ADVANCES IN THE MANAGEMENT OF NEPHROLITHIASIS Glenn M. Preminger, M.D. Comprehensive Kidney Stone...
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Transcript of ADVANCES IN THE MANAGEMENT OF NEPHROLITHIASIS Glenn M. Preminger, M.D. Comprehensive Kidney Stone...
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ADVANCES IN THE MANAGEMENT OF NEPHROLITHIASIS
Glenn M. Preminger, M.D.
Comprehensive Kidney Stone Centerat Duke University Medical Center
Durham, North Carolina
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NEPHROLITHIASISEPIDEMIOLOGY
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
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NEPHROLITHIASIS
ANATOMY
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NEPHROLITHIASIS
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%
NATURAL HISTORY & RISK FACTORS
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STONE BELT
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NEPHROLITHIASISECONOMIC IMPLICATIONS - 1993 DATA
InpatientEvaluation $155
millionHospitalization $848
millionProfessional $762
millionWages $140
millionOutpatient
Evaluation $358 million
Wages $128 million
Total $2.39 Billion
Thompson, et al, 1995
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ASYMPTOMATIC CALCULI
TREATMENT
Solitary kidney
Occupation (pilot, business traveler
Simultaneous contralateral treatment
It’s difficult to make an asymptomatic patient feel any better !
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SURGICAL STONEDEFINITION
Intractable pain
Significant obstruction
Recurrent infection
Severe bleeding
Imminent threat
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STONE MANAGEMENT
OPTIONS
Open surgery
Percutaneous nephrolithotomy
Ureteroscopy
Shock wave lithotripsy
Medical therapy
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STONE MANAGEMENTOPEN NEPHROLITHOTOMY
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SURGICAL STONE MANAGEMENT
CONSIDERATIONS
Residual stone rate
Recurrence rate
Number of procedures
Hospitalization
Convalescence
Cost
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SHOCK WAVE LITHOTRIPSY
HISTORY
1972 - 1980 Preliminary research
Feb, 1980First human treated
May, 1984 Clinical trials begin in USA
Dec, 1984 FDA approval (Dornier)
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SHOCK WAVE LITHOTRIPSYORIGINAL DORNIER HM3
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SHOCK WAVE LITHOTRIPSYSECOND GENERATION MACHINES
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SHOCK WAVE LITHOTRIPSYSTONE FRAGMENTATION
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SHOCK WAVE LITHOTRIPSYSTONE FRAGMENTATION
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SHOCK WAVE LITHOTRIPSY
INDICATIONS
Surgical stone
No obstruction
Reasonable chanceof expeditious removal
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SHOCK WAVE LITHOTRIPSY
RELATIVE CONTAINDICATIONS
Large stonesCalcium oxalate > 20
mmStruvite > 30
mm
Cystine stones
Distal obstruction
Poorly informed patients
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SHOCK WAVE LITHOTRIPSY
CLINICAL SIDE-EFFECTS
Hematuria
Pain
Obstruction
(Steinstrasse)
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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
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SHOCK WAVE LITHOTRIPSY
APPROPRIATE FOLLOW-UP
Plain radiographs (KUB + tomograms)
Renal scan
Intravenous pyelogram
Spiral CT
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SHOCK WAVE LITHOTRIPSYREALITY
<15mm 15-29mm >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%
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SHOCK WAVE LITHOTRIPSYREALITY
Ideal for some
Marginal in some
Contraindicated in few
THE KEY IS PROPER PATIENTSELECTION AND EDUCATION
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SHOCK WAVE LITHOTRIPSY
IDEAL CANDIDATES
Small stone (< 1.5 cm)
Mid or upper pole location
Normal renal anatomy
No distal obstruction
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SURGICAL STONE MANAGEMENT
MODIFIERS OF STONE-FREE RATE
Stone size
Stone location
Stone composition
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SHOCK WAVE LITHOTRIPSY
LIMITATIONS
Completeness of stone fragmentation
Completeness of fragment elimination
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SHOCK WAVE LITHOTRIPSYSTONE FREE RATES
95%87%
48%35%
0%
20%
40%
60%
80%
100%
< 1 cm 1-2 cm 2-3 cm > 3 cmLingeman and Newman, 1990
% Stone Free
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STONE MANAGEMENTPERCUTANEOUS NEPHROLITHOTOMY
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STONE MANAGEMENTPERCUTANEOUS NEPHROLITHOTOMY
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Large stone mass Obstruction
Anatomic abnormality SWL failure Horseshoe, divertic
Certainty of results Cystine stones
Obesity
STONE MANAGEMENTPNL IN THE AGE OF SWL
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SURGICAL STONE MANAGEMENT
CURRENT ROLE OFPERCUTANEOUS STONE REMOVAL
Stone volume 46%
Obstruction 16%
Cystine stones 16%
Body habitus 12%
SWL failures 10%
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SURGICAL STONE MANAGEMENT
CURRENT ROLE OF PNL
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SURGICAL STONE MANAGEMENT
CURRENT ROLE OFPERCUTANEOUS STONE REMOVAL
Pre-op KUB Post-SWL KUB
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SURGICAL STONE MANAGEMENT
CURRENT ROLE OFPERCUTANEOUS STONE REMOVAL
Post-PNL KUB Post-PNL IVP
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SURGICAL STONE MANAGEMENT
STAY OUT OF TROUBLE
Pre-op KUB Pre-op IVP
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SURGICAL STONE MANAGEMENT
STAY OUT OF TROUBLE
Post-op tomogram Post-op IVP
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STAGHORN CALCULICRITERIA FOR EVALUATION
Stone-free rates
Primary procedures
Secondary procedures
Unexplained secondary procedures
Hospital days
AUA Guidelines Panel, 1994
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STAGHORN CALCULISTONE FREE RATE
50%
73%81% 82%
0%
20%
40%
60%
80%
100%
SWL PNL Combo Open
% Stone Free
AUA Guidelines Panel, 1994
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STAGHORN CALCULIPROCEDURES PER PATIENT (20)
42.0%
4.7% 3.4% 0.2%0%
10%
20%
30%
40%
50%
SWL PNL Combo Open
% 20 Procedures
AUA Guidelines Panel, 1994
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STAGHORN CALCULI
SANDWICH THERAPY
PNL
SWL
FLEX NEPHROCOPY
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STAGHORN CALCULI
SANDWICH THERAPY
Allows debulking of large stones (Should push PNL "to the limit")
SWL reserved for inaccessible fragments
Flexible nephroscopy to insure stone-free status
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STAGHORN CALCULISANDWICH THERAPY
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STAGHORN CALCULIAGGRESSIVE PNL - SINGLE PROCEDURE
Pre-op KUB Pre-op KUB
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STAGHORN CALCULIAGGRESSIVE PNL - SINGLE PROCEDURE
Pre-op IVP Pre-op IVP
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STAGHORN CALCULIAGGRESSIVE PNL - SINGLE PROCEDURE
3 N-tracts Upper pole access
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STAGHORN CALCULIAGGRESSIVE PNL - SINGLE PROCEDURE
3 access sheaths Post-op N-tubes
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URETERAL CALCULI
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URETERAL CALCULITREATMENT CONSIDERATIONS
Location
Size
Chronicity
Equipment
Expertise
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URETERAL CALCULITREATMENT OPTIONS
Observation
Shock wave lithotripsy
Ureteroscopy
Blind basket extraction
Percutaneous approach
Open surgery
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URETERAL CALCULI
SPONTANEOUS PASSAGE
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Of all stonesthat pass
spontaneously, 95% will pass within 6 weeks
URETERAL CALCULISPONTANEOUS PASSAGE
Miller & Kane, 1999
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URETERAL CALCULIMEDICAL MANAGEMENT
Hollingsworth & Hollenbeck, 2006
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URETERAL CALCULIMEDICAL MANAGEMENT
Hollingsworth & Hollenbeck, 2006
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URETERAL CALCULI3RD GENERATION SWL
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URETERAL CALCULI
Minimal anesthesia requirements
Non-invasive procedureNo stenting / less complications
Similar approach to ureteral calculi in all locations
IN SITU SWL
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SWL FORURETERAL CALCULI
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URETERAL CALCULI
Stone-free is not everything !!
PARAMETERS FOR COMPARISON
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URETERAL CALCULI
Effectiveness
Morbidity
Convalescence
Cost
PARAMETERS FOR COMPARISON
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SWL FORURETERAL CALCULI
Upper Middle LowerN= 33 N=248 N=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%
DORNIER HM-3
Lingeman, et al, 1993
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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
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DISTAL URETERAL CALCULI
SWL URS
Effectiveness Slightly better
Morbidity Less
Hospitalization Less
Cost Slightly less
OVERVIEW OF HISTORICALCONTROL STUDIES
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DISTAL URETERAL CALCULI
80 patients randomized to receive SWL or URS40 patients had stones > 5 mm40 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
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DISTAL URETERAL CALCULI
URS SWLOR time (min) 19 63Fluoro time (min) 0.8 5.1Stone-free (days) 0.2 10.8Stent (days) 7.2 0Re-treatment rate 0 15%
PROSPECTIVE, RANDOMIZED TRIALSTONES < 5 MM
Peschel & Bartsch, 1999
***
**
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SWL OF DISTALURETERAL CALCULI
Initial animal studies suggest ovarian trauma Impaired fertility
MutagenesisSubsequent animal investigations demonstrate no impact on fertility or offspring
Mice Rats Rabbits
ADVERSE EFFECTS TOFEMALE REPRODUCTIVE TRACT?
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SWL OF DISTALURETERAL CALCULI
Analyzed Rx data and radiation exposure in 84 women of reproductive age7 children born to 6 patients with no malformations or chromosomal anomaliesMiscarriages in 3 patients (but occurred at least 1 year after SWL)
ADVERSE EFFECTS TOFEMALE REPRODUCTIVE TRACT?
Viewig & Miller, 1992
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URETEROSCOPY
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URETERAL CALCULIFLEXIBLE URETEROSCOPY
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ANTEGRADE MANIPULATION OF
URETERAL CALCULI
Large stone burden
Body habitus
Urinary diversion
Transplant kidney
INDICATIONS
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URETERAL CALCULIPERCUTANEOUS APPROACH
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URETERAL STONE MANAGEMENT
AdvantagesMinimal anesthesia requirementsNon-invasive procedureNo stenting/less complicationsSimilar approach for all ureteral calculiDisadvantagesLower success rate than URSHigher re-treatment rate
IN SITU SWL
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URETERAL STONE MANAGEMENT
URETEROSCOPYAdvantages
Highest success rateDefinitive Rx - No waiting for stone passage
DisadvantagesMore invasive than SWLHigher complication rateRequires greater technical expertise
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URETERAL CALCULI: CURRENT OPTIONS
PROX AND MID URETERAL STONES
Approach Invasive Stent S-F Rate Re-RxRate
URS +++ 100% 75-90% 10-15%
Push/Smash ++ Rarely 92% 9%
SWL + Stent + 100% 75-80% 20-25%
In situ SWL 0 No 75-80% 20-25%
*
Defined as complete stone removal with single procedure
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URETERAL CALCULI: CURRENT OPTIONSDISTAL URETERAL STONES
Approach Invasive Stent S-F Rate Re-RxRate
URS +++ 100% 98-100% 0-2%
Push/Smash ++ Rarely 92% 9%
SWL + Stent + 100% 75-80% 20-25%
In situ SWL 0 No 75-80% 20-25%
*
Defined as complete stone removal with single procedure
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SURGICAL STONE MANAGEMENT
CHANGING TREATMENT PHILOSOPHIES
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
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NEPHROLITHIASIS
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%
NATURAL HISTORY & RISK FACTORS
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SHOCK WAVE LITHOTRIPSY
RECURRENT STONE FORMATION
One Year Two YearsPost SWL Post SWL
Stone Free New stones 8% 10%
Residual Stones Stone growth 22% 21%
Lingeman, et al, 1989
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SHOCK WAVE LITHOTRIPSY
EFFECT ON STONE RISK FACTORS
Urine Values Pre- 3 Mo Post- (mg/day) LithotripsyLithotripsyCalcium 254 261Uric Acid 552 548Citrate 249 257Oxalate 42 41Brown, et al, 1989
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MEDICAL MANAGEMENT OF NEPHROLITHIASIS
PROGRESSElucidation
Urinary environment conducive to stone formation
DiagnosisDetection of underlying physiologic
abnormalities
Medical TherapyDevelopment of new treatment
strategies
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STONE FORMATION
Concentration / solubility of stone-forming salts
Promoters of crystallization and aggregation
Inhibitors of crystallization and aggregation
MAJOR FORCES
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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
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DIETARY CALCIUM
Moderate calcium restriction in patients with AH
Limit dietary intake of oxalate
Spinach, tea, chocolate, nuts
Limit dietary sodium intake
RECOMMENDATIONS
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CALCIUM SUPPLEMENTS
Calciuric response to calcium supplementation
Depends on duration of treatment and patient
population
PHYSIOLOGICAL EVIDENCE
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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
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CALCIUM SUPPLEMENTS
Check 24-hour urinary calcium 4 months after starting calcium supplements
Offer thiazide to hypercalciuric patients
RECOMMENDATIONS:POSTMENOPAUSAL WOMEN
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CALCIUM SUPPLEMENTS
“Standard” Calcium Supplements
Calcium carbonate
Calcium phosphate
CURRENT PREPARATIONS
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CALCIUM SUPPLEMENTS
Limitations
Poorly absorbed from intestinal tract
Increased urinary calcium excretion Promotes CaOx, CaPhos stone
disease
CURRENT PREPARATIONS
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CALCIUM SUPPLEMENTS
"Citracal"
Over-the-counter preparationCalcium citrate 950 mgElemental calcium 200 gm
Provides increased intestinal calcium absorption
Prevents supersaturation of stone-forming salts
A more "stone-friendly" calcium supplement
CALCIUM CITRATE
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CALCIUM SUPPLEMENTS
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
CALCIUM CITRATE
Sakhaee & Pak, 1994
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MEDICAL MANAGEMENT OF NEPHROLITHIASIS
Reverse underlying physicochemical and physiologic abnormalities
Inhibit new stone formation
Overcome non-renal complicationsBone disease in RTA
Free of serious side effects
SELECTIVE TREATMENT APPROACH
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Simplified evaluation Comprehensive evaluation
Metabolically inactive Metabolically activeSingle stone, low risk Single stone, high risk
Positive family historyEarly age of onsetNephrocalcinosisAssociate medical conditions
METABOLIC EVALUATIONSELECTION OF PATIENTS
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METABOLIC EVALUATION
Serum Ca, Phos 10 HPTSerum electrolytes RTASerum uric acid Gout, HUCUUrinalysis Crystals, infectionHistory (risk factors) Fluids, diet, medsX-rays Nehprocalcinosis RTA Radiolucent stones Uric acid, ? Cystine Staghorn stones StruviteStone analysis Type of stone
“LOW RISK” STONE FORMER
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METABOLIC EVALUATIONURINARY CRYSTALS
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AMBULATORY EVALUATION
EVOLUTION
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%
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AMBULATORY EVALUATION
Blood UrineCBC 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
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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
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METABOLIC EVALUATION
Sole Combined Occurrence OccurrenceAbsorptive hypercalciuria 20% 40% Type I, Type IIRenal hypercalciuria 5% 8%Resorptive hypercalciuria 3% 5%Unclassified hypercalciuria 15% 25%Hyperuricosuric nephrolithiasis 10% 40%Hyperoxaluric nephrolithiasis 2% 15%
CLASSIFICATION
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METABOLIC EVALUATION
Sole Combined Occurrence OccurrenceHypocitraturia 10% 50%Hypomagnesiuria 5% 10%Gouty diathesis 15% 30%Cystinuria <1%Infection stones 1% 5%Low urine volume 10% 50%No Dx / miscellaneous < 3%
CLASSIFICATION
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MEDICAL MANAGEMENT OF NEPHROLITHIASIS
Reverse underlying physicochemical and physiologic abnormalities
Inhibit new stone formation
Overcome non-renal complicationsBone disease in RTA
Free of serious side effects
SELECTIVE TREATMENT APPROACH
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MEDICAL MANAGEMENT OF NEPHROLITHIASIS
First Line Second LineAHI Thiazide Cellulose phosRH ThiazideHUCU Allopurinol CitrateEnteric hyperox Ca++/ Mg++ CitrateGouty diathesis Citrate AllopurinolHypocit Citrate BicarbCystinuria Thiola d-PenStruvite Remove stone Thiola
SELECTIVE TREATMENT APPROACH
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SELECTIVE MEDICAL THERAPY
0
1
2
3
4
5
6Chronic DiarrheaRTAHyperuricosuriaIdiopathic HypocitUric Acid
Sto
ne F
orm
atio
n R
ate
IMPACT OF MEDICAL RX
Pre-Rx On K-Citrate
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MEDICAL MANAGEMENTOF NEPHROLITHIASIS
Placebo/ Potassium Conservative CitrateStone formation 0.54 0.25 0.52 0.02 rate (no/pt/yr)Reduction in stone 54% 96%formation rateRemission rate 61% 96%
SELECTIVE VS.CONSERVATIVE TREATMENT
*
*Preminger & Pak, 1985
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IMPACT OFMEDICAL THERAPY
Pre- On
Treatment TreatmentDuration (yr/pt) 3.0 3.7Surgery rate (no/pt) 0.21 0.01Patients requiring 58% 2%Surgery
NEED FOR STONE REMOVAL
**
Preminger & Pak, 1985