ACUTE PYELONEPHRITIS
The most frequent of all nephropathies
Experience based on 276 cases over 12 years
Alain Meyrier
Hôpital Georges Pompidou and Broussais
Université René Descartes, Paris
Pierre Rayer
P. Rayer
Pyelo -- renal pelvis
-- nephritis: renal infection
at autopsy
1836
2006
Pyelonephritis
Ascending renal tissue
suppuration and ischemia
Uropathogenic E. coli
CT scan
DMSA scintigraphy
Acute Pyelonephritis
Primary = in a normal urinary tract
250 000 cases per year per million in the US
Secondary = complication of:
Vesico-ureteral reflux
Megaureter
Posterior urethral valves
Major cause of end-stage renal
disease in the third world
Prostatic obstruction
Nephrolithiasis
Medullary sponge kidney
Renal cysts
Indwelling catheter
Still a cause of chronic renal
insufficiency in Western
countries
Cystitis in normal female
Simple pyelonephritis
in normal female
Complicated pyelonephritis
in normal female
Complicated pyelonephritis
in male with prostatitis
Complicated pyelonephritis
(Ureteral stone)
Signs and symptoms
Typical
Lomboabdominal pain. Enlarged, tender kidney
High fever and shaking chills
Cystitis often lacking
ESR >>> 20 mm
CRP >>> 20 mg/L
Pyuria = leukocytes > 105/ml + bacteria > 106/ml
Misleading
Painless: diabetic, malnourished alcoholic (autonomous
neuropathy), elderly
Hypothermia: sepsis
Aseptic bacteriuria: uroculture following treatment
Acute pyelonephritis
Encounter between an aggressor and a host
1)
The vulnerable host
Child
Male
Diabetic
Pregnant woman
Menopause
Alcoholic
Transplant recipient
2) The aggressor: a uropathogenic strain
Enterobacteria, mostly E. coli and Proteus
Staphylococcus saprophyticus
Commensal microorganisms responsible
for community acquired pyelonephritis (%)
FIRST EPISODE
OR REMOTE
RELAPSE
RELAPSE
BY SHORT-TERM
REINFECTION
E. coli
71-89
E. coli
P. mirabilis
1,1-9,7
P. mirabilis
15
Klebsiella
20
Klebsiella,
Enterobacter
Enterococcus
S. saprophyticus
Other
1-9,2
1-3,2
3-7
2-6
Other
60
5
Bacteria responsible for
hospital acquired pyelonephritis
Van Poppel & al, Infection, 16:337, 1988
Factors of uropathogenicity
1)
•
Physico-chemical factors
Enterobacteriaceae are electronegative but their charge is insufficient to
be repelled by the electronegativity of the urothelium, and by the ions
adsorbed on their surface
•
They require and use other virulence factors to adhere to the epithelial
cells, the renal tubules, Bowman's capsule and vessel walls
2) Factors independent of fimbriae
3) Fimbrial adhesion
UPEC = Uropathogenic E. Coli
CrossCross-section of the human kidney displaying UPEC fimbrial adhesinadhesin-binding sites
Source: Lane MC & Mobley HLT
KI, 2007; 72:1972:19-25
Factors of uropathogenicity
E. coli
Factors independent of fimbriae
- Serotype O: O1, O2, O4, O6, O7, O16, O18, O75 are
found in 28 % of the intestinal flora sampling and are
responsible for 80 % of pyelonephritis, 60% of cystitis
and 30% of asymptomatic bacteriuria
- Aerobactin: siderophore that allows acquisition of iron
from the urothelium and the urine
- Hemolysin: cytotoxic to the urothelial cells
- Resistance to serum bactericidal activity, allowing E. coli
encapsulation
Factors of uropathogenicity
E. coli
Fimbrial, and bacterial membrane adhesins
Fimbriae (Pili) carry epitopes (adhesins), lectins that bind to
oligosaccharide motifs of the urothelial (and other) cell membranes,
especially galactose-galactose (Gal-Gal) sequences
They also recognize blood group epitopes such as P (hence: 'Pfimbriae') and M
Women who are non-secretor of some blood group antigens elaborate
glycolipid Gal-globoside receptors and are more susceptible to E.
coli adhesion
The P epitope is located at the tip of fimbriae and assumes a fibrillar
structure
Uropthogenic E. coli: pili ("fimbriae")
UPEC = Uropathogenic E. Coli
Transmission electron micrographs of UPEC expressing different fimbriae. (a and b)
CFT073 fim L-ON, a mutant that constitutively expresses type 1 fimbriae. (c and d) CFT073
fim L-OFF, a mutant that is unable to express type 1 fimbria produces another type of
fimbriae. a and c are at 34 000 magnification, and b and d are at 64 000 magnification.
Source: Lane MC & Mobley HLT
KI, 2007; 72:19-25
UPEC adhesion to epithelial cells
Scanning electron
microscopy
UPEC
Stick to the
urothelial cell
membrane
(Le Bouguenec C & al, J Clin Microbiol, 39:1738, 2001)
Fimbriae are not solely pathogenic
through their adhesive properties
• Type 1 adhesins bind to mannose and elicit
hemagglutination
• Hemagglutination increases the inflammatory
response to infection
• In a murine model of pyelonephritis Dr -fimbriae
bind to Bowman's capsule and tubular cell
basement membranes through the complement
'Decay accelerating factor' and type IV collagen
Factors of uropathogenicity
P. mirabilis
Mobley HLT & al
Kidney Int 46:S129-36, 1994
Specific factors
Four types of adhesins. MR/P in the kidney and PMF in the bladder
Non specific factors
Flagellae
Hemolysin
Urease → NH3 urinary pH → struvite staghorn stones
Lessons from animal models
Roberts JA AJKD 1991
Model: primate
1)
2)
Flushing UPEC into the ureter
Renal vein blood:
Renin Complement Ô
3
Ischemia
Thromboxane A2 2
3)
Renal tissue histology:
Edema, PMNs, haemorrhage,
tubular necrosis, capillary
thromboses
1
Lessons from animal models
Hill GS & Clark RL Invest Radiol 1972
Model: rabbit. Flushing of UPEC in the ureter
Histology
Vascular neoprene injection
Summary
• Gram negative pathogenic bacteria progress from the
perineum to the urethra, the bladder and spread from the
medulla outwards into the renal tissue
• They induce intense vasoconstriction, PMNs influx,
capillary plugging, edema and hemorrhagic suffusions
• The involved areas are ischemic
• Ischemia may lead to necrosis and walled off cavity
formation = abscess
• Ischemia may induce papillary necrosis
• The corresponding cortex may undergo sclerosis leaving
definitive cortical scars
Pyelonephritic
kidney removed
surgically as a
salvage procedure in
a diabetic.
Ñ
*
Ñ
Whitish areas *
denote suppuration.
Arrows show
abscess formation
*
Ñ
Renal biopsy
Edema, inflammatory infiltrate
* leukocyte casts in the tubules Ñ
Renal biopsy, human. Edema, PMNs, hemorrhagic suffusions
Imaging
•
Emergency CT enhanced helical CT scan may reveal a ureteral
calculus requiring immediate referral to the urologist. Sensitivity
98%, specificity 100% (Fielding JR, Am J Radiol 71:1051-3, 1998).
Absolute superiority over IVP
•
Ultrasound examination: not for assessing obstruction (dilatation
lacks in 20% of cases. Found in only 65%), but shows parenchymal
lesions and discloses abscesses > 1 cm
•
CT scan: hypodense images indicating vasoconstriction in
suppurative areas. Shows abscesses
•
DMSA scintigraphy: when available, extremely sensitive, results in
two hours. Inexpensive. The imaging technique of choice in children
•
Gallium scan: rarely indicated nowadays
Ultrasound diagnosis of pyelonephritis
Pyélonéphrite
vue en
échographie
Ultrasound
diagnosis
of pyelonephritis
Abscess
CT scan
Bilateral pyelonephritis
Hypodense radiating appearance of presuppurative areas
CT scan
*
Large nodular hypodense "nephronia" from medulla to cortex
Note the perirenal edema *
Juxta cortical
hypodense area
in a swollen,
edematous
kidney
CT scan
Left sided pyelonephritis. Large edematous kidney with two
hypodense, ischemic areas
Cortical scars two months later
Further progression to chronic interstitial nephritis
Abscess
Ð
Ô
Pseudo-renal cancer: febrile, painless renal abscess in a malnourished
chronic alcoholic patient Ô Note calcifying pancreatitis Ð
Ð
Pseudorenal cancer: febrile, painless renal abscess in a malnourished
chronic alcoholic patient Ô Note calcifying pancreatitis Ð
Gallium scan before
treatment
Gallium scan after
treatment
99mTc-DMSA scintigraphy
L
**
**
R
**
*
Clinically right sided PN. In fact, bilateral on scintigraphy
Scintigraphy
CT scan
Pyelonephritis in pregnancy
• Frequent
• Heralded by asymptomatic bacteriuria
• Occurring in a physiological state of
immunodepression
• Difficult imaging (dilatation of the urinary tract is
physiological)
• Dangerous: risk of contractions and premature
labor
Patterson & al
Kidney Int
45:571, 1994
Patterson & al
Kidney Int
45:571, 1994
VUR
The most common
cause of
pyelonephritis in
children
Risk of renal growth
arrest, cortical scars,
chronic
pyelonephritis
Best diagnostic
procedure:
DMSA scintigraphy
Compound papillae
Diabetics
• Male + Obese + Poor glycemic control
• Bladder autonomic neuropathy + Glycosuria +
Neutrophil phagocytic impairment
• May be painless
• Leads to hyperosmolarity and acidocetosis
• Abscess formation and papillary necrosis
• Rescue nephrectomy may be the last recourse
Necrosis and abscess formation
Papillary necrosis
Papilla recovered in the urine
Acute pyelonephritis
Young woman
No urologic disease
No compromised
background
Male
Elderly
Diabetic
Pregnant
Child
"Simple" pyelonephritis
Apparently
benign
Apparently
severe
Hospitalization
Ten day
ambulatory Rx
Antibiotic treatment
Not advisable before sensitivity tests
• Ampicillin
70 % of community acquired
enterobacteriaceae are now resistant
• Cotrimoxazole
Recommended first line regimen
Aminoglycoside 4 days
Fluoroquinolone 10 days
Pregnancy
3rd generation β lactamin
Children
Aminoglycoside
+ 3rd generation β lactamin