Urolithiasis (1 of 11)

1 Patient presents w/ lower urinary tract symptoms (LUTS) suggestive of urolithiasis

DIAGNOSIS No ALTERNATIVE Is urolithiasis DIAGNOSIS conﬁ rmed?

3 CLASSIFY THE TYPE OF KIDNEY STONES

Calcium Struvite or Urate Calcium oxalate Cystine infection containing phosphate stones stones stones stones stones

A Non-pharmacological A Non-pharmacological therapy therapy • Watchful waiting • Watchful waiting • Diet therapy TREATMENT • Diet therapy B Pharmacological therapy See next page B Pharmacological therapy • Alkaline citrate • iazide diuretic • Allopurinol (Hydrochlorothiazide) • Sodium bicarbonate C Surgery • iazide diuretic D Follow-up (Hydrochlorothiazide) C Surgery D Follow-up© MIMS

Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B1 © MIMS 2019 UROLITHIASIS URATECONTAINING KIDNEY STONES KIDNEY TREATMENT OF CYSTINE STONES CYSTINE © MIMS STONES INFECTION STRUVITE OR OR STRUVITE Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not STONES Speciﬁ c prescribing information may be found in the latest MIMS. latest the in found be may information Speciﬁc prescribing Urolithiasis (2of11) B2 D C B A D C B A D C B A

• • • therapy Pharmacologic • • therapy Non-pharmacological Follow-up Surgery • • • therapy Pharmacological • • therapy Non-pharmacological Follow-up Surgery • • • therapy Pharmacological • • therapy Non-pharmacological Follow-up Surgery Tiopronin bicarbonate Sodium Alkaline citrate or therapyDiet Watchful waiting Sodium bicarbonate Sodium Allopurinol Alkaline citrate therapyDiet Watchful waiting bicarbonate Sodium Antibiotics Acetohydroxamic acid therapyDiet Watchful waiting © MIMS 2019 • • • • • • History • • • • • Vegetables purines &highintake ofanimal-derived - intake offruits Limited - intake Highsodium - fl Low uid intake - intake Calcium that orsignifi isbelow (RDA) allowance cantly the dietary recommended above - w/stonediseases: associated factors Nutritional &vegetables Fruits - highoxalate-containing sodium, Calcium, food - &snacks) (meals habits Eating - Average dailyintake offluids (amount &specifi - c beverages) ofthe patient: history Dietary kidney Solitary - stones Infection - Uric acid&urate-containing stones - Brushite-containing (calcium stones hydrogen phosphate) - Familial stoneformation - inchildren ofurolithiasis (especially &teenagers) onset Early - factors: General Cystic fibrosis - syndrome Lesch-Nyhan - hyperoxaluria Primary - Renal tubular (RTA acidosis 1) type - Xanthinuria - 2,8Dihydroxyandeninuria - B&AB) A, Cystinuria (type - that genetic predisposition: Family may reveal history &treatments evaluations interventions, studies, imaging Previous - ofepisodes &frequency Number - records shouldinclude: ofmedical orough review the from patient elicited shouldbe history A detailed - w/urolithiasis are: associated tractsymptoms urinary Lower among malepatients disorder that urologic ahighrecurrence occursPainful in12%of ratethe & has globalpopulation of71-80% that the radiates from flank tothe ortothe groin genital &inner area thigh intermittent inthe ofexcruciating, isthe ureter ehallmark &renal ofobstruction sudden pain onset pelvis inthe stones kidney, bladder &/orurethra eformation ofurinary - Genetic - Dietary - Ethnic - Climatic - Geographical - Stone factors: incidence onthe following depends ormicroscopic) Hematuria (gross - Dysuria - Urge incontinence -

Urgency © MIMS Frequency Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Speciﬁ c prescribing information may be found in the latest MIMS. latest the in found be may information Speciﬁc prescribing Urolithiasis (3of11) 1 2 UROLITHIASIS DIAGNOSIS B3 © MIMS 2019

UROLITHIASIS • • • (Cont’d)History • • • • • tests Diagnostic • examination Physical - Ureteral stricture - calyceal cyst diverticulum, Calyceal - obstruction Ureteropelvic junction (UPJ) - (tubular ectasia) kidney sponge Medullary - w/stoneformation: associated Anatomical abnormalities &intestinal resection bypass tojejunoileal Due - Sarcoidosis - Nephrocalcinosis - orpancreatic disease Bowel - surgery Bariatric - hyperparathyroidism Primary - disease Bone - 2 mellitus type Diabetes - I Renal tubular type acidosis - Hyperparathyroidism - Gout - Obesity - w/stonedisease: associated Conditions inhibitors(eg anhydrase Topiramate, Carbonic Acetazolamide, Zonisamide) - Vitamins C&D - Chemotherapy - Triamterene - inhibitors Lipase - inhibitors protease Some - Probenecid - include: medications stone-provoking obtained; & supplements vitamins should be well as as & over-the-counterComplete list of current prescription drugs, - whileconsuming twosamples At are collected, their &volumeoffl least usualdiet uid - ecornerstone forwhich the therapeutic recommendations are based - testing collection/metabolic 24-hour urine that are pathognomonic ofstonetype) of crystals &identifi pH,indicators ofinfection (urinary microscopic evaluation shouldincludeUrinalysis dipstick, cation PTH in patients w/elevated Ddefi of vitamin out the topossibility rule investigated of 25-hydroxy be Level D should also vitamin ciency concentration calcium &urine serum ifthere orelevated ishighnormal measured shouldbe Parathyroid level (PTH) hormone acid)to uncover orrenal& uric hypokalemia tubular (RTA) acidosis creatinine, calcium, bicarbonate, chloride, potassium, (eg shouldinclude sodium, chemistries electrolytes Serum &gout inthe assessment hyperparathyroidism (HPT) ofprimary signs as well as pressure, costovertebralShould extremity &lower include angletenderness edema, the blood weight, - kidney Horseshoe - - - - testing urine patients considered forreferral shouldbe ese &/orspecialized forgenetic testing -

Vesico-uretero-renal-refl ux & creatinine potassium oxalate, acid,citrate, totalvolume,pH,calcium, uric sodium, should analyze testing Metabolic Ureterocele to gauge compliance regimens w/medication follow-up, during obtained potassium compared be tourinary can at baseline measured potassium Urinary of cystinuria or for those in whom cystinuria issuspected inwhomcystinuria orforthose of cystinuria history orafamily stones cystine w/known instoneformers measured shouldadditionallybe cystine Urinary bowel dysfunction bowel w/o mg/day inadults oxalate excretion 75 exceeds when urinary suspected shouldbe hyperoxaluria Primary © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing 2 DIAGNOSIS (CONT’D) Urolithiasis (4of11) B4 © MIMS 2019

UROLITHIASIS • • • • • offormation Etiology • • X-ray characteristics • Location • Size Classifi stones ofurinary cation • • Scan CT Low-Dose • • • • NCCT flEvaluation ofpatient w/acute ank pain • • • Ureter radiography (KUB) &Bladder Kidneys, • • (UTZ) Ultrasound • • • Imaging • cases non-emergency in analysis laboratory Basic • • • • cases emergency in analysis laboratory Basic (Cont’d) tests Diagnostic regrowth &isimperative fortheregrowth choice treatment of pharmacological defi it will because statusRisk assessed ofthe should be stone formers ne the probability ofrecurrence or Further &management onthe tests composition diagnostic depends ofthe stone © xanthine, 2,8dihydroxyadenine) (eg causes cystine, Genetic (eg ammoniumphosphate, apatite, carbonate Infectious magnesium, ammoniumurate) (eg oxalate, acid) phosphate,Non-infectious calcium uric calcium according stones todensity, toclassify isused structure &composition NCCT mineral composition Classifi accordinged toplainX-ray radiography), (KUB) according appearance (eg to kidney-ureters-bladder bladder ureters &urinary Classifi upper, accordinged upper, renal toanatomical position: pelvis, middleordistal calyx, middleorlower MIMSlargest diameter Usually inoneortwodimensions given &isstratifi upto 5,5-10,10-20&20mmin measuring tothose ed inpatients stones ureteric w/aBMIof<30 todetect Used reduce radiationCan risk acid&xanthine uric stone that detect are radiolucentCan onplainfilms (SWL) lithotripsy shockwave extracorporeal the diameter, to determine Used density, distance that inner structure & skin-to-stone aff the outcome of ects patients w/acuteurolithiasis Significantly more accurate inevaluating than intravenous (IVP) pyelogram urethrogram (IVU)/intravenous First choice inconfi inpatients stonediagnosis w/acuteflrming ank pain considered isbeing (NCCT) scan ifnon-contrast CT performed Should not be forcomparison follow-up Used during indiffHelpful erentiating radiolucent &radiopaque stones tractdilatation urinary upper Identifi &inpatients w/ &vesicoureteric pyeloureteric junctions, pelvis, presence inthees ofstones calices, tool diagnostic the primary as Used todiffUsed erentiate renal from ureteral stones stones isdoubtful &when diagnosis kidney orsolitary forpatientsIndicated w/fever onthe situation clinical depend ofthe will Choice patient modality ofimaging omitted coagulation be timecan & blood work-upBiochemical issimilarforallpatients butifthere intervention, then isnoplanned sodium, ifintervention islikely orplanned Coagulation test, cell countBlood &potassium) sodium sample calcium, (eg acid,ionized creatinine, blood uric Serum sample, &/orculture) microscopy urine Urine urine (eg ofspot dipstick test 3 CLASSIFICATION & ANALYSIS OF STONES 2 DIAGNOSIS (CONT’D) Urolithiasis (5of11) B5 potassium, potassium, © MIMS 2019

UROLITHIASIS UROLITHIASIS • • stones Uric urate &ammonium acid • • stones orinfection Struvite • (oxalate stones &phosphate) Calcium • • • (oxalate stones &phosphate) Calcium Stone types • • ofstonecomposition Analysis • • • stones &xanthine 2,8-Dihydroxyandenine stones stonetypes Other • • stones Cystine - gout &catabolism drugs, tumor syndrome, lysis disorders, myeloproliferative (enzyme endogenous defects), excess, overproduction duetodietary may be Hyperuricosuria pH urinary orlow w/hyperuricosuria Associated obstruction Uteropelvic junction (UPJ) - diverticulum Caliceal - Cystocele - diverticulum Bladder - prostatic hyperplasia Benign - Urethral stricture - catheter Indwelling urinary - Stone disease - Foreign body - conduit Ileal - diversion Continent urinary - Spinal cord orparalysis injury - Neurogenic bladder - forstoneformation: factors Predisposing bacteria w/urea-splitting infected onpre-existing stones orgrow denovo May originate Enteric hyperoxaluria - hyperoxaluria Primary - Sarcoidosis (granulomatous disease) - disease Kidney - hyperparathyroidism Primary - Nephrocalcinosis - Renal tubular acidosis - condition) (inherited Hypercalciuria - &disorders related stones: tocalcium Diseases either as large orrough &smooth &spiky Characterized Formed when inthe there ofcalcium urine ishighlevel stone ofkidney commonMost type since stonecomposition may period change overtime stone-free aprolonged recurrence after Late - interventional recurrence therapy Early after w/complete stoneclearance - intervention pharmacological Recurrence after - of: incases isneeded stoneanalysis Repeat &X-ray (IRS) spectroscopy diﬀ are infrared procedures analytical Preferred stones ofurinary raction analysis Decreased levels of serum uric acid are seen inpatients xanthine acidare whoforms seen uric stones ofserum levels Decreased excretion that highurinary transferase causes ofadenine phosphoribosyl defect determined Genetically were rare issimilartothat &the acid diagnosis ofuric stonetypes Both ofcystinuria manifestations areClinical the sameforpatients type whoare orphenotypic genotypic pHat 6.0 w/inthe urinary physiological spontaneously &crystallizes Poorly inurine soluble Forms acidstones) &<5.5(uric inthe at urine pH<6.5(ammonium urate crystals) -

laxative abuse, potassium deﬁ abuse, potassium laxative ciency, &malnutrition hypokalemia w/inﬂAmmonium urate are rare stones &are associated diversion, ileostomy (IBD), disease bowel ammatory

Methoxyﬂ urane compounds ofthe drug duetounfavorable composition therapy changes under inurine drug theStones formed &by crystallized

© MIMS 3 CLASSIFICATION & ANALYSIS OF STONES (CONT’D) STONES OF &ANALYSIS CLASSIFICATION Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Urolithiasis (7of11) B7 © MIMS 2019 UROLITHIASIS • • • Tiopronin • • • bicarbonate Sodium • • • (Hydrochlorothiazide) diuretics iazide • • Chlorthalidone • • • Allopurinol • • • • &Potassium) (Sodium citrate Alkaline • • • • • therapy Diet • • Watchful Waiting thrombocytopenia anemia aplastic or agranulocytosis, ofdeveloping inpatients history Contraindicated w/prior calculi the inthe &reduces formation urine ofcystine the amount cystine ofsoluble It decreases disulfi de agentAn activereducing that undergoes athiol-disulfi atiopronin-cystine &forms de exchange w/cystine pain abdominal &unknown hypocalcemia edema, pulmonary severe hypernatremia, inpatientsContraindicated w/alkalosis, pH urinary the desired the &totitrate toachieve toalkalinize urine theUsed dose concentration the hydrogen which neutralizes ion ions, bicarbonate toprovide dissociation pHby &urinary blood Raises drugs toother sulfonamide-derived anuria inpatients &hypersensitivity Contraindicated w/known treatment stonerecurrence &calcium as Used forhypercalciuria & hydrogen ionsincreases water, the excretion ofsodium, aresult, inthe distaltubules &as reabsorption the sodium Inhibits potassium drugs toother sulfonamide-derived anuria inpatients &hypersensitivity Contraindicated w/known the ionsacross renal tubular ofsodium epitheliuminterfering w/the transport A long-actingantihypertensive/diuretic that enhances ions&water chloride the by excretion ofsodium, in patientsContraindicated w/idiopathic hyperuricemia hemochromatosis &asymptomatic acidnephropathyuric oxalate, &treatment acidorcalcium renal prophylaxis duetouric inthe calculi prevention ofgout, Used of purines ofvital the biosynthesis acidw/odisrupting ofuric the &reduces xanthine production Inhibits oxidase damage myocardial & severe untreated Addison’s renal in patientsContraindicated impairment orazotemia, w/severe w/oliguria disease Eff the incorrecting ofcertain acidosis renalective tubular disorders agents anadjuvant w/uricosuric as ingout therapy used Also formation calculi acidorcystine toprevent uric used alkalinizer A urinary counseled to: shouldbe acidstones ofuric Patients w/ ahistory - animalprotein may the intakeLimiting help reduce ofnon-dairy stonerecurrence RTA, by Promoted inhibitor anhydrase chronic &carbonic diarrhea - of20-60% w/aprevalence iscommon amongpatients w/stonedisease, Hypocitrituria - &vegetables the intake offruits Increase the consumption &maintain intake calcium Limit normal ofoxalate-rich foods inthe diet absence calcium Lower ofother specifi the ofstoneformation risk increases measures c dietary - intake &consume day sodium 1,000-1,200mgper Limit tohave afl areAll stoneformers advised 2.5liters daily volumeofatuid intake aurine least that achieve will analysis w/fiA collection kitisprovided & stonefortesting lter &the patient tocollect the passed isinstructed urination, that usuallyhappens w/in2-3days Since the through forthe are 5mminsize, patientofstones small,about passage stones normal most isadvised

- Reduce the urinary acidity Reduce the urinary - thepH urine Increase - the intake the ofacids intake ofalkali&decrease Increase - © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing A B NON-PHARMACOLOGICAL THERAPY PHARMACOLOGICAL THERAPY Urolithiasis (8of11) B8 © MIMS 2019 UROLITHIASIS • • • • Nephrolithotomy (PNL) Percutaneous • • • (SWL) Lithotripsy Shockwave Extracorporeal • • • stoneremoval: in problemsencountered Special • • • • • • • ofstones: removal foractive Indications • • • • &Flexible (URS) -Rigid Lithotripsy Uteroscopic - w/PNL: Complications associated Pregnancy - Potential tumour malignant kidney - Tumour inthe presumptive access tractarea - Untreated UTI - Patients on anticoagulant therapy - Contraindications include: Different &fl rigid onthe preference inthis &itdepends procedure are used endoscopes exible ofthe surgeon Standard forlarge procedure renal calculi Uncontrolled UTIs - obesity Severe - skeletal malformations Severe - Infection - diathesis Bleeding - distaltothe stones Anatomical destruction - aneurysms Arterial - Contraindications include: Performance ofSWL - Patient’s habitus - ofthe composition Size, stones &location - Success onthe effi depends factors: ofthe &some lithotriper cacy &the procedure, &non-aesthetic fiA non-invasive rst choice oftreatment <1.5cm forstonesize Patients obstruction w/UPJ kidneys Patient horseshoe has Presence stones ofcaliceal diverticulum Symptomatic (eg stones presence ofpain&hematuria) waiting ofwatchful aperiod Stone of≥6mmafter size Patients stoneformers whoare high-risk stones by caused Obstruction (egInfection pyelonephritis) obesity, dyslipidemia&gout) Comorbidity (eg diabetes, hypertension, Choice oftreatment orpatient preference Stone-free rate statusStone-free earlier w/URS w/larger isachieved stones disorders &obese inchildren, stones w/bleeding those tumors, strictures, treatment large too stones for ESWL, previous in patients attempts, maywho had used failed URS be intravenous under alocal, orgeneral anesthesia performed be Can SWL analternative treatment &renal as ureteric forboth stones that procedure to A minimallyinvasive isused Steinstrasse - Problems stones duetoresidual - leakage Urinary - Bleeding -

Fever - When large stones fragments are present, shockwave lithotripsy isindicated lithotripsy When shockwave large are present, fragments stones - &fever, w/UTI nephrostomy For isindicated percutaneous associated steinstrasse - treatment then conservative isthe initialoption Ifasymptomatic, - formation isthe ofthe size stone forits factor Major - Accumulation orstonegravel ofstone fragments inthe ureters - © MIMS Urolithiasis (9of11) C SURGERY B9 © MIMS 2019 UROLITHIASIS • • • • • • • • Allopurinol abdominal imaging, renal UTZ or low-dose CT scan) CT orlow-dose renal UTZ imaging, abdominal (eg on stone activity plain formation based or new stone growth studies to assess imaging Obtain follow-up prevent such occurrences to strategies organisms &utilize w/urease-producing forre-infection stones Monitor patients w/struvite totreatment inpatients notresponding when available, especially stoneanalysis, Repeat eﬀ foradverse Assess inpatients therapy onpharmacological ects &vegetables the patient intakeAdvise offruits toincrease testing blood Obtain periodic patient’s Assess adherence response &metabolic - onthe stoneactivity depending annually obtained orw/ greater frequency, should be specimen a24-hr urine the initialAfter follow-up, therapy &/ormedical todietary the response Assess - w/in5mths stone-formers the initiation forknown after oftreatment specimen Obtain asingle24-hrurine Drug

200-300 mg PO 12-24hrly 200-300 mgPO Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not HYPERURICEMIA &GOUTPREPARATIONS Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Dosage Guidelines Urolithiasis (10of11) D FOLLOW-UP B10 • • Instructions Special • Reactions Adverse & asymptomatic hyperuricemia & asymptomatic idiopathic suppression, marrow hemochromatosis bone in patientsContraindicated w/liver disease, acidclearance uric w/poor &those disease Use w/caution hepatic/renal inpatients w/known disturbances) Other eff fever, (arthralgia, &taste visual ects anemia); &aplastic hemolytic thrombocytopenia, effHematological (leucopenia, ects effCNS vertigo, (headache, drowsiness); ects GIeff maculopapular rash); pruritus, (N/V); ects effDermatological (exfoliative dermatitis, ects Remarks © MIMS 2019 UROLITHIASIS Tiopronin balsamifera Leaf) (Blumea Sambong Potassium citrate Drug OTHER DRUGS ACTING ON THE GENITO-URINARY SYSTEM OTHER DRUGSACTINGONTHEGENITO-URINARY Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All

© MIMS 24hrly PO Average 1000mg dose: 8 hrly 800mgPO dose: Initial 8hrly 1,000 mgPO 8hrly PO 60mEq hypocitraturia: Patients w/severe 8hrly PO 30mEq hypocitraturia: Patients w/mild Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Please see end of this section for the reference list. reference the for section this of end see Please Dosage Guidelines Urolithiasis (11of11) • • Instructions Special • Reactions Adverse • Instructions Special • Reactions Adverse • • • Instructions Special • Reactions Adverse from thisfrom medication that developed has anemiaaplastic orthrombocytopenia agranulocytosis, inpatientsContraindicated w/known while takingthis medication Patient should continue 3liters offl at drinking least uid test) ANA positive lymphadenopathy, syndrome, ofsmell,loss lupus-like hypersensitivity, serpiginosa, Others (elastosis perforans infi pulmonary pharyngitis, distress); respiratory ltrates, edema, laryngeal hemoptysis, dyspnea, (bronchiolitis, eff proteinuria); Respiratory syndrome, ects eff nephrotic (Goodpasture’s hematuria, syndrome, ects Renal weakness); myasthenia gravis, myalgia, (arthralgia, Neuromuscular &skeletal eff tests); liver function ects Hepatic effthrombocytopenia); (jaundice,ects abnormal leukopenia, eosinophilia, bleeding, (anemia, eff Hematological perception, oralulceration, N/V); ects fl diarrhea, bloating, anorexia, atulence, oftaste loss GIeff warts); urticaria, wrinkling, pain, (abdominal ects skinfriability/ rash, pruritus, pemphigus, (bruising, effCNS eff Dermatological fever); fatigue, (chills, ects ects ofrenal signs obstruction shows that urogram Use w/caution inpatients w/excretory GI eff N/V, discomfort, (abdominal ects diarrhea) anticholinergic emptying therapy gastric &w/slow patientsintestinal whohave obstruction, to submitted ulcer, activepeptic alkalosis, ormetabolic respiratory adrenal insuffi hyperpotassemia, tract, urinary ciency, ofthe obstruction infections, persistent alkalineurinary in patientsContraindicated w/renal insufficiency, excretion &renal mechanism insufficiency Use w/caution inpatients potassium w/altered intake offluids toincrease insalt&isadvised low Should adiet follow GI eff N/V, discomfort, (abdominal ects diarrhea) B11 Remarks © MIMS 2019