Introduction

Nephrolithiasis, or kidney stones, is the most common condition affecting the urinary system, affecting about 12% of the world population, with a yearly incidence of 600,000 in America. It is the result of a crystal or crystalline concretion traveling from the kidney through the genitourinary system.[1][2] Kidney stones correlate with an increased risk of chronic kidney diseases, end-stage renal failure, cardiovascular diseases, diabetes, and hypertension.[3]

Etiology

Most patients with nephrolithiasis form calcium stones (80%), most of which are composed primarily of calcium oxalate or calcium phosphate. The other main types include uric acid, struvite (magnesium ammonium phosphate), and cystine stones. Of note, one patient may have a stone that contains more than one type of crystal.

Risk Factors - Influenced by certain diseases, habits, composition of urine. 

• Personal history of prior kidney stones increases the risk of kidney stones [4] by 15% within the first year, and 50% within the next ten years. 
• A family history of kidney stones increases the risk by 2.5 times. 
• Increased enteric oxalate absorption, typically due to malabsorption, leads to increased formation of calcium oxalate crystals.  
• Urinary tract infections altering urinary pH in the setting of urease-producing bacteria, producing struvite crystals
• Low fluid intake [5]
• History of diabetes, obesity, gout, and hypertension [6]
• Acidic urine (pH< 5.5), which promotes uric acid formation in the setting of chronic diarrhea and gout

Epidemiology

The prevalence and recurrence rates of nephrolithiasis are increasing, with limited options of effective drugs and procedures, affecting about 12% of the population worldwide. The incidence is estimated at 600,000 in the U.S. Between the ages of 20 to 49; kidney stones affect men more frequently than in women (2 to 1). The lifetime recurrence rate is higher in males than in females. This fact is attributed to the increasing incidence of obesity due to poor dietary habits and lack of physical activity.

Pathophysiology

Renal stone formation involves physicochemical changes and urine supersaturation. In the setting of supersaturation, solutes precipitate in the urine leading to nucleation and crystal concretions. PH and specific concentrations of excess substances influence the transformation of a liquid to a solid. In respect to nephrolithiasis, supersaturation of stone-forming constituents like calcium, phosphorus, uric acid, oxalate, cystine, and low urine volume are risk factors for crystallization.[7] Nephrolithiasis is preventable by avoiding supersaturation.

Histopathology

Urine microscopy is useful in analyzing the kidney stone if they are obtainable via urine straining. Below are the crystal formations typically associated with each stone type [8]:

• Calcium oxalate: envelope or dumbbell-shaped
  • Calcium oxalate is the primary component of the majority of stones. They typically occur in the setting of hypercalciuria, hyperoxaluria, hypomagnesuria, hypercystinuria, hypocitraturia. 

• Calcium phosphate: amorphous, wedge-shaped prisms in rosettes 

• Magnesium ammonium phosphate: coffin lid shaped 
  • Also known as struvite stones, seen in infectious stones. In the setting of infections with bacteria that produce urease, such as Proteus mirabilis, Klebsiella pneumonia, Enterobacter, and Pseudomonas aeruginosa. The urease produces ammonia and CO2, which creates basic pH urine (>7).     

• Uric acid: rhomboid shaped 
  • These stones are typically idiopathic. They occur in patients whose diets are high in protein, which acidifies urines pH (<7), allowing for uric acid stone formation.

• Cystine: hexagon-shaped
  • These stones are caused by a genetic defect in the transport of the amino acid cystine, resulting in hypercystinuria.

History and Physical

Patients with nephrolithiasis, when limited to the kidney, will be asymptomatic. The common symptoms associated with kidney stones, including acute pain radiating to the groin, occurs once the stone begins descending the ureters from the kidneys. It is often described as dull, colicky, sharp, and severe pain.  The pain is often associated with nausea and vomiting due to the severity of pain. These symptoms are attributed to the peristalsis of the genitourinary tract smooth muscle against the stone. Hematuria is commonly reported as well, due to the injury against the genitourinary tract secondary to the stone; this is confirmable via urinalysis. 

If the stone becomes infected, patients may develop fever, chills, or other signs of worsening systemic signs of infection (i.e., shock). The physical exam may reveal costovertebral tenderness.  Obstruction can occur, and pyelonephritis with concurrent hydronephrosis can result. This situation can be severe and life-threatening, requiring emergency decompression surgery.

Evaluation

Laboratory tests to assess renal function, including either a basic or comprehensive metabolic panel, may be used. Additionally, a urinalysis, urine electrolytes, and urine pH can help direct towards a specific type of stone. 

A KUB (kidney-ureter-bladder) X-ray is also an option; however, uric acid stones are difficult to assess with this imaging. A CT of the abdomen and pelvis without contrast can also be performed and has higher sensitivity. Contrast medium is typically avoided when there is a concern for a kidney stone as enhancement of the vessels and ureters can obscure stone findings. 

Treatment / Management

Kidney stones are extremely painful. Pain control is of utmost importance with NSAIDs by decreasing smooth muscle stimulation and ureteral spasm. Additionally, it is essential to increase fluid intake. Tamsulosin, may also aid stone passage, and also reduces smooth muscle stimulation. It is typically useful in those in the distal ureter and sizes between 5 to 10 mm.  

Stones greater than 6mm are likely to require some intervention, including percutaneous nephrolithotomy, rigid and flexible ureteroscopy, and shock wave lithotripsy.[9]

Differential Diagnosis

Conditions listed below may mimic nephrolithiasis-induced flank pain:

• Pyelonephritis, which typically presents with pyuria, fevers, chills and flank pain
• Ovarian cyst torsion
• Ectopic pregnancies 
• Intestinal associated diseases, including obstruction, appendicitis, and diverticulitis
• Cholecystitis, hepatitis, and biliary colic 
• Herpes zoster 
• Narcotic-seeking individuals 
• Renal cell carcinomas

Prognosis

Kidney stones that do not pass can become obstructive and can subsequently cause acute renal failure, or it can also become a nidus for infection, which can eventually be lethal. If the patient undergoes nephrostomy tube placement, then there is a chance of bleeding, renal collecting system injury, injury of visceral organs, pulmonary complications, thromboembolic complications, and extrarenal stone migration.[10]

Complications

Several complications can arise due to kidney stones, and subsequently, stones that cause obstruction. These include:

• Abscess formation
• Urosepsis
• Urinary fistula formation
• Ureteral scarring and stenosis
• Ureteral perforation
• Renal function loss due to long-standing obstruction

Consultations

Failure of stone passage within a month warrants a urology consultation.

Indications for hospitalization and urgent urology consultation and intervention are:

1. An obstructed and infected upper urinary system
2. Intractable vomiting or pain
3. Anuria or deteriorating renal function
4. History of transplanted kidney or solitary kidney with obstructing stone 

Deterrence and Patient Education

Identification and Subsequent Prevention

Effective kidney stone prevention depends on stone identification. Implementing preventive strategies that include primarily dietary changes and/or pharmacological treatments may be required. Additionally, regardless of underlying etiology, increasing water intake to maintain two liters of urine output per day, a low salt diet, and a decreased amount of animal protein consumption should be a daily practice. For absorptive hyperoxaluria, a low oxalate diet and increased dietary calcium intake are both recommended. Calcium supplements can reduce oxalate absorption, and can be protective. For struvite stones, patients must receive careful follow-up until the infection has resolved.[11]

Enhancing Healthcare Team Outcomes

Nephrolithiasis frequently poses a prevention and treatment dilemma. These patients may exhibit non-specific signs and symptoms such as abdominal pain, nausea, and urinating difficulties. Knowledge of the stone type can point the patient to changes in lifestyle habits that would prevent further stone formations. Patient adherence, along with detailed lifestyle changes, should be discussed between the patients, primary physician, and the urologist. Recurrent stone formation can exacerbate worsening renal function, especially in those with a history of end-stage renal disease. If given medication as treatment or prevention, it is also just as necessary for the pharmacist to recognize the use of the medication and further counsel patients on lifestyle habit changes.