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ADVANCES IN THE MANAGEMENT OF NEPHROLITHIASIS. Glenn M. Preminger, M.D. Comprehensive Kidney Stone Center at Duke University Medical Center Durham, North Carolina. NEPHROLITHIASIS. EPIDEMIOLOGY. Affects 1 - 3 % of adult population Annual incidence 1% in white males

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advances in the management of nephrolithiasis
ADVANCES IN THE MANAGEMENT OF NEPHROLITHIASIS

Glenn M. Preminger, M.D.

  • Comprehensive Kidney Stone Center
  • at Duke University Medical Center
  • Durham, North Carolina
nephrolithiasis
NEPHROLITHIASIS

EPIDEMIOLOGY

  • Affects 1 - 3 % of adult population
  • Annual incidence 1% in white males
  • Life - time risk in adult males - 20%
  • Recurrent stones in 63% after 8 years
nephrolithiasis4
NEPHROLITHIASIS

NATURAL HISTORY & RISK FACTORS

Peak incidence age 30 - 60

Gender (Male : Female) 3 : 1

Family history 3 - fold  risk

Body size  risk with  weight

Recurrence after first stone: Year 1 10 - 15% Year 5 50 - 60% Year 10 70 - 80%

nephrolithiasis6
NEPHROLITHIASIS

ECONOMIC IMPLICATIONS - 1993 DATA

  • Inpatient
  • Evaluation $155 million
  • Hospitalization $848 million
  • Professional $762 million
  • Wages $140 million
  • Outpatient
  • Evaluation $358 million
  • Wages $128 million
  • Total $2.39 Billion

Thompson, et al, 1995

asymptomatic calculi
ASYMPTOMATIC CALCULI

TREATMENT

  • Solitary kidney
  • Occupation (pilot, business traveler
  • Simultaneous contralateral treatment
  • It’s difficult to make an asymptomatic patient feel any better !
surgical stone
SURGICAL STONE

DEFINITION

  • Intractable pain
  • Significant obstruction
  • Recurrent infection
  • Severe bleeding
  • Imminent threat
stone management
STONE MANAGEMENT

OPTIONS

  • Open surgery
  • Percutaneous nephrolithotomy
  • Ureteroscopy
  • Shock wave lithotripsy
  • Medical therapy
stone management10
STONE MANAGEMENT

OPEN NEPHROLITHOTOMY

surgical stone management
SURGICAL STONE MANAGEMENT

CONSIDERATIONS

  • Residual stone rate
  • Recurrence rate
  • Number of procedures
  • Hospitalization
  • Convalescence
  • Cost
shock wave lithotripsy
SHOCK WAVE LITHOTRIPSY

HISTORY

  • 1972 - 1980 Preliminary research
  • Feb, 1980 First human treated
  • May, 1984 Clinical trials begin in USA
  • Dec, 1984 FDA approval (Dornier)
shock wave lithotripsy13
SHOCK WAVE LITHOTRIPSY

ORIGINAL DORNIER HM3

shock wave lithotripsy14
SHOCK WAVE LITHOTRIPSY

SECOND GENERATION MACHINES

shock wave lithotripsy15
SHOCK WAVE LITHOTRIPSY

STONE FRAGMENTATION

shock wave lithotripsy16
SHOCK WAVE LITHOTRIPSY

STONE FRAGMENTATION

shock wave lithotripsy17
SHOCK WAVE LITHOTRIPSY

INDICATIONS

  • Surgical stone
  • No obstruction
  • Reasonable chanceof expeditious removal
shock wave lithotripsy18
SHOCK WAVE LITHOTRIPSY

RELATIVE CONTAINDICATIONS

  • Large stones Calcium oxalate > 20 mm Struvite > 30 mm
  • Cystine stones
  • Distal obstruction
  • Poorly informed patients
shock wave lithotripsy19
SHOCK WAVE LITHOTRIPSY

CLINICAL SIDE-EFFECTS

  • Hematuria
  • Pain
  • Obstruction (Steinstrasse)
shock wave lithotripsy20
SHOCK WAVE LITHOTRIPSY

CLINICAL RENAL INJURY

  • Mild contusion - Large hematoma
  • Renal injury in 63 - 85% by MRI
  • Little data on chronic injury
  • Hypertension probably not a problem
shock wave lithotripsy21
SHOCK WAVE LITHOTRIPSY

APPROPRIATE FOLLOW-UP

  • Plain radiographs (KUB + tomograms)
  • Renal scan
  • Intravenous pyelogram
  • Spiral CT
shock wave lithotripsy22
SHOCK WAVE LITHOTRIPSY

REALITY

  • <15mm15-29mm>30mm
  • Multiple SWL 5% 10% 15-30%
  • Stone-free rate >80% 60% 50%
  • Auxiliary procedures 2% 5-7% 15%
  • Repeat procedures 1-2% 10-15% 15-20%
shock wave lithotripsy23
SHOCK WAVE LITHOTRIPSY

REALITY

  • Ideal for some
  • Marginal in some
  • Contraindicated in few
  • THE KEY IS PROPER PATIENTSELECTION AND EDUCATION
shock wave lithotripsy24
SHOCK WAVE LITHOTRIPSY

IDEAL CANDIDATES

  • Small stone (< 1.5 cm)
  • Mid or upper pole location
  • Normal renal anatomy
  • No distal obstruction
surgical stone management25
SURGICAL STONE MANAGEMENT

Stone size

Stone location

Stone composition

MODIFIERS OF STONE-FREE RATE

shock wave lithotripsy26
SHOCK WAVE LITHOTRIPSY

Completeness of stone fragmentation

Completeness of fragment elimination

LIMITATIONS

shock wave lithotripsy27
SHOCK WAVE LITHOTRIPSY

STONE FREE RATES

% Stone Free

Lingeman and Newman, 1990

stone management28
STONE MANAGEMENT

PERCUTANEOUS NEPHROLITHOTOMY

stone management29
STONE MANAGEMENT

PERCUTANEOUS NEPHROLITHOTOMY

stone management30
STONE MANAGEMENT

Large stone mass Obstruction

Anatomic abnormality SWL failure Horseshoe, divertic

Certainty of results Cystine stones

Obesity

PNL IN THE AGE OF SWL

surgical stone management31
SURGICAL STONE MANAGEMENT

Stone volume 46%

Obstruction 16%

Cystine stones 16%

Body habitus 12%

SWL failures 10%

CURRENT ROLE OFPERCUTANEOUS STONE REMOVAL

surgical stone management32
SURGICAL STONE MANAGEMENT

CURRENT ROLE OF PNL

slide33

SURGICAL STONE MANAGEMENT

CURRENT ROLE OFPERCUTANEOUS STONE REMOVAL

Pre-op KUB

Post-SWL KUB

slide34

SURGICAL STONE MANAGEMENT

CURRENT ROLE OFPERCUTANEOUS STONE REMOVAL

Post-PNL KUB

Post-PNL IVP

slide35

SURGICAL STONE MANAGEMENT

STAY OUT OF TROUBLE

Pre-op KUB

Pre-op IVP

slide36

SURGICAL STONE MANAGEMENT

STAY OUT OF TROUBLE

Post-op tomogram

Post-op IVP

staghorn calculi
STAGHORN CALCULI

CRITERIA FOR EVALUATION

Stone-free rates

Primary procedures

Secondary procedures

Unexplained secondary procedures

Hospital days

AUA Guidelines Panel, 1994

staghorn calculi38
STAGHORN CALCULI

STONE FREE RATE

% Stone Free

AUA Guidelines Panel, 1994

staghorn calculi39
STAGHORN CALCULI

PROCEDURES PER PATIENT (20)

% 20 Procedures

AUA Guidelines Panel, 1994

staghorn calculi40
STAGHORN CALCULI

SANDWICH THERAPY

PNL

SWL

FLEX NEPHROCOPY

staghorn calculi41
STAGHORN CALCULI

Allows debulking of large stones (Should push PNL "to the limit")

SWL reserved for inaccessible fragments

Flexible nephroscopy to insure stone-free status

SANDWICH THERAPY

staghorn calculi42
STAGHORN CALCULI

SANDWICH THERAPY

staghorn calculi43
STAGHORN CALCULI

AGGRESSIVE PNL - SINGLE PROCEDURE

Pre-op KUB

Pre-op KUB

staghorn calculi44
STAGHORN CALCULI

AGGRESSIVE PNL - SINGLE PROCEDURE

Pre-op IVP

Pre-op IVP

staghorn calculi45
STAGHORN CALCULI

AGGRESSIVE PNL - SINGLE PROCEDURE

3 N-tracts

Upper pole access

staghorn calculi46
STAGHORN CALCULI

AGGRESSIVE PNL - SINGLE PROCEDURE

3 access sheaths

Post-op N-tubes

ureteral calculi
URETERAL CALCULI

TREATMENT CONSIDERATIONS

Location

Size

Chronicity

Equipment

Expertise

ureteral calculi49
URETERAL CALCULI

TREATMENT OPTIONS

Observation

Shock wave lithotripsy

Ureteroscopy

Blind basket extraction

Percutaneous approach

Open surgery

slide50

URETERAL CALCULI

SPONTANEOUS PASSAGE

slide51

URETERAL CALCULI

SPONTANEOUS PASSAGE

Of all stonesthat pass spontaneously, 95% will pass within 6 weeks

Miller & Kane, 1999

slide52

URETERAL CALCULI

MEDICAL MANAGEMENT

Hollingsworth & Hollenbeck, 2006

slide53

URETERAL CALCULI

MEDICAL MANAGEMENT

Hollingsworth & Hollenbeck, 2006

slide54

URETERAL CALCULI

3RD GENERATION SWL

ureteral calculi55
URETERAL CALCULI

Minimal anesthesia requirements

Non-invasive procedure No stenting / less complications

Similar approach to ureteral calculi in all locations

INSITU SWL

ureteral calculi57
URETERAL CALCULI

Stone-free is not everything !!

PARAMETERS FOR COMPARISON

ureteral calculi58
URETERAL CALCULI

Effectiveness

Morbidity

Convalescence

Cost

PARAMETERS FOR COMPARISON

swl for ureteral calculi59
SWL FORURETERAL CALCULI

DORNIER HM-3

Upper Middle LowerN= 33N=248N=381

Success of 94.8% 85.9% 98.2%1O procedure

Re-tx rate 6.8% 15.7% 1.8%

Complications 10% 15.3% 8.4%

Lingeman, et al, 1993

distal ureteral calculi
DISTAL URETERAL CALCULI

URS is 10 - 18% more effective than SWL (depending on type of SWL unit)

Morbidity / convalescence reduced with SWL

Need for stents 40-60% less with SWL

Cost issues not addressed in monotherapy studies

COMPARISON OFMONOTHERAPY STUDIES

distal ureteral calculi61
DISTAL URETERAL CALCULI

SWLURS

Effectiveness Slightly better

Morbidity Less

Hospitalization Less

Cost Slightly less

OVERVIEW OF HISTORICALCONTROL STUDIES

distal ureteral calculi62
DISTAL URETERAL CALCULI

80 patients randomized to receive SWL or URS 40 patients had stones > 5 mm 40 patients had stones < 5 mm

SWL performed on Dornier MFL 5000

URS performed with 6.5F or 9.5F semi-rigid ureteroscopes (basket vs. pneumatic lithotripsy)

PROSPECTIVE, RANDOMIZED TRIAL

Peschel & Bartsch, 1999

distal ureteral calculi63
DISTAL URETERAL CALCULI

PROSPECTIVE, RANDOMIZED TRIALSTONES < 5 MM

URSSWL

OR time (min) 19 63

Fluoro time (min) 0.8 5.1

Stone-free (days) 0.2 10.8

Stent (days) 7.2 0

Re-treatment rate 0 15%

*

*

*

*

*

Peschel & Bartsch, 1999

swl of distal ureteral calculi
SWL OF DISTALURETERAL CALCULI

Initial animal studies suggest ovarian trauma Impaired fertility Mutagenesis

Subsequent animal investigations demonstrate no impact on fertility or offspring

Mice Rats Rabbits

ADVERSE EFFECTS TOFEMALE REPRODUCTIVE TRACT?

swl of distal ureteral calculi65
SWL OF DISTALURETERAL CALCULI

Analyzed Rx data and radiation exposure in 84 women of reproductive age

7 children born to 6 patients with no malformations or chromosomal anomalies

Miscarriages in 3 patients (but occurred at least 1 year after SWL)

ADVERSE EFFECTS TOFEMALE REPRODUCTIVE TRACT?

Viewig & Miller, 1992

slide67

URETERAL CALCULI

FLEXIBLE URETEROSCOPY

antegrade manipulation of ureteral calculi
ANTEGRADE MANIPULATION OF URETERAL CALCULI

Large stone burden

Body habitus

Urinary diversion

Transplant kidney

INDICATIONS

slide69

URETERAL CALCULI

PERCUTANEOUS APPROACH

ureteral stone management
URETERAL STONE MANAGEMENT

INSITU SWL

AdvantagesMinimal anesthesia requirementsNon-invasive procedureNo stenting/less complicationsSimilar approach for all ureteral calculi

DisadvantagesLower success rate than URSHigher re-treatment rate

ureteral stone management71
URETERAL STONE MANAGEMENT

URETEROSCOPY

AdvantagesHighest success rateDefinitive Rx - No waiting for stone passage

DisadvantagesMore invasive than SWLHigher complication rateRequires greater technical expertise

ureteral calculi current options
URETERAL CALCULI: CURRENT OPTIONS

PROX AND MID URETERAL STONES

ApproachInvasiveStentS-F RateRe-RxRate

URS +++ 100% 75-90% 10-15%Push/Smash ++ Rarely 92% 9% SWL + Stent + 100% 75-80% 20-25%Insitu SWL 0 No 75-80% 20-25%

*

Defined as complete stone removal with single procedure

ureteral calculi current options73
URETERAL CALCULI: CURRENT OPTIONS

DISTAL URETERAL STONES

ApproachInvasiveStentS-F RateRe-RxRate

URS +++ 100% 98-100% 0-2%Push/Smash ++ Rarely 92% 9% SWL + Stent + 100% 75-80% 20-25%Insitu SWL 0 No 75-80% 20-25%

*

Defined as complete stone removal with single procedure

surgical stone management74
SURGICAL STONE MANAGEMENT

1980’s 1990’s 2000’s 2010’s

Shock wave lithotripsy 95% 85% 75% ???

Endoscopic procedures 5% 15% 25% ???

Open stone surgery < 1% < 1% < 1% 0

CHANGING TREATMENT PHILOSOPHIES

nephrolithiasis75
NEPHROLITHIASIS

NATURAL HISTORY & RISK FACTORS

Peak incidence age 30 - 60

Gender (Male : Female) 3 : 1

Family history 3 - fold  risk

Body size  risk with  weight

Recurrence after first stone: Year 1 10 - 15% Year 5 50 - 60% Year 10 70 - 80%

shock wave lithotripsy76
SHOCK WAVE LITHOTRIPSY

RECURRENT STONE FORMATION

  • One Year Two Years
  • Post SWLPost SWL
  • Stone Free New stones 8% 10%
  • Residual Stones Stone growth 22% 21%

Lingeman, et al, 1989

shock wave lithotripsy77
SHOCK WAVE LITHOTRIPSY

EFFECT ON STONE RISK FACTORS

  • Urine Values Pre- 3 Mo Post- (mg/day) Lithotripsy Lithotripsy
  • Calcium 254 261
  • Uric Acid 552 548
  • Citrate 249 257
  • Oxalate 42 41

Brown, et al, 1989

medical management of nephrolithiasis
MEDICAL MANAGEMENT OF NEPHROLITHIASIS

PROGRESS

  • Elucidation Urinary environment conducive to stone formation
  • Diagnosis Detection of underlying physiologic abnormalities
  • Medical Therapy Development of new treatment strategies
stone formation
STONE FORMATION

Concentration / solubility of stone-forming salts

Promoters of crystallization and aggregation

Inhibitors of crystallization and aggregation

MAJOR FORCES

dietary calcium
DIETARY CALCIUM

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

IMPACT OF LOW CALCIUM DIET

dietary calcium81
DIETARY CALCIUM

RECOMMENDATIONS

Moderate calcium restriction in patients with AH

Limit dietary intake of oxalate

Spinach, tea, chocolate, nuts

Limit dietary sodium intake

calcium supplements
CALCIUM SUPPLEMENTS

Calciuric response to calcium supplementation

Depends on duration of treatment and patient population

PHYSIOLOGICAL EVIDENCE

calcium supplements83
CALCIUM SUPPLEMENTS

Give HCTZ during initial three months to prevent hypercalciuria, then discontinue for one month

If urinary calcium up at 4 months, re-start HCTZ

Alternative: Significantly increase fluid intake for first three months and then check 24-hour urinary calcium

RECOMMENDATIONS:PREMENOPAUSAL WOMEN

calcium supplements84
CALCIUM SUPPLEMENTS

Check 24-hour urinary calcium 4 months after starting calcium supplements

Offer thiazide to hypercalciuric patients

RECOMMENDATIONS:POSTMENOPAUSAL WOMEN

calcium supplements85
CALCIUM SUPPLEMENTS

“Standard” Calcium Supplements

Calcium carbonate

Calcium phosphate

CURRENT PREPARATIONS

calcium supplements86
CALCIUM SUPPLEMENTS

Limitations

Poorly absorbed from intestinal tract

Increased urinary calcium excretion Promotes CaOx, CaPhos stone disease

CURRENT PREPARATIONS

calcium supplements87
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

calcium supplements88
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, 1994

medical management of nephrolithiasis89
MEDICAL MANAGEMENT OF NEPHROLITHIASIS

Reverse underlying physicochemical and physiologic abnormalities

Inhibit new stone formation

Overcome non-renal complications Bone disease in RTA

Free of serious side effects

SELECTIVE TREATMENT APPROACH

metabolic evaluation
METABOLIC EVALUATION

SELECTION OF PATIENTS

Simplified evaluation Comprehensive evaluation

Metabolically inactive Metabolically activeSingle stone, low risk Single stone, high risk

Positive family history Early age of onset Nephrocalcinosis Associate medical conditions

metabolic evaluation91
METABOLIC EVALUATION

“LOW RISK” STONE FORMER

Serum Ca, Phos 10 HPT

Serum electrolytes RTA

Serum uric acid Gout, HUCU

Urinalysis Crystals, infection

History (risk factors) Fluids, diet, meds

X-rays Nehprocalcinosis RTA Radiolucent stones Uric acid, ? Cystine Staghorn stones Struvite

Stone analysis Type of stone

metabolic evaluation92
METABOLIC EVALUATION

URINARY CRYSTALS

ambulatory evaluation
EVOLUTIONAMBULATORY EVALUATION

1971 1974 1986 2001

Hospitalization (days) 14 0 0 0

Outpatient visits 0 0 3 1-2

Duration (days) 14 21 21 14

# diagnostic categories 3 4 9 13

Unclassified etiology 43% 11% 11% 3%

ambulatory evaluation94
AMBULATORY EVALUATION

Blood Urine

CBC SMA PTH TV pH Ca Ox UA Na Cit Creat Cyst

Visit 1 x x x x x x x x x x x

Visit 2 x x x x x x x x x

Fast x x x

Load x x x

OUTLINE

metabolic evaluation95
METABOLIC EVALUATION

CLASSIFICATION

Calcareous calculiNon-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

metabolic evaluation96
METABOLIC EVALUATION

CLASSIFICATION

Sole CombinedOccurrenceOccurrence

Absorptive hypercalciuria 20% 40% Type I, Type II

Renal hypercalciuria 5% 8%

Resorptive hypercalciuria 3% 5%

Unclassified hypercalciuria 15% 25%

Hyperuricosuric nephrolithiasis 10% 40%

Hyperoxaluric nephrolithiasis 2% 15%

metabolic evaluation97
METABOLIC EVALUATION

CLASSIFICATION

Sole CombinedOccurrenceOccurrence

Hypocitraturia 10% 50%

Hypomagnesiuria 5% 10%

Gouty diathesis 15% 30%

Cystinuria <1%

Infection stones 1% 5%

Low urine volume 10% 50%

No Dx / miscellaneous < 3%

medical management of nephrolithiasis98
MEDICAL MANAGEMENT OF NEPHROLITHIASIS

Reverse underlying physicochemical and physiologic abnormalities

Inhibit new stone formation

Overcome non-renal complications Bone disease in RTA

Free of serious side effects

SELECTIVE TREATMENT APPROACH

medical management of nephrolithiasis99
MEDICAL MANAGEMENT OF NEPHROLITHIASIS

SELECTIVE TREATMENT APPROACH

First Line Second Line

AHI Thiazide Cellulose phos

RH Thiazide

HUCU Allopurinol Citrate

Enteric hyperox Ca++/ Mg++ Citrate

Gouty diathesis Citrate Allopurinol

Hypocit Citrate Bicarb

Cystinuria Thiola d-Pen

Struvite Remove stone Thiola

impact of medical rx
IMPACT OF MEDICAL RX

SELECTIVE MEDICAL THERAPY

Stone Formation Rate

Pre-Rx

On K-Citrate

medical management of nephrolithiasis101
MEDICAL MANAGEMENTOF NEPHROLITHIASIS

SELECTIVE VS.CONSERVATIVE TREATMENT

Placebo/ Potassium ConservativeCitrate

Stone formation 0.54 0.25 0.52 0.02 rate (no/pt/yr)

Reduction in stone 54% 96%formation rate

Remission rate 61% 96%

*

*

Preminger & Pak, 1985

impact of medical therapy
IMPACT OFMEDICAL THERAPY

Pre- OnTreatmentTreatment

Duration (yr/pt) 3.0 3.7

Surgery rate (no/pt) 0.21 0.01

Patients requiring 58% 2%Surgery

NEED FOR STONE REMOVAL

*

*

Preminger & Pak, 1985