MEDICAL STONE MANAGEMENT MADE EASY PRACTICAL ADVICE

Transcription

1 MEDICAL STONE MANAGEMENT MADE EASY PRACTICAL ADVICE Comprehensive Kidney Stone Center at Duke University Medical Center Durham, North Carolina Glenn M. Preminger, M.D. UCLA State-of-the Art Urology 02 March 2017

2 MEDICAL MANAGEMENT OF NEPHROLITHIASIS RECENT ADVANCES Promoters of Nephrolithiasis Dietary sodium Dietary calcium / Calcium supplements Changing epidemiologic patterns High acid-ash diet, obesity, bariatric surgery Inhibitors of Nephrolithiais Potassium Citrate Long term treatment Lemonade

3 METABOLIC EVALUATION CLASSIFICATION Calcareous calculi Non-calcareous calculi Hypercalciuria (40-75%) Low urinary ph Uric acid stones (5%) Hyperuricosuria (10-50%) Cystinuria Hyperoxaluria (<5%) Cystine stones (1%) Hypomagesuria (<5%) Infection (urea-splitting) Struvite stones (15%) Hypocitraturia (10-50%) * Expressed as percentage of total

4 HYPERCALCIURA ROLE OF SODIUM Oral sodium intake is a major determinate of renal calcium excretion An increased sodium intake of 100 meq / day will increase urinary calcium 50 mg / day Excess urinary sodium will also block the hypocalciuric action of thiazides

5 DIETARY CALCIUM IMPACT OF LOW CALCIUM DIET Early recommendations suggest that low calcium diet will decrease urinary Ca ++ excretion, thereby reducing risk of stone formation Potential risk factors involving low calcium diet: Reduced bone mass Increased urinary oxalate

6 DIETARY CALCIUM IMPACT OF LOW CALCIUM DIET 45,600 men, ages 40-75, with no h/o stones 97,000 women, ages 34-59,with no h/o stones 4-12 year follow-up Ca ++ intake inversely associated with stone formation Low calcium diet increases the risk for renal stone formation Curhan, et al, 1993 Curhan, et al, 1997

7 DIETARY CALCIUM IMPACT OF LOW CALCIUM DIET Five-year randomized, prospective trial in 120 men with hypercalciura (> 300 mg/day) and recurrent nephrolithiasis Low Calcium Diet (400 mg/day) Normal sodium Normal protein Regular Calcium Diet (1200 mg/day) Low sodium Low protein Borghi,et al 2002

8 DIETARY CALCIUM IMPACT OF LOW CALCIUM DIET Calcium (mg/day) * * 236 Baseline 5 Years Rx Low Calcium Norm Calcium Borghi,et al 2002

9 DIETARY CALCIUM IMPACT OF LOW CALCIUM DIET Sodium (meq/day) Baseline 5 Years Rx * 50 0 Low Calcium Norm Calcium Borghi,et al 2002

10 DIETARY CALCIUM IMPACT OF LOW CALCIUM DIET Oxalate (mg/day) * Baseline 5 Years Rx * 10 0 Low Calcium Norm Calcium Borghi,et al 2002

11 DIETARY CALCIUM IMPACT OF LOW CALCIUM DIET p=0.04 Borghi,et al 2002

12 DIETARY ADVICE RECOMMENDATIONS Normal calcium intake in most patients Moderate calcium restriction in patients with absorptive hypercalciuria Moderate dietary intake of oxalate Spinach, tea, chocolate, nuts Limit dietary sodium intake Limit red meat intake

13 CALCIUM SUPPLEMENTS CAUSE OF STONE FORMATION? Initial observations anecdotal Clinical and physicochemical / physiologic data support this concept

14 CALCIUM SUPPLEMENTS PREMENOPAUSAL WOMEN Prominent increase in urinary calcium during first month of supplementation Less prominent with continued therapy due to suppressed parathyroid function ( Vit D) POSTMENOPAUSAL WOMEN Calciuric response is blunted due to impaired intestinal calcium absorption Probably 2 0 to reduced Vit D synthesis

15 CALCIUM SUPPLEMENTS CALCIUM CITRATE "Citracal" Over-the-counter preparation Calcium citrate 950 mg Elemental calcium 200 gm Provides increased intestinal calcium absorption Prevents supersaturation of stone-forming salts A more "stone-friendly" calcium supplement

16 CALCIUM SUPPLEMENTS CALCIUM CITRATE Long-term clinical trial in pre-menopausal women No significant change in urinary saturation of: Calcium oxalate Calcium phosphate (brushite) No increased propensity for crystallization of calcium salts Mainly due to "protective" effects of citrate Sakhaee & Pak, 2004

17 CALCIUM SUPPLEMENTS RECOMMENDATIONS Check 24-hour urinary calcium 4 months after beginning supplementation If nomocalciuric - nothing to do If hypercalciuric - begin thiazides

18 NEPHROLITHIASIS CHANGING EPIDEMIOLOGIC PATTERNS Dietary changes potentially responsible for increasing incidence and changing trends in calcium oxalate and uric acid stone formation High acid-ash diet Obesity

19 MEDICAL MANAGEMENT OF NEPHROLITHIASIS NATURAL HISTORY & RISK FACTORS Peak incidence age Gender (Male : Female) 3 : 1 Family history 3 - fold risk Body size risk with weight Recurrence after first stone: Year % Year % Year %

20 MEDICAL MANAGEMENT OF NEPHROLITHIASIS NATURAL HISTORY & RISK FACTORS Peak incidence age Gender (Male : Female) 1.3 : 1 Family history 3 - fold risk Body size risk with weight Recurrence after first stone: Year % Year % Year %

21 MEDICAL MANAGEMENT OF NEPHROLITHIASIS CHANGING EPIDEMIOLOGY Using nationally representative data, an updated estimate the prevalence of kidney stones in the United States was performed National Health and Nutrition Examination Survey (NHANES) queried participants about kidney stones in 20 1 in 11 Scales, et al, 2012

22 COMMON US HEALTH CONDITIONS 15% 10% 1 in 17 1 in in % 1 in % Stroke CAD Diabetes Stones Scales, et al, 2012

23 CHANGING TRENDS IN NEPHROLITHIASIS IMPACT OF ACIDOSIS Bone Increased Ca resorption Intestine Increased Ca absorption Kidney Decreased Ca reabsorption Decreased Citrate synthesis Increased tubular citrate reabsorption Hypercalciuria & negative Ca ++ balance Hypocitraturia

24 ACID-ASH DIET Veg Protein Veg Animal No Egg Protein Protein ph Calcium, mg/d Citrate, mg/d Sulfate, mg/d Uric acid, mg/d Rel Sat - CaOx Inhib activity-caox * * * * * * * Breslau & Pak, 1988

25 ANIMAL PROTEIN DIET BEEF vs CHICKEN vs FISH Protein rich diets introduce an stone risk 3 phase, randomized cross over metabolic study comparing 3 different animal proteins Gram for gram, fish is associated with higher serum and urinary UA levels than either beef or chicken, which may have ramifications for UA and/or CaOx stone formers Should advise stone formers to limit their intake of all animal proteins, including fish Tracy & Pearle, 2014

26 NEPHROLITHIASIS EFFECT OF ANIMAL PROTEIN DIET Calcium Sulfate ph Citrate Uric acid All increased risk factors for recurrent stone formation

27 PREVALENCE OF OBESITY OBESITY TRENDS AMONG U.S. ADULTS No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%

28 PREVALENCE OF OBESITY GLOBAL OBESITY TRENDS No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%

29 IMPACT OF OBESITY RETROSPECTIVE REVIEW Stone patient population: 1021 Obese patients with stones: 140 (14%) Obese patients with complete 83 metabolic evaluation receiving medical therapy Ekeruo, et al, 2004

30 % Prevalence IMPACT OF OBESITY 70 OBESE GROUP CONTROL GROUP GOUTY DIATHESIS HYPER- URICOSURIA HYPER- CALCIURIA LOW FLUID INTAKE Ekeruo, et al, 2004

31 IMPACT OF OBESITY % PREVALENCE OF URIC ACID STONES 70 Obese Patients % Control Group 63% % Ekeruo, et al, 2004

32 BODY WEIGHT AND URINARY PH Dallas (N=1715) Chicago (N=3168) hour Urinary ph Mechanism is 1 <61 kg Sextile of Weight >95 kg independent of diet Sakhaee, Coe, Pak 2004

33 IMPACT OF OBESITY ETIOLOGY OF LOW URINE ph Obese patient with Type II diabetes Insulin resistance Urinary ph Impaired ammonium excretion Uric acid stones Sakhaee, Coe, Pak 2004

34 IMPACT OF OBESITY POSSIBLE SOLUTIONS Dietary modification & weight loss Reverse insulin resistance Alkali therapy Normal urinary acidity

35 IMPACT OF OBESITY REDUCTION IN NEW STONE FORMATION PRE RX POST RX # stones/ pt/year Obese group 0.1 Control group Ekeruo, et al, 2004

36 POTASSIUM CITRATE PHYSICOCHEMICAL ACTION Potassium Alkali Tubular citrate citrate load reabsorption Urinary ph Undissociated uric acid Urinary citrate Saturation of CaOx Inhibitor activity vs Ca salts

37 LONG TERM RX WITH POTASSIUM CITRATE METHODS 1480 patients were reviewed in the Duke Stone Center Database 954 patients had two 24-hour urinary profiles 515 patients were included in the analysis Mean Duration of KCit therapy 41 months (range months) Robinson, et al, 2008

38 LONG TERM K-CITRATE CHANGE IN ph BY DURATION p < Pre-Rx 6 12 mo mo mo > 36 mo Robinson, et al, 2008

39 LONG TERM K-CITRATE CHANGE IN CITRATE BY DURATION p < 0.01 Pre-Rx 6 12 mo mo mo > 36 mo Robinson, et al, 2008

40 LONG TERM K-CITRATE STONE FORMATION RATE stones/year p < Pre-Rx 0.58 Post-Rx

41 LONG TERM RX WITH POTASSIUM CITRATE CONCLUSIONS KCit provides a significant alkali and citraturic response during both short and long term therapy Urinary metabolic profiles are sustained for as long as 14 years Long term KCit therapy significantly reduces stone formation rates Robinson, et al, 2008

42 POTASSIUM CITRATE CURRENT PREPARATIONS Liquid / crystals - Citra K crystals (generic) Slow-release pills - Urocit K / generic Urocit K - 15

43 ALKALI THERAPY WITH LEMONADE CHEMICAL COMPOSITIONS Cit (gm) Ca (mg) Na (mg) Mag (mg) Orange Grapefruit Lemon Raspberry Pineapple Cranberry Seltzer & Stoller, 1996

44 ALKALI THERAPY WITH LEMONADE URINE BIOCHEMISTRY Mix 120 ml lemon juice with tap water to = 2 liters Average cost for 1 week supply (14 liters) = $2 Baseline During Lemonade Citrate (mg) * Calcium (mg) Oxalate (mg) Volume (L) Seltzer & Stoller, 1996

45 ALKALI THERAPY WITH LEMONADE LONG-TERM FOLLOW UP 32 patients on lemonade therapy (120 ml lemon juice with 2 L water) compared to an age- and sexmatched group treated with potassium citrate Lemonade K-Cit Rx duration (mo) urinary citrate (mg) 354 * 472 SFR (stones/pt/yr) Kang, et al, 2005

46 ALTERNATIVES TO K-CIT ALKALIZATION WITH NA + BICARB 60 meq/day of NaBic provided an equivalent and significant increase in urinary citrate and ph (1300 mg / BID) NaBic led to a significant in sodium excretion without concomitant in urinary calcium This short-term study suggests that NaBic may be an effective alternative for the treatment of hypocitraturia in patients who cannot tolerate or afford the cost of KCit NaBic is not ideal in patients with pure uric acid stones and high urate excretion Pinheiro & Heilberg, 2013

47 MEDICAL MANAGEMENT OF NEPHROLITHIASIS FUTURE DIRECTIONS Dietary Modification Normal calcium, low salt, low protein New Medications Potassium magnesium citrate Enteric Therapy Oxalobactor formigenes Genetic Therapy Hypercalciuria Cystinuria