1st Department of Medicine
István Barna MD.PhD
1st Department of Medicine
Urinary tract infections
and kidney stones
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Overview - UTI
• Definitions
• Pathogenesis
• Virulence factors
• Pathogens
• Diagnosis
• Urine culture, dipstick, pyuria
• Classification
• Types of UTI
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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)
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Pathogenesis: bacteria causing UTI
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Pathogenesis: bacteria
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Diagnosing UTI: pyuria (leucocyturia)
• Centrifuged urine in microscope: >2-5WBC/HPF (females more)
• Uncentrifuged urine: >10000/ml
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Sterile pyuria
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Classification of UTI
Upper vs. lower urinary tract
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
„Complicated” acute cystitis in
adults
• May not be apparent at first presentation
• increased risk for complications (pyelonephritis)
• Different bacterial strains
• Needs urine culture
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Pathogenesis: bacterial colonization
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Pathogenesis: bacterial colonization
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute interstitial nephritis -
presentation
• Urine sediment
• white cell casts
• eosinophiluria (>1%) neither specific nor sensitive !
• Imaging: ultrasound• normal or• enlarged kidneys, cortical edema
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute pyelonephritis
• 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)
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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!)
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute pyelonephritis
Complications
• abscess formation
• perirenal abscess
• sepsis, multi-organ failure
• chronic pyelonephritis /
interstitial nephritis
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute pyelonephritis• Imaging studies
– US: decreased echogenicity, possibly stones, pyelectasia
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute pyelonephritis• Imaging studies
– CT: focal inflammation, decreased density
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute pyelonephritis: therapy
High fluid intake !!
•Higher doses than in cystistis
•Amoxi/clavulinic acid- frequent resistance
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute pyelonephritis: therapy
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute complicated pyelonephritis
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute complicated pyelonephritis
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Acute pyelonephritis:
complications
• Renal abscess
• Perirenal abscess
• Papillary necrosis
• Chronic pyelonephritis
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Chronic pyelonephritis• Etiology
• Ureteral stones
• Infected renal stonesstruvit stonesmagnesium-ammonium-phosphateincreased ammonia production in alkaline urineurease producing organisms: Proteus, Klebsiella
"Staghorn" calculi
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
TIN (pyelonephritis)
Reflux nephropathy
Small, shrunken right kidney,
thinning parenchym
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
DMSA scintigraphy - VUR
scarring on right upper side
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Right side hydronephrosis
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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?
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
NEPHROLITHIASIS
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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 +
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
+
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Ca-Ox dihydrate and monohydrate
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Uric acid crystal
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Cystine crystal
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Mg ammonium phosphate crystal
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
• 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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Cyst and stone
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Stones both side
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
IV urography- stone
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Stones in bladder
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
stone
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
• 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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
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
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
ESWL
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
ureterorendoscopy
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
kalcium-oxalat- monohydrat
( whewellit )
struvit-carbonat apatit
uric –acid
Urinary tract infections
and kidney stonesIstván Barna MD.PhD
cystin
kalcium oxalat
(whewellit+weddellit)
whewellit+struvit+uric acid
mixed stone