medical stone management made easy – … stone management made easy ... high acid-ash diet,...

MEDICAL STONE MANAGEMENT MADE EASY –

PRACTICAL ADVICE

Glenn M. Preminger, M.D.

Comprehensive Kidney Stone Centerat Duke University Medical Center

Durham, North Carolina

UCLA State-of-the Art Urology 02 March 2017

MEDICAL MANAGEMENT OF NEPHROLITHIASISPromoters of Nephrolithiasis

Dietary sodiumDietary calcium / Calcium supplements Changing epidemiologic patterns

High acid-ash diet, obesity, bariatric surgery

Inhibitors of NephrolithiaisPotassium Citrate

Long term treatmentLemonade

RECENT ADVANCES

METABOLIC EVALUATION

Calcareous calculi Non-calcareous calculiHypercalciuria (40-75%) Low urinary pH

Uric acid stones (5%)Hyperuricosuria (10-50%) CystinuriaHyperoxaluria (<5%) Cystine stones (1%)Hypomagesuria (<5%) Infection (urea-splitting)

Struvite stones (15%)Hypocitraturia (10-50%)

* Expressed as percentage of total

CLASSIFICATION

HYPERCALCIURAROLE OF SODIUM

Oral sodium intake is a major determinate of renal calcium excretionAn increased sodium intake of 100 mEq / day will increase urinary calcium 50 mg / dayExcess urinary sodium will also block the hypocalciuric action of thiazides

DIETARY CALCIUM

Early recommendations suggest that low calcium diet will decrease urinary Ca++ excretion, thereby reducing risk of stone formationPotential risk factors involving low calcium diet:

Reduced bone mass Increased urinary oxalate

IMPACT OF LOW CALCIUM DIET

DIETARY CALCIUM

45,600 men, ages 40-75, with no h/o stones97,000 women, ages 34-59,with no h/o stones

4 - 12 year follow-upCa++ intake inversely associated with stone formationLow calcium diet increases the risk for renal stone formation


Curhan, et al, 1993Curhan, et al, 1997

DIETARY CALCIUM

Five-year randomized, prospective trial in 120 men with hypercalciura (> 300 mg/day) and recurrent nephrolithiasis


Borghi,et al 2002

Low Calcium Diet(400 mg/day)

Normal sodiumNormal protein

Regular Calcium Diet(1200 mg/day)Low sodiumLow protein

DIETARY CALCIUMIMPACT OF LOW CALCIUM DIET

Borghi,et al 2002

440

248

460

236

0

100

200

300

400

500

Calcium(mg/day)

Low Calcium Norm Calcium

Baseline5 Years Rx

* *


Borghi,et al 2002

227201

241

123

0

50

100

150

200

250

Sodium(meq/day)


Baseline5 Years Rx

*


Borghi,et al 2002

33.1

39.0 37.0

29.0

0

10

20

30

40

Oxalate(mg/day)


Baseline5 Years Rx

**


Borghi,et al 2002

p=0.04

DIETARY ADVICE

Normal calcium intake in most patientsModerate calcium restriction in patientswith absorptive hypercalciuriaModerate dietary intake of oxalate

Spinach, tea, chocolate, nutsLimit dietary sodium intakeLimit red meat intake

RECOMMENDATIONS

CALCIUM SUPPLEMENTS

Initial observations anecdotal

Clinical and physicochemical / physiologic data support this concept

CAUSE OF STONE FORMATION ?

CALCIUM SUPPLEMENTS

Prominent increase in urinary calcium during first month of supplementationLess prominent with continued therapy due to suppressed parathyroid function (↓ Vit D)

PREMENOPAUSAL WOMEN

POSTMENOPAUSAL WOMENCalciuric response is blunted due to impaired intestinal calcium absorption

Probably 20 to reduced Vit D synthesis

CALCIUM SUPPLEMENTS

"Citracal"Over-the-counter preparation

Calcium citrate 950 mgElemental calcium 200 gm

Provides increased intestinal calcium absorptionPrevents supersaturation of stone-forming saltsA more "stone-friendly" calcium supplement

CALCIUM CITRATE

CALCIUM SUPPLEMENTS

Long-term clinical trial in pre-menopausal womenNo significant change in urinary saturation of:

Calcium oxalate Calcium phosphate (brushite)

No increased propensity for crystallization of calcium saltsMainly due to "protective" effects of citrate

CALCIUM CITRATE

Sakhaee & Pak, 2004

CALCIUM SUPPLEMENTS

Check 24-hour urinary calcium 4 months after beginning supplementation

If nomocalciuric - nothing to do

If hypercalciuric - begin thiazides

RECOMMENDATIONS

Dietary changes potentially responsible for increasing incidence and changing trends in calcium oxalate and uric acid stone formation

High acid-ash dietObesity

CHANGING EPIDEMIOLOGIC PATTERNS

NEPHROLITHIASIS

MEDICAL MANAGEMENT OF NEPHROLITHIASIS

Peak incidence age 30 - 60Gender (Male : Female) 3 : 1Family history 3 - fold ↑ riskBody size ↑ risk with ↑ weightRecurrence after first stone:

Year 1 10 - 15%Year 5 50 - 60%Year 10 70 - 80%

NATURAL HISTORY & RISK FACTORS


Peak incidence age 30 - 60Gender (Male : Female) 1.3 : 1Family history 3 - fold ↑ riskBody size ↑ risk with ↑ weightRecurrence after first stone:

Year 1 10 - 15%Year 5 50 - 60%Year 10 70 - 80%

NATURAL HISTORY & RISK FACTORS


CHANGING EPIDEMIOLOGYUsing nationally representative data, an updated estimate the prevalence of kidney stones in the United States was performedNational Health and Nutrition Examination Survey (NHANES) queried participants about kidney stones

1994 20071 in 20 1 in 11

Scales, et al, 2012

COMMON US HEALTH CONDITIONS

2.6

6.0

8.3 8.8

0%

5%

10%

15%

Stroke CAD Diabetes Stones

1 in 38

1 in 17

1 in 12 1 in 11

Scales, et al, 2012

BoneIncreased Ca resorption

IntestineIncreased Ca absorption

KidneyDecreased Ca reabsorptionDecreased Citrate synthesisIncreased tubular citratereabsorption

IMPACT OF ACIDOSIS

CHANGING TRENDSIN NEPHROLITHIASIS

Hypercalciuria & negative

Ca++ balance

Hypocitraturia

ACID-ASH DIETVeg Protein Veg Animal

No Egg Protein Protein

pH 6.56 6.33 6.16Calcium, mg/d 101 122 149Citrate, mg/d 830 742 655Sulfate, mg/d 14 18 21Uric acid, mg/d 477 494 576Rel Sat - CaOx 3.07 4.03 4.12Inhib activity-CaOx 93 65 53

Breslau & Pak, 1988

*

*

***

*

*

Protein‐rich diets introduce an ↑ stone risk3‐phase, randomized cross‐over metabolic study comparing 3 different animal proteinsGram 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

BEEF vs CHICKEN vs FISH

ANIMAL PROTEIN DIET

Tracy & Pearle, 2014

NEPHROLITHIASISEFFECT OF ANIMAL PROTEIN DIET

Calcium pH

Sulfate Citrate

Uric acidAll increased risk factors for recurrent stone formation

1999OBESITY TRENDS AMONG U.S. ADULTS

2008

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

PREVALENCE OF OBESITY

1999GLOBAL OBESITY TRENDS

2008

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

PREVALENCE OF OBESITY

IMPACT OF OBESITY

Stone patient population: 1021

Obese patients with stones: 140 (14%)

Obese patients with complete 83metabolic evaluation receiving medical therapy

RETROSPECTIVE REVIEW

Ekeruo, et al, 2004

54

18

43

20

59

48

58

70

0

10

20

30

40

50

60

70 OBESE GROUPCONTROL GROUP

GOUTYDIATHESIS

HYPER-URICOSURIA

HYPER-CALCIURIA

LOW FLUID INTAKE

% Prevalence

Ekeruo, et al, 2004

IMPACT OF OBESITY

63%

11%0

10

20

30

40

50

60

70 Obese PatientsControl Group

% PREVALENCE OF URIC ACID STONES

%

Ekeruo, et al, 2004

IMPACT OF OBESITY

Sextile of Weight

24-hour Urinary pH

5.8

5.9

6.0

6.1

6.2

6.3

Dallas (N=1715)Chicago (N=3168)

1<61 kg

261 - 70

370 - 77

477 - 84

584 - 95

6>95 kg

BODY WEIGHT AND URINARY PH

Mechanism is independent of diet Sakhaee, Coe, Pak 2004

IMPACT OF OBESITY

Obese patient withType II diabetes

ETIOLOGY OF LOW URINE pH

Sakhaee, Coe, Pak 2004

Impaired ammonium excretion

Insulinresistance

↓ Urinary pH

Uric acidstones

IMPACT OF OBESITY

Dietary modification & weight loss

POSSIBLE SOLUTIONS

Reverse insulin resistance

Normal urinary acidity

Alkali therapy

1.8

0.2

1.7

0.10

0.5

1

1.5

2PRE RXPOST RX

Obese group Control group

REDUCTION IN NEW STONE FORMATION

# stones/pt/year

Ekeruo, et al, 2004

IMPACT OF OBESITY

POTASSIUM CITRATE

Potassium Alkali Tubular citratecitrate load reabsorption

Urinary pH Urinary citrate

Undissociated Saturationuric acid of CaOx

Inhibitor activityvs Ca salts

PHYSICOCHEMICAL ACTION

LONG TERM RX WITH POTASSIUM CITRATE

1480 patients were reviewed in the Duke Stone Center Database 954 patients had ≥ two 24-hour urinary profiles515 patients were included in the analysisMean Duration of KCit therapy

41 months (range 6 – 168 months)

METHODS

Robinson, et al, 2008

CHANGE IN pH BY DURATION

p < 0.0001


Pre-Rx 6–12 mo 12–24 mo 24–36 mo > 36 mo

LONG TERM K-CITRATE

CHANGE IN CITRATE BY DURATION

Pre-Rx 6–12 mo 12–24 mo 24–36 mo > 36 mo

p < 0.01


LONG TERM K-CITRATE

STONE FORMATION RATE

2.34

0.580.0

0.5

1.0

1.5

2.0

2.5

3.0

ston

es/y

ear

p < 0.0001

Pre-Rx Post-Rx

LONG TERM K-CITRATE

CONCLUSIONSKCit provides a significant alkali and citraturic response during both short and long term therapyUrinary metabolic profiles are sustained for as long as 14 yearsLong term KCit therapy significantly reduces stone formation rates

LONG TERM RX WITH POTASSIUM CITRATE


POTASSIUM CITRATE

Liquid / crystals - Citra–K crystals(generic)

Slow-release pills - Urocit K® / genericUrocit K® - 15

CURRENT PREPARATIONS

ALKALI THERAPYWITH LEMONADE

Cit (gm) Ca (mg) Na (mg) Mag (mg)Orange 11 420 14 140Grapefruit 14 180 16 130Lemon 49 110 27 280Raspberry 17 400 0 300Pineapple 6 160 21 170Cranberry 11 140 20 55

CHEMICAL COMPOSITIONS

Seltzer & Stoller, 1996

URINE BIOCHEMISTRYMix 120 ml lemon juice with tap water to = 2 litersAverage cost for 1 week supply (14 liters) = $2

Baseline During LemonadeCitrate (mg) 142 346Calcium (mg) 131 92Oxalate (mg) 53 42Volume (L) 2.7 2.9


Seltzer & Stoller, 1996

*

LONG-TERM FOLLOW UP32 patients on lemonade therapy (120 ml lemon juice with 2 L water) compared to an age- and sex-matched group treated with potassium citrate

Lemonade K-CitRx duration (mo) 48 42↑ urinary citrate (mg) 354 472↓ SFR (stones/pt/yr) 1.00 → 0.13


Kang, et al, 2005

*

ALTERNATIVES TO K-CIT60 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 KCitNaBic is not ideal in patients with pure uric acid stones and high urate excretion

ALKALIZATION WITH NA+ BICARB

Pinheiro & Heilberg, 2013


Dietary ModificationNormal calcium, low salt, low protein

New MedicationsPotassium magnesium citrate

Enteric TherapyOxalobactor formigenes

Genetic TherapyHypercalciuriaCystinuria

FUTURE DIRECTIONS

medical stone management made easy – … stone management made easy ... high acid-ash diet,...

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