2. Diagnosis and acute management of suspected nephrolithiasis in adults

3.  Renal and ureteral stones are a common problem in primary care practice .
Patients may present with the classic symptoms of renal colic and hematuria.
Others may be asymptomatic or have atypical symptoms such as vague abdominal pain, acute abdominal or flank pain, nausea, urinary urgency or frequency, difficulty urinating, penile pain, or testicular pain.

4. ETIOLOGY 
 Eighty percent of patients with nephrolithiasis form calcium stones, most of which are composed primarily of calcium oxalate or, less often, calcium phosphate
The other main types include uric acid, struvite (magnesium ammonium phosphate), and cystine stones.
The same patient may have more than one type of stone concurrently (eg, calcium oxalate and uric acid)

5. INDIVIDUAL CRYSTALLINE COMPONENTS
Calcium oxalate — Calcium oxalate is the most common component found in kidney stones (approximately 70 to 80 percent). Calcium oxalate can be found in monohydrate and dihydrate forms.
Calcium oxalate can also be present in combination with uric acid or calcium phosphate.

7. Urinary risk factors for calcium oxalate crystal formation are lower urine volume, higher urine calcium excretion, higher urine oxalate excretion, and lower urine citrate excretion.
Calcium oxalate crystals are pH insensitive in the physiologic pH range of 5 to 8.

8. Calcium phosphate — Calcium phosphate is found in approximately 15 percent of kidney stones and can be present in combination with calcium oxalate or struvite.
because of differences in solubility due to urine pH, calcium phosphate is not found mixed with uric acid.
The two forms of calcium phosphate include apatite,, or brushite; the frequency of apatite is much greater than brushite.

9. Urinary risk factors for calcium phosphate crystal formation are lower urine volume, higher urine calcium excretion, lower urine citrate excretion, higher urinary pH, and likely higher urine phosphate excretion.
In contrast to calcium oxalate crystals, calcium phosphate crystals are pH sensitive, forming in "alkaline" urine (usually pH 6.5 or higher).

10.   In general, calcium phosphate stones are associated with the same risk factors as calcium oxalate stones (other than hyperoxaluria)

11. Uric acid — Uric acid is present in approximately 8 percent of analyzed stones, sometimes in combination with calcium oxalate.
The urinary risk factors for uric acid crystal formation are lower urine volume, higher urine uric acid excretion, and most importantly, lower urinary pH. Uric acid crystals are pH sensitive, forming in "acidic" urine (usually pH 5.5 or lower).

13. Struvite — Struvite is the crystal name for stones that form only in the presence of urease-producing bacteria (eg, Proteus mirabilis) .
Other names for this crystal type include "triple phosphate" (because the phosphate is in the triple-negative form) and magnesium ammonium phosphate carbonate apatite.

15. Struvite is found in approximately 1 percent of analyzed stones and is much more common in women than in men (due to the higher risk of urinary tract infections in women).
If a preexisting calcium-containing kidney stone is subsequently infected with a urease-producing bacterium, the stone analysis may report that the composition of the stone includes calcium oxalate or calcium phosphate in addition to struvite.

16. Because urease splits urea into one carbon dioxide molecule and two ammonia molecules, the net reaction often leads to a urine pH outside of the physiologic range (8.5 or 9).
Other than the presence of urease, there are no other urinary risk factors for struvite crystal formation

17.  Struvite stones only form in patients with a chronic upper UTI due to a urease-producing organism such as Proteus or Klebsiella.
The stone may grow rapidly over a period of weeks to months and, if not adequately treated, can develop into a staghorn or branched calculus involving the entire renal collecting system

18. Cystine stones — Cystine stones only develop in patients with cystinuria (an autosomal recessive disorder) due to the poor solubility of cystine in the urine.
The diagnosis of cystinuria is made by identification of the pathognomonic hexagonal cystine crystals on urinalysis (which can be seen in the initial urinalysis in about 25 percent of patients; and by measurement of a urinary cystine concentration of greater than 250 mg/liter

20. Other crystal types — Rare crystal types include:
●Triamterene
●Acyclovir
●Indinavir

22. Risk factors — The risk of nephrolithiasis is influenced by urine composition, which can be affected by certain diseases and patient habits.
For calcium oxalate stones, urinary risk factors include hypercalciuria, hyperoxaluria, hypocitraturia, and dietary risk factors such as a low calcium intake, high oxalate intake, high animal protein intake, high sodium intake, or low fluid intake
Increased intake of Vitamin C has been associated with a higher risk of stones in men

23. There are numerous other factors potentially associated with an increased risk of stone formation: ●A history of prior nephrolithiasis. The rate of stone recurrence is 10 to 30 percent at three to five years among patients with idiopathic calcium oxalate stones

24. Patients with a family history of stones have an increased risk of nephrolithiasis. The risk of stones increases in individuals with enhanced enteric oxalate absorption (eg, gastric bypass procedures, bariatric surgery, short bowel syndrome). Less common causes include frequent upper UTI (eg, as a result of spinal cord injuries) and use of medications that may crystallize in the urine such as indinavir, acyclovir, sulfadiazine, and triamterene Nephrolithiasis has also been reported in children receiving prolonged ceftriaxone therapy

25. Stone disease is approximately twofold higher in patients with hypertension
Additional potential risk factors include diabetes, obesity, gout, and excessive physical exercise (including marathon running), which may increase crystalluria and possibly the risk of stones in predisposed individuals
Low fluid intake is associated with increased stone risk. The type of fluid taken in may be important, although data are sometimes conflicting

26. CLINICAL MANIFESTATIONS — Patients may occasionally be diagnosed with asymptomatic nephrolithiasis when a radiologic imaging study of the abdomen is performed for other purposes or when surveillance imaging is done in those with a prior history of stones.
The asymptomatic phase is more likely to persist in those who have never had a clinical episode of renal colic.

27. EVALUATION — All patients presenting with their first stone should undergo a focused history, radiologic imaging, and at least a limited laboratory evaluation.

28. There is general agreement that a complete metabolic evaluation, in addition to the basic laboratory testing, is indicated in all patients with multiple stones at first presentation, in patients with a strong family history of stones, and in individuals with active stone disease, which is defined as recurrent stone formation, enlargement of existing stones, or the recurrent passage of gravel.

29. Focused history — The purpose of the focused history is to identify stone risk factors, such as a family history of stone disease and certain dietary habits

30. Summarized briefly, adverse dietary habits include:
●Low fluid intake or a high fluid loss (eg, from sweating or gastrointestinal losses), which leads to a lower urine output and, therefore, a higher concentration of lithogenic factors.
●Higher animal protein diet, which can lead to hypercalciuria, hyperuricosuria, hypocitraturia, and elevated urinary acid excretion
●Higher salt diet, which increases urinary calcium excretion.

31. ●Increased intake of higher oxalate-containing foods, particularly spinach. The exact contribution of dietary oxalate to urinary oxalate is controversial and likely varies considerably from person to person. ●Lower calcium intake, which acts by increasing the absorption and subsequent excretion of oxalate due to decreased calcium oxalate complex formation within the intestinal lumen . ●Excessive vitamin C and D supplementation.

34. In addition, certain medications can occasionally crystallize in the urine and lead to stone formation. Examples include, sulfadiazine, and triamterene

35.  Radiologic testing — The diagnosis of nephrolithiasis is initially suspected by the clinical presentation. Helical non-contrast CT or ultrasonography can be used initially to visualize and confirm the presence of a stone.
Women who could potentially be pregnant should undergo a urine pregnancy test before a CT scan is performed.
It is important to appreciate that ureteral dilatation without a stone on radiologic examination could represent recent passage of a stone.

36. ●Non-contrast helical CT
CT is more sensitive than ultrasonography and therefore more likely to visualize a stone, if present. However, CT is also associated with radiation exposure, and cumulative doses of radiation may be high in patients who have recurrent nephrolithiasis and need frequent imaging.

37. Laboratory testing — There is disagreement whether a complete metabolic evaluation should be performed after the first stone. Limited data suggest that single stone formers have similar metabolic abnormalities as patients with recurrent nephrolithiasis
However, there are data suggesting that a comprehensive medical evaluation is not cost-effective for patients who have only formed one stone

38. Three options have been proposed for laboratory evaluation after a first stone: a limited evaluation, a complete metabolic evaluation similar to patients with multiple stones or active stone disease, or a targeted approach

39. Limited evaluation 
The limited evaluation should include routine blood chemistries. At least one repeated measurement of serum calcium should be performed in patients whose first value is high-normal since most patients with urolithiasis due to primary hyperparathyroidism, have values between 10.2 and 11 mg/dL .Other findings that may be important include a low serum phosphorus and a low serum bicarbonate concentration, the latter being suggestive of distal renal tubular acidosis or chronic diarrhea.

40. Complete metabolic evaluation — Other clinicians recommend a complete evaluation after the first stone because of the potentially high rate of recurrence ,potential morbidity from recurrent stones.

41. Targeted approach — A third approach is to base the extent of the laboratory evaluation upon an estimation of the risk for new stone formation
A complete metabolic evaluation, as described below, would be performed in patients at moderate to high risk for recurrent disease. Patients at high risk for recurrent disease include:
●Middle-aged, white males with a family history of stones
●Patients with chronic diarrheal states and/or malabsorption, pathologic skeletal fractures, osteoporosis, urinary tract infection, and/or gout
●Patients with stones composed of cystine, uric acid, calcium phosphate, or struvite

42. THE COMPLETE METABOLIC EVALUATION — The metabolic evaluation for nephrolithiasis consists of both blood and urine testing, including at least two 24-hour urine collections.
Blood tests — A routine chemistry profile should be obtained, including measurement of serum calcium. Although usually normal, the presence of a low serum bicarbonate concentration raises the possibility of Type I RTA.

43. Urinalysis — A careful urinalysis should be performed since certain findings point toward a specific diagnosis. A urine pH above 7 with phosphate crystals in the urine sediment is suggestive of calcium phosphate or struvite calculi, while the presence of hexagonal cystine crystals is diagnostic of cystinuria.
Although uric acid crystals and calcium oxalate crystals may be seen in individuals without stone disease, the specific crystal type in a patient with stone disease is likely to represent the composition of the stone.

44. 24-hour urine collections — At least two 24-hour urine collections should be obtained while the patient maintains their usual diet, fluid intake and physical activities given the high variability of the urine values.
If there is a substantial discrepancy between two results, a third collection may be required.
Urine collections should not be performed if there is evidence of renal/ureteral obstruction or urinary tract infection from existing calculi.

45. The urine volume, pH, and excretion of calcium, uric acid, citrate, oxalate, sodium, and creatinine (to assess the completeness of the collection) should be measured.
Twenty-four hour urine collections may not be helpful in determining the cause of new onset stones in dialysis patients

46. A variety of definitions for "normal" are frequently used for each of the urinary parameters: ●Calcium − less than 250 mg per day in women or less than 300 mg per day in men ●Uric acid − less than 750 mg per day in women or less than 800 mg per day in men ●Oxalate − less than 45 mg per day in both women and men ●Citrate − greater than or equal to 320 mg per day in both women and men

47. Number of collections — Because of daily variations in dietary intake, which are occasionally large, some have recommended that two to three 24-hour collections be obtained.
we recommend that a minimum of two collections be performed as part of the initial evaluation

48. Timing of collections — The urine collections should be obtained in the outpatient setting when the patient is on usual diet; values should not be measured in the hospital. It is common practice to wait at least one to three months after a stone event to obtain the collections .At the least, one should wait until the patient has completely recovered from any surgical interventions and make sure that the urine is not infected or the collecting system obstructed.
We generally suggest waiting one to two months after the last stone episode since the patient may have temporarily modified their diet.

49. if a patient is a recurrent stone former, then it should be made clear to the patient and the treating urologist that a stone must be sent for analysis during the next stone episode.
If stone composition is unknown, then treatment recommendations to prevent future stone episodes will be influenced by the 24-hour urine results and the clinical picture.

50. Hypercalciuria — If the urine calcium is elevated, then attempts to lower the urine calcium concentration should be instituted (often a thiazide diuretic will be necessary).
In addition, primary hyperparathyroidism, sarcoidosis, and distal (type 1) renal tubular acidosis should also be considered in the patient with increased urine calcium levels.

51. Hypocitraturia — If the citrate is low, choosing treatment is a more difficult decision. Supplementing citrate intake (eg, potassium citrate) will increase urinary citrate excretion. However, this will also raise the urinary pH. If the predominant calcium salt is calcium phosphate, which forms more readily in an alkaline urine, supplementation with citrate may, in fact, accelerate the rate of stone formation. In this case, the urine pH may be a useful guide. If the urine pH is 6.5 or higher, the use of citrate supplements should be used with great caution.

52. Hyperoxaluria — If hyperoxaluria is present, a low oxalate diet should be tried first. The primary foods to avoid are spinach and nuts. The following site contains the oxalate value for different foods:
Even if the urine calcium is high, increasing dietary calcium or adding an over the counter calcium citrate supplement with meals should be considered in addition to a low oxalate diet if the low oxalate diet alone is insufficient.
However, the amount of urinary oxalate that is derived from the diet is quite variable; thus, if a patient adheres to a low oxalate diet and the urine oxalate does not fall, then the oxalate restriction can be removed

53. Hyperuricosuria — If hyperuricosuria is present, lifestyle modification with the aim of reducing uric acid production (ie, decreased purine intake and weight loss) should be implemented
However, if the urine pH is 6.0 or higher, the high urine uric acid may not be playing a role, as it will stay in solution.

54. Low urine volume — If the urine volume is less than two liters in 24 hours, then patients should increase their fluid intake with the goal of producing at least two liters of urine per day
Fluid should be ingested throughout the day and at bedtime, and the volume should be increased when sweat losses are greater, such as at higher ambient temperatures and with exercise.

55. RADIOLOGIC MONITORING — Another management issue is whether to monitor a stone former, usually with ultrasonography, (KUB), or (CT), to determine if new stones have formed or previous stones have increased in size
Monitoring should be performed initially at one year and, if negative, every two to four years thereafter, depending upon the likelihood of recurrence.

56. ACUTE THERAPY — Many patients with acute renal colic can be managed conservatively with pain medication and hydration until the stone passes
Forced intravenous hydration does not seem to be more effective in reducing the amount of pain medication required or increasing stone passage compared with minimal intravenous hydration

57. Urgent urologic consultation is warranted in patients with urosepsis, acute renal failure, anuria, and/or unyielding pain, nausea, or vomiting
The likelihood that ureteral stones will pass depends upon the size and location of the stone; smaller and more distal stones are more likely to pass without intervention

58. Straining urine — Patients should be instructed to strain their urine for several days and bring in any stone that passes for analysis. This will enable the clinician to better plan preventive therapy.

59. Pain control — Patients can be managed at home if they are able to take oral medications and fluids.
Hospitalization is required for those who cannot tolerate oral intake or who have uncontrollable pain or fever.
NSAIDs and opioids — Both NSAIDs and opioids have traditionally been used for pain control in patients with acute renal colic. NSAIDs have the possible advantage of decreasing ureteral smooth muscle tone, thereby directly treating the mechanism by which pain is thought to occur (ureteral spasm)
Prospective randomized controlled studies suggest that NSAIDs are at least as effective as opiates

60. NSAIDs should be stopped three days before anticipated shock wave lithotripsy to minimize the risk of bleeding.

61. Stone passage — Stone size is the major determinant of the likelihood of spontaneous stone passage, although stone location is also important
Most stones ≤5 mm in diameter pass spontaneously. For stones larger than 4 mm in diameter, there is a progressive decrease in the spontaneous passage rate, which is unlikely with stones ≥10 mm in diameter.
Proximal ureteral stones are also less likely to pass spontaneously.

62. Facilitating stone passage — Several different medical interventions increase the passage rate of ureteral stones, including antispasmodic agents, calcium channel blockers, and alpha blockers

63. Studies directly comparing nifedipine and tamsulosin have reported similar rates of stone passage, although rates were slightly higher with tamsulosin
A potential advantage of tamsulosin is somewhat faster stone passage and fewer hospitalizations and procedures. Other alpha blockers appear to be similarly effective

64. International guidelines from the American Urological Association and the European Association of Urology on the management of ureteral calculi suggest that:

65. ●"In a patient who has a newly diagnosed ureteral stone <10 mm and whose symptoms are controlled, observation with periodic evaluation is an option for initial treatment.
Such patients may be offered an appropriate medical therapy to facilitate stone passage during the observation period. "

66. Based upon data suggesting faster stone passage with an alpha blocker versus calcium channel blockers, we initiate treatment with tamsulosin (0.4 mg once daily) for four weeks to facilitate spontaneous stone passage in patients with stones ≤10 mm in diameter. Patients are then re-imaged if spontaneous passage has not occurred.

67. Patients with stones larger than 10 mm in diameter, patients with significant discomfort, those with significant obstruction or who have not passed the stone after four to six weeks should be referred to urology for potential intervention.

68. Current options for therapy of stones that do not pass include shock wave lithotripsy (SWL), ureteroscopic lithotripsy with electrohydraulic or laser probes, percutaneous nephrolithotomy and laparoscopic stone removal.
Open surgical stone removal is rarely needed.
SWL is the treatment of choice in 75 percent of patients and works best for stones in the renal pelvis and upper ureter.

69. For patients with larger renal calculi (eg, >1
For patients with larger renal calculi (eg, >1.5 cm), renal stones of harder composition (eg, cystine or calcium oxalate monohydrate) or stones in complex renal or ureteral locations (eg, lower pole calyx or mid-ureter), SWL is only successful in approximately 50 percent of cases.
In these settings, endoscopic stone fragmentation with a percutaneous or ureteroscopic approach is preferred.

71. Thanks for attention