Nephrolithiasis Overview

Nephrolithiasis is characterized by the formation of crystalline aggregates (“kidney stones”) that can develop anywhere along the urinary tract. Kidney stones are common in Western societies; nearly 10% of Americans will develop a symptomatic kidney stone during their lifetime. The 5 major stone compositions are calcium oxalate, calcium phosphate, magnesium ammonium phosphate (struvite), uric acid, and cystine. Calcium–based stones are the most common, causing more than 75% of cases, and calcium oxalate is the most common type of stone overall. A rare but increasingly recognized cause of nephrolithiasis is the use of the protease inhibitor indinavir in treating HIV patients. Kidney Stone type| Population| Circumstances| Details|

Calcium oxalate| 80%| when urine is acidic (low pH)| Some of the oxalate in urine is produced by the body. Calcium and oxalate in the diet play a part but are not the only factors that affect the formation of calcium oxalate stones. Dietary oxalate is an organic molecule found in many vegetables, fruits, and nuts. Calcium from bone may also play a role in kidney stone formation.| Calcium phosphate| ___%| when urine is alkaline (high pH)| | Uric acid| 510%| when urine is persistently acidic| Diets rich in animal proteins and purines: substances found naturally in all food but especially in organ meats, fish, and shellfish.| Struvite| 1015%| infections in the kidney| Preventing struvite stones depends on staying infectionfree. Diet has not been shown to affect struvite stone formation.| Cystine| ___%| rare genetic disorder| Cystine, an amino acid (one of the building blocks of protein), leaks through the kidneys and into the urine to form crystals.| Risk Factors

* Male gender. Males are 3 times more likely to develop stones than females. * History of nephrolithiasis. Individuals who have developed a kidney stone have an 80% chance of recurrence within 10 years. * Geography. Areas of elevated temperatures and high humidity appear to have an increased incidence of stone disease. * Nationality. Developing countries have a much lower risk of nephrolithiasis, compared with developed countries. This is presumed to be due to dietary factors, specifically the absence of a Western–style, meat–based diet. * Obesity. Compared with persons at or near ideal body weight (BMI = 21–23), obese men (BMI ≥30) have a 33% greater risk for stone formation, while obese women have a 200% greater risk.1 * Diet. Diet plays an important role in nephrolithiasis risk, as described below in Nutritional Considerations. * Family history of nephrolithiasis. Patients with a family history of kidney stones have a 2 to 3 times higher risk. * History of cystinuria. Cystinuria is an autosomal recessive disorder that increases risk of cystine stone formation. * Urinary stasis (eg, bladder outlet obstruction).

* Chronic urinary tract infections.
* Dehydration (eg, diarrhea).
Cause
Most often, stones are due to increased concentrations of stone–forming material in the urine, either from increased excretion or decreased urinary volume. Stone formation occurs when a stone–forming material becomes supersaturated in the urine and begins the process of crystal formation. Dietary factors that increase the risk of stone formation include low fluid intake and high dietary intake of animal protein, sodium, refined sugars, fructose and high fructose corn syrup,[5] oxalate,[6] grapefruit juice, apple juice, and cola drinks.

Signs and Symptoms
Excruciating, intermittent flank pain, known as renal colic, occurs with stones that become lodged in the ureter. It may radiate to the lower abdomen, groin, testicles, or perineum. Lower urinary tract symptoms, including dysuria, urgency, and frequency, occur with stones that become lodged at the ureterovesical junction. Nausea, vomiting, hematuria, and costoverterbral angle tenderness may also be present, even in the absence of pain. Diagnosis

Urinalysis
Microscopic examination of the urine for evidence of hematuria and infection is a critical part of the evaluation of a patient thought to have renal colic. Gross or microscopic hematuria is only present in approximately 85% of patients with urinary calculi. The lack of microscopic hematuria does not eliminate renal colic as a potential diagnosis. Urinary crystals of calcium oxalate, uric acid, or cystine may occasionally be found upon urinalysis. When present, these crystals are very good clues to the underlying type and nature of any obstructing calculus. Determining urinary pH also helps. A urine pH greater than 7 suggests presence of ureasplitting organisms, such as Proteus, Pseudomonas, or Klebsiella species, and struvite stones. A urine pH less than 5 suggests uric acid stones. Blood Studies

Complete blood count
Whereas mild leukocytosis often accompanies a renal colic attack, a high index of suspicion for a possible renal or systemic infection should accompany any serum WBC count of 15,000/µL or higher in a patient presenting with an apparent acute kidney stone attack, even if afebrile. A depressed RBC count suggests a chronic disease state or severe ongoing hematuria.

Serum electrolytes, creatinine, calcium, uric acid, parathyroid hormone, and phosphorus Measurements of serum electrolyte, creatinine, calcium, uric acid, parathyroid hormone (PTH), and phosphorus are needed to assess a patient’s current renal function and to begin the assessment of metabolic risk for future stone formation. A high serum uric acid level may indicate gouty diathesis or hyperuricosuria, while hypercalcemia suggests either renalleak hypercalciuria (with secondary hyperparathyroidism) or primary hyperparathyroidism. If the serum calcium level is elevated, serum PTH levels should be obtained. Serum creatinine level is the major predictor of contrastinduced nephrotoxicity. If the creatinine level is higher than 2 mg/dL, use diagnostic techniques that do not require an infusion of contrast, such as ultrasonography or helical CT scanning. Hypokalemia and decreased serum bicarbonate level suggest underlying distal (type 1) renal tubular acidosis, which is associated with formation of calcium phosphate stones. 24Hour Urine Profile

The most common findings on 24hour urine studies include hypercalciuria,hyperoxaluria, hyperuricosuria, hypocitraturia, and low urinary volume. Other factors, such as high urinary sodium and low urinary magnesium concentrations, may also play a role. A finding of hypercalcemia should prompt followup with an intact parathyroid hormone study to evaluate for primary and secondary hyperparathyroidism.

Calcium, oxalate, and uric acid
Elevation of the 24hour excretion rate of calcium, oxalate, or uric acid indicates a predisposition to form calculi.

Sodium and phosphorus
Excess sodium excretion can contribute to hypercalciuria by a phenomenon known as solute drag. Elevated urinary sodium levels are almost always associated with dietary indiscretions. Decreasing the oral sodium intake can decrease calcium excretion, thereby decreasing calcium saturation. An elevated phosphorus level is useful as a marker for a subtype of absorptive hypercalciuria known as renal phosphate leak (absorptive hypercalciuria type III). Renal phosphate leak is identified by high urinary phosphate levels, low serum phosphate levels, high serum 1,25 vitamin D3 (calcitriol) levels, and hypercalciuria. This type of hypercalciuria is uncommon and does not respond well to standard therapies.

Citrate and magnesium
Magnesium and, especially, citrate are important chemical inhibitors of stone formation. Hypocitraturia is one of the most common metabolic defects that predispose to stone formation, and some authorities have recommended citrate therapy as primary or adjunctive therapy to almost all patients who have formed recurrent calciumcontaining stones.

Creatinine
Creatinine is the control that allows verification of a true 24hour sample.
Most individuals excrete 11.5 g of creatinine daily. Values at either extreme that are not explained by estimates of lean body weight should prompt consideration that the sample is inaccurate.

Total urine volume
Patients in whom stones form should strive to achieve a urine output of more than 2 L daily in order to reduce the risk of stone formation. Patients with cystine stones or those with resistant cases may need a daily urinary output of 3 L for adequate prophylaxis.

pH
Some stones, such as those composed of uric acid or cystine, are pHdependent, meaning that they can form only in acidic conditions. Calcium phosphate and struvite only form when the urine pH is alkaline. Although the other parameters in the 24hour urine usually identify patients at risk of forming these stones, pH studies can be important in monitoring these patients, in optimizing therapy with citrate supplementation, and in identifying occult stone disease in some patients. Plain (Flat Plate or KUB) Radiography

Plain abdominal radiography (also referred to as flat plate or KUB radiography) is useful for assessing total stone burden, as well as the size, shape, composition, and location of urinary calculi in some patients. Calciumcontaining stones (approximately 85% of all upper urinary tract calculi) are radiopaque, but pure uric acid, indinavirinduced, and cystine calculi are relatively radiolucent on plain radiography. Ultrasonography

Renal ultrasonography by itself is frequently adequate to determine the presence of a renal stone. The study is mainly used alone in pregnancy[16] or in combination with plain abdominal radiography to determine hydronephrosis or ureteral dilation associated with an abnormal radiographic density believed to be a urinary tract calculus. A stone easily identified with renal ultrasonography but not visible on the plain radiograph may be a uric acid or cystine stone, which is potentially dissolvable with urinary alkalinization therapy. Noncontrast abdominal CT scan

Noncontrast abdominal CT scan is the preferred test to detect stones and urinary tract obstructions. Abdominal x–ray (kidney–ureter–bladder film) will identify many radiopaque stones, but will not detect small or radiolucent stones or urinary tract obstructions. The intravenous pyelogram has largely been replaced by abdominal CT scan. While the intravenous pyelogram has high sensitivity and specificity for detecting stones, its use is restricted by the risk of contrast reactions and by the fact that evaluation time is very limited when obstruction is present. Complications

The morbidity of urinary tract calculi is primarily due to obstruction with its associated pain, although nonobstructing calculi can still produce considerable discomfort. Conversely, patients with obstructing calculi may be asymptomatic, which is the usual scenario in patients who experience loss of renal function due to chronic untreated obstruction. Stoneinduced hematuria is frightening to the patient but is rarely dangerous by itself. Serious complications of urinary tract stone disease include the following:

* Abscess formation
* Serious infection of the kidney that diminishes renal function
* Urinary fistula formation
* Ureteral scarring and stenosis
* Ureteral perforation
* Extravasation
* Urosepsis
* Renal loss due to longstanding obstruction

Infected hydronephrosis is the most deadly complication because the presence of infection adjacent to the highly vascular renal parenchyma places the patient at risk for rapidly progressive sepsis and death. A ureteral stone associated with obstruction and upper UTI is a true urologic emergency. Complications include perinephric abscess, urosepsis, and death. Immediate involvement of the urologist is essential. Calyceal rupture with perinephric urine extravasation due to high intracaliceal pressures occasionally is seen and usually is treated conservatively. Complete ureteral obstruction may occur in patients with tightly impacted stones. This is best diagnosed via IVP and is not discernible on noncontrast CT scan. Patients with 2 healthy kidneys can tolerate several days of complete unilateral ureteral obstruction without longterm effects on the obstructed kidney. If a patient with complete obstruction is well hydrated and pain and vomiting are well controlled, the patient can be discharged from the ED with urologic followup within 12 days Medical Management

Dissolution of calculi
Urinary calculi composed predominantly of calcium cannot be dissolved with current medical therapy; however, medical therapy is important in the longterm chemoprophylaxis of further calculus growth or formation. Uric acid and cystine calculi can be dissolved with medical therapy. Patients with uric acid stones who do not require urgent surgical intervention for reasons of pain, obstruction, or infection can often have their stones dissolved with alkalization of the urine. Sodium bicarbonate can be used as the alkalizing agent, but potassium citrate is usually preferred because of the availability of slowrelease tablets and the avoidance of a high sodium load. The dosage of the alkalizing agent should be adjusted to maintain the urinary pH between 6.5 and 7.0. Urinary pH of more than 7.5 should be avoided because of the potential deposition of calcium phosphate around the uric acid calculus, which would make it undissolvable. Both uric acid and cystine calculi form in acidic environments. Even very large uric acid calculi can be dissolved in patients who comply with therapy. Roughly 1 cm per month dissolution can be achieved. Practical ability to alkalinize the urine significantly limits the ability to dissolve cystine calculi.

Chemoprophylaxis
Prophylactic therapy might include limitation of dietary components, addition of stoneformation inhibitors or intestinal calcium binders, and, most importantly, augmentation of fluid intake. (See Dietary Measures and Prevention of Nephrolithiasis.) Besides advising patients to avoid excessive salt and protein intake and to increase fluid intake, base medical therapy for longterm chemoprophylaxis of urinary calculi on the results of a 24hour urinalysis for chemical constituents. Chemoprophylaxis of uric acid and cystine calculi consists primarily of longterm alkalinization of urine. If hyperuricosuria or hyperuricemia is documented in patients with pure uric acid stones (present in only a relative minority), allopurinol (300 mg qd) is recommended because it reduces uric acid excretion. Pharmaceuticals that can bind free cystine in the urine (eg, Dpenicillamine, 2alphamercaptopropionylglycine) help reduce stone formation in cystinuria. Therapy should also include longterm urinary alkalinization and aggressive fluid intake. Captopril has been shown to be effective in some trials, although, again, strong data are lacking. Routine use should be avoided but can be added in patients who have difficulty in dissolving and preventing cystine stones. Surgical Management

In general, stones that are 4 mm in diameter or smaller will probably pass spontaneously, and stones that are larger than 8 mm are unlikely to pass without surgical intervention. With MET, stones 58 mm in size often pass, especially if located in the distal ureter. The larger the stone, the lower the possibility of spontaneous passage (and thus the greater the possibility that surgery will be required), although many other factors determine what happens with a particular stone.

Indications and contraindications
The primary indications for surgical treatment include pain, infection, and obstruction. Infection combined with urinary tract obstruction is an extremely dangerous situation, with significant risk of urosepsis and death, and must be treated emergently in virtually all cases. Additionally, certain occupational and healthrelated reasons exist. General contraindications to definitive stone manipulation include the following: * Active, untreated UTI

* Uncorrected bleeding diathesis
* Pregnancy (a relative, but not absolute, contraindication)

Stent placement
Internal ureteral stents form a coil at either end when the stiffening insertion guide wire is removed. One coil forms in the renal pelvis and the other in the bladder. Stents are available in lengths from 2030 cm and in 3 widths from 4.6F to 8.5F. Some are designed to soften after placement in the body; others are rather stiff to resist crushing and obstruction by large stones or external compression with occlusion from an extrinsic tumor or scar tissue. To select the correctsize stent, estimates can be made based on the height of the patient, or the ureteral length can be measured. This is best performed by means of a retrograde pyelogram. The distance from the tip of the retrograde catheter to the UPJ is measured in centimeters with a tape measure. To account for the average magnification effect of the film, 10% of this reading is subtracted. If the result is an odd number, a doubleJ stent one size longer is used. The most common lengths used are 26 cm in men and 24 cm in women. The optimal stent width depends on both the relative diameter and course of the ureter and the purpose of the stent. If the patient has a stricture or a tortuous ureter, a stiffer or largerdiameter stent is placed if possible.

When used for stone disease, stents perform several important functions. They virtually guarantee drainage of urine from the kidney into the bladder and bypass any obstruction. This relieves patients of their renal colic pain even if the actual stone remains. Over time, stents gently dilate the ureter, making ureteroscopy and other endoscopic surgical procedures easier to perform later. Because they are also quite radiopaque, stents provide a stable landmark when performing SWL. A landmark is particularly important with small or barely visible stones, especially in the ureter, because the SWL machine uses radiographic visualization to target the stone. Once large stones are broken up, stents tend to prevent the rapid dumping of large amounts of stone fragments and debris into the ureter (called steinstrasse). The stent forces the fragments to pass slowly, which is more efficient and prevents clogging. Stents do have drawbacks.

They can become blocked, kinked, dislodged, or infected. A KUB radiograph can be used to determine stent position, while infection is easily diagnosed by urinalysis. A renal sonogram can sometimes be helpful if there is concern for obstruction. Questionable cases can be evaluated further using a radiographic cystogram or an IVP. The cystogram is performed by filling the urinary bladder with diluted contrast media through a Foley catheter under gravity pressure. A stent that is unclogged and functioning normally should show free reflux of contrast from the bladder into the stented renal pelvis. The major drawback of stents, however, is that they are often quite uncomfortable for patients due to direct bladder irritation, spasm, and reflux. This discomfort can be alleviated to some extent by pain medications, anticholinergics (eg, oxybutynin, tolterodine), alphablockers, and topical analgesics (eg, phenazopyridine).

Percutaneous nephrostomy
In some cases, drainage of an obstructed kidney is necessary and stent placement is inadvisable or impossible. In particular, such cases include patients with pyonephrosis who have a UTI or urosepsis exacerbated by an obstructing calculus. In these patients, retrograde endourological procedures like retrograde pyelography and stent placement may exacerbate infection by pushing infected urinary material into the obstructed renal unit. Percutaneous nephrostomy is useful in such situations.[55]

Extracorporeal shockwave lithotripsy
SWL, the least invasive of the surgical methods of stone removal, utilizes an underwater energy wave focused on the stone to shatter it into passable fragments. It is especially suitable for stones that are smaller than 2 cm and lodged in the upper or middle calyx. It is contraindicated in pregnancy, untreatable bleeding disorders, tightly impacted stones, or in cases of ureteral obstruction distal to the stone. In addition, the effectiveness is limited for very hard stones (which tend to be dense on CT scan), cystine stones, and in very large patients. The patient, under varying degrees of anesthesia (depending on the type of lithotriptor used), is placed on a table or in a gantry that is then brought into contact with the shock head.

The deeper the anesthesia (general endotracheal), the better the results. In addition, evidence is mounting that slower shockwave delivery (6080 per min) improves the results. New lithotriptors that have 2 shock heads, which deliver a synchronous or asynchronous pair of shocks (possibly increasing efficacy), have attracted great interest. The shock head delivers shockwaves developed from an electrohydraulic, electromagnetic, or piezoelectric source. The shockwaves are focused on the calculus, and the energy released as the shockwave impacts the stone produces fragmentation. The resulting small fragments pass in the urine. SWL is limited somewhat by the size and location of the calculus. A stone larger than 1.5 cm in diameter or one located in the lower section of the kidney is treated less successfully. Fragmentation still occurs, but the large volume of fragments or their location in a dependent section of the kidney precludes complete passage. In addition, results may not be optimal in large patients, especially if the skintostone distance exceeds 10 cm.[56]

Ureteroscopy
Along with SWL, ureteroscopic manipulation of a stone (see the image below) is a commonly applied method of stone removal. A small endoscope, which may be rigid, semirigid, or flexible, is passed into the bladder and up the ureter to directly visualize the stone.

Two calculi in a dependent calyx of the kidney (lower pole) visualized through a flexible fiberoptic ureteroscope. In another location, these calculi might have been treated with extracorporeal shockwave lithotripsy (ESWL), but, after being counseled regarding the lower success rate of ESWL for stones in a dependent location, the patient elected ureteroscopy. Note that the image provided by fiberoptics, although still acceptable, is inferior to that provided by the rodlens optics of the rigid ureteroscope in the previous picture.

Ureteroscopy is especially suitable for removal of stones that are 12 cm, lodged in the lower calyx or below, cystine stones, and high attenuation (“hard”) stones. The typical patient has acute symptoms caused by a distal ureteral stone, usually measuring 58 mm. Stones smaller than 5 mm in diameter generally are retrieved using a stone basket, whereas tightly impacted stones or those larger than 5 mm are manipulated proximally for SWL or are fragmented using an endoscopic directcontact fragmentation device. Often, a ureteral stent must be placed after ureteroscopy in order to prevent obstruction from ureteral spasm and edema. Since a ureteral stent is often uncomfortable, many urologists eschew stent placement following ureteroscopy in selected patients.[57]

Percutaneous nephrostolithotomy
Percutaneous nephrostolithotomy allows fragmentation and removal of large calculi from the kidney and ureter. Because of their increased morbidity compared with SWL and ureteroscopy, percutaneous procedures are generally reserved for large and/or complex renal stones and failures from the other 2 modalities. Percutaneous nephrostolithotomy is especially useful for stones larger than 2 cm in diameter. A needle and then a wire, over which is passed a hollow sheath, are inserted directly into the kidney through the skin of the flank. Percutaneous access to the kidney typically involves a sheath with a 1cm lumen, which will admit relatively large endoscopes with powerful and effective lithotrites that can rapidly fragment and remove large stone volumes. Renal calyces, pelvis, and proximal ureter can be examined and stones extracted with or without prior fragmentation. In some cases, a combination of SWL and a percutaneous technique is necessary to completely remove all stone material from a kidney. This technique, called sandwich therapy, is reserved for staghorn or other complicated stone cases. In such cases, experience has shown that the final procedure should be percutaneous nephrostolithotomy.

Open nephrostomy
Open nephrostomy has been used less and less often since the development of SWL and endoscopic and percutaneous techniques; it now constitutes less than 1% of all interventions. Disadvantages include longer hospitalization, longer convalescence, and increased requirements for blood transfusion.

Source:

http://en.wikipedia.org/wiki/Kidney_stone
http://www.nutritionmd.org/health_care_providers/renal/nephrolithiasis_diagnosis.html http://emedicine.medscape.com/article/437096overview