Nephrolithiasis Outline Epidemiology

Transcription

1 Nephrolithiasis Brian Duty, M.D. Assistant Professor Department of Urology Oregon Health & Sciences University Outline Epidemiology Pathophysiology Clinical Presentation Diagnosis Management Medical Surgical Prevention Epidemiology Lifetime Risk Men: 12% Women: 6% Incidence Men Rises after age 20 Peaks between years Women Higher in late 20s Decreases by age 50 Curhan. UrolClinN Am 2007; 34:

2 Epidemiology Recurrence Rates Stone Formation 1 40 to 50% within 5 years 50 to 60% within 10 years Stone Progression 2 77%within 3 years 26% intervention rate 1. Curhan. UrolClinN Am 2007; 34: Burgher. J Endourol 2004; 18: 534. Health Care Cost These costs have likely dramatically increased over the past 16 years 2

3 Nephrolithiasis & Systemic Diseases Nephrolithiasis has been associated with Hypertension Diabetes mellitus Metabolic syndrome Coronary artery disease Hypertension Cappuccioet al men without a history of stones followed for at least 5 years Normotensive: 389 Hypertensive: 114 Hypertensive group had 90% increased risk of developing stones Borghiet al individuals without a history of stones (mean fu8 years) Normotensive: 135 Hypertensive: 132 Stone Events: 14.3% HTN vs 2.9% normotensive Urine Composition: higher Ca, Phosand Oxalate levels in HTN 1. Cappuccio et al. J Hypertens 1999; 17: Borghi et al. Kidney Int 1999; 55: Hypertension Prospective study of the relationship between nephrolithiasisand HTNin the Nurses Health Study 1 Cohort of 89,376 women (15 years of follow-up) Hxof Nephrolithiasis: 24% increased risk of developing HTN Prospective study of the relationship between nephrolithiasisand HTNin the Health Professionals Follow-up Study 2 Cohort of 51,529 men (8years of follow-up) Hxof Nephrolithiasis: 29% increased risk of developing HTN 1. Madore et al. Am J Kidney Diseases 1998; 32: Madore et al. Am J Hypertens 1998; 11: 46. 3

4 Diabetes Mellitus Cross-sectional study from 3 large cohorts Nurses Health Study I (older women) Nurses Health Study II (younger women) Health Professionals Follow-up Study (men) Prospectively studied associated between stones and DM with > 44 years of follow-up Multivariate analysis: age, BMI, diuretic use, fluid intake and dietary factors Taylor et al. Kidney Int2005; 68: Diabetes Mellitus Stone Risk in Diabetics Older Women 1.29( ) Younger Women 1.60( ) Men 0.81 ( ) Diabetes Risk in Stone Individuals Older Women 1.33( ) Younger Women 1.48( ) Men 1.49( ) Taylor et al. Kidney Int2005; 68: Metabolic Syndrome Metabolic Syndrome Diabetes, HTN, obesity, high triglycerides, low HDL Cross-sectional study from the National Health and Nutrition Examination Survey Included 14,870 NHANES participants Examined self reported history of nephrolithiasis West et al. Am J Kidney Diseases 2008; 51:

5 Metabolic Syndrome 1 Trait RR Traits RR Traits RR Traits RR Traits RR 1.93 West et al. Am J Kidney Diseases 2008; 51: 741. Coronary Artery Disease Cross-sectional study from 3 large cohorts Nurses Health Study I (older women) Nurses Health Study II (younger women) Health Professionals Follow-up Study (men) Prospectively studied associated between stones and CAD Younger women 1.18( ) Older women 1.48( ) Men 1.06 ( ) Ferraro et al. JAMA 2008; 310: 408. Other Associated Medical Conditions Gout Hyperparathyroidism Hyperthyroidism Immobility Inflammatory Bowel Disease Malignancy Sarcoidosis Sjogren s Syndrome Urinary Tract Infections 5

6 Types of Stones Calcium Oxalate 70 to 80% Calcium Phosphate 5 to 10% Uric Acid 5 to 10% Struvite 5 to 10% Cystine 1 to 5% Drugs 1% Indinavir, Triamterene Ephedrine, Guaifenesin Stone Physiochemistry Concentration Product Crystal Growth and Aggregation Will Occur Inhibitors Will NOT Prevent Crystal Growth and Aggregation May Occur Inhibitors May Prevent Stones Will Not Form Stones May Dissolve Formation Product Solubility Product Unstable [ ] exceeds the Formation Product Metastable [ ] between Solubility & Formation Product Undersaturated [ ] under the Solubility Product Metastable State Nucleation Inhibitors Citrate Magnesium Nephrocalcin Tamm-Horsfall Protein Uropontin 6

7 Fixed Particle Growth Theory Vascular Mechanism Atherosclerotic-like reaction of the vasa recta Ductile Mechanism Defect basement membrane of the thin loop of Henle Unifying Principle Calcium phosphate plaque that erodes into the collecting system (a.k.a. Randall s Plaque) Randall s Plaques k Classic Presentation Renal colic Ureteral spasm and obstruction Starts in flank Often radiates towards lower abdomen & genitalia +/- Nausea and vomiting Almost always microscopic or gross hematuria 7

8 Differential Diagnosis Urologic Causes Papillary necrosis Renal infarct Renal hemorrhage Pyelonephritis Non-urologic Causes Cholecystitis Appendicitis Diverticulitis Ruptured Ovarian Cyst Atypical Presentations Large Stones Hematuria only Recurrent infections Acute or chronic renal failure Entirely asymptomatic Ureterovesical Junction Stones Urinary frequency / urgency Dysuria / penile pain Work-up Helical CT Scan Sensitivity 96% Specificity ~ 100% Positive Predictive Value ~100% Negative Predictive Value 91% Scans negative for stone disease revealed other abnormalities in 57% of patients Vieweg et al. J Urol1998; 160:

9 Radiation Exposure Review of 176 ptspresenting to ED with renal colic who received CT scans Mean effective dose per study: 6.5 to 8.5 msv 4% of patients had 3 or more studies Their effective dose ranged from 19.5 to msv Katz et al. Am J Roentgenol 2006; 186: Exposure Put in Context Annual Environmental Exposure 3.6 msv(82% natural vs 18% artificial sources) Annual Target Limits from Artificial Sources General Public: 1 msv Occupational Exposure: 50 msv Other Chest x-ray: 0.1 msv Transcontinental flight: 0.03 msv CT versus US for Renal Colic Randomized 2759 pts presenting to ED with renal colic 908 Point-of-Care US / 893 Radiology US 958 Radiology CT Exclusion Criteria High-risk of Alternative Dx: appendicitis, cholecystitis Obesity: men >285 lbs; women > 250 lbs End Points 1 : High-risk diagnoses, cumulative radiation exposure, cost 2 : Pain, return to ED, hospitalization, need for intervention and diagnostic accuracy Smith-Bindman et al. NEJM 2014; 371:

10 Ultrasound Groups Less Radiation No Increase In Adverse events Return to ED Hosp admissions Pain Smith-Bindman et al. NEJM 2014; 371: Final Thought on Imaging Consider KUBin patients with CT showing stone Determines if KUB is adequate surveillance modality KUB exposure (0.4 to 0.7 msv) Determines if candidate for shock wave lithotripsy Indications for Urgent Management Absolute Urosepsis Obstructed solitary kidney Bilateral obstruction Intractable pain, nausea / vomiting Relative Renal insufficiency Immunocompromise No Indication Stone size Degree of hydronephrosis on imaging 10

11 Trial of Passage Review of 172 patients with solitary ureteral stones 115 (66.8%) passedspontaneously 57 (33.1%) required intervention Collet al. AJR 2002; 178: 101. Medical Expulsion Therapy Pooled analysis of 16 alpha & 9 calcium channel blocker randomized studies Alpha Blockers: RR 1.59, NNT 3.3, 4% AE Calcium Channel Blocker: RR 1.50, NNT 3.9, 15.2% AE Alpha Blockers Calcium Channel Blockers Singh et al. Ann EmergMed 2007; 50: 552. Medical Expulsive Therapy Randomized Control Trial of 1136 patients with solitary ureteral stone Tamsulosin0.4 mg per day (391 patients) Nifedipine30 mg per day (387 patients) Placebo 1 pill per day (389 patients) Outcomes Primary: spontaneous stone passage rate Secondary: pain (days requiring analgesic use & severity), time to stone passage, quality of life survey Pickard et al. Lancet 2015; 386:

12 Medical Expulsive Therapy Results Spontaneous Passage Rate: No difference between 3 arms Time to Stone Passage: No difference between 3 arms Pain: No difference between 3 arms Quality of Life: No difference between 3 arms Comments Wide Eligibility Criteria: stones 10 mm, all ureteral locations Underpowered to assess efficacy for smaller distal stones Pickard et al. Lancet 2015; 386: 341. Lithotripsy Modalities Extracorporeal Shock Wave Lithotripsy Ureteroscopic Laser Lithotripsy Percutaneous Nephrolithotomy Shock Wave Lithotripsy Background Developed in Germany in 1980 External shock waves used to fragment stone Advantages Least invasive, best tolerated Disadvantages Stone must be radio-opaque Some stones fragment poorly Fragments may remain in kidney Symptoms during fragment passage 12

13 UreteroscopicLithotripsy Background Developed in the 1990s Under continual refinement with new endoscopes Ureteroscopic Lithotripsy Advantages Laser fragments all types of stones Finer control of fragment size Ability to relocate stone to facilitate stone passage Ability to extract stone fragments Disadvantages More invasive than ESWL Often requires stent Greater risk of ureteral injury Percutaneous Nephrolithotomy Background Developed in

14 Percutaneous Nephrolithotomy Advantages Only modality to efficiently extract stone fragments Disadvantages Most invasive modality Highest Complication Rate Fever > 38.5 C (10.5%) Transfusion Rate (5.7%) Collecting System Perforation (3.4%) Hydrothorax (1.8%) Visceral Injury (<1%) de la Rosette et al. J Endourol 2011; 25: 11. Ureteral Stone Treatment Proximal Ureteral Stone Less than 1 cm ESWL or URS Greater than 1 cm Consider PCNL Distal Ureteral Stone URS Consider AntegradeURS for Stones > 2 cm ESWL = extracorporeal shock wave lithotripsy URS = ureteroscopic lithotripsy PCNL = percutaneous nephrolithotomy Renal Stone Treatment Lower Pole Stone Less than 1 cm ESWL or URS Greater than 1 cm Consider PCNL Non-Lower Pole Stone Less than 1 cm ESWL or URS Between 1 cm and 2 cm ESWL or URS Consider PCNL Greater than 2 cm PCNL Staged URS for the infirm ESWL = extracorporeal shock wave lithotripsy URS = ureteroscopic lithotripsy PCNL = percutaneous nephrolithotomy 14

15 Screening Metabolic Evaluation Indications First time stone former Episodes many years apart Components Medical history Dietary history Medications Serum chemistries Urine dipstick and microscopic exam Associated Medical Conditions Disease Stone Type Mechanism Hyperparathyroidism Calcium Resorptive hypercalciuria Hyperthyroidism Calcium Resorptive hypercalciuria Immobility Calcium Resorptive hypercalciuria Sarcoidosis Calcium Absorptive hypercalciuria (vit D production) Malignancy Calcium Bothtypes hypercalciuria (vitd, PTH production) Sjogrenssyndrome Calcium Phosphate Renaltubular acidosis (hypocitraturia) Inflammatory bowel dz Calcium,Uric Acid Dehydration,hyperoxaluria, hypercalciuria, hypocitraturia Insulin resistance Calcium, Uric Acid Hypocitraturia Gout Uric Acid Hyperuricosuria Infection Struvite Urinary alkalinzation Dietary History Fluid Intake Type and distribution throughout the day Calcium Intake Dietary versus supplementation, timing Animal Protein Intake Fruit and Vegetable Intake 15

16 Stone Provoking Medications Corticosteroids Promote absorptive hypercalciuria Carbonic Anhydrase Inhibitors Systemic acidosis hypercalciuria& hypocitraturia Laxative Abuse Systemic acidosis hypercalciuria & hypocitraturia Ammonium acid urate stones Topiramate Impairs urinary acidification increased urinary ph & hypocitraturia Calcium phosphate stones Laboratory Examination Serum Studies Primary Hyperparathyroidism ❿ Calcium, Phosphorus, PTH Distal Renal Tubular Acidosis Bicarb, Potassium, Chloride Urine Studies Infections Stones: bacteriuria, pyuria, high ph Uric Acid Stones: low ph Crystals Urine Microscopy Calcium oxalate dihydrate Calcium oxalate monohydrate Uric Acid Cystine Struvite 16

17 Comprehensive Metabolic Evaluation Indications Presentation Multiple stones Multiple episodes Demographics Children High-risk occupations History Associated med conditions Strong family history Abnormal renal anatomy Stone Analysis Noncalcium oxalate calculi Comprehensive Metabolic Evaluation Components Screening metabolic evaluation plus One to two 24 hour urine collections on a random diet LithoLink Corporation, Chicago, IL. Tailored Interventions Low Urine Volume: increase fluid intake Hypercalciuria: thiazide diuretic Hyperoxaluria: low oxalate diet Hypocitraturia: potassium citrate supplementation Low Urinary ph: K citrate supplementation Increased fruits/vegetables, decreased animal protein Elevated Urinary Sodium: low sodium diet 17

18 Pearle et al. J Urol2014; 92: 316. Summary Nephrolithiasisaffects 10% of population at a cost of over $2 billon per year Without intervention recurrence rates approach 50% within 5 yrs Work-up First-Line: renal ultrasound for non-complicated patients Consider CT: critically ill, morbidly obese & those with lower index of suspicion for nephrolithiasis Summary Lithotripsyreserved for non-complicated patients failing trial of passage (plus/minus medical expulsive therapy) Shock wave, ureteroscopic, or percutaneous nephrolithotomy Patientswith multiple or recurrent stones should undergo a metabolic work-up Detailed history, serum studies and 24 hour urine collection Risk directed therapy instituted based upon results 18

19 Thank You 19