Kidney Stones: An Overview Gerald Da Roza MD, MHSc, FRCPC March 15, 2010

Overview Case Case Diagnosis of kidney stones Diagnosis of kidney stones Acute management Acute management Epidemiology Epidemiology Risk factors Risk factors Work up and treatment Work up and treatment Diet and kidney stones Diet and kidney stones

Case – A Few Years Ago 30 year old nephrology fellow 30 year old nephrology fellow Bright, hardworking, driven Bright, hardworking, driven Atrocious diet (hospital cafeteria and vending machines, no fruit and vegetables, ++ salt) Atrocious diet (hospital cafeteria and vending machines, no fruit and vegetables, ++ salt) Drinks very little during daytime Drinks very little during daytime Presents with acute onset of R costovertebral pain, radiating around to anterior abdomen, 10/10 in severity, nauseau and vomiting Presents with acute onset of R costovertebral pain, radiating around to anterior abdomen, 10/10 in severity, nauseau and vomiting

Case – A Few Years Ago Physical Exam Physical Exam Tachycardia, normotensive, afebrile Tachycardia, normotensive, afebrile ++ CVA and RUQ tenderness ++ CVA and RUQ tenderness Nil else Nil else Investigations Investigations U/A shows hematuria, U/A shows hematuria, CBC, lytes urea, Cr normal CBC, lytes urea, Cr normal

Diagnosis??? Kidney Stone - Why? Kidney Stone - Why? DDx DDx Renal Cell Ca w/ blood clot Renal Cell Ca w/ blood clot Renal Cyst w/ clot Renal Cyst w/ clot Pyelonephritis Pyelonephritis AAA/dissection AAA/dissection Ectopic Pregnancy (if female) Ectopic Pregnancy (if female) Intestinal Obstruction Intestinal Obstruction Appendicitis Appendicitis

How do we make the diagnosis? Investigative Options: Investigative Options: CT Scan CT Scan US US Abdominal Plain Film Abdominal Plain Film MRI MRI IVP IVP

Non-contrast Helical CT Scan Gold standard Gold standard Sensitivity 95 %, Specificity 98% Sensitivity 95 %, Specificity 98% Dual energy CT (DECT) is new imaging modality may be able to predict stone composition (future tx) Dual energy CT (DECT) is new imaging modality may be able to predict stone composition (future tx) Helps determine if obstruction present Helps determine if obstruction present Provides alternate diagnosis in many cases Provides alternate diagnosis in many cases 33 percent had an alternate diagnosis not suspected on clinical grounds, one-half of whom had significant disease 33 percent had an alternate diagnosis not suspected on clinical grounds, one-half of whom had significant disease Only misses stones due to protease inhibitors Only misses stones due to protease inhibitors

CT KUB

Ultrasound Procedure of choice for pts who should avoid radiation Procedure of choice for pts who should avoid radiation pregnant women and possibly women of childbearing age pregnant women and possibly women of childbearing age Sensitive for the diagnosis of obstruction Sensitive for the diagnosis of obstruction Can detect radiolucent stones missed on x-ray Can detect radiolucent stones missed on x-ray May miss small stones and ureteral stones May miss small stones and ureteral stones

Ultrasound

Abdominal X-ray will identify sufficiently large radiopaque stones will identify sufficiently large radiopaque stones calcium, struvite, and cystine stones calcium, struvite, and cystine stones will miss radiolucent uric acid stones will miss radiolucent uric acid stones may miss small stones or stones overlying bony structures may miss small stones or stones overlying bony structures will not detect obstruction will not detect obstruction

Other Intravenous Pyelogram (IVP) Intravenous Pyelogram (IVP) higher sensitivity and specificity than plain film for the higher sensitivity and specificity than plain film for the provides data about the degree of obstruction provides data about the degree of obstruction previously the diagnostic procedure of choice, no longer because of potential contrast rxn, lower sens, higher radiation previously the diagnostic procedure of choice, no longer because of potential contrast rxn, lower sens, higher radiation Magnetic resonance imaging Magnetic resonance imaging rarely used during the management of stone disease, except in the evaluation of pregnant patients, because this modality is not optimal for identifying stones. rarely used during the management of stone disease, except in the evaluation of pregnant patients, because this modality is not optimal for identifying stones.

Acute Management Many pts with acute renal colic can be managed conservatively with pain medication (NSAIDs & Opiods) and hydration until the stone passes Many pts with acute renal colic can be managed conservatively with pain medication (NSAIDs & Opiods) and hydration until the stone passes If able to take oral medications and fluids can manage at home If able to take oral medications and fluids can manage at home Hospitalization required for those who cannot tolerate oral intake or who have uncontrollable pain or fever Hospitalization required for those who cannot tolerate oral intake or who have uncontrollable pain or fever

Acute Management Pts instructed to strain their urine for several days and bring in any stone that passes for analysis Pts instructed to strain their urine for several days and bring in any stone that passes for analysis will enable clinician to better plan preventive therapy will enable clinician to better plan preventive therapy Data suggests faster stone passage tamsulosin Data suggests faster stone passage tamsulosin CCB is other option CCB is other option Pts are re-imaged if spontaneous passage has not occurred. Pts are re-imaged if spontaneous passage has not occurred.

Acute Management Urgent urologic consultation warranted in: Urgent urologic consultation warranted in: Urosepsis Urosepsis Acute renal failure Acute renal failure Anuria Anuria Unyielding pain, nausea, or vomiting Unyielding pain, nausea, or vomiting

Acute Management Stone size major determinant of the likelihood of spontaneous stone passage, although stone location is also important Stone size major determinant of the likelihood of spontaneous stone passage, although stone location is also important Most stones ≤4 mm in diameter pass spontaneously. For stones larger than 4 mm in diameter, there is a progressive decrease in the spontaneous passage rate, which is unlikely with stones ≥10 mm in diameter Most stones ≤4 mm in diameter pass spontaneously. For stones larger than 4 mm in diameter, there is a progressive decrease in the spontaneous passage rate, which is unlikely with stones ≥10 mm in diameter Proximal ureteral stones are also less likely to pass spontaneously. Proximal ureteral stones are also less likely to pass spontaneously.

Acute Management Referral to urology for potential intervention Referral to urology for potential intervention stones larger than 10 mm in diameter stones larger than 10 mm in diameter significant discomfort significant discomfort significant obstruction or who have not passed the stone after four to six weeks significant obstruction or who have not passed the stone after four to six weeks

Urologic Options Shock wave lithotripsy (SWL) Shock wave lithotripsy (SWL) tx choice in 75% pts tx choice in 75% pts works best for stones in renal pelvis and upper ureter works best for stones in renal pelvis and upper ureter Ureteroscopic lithotripsy with electrohydraulic or laser probes Ureteroscopic lithotripsy with electrohydraulic or laser probes higher stone-free rates, but with an increased incidence of complications over shock wave lithotripsy higher stone-free rates, but with an increased incidence of complications over shock wave lithotripsy Percutaneous nephrolithotomy Percutaneous nephrolithotomy Laparoscopic stone removal Laparoscopic stone removal Rarely needed Rarely needed

Kidney Stones - Epidemiology Renal stones (nephrolithiasis) are a relatively common problem Renal stones (nephrolithiasis) are a relatively common problem In US, up to 12% of men and 5% of women will have at least one symptomatic stone by the age of 70 In US, up to 12% of men and 5% of women will have at least one symptomatic stone by the age of 70

Clinical Presentations Classic Sx Classic Sx Renal Colic Renal Colic Hematuria (gross or microscopic in majority if symptoms but not all) Hematuria (gross or microscopic in majority if symptoms but not all) Atypical Sx Atypical Sx Vague abdominal pain, nausea, urinary urgency or frequency, difficulty urinating, penile pain, or testicular pain. Vague abdominal pain, nausea, urinary urgency or frequency, difficulty urinating, penile pain, or testicular pain. Asymptomatic Asymptomatic

Renal Colic Varies from a mild and barely noticeable ache to discomfort that is so intense that requires parenteral analgesics Varies from a mild and barely noticeable ache to discomfort that is so intense that requires parenteral analgesics typically waxes and wanes in severity, and develops in waves or paroxysms that are related to movement of the stone in the ureter and associated ureteral spasm. typically waxes and wanes in severity, and develops in waves or paroxysms that are related to movement of the stone in the ureter and associated ureteral spasm. Paroxysms of severe pain usually last 20 to 60 minutes Paroxysms of severe pain usually last 20 to 60 minutes Pain is thought to occur primarily from urinary obstruction with distention of the renal capsule. Pain is thought to occur primarily from urinary obstruction with distention of the renal capsule.

Stone Composition 80% are Calcium Stones 80% are Calcium Stones Calcium Oxalate (majority) Calcium Oxalate (majority) Calcium Phosphate (Hydroxapetite stones) Calcium Phosphate (Hydroxapetite stones)

Stone Composition Uric acid Uric acid Struvite (magnesium ammonium phosphate) Struvite (magnesium ammonium phosphate) only form in pts with chronic upper UTI d/t urease- producing organism: Proteus or Klebsiella only form in pts with chronic upper UTI d/t urease- producing organism: Proteus or Klebsiella Cystine stones Cystine stones only develop in pts with cystinuria (an AR disorder) due to the poor solubility of cystine in the urine only develop in pts with cystinuria (an AR disorder) due to the poor solubility of cystine in the urine Mixed stone (eg, calcium oxalate and uric acid) Mixed stone (eg, calcium oxalate and uric acid) Other: indinavir, sulfadiazine, triamterene, acyclovir stone Other: indinavir, sulfadiazine, triamterene, acyclovir stone

Risk Factors for Stones Historical Historical Anatomic Anatomic Dietary Dietary Urinary Urinary

Historical Risk Factors Prior History of Kidney Stones Prior History of Kidney Stones 50% recurrence in 10 yrs 50% recurrence in 10 yrs Family History of kidney stones Family History of kidney stones Twofold increase by Health professionals study Twofold increase by Health professionals study Individuals with enhanced enteric oxalate absorption Individuals with enhanced enteric oxalate absorption gastric bypass procedures, bariatric surgery, short bowel syndrome gastric bypass procedures, bariatric surgery, short bowel syndrome Frequent upper urinary tract infections Frequent upper urinary tract infections Excessive physical exertion Excessive physical exertion

Historical RF Medical conditions assoc w/ stones: Medical conditions assoc w/ stones: Primary Hyperparathyroidism, Sarcoidosis Primary Hyperparathyroidism, Sarcoidosis Gout, Obesity, DM (concentrated acidic urine) Gout, Obesity, DM (concentrated acidic urine) HTN HTN RTA RTA Use of medications that may crystallize urine Use of medications that may crystallize urine Indinavir, acyclovir, sulfadiazine, triamterene Indinavir, acyclovir, sulfadiazine, triamterene

Anatomic RF Medullary sponge kidney Medullary sponge kidney Horseshoe kidney Horseshoe kidney

Medullary Sponge Kidney

Horseshoe Kidney

Dietary Risk Factors ? Low or High ? ? Low or High ? Calcium Calcium Fluids Fluids Oxalate Oxalate Protein Protein Salt Salt Sucrose Sucrose

Dietary Risk Factors Low Calcium Intake Low Calcium Intake increases absorption & excretion of oxalate d/t less complexing with calcium in the intestinal lumen increases absorption & excretion of oxalate d/t less complexing with calcium in the intestinal lumen Low fluid intake Low fluid intake Higher concentration of lithogenic factors in urine Higher concentration of lithogenic factors in urine Low potassium Low potassium Low phytate Low phytate

Dietary Risk Factors High oxalate intake High oxalate intake High animal protein intake High animal protein intake leads to hypercalciuria, hyperuricosuria, hypocitraturia, and inc urinary acid excretion leads to hypercalciuria, hyperuricosuria, hypocitraturia, and inc urinary acid excretion High sodium intake High sodium intake High sucrose intake High sucrose intake may increase calcium and/or oxalate excretion may increase calcium and/or oxalate excretion High Vitamin C Intake High Vitamin C Intake

Urinary Risk Factors Low volume Low volume Hypercalcuria Hypercalcuria Hyperoxaluria Hyperoxaluria Hypocitraturia Hypocitraturia Extremes of pH Extremes of pH pH greater than 7.5 is compatible with infection pH less than 5.5 favours uric acid lithiasis. pH greater than 7.5 is compatible with infection pH less than 5.5 favours uric acid lithiasis. Urine culture +ve urease-producing organism (struvite) Urine culture +ve urease-producing organism (struvite) Proteus or Klebsiella Proteus or Klebsiella

Work Up & Treatment Controversial whether evaluation and therapy warranted or cost effective after the first stone or only in patients with: Controversial whether evaluation and therapy warranted or cost effective after the first stone or only in patients with: Active stone disease Active stone disease formation of new stones, increase in size of old stones, or the continued passage of gravel formation of new stones, increase in size of old stones, or the continued passage of gravel Multiple stones at first presentation Multiple stones at first presentation Pts with a strong family history of stones Pts with a strong family history of stones

Approaches Limited Evaluation Limited Evaluation Targeted Evaluation Targeted Evaluation base the extent of evaluation upon an estimation of the risk for new stone formation base the extent of evaluation upon an estimation of the risk for new stone formation Complete Evaluation Complete Evaluation approach should be followed only in individuals willing to make dietary changes or to take medical therapy if warranted by the work-up. approach should be followed only in individuals willing to make dietary changes or to take medical therapy if warranted by the work-up.

Complete Evaluation CBC, lytes, bicarbonate, urea, creatinine CBC, lytes, bicarbonate, urea, creatinine Calcium, phosphorus, PTH, uric acid Calcium, phosphorus, PTH, uric acid Urinalysis for pH and crystals Urinalysis for pH and crystals 24-hr urine: volume, calcium, uric acid, citrate, oxalate, sodium, and creatinine 24-hr urine: volume, calcium, uric acid, citrate, oxalate, sodium, and creatinine At least two 24-hour urine collections At least two 24-hour urine collections while pt maintains usual diet and physical activities while pt maintains usual diet and physical activities wait at least one to three months after a stone event wait at least one to three months after a stone event should not be performed if renal/ureteral obstruction or urinary tract infection from existing calculi. should not be performed if renal/ureteral obstruction or urinary tract infection from existing calculi.

Treatment of Kidney Stones General treatment strategies for all stone formers General treatment strategies for all stone formers Specific treatment strategy is based on: Specific treatment strategy is based on: stone composition if available (assume calcium if not most of the time) stone composition if available (assume calcium if not most of the time) findings from metabolic evaluation findings from metabolic evaluation Patient dietary patterns Patient dietary patterns

General Treatment Increase fluid intake to target u/o > 2L per day Increase fluid intake to target u/o > 2L per day At 5 yrs, incidence of new stone formation 12% v 27% At 5 yrs, incidence of new stone formation 12% v 27% increases urine flow rate and lower urine solute concentration increases urine flow rate and lower urine solute concentration Avoid high animal protein diet Avoid high animal protein diet Avoid high salt diet Avoid high salt diet

Specific Tx – Calcium Stones If hyperoxaluria present, low oxalate diet should be tried first If hyperoxaluria present, low oxalate diet should be tried first primary foods to avoid are spinach and nuts primary foods to avoid are spinach and nuts increasing dietary calcium or adding calcium supplement with meals should be considered in addition to a low oxalate diet if insufficient. increasing dietary calcium or adding calcium supplement with meals should be considered in addition to a low oxalate diet if insufficient. Thiazide diuretic for refractory hypercalciuria Thiazide diuretic for refractory hypercalciuria Potassium citrate for refractory hypocitraturia Potassium citrate for refractory hypocitraturia

Specific Tx – Uric Acid Stones If hyperuricosuria present, lifestyle modification with the aim of reducing uric acid production If hyperuricosuria present, lifestyle modification with the aim of reducing uric acid production decreased purine intake decreased purine intake weight loss should be implemented weight loss should be implemented Allopurinol for refractory hyperuricosuria Allopurinol for refractory hyperuricosuria Potassium citrate to alkalinize urine Potassium citrate to alkalinize urine

Specific Treatment – Cystine Stones urinary alkalinization urinary alkalinization drugs such as tiopronin drugs such as tiopronin

Specific Tx – Struvite Stones typically require complete stone removal with percutaneous nephrolithotomy & aggressive prevention and tx of future UTI’s typically require complete stone removal with percutaneous nephrolithotomy & aggressive prevention and tx of future UTI’s

Monitoring Monitoring w/ US or plain film for new stone formation Monitoring w/ US or plain film for new stone formation initially at one year initially at one year if –ve then every 2-4 yrs based on risk recurrence if –ve then every 2-4 yrs based on risk recurrence not nearly as sensitive for identifying stones as CT, but CT exposes pt to significant amt of radiation not nearly as sensitive for identifying stones as CT, but CT exposes pt to significant amt of radiation

Asymptomatic Stone Balance risk of stone becoming asymptomatic vs. morbidity assoc with therapy Balance risk of stone becoming asymptomatic vs. morbidity assoc with therapy Specific factors will dictate how to manage Specific factors will dictate how to manage stone size and location stone size and location Active surveillance reasonable approach in asymptomatic pts with Active surveillance reasonable approach in asymptomatic pts with small, non-infected calculi small, non-infected calculi no evidence of obstruction no evidence of obstruction not "at risk" for stone episodes (solitary kidney, urinary tract reconstruction, immunosupression, etc) not "at risk" for stone episodes (solitary kidney, urinary tract reconstruction, immunosupression, etc)

What about overall diet? While one can modify diet after one discovers a kidney stone is there any type of diet that prevents kidney stones? While one can modify diet after one discovers a kidney stone is there any type of diet that prevents kidney stones? Any data available? Any data available?

Dash Diet & Kidney Stones Dash-style Diet Associates with Reduced Risk for Kidney Stones Dash-style Diet Associates with Reduced Risk for Kidney Stones Eric Taylor, Teresa Fung and Gary Curhan Eric Taylor, Teresa Fung and Gary Curhan J am Soc Nephrology 20: , 2009 J am Soc Nephrology 20: , 2009 Dietary Approaches to Stop Hyperstension (DASH) Dietary Approaches to Stop Hyperstension (DASH)

Dash Diet & Kidney Stones Examined relationship between DASH-style Diet and incident kidney stones in Examined relationship between DASH-style Diet and incident kidney stones in Health Professionals Follow-up study (n-45,821 men; 18 yr follow up) Health Professionals Follow-up study (n-45,821 men; 18 yr follow up) Nurses’ Health Study (n= 101,837 women; 14 year follow up) Nurses’ Health Study (n= 101,837 women; 14 year follow up) Goal to look at dietary pattern as opposed to individual dietary factors Goal to look at dietary pattern as opposed to individual dietary factors In many cases consuming less of one dietary factor to decrease stone risk may lead to consumption of other factors that increase risk In many cases consuming less of one dietary factor to decrease stone risk may lead to consumption of other factors that increase risk

Dash Diet & Kidney Stones DASH score based on eight components DASH score based on eight components High intake of High intake of Fruits Fruits Vegetables Vegetables Nuts and legumes Nuts and legumes Low-fat dairy products Low-fat dairy products Whole grains Whole grains Low intake of Low intake of Sodium Sodium Sweetened beverages Sweetened beverages Red and processed meats Red and processed meats

Dash Diet & Kidney Stones Pts with higher DASH scores had Pts with higher DASH scores had higher intakes of calcium, potassium, magnesium, oxalate and vitamin C higher intakes of calcium, potassium, magnesium, oxalate and vitamin C lower intakes of sodium lower intakes of sodium Participants in highest compared to lowest quintile of DASH score had an adjusted relative risk of 0.55 in men and in women for kidney stones Participants in highest compared to lowest quintile of DASH score had an adjusted relative risk of 0.55 in men and in women for kidney stones Robust despite adjustments & substantial differences in individual dietary factors and risk between men and women Robust despite adjustments & substantial differences in individual dietary factors and risk between men and women

Dash Diet & Kidney Stones Study Conclusion Study Conclusion “consumption of DASH style diet is associated with marked decrease in kidney stone risk” (though limited as cohort study) My conclusion: My conclusion: I AM IN BIG TROUBLE ! I AM IN BIG TROUBLE !

Take Home Points Kidney Stones are fairly common Kidney Stones are fairly common CT KUB is best test for diagnosis in acute setting CT KUB is best test for diagnosis in acute setting Most acute renal colic tx conservatively Most acute renal colic tx conservatively Focus on risk factors in work up to guide investigations Focus on risk factors in work up to guide investigations Drink lots of fluids and eat healthy DASH style diet Drink lots of fluids and eat healthy DASH style diet