Download (L15 L16 Hematuria and Poststreptococal GN. Lupus [tryb zgodności])

The most common causes,
diagnosis and treatment in
haematuria in children.
Prof. dr hab.
Anna Wasilewska
Hematuria: Definition
presence of 5 or more red blood cells
(RBCs) per highhigh-power field in 3 of 3
consecutive centrifuged specimens
1
2
3
4
5
dipsticks approximations *
dipstick cells per HPF
trace
0-2
+
3-5
++
6-10
+++
10-20
++++
>20
6
Phase Contrast Microscopy
Presence of a significant number of
dysmorphic RBCs suggests a renal
(glomerular) source of the hematuria.
A urine sample that predominantly
contains eumorphic RBCs suggests an
extrarenal (nonglomerular) source.
Sensitivity of 8383-95% and a specificity of
81
81--95%.
7
Mechanism of erythrocyte deformation:Red cells
traverse trough glomerular basement membrane
Collar JE et al:
Kidney Int. 2002, 59: 2069-2072
8
Hematuria
Symptomatic or asymptomatic
Transient or persistent
Isolated or associated with proteinuria &
other urinary abnormalities
Presentation
Children with hematuria may present in one
of three way
1-Onset of gross hematuria
2-Onset of urinary or other symptoms
with incidental finding
3-Incidental finding during a health
evaluation
9
Role of Pediatrician
Recognize and confirm the finding of
hematuria.
2. Identify common etiologies.
3. Select patients who have significant
urinary system disease that might require
further expertise in either diagnosis or
management and referral
1.
10
GLOMERULAR HEMATURIA
Isolated Renal Disease *
IgA nephropathy (i.e., Berger disease)
Postinfectious GN (i.e., poststreptococcal GN)
Thin glomerular basement membrane nephropathy
Alport syndrome (hereditary nephritis)
Membranous nephropathy
Membranoproliferative GN
Focal segmental glomerulosclerosis
Anti--glomerular basement membrane disease
Anti
GLOMERULAR HEMATURIA
Multisystem Disease *
Henoch-Schönlein purpura nephritis
HenochHemolytic--uremic syndrome
Hemolytic
Sickle cell glomerulopathy
HIV nephropathy
Systemic lupus erythematosus nephritis
Wegener granulomatosis
Polyarteritis nodosa
Goodpasture syndrome
11
EXTRAGLOMERULAR HEMATURIA 1*
Anatomic
Hydronephrosis
Cystic kidney disease
Polycystic kidney disease
Multicystic dysplasia
Tumor (Wilms, rhabdomyosarcoma, angiomyolipoma)
Trauma
Crystalluria
Calcium
Oxalate
Uric acid
Urolithiasis
Trauma
Heavy exercise
EXTRAGLOMERULAR HEMATURIA 2 *
Tubulointerstitial
Pyelonephritis
Interstitial nephritis
Acute tubular necrosis
Papillary necrosis
Nephrocalcinosis
Inflammation (infectious and noninfectious)
Cystitis
Urethritis
Vascular
Arterial/venous thrombosis
Malformations (aneurysms, hemangiomas)
Nutcracker syndrome
12
EXTRAGLOMERULAR HEMATURIA 3
Coagulopathy
Abnormal red cells which destruct:
destruct: sickle
cell, spherocytosis, thallassaemias etc
Paroxysmal nocturnal haemoglobinuria
extrinsic cell factors damaging red cells
toxins & infections - haemolytic anaemias
Red urine
•
•
•
•
•
•
•
•
•
•
blood
free haemoglobin
myoglobin
food and vitamin colourings
beetroot, berries, rhubarb etc
pyridium (local bladder analgesic)
rifampicin (antibiotic)
chloroquine (antimalarial)
plaquenil (rheumatology)
phenolphthaline (laxatives)
13
Other causes of red
coloration of urine
•
•
•
•
Drugs: rifampicine/
pyridium/ phenophthalin
Dyes: aniline
aniline--coloring
agent
Diet: Beetroot
Metabolic disorders:
Hematoporphyrinuria
History taking and phisical examination
will be discussed during the classes
14
Investigations
•
Laboratory investigations:
Urine analysis
The presence of RBCs
Proteins
Casts
Urine culture
Urine cytology – Urothelial tumor cells
Pap smear may reveal malignant cells
Blood examination
Full blood count
Clotting time
Urea & creatinine
Tumour markers (PSA for prostate cancer)
Investigations
Radiography:-Radiography:
•
•
•
•
U/S
Plain IVU
may show stone, tumour filling
defect.
CT scan
renal lesion, tumors, and cysts.
Chest XX-ray
may show pulmonary
involvement
15
CT – Wilms Tumor
Investigations
•
Cystoscopy:-Cystoscopy:
Detection of bladder tumours and interstitial
cystitis
The site of bleeding if in the bladder or prostate
could be visualized.
Pathologic areas are biopsied.
Blood may be seen coming from one ureter.
Selective Renal Angiography:Angiography:Renal arterioarterio-venous malformation.
16
Cystoscopy
Kidney biopsy
17
Any questions ?
SYSTEMIC LUPUS
ERYTHEMATOSUS
Prof. dr hab.
Anna Wasilewska
18
INTRODUCTION
SLE has a multiplicity of presentations
In adolescence it may have an insidious
onset
Can be complicated by other difficulties of
disentangling normal psychological
problems associated with adolescence
Not a common disease
Definition of SLE
Autoimmune rheumatic disease
Commonly effects the skin &
musculoskeletal systems
but can affect every organ
Kidney
Heart
Lungs
- & the Central Nervous System
19
Definition of SLE
(2)
Diversity of presenting symptoms
complicates the diagnosis
American College of Rheumatology (ARA)
published guidelines for disease
classification(1971, revised 1982 & 1997)
Patients need to fulfil 4 of the 11 criteria
to reach a diagnosis of SLE
ARA Classification for SLE
1. Malar rash
2. Discoid rash
3.Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis:
pleuritis
pericarditis
(1)
7. Renal disorder
Proteinuria >0.5g/24h or
>3g persistently or
cellular casts
8. Neurological disorder
Seizures
psycosis (having excluded
other causes)
20
ARA Classification of SLE
(2)
9. Haemotological
disorder
Haemolytic anaemia
or
Leucopenia or <4.0 x
109/l on 2 0r more
occasions
Lymphopenia or
<1.5 x 109/l on 2 or
more occasions
Thrombocytopenia
<100 x 109/l
ARA Classification of SLE
(3)
10. Immunolgical disorders
Raised antinative DNA (antibodies to
genetic material in cells)
anti--Sm antibody (Sm is a protein found in
anti
the cell nucleus)
positive finding of antiphospholipid
antibodies based on
abnormal IgG or IgM
anticardiolipin levels or
positive test for lupus anticoagulant
21
ARA Classification of SLE
(4)
False-positive serological test for syphilis
Falsepresent for at least 6 months
11. Antinuclear antibody in raised titre
(autoantibodies to cell nuclei)
EPIDEMIOLOGY
Estimated incidence of lupus in kids
under 15 yrs is 6 per 100,0003
Incidence varies with racial origin
(1:250 in black American women)
Sex ratio in childhood SLE varies to that
of adults (more boys than girls in
paeds, 9 times as common in women as
men)
? Genetic component (related to
incidence/area) “Twins study”
22
Clinical Features
(1)
Classical photosensitive butterfly rash
Vasculitic lesions of the hands & feet (or
Raynard’s phenomenon
Profound tiredness
Arthralgia or even arthritis
Oral ulcers less common than in adults
Clinical Features
(2)
Pericarditis
Pleuritis
Pulmonary vasculitis or haemorrhage
Some present initially with renal
involvement
?9
9--45% cases in kids present with
some cerebral involvement (most
common headaches & depression)
23
Clinical Features
(3)
Other CNS symptoms chorea, seizures,
CVA, cranial neuropathy + visual loss
Functional psychosis, personality disorder,
& memory alteration
Butterfly rash
24
Vasculitic lesions of the hands &
feet (or Raynard’s phenomenon
Investigations (1)
Serological for end organ dysfunction and
immunological tests (looking for the
autoantibody profile of lupus)
FBC (anaemia,lymphopenia,
thrombocytopaenia)
Raised ESR
Low to normal complement levels
Raised ANA
25
Investigations (2)
Lumber puncture
Electroencephalogram (EEG)
Magnetic resonance imaging (MRI)
Computed tomography (CT)
? Skin biopsy
Lupus Nephritis
(1)
Or “Lupus glomerulonephritis”
glomerulonephritis”
Developed by approx.. 1/3 of lupus patients
(50% in adults within 1 yr of diagnosis)
15 to 20% will require RRT (Pollak & Pirani 1997)
Proteinuria (45 to 65% will develop nephrotic
syndrome
associated fluid retention, weight gain,
oedema
Microscopic Haematuria to 90% of
patients
(Cameron, 1999)
26
Lupus Nephritis
(2)
Mild to severe renal compilcations
Commonly UTI’s
Medications may confuse renal signs ?
BUN, creatinine,
creatinine, serum albumin, U&E’s
EMU
USS, or renal biopsy (for confirmation)
Drug Therapy
Anti-inflammatory drugs
AntiCorticosteroids
Anti--malarial drugs
Anti
Immunosuppressive RX
Symptomatic therapy?
27
Anti--inflammatory Drugs
Anti
Reduce inflammation & pain
Particularly effective for lowlow-grade fever,
fatigue, arthritis & pleurisy
NSAID’s = salicylates (asprin, ibuprofen)
Corticosteroids
For more active disease with arthritis,
pericarditis, pleuritis or serositis.
IV or orally
Maintenance in UK of oral enteric
coated pred.
Acute flares IV methylpred
(don’t forget side effects, osteoporosis,
atherosclerosis)
28
Anti--malarial Drugs
Anti
Particularly effective against arthritis,
skin rashes & mouth ulcers
Hydroxychlorquine (Plaquenil) may take
4-6 months before a benefit is seen
Side effects = ? Harm foetus, gastric
symptoms,rash, darkening of skin,
muscle weakness, retinal damage
Eye exam before then 6 monthly
Immunosuppressive Agents
Which agent? When ? + still
controversial
Azathioprine
Cyclophosphamide in severe cases,
(especially in lupus nephritis & cerebritis)
? IV cyclophos monthly for 6 months,
followed by infusions 22-3 monthly for 2
years (Thomas et al, 2000)
Methotrexate (Ravelli et al, 1998)
29
Plasmapheresis
In conjunction with cyclophos
Role in the management of severe lupus
remains controversial
? “Life“Life-threatening situations” it may `buy
time`……………………………...
General Management
Multi-professional
MultiImmunisations (no live vaccines, Zoster
immune globulin (ZIG))
Diet
Psychological issues + Schooling
Drug compliance
Methods of coping with chronic illness
30
Remember
Poststreptococcal
Glomerulonephritis
Prof. dr hab. Anna Wasilewska
31
DEFINITIONS
GLOMERULONEPHRITIS: Glomerular inflammation
resulting in the triad of hematuria, proteinuria, and
hypertension.
RED CELL CASTS: Injured glomeruli have increased
permeability and leak red cells and proteins into the
proximal convoluted tubule; the material
subsequently clumps in the distal convoluted tubule
and in the collecting ducts. When passed, these cell
clumps retain the shape of the tubule in the urine.
Red cell casts are markers for glomerular injury.
CLINICAL APPROACH
Acute poststreptococcal glomerulonephritis
(APSGN) is the most common of the
postinfectious nephritides, comprising 80% to
90% of cases. Other bacteria, viruses, parasites,
and fungi also have been implicated.
Males are more commonly affected;
it is most common in children between the ages
of 5 and 15 years and is rare in toddlers and
infants.
32
The group A ββ-hemolytic Streptococcus
(GABHS) infection can be in the form of
either pharyngitis (“strep throat”) or a
superficial skin lesion (impetigo).
Not all GABHS infections result in APSGN;
certain GABHS strains are “nephritogenic
“nephritogenic””
and are more likely to result in APSGN.
Rheumatic fever only rarely occurs
concomitantly with APSGN.
Antibiotic use during the initial GABHS infection
may reduce the subsequent rheumatic fever
risk, yet has not been shown to prevent APSGN.
The nephritis risk after infection with a
nephritogenic strain of GABHS remains 10% to
15%.
Generally the interval between GABHS
pharyngitis and APSGN is 1 to 2 weeks;
the interval between GABHS impetigo and
APSGN is 3 to 6 weeks.
33
Symptom onset is abrupt. Although almost all
patients have microscopic hematuria, only 30% to
50% develop gross hematuria.
85% present with edema and 60% to 80% develop
hypertension.
The most important laboratory test in patients with
APSGN is measurement of serum C3 and C4 levels.
C3 is low in 90% of APSGN cases, whereas C4
usually is normal.
If both levels are low, an alternate diagnosis is
considered.
Urinalysis typically reveals high specific gravity, low
pH, hematuria, proteinuria, and red cell casts.
Documentation of a recent streptococcal infection is
helpful;
serum markers include the presence of ASO enzyme
antibodies and antianti-DNase B antibodies. ASO
antibodies are found in 80% of children with recent
GABHS pharyngitis but in less than 50% of children
with recent GABHS skin infection.
34
ASO titers are positive in 16% to 18% of normal
children.
Anti--DNase B antibodies assays are more reliable;
Anti
they are present in almost all patients after
GABHS pharyngitis and in the majority of patients
after GABHS skin infection.
Renal biopsy is no longer routine.
Treatment
Treatment is generally supportive.
Fluid balance is crucial; diuretics, fluid
restriction, or both may be necessary.
Sodium and potassium intake may require
restriction.
Hypertension usually is easily controlled with
calcium--channel blockers.
calcium
Strict bed rest and corticosteroid medications
are not helpful.
Dialysis is rarely required.
35
Resolution usually is rapid and complete. The
edema resolves in 5 to 10 days, and patients
usually are normotensive within 3 weeks.
C3 levels usually normalize in 2 to 3 months; a
persistently low C3 level is uncommon and
suggests an alternate diagnosis.
Urinalysis may be persistently abnormal for
several years.
Case 1
A 1414-yearyear-old Hispanic male presents with a 3
3--day
complaint of “brown urine.” Two weeks ago he had 2
days of fever and a sore throat, but he improved
spontaneously and has been well since. His
review of systems is remarkable only for his slightly
puffy eyes, which he attributes to latelate-night studying
for final examinations.
36
On physical examination he is afebrile, his blood
pressure is 135/90 mm Hg, he is
active and nontoxic in appearance, and he has
some periorbital edema. The urine dipstick has a
specific gravity of 1.035 and contains 2+ blood
and 2+ protein. You spin the urine, resuspend the
sediment, and identify
red blood cell casts under the microscope.
What is the most likely cause of this
patient’s hematuria?
What laboratory tests would support this
diagnosis?
What is the prognosis of this condition?
37
Most likely diagnosis
Acute poststreptococcal glomerulonephritis
(APSGN).
Laboratory studies: C3 (low in 90% of cases),
C4 (usually normal);
antistreptolysin--O (ASO) enzyme antibodies
antistreptolysin
and antideoxyribonuclease B
(anti--DNase B) antibodies provide evidence of
(anti
recent streptococcal infection.
Prognosis: Excellent; 95% to 98% of affected
children recover completely.
Summary::
Summary
A healthy adolescent male with a
preceding pharyngitis has periorbital
edema and mild hypertension, and has
developed teatea-colored urine that on
microscopy reveals red blood cells.
38
Remember
➤ Post streptococcal glomerulonephritis is
the most common postinfectious
nephritis and has a good prognosis.
prognosis.
➤ Confirming the diagnosis of APSGN
requires evidence of invasive streptococcal
infection such as a elevated anti
anti--DNAase B
titer..
titer
Post-Infectious
PostGlomerulonephritis
Things you must know
Child after strep throat
Immune complexes
Hypercellular glomeruli
Subepithelial humps
39
Post-Infectious
PostGlomerulonephritis
Mnemonic
“Sore throat, face bloat, pee
coke”
Considerations
This patient is otherwise healthy, had
pharyngitis, and now has hematuria, proteinuria,
edema, and hypertension. Although APSGN is
likely, other possibilities must be considered.
Strenuous activity can cause rhabdomyolysis and
dark urine, but patients with these conditions
often will have muscle aches, fatigue, nausea
and vomiting, and fever.
40
Immunoglobulin A nephropathy is characterized by
recurrent painless hematuria, usually preceded by
an upper respiratory tract infection.
Henoch--Schönlein purpura (HSP) is a relatively
Henoch
common cause of nephritis in pediatrics, but most
cases occur in younger children, peaking in
incidence between 4 and 5 years of age.
Lupus nephritis (systemic lupus erythematosus
[SLE]) can present as described and is considered if
the hematuria does not resolve or if the C3 level
does not normalize in 6 to 12 weeks.
Comprehension Question 1
A 1616-yearyear-old adolescent male complains of
intermittent colacola-colored urine of several years’
duration, usually when he has a “cold.” He is
otherwise well and has no medical complaints.
When the darkcolored urine is present, he has no
dysuria. None of his family members has similar
complaints or renal disease. On physical
examinationhe is normotensive and appears
healthy.
41
Which of the following is the most
likely cause of his intermittent
hematuria?
ematuria?
A. Acute poststreptococcal glomerulonephritis
B. HenochHenoch-Schönlein purpura nephritis
C. IgA nephropathy
D. Recurrent kidney stones
E. Rapidly progressive glomerulonephritis
C. IgA nephropathy
Recurrent painless gross hematuria, frequently
associated with an upper respiratory tract
infection, is typical of IgA nephropathy. These
patients may develop chronic renal disease over
decades. If proteinuria, hypertension, or
impaired renal function were found, a biopsy
would be necessary. The other options are not
consistent with the asymptomatic, intermittent
nature of this patient’s problem.
42
Comprehension Question 2
The parents of a healthy 1212-yearyear-old girl bring her
to you for a physical examination required for
summer camp. They have no complaints, and the
girl denies any problems. Her last menses was
normal 2 weeks prior. The camp requires a urine
screen. To your surprise, the cleancatch urine
screen has significant hematuria. Red cell casts are
noted. You tell the findings to the parents, and they
respond that “everyone on dad’s side of the family
has blood in their urine and they are all doing well.”
The family history is negative for deafness and for
renal failure
Microscopy of renal tissue from this patient
or from her father will most likely reveal
which of the following?
A. Endothelial cell swelling and fibrin in the
subendothelial space
B. Immune complex deposition in the
mesangium
C. Large numbers of crescentic glomeruli
D. Renal cell carcinoma
E. Thinning of the basement membrane
43
E. Thinning of the basement
membrane
This history is consistent with benign familial
hematuria, an autosomal dominant condition that
causes either persistent or intermittent hematuria
without progression to chronic renal failure.
failure.
Biopsy reveals a thin basement membrane
membrane;; in
some cases the biopsy is normal.
normal.
Comprehension Question 3
A 1717-yearyear-old adolescent female has joint
tenderness for 2 months; the pain has affected her
summer job as a lifeguard.
In the morning, she awakens with bilateral knee
pain and swelling and right hand pain. The pain
eases during the day but never completely resolves.
Nonsteroidal anti
anti--inflammatory drugs help slightly.
She also wants a good “face cream” because “her
job has worsened her acne.”
44
On physical examination you notice facial
erythema on the cheeks and nasolabial
folds. She has several oral ulcers that she
calls cold sores, bilateral knee effusions,
and her right distal interphalangeal joints
on her hand are swollen and tender. Her
liver is palpable 3 cm below the costal
margin. She has microscopic hematuria
and proteinuria.
Which of the following is the most likely
cause of this young woman’s arthritis?
A. Juvenile rheumatoid arthritis
B. Lyme disease
C. Osteoarthritis
D. Postinfectious arthritis
E. Systemic lupus erythematosus
45
E. Systemic lupus erythematosus
Systemic lupus erythematosus affects more
women than men, and nephritis is a
common presenting feature. Her rash,
photosensitivity, oral ulcers, hepatomegaly,
arthritis, and nephritis combine to make
this a likely diagnosis. A positive antinuclear
antibody test and low C3 and C4 levels
would help to confirm the diagnosis.
You are not surprised to see one of your most
challenging patients, a 16
16--yearyear-old adolescent
female who has been seen several times per
week over the last 2 months complaining of cough,
occasional hemoptysis, malaise, and intermittent
low
low--grade fever.
46
Thus far you have identified a microcytic,
hypochromic anemia for which she has
been taking iron (without response) and
migratory patchy infiltrates on chest
radiograph that seem unaffected by
antibiotic treatment. She has no
tuberculosis (TB) exposure risks, and her
TB skin test was negative.
Today she also complains of facial edema
and teatea-colored urine.
You suddenly realize her symptoms can
be grouped as which of the following
syndromes?
A. Alport syndrome
B. DenysDenys-Drash syndrome
C. Goodpasture syndrome
D. HemolyticHemolytic-uremic syndrome
E. Nephrotic syndrome
47
C. Goodpasture syndrome
C. Goodpasture syndrome is the clinical
diagnosis when patients exhibit nephritis and
pulmonary hemorrhage.
hemorrhage. It can be caused by a
number of conditions
conditions,, including SLE and HSP.
HSP.
Alport syndrome is a genetic defect in collagen
synthesis that leads to abnormal basement
membrane formation
formation;; patients will develop
hematuria, proteinuria, and renal failure.
failure. DenysDenysDrash syndrome is a group of findings composed
of Wilms tumor, gonadal dysgenesis,
dysgenesis, and
nephropathy..
nephropathy
48