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Flashcards in Paeds: Proteinuria Deck (38):
1

Transient versus persistant proteinuria

May occur during febrile illnesses or after exercise and does not require investigation.
Does nto exceed 0.15g/24hr

2

If persistent next step?

Should be quantified by measuring the urine protein/creatinine ratio in an early morning sample (protein should not exceed 20mg/mmol of creatinine)

3

Causes – non-pathological proteinuria

Transient
Fever
Exercise
UTI
Orthostatic proteinuria

4

Causes: pathological

Glomerular abnormalities
- Minimal change disease
- Glomerulonephritis
- Abnormal glomerular BM (familial nephritides)
Increased glomerular filtration pressure
Reduced renal mass
Hypertension
Tubular proteinuria – tubular interstitial nephritis
CKD

5

Orthostatic proteinuria

Protein only found when child is upright e.g. during the day
Diagnosed: measuring the urine protein/creatinine ratio in a series of early morning urine specimens
Prognosis: excellent and further investigations are not necessary.

6

Nephrotic Syndrome:
Description

Heavy proteinuria results in a low plasma albumin and oedema.

7

Nephrotic Syndrome:
Cause

Unknown, but a few cases are a secondary to systemic diseases such as henoch-Schonlein purpura and other vasculitides e.g. SLE, infections (e.g. malaria) or allergens (e.g. bee sting)

8

Nephrotic Syndrome:
Clinical signs of the nephrotic syndrome are:

- Periorbital oedema (particularly on waking), the earliest sign
- Scrotal or vulval, leg and ankle oedema
- Ascites
Breathlessness due to pleural effusions and abdominal distension

9

Nephrotic Syndrome:
Initial investigations

- Urine protein – dipstick
- FBC and ESR
- U+E, creatinine and albumin
- Complement levels – C3, C4
- Antistreptolysin O or anti-DNase B titres and throat swab
- Urine microscopy and culture
- Urinary sodium concentration
- Hepatitis B and C screen
Malaria screen if travel abroad

10

Nephrotic Syndrome: Diagnosis

Heavy proteinuria and low plasma albumin

11

Nephrotic Syndrome: Types

- Steroid-nephrotic syndrome
Steroid-resistant syndrome

12



Steroid-sensitive nephrotic syndrome Description

In 85-90% of children with nephrotic syndrome, the proteinuria resolves with corticosteroid therapy (steroid-sensitive nephrotic syndrome). These children do not progress to renal failurev

13


Epi
Steroid-sensitive nephrotic syndrome

Commoner in boys vs. girls
Asian children than in Caucasians
Weak association with atopy

14

Precipitated sometime

Steroid-sensitive nephrotic syndrome

Resp infections

15

Features suggesting steroid-sensitive nephrotic syndrome

Steroid-sensitive nephrotic syndrome

- Age between 1 and 10 years
- No macroscopic haematuria
- Normal blood pressure
- Normal complement levels
Normal renal function

16

Management

Steroid-sensitive nephrotic syndrome

- Oral corticosteroids (60mg/m2 per day of prednisolone), unless atypical features.
After 4 weeks dose reduced to 40mg/m2 on alternate days for 4 weeks and then stopped

17

Median time for urine to be free of protein

Steroid-sensitive nephrotic syndrome

11 days

18

New evidence shows

Steroid-sensitive nephrotic syndrome

Extending the initial course of steroids, by gradually tapering the alternate day part of the course, leads to a marked reduction in the proportion of children who develop relapsing or steroid-dependeant course.

19

Renal histology in steroid-

Steroid-sensitive nephrotic syndrome

Normal on light microscopy but fusion of the specialised epithelial cells that invest the glomerular capillaries (podocytes) is seen on electron microscopy—MINIMAL CHANGE DISEASE

20

With nephrotic syndrome is susceptible to several serious complications at presentation or relapse:

Steroid-sensitive nephrotic syndrome

- Hypovolaemia
- Thrombosis
- Infection
Hypercholesterolaemia

21


Prognosis

Steroid-sensitive nephrotic syndrome

- Relapses are identified by parents on urine testing
- Side-effects of corticosteroid therapy may be reduced by an alternate-day regimen
- Potentially steroid sparing agents
1/3 resolves directly, 1/3 infreqeunt relapses, 1/3 freqeunt relapses – steroid-dependant

22


Steroid sparing agents
Steroid-sensitive nephrotic syndrome

immunomodulator levamisole, alkylating agents (e,g, cyclophosphamide), calcineurin inhibitors such as tacrolimus and ciclosporin A and the ummunosuppressant mycophenolate mofetil

23

Hypovolaemia


Steroid-sensitive nephrotic syndrome

- Initial phase of oedema formation the intravascular compartment may become volume depleted

24


Hypovolaemia symptoms
Steroid-sensitive nephrotic syndrome

Abdominal pain and may feel faint

25

Indications of hypovolaemia

Steroid-sensitive nephrotic syndrome

Low urinary sodium (

26

Management if indications present

Steroid-sensitive nephrotic syndrome

Urgent reatment with intravenous albumin as the child is at risk of vascular thrombosis and shock.

27


Thrombosis:
Processes

Steroid-sensitive nephrotic syndrome

Urinary losses of antithrombin, thrombocytosis which may be exacerbated by steroid therapy, increased synthesis of clotting factors and increased blood viscosity from the raised haematocrit, predisposes to thrombosis.

28

Steroid-sensitive nephrotic syndrome: thombosis complications

May affect the brain, limbs and splanchnic circulation

29

Steroid-sensitive nephrotic syndrome: Hypercholesterolemia:
description

Correlates inversely with the serum albumin, but the cause of the hyperlipidaemia is not fully understood.

30


Steroid-resistant nephrotic syndrome:

Management of the oedema is by

- Referral to a paediatric nephrologist.

- - diuretic therapy, salt restriction, ACE inhibitors and sometimes NSAIDS, which may reduce proteinuria

31

Steroid-resistant nephrotic syndrome:
Cause

Focal segmental glomerulosclerosis
Mesangiocapillary glomerulonephritis (membranoproliferative glomerulonephritis
Membranous nephropathy

32

Focal segmental glomerulosclerosis

Specific features
Prognosis

Most common
30% progress to end-stage renal failure in 5 years
Respond to cyclophosphamide, ciclosporin, tacrolimus or rituximab
Recurrence post-transplant is common

33

Mesangiocapillary glomerulonephritis (membranoproliferative glomerulonephritis
Specific features
Prognosis

- More common in older children
Haematuria and low complement level present
- Decline in renal function over many years

34

Membranous nephropathy
Specific features
Prognosis

Associated with hepatitis B
May precede SLE
Most remit spontaneously within 5 years

35

Congenital Nephrotic syndrome: Presence

- First 3 months of life.
It is rare

36

Congenital Nephrotic syndrome: Aetiology

- Commonest kind is recessively inherited and the gene frequency is particularly high in Finns
UK more common in consanguineous families.

37

Congenital Nephrotic syndrome: Associated with

High mortality due to complication of hypoalbuminaemia rather than renal failure

38

Congenital Nephrotic syndrome:
Outcome

Hypoalbuminaemia may be so severe that a unilateral nephrectomy may be necessary for its control, followed by dialysis for renal failure, which is continued until the child is large and fit enough for renal transplantation.

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