10.1016/j.juro.2016.05.091.
Dr.Sharif Samir Alijla, is a general medical doctor and a well-rounded professional that cares and treats patients. I participated in many medical studies and conferences, I've launched a range of community initiatives and taken part in a variety of leadership and change training programs. I worked as an author for many medical websites such as TebFact . I specialized in writing medical articles from authoritative and updated sources in a simple and smooth the way for the reader.