Epidemiology
A study based on the National Health and Nutrition Examination Survey (NHANES) estimated that 19 percent of males and 9 percent of females would be diagnosed with a kidney stone by the age of 70 years. Incidence rates are also similar in males and females below age 40 years, but above age 40 years, the rates are higher in males than in females. Stone disease is most common in White patients who are not Hispanic, followed by White patients who are Hispanic, and is least common in Black patients and Asian patients. The tendency in the United States to develop stones also depends on geographical location, with an increasing prevalence from north to south and, to a lesser degree, from west to east. The increase in nephrolithiasis rates from north to south may be due to increased environmental temperatures and greater sunlight exposure leading to an increase in insensible losses through sweating and more concentrated urine ^[3].

Types and Composition of Stone
The stone type varies with worldwide geography and genetic predisposition. In the Mediterranean and Middle East, 75% of stones are composed of uric acid. In the United States, most stones are calcium oxalate or calcium phosphate (>70%), with less than 10% being pure uric acid stones.

Magnesium ammonium phosphate (struvite) stones account for 10% to 25% of stones formed (with a higher incidence in the United Kingdom), and cystine stones constitute 2% of all stones formed. ^[4-5]

Pathophysiology _{^{(Fig.1 & 2)}}
The pathogenetic mechanisms of kidney stone formation is complex and involve both metabolic and environmental risk factors. Stones occur in urine that is supersaturated with respect to the ionic constituents of the specific type of stone. When the solution becomes supersaturated with respect to a solid phase, ions can join together to form the more stable, solid phase, a process termed nucleation. Homogeneous nucleation refers to the joining of similar ions into crystals. The more common and thermodynamically favored heterogeneous nucleation results when crystals grow adjacent to crystals or other substances in the urine, such as sloughed epithelial cells. ^[6]

Clinical Manifestations
The two most characteristic symptoms of nephrolithiasis are pain and hematuria. Other presentations include urinary tract infections (UTIs) and acute kidney injury caused by obstructive uropathy if stones cause bilateral renal tract obstruction or unilateral obstruction in a single functioning kidney, sometimes kidney stone remains asymptomatic, although stone size can be large.^[6]

Figure: 1

Figure: 2

Clinical Evaluation of Stone Formers _{(Box.1 & 2)}
Patients with underlying characteristics merit complete metabolic evaluation to determine the cause of their kidney stones. Pertinent medical history, including medications in use, family and social history, and physical examination are important to evaluate kidney stone disease. Basic Investigations include UA with micro (to look for Crystals, Specific gravity, PH, and any presence of infections), Urine Chemistry also Basic Metabolic Profile.

Diagnostic Radiological Evaluation of Nephrolithiasis _{(Algorithm. 1)}
CT of the abdomen and pelvis without contrast performed using low-radiation-dose protocols is the preferred examination for most adults with suspected nephrolithiasis. If CT technology is not available, ultrasound of the kidneys and bladder, sometimes in combination with abdominopelvic radiography, is the second-line option for initial imaging. Following is a radiological diagnostic algorithm for Nephrolithiasis.

A complete evaluation should be undertaken in patients with multiple or metabolically active stones (i.e., stones that increase in size or number within a year), in all children, in patients from demographic groups not typically prone to stone formation, and in those with stones other than those containing calcium.

The complete evaluation should include a measure of urine volume and the quantity of calcium, oxalate, phosphorous, uric acid, sodium, citrate, and creatinine excreted in a 24-hour urine collection.

General Treatment
Non-Pharmacological Treatmen

Fluid intake: An increase in urine volume to more than 2 to 2.5 liters daily has been proven to reduce the incidence of stones.^[7]

Salt intake: Dietary salt restriction is associated with decreased urine calcium excretion.

Patients: should be instructed to limit daily sodium intake to 2 g (87 mmo l sodium). ^[7] Dietary protein. Animal protein ingestion increases the frequency of renal stone formation. ^[7] Dietary calcium: Despite conventional wisdom, several studies have demonstrated a decrease in stone incidence when people consume diets adequate in calcium. ^[8] Fruit and Vegetable: Increase Citrate concentration.^[8]

The specific type of Stone and Treatment
Calcium Oxalate Calcium-based stones most often develop as a result of hypercalciuria. Other causes of calcium stones are hyperoxaluria, hyperuricosuria, hypocitraturia, renal tubular acidosis, certain medications, and congenital abnormalities of the genitourinary tract. Specific therapy for patients with calcium stones depends on the underlying metabolic abnormalities detected on evaluation. General therapy, as outlined earlier, always should be instituted; however, more definitive treatment is often required to significantly decrease the rate of recurrent stone formation. ^[6]

Treatment
For hypercalciuria the usual first-line therapy is a thiazide diuretic, which acts to reduce urinary calcium. In the United States, chlorthalidone 25 to 50 mg is the drug of choice. On commencing these medications, patients should be instructed to increase their dietary potassium intake and as a needed supplement with Potassium Citrate.

Hyperoxaluria
Elevated urinary oxalate results from excessive dietary intake (dietary oxaluria), gastrointestinal disorders that can lead to malabsorption (enteric oxaluria), or an inherited enzyme deficiency that results in excessive metabolism of oxalate (primary hyperoxaluria) ^[9] Treatment of dietary and enteric hyperoxaluria: Consists of dietary oxalate restriction. Patients should be given a list of foods that have high oxalate content to avoid or eat in moderation. Calcium-containing food may be included at each meal to bind intestinal oxalate and prevent its absorption. Treatment of primary hyperoxaluria: Primary hyperoxaluria type 1 (PH1) is a severe disorder that can be cured only with liver transplantation. ^[12]

Hypocitraturia
Citrate inhibits stone formation. A number of conditions reduce urinary citrate excretion, predisposing to stone formation. Excessive protein intake, hypokalemia, metabolic acidosis, exercise, hypomagnesemia, infections, androgens, starvation, and acetazolamide have all been implicated in decreased urinary citrate excretion. Increased supplement of dietary Citrate (Lemon) or oral sodium/potassium citrate is the treatment of choice. ^[6]

Hyperuricosuria
Calcium oxalate crystals often nucleate around other crystal types, such as uric acid. Hyperuricosuria contributes to nephrolithiasis in 10% to 15% of calcium stones. If uric acid excretion remains elevated, allopurinol should be initiated at 100 to 300 mg/day. ^[6]

Uric Acid Stones
The stones are radiolucent and, therefore, poorly visible on plain radiographs. In Mediterranean and Middle Eastern countries, uric acid stones may constitute up to 75% of stones. Three major factors influence uric acid stone formation: low urine pH, low urine volume, and elevated urinary uric acid levels. Treatment: Treatment of uric acid stones involves increasing urine pH and volume as well as decreasing uric acid excretion. Alkaline urine not only can prevent uric acid stone formation but also may result in stone dissolution. To raise urine pH, potassium citrate is recommended. ^[6]

^{Struvite Stones}
Struvite stones are also referred to as infection stones or triple phosphate stones. The stones grow rapidly to a large size, can reduce renal function in the affected kidney, and are difficult to eradicate. Most staghorn calculi, large stones that penetrate more than one renal calyx, are composed of struvite. Their formation requires the presence of urease-producing bacteria in the urine, like Proteus Mirabilis. Treatment: Struvite stones require aggressive medical and surgical management. Antibiotic therapy is important to reduce further stone growth and for stone prevention.

Given the need for complete stone removal to effect a cure, early urologic intervention is advised. Stones smaller than 2 cm may respond well to ESWL; however, larger stones will likely require percutaneous nephrolithotomy, often in combination with ESWL ^[10]

Cystine Stones
Cystinuria is an autosomal disorder with a tubular defect in dibasic amino acid transport, resulting in increased cystine, ornithine, lysine, and arginine excretion. Stone disease is usually clinically manifested in the second and third decades of life. Because of the high sulfur content of the cystine molecule, the stones are apparent on plain radiographs. Treatment is directed at decreasing the urinary cystine concentration below the limits of solubility. ^[11]

References

1. Stamatelou KK, Francis ME, Jones CA, et al. Time trends in reported prevalence of kidney stones in the United States. Kidney Int. 2003; 63:1817–1823.

2. Sakhaee K, Maalouf NM, Sinnott B. Clinical review. Kidney stones 2012: pathogenesis, diagnosis, and management. J Clin Endocrinol Metab. 2012; 97:1847–1860.

3. Scales CD Jr, Smith AV, Hanley JM et al. Prevalence of Kidney stones in the United State.Eur Urol 2012, 62:160

4. Lieske JC,Rule AD, Krambeck AE,et al. Stone composition as a function of age and sex.Clin J Am Soc Nephrol 2014;9:2141

5. Maalouf NM, Cameron MA, Moe OW, Sakhaee K. Novel insights into the pathogenesis of uric acid nephrolithiasis. Curr Opin Nephrol Hypertens. 2004; 13:181–189

6. Nephrolithiasis and Nephrocalcinosis. John Feehally, Jurgen Floege, Marcello,Tonelli,Richard J Johnson. Sixth Edition; 57; 689

7. Borghi L, Schianchi T, Meschi T, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Eng J Med. 2002; 346:77–84

8. Hosking DH, Erickson SB, Van Den Berg CJ, et al. The stone clinic effect in patients with idiopathic calcium urolithiasis. J Urol. 1983; 130:1115–1118

9. Asplin JR. Hyperoxaluric calcium nephrolithiasis. Endocinol Metabol Clin North Am. 2002; 31:927– 949.

10. Rodman JS. Struvite stones. Nephron. 1999; 81(suppl 1):50–59

11. Goldfarb DS, Coe FL, Asplin JR. Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int. 2006; 69(6):1041–1047.

12. Coe FL, Evan A, Worcester E. Kidney stone disease. J Clin Invest. 2005; 115(10):2598–2608

 

                                                                                            

                                                                                  Dr. Mahfuzur Rahman MD, MPH

Dr. Mahfuzur Rahman MD, MPH, a board-certified Internist, and Nephrologist is a graduate of Sir Salimullah Medical College and Mitford Hospital. He did master’s degree in public health from Kansas University in 2003. He completed a residency in Internal Medicine at St. Luke’s Hospital, St Louis, Missouri (Class of 2003), and served as a Chief Resident for the program. He had worked as an academic hospitalist for a couple of years before transitioning to Fellowship training in Nephrology and Hypertension at Tulane University School of Medicine, New Orleans, LA. (Class of 2009). Since 2011 practicing as a Nephrologist. He is currently practicing in Sacramento, California, and is part of Capital Nephrology Medical Group. He is serving as section Chief, Nephrology at Sutter Medical Center, Sacramento, and also medical director for the chronic dialysis facility in the Sacramento area.