URINARY TRACT INFECTION

ETIOLOGY
Urinary tract infections (UTIs) include cystitis (infection localized to the
bladder), pyelonephritis (infection of the renal parenchyma, calyces,
and renal pelvis), and renal abscess, which may be intrarenal or
perinephric. The urinary tract and urine are normally sterile.
Escherichia coli, ascending from bowel flora, accounts for 90% of first
infections and 75% of recurrent infections.
Other bacteria commonly causing infection include Klebsiella, Proteus,
Enterococcus, and Pseudomonas. Staphylococcus saprophyticus is
associated with UTI in some children and in sexually active adolescent
girls.
Approximately 8% of girls and 2% of boys have a UTI by 11 years of age.
A short urethra predisposes girls to UTI. Uncircumcised male infants are
at 5- to 12-fold increased risk for UTI compared with circumcised male
infants. Obstruction to urine flow and urinary stasis is the major risk
factor and may result from anatomic abnormalities, nephrolithiasis,
renal tumor, indwelling urinary catheter, ureteropelvic junction
obstruction, megaureter, extrinsic compression, and pregnancy.
Vesicoureteral reflux, whether primary (70% of cases) or secondary to
urinary tract obstruction, predisposes to chronic infection and renal
scarring. Scarring also may develop in the absence of reflux.
CLINICAL MANIFESTATIONS
The symptoms and signs of UTI vary markedly with age. Few have high
positive predictive values in neonates, with failure to thrive, feeding
problems, and fever as the most consistent symptoms. Direct
hyperbilirubinemia may develop secondary to gram-negative endotoxin.
Infants 1 month to 2 years old may present with feeding problems, failure
to thrive, diarrhea, vomiting, or unexplained fever. The symptoms may
masquerade as gastrointestinal illness with colic, irritability, and screaming
periods. At 2 years of age, children begin to show the classic signs of UTI
such as urgency, dysuria, frequency, and abdominal or back pain. The
presence of UTI should be suspected in all infants and young children with
unexplained fever and in patients of all ages with fever and congenital
anomalies of the urinary tract.
LABORATORY AND IMAGING
STUDIES
The diagnosis of UTI in infants and young children requires the presence of
both pyuria and at least 50,000 CFU/mL of a single pathogenic organism.
For older children and adolescents, >100,000 CFU/mL indicates infection.
Urine samples for urinalysis should be examined promptly (within 20
minutes) or refrigerated until cultured. Urine obtained by midstream,
clean-catch technique for older children and adolescents is an appropriate
collection method, whereas transurethral catheterization is the
appropriate method for younger children and infants in which antibiotics
are being started. Perineal bags for urine collection are prone to
contamination and are not recommended for urine collection for culture.
If there is uncertainty about diagnosis of UTI in a younger child or infant,
urine can be collected by the most convenient method for urinalysis and if
suggestive of infection, collect urine by catheterization prior to starting
antibiotics.
Urinalysis showing pyuria (leukocyturia of >10 white blood cells
[WBCs]/mm3) suggests infection, but also is consistent with urethritis,
vaginitis, nephrolithiasis, glomerulonephritis, and interstitial nephritis.
Urinary dipstick tests that combine both the leukocyte esterase and
nitrite (or positive leukocyte esterase and positive microscopy for
bacteria) have sensitivity of 70% and specificity of 99% for detecting a
UTI.
Ultrasonography of the bladder and kidneys is recommended for
infants with febrile UTIs to exclude structural abnormalities or detect
hydronephrosis.
TREATMENT - CEPHALOSPORINS
Empirical therapy should be initiated for symptomatic children and for
all children with a urine culture confirming UTI. For an older child who
does not appear ill but has a positive urine culture, oral antibiotic
therapy should be initiated. For a child with suspected UTI who appears
toxic, appears dehydrated, or is unable to retain oral fluids, initial
antibiotic therapy should be administered parenterally, and
hospitalization should be considered. Neonates with UTI are treated for
10 to 14 days with parenteral antibiotics because of the higher rate of
bacteremia. Older children with UTI are treated for 7 to 14 days. Initial
treatment with parenteral antibiotics is determined by clinical status.
Vesicourethral reflux
Parenteral antibiotics should be continued until there is clinical
improvement (typically 24 to 48 hours). Specific antibiotic therapy
should be guided by the local antimicrobial susceptibility patterns and
the results of the patient’s urine cultures because of increasing
problems related to antimicrobial resistance. Commonly used
parenteral antibiotics include ceftriaxone or gentamicin.
Oral regimens include a cephalosporin, amoxicillin plus clavulanic acid,
or trimethoprim sulfamethoxazole.
NEPHROTIC SYNDROME AND
PROTEINURIA
• ETIOLOGY AND EPIDEMIOLOGY
NS may be primary or secondary. A child with apparent primary NS, prior to
renal biopsy, is considered to have idiopathic nephrotic syndrome. Minimal
change nephrotic syndrome (MCNS) is the most common histologic form of
primary NS in children. More than 80% of children less than 7 years of age with
NS have MCNS. Children 7 to 16 years old with NS have a 50% chance of having
MCNS. Males are affected more frequently than females (2:1).
Focal segmental glomerulosclerosis (FSGS) accounts for approximately 10% to
20% of children with primary NS. FSGS may develop from MCNS or represent a
separate entity. A circulating factor that increases glomerular permeability is
found in some patients with FSGS. More than 35% of children with FSGS
progress to renal failure
Membranoproliferative glomerulonephritis (MPGN) is characterized by
hypocomplementemia with signs of glomerular renal disease. MPGN
represents 5% to 15% of children with primary NS, is typically
persistent, and has a high likelihood of progression to renal failure over
time.
Membranous nephropathy represents less than 5% of children with
primary NS. It is seen most commonly in adolescents and children with
systemic infections, such as hepatitis B, syphilis, malaria, and
toxoplasmosis, or on specific medications.
Congenital NS presents during the first 2 months of life. There are two
common types. The Finnish type is an autosomal recessive disorder
most common in persons of Scandinavian descent and is due to a
mutation in the nephrin protein component in the glomerular filtration
slit. The second type is a heterogeneous group of abnormalities,
including diffuse mesangial sclerosis and conditions associated with
drugs or infections.
CLINICAL MANIFESTATIONS

The sudden onset of dependent pitting edema or ascites is the most

common presentation for children with NS. Anorexia, malaise, and
abdominal pain are often present. Blood pressure may be elevated in
up to 25% of children on presentation; acute tubular necrosis and
significant hypotension may occur with sudden decline in serum
albumin and significant volume depletion. Diarrhea (intestinal edema)
and respiratory distress (pulmonary edema or pleural effusion) may be
present. Typical MCNS is characterized by the absence of gross
hematuria, renal insufficiency, hypertension, and
hypocomplementemia.
DIAGNOSTIC STUDIES
Proteinuria of 1+ or higher on 2 to 3 random urine specimens suggests
persistent proteinuria that should be further quantified. A UPr/Cr >0.2
on a first morning specimen excludes orthostatic proteinuria. UPr/Cr
>2.0 indicates nephrotic range proteinuria.
TREATMENT
Because greater than 80% of children less than 13 years of age with
primary NS have steroid-responsive forms (chiefly MCNS), steroid
therapy may be initiated without a renal biopsy if a child has typical
features of NS. Typical therapy for MCNS is prednisone, 2 mg/kg/day,
provided once a day or split into multiple doses. Over 90% of children
who respond to steroids do so within 4 weeks. Responders should
receive steroids for 12 weeks. A renal biopsy is indicated for
nonresponseders because steroid resistance decreases the chance that
MCNS is the underlying disease. Frequent relapses or steroid resistance
may necessitate additional immunosuppressive therapy.
NS edema is treated by restricting salt intake. Severe edema may
require the use of loop diuretics. When these therapies do not alleviate
severe edema, cautious parenteral administration of 25% albumin (0.5
to 1.0 g/kg intravenously over 1 to 2 hours) with an intravenous loop
diuretic usually results in diuresis. The administered albumin is excreted
rapidly, and, thus, salt restriction and diuretics must be continued.
Significant pleural effusions may require drainage. Acute HTN is treated
with β-blockers or calcium channel blockers.
HEMOLYTIC UREMIC SYNDROME
ETIOLOGY AND EPIDEMIOLOGY
Hemolytic uremic syndrome (HUS) is characterized by the triad of
microangiopathic hemolytic anemia, thrombocyto- penia, and renal
injury and is an important cause of acute kidney injury in children. HUS
typically occurs in children less than 5 years of age but can occur in older
children. The most common type of HUS is associated with a prodromal
diarrheal illness (D+HUS). Contamination of meat, fruit, veg- etables, or
water with verotoxin (VT)-producing Escherichia coli (most commonly E.
coli O157:H7) is responsible for many outbreaks. VT may be produced by
other E. coli strains as well as other bacteria such as Shigella. VT causes
hemorrhagic enterocolitis of variable severity and results in HUS in 5% to
15% of affected children.
HUS presenting without a prodrome of diarrhea (atypical HUS) may occur
at any age. The clinical course is usually more severe than that of D+HUS.
CLINICAL MANIFESTATIONS

Classic D+HUS begins with enterocolitis, often with bloody stools,

followed in 7 to 10 days by weakness, lethargy, and
oliguria/anuria. Physical examination reveals irritability, pallor, and
petechiae. Dehydration is often present; however some children
have volume overload. Hypertension may be due to volume
overload and/or renal injury. Central nervous system (CNS)
involvement, including seizures, occurs in up to 25% of cases.
Other potential organ involvement includes pancreatitis, cardiac
dysfunction, and colonic perforation.
Children without evidence of a diarrheal prodrome may have a
similar microangiopathic syndrome, identified as thrombotic
thrombocytopenic purpura (TTP).
 Common Laboratory Findings with Hemolytic Uremic
Syndrome

EVIDENCE OF MICROANGIOPATHIC HEMOLYTIC ANEMIA

Anemia
Thrombocytopenia
Presence of schistocytes, helmet cells, and burr cells on peripheral blood
smear
Increased LDH
Decreased haptoglobin
Increased indirect bilirubin DIAGNOSTIC STUDIES
Increased AST Common laboratory
Elevated reticulocyte count findings in HUS are listed
EVIDENCE OF RENAL INJURY in Table. Peripheral blood
smear reveals evidence
Elevated creatinine
Presence of hematuria, proteinuria, pyuria, casts on urinalysis of microangiopathic
hemolysis. Coombs test is
OTHER POTENTIAL FINDINGS
negative. The diarrhea
Leukocytosis and presence of toxin-
Positive stool culture for E. coli O157:H7 Positive stool test for shiga-toxin
Elevated amylase/lipase
producing E. coli may
have resolved by the time
HUS is diagnosed.
TREATMENT AND PROGNOSIS

Therapy for HUS is supportive and includes volume repletion,

control of hypertension, and managing complications of renal
insufficiency, including dialysis when indicated. Red blood cell
transfusions are provided as needed. Platelet transfusions should
be avoided because they may add to the thrombotic
microangiopathy and are indicated only by active hemorrhage or
in anticipation of a procedure. Antibiotics and antidiarrheal agents
may increase the risk of developing HUS. Early hydra- tion during
the diarrheal phase may lessen the severity of renal insufficiency.
Most children (>95%) with D+HUS survive the acute phase and
recover normal renal function, although some may have evidence
of long-term morbidity.
Potter sequence