Kidney Stone Update Michael Emmett MD Baylor University Medical Center Dallas, Texas Epidemiology of Kidney Stones Incidence About 0.3% Prevalence 10% Men 12% Women 8% Hospitalization Peak Age Stone Composition Calcium Non-Calcium 1/1000/year 18-45 years old Calcium Oxalate Calcium Phosphate Uric Acid Struvite Cystine Lifetime Risk of Kidney Stone White Men 20% White Women 5-10% African American Men 5-6% African American Women 1-2% Annual Cost in USA ~$2 Billion/year 1
Prevalence of Kidney Stone History in Two Eras National Health and Nutrition Examination Surveys NHANES II & III % with Kidney Stones 12 10 8 6 4 2 0 Men 20-39 yo 1976-1980 1988-1994 Men 40-59 yo Men 60-74 yo Women 20-39 yo Women 40-59 yo Women 60-74 yo Stamatelou K.K. et al Kidney Int 2003 Overall Prevalence Of Kidney Stones Continues to Increase 1988-1994 2007-2010 1:20 1:10 Obesity and the Risk of Kidney Stones Relative Risk 2.5 2 1.5 1 0.5 Health Professionals Followup Study 46,000 men (40-75 yo) Nurses Health Study I 94,000 older women (34-59 yo) Nurses Health Study II 102,000 younger women (27-44 yo) HPFS NHS I NHS II 0 <21 21-22.9 23-24.9 25-27.4 27.5-29.9 >30 BMI Taylor et al JAMA 2005 Heredity & Kidney Stones Family History of Stone Disease is reported in 16 37% of Patients with Stones Family History of Stone Disease is reported in 4 12% of Healthy Controls Curhan, GC et al JASN 1997 Trinchieri A et al J Urol 1988 Resnick et al NEJM 1968 2
Twin Concordance Study Goldfarb, DS et al KI 2005 HYPERCALCIURIA Hypercalciuria is the best established risk factor for calcium containing stones 43% of 1 st degree relatives of hypercalciuric patients also have hypercalciuria Coe, FL et al NEJM 1979 URINE CITRATE EXCRETION Familial Patterns Shah, Q, Assimos, DG, Holmes, RP J of Endourology 19; 2005 3
Temperature - A Contributor to Kidney Stone Formation Prevelance by US States Fakheri, RJ & Goldfarb, DS Temperature as a contributor to kidney stone formation: implications of global warming KI 2011 Prevalence of Kidney Stone Disease Among White Men from (CATS) Prevention Study #2 Stone Belt Growth BRIKOWSKI, LOTAN, PEARLE PNAS 2008 4
Lifetime Risk for Kidney Stones for Men Age 60-70 yo Kingdom of Saudi Arabia United Arab Emirates Kidney stone pain usually starts rapidly & then waxes and wanes. Nausea & vomiting common. Gross or microhematuria may be present. Fever generally absent Kidney Stone Presentation 10-15% Flank Pain 25% Flank Pain Radiation to Genital Area 60% Suprapubic Pain Voiding Urgency Suprapubic Pain Anuria Laboratory Tests CBC; Serum Electrolytes, BUN, Creatinine, Calcium, Phosphorus, & Uric Acid Urine Analysis R/O infection Stone composition by infrared spectroscopy or X-ray crystallography Almost all ureteral & renal stones (including uric acid stones) are detected by non-contrast CT imaging. Sensitivity 95% Specificity 98% Plane Film Abdomen sensitivity is 45-58%. 5
Rx of Moderate to Severe Pain Opiates or nonsteroidal antiinflammatory drugs used alone or in combination for pain. Ketorolac (Toradol ) 60 mg IM or 30 mg IV provides effective pain relief with less sedation than opiates and is preferred for patients who are to be discharged from the ED. RCT of 130 patients with renal colic: Pts received either: a. IV morphine (5 mg and then another 5 mg after 20 minutes) b. IV ketorolac (15 mg and then another 15 mg after 20 minutes) c. A combination of both. The combination was superior to either drug alone. Size Matters The Likelihood of a Stone Passing Size mm Size of Stone # Men # Women Total 2 or Less 32 9 41 2-4 10 8 18 4 or Greater 13 3 16 Side 30/25 10/10 40/35 Ureteral Location Mean Days to Pass Need for Intervention % < 2 mm 8 3 3 mm 12 14 4-6 mm 22 50 > 6 mm -- 99 Proximal 10 2 12 Mid 3 2 5 Distal 42 16 58 Miller, OF & Kane, CJ Time to Stone Passage Urology 162: 688-691.1999 Days For Stone to Pass 40 Days to Pass 35 to 30 s y a e g 25 D a e s g 20 a ra P e 15 v A 10 Days to Pass 2 mm 3 mm 4-6 mm 5 2 mm 3 mm Stone Size 4-6 mm 0 LEFT RIGHT Miller, OF & Kane, CJ Time to Stone Passage for Observed Ureteral Calculi J Urology 162: 688-691.1999 6
Tamsulosin, an α 1 -adrenergic antagonist (usually used for BPH) can be used to Rx patients with distal ureteral stones <10 mm to aid stone passage. It is generally well-tolerated - infrequently it does lower BP lightheadedness/dizziness. Nifedipine, a calcium-channel blocker, can also be used to generate ureteral dilatation and relaxation. It often lowers BP. These drugs are often used together with glucocorticosteroids such as methylprednisolone or non-steroidal antiinflammatory drugs When should patients with Nephrolithiasis be admitted? Consider hospitalization for patients when stones are >5 mm and parenteral therapy is required to manage pain. Admit all patients when pain or nausea and vomiting canno be managed in the outpatient setting. Admit patient when infection complicates nephrolithiasis Kidney Stone Recurrence after the First Stone Cumulative Recurrence Rate % 80 70 60 Men 50 40 Woman 30 20 10 0 0 2 4 6 8 10 YEARS Uribarri, Oh & Carroll Ann Intern Med 1989 7
Likelihood of Stone Recurrence From: Rule et al J Am Soc Nephrol 2014;25 Type of Stones in Adults CaOx CaOx CaP Ca & UA UA Cys Struv Unk Key Findings on Urinalysis ph R/O infection Crystals Triple Phosphate Struvite Urine ph very alkaline Cysteine 8
Medication Crystals/Stones Indinavir Crystals Sulfonamide Crystals Acyclovir Crystals atazanavir, methotrexate, triamterene, quinolones, or aminopenicillins Impact of Urine ph Uric Acid Calcium Phosphate Triple Phosphate Struvite Urine ph very alkaline Ennis JL & Asplin JR. The role of the 24-h urine collection in the management of nephrolithiasis. Int J Surg. 36; 633-637. 2013 Preventing Another Stone 1. Urine Volume >2-2.5 L/day 2. Calcium Stones a. Citrate > 350 mg/day b. Calcium < 250 mg/day Calcium Oxalate Oxalate < 45 mg/day Calcium Phosphate Phosphate < 1000 mg/day Urine ph - Alkaline predisposes 9
Kidney Citrate Physiology Na-Dependent Dicarboxylate Cotransporter NaDC1 (SLC13 family) Aconitase ATP Citrate lyase Proximal Tubule Na 3 Citrate 3 Na + Citrate -2 ~100 um/l 20 mm/day 3800 mg/day Citrate -2 Ca +2 2-4 mm/day 380-760 mg/day Citrate -3 Ca +2 Metabolic Acidosis Kidney Citrate Physiology ph Aconitase ATP Citrate lyase Proximal Tubule Na 3 Citrate 3 Na + ph More Acidic Citrate -2 Adapted from: Brennan et al Am. J. Phys 255; F301, 1988 Ca +2 Distal Tubule Urine Less Acidic Citrate -3 Ca +2 Preventing Another Stone 1. Urine Volume >2-2.5 L/day Calcium Oxalate Urine [Ca] Urine [Oxalate] Urine [Citrate] 10
Relative Risk RISK OF KIDNEY STONES vs DAILY CALCIUM INTAKE 1.1 NHS I (77,436 1976) 1.0 NHS II (93,803 1989) 0.9 HPFS (51,529 1986) 0.8 0.7 0.6 0.5 Curhan, NEJM 1993 Annals Int Med 1997 Archives Int Med 2004 < 600 700 800 900 >1000 Dietary Calcium Intake (mg/d) A 5-year randomized trial comparing two diets in 120 men with recurrent calcium oxalate stones and hypercalciuria Calcium Intake 400 mg/day Calcium Intake 1200 mg/day Borghi, L. et al N Engl J Med 346 2002 11
400 mg/day 1200 mg/day Borghi, L. et al N Engl J Med 346 2002 NORMAL Small Bowel Oxalate Calcium Colon Normal Oxalate Absorption is 10-20% Steatorrhea Small Bowel Fatty Acids Oxalate Calcium Colon Oxalate Absorption 12
Causes of Enteric Hyperoxaluria Small Bowel Disease Crohn Disease Celiac Disease Surgical Resection Jejuno-ileal Bypass Ileal Resection Malabsorption/Steatorrhea Pancreatic Insufficiency Cystic Fibrosis Biliary Obstruction Bacterial Overgrowth Blind Loops 25-40% of Urine Oxalate is Derived from Absorption of Oxalate in the Diet Meat Protein in Some Patients Thiazides vs. Placebo or Control HCTZ 25 mg BID or Chlorthalidone 25 mg QD Fink HA, et al Mgt to Prevent Recurrent Nephrolithiasis in Adults: Ann Intern Med. 2013 Apr 2;158(7):535-43. 13
Citrate vs. Placebo or Control K Citrate 20-80 meq/d divided into 3-4 doses Fink HA, et al Mgt to Prevent Recurrent Nephrolithiasis in Adults: Ann Intern Med. 2013 Apr 2;158(7):535-43. Allopurinol vs. Placebo or Control 100-300 mg/d Fink HA, et al Mgt to Prevent Recurrent Nephrolithiasis in Adults: Ann Intern Med. 2013 Apr 2;158(7):535-43. URIC ACID STONES 14
600 4.5 5.0 5.35 Urine ph Undissociated Uric Acid (mg/l) 500 400 300 200 100 5.5 5.75 6.0 6.5 0 200 400 600 800 1000 1200 After Fred Coe Total Uric Acid (mg/l) RELATION BETWEEN BODY SIZE & URINARY STONE RISK FACTORS URINARY ph BY SEXTILE OF BODY WEIGHT 6.3 6.2 URINE ph 6.1 6 5.9 5.8 5.7 5.6 Chicago Dallas 1 2 3 4 5 6 <61 61-70 70-77 77-84 84-95 >95 SEXTILE OF WEIGHT (KG) Maalouf et al KI 2004 15
Obesity, Insulin Resistance & the Gouty Diathesis Obesity Insulin Resistance Insulin Resistance Reduces urine NH 4 Reduced urine NH 4 generates a very acidic urine Persistently low urine ph leads to uric acid precipitation Patients with DM who develop kidney stones have urate stones about 1/3 time Patients without DM who develop kidney stones have urate stones about 6% time Sakhaee, Moe, Pak Kidney Stones Kidney Stones are very common and very often recur To prevent recurrence it is imperative to identify the composition of the stone and to recognize major risk factors Based on these results, intervene to reduce the likelihood of recurrence by manipulating risk factors 16