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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.

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Presentation on theme: "ADVANCES IN THE MANAGEMENT OF NEPHROLITHIASIS Glenn M. Preminger, M.D. Comprehensive Kidney Stone Center at Duke University Medical Center Durham, North."— Presentation transcript:

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

3 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

4 NEPHROLITHIASIS ANATOMY

5 NEPHROLITHIASIS Peak incidence age 30 - 60 Gender (Male : Female) 3 : 1 Family history3 - fold risk Body size risk with weight Recurrence after first stone: Year 110 - 15% Year 550 - 60% Year 1070 - 80% NATURAL HISTORY & RISK FACTORS

6 STONE BELT

7 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

8 ASYMPTOMATIC CALCULI TREATMENT Solitary kidney Occupation (pilot, business traveler Simultaneous contralateral treatment Its difficult to make an asymptomatic patient feel any better !

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

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

11 STONE MANAGEMENT OPEN NEPHROLITHOTOMY

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

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

14 SHOCK WAVE LITHOTRIPSY ORIGINAL DORNIER HM3

15 SHOCK WAVE LITHOTRIPSY SECOND GENERATION MACHINES

16 SHOCK WAVE LITHOTRIPSY STONE FRAGMENTATION

17 SHOCK WAVE LITHOTRIPSY STONE FRAGMENTATION

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

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

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

21 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

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

23 SHOCK WAVE LITHOTRIPSY REALITY 30mm Multiple SWL5%10%15-30% Stone-free rate>80%60%50% Auxiliary procedures2%5-7%15% Repeat procedures1-2%10-15%15-20%

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

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

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

27 SHOCK WAVE LITHOTRIPSY LIMITATIONS Completeness of stone fragmentation Completeness of fragment elimination

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

29 STONE MANAGEMENT PERCUTANEOUS NEPHROLITHOTOMY

30 STONE MANAGEMENT PERCUTANEOUS NEPHROLITHOTOMY

31 Large stone massObstruction Anatomic abnormalitySWL failure Horseshoe, divertic Certainty of resultsCystine stones Obesity STONE MANAGEMENT PNL IN THE AGE OF SWL

32 SURGICAL STONE MANAGEMENT CURRENT ROLE OF PERCUTANEOUS STONE REMOVAL Stone volume46% Obstruction16% Cystine stones16% Body habitus12% SWL failures10%

33 SURGICAL STONE MANAGEMENT CURRENT ROLE OF PNL

34 SURGICAL STONE MANAGEMENT CURRENT ROLE OF PERCUTANEOUS STONE REMOVAL Pre-op KUBPost-SWL KUB

35 SURGICAL STONE MANAGEMENT CURRENT ROLE OF PERCUTANEOUS STONE REMOVAL Post-PNL KUBPost-PNL IVP

36 SURGICAL STONE MANAGEMENT STAY OUT OF TROUBLE Pre-op KUBPre-op IVP

37 SURGICAL STONE MANAGEMENT STAY OUT OF TROUBLE Post-op tomogramPost-op IVP

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

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

40 STAGHORN CALCULI PROCEDURES PER PATIENT (2 0 ) % 2 0 Procedures AUA Guidelines Panel, 1994

41 STAGHORN CALCULI SANDWICH THERAPY PNL SWL FLEX NEPHROCOPY

42 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

43 STAGHORN CALCULI SANDWICH THERAPY

44 STAGHORN CALCULI AGGRESSIVE PNL - SINGLE PROCEDURE Pre-op KUB

45 STAGHORN CALCULI AGGRESSIVE PNL - SINGLE PROCEDURE Pre-op IVP

46 STAGHORN CALCULI AGGRESSIVE PNL - SINGLE PROCEDURE 3 N-tractsUpper pole access

47 STAGHORN CALCULI AGGRESSIVE PNL - SINGLE PROCEDURE 3 access sheathsPost-op N-tubes

48 URETERAL CALCULI

49 TREATMENT CONSIDERATIONS Location Size Chronicity Equipment Expertise

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

51 URETERAL CALCULI SPONTANEOUS PASSAGE

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

53 URETERAL CALCULI MEDICAL MANAGEMENT Hollingsworth & Hollenbeck, 2006

54 URETERAL CALCULI MEDICAL MANAGEMENT Hollingsworth & Hollenbeck, 2006

55 URETERAL CALCULI 3RD GENERATION SWL

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

57 SWL FOR URETERAL CALCULI

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

59 URETERAL CALCULI Effectiveness Morbidity Convalescence Cost PARAMETERS FOR COMPARISON

60 SWL FOR URETERAL CALCULI UpperMiddleLower N= 33N=248N=381 Success of94.8%85.9%98.2% 1 O procedure Re-tx rate6.8%15.7%1.8% Complications10%15.3%8.4% DORNIER HM-3 Lingeman, et al, 1993

61 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 OF MONOTHERAPY STUDIES

62 DISTAL URETERAL CALCULI SWLURS EffectivenessSlightly better MorbidityLess HospitalizationLess CostSlightly less OVERVIEW OF HISTORICAL CONTROL STUDIES

63 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

64 DISTAL URETERAL CALCULI URSSWL OR time (min)19 63 Fluoro time (min)0.85.1 Stone-free (days)0.210.8 Stent (days)7.20 Re-treatment rate015% PROSPECTIVE, RANDOMIZED TRIAL STONES < 5 MM Peschel & Bartsch, 1999 * * * * *

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

66 SWL OF DISTAL URETERAL 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 TO FEMALE REPRODUCTIVE TRACT? Viewig & Miller, 1992

67 URETEROSCOPY

68 URETERAL CALCULI FLEXIBLE URETEROSCOPY

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

70 URETERAL CALCULI PERCUTANEOUS APPROACH

71 URETERAL STONE MANAGEMENT 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 IN SITU SWL

72 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

73 URETERAL CALCULI: CURRENT OPTIONS PROX AND MID URETERAL STONES ApproachInvasiveStentS-F RateRe-RxRate URS+++100%75-90%10-15% Push/Smash++Rarely92%9% SWL + Stent+100%75-80%20-25% In situ SWL0No75-80%20-25% * Defined as complete stone removal with single procedure

74 URETERAL CALCULI: CURRENT OPTIONS DISTAL URETERAL STONES ApproachInvasiveStentS-F RateRe-RxRate URS+++100%98-100%0-2% Push/Smash++Rarely92%9% SWL + Stent+100%75-80%20-25% In situ SWL0No75-80%20-25% * Defined as complete stone removal with single procedure

75 SURGICAL STONE MANAGEMENT CHANGING TREATMENT PHILOSOPHIES 1980s1990s2000s2010s Shock wave lithotripsy95%85%75%??? Endoscopic procedures5%15%25%??? Open stone surgery< 1% < 1% < 1%0

76 NEPHROLITHIASIS Peak incidence age 30 - 60 Gender (Male : Female) 3 : 1 Family history3 - fold risk Body size risk with weight Recurrence after first stone: Year 110 - 15% Year 550 - 60% Year 1070 - 80% NATURAL HISTORY & RISK FACTORS

77 SHOCK WAVE LITHOTRIPSY RECURRENT STONE FORMATION One YearTwo YearsPost SWL Stone Free New stones8%10% Residual Stones Stone growth22%21% Lingeman, et al, 1989

78 SHOCK WAVE LITHOTRIPSY EFFECT ON STONE RISK FACTORS Urine ValuesPre-3 Mo Post- (mg/day) LithotripsyLithotripsy Calcium254261 Uric Acid552548 Citrate249257 Oxalate4241 Brown, et al, 1989

79 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

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

81 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

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

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

84 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

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

86 CALCIUM SUPPLEMENTS Standard Calcium Supplements Calcium carbonate Calcium phosphate CURRENT PREPARATIONS

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

88 CALCIUM SUPPLEMENTS "Citracal" Over-the-counter preparation Calcium citrate950 mg Elemental calcium200 gm Provides increased intestinal calcium absorption Prevents supersaturation of stone-forming salts A more "stone-friendly" calcium supplement CALCIUM CITRATE

89 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

90 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

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

92 METABOLIC EVALUATION Serum Ca, Phos1 0 HPT Serum electrolytesRTA Serum uric acidGout, HUCU UrinalysisCrystals, infection History (risk factors)Fluids, diet, meds X-rays NehprocalcinosisRTA Radiolucent stonesUric acid, ? Cystine Staghorn stonesStruvite Stone analysisType of stone LOW RISK STONE FORMER

93 METABOLIC EVALUATION URINARY CRYSTALS

94 AMBULATORY EVALUATION EVOLUTION 1971197419862001 Hospitalization (days)14000 Outpatient visits0031-2 Duration (days)14212114 # diagnostic categories34913 Unclassified etiology43%11%11%3%

95 AMBULATORY EVALUATION Blood Urine CBCSMAPTHTVpHCaOxUANaCitCreatCyst Visit 1xxxxxxxxxxx Visit 2xxxxxxxxx Fastxxx Loadxxx OUTLINE

96 METABOLIC EVALUATION 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 CLASSIFICATION

97 METABOLIC EVALUATION SoleCombined OccurrenceOccurrence Absorptive hypercalciuria 20%40% Type I, Type II Renal hypercalciuria 5%8% Resorptive hypercalciuria 3%5% Unclassified hypercalciuria 15%25% Hyperuricosuric nephrolithiasis10%40% Hyperoxaluric nephrolithiasis 2%15% CLASSIFICATION

98 METABOLIC EVALUATION SoleCombined OccurrenceOccurrence Hypocitraturia10%50% Hypomagnesiuria 5%10% Gouty diathesis 15%30% Cystinuria <1% Infection stones 1%5% Low urine volume 10%50% No Dx / miscellaneous < 3% CLASSIFICATION

99 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

100 MEDICAL MANAGEMENT OF NEPHROLITHIASIS First LineSecond Line AHIThiazideCellulose phos RHThiazide HUCUAllopurinolCitrate Enteric hyperoxCa ++ / Mg ++ Citrate Gouty diathesisCitrateAllopurinol HypocitCitrateBicarb CystinuriaThiolad-Pen StruviteRemove stoneThiola SELECTIVE TREATMENT APPROACH

101 SELECTIVE MEDICAL THERAPY Stone Formation Rate IMPACT OF MEDICAL RX Pre-RxOn K-Citrate

102 MEDICAL MANAGEMENT OF NEPHROLITHIASIS Placebo/ Potassium Conservative Citrate 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% SELECTIVE VS. CONSERVATIVE TREATMENT * * Preminger & Pak, 1985

103 IMPACT OF MEDICAL THERAPY Pre-On Treatment Treatment Duration (yr/pt) 3.03.7 Surgery rate (no/pt) 0.210.01 Patients requiring 58%2% Surgery NEED FOR STONE REMOVAL * * Preminger & Pak, 1985


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