Urinary Tract Urinary Tract Infections Infections &&

Tubulointertitial Tubulointertitial DiseasesDiseases

Dr Y-AtaipourDr Y-Ataipour

IUMSIUMS

Hashemi-Nejad HospitalHashemi-Nejad Hospital

EpidemiologyEpidemiology

More commom in female than maleMore commom in female than maleIn infants & elderly more common in malesIn infants & elderly more common in males

ABUABU in 5% of women ( 20-40 years old ) in 5% of women ( 20-40 years old ) 5050 – – 80%80% of women acquire at least one of women acquire at least one

episode of UTI during their lifeepisode of UTI during their life . .2020 – – 30%30% of UTI in women become of UTI in women become

recurrentrecurrentEarly recurrent ( in 2 wks ) = Early recurrent ( in 2 wks ) = relapserelapse

Etiology ( uropathogen )Etiology ( uropathogen )

UTI is caused usually by enteric UTI is caused usually by enteric g g neg rodsneg rods

In cystitis In cystitis E coli E coli in in 75 – 90%75 – 90% Staph saprophyticus in Staph saprophyticus in 5 – 15%5 – 15% Klebsiella , proteus , enterococcus, Klebsiella , proteus , enterococcus,

citrobacter in citrobacter in 5 – 10%5 – 10% In pyelonephritis also In pyelonephritis also E coli E coli is is

commoncommon microorganism . microorganism .

Recurrent UTIRecurrent UTI ReinfectionReinfection UTI UTI

RelapsingRelapsing UTI UTI

UTIUTI

Symptomatic ( Symptomatic ( ABUABU ) )

AsymptomaticAsymptomatic

UTIUTI

Upper UTIUpper UTI Acute pyelonephritisAcute pyelonephritis Acute prostatitisAcute prostatitis Perinephric abcessePerinephric abcesse Intrarenal abcessIntrarenal abcess Lower UTILower UTI CyctitisCyctitis UrethritisUrethritis

UTIUTI

Community aquired (non-catheter )Community aquired (non-catheter )

Nosocomial ( catheter associated )Nosocomial ( catheter associated )

UTIUTI

ComplicatedComplicated

UncomplicatedUncomplicated

Uncomplicated UTIUncomplicated UTI

Normal urinary tractNormal urinary tract Normal renal functionNormal renal function Nonvirulent pathogens ( Nonvirulent pathogens ( E.coliE.coli ) )

Complicated UTIComplicated UTI

Urinary tract abnormalitiesUrinary tract abnormalities Impaired host defence ( Impaired host defence ( DMDM ) ) Virulent pathogensVirulent pathogens Proteus Proteus , , Pseudomonas Pseudomonas ,,StaphStaph Renal failureRenal failure

UTIUTI existes when more than 100000existes when more than 100000 bacteria per ml of urine is bacteria per ml of urine is

detected.detected.

In In symptomatic symptomatic patients bacterial patients bacterial count ofcount of

100-10000 may signifays infection. 100-10000 may signifays infection.

Multiple bacteria in culture= Multiple bacteria in culture= contamination.contamination.

Acute urethralAcute urethral syndromesyndrome:dysuria,frequency:dysuria,frequency without significant without significant

bacteriuria.bacteriuria.

Sterile PyuriaSterile Pyuria

Recently treated UTI (<2 wk ) & Partially treated Recently treated UTI (<2 wk ) & Partially treated UTIUTI

ProstatitisProstatitis CalculiCalculi Interstitial nephritisInterstitial nephritis Lupus NephritisLupus Nephritis Polycystic kidneyPolycystic kidney AppendisitisAppendisitis Chemical cystitisChemical cystitis Bladder tumorBladder tumor Papillary NecrosisPapillary Necrosis Acute RejectionAcute Rejection

Risk Factors For UTIRisk Factors For UTI

Urinary Tract ObstructionsUrinary Tract Obstructions Female genderFemale gender PregnancyPregnancy DMDM Sexual intercoursSexual intercours ImmunosuppressionImmunosuppression StoneStone CatheterCatheter Urinary tract malformationUrinary tract malformation Decreased host defenceDecreased host defence

Pathogenesis of UTIPathogenesis of UTI

AscendingAscending of bacteria from periurethral of bacteria from periurethral area to the bladder is most area to the bladder is most

commoncommon mechanism of UTI ( mechanism of UTI ( g- bacillig- bacilli ). ).

HemategenousHemategenous access of bacteria to the access of bacteria to the kidneys is seen in kidneys is seen in staph aureusstaph aureus

pyelonephritispyelonephritis

Host Defences in UTIHost Defences in UTI

Flushing & dilutingFlushing & diluting effect of urine effect of urine

Antibacterial effect of urine & bladderAntibacterial effect of urine & bladder mucosamucosa

High urea concentration & high osmolarityHigh urea concentration & high osmolarity of urineof urine Prostatic secretions have antibacterial propertiesProstatic secretions have antibacterial properties

Bladder epithelial cells secrete cytokines & chemokinesBladder epithelial cells secrete cytokines & chemokines as as IL6 , IL8IL6 , IL8 which interact with bacteria causing which interact with bacteria causing

PMNPMN to enter to the bladder epithelia to clear bacteriato enter to the bladder epithelia to clear bacteria

Conditions affecting Conditions affecting pathogenesispathogenesis

PregnancyPregnancy;UTI seen in 2-8% of pregnants;UTI seen in 2-8% of pregnants 20-30% of asymptomatic bacteriuria will20-30% of asymptomatic bacteriuria will end to acute pyelonephritis.end to acute pyelonephritis. ObstructionObstruction NeurogenicNeurogenic BladderBladder VURVUR Sexual activitySexual activity Bacterial virulenceBacterial virulence Genetic FactorsGenetic Factors

Bacterial VirulenceBacterial Virulence E.coli strains causing symptomatic UTIE.coli strains causing symptomatic UTI belong to belong to OO , , KK , , H H serogroups havingserogroups having virulence virulence genesgenes.. Bacterial Bacterial adherenceadherence to uroepithelial cells is to uroepithelial cells is critical step .critical step . Bacterial Bacterial fimbriafimbria mediate this attachement mediate this attachement to specific to specific receptorsreceptors on epithelial cell, on epithelial cell, causing causing IL6IL6 & & IL8IL8 production. production. Uropathogenic E.coli also produces the cytokinesUropathogenic E.coli also produces the cytokines like like HemolysinHemolysin & & aerobactinaerobactin resistant to resistant to

bactericidalbactericidal action of serum.action of serum.

Genetic FactorsGenetic Factors

Positive Positive maternal Hxmaternal Hx existes in some pts existes in some pts P fimbriaeP fimbriae mediate attachement of mediate attachement of

E.coliE.coli to P-positive RBC can causeto P-positive RBC can cause PyelonephritisPyelonephritis

P-negative groups have lower risk ofP-negative groups have lower risk of PyelonephritisPyelonephritis

Bacterial clonizationBacterial clonization

LactobacilliLactobacilli as a normal vaginal flora could as a normal vaginal flora could protect against the initiation of UTI by :protect against the initiation of UTI by : maitenance of an maitenance of an acidic vaginal acidic vaginal

enviromentenviroment which diminishes which diminishes E.coli clonizationE.coli clonization , , interfering with the interfering with the adherance of adherance of

uropathogensuropathogens , , producing the producing the H2O2H2O2 . . production of production of antibacterialantibacterial agents . agents .

Bacterial clonizationBacterial clonization

In post menopausal women , because the lackIn post menopausal women , because the lack of of estrogenestrogen , they have higher , they have higher PH PH in the in the vagina, fewer vagina, fewer LactobacilliLactobacilli ,and higher risk ,and higher risk of clonization of uropathgens ( of clonization of uropathgens ( E.coli E.coli ))

Estrogen replacementEstrogen replacement can reduce incidence can reduce incidence of UTI in post menopausal women .of UTI in post menopausal women .

Acute PyelonephritisAcute Pyelonephritis Complicated UTIComplicated UTI Emergency state needing hospitalizationEmergency state needing hospitalization High fever , chills(shaking) , flank pain , toxic High fever , chills(shaking) , flank pain , toxic

appearance appearance CVA tendernessCVA tenderness, dysuria , frequency, dysuria , frequency Superimposing on pregnancy, ObstructionSuperimposing on pregnancy, Obstruction Complications : Complications : SepticemiaSepticemia, Renal failure, Renal failure Fetal growth retardationFetal growth retardation AbortionAbortion

Acute Pyelonephritis Acute Pyelonephritis (Diagnosis)(Diagnosis)

Clinical (signs & symptoms )Clinical (signs & symptoms ) Leukocytosis , Leukocyturia, Leukocytosis , Leukocyturia, BacteriuriaBacteriuria Urine culture , blood cultureUrine culture , blood culture UltasonographyUltasonography

Acute Acute pylonephritis(therapy)pylonephritis(therapy)

Parenteral AntibioticsParenteral Antibiotics cephalosporines (3cephalosporines (3rdrd generation ) generation ) QuinolonesQuinolones

Other types of Other types of pyelonephritispyelonephritis

Emphysematous Emphysematous pyelonephritis (in pyelonephritis (in DM)DM)

XantogranulomatousXantogranulomatous pyelonephritis pyelonephritis in Stag hornin Stag horn

stone with stone with UTIUTI

Acute CystitisAcute Cystitis

More common in young femalesMore common in young females Symptoms more than signsSymptoms more than signs Low grade fever, Low grade fever, dysuria, frequencydysuria, frequency suprapubic painsuprapubic pain Can presente as Can presente as gross Hematuriagross Hematuria Hony moon cystitisHony moon cystitis Treatment(ciprofloxacin,co-tri Treatment(ciprofloxacin,co-tri

moxasol)moxasol) Nitrofurantoin, Nalidixic acideNitrofurantoin, Nalidixic acide

Acute UrethritisAcute Urethritis

GonococcusGonococcus ChlamydiaChlamydia E.coliE.coli Staph. SarophyticusStaph. Sarophyticus HSVHSV

Acute UrethritisAcute Urethritis

DysuriaDysuria FrequencyFrequency Urethral DischargeUrethral Discharge Fever & Chills ( Fever & Chills ( gonococcal gonococcal ))

Acute Acute Urethritis(Treatment )Urethritis(Treatment )

Chlamydial : Azithromycin: 1 gr in a Chlamydial : Azithromycin: 1 gr in a single dosesingle dose

Doxycycline: 100 mg BID for 7dayDoxycycline: 100 mg BID for 7day

GonococcalGonococcal :Ciprofloxacin :Ciprofloxacin CefiximeCefixime

Acute ProstatitisAcute Prostatitis

Usually in young males ( E.coli , Usually in young males ( E.coli , Klebsiella )Klebsiella )

Fever , Chills, dysuriaFever , Chills, dysuria Perinial discomfortPerinial discomfort Tense ,boggy and tender prostate on Tense ,boggy and tender prostate on

RE .RE .

Treatment : CiprofloxacinTreatment : Ciprofloxacin 33rdrd generation cephalosporin generation cephalosporin Imipenem , AminoglycosideImipenem , Aminoglycoside

Perinephric AbcessPerinephric Abcess

Complication of pyelonephritisComplication of pyelonephritis SepticemiaSepticemia ResistantResistant UTI to medical treatment UTI to medical treatment PersistantPersistant Fever Fever Diagnosed by Diagnosed by ultrasoundultrasound study study Treatment : Treatment : Surgical drainageSurgical drainage + +

AntibioticsAntibiotics

Catheter associated UTICatheter associated UTI

Treatment of symptomatic patients .Treatment of symptomatic patients .

Sterile closed system .Sterile closed system .

Attention to aseptic technique.Attention to aseptic technique.

Topical periurethral antimicrobial ointmentTopical periurethral antimicrobial ointment If If CandidaCandida is detected in urine : is detected in urine : RemoveRemove catheter catheter

Prevevtion of Recurrent Prevevtion of Recurrent UTI(prophylaxy)UTI(prophylaxy)

Low doseLow dose& long term antibiotics& long term antibiotics Single dose Single dose antibiotic for females antibiotic for females

( post coital )( post coital ) Co trimoxsasol , fluquinolon , Co trimoxsasol , fluquinolon ,

nitrofurantoin nitrofurantoin

Urinary Tract Infections & Urinary Tract Infections & AINAIN

Dr : Y _ AtaipourDr : Y _ AtaipourHashemi Nejad HospitalHashemi Nejad Hospital

TUMSTUMS

TIN )TIN )) ) Tubulointerstitial Tubulointerstitial NephritisNephritis

AllergicAllergic ( mostly drug induced ) ( mostly drug induced ) SjogrenSjogren syndrome syndrome TIN with TIN with UveitisUveitis TIN in SLETIN in SLE GranulomatousGranulomatous Interstitial Nephritis Interstitial Nephritis Infection associated AINInfection associated AIN Crystal depositionCrystal deposition Light chain Light chain cast nephropathycast nephropathy LymphomatousLymphomatous infiltration infiltration IdiopathicIdiopathic AIN AIN

Allergic AIN ( acute )Allergic AIN ( acute ) AntibioticsAntibiotics : : beta-lactambeta-lactam, sulfonamides , , sulfonamides , quinolones, rifampicinquinolones, rifampicin ethambutal, vancomycinethambutal, vancomycin erythromycin, acyclovirerythromycin, acyclovir NSAIDNSAID DiureticsDiuretics AnticonvulsantsAnticonvulsants : phenytoin , valporate : phenytoin , valporate carbamazepine,phenobarbitalcarbamazepine,phenobarbital MiscellaneousMiscellaneous : proton pump inhibitors,H2 bloc : proton pump inhibitors,H2 bloc allopurinol , captoprilallopurinol , captopril

Infection associated AINInfection associated AIN

Bacterial : strep , staph , legionella, Bacterial : strep , staph , legionella, salmonellasalmonella

Brucella , E coliBrucella , E coli Viral : EBV , CMV , HIV, polyomaViral : EBV , CMV , HIV, polyoma HantavirusHantavirus Miscellaneous : leptospira , Miscellaneous : leptospira ,

mycoplasmamycoplasma RickettsiaRickettsia

Crystal associated AINCrystal associated AIN

Uric acideUric acide CalciumCalcium Calcium oxalateCalcium oxalate PhosphatePhosphate IndinavirIndinavir AcyclovirAcyclovir SulfonamidesSulfonamides

Clinical presentation of Clinical presentation of AINAIN

ARFARF FeverFever Skin rashesSkin rashes Positive drug history(Positive drug history(antibioticsantibiotics or or

other drugs)other drugs) EosinophiliaEosinophilia EosinophiluriaEosinophiluria ? ?

Treatment of AINTreatment of AIN Stopping the drugs responsible for Stopping the drugs responsible for

AINAIN Corticosteroides in :Corticosteroides in : Drug induced AINDrug induced AIN SarcoidosisSarcoidosis SLESLE SjogrenSjogren Idiopathic AINIdiopathic AIN

Chronic Tubulointertitial Chronic Tubulointertitial NephritisNephritis

PhenacetinPhenacetin containing analgesic was the most containing analgesic was the most common cause of CTIN in USA until common cause of CTIN in USA until 19831983 . . Now CIN is mostly due to renal ischemia or Now CIN is mostly due to renal ischemia or secondary to a primary glomerular diseases .secondary to a primary glomerular diseases . VURVUR Sickle cell NephropathySickle cell Nephropathy Analgesic Nephropathy & Analgesic Nephropathy & Papillary NecrosisPapillary Necrosis LithiumLithium associated Nephropathy associated Nephropathy Calcineurin inhibitors(Calcineurin inhibitors(cyclosporinecyclosporine , ,

Tacrolimus)Tacrolimus) ) )

Chronic TIN (cont.. )Chronic TIN (cont.. )

Metabolic Disorders :Metabolic Disorders : Chronic uric acid NephropathyChronic uric acid Nephropathy HypercalcemicHypercalcemic Nephropathy Nephropathy HypokalemicHypokalemic Nephropathy Nephropathy HperoxaluriaHperoxaluria CystinuriaCystinuria

Cystic & Hereditary Cystic & Hereditary disordersdisorders

Polycystic kidney diseasePolycystic kidney disease Medullary sponge kidneyMedullary sponge kidney Medullry cystic diseaseMedullry cystic disease

MiscellaneousMiscellaneous

Chronic GNChronic GN Chronic obstructionChronic obstruction Radiation NephritisRadiation Nephritis AgingAging

Papillary NecrosisPapillary Necrosis

One of the clinical presentation of CINOne of the clinical presentation of CIN Presenting with renal colic due to Presenting with renal colic due to

passage ofpassage of necrotic papillanecrotic papilla Papillary Necrosis can occure inPapillary Necrosis can occure in Analgesic nephropathyAnalgesic nephropathy Sickle cell nephropathySickle cell nephropathy DM with UTIDM with UTI

Clinical picture of CTINClinical picture of CTIN

Progressive decline in renal functionProgressive decline in renal function Urinary Urinary concentrating concentrating defect ( DI )defect ( DI ) Fanconi synd , RTA , ProteinuriaFanconi synd , RTA , Proteinuria Prominent Prominent anemiaanemia History of History of analgesicanalgesic use or exposure use or exposure

toto heavy heavy metals ( metals ( leadlead , , cadmiumcadmium ) ) , other , other

agentsagents