Historical Figures with Stone Disease. Egyptian mummies Pliny Sr. Walter Scott Sydenham Benjamin Franklin Napoleon Lyndon B.

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2 Historical Figures with Stone Disease Egyptian mummies Pliny Sr. Walter Scott Sydenham Benjamin Franklin Napoleon Lyndon B. Johnson

3 goals Review epidemiology of stones and hypercalciuria Discuss risk factors for kidney stones Provide framework for the evaluation and therapy of hypercalciuria in pediatric patients with an emphasis on diet Prevention is key

4 Outline Clinical manifestations Epidemiology of stone disease Factors influencing stone formation Hypercalciuria etiologies Nutritional factors Evaluation and therapy

5 Classification of Renal Stones By Predominant Component Calcium oxalate 73% Calcium phosphate 8% Mg Ammonium Phosphate (struvite) 9% Uric acid 7% Cystine 1% Other 2%

6 The NEW ENGLAND JOURNAL of MEDICINE december 25, 2008 Melamine and the Global Implications of Food Contamination Julie Ingelfinger, M.D. Affected more than 294k children in china, plus others in Asia >50k hospitalized, 6 + deaths 22 brands of formula Prior contamination and deaths from pet food contamination Synthesized multiple countries including USA Use in plastics, adhesives, glues, laminated products, cements, etc etc Also found in other foods worldwide Can leach into food Found in soil when used as fertilizer Detected in animal feed and eggs in China, and in US 66% nitrogen by mass?surreptitious use to enhance apparent protein content

7 Milner et al, Mayo Clin proc 1993; 68:241

8 Clinical manifestations: pain Flank/back Abdominal Bladder / voiding symptoms Pain radiation to testicle or vulva Hematuria patterns

9 Epidemiology Incidence 12% lifetime Race Caucasian predominance Sex male > female (3-4:1) Age peak 3-53 th decade Geographic stone belts

10 A Rise in Kidney Stones Is Seen in U.S. Children The New York Times October 2008 YOUNG VICTIM Tessa Cesario, 11, developed a kidney stone in February. She has since cut back on salt and is drinking more water.

11 Imaging studies KUB Ultrasound CT noncontrast (helical)

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14 Complications of Nephrolithiasis Pain Obstruction hydronephrosis Infection Bleeding Surgery scar formation

15 Recurrence risk % of children develop stones within 1 4 years

16 Why do stones develop?

17 Factors Influencing Stone Formation Concentration of salts in solution Urine flow rate ph Availability of homogeneous or heterogeneous nuclei Inhibitors

18 calcium

19 Bone Food 15 mg/kg/day Formation 4 mg/kg/day Resorption 4 mg/kg/day Intestine 18 mg/kg/day Digestive Juice Calcium 3 mg/kg/day Total Absorbed Intestinal Calcium 7 mg/kg/day Calcium Pool Feces 11 mg/kg/day Urine <4 mg/kg/day

20 Hypercalciuria-etiologies etiologies Increased GI absorption Vit D Milk-alkali Bone Immobilization Rickets Malignancies JRA Hormonal Adrenocortical excess Hyperparathyroidism Hyperthyroidism

21 Hypercalciuria-etiologies etiologies Renal tubular RTA Dent s, Bartter s s syndrome Diuretics Other ***Idiopathic Hypercalciuria William s s Syndrome Medullary Sponge Kidney Sarcoidosis

22 Stones - medications Prednisone Protease inhibitors indinavir Furosemide Anticonvulsants Topiramate (Topamax) Zonisamide (Zonegran) Hyperalimentation

23 Idiopathic Hypercalciuria 3% of children 3 14 % of adults 30 40% of calcium stone formers Genetics Autosomal dominant sporadic Incidence:

24 To prevent calcium oxalate stones should we limit dietary calcium?

25 Most stones are calcium oxalate.. What about the oxalate?

26 Urine Oxalate Sources diet 10-50% Vitamin C metabolism 50-85% Low = 50 mg High = 250 mg

27 Foods with High Oxalate Content Rhubarb Parsley Spinach Beet greens Swiss chard Sorrel Asparagus Strawberries Turnip greens Dill Chocolate Cocoa Tea Nuts Dried figs

28 Oxalate Concentrations of Common Beverages Beverage Oxalate (mg/100 ml) Cola drinks 0.5 Coffee 0.7 Apple juice 1.1 Beer 1.7 Tea Instant 3.5 Leaf 5.8 Grape juice 5.8 Cranberry juice 6.6 Orange juice 8.5 Grapefruit juice 11.0 Derric FC and Carter WC, Postgrad. Med. 66:115, 1979

29 Oxalate Enhanced Intestinal absorption Clinical settings Inflammatory bowel disease Short gut/intestinal bypass Low calcium diet Causes Lack of availability of calcium for binding Increased colonic permeability Deficiency of oxalate metabolizing bacteria? Oxalobacter formigenes

30 Von Unruh et al, JASN 15:1576, 2004

31 Calcium and oxalate diet influences Oxalate too high Calcium too Low as well as too High

32 Calcium, oxalate, fluids. Have we modified diet enough?

33 Diet and stones Fluids Calcium Oxalate Sodium Protein / uric acid

34 Alon and Berenbom Pediatr Nephrol 2004 Muldowney etal KI 1982

35 From John r. asplin Normal none stone pts Fixed calcium and sodium diet

36 Diet and stones Fluids Calcium Oxalate Sodium Protein / uric acid

37 Stone Inhibitors What does this have to do with diet?

38 Possible Inhibitors of Crystallization Citrate Magnesium Pyrophosphate Sulfate Fluoride Trace Elements zinc, tin Glucosaminoglycans heparin, hyaluronic acid, chondroitin sulfate, dermatan sulfate Nephrocalcin Tamm-Horsfall glycoprotein Osteopontin Prothrombin fragment 1

39 Ubiquitous within the Citric Acid Cycle Small amounts of dietary citrate appears in urine Less potent per weight than other inhibitors High concentration achievable in urine makes it important Stone Inhibitors Citrate

40 Pak,Endocrinologist 16:

41 Stone formers on diet high in fruit and vegetables Meschi et al Kidney Int, 2004, 66:

42 Stone prevention diet Fluids high Sodium low Calcium normal Protein normal Oxalate low Vitamins not excessive esp D, C

43 Borghi et al ; NEJM january 2002 Male, mean age 45 years Weight kg Diet 1. low calcium 400 mg 2. normal calcium 1200 mg low sodium (2900 mg), low protein (52 gms) All low oxalate advice, fluids L seasonally adjusted

44 Borghi et al ; NEJM january 2002

45 High protein, low carb diet stone risk Increased urine Uric acid Calcium Decreased urine Citrate Urine volume

46 evaluation

47 Diet Nephrolithiasis History Fluids, Calcium, Sodium, Protein, Oxalate, fruit and veggies Medications Vitamins, especially D & C Mineral supplements, steroids, other meds (antisz) History UTI, Diarrhea/Dehydration Stone activity, prolonged bed rest, excessive weight loss, other Family history Stones, gout, etc

48 lab evaluation therapy Timing? How much?

49 Nephrolithiasis Laboratory Evaluation Blood Tests CBC Calcium Phosphorous, magnesium Uric Acid Alkaline Phosphatase Electrolytes with Bicarbonate BUN & Creatinine PTH Vit D

50 Nephrolithiasis evaluation Urine analysis urine Infection/inflammation Hematuria Crystals ph Specific Gravity Random urine chem (ratios) 24 hour urine collections (stone panels)

51 Treatment - How aggressive? Stone burden Stone history Removal of risk factors? Underlying cause

52 Prevention is the best therapy

53 Diet Hydration /fluids Uric acid / animal protein Calcium normal Sodium low Oxalate limited Fruit and Veg Mg/K

54 The typical American diet promotes kidney stones

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56 Therapy other nonspecific Stone inhibitors citrate Infection control

57 Treatment - specific Treat underlying cause Uric acid Urine ph Allopurinol Low purine diet Calcium Thiazide diuretics-stimulate stimulate distal Ca absorption

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61 summary Symptoms of stones Pain Hematuria Bladder symptoms Common causes Idiopathic hypercalciuria Medications / supplements Diet Immobilization Therapy DIET FLUIDS Citrate other

62 nephrolithiasis Nephrologist Urologist nutritionist

63 Thank you