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PYELONEPHRITIS

DARSHINII NAGAPPAN
GROUP NO.5
KURSK STATE MEDICAL UNIVERYSITY
DEFINITION
Its a disease of the kidney primarily showed by
the combination of fever, loin pain with
tenderness and significant bacteriuria.
Small renal cortical abscesses and streaks of pus
in the renal medulla are often.
Histologically there is focal infiltration by
polymorphonuclear leucocytes and many
polymorphs in the tubular lamina.
Causes
Bacterial pathogens are the most common cause of
pyelonephritis.

Escherichia coli - By far the most common organism,
causing more than 90% of all cases of APN.
Klebsiella oxytoca and species
Proteus species
Enterococcus faecalis and species
Gram-positive organisms, including staphylococcal
species and group B Streptococcus - Rare causes of
APN


Bacteremia is the leading cause of infection in neonates, whereas ascending
infection from bacteriuria involving the lower urinary tract predominates in
other age groups.

VUR increases the risk for pyelonephritis.

Delayed or incomplete voiding, as seen with neurogenic bladder or
obstruction, increases the risk for urinary stasis and overgrowth of
colonizing bacteria.

Catheterization may increase the risk of introducing periurethral bacteria
into the bladder. Clean intermittent catheterization leads to colonization of
the bladder that might lead to pyelonephritis if stasis allows any infection to
ascend.

Constipation may impair bladder emptying leading to stasis and ascending
infection.

Boys who are uncircumcised have a risk of UTI 2.2% higher than that of
uncircumcised boys. The risk of APN is not established.

Sexual activity may cause urethral inflammation, lead to bladder
colonization, and increase the risk for APN.

VUR increases the risk for and size of renal cortical lesions, though clinically
significant lesions can develop in the absence of VUR.


Pathophysiology
UTIs are generally ascending in origin and caused by
perineal contaminants, usually bowel flora.
Bacterial colonization of the bladder is most likely to
develop into infection if urinary stasis or low-flow
conditions are present.
Some causes of these conditions include infrequent
voiding, incomplete voiding, vesicoureteral reflux (VUR),
obstruction or other urinary tract abnormalities.
Chronic or recurrent pyelonephritis results in renal
damage, scarring, and, if severe, chronic renal failure.
Mortality/Morbidity
Generalized bacteremia or sepsis may develop from pyelonephritis.
In patients younger than 2 years with APN, 8-10% have bacteremia.

Acute renal parenchymal injury occurs in 20-90% of children with
APN. About 40% of these children have long-term renal scarring,
which may lead to hypertension and renal insufficiency. Treatment
of pyelonephritis within the first 5-7 days after onset is necessary to
prevent renal damage.

Impaired renal tubular function and secondary
pseudohypoaldosteronism may develop in infants with
pyelonephritis. Infants may develop hyperkalemia and
hyponatremia.
CLINICAL PICTURE
History:
Signs and symptoms of UTI and pyelonephritis vary with
the age of the patient.

Neonates often present with nonspecific symptoms of
jaundice, hypothermia or fever, poor feeding, vomiting,
and failure to thrive. Neonates, especially male
newborns, may develop hyponatremia and hyperkalemia
as a result of secondary pseudohypoaldosteronism.

Infants and young children aged 2 months to 2 years
often present with nonspecific symptoms of fever lasting
longer than 48 hours, poor feeding, vomiting, and
diarrhea. Their urine may be malodorous; hematuria
may be noted.

Preschoolers and school age children present with fever
for greater than 48 hours. They may complain of
abdominal pain or flank pain. Vomiting, diarrhea, and
anorexia may be present. Their urine is typically
malodorous, and hematuria may be noted. Voiding-
related symptoms including enuresis, dysuria, urgency,
and frequency, may occur but need not be present.

Adolescents are most likely to present with classic adult
symptoms of fever, often with chills, rigors, and flank
pain. They may have abdominal and suprapubic pain,
along with voiding-related symptoms of frequency,
dysuria, and hesitancy. Their urine is most often
malodorous, though hematuria is variably present.

Physical Findings
Because many symptoms of pyelonephritis are nonspecific, complete
physical examination is necessary to exclude other causes of
thepatient's symptoms. Specific findings to look for are describe below.

General appearance
Most infants and children are uncomfortable and appear ill.
Older children and adolescents may be mildly to moderately ill.

Vital signs
Fever, with body temperature >38.0C and often >39C
Tachycardia may be present, secondary to fever and pain.
Blood pressure is usually normal. Hypertension should raise
concern for clinically significant obstruction or renal parenchymal
disease. Hypotension may occur if sepsis and shock are present.
Abdominal findings
Abdominal pain may be present.
A mass may indicate obstruction, hydronephrosis, or another anatomic
abnormality.
Suprapubic pain may be present, though this is more common with
cystitis than with polynephritis.
A palpable bladder indicates obstruction or functional difficulty in
starting or completing voiding.

Back findings
Tenderness in the costovertebral angle (CVA), back, or flank is likely to
be present in older children and adolescents.
Sacral dimple or birthmarks overlying the spine may be associated with
an underlying anomaly of the spinal cord.
Vertebral abnormalities may be evident.


Genitourinary findings

Assess for irritation, pinworms, vaginitis, trauma
A bulging hymen suggests an imperforate hymen and
urethral obstruction.

Neurologic findings

Weak lower extremities or diminished reflexes may be
signs of spinal-cord dysfunction, and they may be
associated with a neurogenic bladder.
DIAGNOSIS
Urine analysis

Urine must be collected with proper technique to be useful for
diagnosing cystitis or APN. Suprapubic bladder aspiration should
be performed in uncircumcised male patients in whom the
urethral meatus is not visible, as well as in infants with
periurethral irritation. Bladder catheterization is the appropriate
technique for obtaining a urine sample in most infants and
young children. A clean-catch, midstream urine sample may be
obtained in children who can cooperate and void on request. A
specimen collected by using sterile bag may be used for
urinalysis but not urine culture.
A urine specimen that is positive for nitrite, leukocyte esterase,
or blood may indicate UTI.
Microscopic examination of an unspun sample that contains >10
WBCs per high-powered field or any bacteria is highly predictive
of a positive urine culture. RBC or WBC casts suggest underlying
renal parenchymal disease. Epithelial cells suggest skin
contamination.
A normal result from urinalysis does not exclude pyelonephritis.

Urine culture

Urine cultures must be obtained in all people with suspected pyelonephritis.
Treatment should not be commenced on the basis of urinalysis results, and
normal urinalysis findings do no exclude an infection. APN may be present even
if urine cultures demonstrate no growth.

A clean-catch urine specimen with more than 100,000 colony-forming units
(CFUs) of a single organism is considered diagnostic of a UTI. Organisms, such
as Lactobacillus, Staphylococcus, or Corynebacterium species may not be
clinically relevant.

Cultures showing >100,000 CFUs of a single organism obtained by means of
transurethral catheterization demonstrate is 95% sensitive and 99% specific for
UTI. Specimens growing 104 CFUs may be consistent with infection, but the test
should be repeated if infection is not likely and if treatment has not yet
commenced.

Cultures from bagged urine specimens are useful only if no growth is observed.
Bagged urine specimens result in a false-positive rate of 85%. Before treatment
is started on the basis of results from a bagged-specimen test, a catheterized or
suprapubic specimen should be obtained.

Structural abnormalities of the urinary tract may be associated with infections
secondary to multiple organisms or unusual gram-negative bacteria, such as
Pseudomonas aeruginosa.



Electrolyte measurements

Some patients may have abnormalities, which may be secondary
to vomiting or diarrhea. In cases of recurrent or chronic
infection, renal scarring may lead to renal failure.

Secondary pseudohypoaldosteronism may develop, with
impaired renal tubular function, in infants with pyelonephritis.
Mild hyponatremia and hyperkalemia may be present. Infants
with underlying urinary-tract anomalies have an increased risk of
this electrolyte imbalance, which resolves when the infection is
treated.
Renal function testing
An increased blood urea nitrogen (BUN) and/or creatinine level should
raise the suspicion for hydronephrosis or renal parenchymal disease.
Determination of inflammatory markers

An elevated WBC count is nonspecific and does not help in distinguishing
lower UTI from upper UTI.
In the presence of a febrile UTI, a erythrocyte sedimentation rate (ESR)
> 30 mm/h is highly predictive of APN.
C-reactive protein (CRP) levels are correlated with parenchymal defects
on dimercaptosuccinic acid (DMSA) scanning. Elevated CRP
concentrations are sensitive but nonspecific markers of renal
parenchymal involvement in the febrile infant and child with UTI. CRP
values may be used to distinguish bladder colonization from APN in a
febrile child with bacteriuria and a neurogenic bladder.
Serum procalcitonin is an acute inflammatory marker with a sensitivity
of 70-95% and a specificity of 80-85% for renal involvement compared
with results of DMSA scan in infants and children with febrile UTI.
Although less sensitive than CRP, procalcitonin is more specific for the
diagnosis of APN. Procalcitonin values are better correlated with long-
term renal scarring than CRP.
Elevated plasma levels of polymorphonuclear elastase have a specificity
and sensitivity of 96% and 50%, respectively, for renal parenchymal
involvement in young children with febrile UTI.
An elevated level of urinary interleukin-6 is correlated with renal
involvement in neonates with UTI.


Imaging Studies
Radiography
Radiographic studies are generally not indicated to diagnose
APN.

Studies may be indicated if the child's condition does not
respond to treatment as expected and if colonization must be
distinguished from infection in the patient with chronic
bacteriuria.

Guidelines from the American Academy of Pediatrics recommend
imaging after first febrile UTIs in infants and young children to
identify abnormalities that may predispose them to recurrent
infection or renal scarring.

Renal ultrasonography
This study is useful to determine the size and shape
of the kidneys, but it is generally poor for visualizing
nondilated ureters. Renal ultrasonography does not
provide information regarding renal function.

Renal ultrasonography has low sensitivity (50%) in
detecting APN, though focal abnormalities on
sonograms, combined with a CRP level of greater
than 70 mg/L may be predictive of renal scarring.

Findings on power Doppler ultrasonography were
recently correlated with DMSA findings of APN.

A renal sonogram is useful in the diagnosis of
urolithiasis, hydronephrosis, hydroureter,
ureteroceles, and bladder distention.


Voiding cystourethrography (VCUG)
VCUG is useful for visualizing the urethral and bladder anatomy and for
the detecting VUR.
VCUG may be performed after 3-4 days of therapy to ensure that
bladder irritability has resolved and that the urine is sterilized. VCUG
should be performed at the earliest convenient time.
The voiding phase is needed to evaluate for VUR and posterior urethral
valves.

Nuclear cystography
This study is good for evaluating the bladder and detecting
VUR. However, it does not permit adequate evaluation of
the urethra and is therefore not used for an initial
evaluation of the urologic anatomy.
Cystography has only about 1% of radiation dose of fluoroscopic study.
Cystography may be used for serial follow-up studies.

Nuclear cortical scanning

Nuclear cortical scanning depicts tubular damage and scarring. It
provides information regarding the general size of the kidneys;
however, it does not provide detailed information regarding the
collecting system. DMSA scanning is not necessary to evaluate
or follow up most episodes of APN.
This study most frequently involves the use of technetium-99m
DMSA to depict renal cortical scarring. The volume of initial
defect is useful in predicting the development of renal scars.
Follow-up DMSA scans performed >6 months after APN resolves
are useful to detect permanent renal scarring. Studies performed
< 6 months after APN may show residua of the original infection
rather than permanent scars.
DMSA scans can help in determining the cause of fever in
children with chronic bacteriuria, such as patients with spinal-
cord injury and those who undergo clean intermittent
catheterization.
Radiation exposure to the patient undergoing this procedure is
low.

MRI: Gadolinium-enhanced MRIs are
correlated with DMSA scans in detecting
renal parenchymal defects and is effective
in distinguishing acute inflammation from
scars.
CT: Enhanced CT may be useful in
distinguishing APN from other causes of
fever.

Gross specimen of kidney in acute severe
complicated pyelonephritis showing multiple
microabcessess. The surface of the kdney is
dotted with widespread, small, yellowish
microabcessess.
Pyelonephritis in renal transplantation
Histopathologic examination in pyelonephritis. Higher magnification
of the kidney shows severe infiltration of lymphocytes and plasma
cells; glomerular, periglomerular and interstitial fibrosis with
extensive tubule loss and atrophy.
TREATMENT
Medical Care

Routine supportive care includes adequate hydration, analgesia, and use of
antipyretics.

Intravenous (IV) fluid replacement and parenteral antibiotics are indicated for
children unable to take medication and fluids orally (PO). IV therapy may
be continued until the child can receive PO medication and fluids.

Septic or toxic patients require hospitalization for treatment.

Treatment with fluids and PO antibiotics may be given on an outpatient basis if
children are not vomiting and not markedly ill.

The optimal duration of therapy is not well studied, though recommended
treatment is in the range of 7-14 days. Some studies have shown that
recurrent infection rates increase with short courses of treatment.

The results of urine cultures ultimately dictate the choice of antibiotics.
Because E coli causes more than 95% of all cases of APN in children, initial
treatment should be based on regional susceptibility to this pathogen.
Because of high resistance rates to amoxicillin, initial treatment should
include a cephalosporin (third or fourth generation), amoxicillin-clavulanic
acid, trimethoprim-sulfamethoxazole (TMP-SMZ), or aminoglycoside.

Initial PO therapy with cefixime or amoxicillin-clavulanate is equivalent to IV
ceftriaxone for 3 days followed by PO therapy. Rates of renal scarring are equal
in children treated PO and IV, though further study is needed to determine
whether a subgroup of children with dilating VUR may have high rates of renal
scarring if treated with PO antibiotics. Further studies are needed to ensure that
currently available antibiotics have the same efficacy.

Initial therapy with IV antibiotics for 3-4 days followed by PO therapy to
complete a 10-14 day course is equivalent to 10-14 days of IV therapy.

A single dose of ceftriaxone given intramuscularly (IM) followed by PO therapy
offers no advantage over 10 days of PO therapy alone. Hospitalization is required
in similar numbers because of vomiting.

IV gentamicin may be dosed daily rather than 3 times a day for children who
require IV treatment or who are infected with multiresistant organisms.

To the authors' knowledge, recommendations for treatment of infants and
children with neurogenic bladder or clinically significant anatomic abnormality
have not been studied.

MEDICATION
Antibiotic therapy should be started after
the urinalysis and cultures have been
performed. A 7-14-day course of
antibiotics is recommended.
Drug Category :Antibiotic agents -- Empiric
antibiotics should be chosen to cover E
coli and Enterococcus, Proteus ,and
Klebsiella species .
Drug Name
Ampicillin (Omnipen, Polycillin, Principen)
Bactericidal activity against susceptible
organisms. Alternative to amoxicillin when
patients unable to take medication PO.
Administered parenterally and used in
combination with gentamicin or cefotaxime .
Adult Dose 250 - 500 mg PO q6h
500mg to 3 g IV q4-6h; not to exceed 12 g/d
Contraindications Documented
hypersensitivity
Precautions Adjust dose in renal failure;
evaluate rash and differentiate from
hypersensitivity reaction
Drug Name
Gentamicin (Garamycin)
Aminoglycoside antibiotic for gram-negative coverage.
Administered parenterally; may be used with ampicillin .
Adult Dose 3 - 6 mg/kg/d IV divided q8h
Contraindications Documented hypersensitivity
Interactions Coadministration with other
aminoglycosides, cephalosporins, penicillins, and
amphotericin B may increase nephrotoxicity; because
aminoglycosides enhance effects of neuromuscular
blocking agents, prolonged respiratory depression may
occur; coadministration with other ototoxic drugs (eg,
loop diuretics, cisplatin) may increase auditory toxicity of
aminoglycosides; possible irreversible hearing loss of
various degrees may occur (monitor regularly )
Precautions Adjust dose in renal failure; monitor
gentamicin levels to prevent ototoxicity
Drug Name
Cefotaxime (Claforan)
Third-generation cephalosporin with gram-negative
spectrum. Decreased efficacy against gram-positive
organisms. Arrests bacterial cell-wall synthesis .
Adult Dose 1 - 2 g IV q6-8h; not to exceed 12 g/d

Drug Name
Amoxicillin (Trimox, Amoxil)
Interferes with synthesis of cell-wall mucopeptides
during active multiplication, resulting in bactericidal
activity against susceptible bacteria.
Adult Dose250-500 mg PO q8h, or 500-875 mg PO
q12h; not to exceed 3 g/d
Drug Name
TMP-SMZ (Bactrim, Septra)
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.
Antibacterial activity against common urinary-tract pathogens .
Adult Dose 160mg TMP and 800 mg SMZ (ie, 1 double-strength
tab) PO bid

Drug Name
Amoxicillin and clavulanic acid (Augmentin)
Amino penicillin with beta-lactamase inhibitor. For infants and
children >3 mo, base dosing on amoxicillin content. Because of
different amoxicillinclavulanic acid ratios in 250-mg (250 mg/125
mg) vs 250-mg chewable tab (250 mg/62.5 mg), do not use 250-mg
tab until child weighs >40 kg.
Adult Dose250-500 mg PO tid; 875 mg PO bid for severe
infections; not to exceed 2 g/24 h
Complication :

Dehydration is the most common acute
complication of pyelonephritis. IV fluid
replacement is necessary in severe cases.
APN may lead to renal abscess formation.
Long-term complications include renal
parenchyma scarring, hypertension,
decreased renal function, and, in severe
cases, renal failure.
Prognosis
Most cases of pyelonephritis respond readily to antibiotic
treatments without further sequelae.
Permanent renal scars develop in 18-24% of children
after APN. Treatment within 5 days from the onset
significantly reduces the formation of renal scars.
For patients with severe cases or chronic infections,
appropriate treatment, imaging, and follow-up help
prevent long-term sequelae.
VUR often resolves without permanent damage,
provided that patients adhere to prophylactic
antimicrobial therapy. Recurrent pyelonephritis in the
setting of VUR may be an indication for ureteral
reimplantation.