Metabolic Stone Work-Up For Stone Prevention. Dr. Hazem Elmansy, MD, MSC, FRCSC Assistant Professor, NOSM, Urology Department

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1 Metabolic Stone Work-Up For Stone Prevention Dr. Hazem Elmansy, MD, MSC, FRCSC Assistant Professor, NOSM, Urology Department

2 Faculty/Presenter Disclosure Slide Faculty: Hazem Elmansy Relationships with commercial interests: Janssen, Sanofi, Pfizer

3 Learning Objectives To aid practitioners in the evaluation, treatment and follow-up of first time and recurrent stone formers To reduce the likelihood of stone occurrence through diet, lifestyle changes To provide an overview of pharmacologic management of stone disease

4 Prevalence of Kidney Stones 2012 data from the U.S. National Health and Nutrition Examination Survey (NHANES) Kidney stone prevalence Men: 10.6% Women: 7.1%

5

6 Recurrence rates after an initial symptomatic stone event are reported to be from 30 50% within 10 years of first presentation Studies have shown that patients are more willing to undergo metabolic evaluation compared to physicians willingness to further investigate them Epidemiological data from the U.S. show that only 7% of patients with a high risk of recurrent stone disease undergo metabolic evaluation by any physician

7 Indications for metabolic evaluation First time stone-former, without any identifiable risk factors metabolic evaluation a limited To rule out potential systemic disorders, such as hyperparathyroidism and renal dysfunction Urinalysis ± culture Serum electrolytes (Na, K, Cl, HCO3) Serum Ca Serum creatinine

8 Indications for metabolic evaluation Known risk factors in-depth metabolic investigation

9 Risk Factors Children (<18 years of age) Bilateral or multiple stones Recurrent stones Non-calcium stones (e.g., uric acid, cystine) Pure calcium phosphate stones Complicated stone: Acute kidney injury Sepsis Complicated hospital admission

10 Risk Factors Any stone requiring percutaneous nephrolithotomy treatment Stones in the setting of a solitary (anatomical or functional) kidney Patients with renal insufficiency History of kidney stones and systemic disease Gout Osteoporosis Bowel disorders Hyperparathyroidism Renal tubular acidosis

11 Risk Factors Occupation where public safety is at risk Pilots Air traffic controller Police officer Military personnel Firemen

12 In-Depth Evaluation Serum 24-hour urine collection Spot Urine

13 In-Depth Evaluation Serum Tests Creatinine, sodium, potassium, chloride, calcium, albumin, uric acid, bicarbonate Parathyroid hormone (PTH) level If serum calcium is high Vitamin D If low normal serum calcium or elevated serum PTH

14 In-Depth Evaluation 24-hour Urine Collection Volume Creatinine Calcium Sodium Potassium Oxalate Citrate Uric acid Magnesium Cystine if suspect cystine stone or if the stone analysis is cystine

15 In-depth Evaluation Spot Urine Urine ph Urinalysis Specific gravity

16 Number of 24-hour urine collections Two 24-hour urine collections be obtained in order to correctly identify metabolic abnormalities

17 Importance of Stone Analysis Patients collect stones they have passed Stones removed at the time of surgical intervention

18 General Dietary Measures

19 General Dietary Measures Healthy diet can be a wonderful life option For someone who forms stones: not an option Assessment with a Dietitian is strongly suggested

20 Fluid intake CUA Guidelines All stone-formers should be counselled To achieve a daily urine output of 2.5 L Fluid intake between L Tips to help you increase your fluid intake (read online) Carry a refillable water bottle everywhere

21 Water Hardness Water pressure will be lower May clog completely Pipes will have to be replaced

22 Water Hardness Water pressure will be lower May clog completely Pipes will have to be replaced

23 Water Hardness Although water hardness can alter urinary parameters, it does not play a significant role in recurrence risk

24 Fluid Intake Soft drinks, caffeinated beverages (such as coffee and tea), and alcohol Some or no benefit in various trials Restriction of these fluids is not necessary As long as a good amount of the patient s fluid intake consists of water

25 May increase protection by increase citrate level Carbonated Water

26 Fluid Intake Drinking fruit juices (orange, lemon) appears to increase citrate levels in the urine

27 Healthy Weight Higher BMI high uric acid levels Overweight individuals Urine ph tends to be acidic Increased risk of most stone types

28 Calcium Calcium in the diet can be helpful Binds oxalate in the gut Prevents it from being absorbed Low-calcium diets are not recommended: Increased oxalate absorption to the body higher levels in the urine and increased risk of stone formation Recommended calcium daily intake: mg

29 Calcium Supplement Take them at meal times with your food: It binds to oxalate in the gut Calcium citrate rather than calcium carbonate conflicting results

30 Vitamin D In calcium oxalate stone-formers with documented vitamin D deficiency, repletion is appropriate Monitoring for hypercalciuria on 24-hour urine in follow-up is suggested

31 Salt 75% of our salt intake is from processed foods Limit/avoid the amount of salt you add to your food More sodium you take in and excrete more calcium you waste in the urine Salt In Diet Salt Out in Urine Calcium Out in Urine Calcium Stone Risk

32 Salt Safe and adequate intake level for sodium 1,100 to 3,300 mg or ½ to 1 ½ teaspoons/day (USA) Level teaspoon: approximately 2,000 mg Patients with recurrent calcium stones Sodium intake of 1500 mg daily Do not exceed 2300 mg daily (CUA Guidelines)

33 Animal Protein Protein is an important nutrient in the body Animal and vegetable sources A reduction of animal protein: Decreases calcium and uric acid in the urine Increases citrate Decreases the overall risk of stone formation Protein build-up drinks should be avoided

34 Animal Protein Animal Protein Foods Meat Poultry Fish Eggs Cheese Yoghurt Vegetable Protein Foods Lentils Chickpeas Beans, such as kidney beans, butter beans, baked beans Hummus Quorn

35 Uric Acid Stones

36 Animal Protein High animal protein was found to be associated with increased excretion of uric acid Reduction in urinary ph Reduction in citrate excretion A vegetarian diet reduce the risk of uric acid crystallization by 93% compared to a typical Western diet

37 Animal protein Different types of animal protein were compared in a randomized crossover study in 15 healthy volunteers using beef, chicken, and fish Fish had high purine content resulted in increased urinary uric acid excretion Beef resulted in the highest saturation of calcium oxalate compared to chicken, but was similar to fish

38 Animal Protein CUA In patients with recurrent calcium oxalate and uric acid stones, moderation of animal protein intake and avoidance of purine rich foods is suggested

39 Animal Protein Limit your daily protein intake to 12 ounces per day of beef, poultry, fish and pork Twelve ounces is equivalent in size to about three decks of cards USA

40 Oxalates Small proportion of urinary oxalate is of dietary origin (10 15%) It isn t necessary to completely avoid foods containing oxalate, but you should aim for a moderate intake Many foods contain low to moderate amounts of oxalate There are some foods that are particularly high in oxalates

41 Oxalates

42 Oxalates Limit your intake to no more than one item from this list per day

43 Oxalates Tea and coffee have a moderate oxalate content, aim to have no more than two to three cups per day

44 Oxalates Green tea is ok

45 Stones in Thunder Bay

46 Fruit and Vegetables Diet high in fiber, fruits, and vegetables may offer a small protective effect against stone formation (CUA Guidelines)

47 Vitamin C Vitamin C supplementation: >1000 mg daily not recommended Risk of hyperoxaluria and stones

48 Index patient 1: Calcium oxalate or mixed calcium oxalate/calcium phosphate stone

49 Index patient 1: Calcium oxalate or mixed calcium oxalate/calcium phosphate stone

50 Thiazides Decreases urinary calcium and decreases stone recurrence Dosages: Hydrochlorothiazide (25 mg orally, twice daily; 50mg orally, once daily) Chlorthalidone (25 mg orally, once daily) Indapamide (2.5 mg orally, once daily)

51 Side effects Hypokalemia Hyperglycemia Hyperlipidemia Hyperuricemia Hypomagnesemia Hypocitraturia Thiazides Combining thiazide with potassium citrate or potassium chloride prevents hypokalemia and hypochloremic metabolic alkalosis

52 Index patient 1: Calcium oxalate or mixed calcium oxalate/calcium phosphate stone

53 Index patient 1: Calcium oxalate or mixed calcium oxalate/calcium phosphate stone

54 Allopurinol Dosage: mg daily Major side effects: Rash Gastrointestinal upset Abnormal liver enzyme levels Prolonged elimination in renal disease

55 Allopurinol In patients with calcium oxalate stones, hyperuricosuria, and normocalciuria Not effective in prevention of stones in patients with normal urinary uric acid levels

56 Index patient 1: Calcium oxalate or mixed calcium oxalate/calcium phosphate stone

57 Alkali Citrate Alkali citrate (potassium citrate, potassium, magnesium citrate, sodium citrate) Alkali citrate results in increase in urinary ph and urinary citrate Potassium citrate is the most commonly studied Dosages: meq in divided doses daily

58 Alkali Citrate Monitoring of urine ph: Risk of calcium phosphate stone Side effects: Gastrointestinal upset Renal insufficiency: Hyperkalemia Use sodium citrate, sodium bicarbonate, Potassium citrate is preferred over sodium citrate, as the sodium load may increase urinary calcium excretion

59 Alkali Citrate CUA Alkali citrates are effective in increasing urinary citrate, urinary ph, and reducing stone recurrence in calcium stone-formers

60 Index patient 2: Pure calcium phosphate stone There is not much evidence for diet advice in patients who form calcium phosphate stones Distal renal tubular acidosis Primary hyperparathyroidism Chronic urinary tract infection

61 Index patient 3: Uric acid stone Obesity Metabolic syndrome Diabetes mellitus Gout Excessive bicarbonate loss due to high output bowel disease, Myeloproliferative disorders Tumour lysis syndrome

62 Index patient 3: Uric acid stone Uric acid stone formation is most commonly associated with Low urinary ph Low urine volume Rather than hyperuricosuria

63 Index patient 3: Uric acid stone

64 Index patient 3: Uric acid stone CUA In patients with uric acid stones, alkalinization of the urine targeting a urine ph of 6.5 is the first-line therapy Allopurinol may be used as adjunctive therapy in patients with hyperuricemia or hyperuricosuria

65 Cystine Stones Common genetic disorder affecting 1/7000 individuals Present in childhood or as teenagers and characterized by recurrent stone formation especially if prophylaxis is not optimized

66 Cystine Stones

67 Cystine Stones

68 Cystine Stones Maintain a urine output of at least 3 L daily )( oral intake of L of fluid) The success of stone prevention will be poor in patients who do not comply with increased fluid intake

69 Cystine Stones

70 Cystine Stones

71 Cystine Stones

72 Cystine Stones The solubility of cystine increases significantly between urine ph of 7.0 to 7.5 Urinary alkalinization is the initial step in medical therapy, with the goal of achieving a urine ph of > 7.0 A urinary ph > 7.5 should be avoided, as this may promote calcium phosphate stone formation

73 Cystine Stones

74 Cystine Stones Penicillamine: thiol binding agents Dose: 1 2 g Side effects Fever Arthralgias Rash Leucopenia Proteinuria Monitor: Urinary supersaturation of cystine Cystine capacity

75 Cystine Stones Captopril is not currently recommended for cystine stone prevention

76 Struvite Stone Not considered a metabolic condition It occurs as a consequence of urinary infection with urease producing organisms Surgical removal of stone is the standard therapy Prevention strategy may be low-dose suppressive antibiotic therapy

77 HOW DO YOU KNOW IF YOUR TREATMENT IS WORKING?

78 HOW DO YOU KNOW IF YOUR TREATMENT IS WORKING? Do another 24 hour urine collection

79

80

81

82 Take Home Message For patients at risk of recurrent renal stones: detailed medical evaluation Individualized approach to dietary and pharmacological prevention are important aspects of their care Frequency of follow-up and the need for repeat metabolic testing not clearly defined must be individualized

83 Take Home Message Re-evaluations with repeat metabolic testing within 6 months and yearly to monitor treatment efficacy and side effects Periodic imaging is recommended for small asymptomatic stones

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