Kidney stones, one of the most painful of the urologic disorders, are not a product of modern life. Scientists have found evidence of kidney stones in a 7,000-year-old Egyptian mummy. Unfortunately, kidney stones are one of the most common disorders of the urinary tract. Men tend to be affected more frequently than women. Kidney stones may contain various combinations of chemicals. The term nephrolithiasis (or "renal calculus") refers to stones located in the kidney, while ureterolithiasis refers to stones in the ureter. The term cystolithiasis (or vesical calculi) refers to stones which form or have passed into the bladder (Fig. 1).

The most common type of stone contains calcium in combination with either oxalate or phosphate. These chemicals are part of a person's normal diet and make up important parts of the body, such as bones and muscles. Cystinuria and hyperoxaluria are two other rare, inherited metabolic disorders that often cause kidney stones. Hyperuricosuria is a disorder of uric acid metabolism, gout, and excess intake of vitamin D, urinary tract infections, and blockage of the urinary tract. Struvite stones are formed due to the unknown infections. Certain diuretics which are commonly called water pills or calcium-based antacids may increase the risk of forming kidney stones by increasing the amount of calcium in the urine. ⁶

Major cause of acute and chronic renal failure is lithiasis (stone formation), which includes both nephrolithiasis (stone formation in kidney) and urolithiasis (stone formation in ureters or bladder or both) ⁷. Kidney stone disease is a common disorder estimated to occur in approximately 12% of the population ⁸. Lithiasis is male predominant disorder, with a recurrence rate of 70-81% in male and 47-60% in female ⁷. Urinary stone disease is a serious medical consequences, throughout a patients lifetime. In addition, the incidence of kidney stones has been increased in western societies in the last five decades, in association with economic development.

Most calculi in the urinary system arise from a common component of urine eg calcium oxalate (CaOx), representing up to 80% of analyzed stone ⁹.

The recurrence of urolithiasis represents a major problem as patients who have formed one stone are more likely to form another. The standard drugs used to prevent urolithiasis are not effective in all patients, and many of them have adverse effects that compromise their long term use. The present day management of nephrolithiasis with open renal surgery is unusual and rarely used only since the introduction of Extracorporeal Shock Wave Lithotripsy (ESWL) which has almost become the standard procedure for eliminating kidney stones.

However, in addition to the traumatic effect of shockwaves, persistent residue stone fragments and the possibility of infection suggests that ESWL may cause acute renal injury, a decrease in renal function and an increase in stone recurrence ^{10, 11}. Hence the search for antilithiatic drugs to be effective without side effects from natural sources has gained great potential. Many plants conveniently available in India are used in traditional folklore medicine for the treatment of lithiasis (kidney stone).

Endoscopic stone removal and extracorporeal shock wave lithotripsy have revolutionized the treatment of urolithiasis but do not prevent the likelihood of new stone formation ¹². Various therapies including thiazide diuretics and alkali-citrate are being used in attempt to prevent recurrence of hypercalciuria- and hyperoxaluria-induced calculi but scientific evidence for their efficacy is less convincing ¹³. Medicinal plants have played a significant role in various ancient traditional systems of medication. Even today, plants provide a cheap source of drugs for majority of world’s population ¹⁴. Several pharmacological investigations on the medicinal plants used in traditional antiurolithic therapy have revealed their therapeutic potential in the in vitro or in vivo model ^{15, 16}.

Classification of Kidney Stone:

Kidney Stones can be classified according to the Composition and Location of Kidney Stones.

Chemical composition wise classification:

Calcium-containing stones:

By far, the most common type of kidney stones worldwide contains calcium. For example, calcium-containing stones represent about 80% of all cases in the United States; these typically contain calcium oxalate either alone or in combination with calcium phosphate in the form of apatite or brushite ^{17, 18}. Factors that promote the precipitation of oxalate crystals in the urine, such as primary hyperoxaluria, are associated with the development of calcium oxalate stones ¹⁹. The formation of calcium phosphate stones is associated with conditions such as hyperparathyroidism ²⁰ and renal tubular acidosis ²¹.

Struvite stones

About 10–15% of urinary calculi are composed of struvite (ammonium magnesium phosphate, NH₄MgPO₄·6H₂O) ²². Struvite stones (also known as "infection stones", urease or triple-phosphate stones), form most often in the presence of infection by urea-splitting bacteria. Using the enzyme urease, these organisms metabolize urea into ammonia and carbon dioxide. This alkalinizes the urine, resulting in favorable conditions for the formation of struvite stones. Proteus mirabilis, Proteus vulgaris and Morganella morganii are the most common organisms isolated; less common organisms include Ureaplasma urealyticum, and some species of Providencia, Klebsiella, Serratia, and Enterobacter. These infection stones are commonly observed in people who have factors that predispose them to urinary tract infections, such as those with spinal cord injury and other forms of neurogenic bladder, vesicoureteral reflux, and obstructive uropathies. They are also commonly seen in people with underlying metabolic disorders, such as idiopathic hypercalciuria, hyperparathyroidism, and gout. Infection stones can grow rapidly, forming large calyceal staghorn (antler-shaped) calculi requiring invasive surgery such as percutaneous nephrolithotomy for definitive treatment ²².

Uric acid stones

About 5–10% of all stones are formed from uric acid ²³. People with certain metabolic abnormalities, including obesity ²⁴, may produce uric acid stones. They also may form in association with conditions that cause hyperuricosuria (an excessive amount of uric acid in the urine) with or without hyperuricemia (an excessive amount of uric acid in the serum). They may also form in association with disorders of acid/base metabolism where the urine is excessively acidic (low pH), resulting in precipitation of uric acid crystals. A diagnosis of uric acid urolithiasis is supported by the presence of a radiolucent stone in the face of persistent urine acidity, in conjunction with the finding of uric acid crystals in fresh urine samples ²⁵.

Other types

People with certain rare inborn errors of metabolism have a propensity to accumulate crystal-forming substances in their urine. For example, those with cystinuria, cystinosis, and Fanconi syndrome may form stones composed of cystine. People afflicted with xanthinuria often produce stones composed of xanthine. People afflicted with adenine phosphoribosyltransferase deficiency may produce 2,8-dihydroxyadenine stones²⁶, alkaptonurics produce homogentisic acid stones, and iminoglycinurics produce stones of glycine, proline and hydroxyproline^27,28. Urolithiasis has also been noted to occur in the setting of therapeutic drug use, with crystals of drug forming within the renal tract in some people currently being treated with agents such as indinavir ²⁹, sulfadiazine ³⁰ and triamterene ³¹.

Location wise classification:

Urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder. Nephrolithiasis refers to the presence of such calculi in the kidneys. Calyceal calculi refers to aggregations in either the minor or major calyx, parts of the kidney that pass urine into the ureter (the tube connecting the kidneys to the urinary bladder). The condition is called ureterolithiasis when a calculus is located in the ureter. Stones may also form or pass into the bladder, a condition referred to as cystolithiasis ³².

Causes of Kidney stones: ³⁸

While certain foods may promote stone formation in people who are susceptible, scientists do not believe that eating any specific food causes stones to form in people who are not susceptible.

A person with a family history of kidney stones may be more likely to develop stones. Urinary tract infections, kidney disorders such as cystic kidney diseases, and certain metabolic disorders such as hyperparathyroidism are also linked to stone formation.

In addition, more than 70 percent of people with a rare hereditary disease called renal tubular acidosis develop kidney stones.

Cystinuria and hyperoxaluria are two other rare, inherited metabolic disorders that often cause kidney stones. In cystinuria, too much of the amino acid cystine, which does not dissolve in urine, is voided, leading to the formation of stones made of cystine. In patients with hyperoxaluria, the body produces too much oxalate, a salt. When the urine contains more oxalate than can be dissolved, the crystals settle out and form stones.

Hypercalciuria is inherited, and it may be the cause of stones in more than half of patients. Calcium is absorbed from food in excess and is lost into the urine. This high level of calcium in the urine causes crystals of calcium oxalate or calcium phosphate to form in the kidneys or elsewhere in the urinary tract.

Other causes of kidney stones are hyperuricosuria, which is a disorder of uric acid metabolism; gout; excess intake of vitamin D; urinary tract infections; and blockage of the urinary tract. Calcium oxalate stones may also form in people who have chronic inflammation of the bowel or who have had an intestinal bypass operation, or ostomy surgery. As mentioned earlier, struvite stones can form in people who have had a urinary tract infection. People who take the protease inhibitor indinavir, a medicine used to treat HIV infection, may also be at increased risk of developing kidney stones.

Symptoms of Kidney stones:

The hallmark of stones that obstruct the ureter or renal pelvis is excruciating, intermittent pain that radiates from the flank to the groin or to the genital area and inner thigh ³³. This particular type of pain, known as renal colic, is often described as one of the strongest pain sensations known ³⁴. Renal colic caused by kidney stones is commonly accompanied by urinary urgency, restlessness, hematuria, sweating, nausea and vomiting. It typically comes in waves lasting 20 to 60 minutes caused by peristaltic contractions of the ureter as it attempts to expel the stone ³³. http://en.wikipedia.org/wiki/Kidney_stone. The embryological link between the urinary tract, the genital system and the gastrointestinal tract is the basis of the radiation of pain to the gonads, as well as the nausea and vomiting that are also common in urolithiasis ³⁵. Postrenal azotemia and hydronephrosis can be observed following the obstruction of urine flow through one or both ureters ³⁶.

Kidney stones often do not cause any symptoms. Usually, the first symptom of a kidney stone is extreme pain, which begins suddenly when a stone moves in the urinary tract and blocks the flow of urine. Typically, a person feels a sharp, cramping pain in the back and side in the area of the kidney or in the lower abdomen. Later, pain may spread to the groin.

If the stone is too large to pass easily, pain continues as the muscles in the wall of the narrow ureter try to squeeze the stone into the bladder. As the stone moves and the body tries to push it out, blood may appear in the urine, making the urine pink. As the stone moves down the ureter, closer to the bladder, a person may feel the need to urinate more often or feel a burning sensation during urination.

If fever and chills accompany any of these symptoms, an infection may be present. In this case, a person should contact a doctor immediately.

Treatment of Kidney stones: ³⁸

Kidney Stones can be treated by one of the following way,

Lifestyle Changes

A simple and most important lifestyle change to prevent stones is to drink more liquids—water is best. Someone who tends to form stones should try to drink enough liquids throughout the day to produce at least 2 quarts of urine in every 24-hour period.

In the past, people who form calcium stones were told to avoid dairy products and other foods with high calcium content. Recent studies have shown that foods high in calcium, including dairy products, may help prevent calcium stones. Taking calcium in pill form, however, may increase the risk of developing stones.

Patients may be told to avoid food with added vitamin D and certain types of antacids that have a calcium base. Someone who has highly acidic urine may need to eat less meat, fish, and poultry. These foods increase the amount of acid in the urine.

To prevent cystine stones, a person should drink enough water each day to dilute the concentration of cystine that escapes into the urine, which may be difficult. More than a gallon of water may be needed every 24 hours, and a third of that must be drunk during the night.

Medical Therapy

A doctor may prescribe certain medications to help prevent calcium and uric acid stones. These medicines control the amount of acid or alkali in the urine, key factors in crystal formation. The medicine allopurinol may also be useful in some cases of hyperuricosuria.

Doctors usually try to control hypercalciuria, and thus prevent calcium stones, by prescribing certain diuretics, such as hydrochlorothiazide. These medicines decrease the amount of calcium released by the kidneys into the urine by favoring calcium retention in bone. They work best when sodium intake is low.

Rarely, patients with hypercalciuria are given the medicine sodium cellulose phosphate, which binds calcium in the intestines and prevents it from leaking into the urine.

If cystine stones cannot be controlled by drinking more fluids, a doctor may prescribe medicines such as Thiola and Cuprimine, which help reduce the amount of cystine in the urine.

For struvite stones that have been totally removed, the first line of prevention is to keep the urine free of bacteria that can cause infection. A patient’s urine will be tested regularly to ensure no bacteria are present.

If struvite stones cannot be removed, a doctor may prescribe a medicine called acetohydroxamic acid (AHA). AHA is used with long-term antibiotic medicines to prevent the infection that leads to stone growth.

People with hyperparathyroidism sometimes develop calcium stones. Treatment in these cases is usually surgery to remove the parathyroid glands, which are located in the neck. In most cases, only one of the glands is enlarged. Removing the glands cures the patient’s problem with hyperparathyroidism and kidney stones.

Surgical Treatment

Surgery may be needed to remove a kidney stone if it

 does not pass after a reasonable period of time and causes constant pain

 is too large to pass on its own or is caught in a difficult place

 blocks the flow of urine

 causes an ongoing urinary tract infection

 damages kidney tissue or causes constant bleeding

 has grown larger, as seen on follow-up x rays

Until 20 years ago, open surgery was necessary to remove a stone. The surgery required a recovery time of 4 to 6 weeks. Today, treatment for these stones is greatly improved, and many options do not require major open surgery and can be performed in an outpatient setting.

Fig.: 2 Extracorporeal shock wave lithotripsy

Extracorporeal Shock Wave Lithotripsy:

Extracorporeal shock wave lithotripsy (ESWL) is the most frequently used procedure for the treatment of kidney stones. In ESWL, shock waves that are created outside the body travel through the skin and body tissues until they hit the denser stones. The stones break down into small particles and are easily passed through the urinary tract in the urine (Fig. 2).

Fig.: 3 Percutaneous Nephrolithotomy

Several types of ESWL devices exist. Most devices use either x rays or ultrasound to help the surgeon pinpoint the stone during treatment. For most types of ESWL procedures, anesthesia is needed.

In many cases, ESWL may be done on an outpatient basis. Recovery time is relatively short, and most people can resume normal activities in a few days.

Complications may occur with ESWL. Some patients have blood in their urine for a few days after treatment. Bruising and minor discomfort in the back or abdomen from the shock waves can occur. To reduce the risk of complications, doctors usually tell patients to avoid taking aspirin and other medicines that affect blood clotting for several weeks before treatment.

Sometimes, the shattered stone particles cause minor blockage as they pass through the urinary tract and cause discomfort. In some cases, the doctor will insert a small tube called a stent through the bladder into the ureter to help the fragments pass. Sometimes the stone is not completely shattered with one treatment, and additional treatments may be needed.

As with any interventional, surgical procedure, potential risks and complications should be discussed with the doctor before making a treatment decision.

Percutaneous Nephrolithotomy:

Sometimes a procedure called percutaneous nephrolithotomy is recommended to remove a stone. This treatment is often used when the stone is quite large or in a location that does not allow effective use of ESWL.

In this procedure, the surgeon makes a tiny incision in the back and creates a tunnel directly into the kidney. Using an instrument called a nephroscope, the surgeon locates and removes the stone. For large stones, some type of energy probe—ultrasonic or electrohydraulic—may be needed to break the stone into small pieces. Often, patients stay in the hospital for several days and may have a small tube called a nephrostomy tube left in the kidney during the healing process (Fig. 3).

One advantage of percutaneous nephrolithotomy is that the surgeon can remove some of the stone fragments directly instead of relying solely on their natural passage from the kidney.

Fig.: 4 Ureteroscopic Stone Removal

Evaluation Technique for Kidney Stone:

Table: 1 List of evaluation Techniques for of Kidney Stone:

In vitro	In vivo
In vitro activity on crystallization & renal tubular epithelial cell injury.	Ethylene glycol induced Nephrolithiasis.
In vitro Urolithiatic action by a Double diffusion gel growth technique.	Trans 4-hydroxy-1-proline Induced urolithiasis.
By homogenous precipitation method.	Urolithiasis in rat model Using cal. Oxalate/Zinc Disc implants.

Following are the list of Plants used for Kidney Stone ³⁷:

Table: 2 List of Plants used for Kidney Stone

PLANT	FAMILY	USES
Achyranthus aspera	Amaranthaceae	Herb Diuretic, Renal dropsies
Aerva javanica	Amaranthaceae	Herb Diuretic, Purgative, Demulcent
Aerva lanata	Amaranthaceae	Cough, Sore throat, Diabetes, Lithiasis
Ammannia baccifera	Lythraceae	Ringworm, Parasitic skin affection, Anti-typhoid, Anti-tubercular properties
Arctostaphylos ura ursi	Asteraceaer	Diuretic, Diaphoretic, Gout, Skin affection
Ascyrum hypericoides	Asclepidaceae	Emetic and Cathartic
Asparagus racemosus	Liliaceae	Herb tonic, Diuretic, Galactagogue
Berginia ligulata	Saxifragaceae	Astringent. Diuretic, Lithontriptic
Bridolia montana	Euphobiaceae	Bark Astringent, Anthelminetic
Bueta frondosa	Papilionaceae	Diuretic, Purgative
Caesalpinia huga	caesalpinioceae	Root Diuretic, Lithontriptic
Celosia argentla	Amararanthaceae	Diarrhoea, Eye troubles, Sore mouth
Chelidonium majus	Papaveraceae	Diuretic, Antispasmodic, bitter
Chimaphila numbellata	Cruciferae	Diuretic, Expectorant, Stimulant
Crateva religiosa	Capparidaceae	Laxative, Calculus, Urinary affection
Curcuma longa	Zingiberaceae	Diuretic, Choleretic, Hepatoprotective
Cyperus scariogus	Cyperaceae	Diuretic, Diaphoretic, Astringent
Desmodium styracifolium	Papilionaceae	Roots Emmenagogue, Stomachic
Didymocarpus pedicellata	Gesneriaceae	Leaves Lithontriptic
Didymocarpus pedicellata	Gesneriaceae	Lithontriptic
Dolichos biflorus	Leguminoceae	Diuretic, Astringent, Tonic
Dolichos biflorus	Leguminaceae	Diuretic, Astringent, Tonic
Elettaria cardamomum	Zingiberaceae	Diuretic, Carminative, Aromatic stimulant
Equisitum arvense	Equisetaceae	Diuretic, Dropsy, Gravel, Renal affection
Eupatorium puipurecum	Compositae	Diuretic, Antiscorbutic, cathartic, emetic
Fogonia bruguieri	Umbelliferae	Diuretic, Mildly carminative
Garcinia pictoria	Guttiferae	Dropsical affection
Gynocardia odorata	Flacourtiaceae	Fish poison ,Insecticidal, Skin aliments
Homonia riparia	Euphorbiaceae	Root Laxative, Diuretic, Stone in bladder
Hygrophila spinosa	Acanthaceae	Strongly Diuretic
Mentha piperita	Labiatae	Spasmolytic, Carminatives, Febrifuge
Mimosa pudica	Mimosaceae	Gravel, Urinary complaints
Musa pardisiaca	Musaceae	Laxative, Uraemia, Nephritis, Hypertension
Nothosaerva brachiata	Laminaceae	Diuretic, Neuralgia, Convulsions
Ocimum basilicum	Labiatae	Stomachic, Alexipharmac, Antipyretic, Antihelminitic
Onosma bracteatum	Boraginaceae	Tonic, Demulcent, Diuretic, Spasmolytic
Orthosiphon aristatus	Labiatae	Diuretic, Anti-inflammatory, Antibacterial
Parmelia perlata	Parmelialannostene	Diuretic, Lithontriptic, Astringent
Pavonia odorata	Malvaceae	Antipyretic, Stomachic, Refrigerant, Dysentery
Petroselinum crispum	Umbelliferae	Mild diuretic, Abortifacient, Digestive
Rotula	Baraginaceae	Diuretic, Laxative, Piles, Stone in bladder
Rubia cordifolia	Rubiaceae	Antidysentric, Antiseptic, Deobstruent
Rubia cordifolia	Rubiaceae	Antidysentric, Antiseptic, Deobstruent
Spergularia rubra	Caryophyllaceae	Cystitis and Urethral pain
Tectona grandis	Verbenaceae	Biliousness, Bronchitis, Urinary discharge
Trianthema porlulacastrum	Azizoaceae	Roots Cathartic, Irritant, Abortifacient, Asthma, Leaves Diuretic
Tribulus terrestris	Zygophyllaceae	Diuretic, Micturition, Calculous affection
Vernomia cineea	Compositae	Anthelmintic, Diarrhoea
Zingiber officinale	Zingiberaceae	Carminative, Diaphoretic, Bronchitis

Ureteroscopic Stone Removal:

Although some stones in the ureters can be treated with ESWL, ureteroscopy may be needed for mid- and lower-ureter stones. No incision is made in this procedure. Instead, the surgeon passes a small fiberoptic instrument called a ureteroscope through the urethra and bladder into the ureter (Fig. 4). The surgeon then locates the stone and either removes it with a cage-like device or shatters it with a special instrument that produces a form of shock wave. A small tube or stent may be left in the ureter for a few days to help urine flow. Before fiber optics made ureteroscopy possible, physicians used a similar “blind basket” extraction method. But this technique is rarely used now because of the higher risks of damage to the ureters.

Herbal Drugs for Kidney Stone:

Though the large numbers of drugs are available for the treatment of Kidney Stone, the relief offered by them is mainly symptomatic and short lived. Moreover the side effects of these drugs are also quite disturbing. Recently there has been a shift in universal trend from synthetic to herbal medicine, which we can say ‘Return to Nature’.

Medicinal plants have been known for millennia and are highly esteemed all over the world as a rich source of therapeutic agents for the prevention of diseases and ailments. A large number of medicinal plants have been used traditionally for the treatment of Kidney Stone and have been scientifically proven to have antilithiatic properties. Various therapies including thiazide diuretics and alkali-citrate are being used in attempt to prevent recurrence of hypercalciuria- and hyperoxaluria-induced calculi but scientific evidence for their efficacy is less convincing ¹³.

Medicinal plants have played a significant role in various ancient traditional systems of medication. Even today, plants provide a cheap source of drugs for majority of world’s population ¹⁴. Several pharmacological investigations on the medicinal plants used in traditional antiurolithic therapy have revealed their therapeutic potential in the in vitro or in vivo models ^{15, 16}. The standard drugs used to prevent urolithiasis are not effective in all patients, and many of them have adverse effects that compromise their long term use. The present day management of nephrolithiasis with open renal surgery is unusual and rarely used only since the introduction of Extracorporeal Shock Wave Lithotripsy (ESWL) which has almost become the standard procedure for eliminating kidney stones.

However, in addition to the traumatic effect of shockwaves, persistent residue stone fragments and the possibility of infection suggests that ESWL may cause acute renal injury, a decrease in renal function and an increase in stone recurrence. Hence the search for antilithiatic drugs to be effective without side effects from natural sources has gained great potential.

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sadults.

Received on 28.07.2012

Modified on 05.08.2012

Accepted on 02.09.2012

Research Journal of Pharmacognosy and Phytochemistry. 5(1): January–February 2013, 1-8