1
Pediatrics
Renal system
----------------------------------------------------------------------------------------------
www.facebook.com/ibnlatef
https://goo.gl/RpvNsl
Ibnlatef
Notes
2
Subject1:
Urinary tract infection
Introduction:
Urinary tract infections (UTI) is common in the pediatric age group.
Early recognition and prompt treatment of UTI are important to prevent progression of
infection to pyelonephritis or urosepsis and to avoid late sequelae such as renal
scarring or renal failure.
UTI include:
o
Cystitis infection localized to the bladder.
o
Pyelonephritis infection of the renal parenchyma, calyces, renal pelvis.
o
Renal abscess which may be intrarenal or perinephric.
Epidemiology:
UTI is more frequent in females than males at all ages with the exception of the
infantile period.
Approximately 8% of girls and 2% of boys have a UTI by 11 years of age.
In infants, boys are affected more than five times as often as girls.
After 12 months of age, UTI in healthy children usually is seen in girls.
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.
The prevalence of UTIs varies with age :
o
During the 1st year of life the male : female ratio is 2.8-5.4 : 1.
o
Beyond 1-2 year there is female preponderance, with a male : female ratio of
1 : 10 .
Etiology:
Bacteria:
o
UTIs are caused mainly by colonic bacteria.
o
Gram-negative enteric bacteria of the Enterobacteriaceae family cause most UTIs in
children of all ages, t
o
Enterobacteriaceae includes Escherichia coli (which are responsible for 80–85%
of all UTIs among children), Klebsiella, Proteus, and Enterobacter spp
o
The other members of the Enterobacteriaceae family are less frequent causes of
UTI .
3
o
Less commonly, Pseudomonas aeruginosa, Gram-positive organisms such as
Enterococcus and Staphylococcus, and Group B Streptococcus also cause UTI in
children.
o
Group B Streptococcus is almost exclusively seen as a cause of UTI in neonates,
whereas Staphylococcus saprophyticus is typically seen in adolescent.
o
Staphylococcus aureus is an uncommon cause of UTI and may be the result of
hematogenous spread to the kidney.
o
Infection with S. aureus often results in focal renal lesions, such as intrarenal and
perinephric abscesses .
Others:
o
Adenovirus infections also can occur, especially as a cause of hemorrhagic cystitis
and it more common in male .
o
Fungal and parasitic and other viral infections of the urinary tract are also
encountered especially in immunocompromised and susceptible subpopulations .
o
In neonates, infection of the urinary tract is assumed to be due to hematogenous
rather than ascending infection, this etiology may explain the nonspecific symptoms
associated with UTI in these patients.
Risk factors:
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.
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.
4
Management :
1-Introduction:
There are four main steps in the clinical management of UTIs in childhood :
o
Diagnosis of UTI.
o
Determination of the site of the infection.
o
Search for the cause of the UTI.
o
Treatment.
Diagnosis of UTI depend on clinical presentations and investigations .
Manifestations of UTI vary with :
o
Age.
o
Site of infection within the urinary tract.
o
Severity of infection .
2-History:
Symptoms:
o
Urinary tract infections may occur without
symptoms, with symptoms that direct attention to
the urinary system, or with symptoms that divert
the attention to other organ systems.
o
Thus, the clinician must maintain a high index of
suspicion for UTI, particularly in infants and young
children with vague or nonspecific infectious symptoms.
In neonates and first 3 months:
o
Lethargy, irritability, poor feeding, vomiting, diarrhea, apnea, fever or hypothermia,
and prolonged jaundice are all frequent findings.
o
Although very nonspecific and often more suggestive of acute gastroenteritis than
UTI, the diagnosis is rarely missed, since a urinalysis and urine culture are routinely
part of the septic screen evaluation performed in this age group .
3 months to 3 years old :
o
Fever, constitutional complaints, abdominal discomfort, and GI symptoms are
common in pyelonephritis .
o
Whereas frequency and irritability on micturition are often the only indicators of
cystitis .
In older children who are both verbal and toilet trained:
o
The diagnosis becomes more straightforward.
o
With cystitis, all or some combination of the classic signs of dysuria, frequency,
urgency, suprapubic discomfort, daytime or nocturnal enuresis, and perhaps low-
grade fever are present.
5
o
With pyelonephritis, high fever, clinical toxicity, vomiting, and abdominal and/or
flank pain are most common, these upper tract symptoms may or may not be
accompanied by lower tract complaints .
3-Physical examination:
Findings in infants who have a UTI may be normal except for fever and irritability.
Older children may report direct tenderness on palpation of the abdomen, suprapubic
area, or costovertebral angle (CVA) (Murphy test), if -ve is not reliable to exclude
parenchymal infection in young children.
However, when present it is helpful and should be performed as part of the physical
examination of all children suspected of UTI .
Patients who have urinary tract obstruction may have palpable abdominal masses .
Dribbling, poor stream, or straining to void
Examine external genitalia for signs of irritation, pinworms, vaginitis, trauma, phimosis
or meatal stenosis .
Hypertension should raise suspicion of hydronephrosis or renal parenchyma disease .
4-Localization of the UTI:
The differentiation between upper (pyelonephritis) and lower (cystitis) UTI is very
important.
It particularly has major clinical implications in young children.
The risk of renal scarring is significant with pyelonephritis, and not a concern with
cystitis.
Therefore the management (investigations, antibiotic used, length of therapy) is totally
different for pyelonephritis and cystitis.
The location of the site of infection is based on a combination of clinical, laboratory
and imaging findings .
In the cystitis syndrome:
o
The bladder/voiding symptoms is common such as frequency, pain with micturition,
suprapubic discomfort, difficulty in voiding (retention) or hesitancy, urgency, and
enuresis .
o
Back and suprapubic pain, as well as fever, may occur.
o
Gross hematuria (without casts) is a common finding.
o
Bacterial infection, particularly E.coli cause hematuria in girls whereas in boys,
adenovirus infection occurs frequently.
o
The urine culture will reveal the offending organisms in the former instance and will
be sterile in the latter.
In the classic pyelonephritis syndrome:
6
o
The patient has generalized symptoms that may include a toxic appearance, high
fever, chills, vomiting, diarrhea, and abdominal pain in addition to the urinary outlet
symptoms.
o
The urinalysis usually reveals typical pyuria and bacteria, and often, white blood cell
(WBC) casts are observed.
5-Investigations:
Methods to Obtain urine specimens :
o
The gold standard for obtaining urine in an infant is by suprapubic aspiration, by
using this method the risk of contamination is very low, complications are rare with
the use of ultrasound guidance .
o
Urinary catheterization is also a very reliable method for obtaining urine without
contamination.
o
Clean-catch mid-stream urine specimens can be collected in toilet-trained children .
o
Urine collected in bags is generally not suitable for culture because of the high
incidence of contamination, If a scaled adhesive bag is to be used for collection of
urine sample, the following conditions should be considered for better results :
The skin should be dried thoroughly after cleaning the periurethral area.
The child should be kept in an upright position to prevent having urine come in
contact with the skin or entering the vagina.
The bag should be removed immediately after the child has voided.
o
The urine should examined within 20 min or refrigerated immediately at +4c until
cultured to prevent growth of contaminating bacteria and it is essential that this
temperature be maintained during transport .
Urinalysis:
o
Urine color and smell:
Turbid urine may be an indication of pyuria and UTI.
Abnormal smell may be suggestive of onset of UTI but it is a poor indicator of
screening for UTI .
o
Urine microscopy :
Bacteriuria Detection of any bacteria in the uncentrifuged urine slide stained
with Gram stain has been used as the gold standard for presumptive diagnosis of
UTI .
Pyuria light-microscopy visualization of more than 10 WBCs/hpf in
centrifuged urinary sediment is considered presumptive evidence of UTI .
o
Leukocyte esterase :
Testing for leukocyte esterase may overcome some of the limitations of urinary
microscopy in identifying leukocyturia.
Leukocyte esterase is present in the neutrophils and can be assayed in the urine
by dipstick strips.
7
False-negative tests may be caused by the presence of ascorbic acid, high
urinary protein, glycosuria, urobilinogen, gentamicin, nitrofurantoin, cephalexin,
and boric acid.
False-positive tests can results from the presence of imipenem and clavulanic
acid in the urine .
o
Nitrite test :
This test is based on the fact that the bacterial enzyme nitrate reductase can
convert urinary nitrate to nitrite, which can be detected by several chemical
methods .
Urine culture:
o
Culturing urine is gold standard for confirming the diagnosis of UTI .
o
The interpretation of culture depends on the :
Method of urine collection.
Clinical background (signs & symptoms).
Number of colony forming units per ml.
Result of urinalysis.
o
If urine obtained by suprapubic aspiration any growth is considered significant .
o
In catheterized specimens the cutoff level suggested is 50,000 CFU/ml .
o
In midstream urine sample If the culture shows >100,000 colonies of a single
pathogen, or if there are 10,000 colonies and the child is symptomatic, the child is
considered to have a UTI .
o
In collection bag can be useful, particularly if the culture is negative, A positive
culture may reflect a contaminant, particularly in girls and uncircumcised boys, in
such cases:
If the urinalysis result is positive, the patient is symptomatic, and there is a
single organism cultured with a colony count greater than 100,000, there is a
presumed UTI.
8
If any of these criteria are not met, confirmation of infection with a catheterized
sample is recommended .
o
Cultures from bagged urine specimens are significant only if there is no growth .
Imaging Studies:
o
The goal of imaging studies in children with a UTI is to identify :
Anatomic abnormalities.
Active renal involvement.
Renal scaring.
Assess renal function .
o
Ultrasonography, VCUG, radionuclide cystography, renal nucleotide scans, and CT
or MRI can be used for anatomic and functional assessment of the urinary tract.
o
Ultrasound:
Provides limited information about renal scarring and is performed to exclude an
anatomic abnormality.
Indication of renal US :
In children with their 1st episode of clinical pyelonephritis (those with a
febrile UTI, or in infants those with systemic illness).
Positive urine culture, irrespective of temperature .
A sonogram of kidneys and bladder should be performed to assess kidney
size, detect hydronephrosis and ureteral dilation, identify the duplicated
urinary tract, and evaluate bladder anatomy .
o
VCUG is the best imaging study for determining the presence or absence of
vesicoureteral reflux,
which is identified in approximately 40% of patients.
o
CT is another diagnostic tool that can image acute pyelonephritis, but clinical
experience with DMSA is much greater, and CT scans have more radiation.
o
Technetium-99m DMSA scan:
Can identify acute pyelonephritis, but is most useful to define renal scarring as a
late effect of UTI.
The NICE (National Institute for Health and Clinical Excellence, UK) guidelines
recommendations include upper tract imaging with a DMSA scan for :
All <6 months with a UTI.
All children <3 years with an :
1.
Atypical UTI (sepsis, non–E. coli UTI, suprapubic mass, elevated serum
creatinine, hypertension)
2.
Recurrent UTI .
For children >3 years, a DMSA scan is recommended only for recurrent UTI .
6-Treatment:
The aims of antimicrobial treatment for urinary tract infection are :
o
To clear the acute infection.
o
To prevent urosepsis.
9
o
To reduce the likelihood of renal damage .
Acute cystitis:
o
Should be treated promptly to prevent possible progression to pyelonephritis.
o
If the symptoms are severe, presumptive treatment is started pending results of the
culture.
o
If the symptoms are mild or the diagnosis is doubtful, treatment can be delayed
until the results of culture are known, and the culture can be repeated if the results
are uncertain .
o
If treatment is initiated before the results of a culture and sensitivities are available,
a 5-7day course of therapy with:
Trimethoprim-sulfamethoxazole or trimethoprim is effective against most
strains of E. coli .
Nitrofurantoin (5-7 mg/kg/24 hr in 3-4 divided doses) also is effective and has
the advantage of being active against Klebsiella and Enterobacter organisms .
Amoxicillin (50 mg/kg/24 hr) also is effective as initial treatment but has no
clear advantages over sulfonamides or nitrofurantoin .
Acute pyelonephritis:
o
10 to 14 day course of broad-spectrum antibiotics capable of reaching significant
tissue levels is preferable .
o
Indication of hospitalization for IV rehydration and IV antibiotic therapy include :
Children who are dehydrated.
Vomiting .
Are unable to drink fluids .
Are ≤1mo of age .
In whom urosepsis is a possibility .
o
Parenteral treatment with :
Ceftriaxone (50-75 mg/kg/24 hr) or cefotaxime (100 mg/kg/24 hr).
Ampicillin (100 mg/kg/24 hr) with an aminoglycoside such as gentamicin (3-
5 mg/kg/24 hr in 1-3 divided doses) is preferable.
Treatment with aminoglycosides is particularly effective against Pseudomonas
spp, and alkalinization of urine with sodium bicarbonate increases its
effectiveness in the urinary tract .
o
Oral therapy :
Oral 3rd-generation cephalosporins such as cefixime considered the treatment
of choice for oral outpatient therapy .
Nitrofurantoin should not be used routinely in children with a febrile UTI
because it does not achieve significant renal tissue levels .
Other measures:
o
Then after initial improvement therapy can be continued orally for a total of 14
days
o
The degree of toxicity, dehydration, and ability to retain oral intake of fluids should
be assessed carefully.
10
o
Restoring or maintaining adequate hydration, including correction of electrolyte
abnormalities that are often associated with vomiting or poor oral intake.
o
Infants and children who do not show the expected clinical response within 2 days
of starting antimicrobial therapy should be re-evaluated, have another urine
specimen obtained for culture, and undergo ultrasound.
o
A urine culture 1 week after the termination of treatment of a UTI ensures that the
urine is sterile but is not routinely needed.
o
Children with a renal or perirenal abscess or with infection in obstructed urinary
tracts can require surgical or percutaneous drainage in addition to antibiotic
therapy and other supportive measures.
Differential diagnosis:
The manifestations of UTI overlap with signs of sepsis seen in young infants and
with enteritis, appendicitis, mesenteric lymphadenitis, and pneumonia in older
children.
Dysuria may indicate pinworm infection, hypersensitivity to soaps or detergents,
vaginitis, or sexual abuse and infection.
Localization of a UTI is important because upper UTI is associated more frequently
with bacteremia and with anatomic abnormalities than is cystitis.
The clinical manifestations of UTI do not reliably distinguish the site of infection in
neonates, infants, and toddlers.
Fever and abdominal pain may occur with either lower or upper UTI, although high
fever, costovertebral tenderness, high erythrocyte sedimentation rate (ESR),
leukocytosis, and bacteremia each suggest upper tract involvement.
Indirect findings such as WBC casts, inability to concentrate urine maximally,
presence of antibody-coated bacteria detected by immunofluorescence, are of limited
value in localizing the site of the UTI to the upper tract.
11
Complications and prognosis:
Bacteremia occurs in 2% to 5% of episodes of pyelonephritis and is more likely in
infants than in older children.
Focal renal abscesses are an uncommon complication.
The relapse rate of UTI is approximately 25% to 40%.
Most relapses occur within 2 to 3 weeks of treatment.
Follow-up urine cultures should be obtained 1 to 2 weeks after completing therapy to
document sterility of the urine.
Prophylactic antibiotics should be administered until the VCUG has been completed
and the presence of reflux is known.
TMP-SMZ (2 mg/kg TMP, 10 mg/kg SMZ) and nitrofurantoin (1 to 2 mg/kg) given once
daily at bedtime are recommended as prophylactic agents, which, in contrast to
amoxicillin and cephalosporins, are associated with low rates of developing antibiotic
resistance.
Clinical follow-up for at least 2 to 3 years is prudent, with repeat urine culture as
indicated.
Some experts recommend that follow-up urine cultures after recurrent cystitis or
pyelonephritis are obtained monthly for 3 months, at 3-month intervals for 6 months,
then yearly for 2 to 3 years.
Grade 1 to 3 reflux resolves at a rate of about 13% per year and is treated medically.
Grade 4 to 5 reflux resolves at a rate of about 5% per year and is treated surgically.
Bilateral reflux resolves more slowly than unilateral reflux.
Recurrent UTI
:
In a child with recurrent UTIs, identification of predisposing factors & treated it is
beneficial, as voiding dysfunction, some children with UTIs void infrequently, and many
also have severe constipation.
Counseling of parents and patients to try to establish more normal patterns of voiding
and defecation is most important in controlling recurrences .
Prophylaxis against reinfection, using TMP-SMX, trimethoprim, or nitrofurantoin at
30% of the normal therapeutic dose once a day, is one approach to this problem.
Prophylaxis with amoxicillin or cephalexin can also be effective, but the risk of
breakthrough UTI may be higher because bacterial resistance may be induced .
Other more high risk conditions for recurrent UTIs that might need long-term
prophylaxis include neurogenic bladder, urinary tract stasis and obstruction, reflux,
and calculi .
The main consequences of chronic renal damage caused by pyelonephritis are arterial
hypertension and end-stage renal insufficiency; when they are found they should be
treated appropriately .
12
Prevention:
Primary prevention is achieved by promoting good perineal hygiene and managing
underlying risk factors for UTI, such as chronic constipation, encopresis, daytime and
nighttime urinary incontinence.
Secondary prevention with antibiotic prophylaxis given once daily is directed
toward preventing recurrent infections, although the impact of secondary prophylaxis
to prevent renal scarring is unknown.
Instruction to mothers:
Avoid constipation.
If your child has any problems with WORMS let the doctor know.
WIPING should be done in a front to back direction.
It is better to take a shower rather than a bath.
Always avoid irritating soaps and bubble baths.
Cleanliness is very important to help prevent infection.
Emptying the bladder properly is very important.
Always encourage your child to DRINK as much as possible during the day, and to
empty the bladder properly last thing at night.
Correct underwear, avoid tight underpants or pantyhose, they prevent air from
circulating freely and encourage the warm, moist environment which favors infection.
When taking antibiotics the full course must be taken at the time required.
Any problems such as burning when passing water, going to the toilet often, or blood
in the water should be reported to the doctor.
Indications of hospitalization:
Treatment of suspected pyelonephritis in an infant younger than 3 months of age.
Patients who have clinical urosepsis.
Patients who have clinical pyelonephritis whose symptoms worsen despite 24 hours of
appropriate antibiotics.
Those not significantly improved within 48 to 72 hours.
For initiation of parenteral therapy if home treatment compliance is in question.
13
14
Subject2:
Enuresis
Enuresis (Bed-wetting):
Enuresis is defined as the repeated voiding of urine into clothes or bed at least twice a
week for at least 3 consecutive months in a child who is at least 5 year of age (the age
when volitional control of micturition is expected).
Enuresis is classified as:
o
Diurnal (daytime).
o
Nocturnal (nighttime).
Another useful classification of enuresis is:
o
Primary (incontinence in a child who has never achieved dryness).
o
Secondary (incontinence in a child who has been dry for at least 6 months).
Epidemiology:
Approximately 60% of children with nocturnal enuresis are boys.
Nocturnal enuresis has a reported prevalence of:
o
15% in 5 year old.
o
7% in 8 year old.
o
1% in 15 year old.
Etiology:
Multifactorial: Genetic + physiologic + psychologic factors.
Primary enuresis:
o
Often is associated with a family history of delayed acquisition of bladder control.
o
A genetic etiology has been hypothesized, and familial groups with AD inheritance
have been identified.
Secondary enuresis:
o
Psychosocial stress.
o
UTI.
o
Fecal retention severe enough to reduce bladder volume and cause bladder neck
dysfunction.
o
Polyuria from osmotic diuresis (DM), or renal concentrating disorders (CRF).
Investigations:
Urinalysis:
o
Pus, protein cast, glucose & specific gravity.
15
o
To look for evidence of chronic UTI, renal disease, and diabetes mellitus.
Further testing, such as urine culture, is based on the urinalysis.
Children with complicated enuresis, may need evaluation with a renal sonogram and a
voiding cystourethrogram.
Treatment:
Non pharmacologic therapy:
o
The best approach to treatment is to reassure the child and parents that the
condition is self-limited and to avoid punitive measures that can affect the child’s
psychologic development adversely.
o
Fluid intake should be restricted to 2 oz after 6 or 7 pm.
o
The parents should be certain that the child voids at bedtime.
o
Avoiding extraneous sugar and caffeine after 4 pm also is beneficial.
o
If the child snores and the adenoids are enlarged, referral to an otolaryngologist
should be considered, because adenoidectomy can cure the enuresis.
o
Star chart for dry nights, child earns praise and a star each morning if his bed is dry.
o
The child should not be blamed for wet bed.
o
Waking children a few hours after they go to sleep to have them void often allows
them to awaken dry.
o
Enuresis alarm: effective in most cases.
Pharmacologic therapy:
o
Desmopressin short-term relief from bedwetting.
o
Imipramine the drug may affect heart rhythm & therefore, If there is any history
of palpitations, syncope or long QT syndrome in the child, or sudden cardiac death
or unstable arrhythmia in the family, the drug should not given.
o
Anticholinergic therapy as oxybutynin.
16
Subject3:
Nephrotic syndrome
Definition:
Nephrotic syndrome is defined by the clinical findings of heavy proteinuria,
hypoalbuminemia, generalized edema and hyperlipidemia.
Etiology:
Examples of primary and secondary causes:
o
Minimal change nephrotic syndrome.
o
Focal segmental glomerulosclerosis.
o
Mesangial hypercellularity.
o
Membranoproliferative glomerulonephritis.
o
Membranous nephropathy.
Secondary nephrotic syndrome:
o
Inherited diseases congenital nephrotic syndrome, diffuse mesangial sclerosis,
alport syndrome, nail-patella syndrome, Lowe syndrome.
o
Vasculitis lupus nephritis, Henoch-Schönlein purpura nephritis, Wegener's
granulomatosis, Goodpasture's syndrome.
o
Postinfectious poststreptococcal, HIV, hepatitis B and C, malaria, syphilis,
intrauterine infections, other viruses and bacteria.
o
Drugs and toxins nonsteroidal anti-inflammatory drugs, gold.
o
Diabetes mellitus rare in children.
Pathophysiology:
Nephrotic syndrome (NS) is characterized by:
o
Persistent heavy proteinuria (mainly albuminuria) (>2 g/24 hours).
o
Hypoproteinemia (serum albumin <3.0 g/dL).
o
Hypercholesterolemia (>250 mg/dL).
o
Edema.
Age, race, and geography affect the incidence of NS.
Certain HLA types (HLA-DR7, HLA-B8, and HLA-B12) are associated with an increased
incidence of NS.
The increased glomerular permeability to serum proteins is due to alterations in
glomerular basement membrane proteins and their normal negative charge that
restricts filtration of serum proteins.
The resultant massive proteinuria leads to a decline in serum proteins, especially
albumin.
Plasma oncotic pressure is diminished, resulting in fluid shifts from the vascular to the
interstitial compartment and plasma volume contraction.
17
Edema formation is enhanced by reduction in effective circulating blood volume and
increase in tubular sodium chloride reabsorption secondary to activation of the renin-
angiotensin-aldosterone system.
Hypoproteinemia stimulates hepatic lipoprotein synthesis and diminishes lipoprotein
metabolism, leading to elevated serum lipids (cholesterol, triglycerides) and
lipoproteins.
Clinical presentation:
Typically presents with the gradual development of edema and inappropriate weight
gain.
The presence of periorbital edema upon arising in the morning that resolve during the
course of the day often is mistaken for allergy.
Clothing may be tight and socks may leave indentations in the skin of the shins and
ankles.
The abdomen may be distended, and a fluid wave may be discernible on examination.
Breath sounds may be decreased at the lungs bases because of accumulation of pleural
fluid .
Although intravascular volume is low in most children with nephrotic syndrome, in
some it will be increased.
These latter children may present with a gallop on auscultation of the heart, rales over
the lung fields, and hepatomegaly.
The child or parents may report decreased frequency of urination and the passage of a
dark, amber-colored, concentrated-appearing urine that appears to foam when voided
into the toilet.
Overall, 16% of children with nephrotic syndrome have diastolic hypertension on
presentation .
The presence of significant hypertension should raise the possibility of underlying
glomerulonephritis.
Investigations:
Laboratory evaluation begins with a urinalysis in the child with edema, this will
demonstrate significant proteinuria in cases of nephrotic syndrome.
Urinary protein losses can be quantified with a 24-hour urine collection.
Nephrotic-range proteinuria is defined as:
o
1 urinary protein excretion on a timed urine collection of greater than 2 g/day or
greater than 40mg per M 2 per hr.
o
1+ or higher on two to three random urine specimens suggests persistent
proteinuria that should be further quantified.
o
+3 or+4 Urinary protein quantification is not critical in the management of the
nephrotic child who has heavy proteinuria as demonstrated by dipstick
18
determination and a typical clinical presentation, it is more helpful for following the
response of children with resistant forms of nephrotic syndrome .
A small amount of protein is found in the urine of healthy children (<4 mg/m2/hour or
UPr/Cr < 0.2).
Nephrotic proteinuria in children is defined as protein greater than 40 mg/m2/hour or
UPr/Cr greater than 2.0. proteinuria between these two levels is mildly to moderately
elevated, but not nephrotic.
The presence of significant microscopic hematuria or gross hematuria should suggest
that nephrotic syndrome might be secondary to an underlying nephritic process.
The presence of glycosuria in untreated children with nephrotic syndrome suggests
underlying tubular injury that may be seen with focal segmental glomerulosclerosis.
Blood urea and creatinine values generally are normal or only slightly elevated in
primary nephrotic syndrome.
Serum total protein and albumin levels are low.
Mild hyponatremia may be present because of water retention.
Total calcium levels are low because of the low serum albumin level, but ionized
calcium levels usually are normal.
The serum cholesterol level usually is elevated.
The third component of complement generally is normal, a depressed level suggests
membrano-proliferative glomerulonephritis, post-streptococcal glomerulonephritis, or
lupus nephritis.
Chest radiographs usually will show a small cardiac silhouette and, in severe cases, the
presence of pleural fluid.
Cardiomegaly may be seen in those cases with increased intravascular volume .
Complications:
Infection:
o
Morbidity and mortality were high in nephrotic syndrome before the introduction
of corticosteroids and antibiotics.
o
Infection was the leading cause of death in children with nephrotic syndrome.
o
Infectious complications include spontaneous bacterial peritonitis, sepsis, cellulitis,
and pneumoniae .
o
Staphylococcus and gram-negative bacteria are responsible for the majority of
infections in nephrotic syndrome .
o
Predisposing factors for the development of bacterial infections include:
Tissue edema that may facilitate the spread of infection.
Defective opsonization of invading bacteria caused by loss into the urine of small
components of the alternative pathway of complement.
Impaired cellular immunity.
19
Effects of immunosuppressive therapies used in the treatment of nephrotic
syndrome may increase the susceptibility to infection.
o
Children with recurrent nephrotic syndrome should receive multivalent
pneumococcal vaccination.
o
A role for prophylactic antibiotic therapy has not been established .
Thromboembolism:
o
Thromboembolic events such as deep-vein thrombosis, pulmonary embolism, and
renal vein thrombosis are well-described complications of nephrotic syndrome in
both children.
o
Contributory factors include elevated plasma levels of pro-coagulant factors,
urinary loss of inhibitors of coagulation, and thrombocytosis .
o
The predisposition to thrombus formation may be exacerbated by decreased
intravascular volume, especially in the face of vigorous forced diuresis .
Hyperlipidemia:
o
Elevated plasma cholesterol in nephrotic syndrome results from increased hepatic
lipoprotein synthesis caused by generalized increased hepatic protein synthesis in
response to a lowered plasma albumin level .
o
In addition, in severe disease there may be decreased lipolysis, resulting in elevated
triglycerides.
Minimal change nephrotic syndrome (MCNS):
Minimal change nephrotic syndrome (MCNS), also known as lipoid nephrosis
Is the most common histologic form of primary nephrotic syndrome in children.
More than 80% of children under 7 years of age with nephrotic syndrome have MCNS.
Children 7 to 16 years old with NS have a 50% chance of having MCNS, and males are
affected more frequently than females (2:1).
Male-to-female ratio is reported to be 2:1 for children and 1:1 in adolescents & adults.
Most of MCNS have remission of their disease with a course of prednisone .
92% will achieve a remission with a course of corticosteroid,
Hematuria is found in about 13% and hypertension in 10% to 20% .
Relapses are common, but the long-term prognosis is excellent.
Relapses tend to become less frequent with age, and the disorder usually resolves
around the time of puberty without permanent renal impairment.
Often, the diagnosis is assumed in most children since biopsy generally is not
performed in those who follow a typical course and respond to steroids.
These children should more correctly be considered to have the clinical diagnosis of
steroid-responsive idiopathic nephrotic syndrome of childhood.
20
Treatment:
Information:
o
Eighty-five percent of nephrotic children regardless of underlying pathology will
respond to a trial of prednisone.
o
Seventy-five percent of those who will respond do so within 2 weeks of starting
corticosteroids, and 94% will have responded by 4 weeks .
o
The majority of steroid-responsive patients have MCNS. However, up to 25% of
steroid-resistant nephrotic children have MCNS on biopsy, whereas 5% to 10% of
the steroid-responsive patients have FSGS.
o
In general, nephrotic patients who achieve a remission on steroids, whether they
have MCNS or FSGS by biopsy, do not progress to renal failure if they remain
steroid responsive .
o
Children between the ages of 1 and 6 years are most likely to have MCNS by renal
biopsy and respond clinically to a trial of steroids by achieving a remission.
o
Therefore, it is now customary to treat a child in this age range (or even up to age
10) who presents with the new onset of typical, pure nephrotic syndrome with a
trial of corticosteroids.
Drugs:
o
Treatment consists of prednisone 2 mg/kg/day or 60 mg/M day (maximum 60 to 80
mg/day) for 4 to 6 weeks, this usually is given in divided doses.
o
This is followed by a single dose of 2 mg/kg or 60 mg/M for an additional 4 to 6
weeks given in the morning on alternate days with the medication gradually
tapered off.
Relapse:
o
Depending on the treatment regimen employed, from 36% to 61% of children will
have a relapse of nephrotic syndrome within the first year of the initial episode .
o
A relapse is diagnosed if the urine tests 2+ or greater for protein for 3 consecutive
days with edema.
o
Relapses usually are triggered by intercurrent illnesses or allergies, and parents can
be taught to use albumin test sticks or sulfosalicylic acid at home to monitor urinary
protein excretion.
o
Relapses are treated with prednisone 2 mg/kg/day or 60 mg/M day until the urine
is free of protein (negative or trace or+1) for 3 consecutive days that is in the same
manner of the first episode .
o
About 25% of children with relapses will follow a frequently relapsing course,
defined as 2 relapses occurring within 6 months of completing a course of steroids
or 3 relapses within 1 year.
o
Children who develop a relapse while corticosteroids are being tapered or within 2
weeks of completing a course of steroids are considered to be steroid-dependent.
o
Both children who have frequently relapsing and steroid-dependent nephrotic
syndrome are more likely to develop steroid toxicity.
21
Secondary, tertiary, and complementary therapies for difficult cases of nephrotic
syndrome are listed:
o
o
o
o
o
o
o
Angiotensin-converting enzyme inhibitors.
o
Nonsteroidal antiinflammatory drugs.
Not response:
o
Children who fail to respond to the initial or subsequent courses of corticosteroids
have steroid-resistant nephrotic syndrome and a more guarded prognosis.
o
Consultation with a pediatric nephrologist should be made for consideration of a
renal biopsy and more aggressive treatment.
Side effects of treatment:
o
Significant complications of therapy include the development of cushingoid
features, cataract formation, glaucoma, gastritis, peptic ulcer disease, pancreatitis,
hypokalemia, hypertension, increased risk of infection, behavioral changes, growth
delay if treatment is prolonged .
Cytotoxic agents:
o
Cyclophosphamide, chlorambucil, nitrogen mustard, and cyclosporine.
o
Can be associated with increased risk of infection, malignancy, and sterility, but
usually only with higher doses than those typically used for nephrotic syndrome or
after repeated or prolonged courses.
o
Cyclophosphamide can cause hemorrhagic cystitis.
o
Therefore, a large fluid intake and frequent voiding should be encouraged.
o
Chlorambucil therapy has been associated with induction of seizure activity .
Nonsteroidal anti-inflammatory drugs:
o
Can cause salt retention and edema.
o
There is a risk of renal failure, especially in patients with severely decreased
intravascular volume .
Diuretics:
o
Are used judiciously given the already reduced intravascular volume in most
nephrotic patients and the attendant risk of thromboembolism.
o
Furosemide alone or in combination with a thiazide diuretic is used for significant
edema.
o
Severe edema interfering with ambulation, compromising respiratory status, or
causing tissue breakdown can be treated with intravenous 25% albumin, 1 g/kg,
followed by intravenous furosemide if renal function and urine output are fairly
well maintained.
22
Angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril):
o
Can be tried in resistant nephrotic syndrome, even in the presence of
normotension, to decrease urinary protein excretion.
o
The ACE inhibitors act by decreasing glomerular capillary pressure and can cause a
reversible rise in serum creatinine and hyperkalemia that must be monitored.
When to refer:
o
Complicated nephrotic syndrome.
o
Outside the expected age range (younger than 1 year or older than 10 years).
o
Accompanied by signs of glomerulonephritis (renal insufficiency, hypertension,
hematuria, hypocomplementemia).
o
Refractory edema.
o
Frequently relapsing nephrotic syndrome.
o
Steroid-dependent nephrotic syndrome.
o
Steroid-resistant nephrotic syndrome.
When to hospitalize:
o
Initial episode for teaching of parents.
o
Anasarca interfering with ambulation or compromising ventilation.
o
Pleural effusions or ascites interfering with ventilation.
o
Signs of volume overload (congestive heart failure(.
o
Infection (severe cellulitis, peritonitis).
o
Significant hypertension.
o
Significant electrolyte abnormalities.
o
Compromised renal function.
23
Subject4:
Acute glomerulonephritis
Introduction:
Acute glomerulonephritis is characterized by hematuria (65%), hypertension (75%),
and edema (50%).
The hematuria is usually grossly evident as tea-colored or cola-colored urine.
In some children, however, the hematuria may be microscopic only.
This clinical syndrome can be considered to present in many ways:
o
Acute nephritis with no or mild renal failure.
o
Acute nephritis with rapidly progressive renal failure.
o
Nephritis-nephrotic.
o
Subclinical form.
Diseases that usually presented as acute glomerulonephritis:
Acute posts-treptococcal glomerulonephritis.
Henoch-Schönlein purpura with nephritis.
Post-infectious (non-streptococcal) glomerulonephritis.
Interstitial glomerulonephritis.
Radiation nephritis.
Acute poststreptococcal glomerulonephritis:
Acute poststreptococcal glomerulonephritis (APSGN) is a common form of
glomerulonephritis in childhood.
Although poststreptococcal nephritis may happen at any age, the peak incidence
occurs at age 7 years, with a slight predominance among boys.
It is uncommon before age 3 years and in adults.
Etiology:
Poststreptococcal nephritis is the consequence of the host's immune response to a
non-renal infection with group A beta-hemolytic streptococci (GABHS).
Not all GABHS strains are nephritogenic.
Types 12 and 49 are the strains most commonly associated with nephritis.
Infection with a nephritogenic strain does not guarantee an episode of nephritis,
because a variety of incompletely understood factors determines the host response.
Clinical presentation:
Mild and subclinical cases are common.
Renal involvement characteristically manifests 8 to 14 days after a pharyngeal infection
or 14 to 21 days after a skin infection caused by the nephritogenic streptococci.
24
Most patients who have acute poststreptococcal nephritis present as an acute
glomerulonephritis, with macroscopic hematuria present in about 65% of the cases.
Patients will usually have oliguria and, in rare cases, anuria.
Fluid retention leads to edema that usually is periorbital and rarely, severe
Intravascular overload caused by salt and water retention can lead to signs of
congestive heart failure.
Approximately 75%of the patients have hypertension also related to salt and water
retention.
Patients who have severe hypertension may have symptoms of headache, drowsiness,
vomiting, personality and visual changes, and convulsions.
Although arteriolar spasm is commonly found on funduscopic examination,
papilledema and hemorrhages are rare, even with severe hypertension.
Anorexia and pain in the abdomen or flank are common, although palpation of the
abdomen usually reveals no significant findings.
Although a history of preceding skin or pharyngeal infection supports the diagnosis,
such a history cannot be elicited in many cases.
In rare cases, in which convulsions or symptoms of cardiovascular dysfunction are the
primary complaint, unrecognized poststreptococcal nephritis is the underlying
etiology.
Investigations:
The urine usually is tea colored and opaque.
The specific gravity generally is increased, and hemoglobin can be detected by
chemical testing.
Any proteinuria that is present usually parallels the degree of hematuria and rarely
reaches the nephrotic syndrome range.
Microscopic examination usually reveals erythrocyturia, pyuria and granular or cellular
casts.
Measurement of serum complement shows a reduction of C3 in most of the patients
and, early in the course, a reduction of C4 in 50%.
The erythrocyte sedimentation rate (ESR) usually is elevated.
With severe oliguria, azotemia and acidosis may been seen.
The plasma volume usually is expanded, causing a decline in hemoglobin, and
hematocrit levels by dilution.
Hemolysis, a shortened erythrocyte half-life, and reduced erythrocyte production may
contribute to these hematological changes.
Salt retention with a decreased fractional excretion of sodium.
Evidence of a preceding streptococcal infection is important to support the diagnosis.
25
The antistreptolysin O (ASO) titer is elevated in 80% of patients, although increases in
titer are less common in patients who have skin infection and in those who receive
early treatment with antibiotics.
If other streptococcal antibodies (antihyaluronidase, antideoxyribonuclease B) are
measured, 95% of patients will have serological evidence of preceding streptococcal
infection.
Cultures often are negative for GABHS by the time nephritis develops and are
particularly affected by pretreatment with antibiotics.
The chest roentgenogram in patients who have hypertension usually reveals a large
heart with prominent pulmonary vasculature& pulmonary edema.
Ultrasound examination usually reveals bilaterally enlarged kidneys.
Renal biopsy should be considered only in the presence of:
o
ARF, NS.
o
Absence of evidence of streptococcal infection.
o
Normal complement levels.
o
When hematuria and proteinuria, diminished renal function, and/or a low C3 level
persist more than 2 mo after onset. (Persistent hypocomplementemia can indicate
a chronic form of postinfectious GN or another disease such as
membranoproliferative GN.).
Treatment:
Acute poststreptococcal glomerulonephritis most often resolves spontaneously.
Even so, the practitioner must be aggressive in treating hypertension, oliguria, and the
resulting vascular overload, pulmonary edema, and encephalopathy that occur in the
acute phase of the illness, because these can be fatal.
Although mild hypertension may resolve spontaneously, more severe degrees of
hypertension should be controlled with antihypertensive agents that act quickly.
Because increased intravascular volume is theorized to be the main determinant of
hypertension in acute glomerulonephritis, diuretics are a mainstay of therapy.
Control of severe hypertension often will require the use of intravenous sodium
nitroprusside, labetalol, oral minoxidil in a dose of 0.1 to 0.2 mg/kg may be effective.
Slower-acting, less potent antihypertensive drugs are not good initial choices but can
be substituted once blood pressure has been acutely stabilized .
The signs of congestive heart failure usually resolve with control of the hypertension.
Occasionally a patient develops acute renal failure severe enough to require dialysis.
A 10-day course of antibiotics usually is given to eradicate any remaining GABHS and,
thus, prevent the spread of the organism to others.
There is no evidence that such treatment affects the course of nephritis in the patient.
Close contacts should be screened for streptococcal infection and treated if present.
Hospitalization for patients who have this disease needs to be determined individually.
26
Although many children who have mild episodes do well as outpatients, the sudden
development of hypertension and oliguria may produce life-threatening symptoms
quite rapidly, necessitating hospitalization.
After the acute phase, the child may be allowed to resume normal activities gradually.
Every child should be followed up regularly until the serum complement values return
to normal.
To be certain of the diagnosis, a renal biopsy may be indicated for a child whose
clinical or laboratory findings are atypical.
Any child whose C3 value does not return to normal within 8 weeks should have a
kidney biopsy .
Course:
Diuresis usually ensues by one week from onset, heralding resolution of the acute
illness.
Creatinine should normalize by 3 to 4 weeks.
Gross hematuria resolves within 1 or 2 weeks, although microscopic hematuria may
persist for more than 1 year.
Proteinuria should resolve by 3 months.
Complement levels should normalize by 6 to 8 weeks.
Complications:
Acute renal failure can require treatment with dialysis.
Hypertension is seen in 60% of patients and is associated with hypertensive
encephalopathy in 10% of cases.
Electrolytes disturbance: hyperkalemia, hyperphosphatemia, hypocalcemia.
Heart failure.
Prognosis:
Studies have shown that more than 95% of children who have acute poststreptococcal
glomerulonephritis recover from their illness.
For most children, the critical period (5-10) early in the illness when potentially fatal
hypertension or fluid overload presents a danger.
Treating the streptococcal infection does not prevent PSGN, however if the patient still
has active streptococcal infection, antibiotic treatment is warranted.
Recurrences of APSGN are rare.
The presence of nephrotic-range proteinuria or extensive crescents by biopsy indicate
a poor prognosis.
The failure of complement levels to normalize by 8 weeks suggests the presence of a
form of nephritis other than ASPGN, such as membranoproliferative
glomerulonephritis, the nephritis of chronic infection, or lupus nephritis .
The prognosis for renal recovery in other forms of chronic GN and in RPGN is variable
and related to the disorder and disease severity at diagnosis.
27
Evaluation of a child with Hematuria:
Complete history and physical examination (particularly blood pressure, optic discs,
skin, abdomen, genitalia).
Confirmation of true hematuria by urine microscopic examination.
Urine culture.
Urine calcium, protein, creatinine.
Complete blood count including platelets, serum electrolytes, BUN/serum creatinine
(calculate creatinine clearance), calcium, total protein and albumin.
Streptozyme, C3, C4, ANA.
Renal ultrasonography.
Renal biopsy in selected cases.
NEPHROTIC SYNDROME
GLOMERULONEPHRITIS
Characters
M>F
M=F
Sex
2-6 yr
5-12 yr
Age
Generalized
Mainly peripheral
Edema
Pleural effusion
Pulmonary edema
Chest
Normal
Hypertension and cardiomegaly
Heart
>40mg/m2/hr
+ve but less than nephrotic range
Proteinuria
Absent or microscopic
Gross
Hematuria
NR/low
NR/high
BP
NR
NR/RF
Renal function
Low <2.5mg/dl
NR
S. albumin
>250mg/dl
NR
s. cholesterol
NR
reduced
S. complement
Need
No need
Steroid therapy
28
Subject5:
Vesicoureteral reflux VUR
Definition:
VUR is the retrograde flow of urine from the bladder
to the ureter or up to the kidney.
Classification of VUR:
Various anatomic defects of the ureterovesical junction associated with VUR.
Grading of VUR (Very Important):
Grade I: into a nondilated ureter.
Grade II: into the pelvis and calyces without dilatation.
Grade III: mild to moderate dilatation of the ureter, renal pelvis, and calyces with
minimal blunting of the fornices.
Grade IV: moderate ureteral tortuosity and dilatation of the pelvis and calyces.
Grade V: gross dilatation of the ureter, pelvis, and calyces; loss of papillary
impressions; and ureteral tortuosity.
29
Clinical manifestations:
VUR is most often identified during radiologic evaluation following a UTI.
The younger the patient with a UTI, the more likely VUR is present.
No clinical signs are reliable in differentiating children with UTI with and without VUR.
Investigations:
An imaging study can be performed after initiation treatment of UTI.
RUS.
VCUG (radionuclide cystogram): anatomical details.
NCG (radionuclide cystogram): less anatomical details but less radiation risk.
Indication of VSUG:
Infant with 1st UTI between 2-24 months in whom RUS reveals
hydronephrosis, scarring, other finding suggestive high grade VUR or
obstructive uropathy.
Recurrent febrile UTI.
Atypical infection.
Complications:
Hypertension.
CKD.
Treatment:
Controversy remains about whether long term prophylactic antibiotics is indicated in
mild-moderate VUR.
Surgery: open or laparoscopic.
Endoscopic repair of VUR involves injection of a bulking agent through a cystoscope
just beneath the ureteral orifice, creating an artificial flap-valve.
The FDA approved the use of a biodegradable material, dextranomer microspheres
suspended in hyaluronic acid (Deflux), for subureteral injection.
Endoscopic correction of VUR. through a cystoscope, a needle is inserted into the
submucosal plane deep to the ureteral orifice and bulking agent is injected, creating a
flap-valve to prevent VUR.
VSUG: showing G 4 right VUR
30
Subject6:
Henoch-Schönlein Purpura HSP
Etiology:
Henoch-Schönlein purpura (HSP) is a vasculitis of
unknown etiology characterized by
inflammation
of small blood vessels with leukocytic infiltration
of tissue, hemorrhage, ischemia.
The immune
complexes associated with HSP are
predominantly composed of IgA.
Epidemiology:
It occurs primarily in children 3 to 15 years of
age, although it has been described in adults.
HSP is slightly more common in boys than girls
and occurs more frequently in the winter than
the summer months.
Clinical manifestations:
HSP is characterized by rash, arthritis, and, less frequently, gastrointestinal or renal
vasculitis.
Rash:
o
The hallmark of HSP is palpable purpura, caused by small vessel inflammation in the
skin leading to extravasation of blood into the surrounding tissues.
o
IgA often is deposited in the lesions.
o
Although the rash can occur anywhere on the body, it is classically, below the waist
on the buttocks and lower extremities.
Arthritis:
o
Arthritis occurs in 80% of patients with HSP, it can occur in any joint but tends to
affect the lower extremities, most commonly the ankles and knees.
o
The arthritis is acute and can be very painful with refusal to bear weight.
GIT:
o
Gastrointestinal involvement occurs in about one half of affected children and most
typically presents as mild to moderate crampy abdominal pain, thought to be due
to small vessel involvement of the gastrointestinal tract leading to ischemia.
o
Less commonly, significant abdominal distention, bloody diarrhea, intussusception,
or abdominal perforation occurs and requires emergent intervention.
o
Gastrointestinal involvement is typically seen during the acute phase of the illness,
it may precede the onset of rash.
31
Renal:
o
One third of children with HSP develop renal involvement, which can be acute or
chronic.
o
Although renal involvement is mild in most cases, acute glomerulonephritis
manifested by hematuria, hypertension, or acute renal failure can occur.
o
Most cases of glomerulonephritis occur within the first few months of presentation,
but rarely patients develop late renal disease, which ultimately can lead to chronic
renal disease, including renal failure.
CNS:
o
Neurologic manifestations of HSP, caused by hypertension or CNS vasculitis, may
also occur.
o
They include intracerebral hemorrhage, seizures, headaches, behavior changes.
Other less-common potential manifestations:
o
Orchitis.
o
Testicular torsion.
o
Pancreatitis.
o
Carditis.
o
Pulmonary hemorrhage.
o
Inflammatory eye disease.
Investigations:
Erythrocyte sedimentation rate, C-reactive protein, and white blood cell count are
elevated in patients with HSP.
The platelet count is the most important test, because HSP is characterized by non-
thrombocytopenic purpura with a normal, or even high, platelet count, differentiating
HSP from other causes of purpura that are associated with thrombocytopenia.
A urinalysis screens for evidence of hematuria.
A serum blood urea nitrogen and creatinine should be obtained to evaluate renal
function.
Testing the stool for blood may identify evidence of gut ischemia.
Any question of gut perforation requires radiologic investigation.
Ultrasound is often used in the setting of gastrointestinal complaints to look for bowel
wall edema or the rare occurrence of an associated intussusception.
Barium enema can also be used to both diagnose and treat intussusception.
Although often unnecessary in typical HSP, biopsies of skin and kidney can provide
important diagnostic information, particularly in atypical or severe cases, and
characteristically show IgA deposition in affected tissues.
32
Criteria for Diagnosis of Henoch-Schönlein Purpura:
The diagnosis of HSP is based on the presence of two of four criteria.
Treatment:
Therapy for HSP is supportive, an emphasis on assuring adequate hydration, nutrition,
and analgesia.
A short-term course of NSAIDs can be administered for the acute arthritis.
Systemic corticosteroids usually are reserved for children with GIT disease and provide
significant relief of abdominal pain. A typical dosing regimen is prednisone, 1
mg/kg/day for 1 to 2 weeks, followed by a taper schedule. Recurrence of abdominal
pain as corticosteroids are weaned may necessitate a longer course of treatment.
Acute nephritis typically is treated with corticosteroids but may require more
aggressive immunosuppressive therapy.
Although few data are available to demonstrate efficacy, IVIG and plasma exchange
are sometimes used in the setting of severe disease.
Prognosis:
The prognosis of HSP is excellent.
Most children have complete resolution of the illness without any significant sequelae.
Patients with HSP renal disease (elevated blood urea nitrogen, persistent high-grade
proteinuria) are at highest risk for long-term complications, such as hypertension or
renal insufficiency, particularly if the initial course was marked by significant nephritis.
There is a long-term risk of progression to end-stage renal disease in less than 1% of
children with HSP.
The rare patients who develop end-stage renal disease may require renal
transplantation.
HSP may recur in the transplanted kidney.
33
Subject7:
Hemolytic-Uremic Syndrome HUS
Introduction:
Hemolytic-uremic syndrome (HUS) is defined as the triad of acute microangiopathic
hemolytic anemia, thrombocytopenia, and acute renal insufficiency or failure.
It occur as a common pathway resulting from a variety of initiating causes:
o
Epidemic, diarrhea-associated HUS is the most common form.
o
Atypical HUS (also known as sporadic or nondiarrhea-associated HUS) occurs less
frequently in children and is classified according to the suspected underlying
primary cause
Typically the illness affects infants and young children of all races and both genders,
with the majority of diarrhea-associated cases occurring in the summer months.
Even in non-epidemic areas, cases commonly cluster.
Although the frequency varies, typical childhood HUS is one of the most common
causes of acute renal failure among pediatric patients.
The diarrheal form of HUS in children is associated most commonly with colonic
infection by Escherichia coli
( most commonly E. coli subtype 0157:H7) capable of
producing a Shiga-like toxin
Types of HUS:
Typical HUS (D+HUS):
o
It is the most common type of HUS.
o
It occurs in children <5 years of age.
o
It is associated with a prodromal diarrheal illness “D+HUS”, contamination of meat,
fruit, vegetables, or water with verotoxin (VT) producing E. coli ( most commonly
E.coli O157:H7) is responsible for many outbreaks.
Atypical HUS:
o
HUS presenting without a prodrome of diarrhea (D-HUS), may occur at any age.
o
The clinical course is usually more severe than that of D+HUS.
o
D-HUS due to:
Secondary to infection (Streptococcus pneumoniae, HIV).
Genetic & acquired defects in complement regulation.
Medications.
Malignancy.
SLE.
Pregnancy.
34
History:
The child who has typical HUS usually experiences a 3- to 10-day prodrome of bloody
or watery diarrhea often associated with cramping abdominal pain.
Nausea, vomiting, and fever are present variably.
Extreme pallor and malaise, when reported, usually occur suddenly at a time when the
gastrointestinal illness has appeared to have stabilized or improved .
Acute gastrointestinal manifestations may include abdominal distention, bleeding,
intussusception, rectal prolapse, and strictures. Gangrene of the colon and intestinal
perforation also have been reported.
Extrarenal involvement in HUS often is seen.
CNS abnormalities such as somnolence, irritability, seizures, or stroke.
In atypical HUS a prodrome usually is absent or consists of an upper respiratory tract
infection.
The manifestations at the onset of HUS are similar, except that gastrointestinal
complaints are less common .
Physical findings:
Children who have HUS usually appear acutely ill with pallor, petechiae, purpura.
They often are irritable or drowsy and may have hypertension.
Hepatomegaly frequently is present.
The presence of congestive heart failure and pulmonary or peripheral edema results
from a combination of oliguria with consequent intravascular volume overload and/or
a rapidly developing anemia.
Investigations:
A Coombs-negative and anemia is a typical finding.
The blood smear shows the fragmented erythrocytes characteristic of the
microangiopathic process as well as the thrombocytopenia.
Leukocytosis often is present, and is frequently associated with more severe disease.
Urinalysis usually demonstrates proteinuria, microscopic or macroscopic hematuria.
Laboratory abnormalities resulting from renal dysfunction, including azotemia,
hyperkalemia, hyperphosphatemia, and metabolic acidosis, are variable in their degree
depending on the magnitude and duration of the renal disease and the degree of red
cell hemolysis .
The child who has suspected HUS should have some form of electrocardiographic
monitoring until the initial laboratory data are obtained .
Atypical HUS is more common in older children and adults, although diarrhea-
associated HUS is being recognized with increasing frequency.
The occurrence of atypical HUS tends to be sporadic without geographical or seasonal
characteristics.
35
Differential diagnosis:
The features of HUS are not specific and also may occur in disseminated intravascular
coagulation (DIC), overwhelming sepsis, malignant hypertension, and some instances
of vasculitis.
Treatment:
Management of the oliguric acute renal failure, hypertension, anemia, and CNS
disturbances is the most common initial therapeutic consideration in patients who
have HUS.
Prevention of fluid overload (which often provokes significant worsening of
hypertension), correction of electrolyte imbalances, and control of uremia is achieved
by careful medical management and, if necessary, dialysis .
To avoid rapid changes of intravascular volume, where possible, blood cells should be
transfused in small quantities as needed.
Seizures should be treated aggressively and conventionally.
Prognosis:
More than 80% of children who have typical childhood HUS recover without renal or
CNS sequelae.
More than 10% may have some degree of persistent renal insufficiency or
hypertension.
Children who have atypical HUS are at increased risk for permanently impaired renal
function.
Patients who have recurrent or familial forms of HUS also are at increased risk for
progressive deterioration of renal function.
36
Subject8:
Renal failure
Acute kidney injury
Definition:
Acute kidney injury has acute renal failure at the most severe end of the spectrum
where there is a sudden, potentially reversible, reduction in renal function.
Oliguria (<0.5 ml/kg per hour) is usually present.
Classified as:
Prerenal the commonest cause in children.
Renal there is salt and water retention; blood, protein and casts are often present
in the urine; and there may be symptoms specific to an accompanying disease (e.g.
hemolytic uremic syndrome).
Postrenal from urinary obstruction.
Note:
Acute-on-chronic renal failure is suggested by the child having growth failure, anemia
and disordered bone mineralization (renal osteodystrophy).
Management:
Children with acute renal failure should have their circulation and fluid balance
meticulously monitored.
Investigation by ultrasound scan will identify obstruction of the urinary tract, the small
kidneys of chronic renal failure, or large, bright kidneys with loss of cortical medullary
differentiation typical of an acute process.
Prerenal failure:
o
This is suggested by hypovolemia.
37
o
The fractional excretion of sodium is very low as the body tries to retain fluid.
o
The hypovolemia needs to be urgently corrected with fluid replacement and
circulatory support if acute tubular necrosis is to be avoided.
Renal failure:
o
If there is circulatory overload, restriction of fluid
intake and challenge with a diuretic may increase
urine output sufficiently to allow gradual
correction of sodium and water balance.
o
A high-calorie, normal protein feed will decrease
catabolism, uremia and hyperkaliemia.
o
Emergency management of metabolic acidosis,
hyperkaliemia and hyperphosphatasemia.
o
If the cause of renal failure is not obvious, a renal
biopsy should be performed to identify rapidly
progressive glomerulonephritis, as this may need
immediate treatment with immunosuppression.
o
The two commonest renal causes of acute renal failure in children in the UK are the
hemolytic uremic syndrome and acute tubular necrosis, the latter usually in the
setting of multisystem failure in the intensive care unit or following cardiac surgery.
Postrenal failure:
o
This requires assessment of the site of obstruction and relief by nephrostomy or
bladder catheterisation.
o
Surgery can be performed once fluid volume and electrolyte abnormalities have
been corrected.
Dialysis:
o
Dialysis in acute renal failure is indicated when there is:
Failure of conservative management.
Hyperkaliemia.
Severe hypo- or hypernatremia.
Pulmonary edema or hypertension.
Severe acidosis.
Multisystem failure.
o
Peritoneal dialysis or hemodialysis can be undertaken for acute renal failure.
o
If plasma exchange is part of the treatment, hemodialysis is used.
o
If there is cardiac decompensation or hypercatabolism, continuous arteriovenous or
venovenous hemofiltration provides gentle, continuous dialysis and fluid removal.
o
Acute renal failure in childhood generally carries a good prognosis for renal
recovery unless complicating a life-threatening condition, e.g. severe infection,
following cardiac surgery or multisystem failure.
38
Chronic kidney disease
Introduction:
Chronic renal failure, with GFR <15 ml/min per 1.73 m2, is much less common in
children than in adults, with an incidence of only 10 per million of the child population
each year.
Congenital and familial causes are more common in childhood than are acquired
diseases Structural malformations, Glomerulonephritis, Hereditary nephropathies,
Systemic diseases, Miscellaneous/unknown.
Clinical features:
Chronic renal failure presents with:
o
Anorexia and lethargy.
o
Polydipsia and polyuria.
o
Failure to thrive/growth failure.
o
Bony deformities from renal osteodystrophy (renal rickets).
o
Hypertension.
o
Acute-on-chronic renal failure (precipitated by infection or dehydration).
o
Incidental finding of proteinuria.
o
Unexplained normochromic, normocytic anemia.
Many children with chronic renal failure have had their renal disease detected before
birth by antenatal ultrasound or have previously identified renal disease.
Symptoms rarely develop before renal function falls to less than one-third of normal.
Management:
The aims of management are to prevent the symptoms and metabolic abnormalities of
chronic renal failure, to allow normal growth and development and to preserve
residual renal function.
The management of these children should be conducted in a specialist pediatric
nephrology center.
Diet:
o
Anorexia and vomiting are common.
o
Improving nutrition using calorie supplements and nasogastric or gastrostomy
feeding is often necessary to optimize growth.
o
Protein intake should be sufficient to maintain growth and a normal albumin, whilst
preventing the accumulation of toxic metabolic byproducts.
Prevention of renal osteodystrophy
o
Phosphate retention and hypocalcaemia due to decreased activation of vitamin D
leads to secondary hyperparathyroidism, which results in osteitis fibrosa and
osteomalacia.
39
o
Phosphate restriction by decreasing the dietary intake of milk products, calcium
carbonate as a phosphate binder, and activated vitamin D supplements help to
prevent renal osteodystrophy.
Control of salt and water balance and acidosis:
o
Many children with chronic renal failure caused by congenital structural
malformations and renal dysplasia have an obligatory loss of salt and water.
o
They need salt supplements and free access to water.
o
Treatment with bicarbonate supplements is necessary to prevent acidosis.
Anemia:
o
Reduced production of erythropoietin and circulation of metabolites that are toxic
to the bone marrow result in anemia.
o
This responds well to the administration of recombinant human erythropoietin.
Hormonal abnormalities:
o
Many hormonal abnormalities occur in chronic renal failure.
o
Most importantly, there is growth hormone resistance with high growth hormone
levels but poor growth.
o
Recombinant human growth hormone has been shown to be effective in improving
growth for up to 5 years of treatment, but it improves final height remain unknown.
o
Many children with chronic renal failure have delayed puberty and a subnormal
pubertal growth spurt.
Dialysis and transplantation:
o
The optimum management is by renal transplantation.
o
Technically, this is difficult in very small children and a minimum weight, e.g. 10 kg,
needs to be reached before transplantation to avoid renal vein thrombosis.
o
Kidneys obtained from living related donors have a higher success rate than
deceased donor kidneys, which are matched as far as possible to the recipient’s
HLA type.
o
Graft losses from both acute and chronic rejection or recurrent disease mean that
the 5-year graft survival is reduced to 91% for living related kidneys and 79% for
deceased donor kidney transplants and some children need re-transplantation.
o
Current immunosuppression is mainly with combinations of prednisolone,
tacrolimus and azathioprine or mycophenolate mofetil.
o
Ideally, a child is transplanted before dialysis is required, but if this is not possible, a
period of dialysis may be necessary.
o
Peritoneal dialysis, either by cycling overnight using a machine (continuous cycling
peritoneal dialysis) or by manual exchanges over 24 h (continuous ambulatory
peritoneal dialysis), can be done by the parents at home and is therefore less
disruptive to family life and the child’s schooling.
o
Hemodialysis is an alternative and is usually done in hospital 3–4 times a week.
40
Subject9:
Other renal diseases
41
Causes of palpable kidneys:
Unilateral:
o
Multicystic kidney
o
Compensatory hypertrophy.
o
Obstructed hydronephrosis.
o
Renal tumor (Wilms tumor).
o
Renal vein thrombosis.
Bilateral:
o
Autosomal recessive (infantile) polycystic kidneys.
o
Autosomal dominant (adult) polycystic kidneys.
o
Tuberous sclerosis.
o
Renal vein thrombosis.
Renal calculi:
Renal stones are uncommon in childhood.
When they occur, predisposing causes must be sought:
o
Urinary tract infection.
o
Structural anomalies of the urinary tract.
o
Metabolic abnormalities.
The commonest are phosphate stones associated with infection, especially with
Proteus.
Calcium-containing stones occur in idiopathic hypercalciuria, the most common
metabolic abnormality, and with increased urinary urate and oxalate excretion.
Deposition of calcium in the parenchyma (nephrocalcinosis) may occur with
hypercalciuria, hyperoxaluria and distal renal tubular acidosis.
Nephrocalcinosis may be a complication of furosemide therapy in the neonate.
Cystine and xanthine stones are rare.
Presentation may be with haematuria, loin or abdominal pain, UTI or passage of a
stone.
Stones that are not passed spontaneously should be removed, by either lithotripsy or
surgery, and any predisposing structural anomaly repaired.
A highfluid intake is recommended in all affected children.
If the cause is a metabolic abnormality, specific therapy may be possible.
Generalized proximal tubular dysfunction (Fanconi syndrome):
Proximal tubule cells are among the most metabolically active in the body, so are
especially vulnerable to cellular damage.
The cardinal features are excessive urinary loss of amino acids, glucose, phosphate,
bicarbonate, sodium, calcium, potassium and urate.
Fanconi syndrome should be considered in a child presenting with:
42
o
Polydypsia and polyuria.
o
Salt depletion and dehydration.
o
Hyperchloraemic metabolic acidosis.
o
Rickets.
o
Failure to thrive/poor growth.
Causes:
o
Idiopathic.
o
Secondary to inborn errors of metabolism:
Cystinosis.
Glycogen storage disorders.
Lowe syndrome (oculocerebrorenal dystrophy).
Galactosemia.
Fructose intolerance.
Tyrosinaemia.
Wilson disease.
o
Acquired:
Heavy metals.
Drugs and toxins.
Vitamin D deficiency.
Specific transport defects in some renal tubular disorders:
Ibnlatef
Notes
Pediatric – Renal system