Transcript Renal-CPC-17-y-old

Renal CPC
February 2009
‘A 17 year old girl with chest pain
and haemoptysis….’
Patient history
• 17 y old girl admitted to hospital with a
history of chest pain and haemoptysis
• Previous history of mild asthma
• Developed bi-pedal oedema 4 months
previously
• 3+ proteinuria in her urine, haematuria
and hyperlipidaemia
Patient history
• Past and family history:
– Mild intermittent asthma
– Mother had MS and asthma and sickle cell
trait
– Siblings: sickle cell trait
– Father had hypertension
– Cousins had ?connective tissue disorder
– One cousin on dialysis ?cause
Patient history
• Renal biopsy at that time [4 months
previously] indicated membranous GN
• Negative for antibodies to:
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Hep B
Hep C
Anti-ribonuclear protein
Anti-topoisomerase I,
Anti-Ro [SS-A]
Anti-double stranded DNA
Anti-nuclear antibody
Patient history
• Levels of serum C3 and C4 complement were
normal
• Commenced on enalapril, atorvastatin and
fluid restriction begun
• Developed muscle cramps and pain and
atorvastatin stopped
• Persistent abdominal and back pain
• US of the kidney: small peri-nephric
haematoma
Patient history
• Over the next 2 months, continuing back pain with
evidence of reduction of the peri-nephric haematoma
• Treated with routine analgesics
• Condition continued to deteriorate until she was
unable to walk
• Bilateral lower limb oedema occurred intermittently
• 2 weeks before admission to hospital, the severity of
the abdominal and back pain increased significantly,
and also developed chest pain [radiating to the neck
and shoulder area, made worse by coughing and
deep inspiration]
Patient history
• 6 days before admission, a diagnosis on intercostal
nerve ‘neuralgia’ was made
• The chest pain continued to get more severe and
cough and haemoptysis developed
• She experienced one episode of significant dyspnoea
which was relieved by the use of an albuterol inhaler
• The day before admission to this hospital she
attended the A&E room in another facility:
– 390C, 115/69mmHg, HR 156, RR 50, O2 sats –98% [on room
air], looked de-hyrdrated
– Breathing shallow, lungs clear, other observations and
clinical examination normal
Patient history
• She was given 2L of normal saline by the
attending physician and pain relief
• What investigations would you order on this
patient?
Patient history
• O2 saturation dipped intermittently to 92-93% on
room air
• Urinalysis:
– protein +3, blood +2, SG 1.041
• CXR:
– Patchy density in the left costo-phrenic angle
• ECG:
– Tachycardia
• Cardiac echcocardiography:
– Right ventricular dilatation, pulmonary arterial pressure of
60mmHg and a small pericardial effusion. No clots were
visible
Patient history
• Spiral CT scan and CT angiography of the
chest were performed:
– Emboli in both pulmonary arteries
– Multiple bilateral pulmonary infracts
– Bilateral pleural effusions
• Renal ultrasound:
– Haematoma around the left kidney
• Doppler studies:
– No clot in the deep veins of the leg, or the inferior
vena cava
• Heparin treatment commenced
Patient history
• Transferred to ICU
• On admission to ICU:
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38.30C, HR 148, RR 34, O2 sat 92%
Blood pressure increased
Increased respiratory effort
Prominent second heart sound
JVP: increased to 7cm [at 30degree recline]
Systolic murmur [grade 2/6], lower sternal border
Right ventricular heave
Tender abdomen
1+ oedema of both legs extending to above the
knee
Patient history
• ECG:
– S wave in lead I and Q and T waves in lead III
Laboratory investigations
Haemaglobin – normal
HcT –normal
WBCs – normal
Diff – normal
Platelets 497,000 [increased]
MCV – normal
PTT 70.3 [on heparin]
PT 1.1 [normal]
D-dimers –5,656 [increased]
Glucose – normal
Na+ – normal
K+ – normal
Cl- – normal
Laboratory investigations
BUN – normal
Bilirubin –normal
Protein:
total – normal
albumin – low
Ca++ – normal
CK – normal
CK-MB – normal
Alk phos – normal
AST – normal
ALT – normal
C-reactive protein –22.6 [increased]
Cardiac troponin – elevated
Amylase – normal
NT-pro-BNP 2571 [increased]
Lipoprotein [increased]
Laboratory investigations
Lipase – normal
Activated protein C screen – normal
Functional protein S – normal
Anticardiolipin IgG phospholipid units [GPL] – normal
Anticardiolipin IgM phospholipid units [MPL] – normal
Antithrombin III – normal
Lupus anticoagulant – negative
PT gene G201210A – not detected
Antinuclear antibody 1:40 speckled
Anti-double stranded DNA Ab titre – negative
Anti-Ro [SS-A] antibody – negative
Anti-smooth muscle antibody – negative
Goodpasture’s antigen – negative
ABGs:
pH 7.51
pCO2 increased
paO2 normal
Urine total protein [mg/24 hrs] – 2690 (increased)
Urine creatinine [g/24 hrs] 0.25
Cardiac echo:
- panel A: flattening of the interventricular
septum
- pericardial effusion [black arrows]
- panel B: enlarged right ventricle and a
pericardial effusion [white arrow]
Magnetic Resonance Venogram
Small area of hypointense
thrombus extending from the
right renal vein into the
inferior vena cava
What is your differential
diagnosis?
• What would you do next?
• What about anti-coagulation?
• Will the low albumin level effect the use of
heparin?
• Should we use a direct thrombin inhibitor?
• Should we transition to warfarin and what INR
would you attempt to achieve?
Summary of abnormalities
• Proteinuria, haematuria, hyperlipdaemia [the
nephrotic syndrome]
• Pulmonary embolism [haemoptysis, chest
pain and ECG changes]
• Elevated cardiac troponins
• Elevated pro-BNP
• Elevated d-dimers on admission
• Elevated platelet count
• Variable hypertension
• Anti-nuclear antibody
• Membranous GN
Causes of the nephrotic syndrome
Proteinuria> 3.5 g of urinary protein:hypoalbuminaemia <3g/dl: oedema, hyperlipidaemia and lipiduria
Differential diagnosis
• Pulmonary embolism
• Pulmonary embolism and features of
the nephrotic syndrome
• Pulmonary embolism and features of
the nephrotic syndrome plus something
else????
What test would you order
now or would review any
previous test?
Renal biopsy appearances
• Glomeruli:
– normal or showed mild mesangial
hyeprcellularity
– granular staining of the BM with IgG
• EM:
– sub-epithelial deposits with effacement of
the podocyte foot processes
– mesangial and sub-endothelial deposits
Diagnosis
• Membranous GN
– Primary
– Secondary
• Drugs, cancer, infection, autoimmune disease
[most commonly SLE]
Features suggestive of SLE
in this case
Treatment approaches
• Improve proteinuria and treat
hyperlipidaemia:
– ACE inhibitors, statins
• Add in immunosuppressive therapy:
– If proteinuria persists
A – minimal change
B – membranous GN
Features of SLE
Immune response to self or foreign antigen
Genetic deficiency in components of the innate immune system, such as
complement component 1q (C1q), C4, serum amyloid protein, natural IgM or
complement receptor 2 (CR2) leads to increased susceptibility to systemic lupus
erythematosus (SLE).
Two general hypotheses have been proposed to explain the genetic association with disease.
a | The clearance hypothesis states that failure to clear apoptotic bodies — a principal source of SLE
antigens — leads to inappropriate activation of mature, self-reactive B and T cells. Accordingly, apoptotic bodies
are usually sequestered from the adaptive immune system by efficient recognition, binding and uptake by
components of the innate immune system. So, SLE antigens are effectively 'hidden' from self-reactive
lymphocytes. Defects in clearance of apoptotic bodies, such as those that occur in the absence of C1q or C4,
would lead to the exposure of self-antigens to autoreactive lymphocytes and the development of SLE.
b | The tolerance hypothesis states that innate immunity is important in the negative selection of selfreactive lymphocytes, especially B cells that are specific for SLE antigens. The innate immune pathway functions
to recognize, degrade and bind SLE antigens to stromal cells present in the bone marrow and spleen. Immature B
cells that encounter concentrations of cognate antigen above a certain threshold are negatively selected; that is,
they undergo receptor editing, clonal deletion or anergy. C1q and C4 function to enhance 'presentation' of SLE
antigens to specific immature B cells in the bone marrow. Alternatively, coupling of C4b to self-antigen could result
in co-receptor stimulation of immature B cells displaying the CR1–CD19–CD81 co-receptor. The co-receptor is
expressed at the surface of immature B cells during transitional stages in the spleen, in which co-ligation with the
B-cell receptor could result in enhanced negative selection and 'escape' of self-reactive B cells into the peripheral
mature compartment, where they encounter SLE antigens and become activated.
Summary of the multiple factors that are known to contribute to
abnormal lipid profiles in SLE
Sandborg C et al. (2008) Therapy Insight: cardiovascular disease in pediatric /early adult systemic lupus
erythematosus
Nat Clin Pract Rheumatol doi:10.1038/ncprheum0789
Topics for revision
• Pulmonary embolism
– Risk factors
– Investigation
• The nephrotic syndrome
– Causes of..
– Investigation of..
• Membranous GN