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8/14/2019 Sickle Cell Renal Involvement 2
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Sickle Cell Nephropathy
Caroline Booth
Paediatric Nephrology
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Powars et al (1991)
25 yr observational study
725 patients most observed from birth or
early childhood 4% developed renal failure at a median age
of 23 yrs
Survival once in renal failure 4yrs Study increased and extended by 15yrs
12% patients developed ESRF by 37yrs
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Renal involvement
More frequent in HbSS than HbSC
Exception renal medullary carcinoma
Develop nephron loss and compensatoryhypertrophy
Prevalence of proteinuria increases with age,estimated at 20-30%.
Decreased renal function 5-25% Renal infarcts and papillary necrosis 30-40% in
radiological studies
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Pathologies
Papillary necrosis
Glomerular enlargement
Focal segmental glomerulosclerosis
Type 1 membranoproliferative
glomerulonephritis without immune
complex deposits
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Tubular defects
Concentrating defect irreversible by age
15yrs
incomplete type IV renal tubular acidosis
Impaired potassium secretion
Hyponatraemia in crisesIncreased tubular reabsorption of phosphate &
b-microglobulin and increased secretion of uric
acid and creatinine
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Renal haemodynamics
Increased glomerular filtration rate
Increased renal plasma blood flow
Biopsy increase in glomerular size - 87% larger
May be mediated by increased production of prostaglandins,
prostacyclin,
nitirc acid
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FSGS
Oxidative stress ischemic reperfusion
injury with associated chronic inflammatory
response
Hyperfiltration very common lesion in
Sickle cell disease
Proteinuria
?ongoing vascular endothelial damage
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Issues in Paediatrics
High prevalance of proteinuria (P) in
children 19 -26% increasing with age
Microalbuminuria (MA) 46% by teens
Some papers have shown correlation with
degree of anaemia (Alvarez et al 2008)
Others do not (Guasch et al 2008)
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Diabetes
Strong association with hyperfiltrationmicroalbuminuria and renal impairment
Long term studies strong associationbetween progression of microalbuminuriaand future development of renal impairment
These studies are not available for HBSS Alvarez et al (2008) showed no progressionbut retrospective and short term
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Monitoring
Progression to renal impairment uncertain
Need to monitor in all children
Recommend annual urinary albumin
measurements
Blood pressure review should be low
hypertension poor prognostic indicator
Renal function ?best way
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Early Markers
Voskaridou et al 2006
Studied cystatin C, NAG, b2-microglobulin,
creatinine clearance
Cystatin C and serum b2- microglobulin
showed strong correlation with creatinine
clearance and age
NAG positively correlated with proteinuria
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Intervention
Optimise sickle cell management
NSAIDS isolated reports no long term
benefit Immunosuppressive drugs as above
Hydroxyurea Shown to decrease
proteinuria short term ACE1 short term use reduce proteinuria but
with cessation worsening
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What we are doing
Initially looking at a cross section of
patients
The first groups were transfusion dependent
patients
Performed GFRs and measuring true
creatinine, ADMA and SDMA,NAG, RBPand looking for microalbuminuria
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Plasma creatinine v Inutest GFR
y = -0.1478x + 58.373
R2
= 0.1325
0
10
20
30
40
50
60
70
0 20 40 60 80 100 120 140 160 180 200
Inutest GFR (ml/min/1.73m2)
Plasmacreatin
ine(mol/l)
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eGFR v Inutest GFR
y = 0.7323x + 51.911
R2
= 0.2888
0
50
100
150
200
250
0 20 40 60 80 100 120 140 160 180 200
Inutest GFR (ml/min/1.73m2)
eGFR
(ml/m
in/1.7
3m2
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Figure 2. Plasma SDMA v GFR
y = 20.563x-0.7998
R2
= 0.8888
0.00
1.00
2.00
3.00
4.00
5.00
6.00
0 20 40 60 80 100 120 140
GFR (ml/min/1.73m2)
SDMA(m
ol/l)
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Plasma SDMA v Inutest GFR
y = -0.0029x + 0.7951
R2
= 0.49970
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0 20 40 60 80 100 120 140 160 180 200
Inutest GFR (ml/min/1.73m2)
PlasmaSDMA(mol/l
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Future
Big questions remain as
When to start treatment
What with
How long for
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