Nephrology

Pyelonephritis
Dr. / Soha M. Nageb
Lecturer of Internal Medicine
MUE
 URINARY TRACT INFECTION
Incidence:
 Urinary tract infection (UTI) is common in women, in whom it
usually occurs in an anatomically normal urinary tract.
 Conversely, it is uncommon in men and children, and the urinary

tract is often abnormal and requires investigation.

Etiology and pathogenesis:
Organism and route of infection:
1- Ascending route from bowel flora (the most common, mainly
gram –ve bacteria).
2-Hematogenous or lymphatic spread.
2- Direct extension (e.g. vesicocolic fistula).
Virulence of the organisms:
Ability to adhere to epithelial cells determines the degree of virulence
of the organism. For E. coli, these adhesive factors include flagella (for
motility), aerobactin (for iron acquisition in the iron-poor environment
of the urinary tract), haemolysin (for pore forming) and adhesins on
the bacterial fimbriae.
Innate host defense: The following host defense mechanisms are
necessary to prevent UTI:
1- Neutrophils: Activation of neutrophils is essential for bacterial
killing. impaired function of neutrophils predisposes an individual
to severe UTI.
2- Urine osmolality and pH – urinary osmolality >800 mOsm/kg and
low or high pH reduce bacterial survival.
3- Complement – complement activation with IgA production by
uroepithelium (acquired immunity) also plays a major role in
defense against UTI.
4- Commensal organisms – such as lactobacilli, corynebacteria,
streptococci and bacteroides are part of the normal host defense.
Eradication of these commensal organisms by spermicidal jelly or
disruption by certain antibiotics results in the overgrowth of
E. coli.
5- Urine flow: urine flow and normal micturition wash out bacteria.
Urine stasis promotes UTI.
6- The glycocalyx covering uroepithelium, has antibacterial
properties. These proteins interfere with bacterial binding to
uroepithelium. Disruption of this uroepithelium by trauma (e.g.
sexual intercourse or catheterization) predisposes to UTI.
7- Blood group antigens – women who are non-secretors of ABH
blood group antigens are three to four times more likely to have
recurrent UTIs.

Natural history:
UTI is
 isolated, or repeated
 Complicated versus uncomplicated infection.
  It is necessary to distinguish between UTI occurring in
patients with functionally normal urinary tracts and in
those with abnormal tracts.
Complicated versus uncomplicated infection
 Functionally normal urinary tracts (with normal renal
imaging): Here, persistent or recurrent infection seldom
results in serious kidney damage (uncomplicated UTI).
 Abnormal urinary tracts: Tracts with stones, or associated
diseases such as diabetes mellitus which themselves cause
kidney damage, may be made worse with infection
(complicated UTI). UTI, particularly with Proteus, may
predispose to stone formation. The combination of infection
and obstruction results in severe, sometimes rapid, kidney
damage (obstructive pyonephrosis) and is a major cause of
Gram-negative septicemia.
Reinfection versus relapsing infection :

When UTI is recurrent, it is necessary to distinguish between relapse

and reinfection:
Relapse is diagnosed by the recurrence of bacteriuria with the same
organism within 7 days of completion of antibacterial treatment and
implies failure to eradicate infection usually in conditions such as
stones, scarred kidneys, polycystic disease or bacterial prostatitis.
Reinfection is when bacteriuria is absent after treatment for at least 14
days, usually longer, followed by recurrence of infection with the same
or different organisms. This is not due to failure to eradicate infection,
but is the result of reinvasion of a susceptible tract with new organisms.
Approximately 80% of recurrent infections are due to reinfection.
 Reinfection implies that the patient has a predisposition to
periurethral colonization or poor bladder defense mechanisms
(the use of a diaphragm and spermicidal jelly discouraged. Atrophic
vaginitis in postmenopausal women).

Clinical picture:
 Symptoms of lower urinary tract infection (cystitis, urethritis):
1-Frequency of micturition by day and night
2- Painful voiding (dysuria), children cannot express dysuria but rather
may complain of abdominal pain.
3-Suprapubic pain and tenderness
4-Haematuria
5- Smelly urine.
 The combination of fever, loin pain with tenderness suggests
pyelonephritis.
 Take care: the presence of fever with urinary symptoms suggests
parynchematous organ infection: prostatitis, orchitis,
epidydymitis, and pyelonephritis.
Complications:
1- Recurrent infection causes considerable morbidity; if complicated, it
can cause severe renal disease including ESKD.
2- It is also a common source of life-threatening Gram-negative
septicemia.
Investigation:
1- Urine analysis( dipstick)
 Pyuria.
 Most Gram negative organisms reduce nitrates to nitrites.
 Esterases released from leucocytes.
2- Quantitative culture of a clean-catch midstream specimen:
• Significant bacteriuria.

 ‘Sterile pyuria’, Chlamydia infection and tuberculosis must be

excluded.
3- Special investigations: radiological investigations is needed in
cases of;
 Recurrent infection
 Males and children
 Unusually severe symptoms.
 Diabetes mellitus or immunocompromised state.
 Complicated UTI.
1- Ultrasound: calculi, obstruction
2- CT: is a more sensitive modality.
3-MRI is particularly useful in those with iodinated contrast
Allergies
Treatment:
1- Single isolated attack
‘Pre-treatment urine culture is desirable’.
 Antibiotics for 3–5 days with amoxicillin (250 mg three times
daily), nitrofurantoin (50 mg three times daily), trimethoprim
(200 mg twice daily) or an oral cephalosporin.
-The treatment regimen is modified in light of the result of urine
culture and sensitivity testing, and/or the clinical response.
- For resistant organisms the alternative drugs are co-amoxiclav or
ciprofloxacin.

 A high (2 L daily) fluid intake should be encouraged during

treatment and for some subsequent weeks.
-Urine culture should be repeated 5 days after treatment.
-Recurrent or relapse infection?
 Pre-treatment and post-treatment urine cultures are necessary to
confirm the diagnosis and identify whether recurrent infection is
due to relapse or reinfection.
 Relapse. A search should be made for a cause (e.g. stones or
scarred kidneys), and this should be eradicated.
 Intense or prolonged treatment intravenous or intramuscular
aminoglycoside for 7 days or oral antibiotics for 4–6 weeks – is
required.
 If this fails, long-term antibiotics are required.
  Identify and manage risk factor for reinfection: contraceptive
practice and the use of a diaphragm and spermicidal jelly.
Atrophic vaginitis should be identified in postmenopausal
women.
 Prophylactic measures:
-A 2 L daily fluid intake
-Voiding at 2–3-hour intervals, before bedtime and after
intercourse
-Avoidance of spermicidal jellies and bubble baths and other
chemicals in bath water
-Avoidance of constipation, which may impair bladder emptying.
 If UTI continues to recur, treatment for 6–12 months with low-
dose prophylaxis (trimethoprim 100 mg, co-trimoxazole 480 mg,
cefalexin 125 mg at night) is required.
-it should be taken last thing at night when urine flow is low.
Urinary infections in the presence of an indwelling catheter
Urinary infections in the presence of an indwelling catheter
1-Colonization of the bladder by a urinary pathogen is common
after a urinary catheter has been present for more than a few
days, partly due to organisms forming biofilms.
2-So long as the bladder catheter is in situ, antibiotic treatment is
likely to be ineffective and will encourage the development of
resistant organisms.
3-Treatment with antibiotics is indicated only if the patient has
symptoms or evidence of infection, and should be accompanied
by replacement of the catheter.
 4-When changing catheters, a single injection of gentamicin is
recommended.
5- Infection by Candida is a frequent complication of prolonged
bladder catheterization. Treatment should be reserved for
patients with evidence of invasive infection or those who are
immunosuppressed, and should consist of removal or
replacement of the catheter. In severe infections continuous
bladder irrigation with amphotericin 50 µg/mL is used.

Bacteriuria in pregnancy
The urine of all pregnant women must be cultured, as 2–6% have
asymptomatic bacteriuria. While asymptomatic bacteriuria in the
non-pregnant female seldom leads to acute pyelonephritis and
often does not require treatment,
acute pyelonephritis frequently occurs in pregnancy under these
circumstances. Failure to treat may thus result in severe
symptomatic pyelonephritis later in pregnancy, with the possibility
of premature labour.
Asymptomatic bacteriuria, in the presence of previous renal
disease, may predispose to pre-eclampsia toxemia, anemia of
pregnancy, and small or premature babies.
Treatment: Tetracycline, trimethoprim, sulphonamides,
Amoxicillin, ampicillin, nitrofurantoin and oral cephalosporin
-Quinolones must be avoided in pregnancy
Tuberculosis of the urinary tract
Pathology:
1-Cortical lesions result from hematogenous spread in the primary
phase of infection.
2-infection may spread to the papillae, with the formation of
cavitating lesions and the discharge of mycobacteria into the urine.
3-Infection of the ureters and bladder commonly follows, with the
potential for the development of ureteral stricture and a contracted
bladder.
Presentation: frequency, dysuria or hematuria.
Diagnosis: patients presents with
 Sterile pyuria.
 Culture of mycobacteria from early-morning urine samples.
 Imaging may show cavitating lesions in the renal papillary
areas, commonly with calcification. There may also be
evidence of ureteral obstruction with hydronephrosis.
 Renal biopsy demonstrating caseating granuloma with
multinucleate giant cells and acid-fast bacilli on Ziehl–Neelsen
staining.
Treatment. The treatment is antituberculous regimen.

Acute pyelonephritis
Pathological picture: Macroscopic: Small renal cortical
abscesses and streaks of pus in the renal medulla are often present.
Microscopic: focal infiltration by polymorphonuclear leucocytes and
many polymorphs in tubular lumina.

Investigations: as above but;

-urgent renal ultrasound examination is required to exclude an
obstructed pyonephrosis.

Treatment:
1-Antibiotics are given intravenously, e.g. aztreonam, cefuroxime,
ciprofloxacin or gentamicin (2–5 mg/kg daily in divided doses),
switching to a further 7 days’ treatment with oral therapy as
symptoms improve.
2-Intravenous fluids may be required to achieve a good urine output.
3-percutaneous nephrostomy: in cases of pyonephrosis.

Complications: Although, with antibiotics, significant

permanent kidney damage in adults with normal urinary tracts is rare,
CT scanning can show wedge-shaped areas of inflammation in the renal
cortex and hence damage to renal function.
 Reflux nephropathy
It results from a combination of:
1- Vesicoureteral reflux, and
2- Infection acquired in infancy or early childhood.
Pathophysiology:
• Normally, the vesicoureteral junction acts as a one-way valve,
urine entering the bladder from above; the ureter is shut off
during bladder contraction, thus preventing reflux of urine. In
some infants and children, (possibly even in utero), this valve
mechanism is incompetent, bladder voiding being associated
with variable reflux of a jet of urine up the ureter.
• A secondary consequence is incomplete bladder emptying, as
refluxed urine returns to the bladder after voiding. This latter
event predisposes to infection, and the reflux of infected urine
leads to kidney damage.
• Typically, there is papillary damage, tubulointerstitial nephritis
and cortical scarring in areas adjacent to ‘clubbed calyces’.
• Reflux usually ceases around puberty with growth of the bladder
base. But Damage already done persists and progressive renal
fibrosis and further loss of function occur in severe cases even
though there is no further infection.
Diagnosis: CT scan of the kidneys, which shows irregular renal
outlines, clubbed calyces and a variable reduction in renal size. The condition
may be unilateral or bilateral and affect all or part of the kidney.
Complications:
Chronic reflux nephropathy acquired in infancy predisposes to hypertension
in later life and, if severe, is a relatively common cause of ESKD in childhood
or adult life.
Management:
Meticulous early detection and control of infection, with or without ureteral
reimplantation to create a competent valve, can prevent further scarring and
allow normal growth of the kidneys.

Conditions that simulates UTI

Interstitial cystitis (autoimmune disorder)
-most often affecting women over the age of 40 years.
-It presents with frequency, dysuria and often severe suprapubic pain.
-Urine cultures are sterile.
- Cystoscopy shows typical inflammatory changes with ulceration of the
bladder base.
-treatments include oral prednisolone therapy
Irritable bladder (Overactive bladder)
-Predominant frequency and passage of small volumes of urine with
no organic cause identified.