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
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
NEPHROLITHIASIS
ANATOMY
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
STONE BELT
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
ASYMPTOMATIC CALCULI
TREATMENT
Solitary kidney
Occupation (pilot, business traveler
Simultaneous contralateral treatment
It’s difficult to make an asymptomatic patient feel any better !
SURGICAL STONEDEFINITION
Intractable pain
Significant obstruction
Recurrent infection
Severe bleeding
Imminent threat
STONE MANAGEMENT
OPTIONS
Open surgery
Percutaneous nephrolithotomy
Ureteroscopy
Shock wave lithotripsy
Medical therapy
STONE MANAGEMENTOPEN NEPHROLITHOTOMY
SURGICAL STONE MANAGEMENT
CONSIDERATIONS
Residual stone rate
Recurrence rate
Number of procedures
Hospitalization
Convalescence
Cost
SHOCK WAVE LITHOTRIPSY
HISTORY
1972 - 1980 Preliminary research
Feb, 1980First human treated
May, 1984 Clinical trials begin in USA
Dec, 1984 FDA approval (Dornier)
SHOCK WAVE LITHOTRIPSYORIGINAL DORNIER HM3
SHOCK WAVE LITHOTRIPSYSECOND GENERATION MACHINES
SHOCK WAVE LITHOTRIPSYSTONE FRAGMENTATION
SHOCK WAVE LITHOTRIPSYSTONE FRAGMENTATION
SHOCK WAVE LITHOTRIPSY
INDICATIONS
Surgical stone
No obstruction
Reasonable chanceof expeditious removal
SHOCK WAVE LITHOTRIPSY
RELATIVE CONTAINDICATIONS
Large stonesCalcium oxalate > 20
mmStruvite > 30
mm
Cystine stones
Distal obstruction
Poorly informed patients
SHOCK WAVE LITHOTRIPSY
CLINICAL SIDE-EFFECTS
Hematuria
Pain
Obstruction
(Steinstrasse)
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 LITHOTRIPSY
APPROPRIATE FOLLOW-UP
Plain radiographs (KUB + tomograms)
Renal scan
Intravenous pyelogram
Spiral CT
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%
SHOCK WAVE LITHOTRIPSYREALITY
Ideal for some
Marginal in some
Contraindicated in few
THE KEY IS PROPER PATIENTSELECTION AND EDUCATION
SHOCK WAVE LITHOTRIPSY
IDEAL CANDIDATES
Small stone (< 1.5 cm)
Mid or upper pole location
Normal renal anatomy
No distal obstruction
SURGICAL STONE MANAGEMENT
MODIFIERS OF STONE-FREE RATE
Stone size
Stone location
Stone composition
SHOCK WAVE LITHOTRIPSY
LIMITATIONS
Completeness of stone fragmentation
Completeness of fragment elimination
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
STONE MANAGEMENTPERCUTANEOUS NEPHROLITHOTOMY
STONE MANAGEMENTPERCUTANEOUS NEPHROLITHOTOMY
Large stone mass Obstruction
Anatomic abnormality SWL failure Horseshoe, divertic
Certainty of results Cystine stones
Obesity
STONE MANAGEMENTPNL IN THE AGE OF SWL
SURGICAL STONE MANAGEMENT
CURRENT ROLE OFPERCUTANEOUS STONE REMOVAL
Stone volume 46%
Obstruction 16%
Cystine stones 16%
Body habitus 12%
SWL failures 10%
SURGICAL STONE MANAGEMENT
CURRENT ROLE OF PNL
SURGICAL STONE MANAGEMENT
CURRENT ROLE OFPERCUTANEOUS STONE REMOVAL
Pre-op KUB Post-SWL KUB
SURGICAL STONE MANAGEMENT
CURRENT ROLE OFPERCUTANEOUS STONE REMOVAL
Post-PNL KUB Post-PNL IVP
SURGICAL STONE MANAGEMENT
STAY OUT OF TROUBLE
Pre-op KUB Pre-op IVP
SURGICAL STONE MANAGEMENT
STAY OUT OF TROUBLE
Post-op tomogram Post-op IVP
STAGHORN CALCULICRITERIA FOR EVALUATION
Stone-free rates
Primary procedures
Secondary procedures
Unexplained secondary procedures
Hospital days
AUA Guidelines Panel, 1994
STAGHORN CALCULISTONE FREE RATE
50%
73%81% 82%
0%
20%
40%
60%
80%
100%
SWL PNL Combo Open
% Stone Free
AUA Guidelines Panel, 1994
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
STAGHORN CALCULI
SANDWICH THERAPY
PNL
SWL
FLEX NEPHROCOPY
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
STAGHORN CALCULISANDWICH THERAPY
STAGHORN CALCULIAGGRESSIVE PNL - SINGLE PROCEDURE
Pre-op KUB Pre-op KUB
STAGHORN CALCULIAGGRESSIVE PNL - SINGLE PROCEDURE
Pre-op IVP Pre-op IVP
STAGHORN CALCULIAGGRESSIVE PNL - SINGLE PROCEDURE
3 N-tracts Upper pole access
STAGHORN CALCULIAGGRESSIVE PNL - SINGLE PROCEDURE
3 access sheaths Post-op N-tubes
URETERAL CALCULI
URETERAL CALCULITREATMENT CONSIDERATIONS
Location
Size
Chronicity
Equipment
Expertise
URETERAL CALCULITREATMENT OPTIONS
Observation
Shock wave lithotripsy
Ureteroscopy
Blind basket extraction
Percutaneous approach
Open surgery
URETERAL CALCULI
SPONTANEOUS PASSAGE
Of all stonesthat pass
spontaneously, 95% will pass within 6 weeks
URETERAL CALCULISPONTANEOUS PASSAGE
Miller & Kane, 1999
URETERAL CALCULIMEDICAL MANAGEMENT
Hollingsworth & Hollenbeck, 2006
URETERAL CALCULIMEDICAL MANAGEMENT
Hollingsworth & Hollenbeck, 2006
URETERAL CALCULI3RD GENERATION SWL
URETERAL CALCULI
Minimal anesthesia requirements
Non-invasive procedureNo stenting / less complications
Similar approach to ureteral calculi in all locations
IN SITU SWL
SWL FORURETERAL CALCULI
URETERAL CALCULI
Stone-free is not everything !!
PARAMETERS FOR COMPARISON
URETERAL CALCULI
Effectiveness
Morbidity
Convalescence
Cost
PARAMETERS FOR COMPARISON
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
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 CALCULI
SWL URS
Effectiveness Slightly better
Morbidity Less
Hospitalization Less
Cost Slightly less
OVERVIEW OF HISTORICALCONTROL STUDIES
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
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
***
**
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?
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
URETEROSCOPY
URETERAL CALCULIFLEXIBLE URETEROSCOPY
ANTEGRADE MANIPULATION OF
URETERAL CALCULI
Large stone burden
Body habitus
Urinary diversion
Transplant kidney
INDICATIONS
URETERAL CALCULIPERCUTANEOUS APPROACH
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
URETERAL STONE MANAGEMENT
URETEROSCOPYAdvantages
Highest success rateDefinitive Rx - No waiting for stone passage
DisadvantagesMore invasive than SWLHigher complication rateRequires greater technical expertise
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
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
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
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
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
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
MEDICAL MANAGEMENT OF NEPHROLITHIASIS
PROGRESSElucidation
Urinary environment conducive to stone formation
DiagnosisDetection of underlying physiologic
abnormalities
Medical TherapyDevelopment of new treatment
strategies
STONE FORMATION
Concentration / solubility of stone-forming salts
Promoters of crystallization and aggregation
Inhibitors of crystallization and aggregation
MAJOR FORCES
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 CALCIUM
Moderate calcium restriction in patients with AH
Limit dietary intake of oxalate
Spinach, tea, chocolate, nuts
Limit dietary sodium intake
RECOMMENDATIONS
CALCIUM SUPPLEMENTS
Calciuric response to calcium supplementation
Depends on duration of treatment and patient
population
PHYSIOLOGICAL EVIDENCE
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 SUPPLEMENTS
Check 24-hour urinary calcium 4 months after starting calcium supplements
Offer thiazide to hypercalciuric patients
RECOMMENDATIONS:POSTMENOPAUSAL WOMEN
CALCIUM SUPPLEMENTS
“Standard” Calcium Supplements
Calcium carbonate
Calcium phosphate
CURRENT PREPARATIONS
CALCIUM SUPPLEMENTS
Limitations
Poorly absorbed from intestinal tract
Increased urinary calcium excretion Promotes CaOx, CaPhos stone
disease
CURRENT PREPARATIONS
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
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
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
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
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
METABOLIC EVALUATIONURINARY CRYSTALS
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%
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
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
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
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
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
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
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
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
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