sickle cell renal involvement 2

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


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


PlasmaSDMA(mol/l


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Future

Big questions remain as

When to start treatment

What with

How long for

sickle cell renal involvement 2

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