Recurrent / Persistent - PowerPoint Presentation

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Recurrent / Persistent UTI and Management of Kidney Stones Julian Mander RPH Urology

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Persistent UTIPersistent UTI implicates an underlying infective focus, not cleared until the underlying problem is dealt with.Always the same organism on MSU. MSUs remain positive after treatment and between clinical episodes.Classically Proteus and infection staghorn stones, classically older females. Infection not cleared unless stone cleared.In males, commonly persisting prostatic infection, typically not cleared with cephalexin or amoxycillin – use trimethoprim or norfloxacin (or ciprofloxacin) in men.Slide3

Recurrent UTIRecurrent UTI means reinfection, typically with varying or different organisms.Definition: Three or more MSU documented UTIs within 12 months.3% of women, uncommon in men.Urine cleared of bacteria in between clinical episodes c/f persistent UTI not cleared.Slide4

Recurrent UTI1/3 of women with recurrent UTI in adult life had their initial UTI during childhood.UTIs tend to occur in clusters in those with recurrent UTI.Predisposing factors are unclear – sexual intercourse in women estrogen deficiency in post menopausal women altering vaginal floraRole of residual urine poorly studied, assumed that PVR > 100 ml associated with recurrent UTI (?180 ml), but PVR proportional to starting volume and bladders always overfilled for U/S.Slide5

Pathophysiology Recurrent UTIBacteriuria is common in women, but established UTI/cystitis relatively uncommon – why do some women get recurrent UTI whilst most don’t ?All bacteria invading the urinary tract activate an inflammatory response in terms of neutrophil infiltration, important to clear the bacteria.Extent to which different organisms activate the inflammatory response varies markedly, and the relationship of this activation to different disease states is complex.Deficiency in activation of inflammatory response in some people predisposes them to infection.Bacterial attachment to mucosa is important, bacteria – host interaction here is important and poorly understood.Slide6

Secretor StatusMendelian dominant inherited characteristic of secretion of water soluble form of antigen immunodominant sugars - Blood group A: N acetyl-D-galactosamine B: D-galactosamineNon secretors linked with relative deficiency of certain immunoglobulin classes. Non secretors have more infections, including UTI’s.Suggestion that non-secretors have less efficient immune systemsSlide7

ABO Blood Group StatusBlood group B have 50% greater chance of UTI than non-B group.Blood group AB also have a higher incidence of UTI.Absence of anti-B isohaemaglutinin renders individual more susceptible to UTI. Large number of bacteria cross react with anti ABO blood group isohaemaglutinins. These cross reacting antigens vary in their immunogenicity. “B-like” immunogen is particularly antigenic and may increase the naturally occurring isohaemaglutinins, inhibiting bacterial attachment and colonization and increasing susceptibility to

compliment.

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Humoral ResponseSuperficial infection results in the formation and release of secretory IgA.UTI causes a selective and up to four fold increase in IgA secretion.Some adults with UTI appear to have a defect in the maturation of sIgA.Superficial vs Intracellular infection – recent work on intracellular infection and the detection of IBCs – intracellular bacterial communities – relevant to clearance of infection and persistent UTIs.Moving from superficial to intracellular infection is poorly understood, but humoral and subsequent inflammatory response and neutrophil recruitment is thought to be important.Slide9

InvestigationMSUs critical for correct managementUltrasound kidneys and bladder residual (n.b. without bladder overdistension, which will give artificially elevated PVR – good U.K. study showing PVR proportional to pre void volume)Cystoscopy usually unnecessary if PVR is OK and patient not had frank haematuria.Slide10

MSU testsCritical in the management of recurrent / persistent UTIs.Irritative LUTS not always UTI! - Interstistial cystitis, lower ureteric stone, bladder cancer esp CIS.Urinalysis dipstick tests – OK for screening / diagnosis in non complicated UTI 90% specificity 90% sensitivity.►Females - if more than one presentation with cystitis within 12 month time frame – DO MSUs.◄►Males – any presentation with cystitis symptoms – DO MSUs◄ Slide11

Treatment Persistent UTIsRemove the source of persisting infection: Staghorn stones – require complete clearance and follow up. Clear prostatic infection in men. Remove foreign bodies – JJ stents, cathetersSlide12

Treatment Recurrent UTIs Behavioural modificationCranberry juiceProbiotics – “Good bacteria”Antibiotic treatmentAntibiotic prophylaxisBacterial vaccinesSlide13

Behavioural ModificationAvoiding sex works for some women, but strains relationships.Anal sex probably predisposes men to UTI, but is generally not discussed, and there are no scientific papers discussing this.General hygiene advice is a waste of time, and makes women feel they have poor hygiene.Slide14

Cranberry JuiceAntibacterial action due to aromatization of quinic to benzoic acid in the gut.Benzoic acid converted to hippuric acid in the liver, excreted in urine.Hippuric acid (Hiprex!) converted to formalin in the bladder in the presence of acidic urine (Hence Hiprex + NH4Cl or ascorbic acid). Requires high residual volumes. (Kass 1959)Also said to release organic molecules into urine which block bacterial adherence (pro-anthocyanidins which prevent docking of bacteria on A-type linkage of flavanols). (Analogous to secretion blood gp Antigns)Some evidence for effectiveness in simple recurrent UTI in women (300ml/day)Slide15

Probiotics “Good Bacteria”(By definition, a probiotic is any substance containing live organisms that, when ingested, have a beneficial effect on the host by altering the body's intestinal microflora)No evidence that they reduce incidence of UTIsLactobacillus preparation and antibiotic associated diarrhea with Rx UTI17% absolute risk reduction in diarrhea associated with antibiotic administration, and significant reduction in risk of Clostridium difficile infection, in patients given lactobacillus drink – suggested as routine admin to hospital patients > 50 that are receiving antibiotics Use of probiotic Lactobacillus preparation Hickson et al BMJ 2007; 335 (7610): 80 Slide16

Antibiotic ResistanceMost commonly associated with multiple courses of full dose antibiotics for recurrent UTIs.Do not use antibiotics in patient with an indwelling catheter unless they are septicaemic.Do not use antibiotics in patients with infection stones, unless septicaemic.Do not use antibiotics in pateints with JJ stent unless MSU positive.In patient with recurrent UTIs, MSU documentation is vital for assessment of antibiotic sensitivities and resistance.Slide17

Antibiotic TreatmentAmoxycillin simply doesn’t work – always recurs (Kincaid Smith) – seems OK with clavulinic acid though.Urosepsis T > 38 = hospital and I/V antibiotics + renal U/S exclude infected obstructed. Gentamicin + Amoxycillin (Enterococcus) monitor levels or TimentinMales – all males with UTI have prostatitis (just (don’t) do PSA!!) – prostatic persistence allegedly due to inactivity Abs in acidic pH prostatic fluid. Trimethoprim or fluoroquinolones (Norfloxacin) best – requires 2 weeks Rx, 4 weeks if recurs. Most commonly older men with Rx Cephalexin failure seen.Pyelonephritis best at least 2 weeks antibiotics.Slide18

Antibiotic TreatmentNew work on intracellular infection as cause of complicated UTI.Diagnosis of IBCs on urine cytology or biopsy with EM.Most effective intracellular Abs are fluoroquinolones. May explain observed increased efficacy for these drugs – but should be reserved for complicated UTI. Slide19

Antibiotic ProphylaxisTreatment for recurrent UTIs 95% success Use after clearance of UTI with full dose Ab, U/S clear. Prescribe antibiotic pending sensitivities.Not for catheter (IDC) related infection, or persisting UTI.Nitrofurantoin most commonly 50 mg before bed (no alteration gut/vaginal flora)Cephalexin 250 mgAugmentin DuoTrimethoprim (150 mg) linked to early multi resistanceAuthority prescription for “complicated UTI” on 1800 8883336 months generally ? 12 months for elderly. Permanent on 6 month rotation for early

recurrence or repeated problems. Post intercourse tablet can work.Slide20

Bacterial VaccinesPhase II trial published April 07 in a group of women with 3 or more UTIs in 12 monthsVaginal pessaries containing “Urovac” vaccine contains heat killed bacteria from 10 human uropathogenic bacteria: 6 strains E coli 1 strain each of Proteus, Morganella, Klebsiella, EnterococcusVaccine with or without boosters. 3 pessaries at weekly intervals with boosters 1 pessary monthly for 3 months.

72% infection free over 6months in treatment group with boosters

vs

30% infection free in placebo group, but placebo group only 3 subjects.

Vaginal Mucosal Vaccine for Recurrent UTI in Women Hopkins et al J

Urol

2007; 177:1349

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Management of Kidney Stones Julian ManderSlide22

Spontaneous Stone PassageMost stones will pass spontaneously and don’t require surgical intervention.80% of 5 mm stones will pass spontaneously.50% of 8 mm stones will pass spontaneously.Stones in the lower ureter at presentation more likely to pass than stones in the upper ureter.Typically episodic pain will be experienced while stone is passing.Adequate pain relief is important for expectant management – NSAIDs.Irritative LUTS with stone in lower 1/3 ureter ≠ UTI.Slide23

Dissolution of Uric Acid StonespKa Uric acid = 5.75 Urine pH 7 80% urate ionizedUrine pH > 7.5, increase Ca deposition on stone -> insolubleRx Sodibic 840 mg qid or Ural sachets one qidRepeat imaging 6 +/- 12 weeksNot dissolved -> surgeryPrevention increase urine output > 2 li / 24 hours

allopurinol

300 mg or 100 mg daily

? decrease protein intake 90 gm / 24 hours

? Run urine pH 7 Slide24

Indications for Surgical Intervention1. Infected obstructed kidney = surgical emergency2. Pain uncontrolled despite PR NSAIDS3. Stone clearly too large to pass > 8mm4. Significant CRF creatinine >2005. Solitary kidney – risk obstructive uropathySlide25

Surgical Intervention – JJ StentsGA + Cystoscopy – low morbidity Initially described late 1970’s, not in common usage until 1980’sInitially no longer than 6 or 12 weeks because of encrustationNow new polymers 6 months, silastic stents 12 monthsRisks - septicaemia following insertion infected obstructed - ureteric perforation - misplacement if not done with contrast and II - stent pain 15% unable to tolerate Rx as renal colic NSAIDs - loin pain with voiding

- cystitis symptoms - do MSU not dipstick which is always +

ve

- delays stone passage, but enables future instrumentationSlide26

JJ StentsSlide27

Surgical Intervention – Rigid Ureteroscopy Scopes Perez – Castro early 1980’s 12 F Uromat water pressure devices mid 1980’s 7.5 – 8.5 scopes 1990sFragmentation EHL probes and U/S probes 1980’s Pneumatic lithoclast probes 1990’sRisks: -

ureteric

perforation

-

ureteric

stricture

Use:

still best option for lower 1/3

ureteric

stonesSlide28

Rigid UreteroscopeSlide29

Surgical Intervention – Flexible Ureteroscopy and LaserFlexible ureteroscopes 1990’s 7.5 F late ’90s poor durability – 6 week lifespan @ $15,000Holmium YAG laser 1990’s, prostates initially $120,000 machine 200 micron fibers $800 - $2000Risks - ureteric strictures - urosepsis and death still with infection staghorns

Failures – narrow UOs - dilators

- narrow

ureters

– pre stent

- lower pole accessSlide30

Flexible UreteroscopySlide31
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Flexible Ureteroscopy ViewsSlide35

Surgical Intervention - ESWLFirst treatment Stuttgart 1980Dornier HM3 1983RPH Seimens Lithostar 1991RPH Dornier 2001GA or LAOpaque stones only (U/S guidance available)3000 shocks – treatment about one hourPre stenting – stones > 2 cm - infection stonesRisks – pain passing stone fragments ?late hypertension

- obstruction (

steinstrasse

) +/- infection

- renal

haemorrhage

and kidney loss (beware

coagulopathies

)

Success rates –

pelvicalyceal

80% stone free ratesSlide36
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Surgical Intervention – Percutaneous Nephrolithotomy1970’s Whickham, London – Seldinger technique for renal puncture1982 – 83 Pat Bary RPH pioneered in WAUpper vs Lower pole punctures – upper pole later + supra 11th ribAccess failuresAnatomical failures – parallel punctures, coagulum extractionSingle stage 30F

Amplatz

dilatation eventually

Fragmentation development – EHL, U/S, pneumatic

Lithoclast

Risks – bleeding 7% transfusion rate RPH (Kaye

tamponade

balloon)

- 1/200 kidney lost with each puncture & dilatation

-

nephrectomy

for bleeding occasionally

- deaths from

urosepsis

with infection

staghorns

- bowel,

sleen

and liver injuries Slide40

PCNSlide41

Open Surgery Uretero/Pyelo/NephrolithotomyOccasionally pyeloplasty for PUJ obstruction, with pyelolithotomyPyelonephrolithotomy for staghorn stones – lost art - splitting kidney on Brodel’s line - Renacidin irrigation

- Coagulum

pyelolithotomy

- renal

Xray

plate

- Gil –

Vernet’s

plane in

pyelolithotomy

- clamp and cool kidney

Risks – loss renal function

- sepsis

- loss kidneySlide42

Staghorn StonesGenerally elderly, unfit and infectedMortality from urosepisHigh recurrence rate 15 – 30%Sepsis not cleared unless stone clearedCommonest cause of persisting Proteus infectionSurgery - now the most common indication for PCN

- “sandwich” with ESWL

- ? role of flexi

ureteroscopy

and laser

- ? ESWL de novo – some reportsSlide43

Staghorn StonesSlide44

Pregnancy – Special CaseConcern is preterm labour – with or without interventionGreater concern the earlier the pregnancyXray exposure concerns at all stages, greater in first trimesterNSAIDs unable to use because of ductus closure risks Traditional management: U/S diagnosis hydronephrosis +/- stone manage with U/S alone if small and pain manageable – rare intervention required – do V. Limited IVP - control +5min + 30min

ureteroscopic

vs

open - issues with stents AVOID

Latest: U/S diagnosis followed by immediate flexi

ureteroscopy

+ laser

No

Xray

usage at all

Waterson

et al Urology 60:383-7 2002Slide45

“Metabolic Workup”Recurent stone former = 2 or more stonesBiochemical stone analysis importantIVP for medullary sponge kidney in Ca Ox stonesSerum calcium, albumin, uric acid repeatedMSU ?UTI ?pH (Type 1 distal RTA fasting urine always pH > 5.3)24 hour urine Calcium Oxalate Uric acid +/- CystinePTH assay in Calcium stone patientsRenal Acid load test for RTA “persisting fasting alkaline urine in presence of hypercalciuria and CaPO4 stones Slide46

Medical Management – Cystine StonesInherited defect renal tubular reabsorption 4 amino acids COLAAutosomal recessive, but some heterozygous have problempKa cystine higher than uric acid - increase solubility only at pH > 7.2 - double solubility at pH 7.8Dissolution - > 2 li urine / 24 hours – best 3 – 4

li

!!

- pH > 7.8

Kcitrate

thought best, but can use NaHCO3

- often not successful

Thiol

group donors – D

Penicillamine

1.5 gm / day

- form

cystine

-S-

penicillamine

soluble molecule

? ACE inhibitor -

captoprilSlide47

Medical Management – Infection StonesMgNH4PO4 = struvite with proteinaceous matrixUrea splitting bacteria, produce urease enzymes, splitting urea to ammonium, increase urine pH and may provide initial glycocalyx proteinaceous compound.Urine pH > 7.2 requiredProteus commonly, also some Pseudomonas, Klebsiella, E coliPersisting Proteus UTI is hallmark (esp diabetic Aboriginals – E coli)

Surgery to clear stone, followed by one month full dose

bacteriocidal

antibiotic, followed by 12 month surveillance with monthly MSUs

?

Hemiacidrin

irrigation following surgery

? Oral

urease

inhibitorsSlide48

Medical Management – Calcium Stones47gm calcium filtered daily, UOP 200 mg Ca/day = > 99% reabsorbedTubular transport max exceeded -> hypercalciuriaKsp need only exceed 15 – 30 minutes to nucleate stoneConcept of heterogenous nucleationHypercalciuria Vs Hyperoxaluria - Ionic activity ? Oxalate 10 x more important in

CaOx

stone formation Slide49

Medical Management - HypercalciuriaHypercalciuria Absorptive 1. Type 1 hypercalciuric on low Ca diet 2. Type 2 hypercalciuric on normal Ca diet 3. Type 3 hypercalciuric + hyperphosphatemic + low renal tubular reabsorption of phosphorous Excretive 4. Renal leak hypercalciuria

5. Hyperparathyroidism

6.

Hypercalciuria

in response to CHO ingestion

+

sarcoidosis

, multiple myeloma, hyperthyroidism, leukemia, lymphoma, milk – alkali syndrome,

Vit

D intoxication, immobilization syndrome, renal tubular acidosisSlide50

Medical Management – HypercalciuriaTreatment – Theoretical Hyperabsorbers – methylcellulose - oral oxalate! Hyperexcretors - diuresis > 2 li / day - thiazides decrease calcium excretion ? just work through volume –

polyuria

- all

hyperabsorber

treatments Slide51

Medical Management – Renal Tubular AcidosisDistal (Type 1) RTA only form stones – mostly Ca PO4 = hyperchloremic acidosis, Buttler Albright syndrome, idiopathic acidosisDecrease H+ excretion by distal tubule – increase distal tubular K+ excretion to compensate - excessive loss Na, K, Ca in urine - decrease serum Na - decrease ADH - water diuresis - decrease ECFV - increase

aldosterone

- increase Na,

Cl

reabsorption

by kidney

-

hypochloremia

,

hypokalemia

, metabolic acidosis with

hypercalciuria

!

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Medical Management – Renal Tubular AcidosisDiagnosis: Renal acid load test NH4Cl -> urine pH 5Treatment: Shohl’s solution 98 gm Nacitrate + 140 gm citric acid in 100 ml water Dose 15 ml qidSlide53

Medical Management - HyperoxaluriaHyperoxaluria Oxalate 10 x ionic activity of Ca or PO4 Endogenous production enzymatic cleavage glyoxalate to oxalic acid + glycine Exogenous gut absorption – chocolate, rhubarb, brocholi (???)Treatment Oral calcium!!! Dietary modification

24 hour urine output > 2

li

/ daySlide54

Management in Practice – Idiopathic CaOx StonesUrine output 2 li per 24 hours halves stone production ( induce nocturia )Thiazide diuretics? Potassium CitrateNo scientific evidence for dietary recommendations

( N.B. Advice to push oral fluids during renal colic is ill founded – stones shown to pass more rapidly if urine diverted with

nephrostomy

tube

=> better to reduce fluid intake while passing stone)