1. ADVANCES IN THE MANAGEMENT OF NEPHROLITHIASIS
Comprehensive Kidney Stone Center
at Duke University Medical Center
Durham, North Carolina
Glenn M. Preminger, M.D.

2. 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

3. NEPHROLITHIASIS
ANATOMY

4. NATURAL HISTORY & RISK FACTORS
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 %

5. STONE BELT

6. ECONOMIC IMPLICATIONS - 1993 DATA
NEPHROLITHIASIS
ECONOMIC IMPLICATIONS 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

7. ASYMPTOMATIC CALCULI TREATMENT Solitary kidney
Occupation (pilot, business traveler
Simultaneous contralateral treatment
It’s difficult to make an asymptomatic patient feel any better !

8. SURGICAL STONE DEFINITION Intractable pain Significant obstruction
Recurrent infection
Severe bleeding
Imminent threat

9. STONE MANAGEMENT OPTIONS Open surgery Percutaneous nephrolithotomy
Ureteroscopy
Shock wave lithotripsy
Medical therapy

10. STONE MANAGEMENT
OPEN NEPHROLITHOTOMY

11. SURGICAL STONE MANAGEMENT
CONSIDERATIONS
Residual stone rate
Recurrence rate
Number of procedures
Hospitalization
Convalescence
Cost

12. SHOCK WAVE LITHOTRIPSY
HISTORY
Preliminary research
Feb, 1980 First human treated
May, 1984 Clinical trials begin in USA
Dec, 1984 FDA approval (Dornier)

13. SHOCK WAVE LITHOTRIPSY
ORIGINAL DORNIER HM3

14. SHOCK WAVE LITHOTRIPSY
SECOND GENERATION MACHINES

15. SHOCK WAVE LITHOTRIPSY
STONE FRAGMENTATION

16. SHOCK WAVE LITHOTRIPSY
STONE FRAGMENTATION

17. SHOCK WAVE LITHOTRIPSY
INDICATIONS
Surgical stone
No obstruction
Reasonable chance of expeditious removal

18. SHOCK WAVE LITHOTRIPSY
RELATIVE CONTAINDICATIONS
Large stones Calcium oxalate > 20 mm Struvite > 30 mm
Cystine stones
Distal obstruction
Poorly informed patients

19. SHOCK WAVE LITHOTRIPSY
CLINICAL SIDE-EFFECTS
Hematuria
Pain
Obstruction (Steinstrasse)

20. SHOCK WAVE LITHOTRIPSY
CLINICAL RENAL INJURY
Mild contusion - Large hematoma
Renal injury in % by MRI
Little data on chronic injury
Hypertension probably not a problem

21. SHOCK WAVE LITHOTRIPSY
APPROPRIATE FOLLOW-UP
Plain radiographs (KUB + tomograms)
Renal scan
Intravenous pyelogram
Spiral CT

22. SHOCK WAVE LITHOTRIPSY
REALITY
<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%

23. SHOCK WAVE LITHOTRIPSY
REALITY
Ideal for some
Marginal in some
Contraindicated in few
THE KEY IS PROPER PATIENT SELECTION AND EDUCATION

24. SHOCK WAVE LITHOTRIPSY
IDEAL CANDIDATES
Small stone (< 1.5 cm)
Mid or upper pole location
Normal renal anatomy
No distal obstruction

25. SURGICAL STONE MANAGEMENT
MODIFIERS OF STONE-FREE RATE
Stone size
Stone location
Stone composition

26. SHOCK WAVE LITHOTRIPSY
LIMITATIONS
Completeness of stone fragmentation
Completeness of fragment elimination

27. SHOCK WAVE LITHOTRIPSY
STONE FREE RATES
% Stone Free
Lingeman and Newman, 1990

28. PERCUTANEOUS NEPHROLITHOTOMY
STONE MANAGEMENT
PERCUTANEOUS NEPHROLITHOTOMY

29. PERCUTANEOUS NEPHROLITHOTOMY
STONE MANAGEMENT
PERCUTANEOUS NEPHROLITHOTOMY

30. STONE MANAGEMENT PNL IN THE AGE OF SWL Large stone mass Obstruction
Anatomic abnormality SWL failure Horseshoe, divertic
Certainty of results Cystine stones
Obesity

31. SURGICAL STONE MANAGEMENT
CURRENT ROLE OF PERCUTANEOUS STONE REMOVAL
Stone volume 46%
Obstruction 16%
Cystine stones 16%
Body habitus 12%
SWL failures 10%

32. SURGICAL STONE MANAGEMENT
CURRENT ROLE OF PNL

33. SURGICAL STONE MANAGEMENT
CURRENT ROLE OF PERCUTANEOUS STONE REMOVAL
Pre-op KUB
Post-SWL KUB

34. SURGICAL STONE MANAGEMENT
CURRENT ROLE OF PERCUTANEOUS STONE REMOVAL
Post-PNL KUB
Post-PNL IVP

35. SURGICAL STONE MANAGEMENT
STAY OUT OF TROUBLE
Pre-op KUB
Pre-op IVP

36. SURGICAL STONE MANAGEMENT
STAY OUT OF TROUBLE
Post-op tomogram
Post-op IVP

37. CRITERIA FOR EVALUATION
STAGHORN CALCULI
CRITERIA FOR EVALUATION
Stone-free rates
Primary procedures
Secondary procedures
Unexplained secondary procedures
Hospital days
AUA Guidelines Panel, 1994

38. STAGHORN CALCULI STONE FREE RATE % Stone Free
AUA Guidelines Panel, 1994

39. PROCEDURES PER PATIENT (20)
STAGHORN CALCULI
PROCEDURES PER PATIENT (20)
% 20 Procedures
AUA Guidelines Panel, 1994

40. STAGHORN CALCULI
SANDWICH THERAPY
PNL
SWL
FLEX NEPHROCOPY

41. 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

42. STAGHORN CALCULI
SANDWICH THERAPY

43. AGGRESSIVE PNL - SINGLE PROCEDURE
STAGHORN CALCULI
AGGRESSIVE PNL - SINGLE PROCEDURE
Pre-op KUB
Pre-op KUB

44. AGGRESSIVE PNL - SINGLE PROCEDURE
STAGHORN CALCULI
AGGRESSIVE PNL - SINGLE PROCEDURE
Pre-op IVP
Pre-op IVP

45. AGGRESSIVE PNL - SINGLE PROCEDURE
STAGHORN CALCULI
AGGRESSIVE PNL - SINGLE PROCEDURE
3 N-tracts
Upper pole access

46. AGGRESSIVE PNL - SINGLE PROCEDURE
STAGHORN CALCULI
AGGRESSIVE PNL - SINGLE PROCEDURE
3 access sheaths
Post-op N-tubes

47. URETERAL CALCULI

48. TREATMENT CONSIDERATIONS
URETERAL CALCULI
TREATMENT CONSIDERATIONS
Location
Size
Chronicity
Equipment
Expertise

49. URETERAL CALCULI TREATMENT OPTIONS Observation Shock wave lithotripsy
Ureteroscopy
Blind basket extraction
Percutaneous approach
Open surgery

50. URETERAL CALCULI
SPONTANEOUS PASSAGE

51. Of all stones that pass spontaneously, 95% will pass within 6 weeks
URETERAL CALCULI
SPONTANEOUS PASSAGE
Of all stones that pass spontaneously, 95% will pass within 6 weeks
Miller & Kane, 1999

52. URETERAL CALCULI
MEDICAL MANAGEMENT
Hollingsworth & Hollenbeck, 2006

53. URETERAL CALCULI
MEDICAL MANAGEMENT
Hollingsworth & Hollenbeck, 2006

54. URETERAL CALCULI
3RD GENERATION SWL

55. URETERAL CALCULI IN SITU SWL Minimal anesthesia requirements
Non-invasive procedure No stenting / less complications
Similar approach to ureteral calculi in all locations

56. SWL FOR URETERAL CALCULI

57. URETERAL CALCULI PARAMETERS FOR COMPARISON
Stone-free is not everything !!

58. PARAMETERS FOR COMPARISON
URETERAL CALCULI
PARAMETERS FOR COMPARISON
Effectiveness
Morbidity
Convalescence
Cost

59. SWL FOR URETERAL CALCULI
DORNIER HM-3
Upper Middle Lower N= 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%
Lingeman, et al, 1993

60. DISTAL URETERAL CALCULI
COMPARISON OF MONOTHERAPY STUDIES
URS is % 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

61. DISTAL URETERAL CALCULI
OVERVIEW OF HISTORICAL CONTROL STUDIES
SWL URS
Effectiveness Slightly better
Morbidity Less
Hospitalization Less
Cost Slightly less

62. DISTAL URETERAL CALCULI
PROSPECTIVE, RANDOMIZED TRIAL
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)
Peschel & Bartsch, 1999

63. DISTAL URETERAL CALCULI
PROSPECTIVE, RANDOMIZED TRIAL STONES < 5 MM
URS SWL
OR time (min)
Fluoro time (min)
Stone-free (days)
Stent (days) 7.2 0
Re-treatment rate 0 15% * * * * *
Peschel & Bartsch, 1999

64. SWL OF DISTAL URETERAL CALCULI
ADVERSE EFFECTS TO FEMALE REPRODUCTIVE TRACT?
Initial animal studies suggest ovarian trauma Impaired fertility Mutagenesis
Subsequent animal investigations demonstrate no impact on fertility or offspring
Mice Rats Rabbits

65. SWL OF DISTAL URETERAL CALCULI
ADVERSE EFFECTS TO FEMALE REPRODUCTIVE TRACT?
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)
Viewig & Miller, 1992

66. URETEROSCOPY

67. FLEXIBLE URETEROSCOPY
URETERAL CALCULI
FLEXIBLE URETEROSCOPY

68. ANTEGRADE MANIPULATION OF URETERAL CALCULI
INDICATIONS
Large stone burden
Body habitus
Urinary diversion
Transplant kidney

69. PERCUTANEOUS APPROACH
URETERAL CALCULI
PERCUTANEOUS APPROACH

70. URETERAL STONE MANAGEMENT
IN SITU SWL
Advantages Minimal anesthesia requirements Non-invasive procedure No stenting/less complications Similar approach for all ureteral calculi
Disadvantages Lower success rate than URS Higher re-treatment rate

71. URETERAL STONE MANAGEMENT
URETEROSCOPY
Advantages Highest success rate Definitive Rx - No waiting for stone passage
Disadvantages More invasive than SWL Higher complication rate Requires greater technical expertise

72. URETERAL CALCULI: CURRENT OPTIONS
PROX AND MID URETERAL STONES
Approach Invasive Stent S-F Rate Re-RxRate
URS % 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

73. URETERAL CALCULI: CURRENT OPTIONS
DISTAL URETERAL STONES
Approach Invasive Stent S-F Rate Re-RxRate
URS % % 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

74. 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

75. NATURAL HISTORY & RISK FACTORS
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 %

76. SHOCK WAVE LITHOTRIPSY
RECURRENT STONE FORMATION
One Year Two Years
Post SWL Post SWL
Stone Free New stones 8% 10%
Residual Stones Stone growth 22% 21%
Lingeman, et al, 1989

77. SHOCK WAVE LITHOTRIPSY
EFFECT ON STONE RISK FACTORS
Urine Values Pre- 3 Mo Post- (mg/day) Lithotripsy Lithotripsy
Calcium
Uric Acid
Citrate
Oxalate 42 41
Brown, et al, 1989

78. 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

79. STONE FORMATION MAJOR FORCES
Concentration / solubility of stone-forming salts
Promoters of crystallization and aggregation
Inhibitors of crystallization and aggregation

80. IMPACT OF LOW CALCIUM DIET
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

81. DIETARY CALCIUM RECOMMENDATIONS
Moderate calcium restriction in patients with AH
Limit dietary intake of oxalate
Spinach, tea, chocolate, nuts
Limit dietary sodium intake

82. PHYSIOLOGICAL EVIDENCE
CALCIUM SUPPLEMENTS
PHYSIOLOGICAL EVIDENCE
Calciuric response to calcium supplementation
Depends on duration of treatment and patient population

83. RECOMMENDATIONS: PREMENOPAUSAL WOMEN
CALCIUM SUPPLEMENTS
RECOMMENDATIONS: PREMENOPAUSAL WOMEN
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

84. RECOMMENDATIONS: POSTMENOPAUSAL WOMEN
CALCIUM SUPPLEMENTS
RECOMMENDATIONS: POSTMENOPAUSAL WOMEN
Check 24-hour urinary calcium 4 months after starting calcium supplements
Offer thiazide to hypercalciuric patients

85. CALCIUM SUPPLEMENTS CURRENT PREPARATIONS
“Standard” Calcium Supplements
Calcium carbonate
Calcium phosphate

86. CALCIUM SUPPLEMENTS CURRENT PREPARATIONS Limitations
Poorly absorbed from intestinal tract
Increased urinary calcium excretion Promotes CaOx, CaPhos stone disease

87. 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

88. 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

89. MEDICAL MANAGEMENT OF NEPHROLITHIASIS
SELECTIVE TREATMENT APPROACH
Reverse underlying physicochemical and physiologic abnormalities
Inhibit new stone formation
Overcome non-renal complications Bone disease in RTA
Free of serious side effects

90. METABOLIC EVALUATION SELECTION OF PATIENTS
Simplified evaluation Comprehensive evaluation
Metabolically inactive Metabolically active Single stone, low risk Single stone, high risk
Positive family history Early age of onset Nephrocalcinosis Associate medical conditions

91. “LOW RISK” STONE FORMER
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

92. METABOLIC EVALUATION
URINARY CRYSTALS

93. AMBULATORY EVALUATION
EVOLUTION
Hospitalization (days)
Outpatient visits
Duration (days)
# diagnostic categories
Unclassified etiology 43% 11% 11% 3%

94. AMBULATORY EVALUATION
OUTLINE
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

95. 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

96. METABOLIC EVALUATION CLASSIFICATION
Sole Combined Occurrence Occurrence
Absorptive hypercalciuria % 40% Type I, Type II
Renal hypercalciuria % 8%
Resorptive hypercalciuria % 5%
Unclassified hypercalciuria % 25%
Hyperuricosuric nephrolithiasis 10% 40%
Hyperoxaluric nephrolithiasis 2% 15%

97. METABOLIC EVALUATION CLASSIFICATION
Sole Combined Occurrence Occurrence
Hypocitraturia 10% 50%
Hypomagnesiuria % 10%
Gouty diathesis % 30%
Cystinuria <1%
Infection stones % 5%
Low urine volume % 50%
No Dx / miscellaneous < 3%

98. MEDICAL MANAGEMENT OF NEPHROLITHIASIS
SELECTIVE TREATMENT APPROACH
Reverse underlying physicochemical and physiologic abnormalities
Inhibit new stone formation
Overcome non-renal complications Bone disease in RTA
Free of serious side effects

99. 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

100. SELECTIVE MEDICAL THERAPY
IMPACT OF MEDICAL RX
SELECTIVE MEDICAL THERAPY
Stone Formation Rate
Pre-Rx
On K-Citrate

101. MEDICAL MANAGEMENT OF NEPHROLITHIASIS
SELECTIVE VS. CONSERVATIVE TREATMENT
Placebo/ Potassium Conservative Citrate
Stone formation rate (no/pt/yr)
Reduction in stone % % formation rate
Remission rate % % * *
Preminger & Pak, 1985

102. IMPACT OF MEDICAL THERAPY
NEED FOR STONE REMOVAL
Pre- On Treatment Treatment
Duration (yr/pt)
Surgery rate (no/pt)
Patients requiring 58% 2% Surgery * *
Preminger & Pak, 1985