urinary tract infections and kidney stones

1st Department of Medicine

István Barna MD.PhD

1st Department of Medicine

Urinary tract infections

and kidney stones


and kidney stonesIstván Barna MD.PhD

Overview - UTI

• Definitions

• Pathogenesis

• Virulence factors

• Pathogens

• Diagnosis

• Urine culture, dipstick, pyuria

• Classification

• Types of UTI



Introduction

• UTI – most frequent bacterial infections

• Occurs in all ages, wide clinical spectrum

• 10%/year in young, middle age females

• Incidence 53/1000 patients

• by the age 20-40, 30% of females had at least 1episode

• Needs special attention in children, males, diabetics,

pregnant woman, elderly, those with indwelling catheter



Some definitions

• Colonization• Bacterial attachment to skin, mucosal surfaces

• Contamination• Bacteria entering the urine during sample collection

• Sterile leucocyturia• Leucocyturia with no bacterial growth in the sample

• Asymptomatic bacteriuria• Significant bacteriuria without symptoms

• Relapse• Recurrent infection with same organism

• Reinfection• Recurrent infection with other organisms



Pathogenesis: bacterial colonization

• Virulence factors

• Fimbriae

• Adesins

• Flagellae

• Iron uptake

• Hemolysin, aerobactin

• Urease synthesis

• Defence mechanisms

• Normal flora (lactobacillus)

• mannose in Tamm-Horsfall protein

• Secretory IgA, IgG

• P1 genotype (increased risk)



Pathogenesis: bacteria causing UTI



Pathogenesis: bacteria



Diagnosing UTI: urine culture

• Indications

• Complicated UTI

• Atypical symptoms

• Failure to respond initial therapy

• Sampling

• First morning sample best

• Local desinfection (nonfoaming antiseptic), drying

• Spreading the labia - pulling back foreskin

• Midstearm sample

• Last drops after prostate massage

• Immediate culturing or store on +4 degrees

• Use of dip-slide



Diagnosing UTI: definition of positive

culture

• Classically significant bacteriuria 105 CFU/ml

• If typical symptoms then lower counts are

diagnostic (as low as 103 CFU/ml)

• Consider already treated patients with lower

counts

• Urine culture typically grows monoflora unless• Contamination during sampling

• Fecal contamination of the bladder



Diagnosing UTI: pyuria (leucocyturia)

• Centrifuged urine in microscope: >2-5WBC/HPF (females more)

• Uncentrifuged urine: >10000/ml



Sterile pyuria



Diagnosing UTI: dipstick

• Dipstick diagnosis of UTI

– Leucocyte esterase: figh spec, lower sens – beware of false

negatives

– Nitrit (enterobactericae) : false negatives

– Combination of both to detect but not to exclude



Classification of UTI

Upper vs. lower urinary tract



Classification of UTI:

Non-complicated vs. complicated

• Male sex

• Age <15years, >65y

• Diabetes

• Pregnancy

• Immunocompromised patient

• Steroids, chemotherapy, transplanted

• Urinary tract abnormalities

• Structural: stone, stricture, obstruction, cysts, prostate hypertrophy

• Functional: neurogenic bladder, VUR, dialyzed

• Urological procedure within 14 days

• Risk for resistant strains

• Hospital aquired

• ABx within 30 days

• Symptoms more than 7 days



Acute cystitis in adults• In otherwise healthy adult woman: non complicated

• 50-60 % of adult women had at least one episode

• In men less cystitis

– Longer urethra

– Less frequent colonization

– antibacterial substance in the prostatic fluid

• Microbiology

– E. coli, S saprophyticus

• Signs/symptoms

– Dysuria, frequency, hematuria, no fever

– Suprapubic tenderness

• Dx

– Pyuria, culture not necessary if typical clinical picture

– Dipstick: false negatives !

• DDx

– Urethritis, vaginal discharge, pyelonephritis, pelvic inflammation



„Complicated” acute cystitis in

adults

• May not be apparent at first presentation

• increased risk for complications (pyelonephritis)

• Different bacterial strains

• Needs urine culture



Recurrent UTI in women

• In young college students 27% experienced at least one

recurrence, 2,7% a second recurrence

• Reinfection vs relapse

– Relapse: recurrence with the same strain within 2 weeks

– Reinfection: >2 weeks, possibly different stain, sterile urine in-

between

• Risk factors

• Bacterial virulence

• Genetic factors

• Behavioral

– Spermicide, new partner,

• Pelvic anatomy

• Postmenopausal

– Cystocele, urinary incontinence, postvoidal residual volume



Recurrent UTI in women

• Rx

– Contraception, postcoital voiding, fluid intake

– Cranberry juice

– Lactobacilli

– Postmenopausal:estrogen cream

• According to culture and sensitivity

• Profilaxis

– Continous

– Postcoital

– Self-treatment



Pathogenesis: bacterial colonization



Asymptomatic bacteriuria

• Definition:Presence of positive culture in the absence of

symptoms

• For woman x2 105 CFU/ml

• For men single culture

• Prevalence

• 3-6 % in woman, 2% in nuns

• More common in diabetics, elderly, with catheter,

• Why asymptomatic ?

• Less virulence, better host defence

• Particular attention

• Pregnant, catheter, transplant, stuvite stones



Asymptomatic bacteriuria

• No evidence for benefit in treating asymptomatic

bacteriuria in

– Nonpregnant woman, girls, diabetics, elderly, spinal

cord injury – no screening needed

• Screening is needed in

– Pregnant women

– Before urological procedures

– >48h after removal of an indwellin catheter

– VUR

– Struvite stones



Acute urethritis• Pathogens

– Chlamydia trachomatis, N ghonorrhoeae

– May involve genitals

– Considered to be a STD

• S&S

– Dysuria, leucocyturia, no hematuria

– urethral discharge

• DDx

– Candidiasis, trychomoniasis

• Complication

– Cervicitis, pelvic inflammation, stricture

• Rx

– Macrolid ABx, doxicyclin, treat sexual partner



Acute pyelonephritis• Only in young female may be considered an „uncomplicated” UTI,

otherwise search for susceptibility factors

– May be a life threathening condition

• Pathology

– Focal interstitial inflammation (acute tubulointerstitial nephritis)

– Tissue invasion !

• Etiology

– E. coli, Proteus, Clebsiella, Enterococci

– Usualy no S. saprophyticus

• Signs, Symptoms

– Dysuria, frequency, hematuria AND fever, flank pain,

nauesea/vomiting (signs of tissue invasion)

– Bacteriemia in 30%

– Pyuria, leucocyte casts - diagnostic for tubulointerstitial nephritis



Acute interstitial nephritis -

presentation

• Urine sediment

• white cell casts

• eosinophiluria (>1%) neither specific nor sensitive !

• Imaging: ultrasound• normal or• enlarged kidneys, cortical edema



Acute pyelonephritis

• potentially organ and/or life threatening infection

• bacterial invasion of renal parenchyma

ascending urinary tract infection, rarely via bloodstream

Usual pathogens:

• E. coli (> 80%)

• Klebsiella, Proteus

• Enterococci

• Pseudomonas

• Yeast




• Complicated or uncomplicated?

• uncomplicated:

adult, non-pregnant female patient, without any risk factors

• Risk ractors

• infants, elderly, pregnancy

• anatomic abnormality (polycystic disease, double ureter,

vesico-ureteric reflux, prostate hyperplasia)

• obstruction (nephrolith)

• foreign body (cathters)

• immunosuppressive state (diabetes, transplantation)



Acute pyelonephritis - presentation

• Presentation

• fever, chills, flank / costovertebral pain, nausea, vomiting

• gross hematuria 30-40%

• mental status change

• another organ system involvement (heart failure, constipation)

• mild illness, ambulating / septic

• Laboratory

• inflammation: elevated WBC, CRP

• kidney dysfunction: creatinine, urea

• urinalysis: pyuria, white cell casts, bacteria

• leukocyte esterase and nitrite tests positive

• positive urine culture

(collect sample before antibiotic given!)



Acute pyelonephritis - presentation

• Imaging studies: ultrasound / CT

• to rule out urinary tract abnormality, kidney stone

• persisiting or worsening condition despite antibiotic treatment

• Histology

• biopsy usually not needed

• suppurative necrosis, abscesses

• polymorphonulear neutrophils




Complications

• abscess formation

• perirenal abscess

• sepsis, multi-organ failure

• chronic pyelonephritis /

interstitial nephritis



Acute pyelonephritis - treatment

• inpatient / outpatient

• supportive therapy

• bed rest, fever and pain management

• appropriate fluid intake (oral, parenteral)

• removal of catheters

• surgical drainage of abscesses

• antibiotics

• empiric therapy

beta lactam, fluoroquinolones, aminoglicosides, TMP-SMX

• targeted based on cultures

• treatment for 10-14 days



Acute pyelonephritis• Imaging studies

– US: decreased echogenicity, possibly stones, pyelectasia



Acute pyelonephritis• Imaging studies

– CT: focal inflammation, decreased density



Acute pyelonephritis: therapy

High fluid intake !!

•Higher doses than in cystistis

•Amoxi/clavulinic acid- frequent resistance



Acute pyelonephritis: therapy



Acute complicated pyelonephritis



Acute pyelonephritis:

complications

• Renal abscess

• Perirenal abscess

• Papillary necrosis

• Chronic pyelonephritis



UTI: fungal infections• Susceptible

– Diabetic, immunocompromized,

catheter, nephrostoma

• Primary

– Blastomyces, Coccidioides

• Secondary

– Oppurtunistic: Candida,

Aspergillus, cryptococcus

• S&S

– Less acute than bacterial

• Rx

– Fluconazole, itroconazole,

amphotericin B



Chronic pyelonephritis• Etiology

• Vesicoureteral reflux (VUR)• congenital condition (40% of children with recurrent UTI, 1% of all

newborn)

• acquired by patients with flaccid bladder - spinal cord injury

Moritoki Y, Case Rep Med 2012

medindia.net



Chronic pyelonephritis• Etiology

• Ureteral stones

• Infected renal stonesstruvit stonesmagnesium-ammonium-phosphateincreased ammonia production in alkaline urineurease producing organisms: Proteus, Klebsiella

"Staghorn" calculi



Chronic pyelonephritis - presentation

• Imaging

• ultrasound, CT, iv. urography

• large, deep, segmental cortical

scars - commonly: upper pole

• lost renal cortex, thin parenchyma

• ureteral dilatation

• Treatment and prognosis

• eliminate obstruction

• long-term antibiotic therapy

TMP-SMX, fluoroquinolones

• slowly progressing disease

• exacerbations of pyelonephritis

further deteriorate kidney function



Chronic bacterial pyelonephritis

• Is there such a thing?

• Low grade bacterial inflammation, with occasional flare ups

• Inflammation: CRP, ESR

• pyuria, bacteriuria

• Sign and symptomps

• Increased ESR, CRP, pyuria, isostenuria

• Low grade fever

• Complicated infection

• Chronic renal disease

• Smaller kidneys

• Chronic renal insufficiency



Differential diagnosis of chronic

pyelonephritis

• „True” chronic pyelonephritis

• Nephrosclerosis (aging, hypertension, diabetes..)

• Analgetic nephropathy

• Heavy metals

• Balkan nephropathy

• Chenese herb nephropathy

• Nephrocalcinosis

• Chronic urate nephropathy



TIN (pyelonephritis)

Reflux nephropathy

Small, shrunken right kidney,

thinning parenchym



DMSA scintigraphy - VUR

scarring on right upper side



Right side hydronephrosis



Summary: UTI

• Extremely frequent disease

• Consider them as complicated and non-complicated diseases

• Consider them as lower and upper UTIs

• Asymptomatic bacteriuria is to be aware of in diabetics and pregnant patients

• Pyelonephritis is a major concern

• Chronic pyelonephritis

• Is it truly an infection?



NEPHROLITHIASIS



Classification: stone compositionCaOx Monohydrate

Dihydrate

35% gray-black, hard,

round, granular

surface

electrondense

++

Ca P Monohydrate P (brushite)

Hydroxyapatit

Carbonate apatit

Orthophosphate

(whitlockite)

5%

combined

CaOx Ca P

35%

Uric acid Uric acid, Na urate,

ammonium urate

+5 Round, smooth,

yellowish

lucent

Combined uric acid

+ CaOx

1-2%

Infection related

Staghorn

Carbonate apatit Mg

ammonium foszfate (struvit)

20% Large, laminated,

dark, coral like

electrondense +

Cystine 1-2% grayish, christalline electrondense +



Nephrolithiasis – stone typesCaOx monohidrate

dihidrate

35% greyish-black,

hard, round,

granular surface

radioopaque

++

Ca P monohidrate P (brushite)

hydroxyapatite

carbonate apatit

orthophosphate(whitlockit)

5%

combined

CaOx- Ca P

35%

Urate Urica acid, Na-urate,

ammonium-urate

5% yellow, round,

smooth

radiolucent

combined urate +

CaOx

1-2%

Infection-associated Mg-ammonium-phosphate

(struvite)

20% large, dark,

staghorn

radioopaque

+

Cystine 1-2% greyish, crystal-

like

radioopaque

+



Ca-Ox dihydrate and monohydrate



Uric acid crystal



Cystine crystal



Mg ammonium phosphate crystal



Optimal 24-h urine excretions

Volumen 2-2-5l

pH >5,5 and <7,0

Ca <0,1 mmol/kg,

male <7,5, female <6,3 mmol

oxalate 0,18-0,35 mmol

urate 1,5-4,4 mmol

Citrate 2,4-5,1 mmol

Na <200 mmol

Phosphate <35,2 mmol

creatinine male 7,1-15,9 mmol,

female 5,2-14,1 mmol



Ca-containing stones

Hypercalciuria

idiopathic (renal or absorptive)

primary hyperparathyroidism

other hypercalcemia (sarcoidosis, tumor, immobilisation)

renal tubular acidosis

drugs (Vitamin D)

diet (large amount of Na, protein, little fluid)

Hyperuricosuria

Hyperoxaluria

enteral (malabsorption, small bowel disorders)

metabolic hyperoxaluria, low Ca-intake

primary hyperoxaluria

Hypocitraturia

Idiopathic (Na-citrate transport defect ?)

Hypokalemia, acidosis

Nephrolithiasis - etiology



Etiology

• Uric acid containing stone

• Hyperuricosuria

• Dietary (purine rich food)

• Gout, myeloproliferative disease, enzime defect)

• Drugs (thiazide ?, probenicid)

• Cystine stone

• Heterozygote cystinuria

• Struvite stone

• Infection with urease splitting bacteria



• Urate stone

• Hyperuricosuria

• Diet (purine rich diet)

• Gout, myeloproliferative disorders, rare enzime deficiencies Drugs (thiazide?, probenicid)

• Cystine stone

• Heterozygote cystinuria

• Struvite

• Urease-producing bacteria

Nephrolithiasis - etiology



Infection-related stone: serum creatinine, urine pH, urine culture.

Cystine stone: serum creatinine, urine pH, 24-hour cystine excretion.

Urate stone: serum creatinine and uric acid, urine pH, 24-hour urateexcretion

Calcium-containing stone (recidive stone, specific risk factors):

serum calcium, (ionised calcium), creatinine, potassium, uric acid, in case of brushite stone: serum and urine pH, in case of hypercalcaemia: PTH

Urine pH, sediment

24-hour urine collection: volume, Ca-, oxalate-, citrate-, urate-, magnesium-, phosphate-, urea-, Na- and K-excretion

Nephrolithiasis – patient evaluation



Cyst and stone



Stones both side



IV urography- stone



Stones in bladder



stone



• General advice

• Fluid intake that provides 2000-2500 ml daily urine output

• Water, fruit juice with large citrate content

• Coke, grapefruit juice not recommended

• Dietary advice

• Protein: 0,8-1 g/kg, <150 g

• Normal Ca intake (800-1000 mg/day)

• Salt restriction (< 9g NaCl/day)

• Low oxalate diet

• Low purine diet

Nephrolithiasis - prevention



Medical prevention

• General advice

• Increase urine output to >2000 ml day

• Not coke

• Prefer lemonade

• Dietary advice

• protein 0,8-1 g/kg, <150 g

• Avoid low calciumm diet (800-1000 m/d) !

• Low Na diet

• Low oxalate diet

• Avoid purine rich diet



Medical prevention of recurrence

• Drugs for prevention

• In case of cystine, uric acid, struvite and brushit stones immediatley withdiet

• Thiazide diuretics

• Decreases Ca excretion

• Needs K and Mg supplementation, preferablyin the form of citrate

• K-,K- Na-citrat, Mg Citrate

• pH increases, citrate excretion increases, inhibition of Ca crystallisation

• Allopurinol

• Uric acid excretion decreases

• Pyridoxin

• Pimary hyperoxaluria

• Urinary alkalisation (uric acid and cystine stones)

• Antibiotics (struvite stones), removal of stone fragments

• Inhibition of urease: acetohydroxamic acid

• Captopril, D penicillamine, tiopronine for cystine stones



Drug treatment

• Thiazide diuretics

• Ca- excretion ↓

• K- and Mg- supplementation (optimally citrate)

• higher pH and high urine citrate concentration inhibits Ca-crystal formation

• Allopurinol

• urate excretion ↓

• Pyridoxin

• Primary hyperoxaluria

• Urine alkalinization (urate and cystine stones)

• Antibiotics (struvite stones), removal of stone fragments

• Captopril, D penicillamine, tiopronine in case of cystine stones

Nephrolithiasis - prevention



ESWL



ureterorendoscopy



kalcium-oxalat- monohydrat

( whewellit )

struvit-carbonat apatit

uric –acid



cystin

kalcium oxalat

(whewellit+weddellit)

whewellit+struvit+uric acid

mixed stone

urinary tract infections and kidney stones

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