Kidney stone overview

# Overview
Nephrolithiasis  is a common condition encountered in emergency rooms and also as an outpatient in the primary care setting. Its incidence and prevalence is increasing both in women and men, with women slightly incraing recently due to obesity and lifestyle changes. Nephrolithiasis may be classified into 4 subtypes/groups: calcium stones, struvite stones, uric acid stones and cystine stones. The common causes of nephrolithiasis include hypercalcemia, hyperparathyroidism, hypercalciuria, infection with urea splitting microorganisms like Proteus and Pseudomonas, gout, dehydration, inflammatory bowel disease. Less common causes of nephrolithiasis include drugs such as loop diuretics, Acetazolamide, ciprofloxacin, indinavir, guaifenesin triamterene and magnesium trisilicate. It is understood that nephrolithiasis is the result of combination of different mechanism responsible for different types of stones. Calcium stones are the most common type of kidney stones. Approximately 80% of all calcium stones are calcium oxalate stones. The pathophysiology of calcium stones is complex and involves dietary concerns, hypercalciuria, hypocitaturia, hyperoxaluria, hyperuricosuria and biomineralization. The underlying pathophysiological mechanisms responsible for uric acid stones are low urine volume, hyperuricosuria and high acidic urine. Cystinuria is a rare hereditary gene disorder which causes impaired renal reabsorption of cationic amino acids and cystine. It is caused by mutations in either of the two subunits (rBAT(SLC3A2) and b0,+AT(SLC7A9)) forming cystine stones. Struvite stones are usually seen in patients which have infection with urease +ve organisms. Urine pH is usually alkaline (>7.2). Nephrolithiasis can be passed on to following generations due to rare causes of hypercalciuria such as hereditary distal renal tubular acidosis, dent disease, Bartter syndrome types III and IV, autosomal dominant hypocalcemic hypercalciuria and familial hypomagnesemia. Nephrolithiasis associated with Hyperparathyroidism, Gout, Hypocitaturia, Sarcoidosis, chronic urinary tract infections and Obesity.On gross pathology, the characteristic findings of nephrolithiasis include location = 80% unilateral, usually in calyces, pelvis or bladder. The size=variable, 2-3 mm usually. All stones contain an organic matrix of mucoprotein. The shape of struvite stone is staghorn shaped. On microscopic histopathological analysis, the characteristic findings of nephrolithiasis include different shapes of stones/crystals are such as cystine= hexagonal, struvite= coffin lid shape, calcium oxalate= pyramid shape to dumbbell shape and uric acid= rectangular/rhomboidal. Oxalate crystals are highlighted by polarized light. Also, foreign body giant cells and macrophages are seen with the stones.It has increased from every 1 in 20 to 1 in 11 person in United States has kidney stones. If left untreated, 10 mm in diameter, uncontrolled pain, Anuria, or there is Acute kidney injury. The mainstay of treatment for nephrolithiasis is medical therapy. Surgery is usually reserved for patients with either persistent and severe pain, renal failure, kidney infection and when stone fails to pass or move after 30 days. The surgeries which are being used currently include extracorporeal shockwave lithotripsy, ureteroscopy and percutaneous nephrolithotomy. Effective measures for the primary prevention of nephrolithiais include diet control and high fluid intake. Effective measures for the secondary prevention of nephrolithiasis include measures to prevent recurrence of the stones and prevent complications. It includes measures like correcting hydration and dietary habits. Drugs like allopurinol to prevent hyperuricemia, potassium citrate to alkalinize the urine and avoidance or judicious use of diuretics.

# Historical Perspective
Urinary stones was first discovered by  E. Smith, an English archaeologist, in 1901 when he found bladder stone in Egyptian mummy aged 4500-7000 year. In the 4th century B.C., when Hipprocratic Oath was made,the line that refers to stones was mentioned:  I will not use the knife, not even on sufferers from stone, but will withdraw in favor of such men as are engaged in this work....I will not cut for the stone, but will leave this to be done by practitioners of this work.In the 8th century B.C, treatment strategy for stone removal was developed by an Indian surgeon, Sushruta as written in Sushruta Samhita. In 1976, the first percutaneous stone surgery was performed by Fernstrom and Johansson. The famous cases of nephrolithiasis includes: in 1549, Michelangelo was diagnosed and treated for uric acid stones;in 1724, Sir Isaac Newton noted that he passed two small pea-sized stones and in 1961, Roger Moore, aka James Bond, experienced three kidney stone episodes and treated with surgery.

# Classification
Nephrolithiasis may be classified into 4 subtypes/groups: calcium stones, struvite stones, uric acid stones and cystine stones

# Pathophysiology
It is understood that nephrolithiasis is the result of combination of different mechanism responsible for different types of stones. Calcium stones are the most common type of kidney stones. Approximately 80% of all calcium stones are calcium oxalate stones. The pathophysiology of calcium stones is complex and involves dietary concerns, hypercalciuria, hypocitaturia, hyperoxaluria, hyperuricosuria and biomineralization. The underlying pathophysiological mechanisms responsible for uric acid stones are low urine volume, hyperuricosuria and high acidic urine. Cystinuria is a rare hereditary gene disorder which causes impaired renal reabsorption of cationic amino acids and cystine. It is caused by mutations in either of the two subunits (rBAT(SLC3A2) and b0,+AT(SLC7A9)) forming cystine stones. Struvite stones are usually seen in patients which have infection with urease +ve organisms. Urine pH is usually alkaline (>7.2). Nephrolithiasis can be passed on to following generations due to rare causes of hypercalciuria such as hereditary distal renal tubular acidosis, dent disease, Bartter syndrome types III and IV, autosomal dominant hypocalcemic hypercalciuria and familial hypomagnesemia. Nephrolithiasis associated with Hyperparathyroidism, Gout, Hypocitaturia, Sarcoidosis, chronic urinary tract infections and Obesity.On gross pathology, the characteristic findings of nephrolithiasis include location = 80% unilateral, usually in calyces, pelvis or bladder. The size=variable, 2-3 mm usually. All stones contain an organic matrix of mucoprotein. The shape of struvite stone is staghorn shaped. On microscopic histopathological analysis, the characteristic findings of nephrolithiasis include different shapes of stones/crystals are such as cystine= hexagonal, struvite= coffin lid shape, calcium oxalate= pyramid shape to dumbbell shape and uric acid= rectangular/rhomboidal. Oxalate crystals are highlighted by polarized light. Also, foreign body giant cells and macrophages are seen with the stones.

# Causes
The common causes of nephrolithiasis include hypercalcemia, hyperparathyroidism, hypercalciuria, infection with urea splitting microorganisms like Proteus and Pseudomonas, gout, dehydration, inflammatory bowel disease. Less common causes of nephrolithiasis include drugs such as loop diuretics, Acetazolamide, ciprofloxacin, indinavir, guaifenesin triamterene and magnesium trisilicate.

# Differentiating Nephrolithiasis from Other Diseases
Nephrolithiasis should be differentiated from other conditions presenting with acute flank or upper abdominal pain, hematuria, nausea and vomiting.

# Epidemiology and Demographics
In 2000, the incidence/prevalence of nephrolithiasis was estimated to be 116 cases per 100,000 individuals in the United States.The prevalence of nephrolithiasis is approximately 1116 per 100,000 individuals worldwide. It has increased from every 1 in 20 to 1 in 11 person in United States has kidney stones. According to American Journal of Kidney disease, 2016, 8% of women and 16% of men are developing nephrolithiasis by the age of 70 years. According to 2000 National Hospital Ambulatory Medical Care Survey of the United State,s there is an annual burden of more than 1,100,000 emergency department visits with a primary diagnosis of renal calculus or colic. Patients of all age groups may develop nephrolithiasis. The incidence of nephrolithiasis increases with age.  At initial diagnosis, the mean age was 44.8 years in men and 40.9 years in women. Nephrolithiasis usually affects individuals of the white/Caucasian ethnicity. Males are more commonly affected by nephrolithiaisis than females. The male to female ratio is approximately 2 to 1. The trend keeps on changing , a study in 2010 claims the incidence rate ratio of men to women with urinary tract stones has narrowed from 3.4 to 1.3. Females are having increasing incidence rates owing to increase lifestyle disease like obesity. The majority of nephrolithiasis cases are reported in southeast belt of the United States. The number of cases increase from north to south and from west to east. The states of North Carolina, South Carolina, Georgia, Alabama, Mississippi, and Tennessee are considered in the stone belt. The ambient temperature and sunlight levels as risk factors for stones and differences in exposure to temperature and sunlight and beverages are also responsible for geographic variability.

# Risk Factors
Common risk factors in the development of nephrolithiasis include dietary habits, low urinary pH, hypercalcemia, hypercalciuria, hyperoxaluria, hyperuricemia, hyperuricosuria, obesity, diabetes mellitus, environmental factors such as hot climate, drugs such as thiazide, furosemide, sulfadiazine, indinavir. Less common risk factors in the development of nephrolithiasis include hypocitraturia, beverage use, drugs like ciprofloxacin and triamterene.

# Screening
There is insufficient evidence to recommend routine screening for nephrolithiaisis.

# Natural History, Complications, and Prognosis
If left untreated, <30% of patients with nephrolithiasis may progress to develop renal colicky pain due to increase in rate of growth.Most of the stones pass spontaneously. about 10-20% of symptom-causing stones fail to pass. Lower poles stones were significantly less likely to cause symptoms or pass spontaneously. They can progress to hydronephrosis especially when combined or superimposed by urinary tract infection. Common complications of nephrolithiasis include hydronephrosis, chronic renal failure, hypertension, cardiovascular disease, and increased risk of fracture. Prognosis is generally excellent. Approximately 80-85% resolve spontaneously. Recurrence rates for calcium stones after the initial event is 4050% at the end of 5 years and 5060% at the end of 10 years.

# Diagnosis

## Diagnostic Study of choice
CT scan is the gold standard test for the diagnosis of nephrolithiasis.

## History and Symptoms
The patients with nephrolithiasis may have a positive history of flank pain. Common symptoms of nephrolithiasis include flank pain progressing downward and anteriorly into the groin as the stone moves, hematuria, nausea and vomiting urinary frequency and urgency. Less common symptoms include burning micturition.

## Physical Examination
Patients with nephrolithiasis usually appear in pain and trying to achieve a comfortable position. Common physical examination findings of nephrolithiasis include costovertebral angle tenderness, may accompany fever with increased heart rate and respiratory rate. They can have hypoactive bowel sounds due to ileus caused by severe pain. They can have hematuria in microscopic exmaination.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of nephrolithiasis include hypercalcemia, hypercalciuria, hyperoxaluria, hypocitraturia, hyperuricemia and hyperuricosuria.

## Electrocardiogram
There are no ECG findings associated with nephrolithiasis.

## X-ray
An x-ray may be helpfulin  the diagnosis of nephrolithiasis. Findings on an x-ray suggestive of nephrolithiasis include radiopaque stones such as Calcium oxalate, calcium phosphate, struvite and radiolucent stones which includes uric acid stones and cystine stones.

## Ultrasound
Abdominal ultrasound may be helpful in the diagnosis of nephrolithiasis Findings on an ultrasound suggestive of/diagnostic of nephrolithiasis include: echogenic or hyperechogenic foci, acoustic shadowing, twinkle artefact on colour Doppler, colour comet-tail artefact , and increased resistive index which signifies acute obstruction.

## CT scan
Abdominal and pelvic CT scan is helpful in the diagnosis of nephrolithiasis. Findings on CT scan diagnostic of nephrolithiasis include radiopacity showing the location, density and composition of stones calcium oxalate +/- calcium phosphate: 400-600 HU, struvite (triple phosphate): usually opaque but variable, pure calcium phosphate 400-600 HU, uric acid: 100-200 HU and cystine: opaque.

## MRI
There are no MRI findings associated with nephrolithiasis. However, a MRI may be helpful in the diagnosis of complications of nephrolithiasis, which include hydronephrosis.

## Other Imaging Findings
There are no other imaging findings associated with nephrolithiasis.

## Other Diagnostic Studies
There are no other diagnostic studies associated with nephrolithiasis.

# Treatment

## Medical Therapy
The treatment of nephrolithiasis involves different measures e.g non pharmacological measures consisting of increased fluid intake, straining an dietary restrictions. Pharmacological measures include pain relief using NSAIDs and opioids., helping passage of stone spontaneously with drugs like tamsulosin and nifedipine. The treatment of underlying cause and being specific to type of stones is very important.It involves treating primary hyperparathyroidism and Renal tubular acidosis. For those having high urinary calcium, Hydrochlorothiazide or Chlorthalidone are used. For recurrent stones and high urine uric acid, Allopurinol is used. For recurrent stones and hypocitraturia, Potassium citrate is sued to alkalinize the urine. For uric acid stones, alkalinizing urine with potassium citrate/potassium bicarbonate is done and if needed Allopurinol is also used. For struvite stones, medical therapy is not of much help, although urease inhibitors such as acetohydroxamic acid can be given in urease +ve etiology. For cysteine stones, again alkalinizing urine helps along with Tiopronin. The Urological consult is needed when stone >10 mm in diameter, uncontrolled pain, Anuria, or there is Acute kidney injury.

## Surgery
The mainstay of treatment for nephrolithiasis is medical therapy. Surgery is usually reserved for patients with either persistent and severe pain, renal failure, kidney infection and when stone fails to pass or move after 30 days. The surgeries which are being used currently include extracorporeal shockwave lithotripsy, ureteroscopy and percutaneous nephrolithotomy.

## Primary Prevention
Effective measures for the primary prevention of nephrolithiais include diet control and high fluid intake.

## Secondary Prevention
Effective measures for the secondary prevention of nephrolithiasis include measures to prevent recurrence of the stones and prevent complications. It includes measures like correcting hydration and dietary habits. Drugs like allopurinol to prevent hyperuricemia, potassium citrate to alkalinize the urine and avoidance or judicious use of diuretics.