paediatric nephrology Flashcards
1
Q
CO to nephron
A
recieves 25% CO/min
2
Q
GFR in children
A
neonate 20-30ml/min/1.73m2
2yrs - equivalent to adult, 90-120
3
Q
GFR in children
A
neonate 20-30ml/min/1.73m
4
Q
label the nephron
A
5
Q
what are the 5 functions of the kidney
A
- waste handling
- water handling
- salt balance
- acid base control
- endocrine - RBC, BP, bone health
6
Q
components of the glomerular filtration barrier
A
endothelial cell:
- fenestrated
- vulnerable to immune mediated injury
GBM
- type IV collagen and laminin
- synthesis from podocytes and endothelial cells
- mesangial cells playing a role in turnover
podocyte
- proteins - podocin, nephrin
mesangial cells
- glomerular structural support
- embedded in GBM
- regulates blood flow of the glomerular capillaries
7
Q
how does the glomerular filtration barrier work
A
- works like a sieve
- larger holes = greater leak
- glomerular filtration within the capillary lumen
8
Q
how do patients present with glomerulopathy
A
proteinuria and haematuria
9
Q
clinical presentation of glomerulopathy
A
- blood and protein in varying amounts dictate clinical presentation and suggest diagnosis
- BUT injury to one part of the GFB affects the other components
- proteinuria signifies glomerular injury
10
Q
what do different amounts of haematuria and proteinuria indicate
A
11
Q
how common is acquired glomerulopathy
A
common
12
Q
which components are affected in the different types of acquired glomerulopathies
A
epithelial cell (podocyte) - minimal change disease (nephrotic)
basement membrane - post infectious glomerulonephritis (nephritic)
endothelial cell - PIGN, haemolytic uraemic syndrome (nephritic)
mesangial cell - HSP/IgA nephropathy (mixed picture)
13
Q
how common are congenital glomerulopathies
A
rare
14
Q
layers involved in congenital glomerulopathies
A
podocyte skeletal integrity - congenital nephrotic syndrome (podocin - AR, nephrin - AR)
basement membrane proteins - alport syndrome (XL), thin basement membrane disease (AD)
endothelial/microvascular integrity - complement regulatory proteins (MPGN)
15
Q
how much proteinuria is too much
A
dipstix
- measures concentration
- ≥3+ usually abnormal
- false +ves/-ves
protein creatinine ratio (practical)
- early morning urine best
- normal: Pr:CR ration <20mg/mmol
- nephrotic range: >250mg/mmol
24hr urine collection (gold standard)
- normal <60mg/m2/24hrs
- nephrotic range >1g/m2/24hrs
- adults >3.5g/24hrs
16
Q
what is nephrotic syndrome
A
nephrotic range proteinuria → hypoalbuminaemia → oedema (increasing 3rd space vol)
17
Q
Starling’s forces
A
oncotic (osmotic) vs hydrostatic pressure
proteins hold water intravasculary
hypoalbuminaemia → 3rd space fluid loss (hydrostatic pressure drives fluid out)
18
Q
typical presentation of nephrotic syndrome - hx
A
young child
present w/ minimal change disease or steroid sensitive nephrotic syndrome
prev/intercurrent illness e.g. gastroenteritis
short hx of oedema (face worse in AM, legs worse in PM)
19
Q
nephrotic syndrome - features on examination
A
pallor
inflated weight
periorbital oedema, pitting oedema in lower limbs, ascites, pleural effusions
BP normal/raised/low
frothy urine
20
Q
making a diagnosis of nephrotic syndrome
A
- odema
-
proteinuria
- urine dipstix - protein +++, blood ++ (not frank, 50% w/ MCD have microscopic haematuria)
- Pr:CR - 1200mg/mmol creatinine
- urine Na - 10mmol/l - low, holding onto water
-
bloods
- hypoalbuminaemia - 12mg/dl (n >32)
- normal creatinine
21
Q
type of nephrotic syndrome and age at presentation
A
80% of children have minimal change disease
steroid resistance - focal segmental glomerulonephritis, membranoproliferative glomerulonephritis
22
Q
typical features of minimal change disease
A
1-10y/o
normal BP
no frank haematuria - microscopic haematuria normally resolves
normal renal function
23
Q
atypical features in MCD
A
suggestions of AI disease
abnormal renal function
steroid resistance - failure to go into remission after 4wks high dose oral steroid
- only then consider renal biopsy
24
Q
do we biopsy for MCD
A
no
25
treatment of nephrotic syndrome
if typical features - 8wks prednisolone
26
side effects from high dose glucocorticoids
**Cushing's syndrome**
parents notice - behaviour, mood lability, sleep disturbance
infection risk - varicella status, pneumococcal vaccination, abx prophylaxis
27
features of Cushing's syndrome - which are more common in children
**personality change**, moon face, **increased susceptibility to infection**, gynaecomastia, fat deposits on face and back of shoulders, **growth**/osteoporosis, bruising and petechiae, striae, skin thinning, amenorrhoea, hirsutism, **GI distress - increased acid,** thin extremities, **hypertension**, oedema, CNS irritability, hyperglycaemia
28
idiopathic NS in childhood
steroid sensitivity predicts diagnosis and prognosis
90% steroid sensitive - non relapsing, infrequently relapsing, frequently relapsing, steroid dependent → more likely to be MCD
steroid resistance → more suggestive of FSGN
29
interaction between immune system and podocytes
* if we affect functioning of B and T cells you can reduce the number of relapses in nephrotic syndrome
30
outcome in nephrotic syndrome
relapse - 95% in 2-4wks
relapse - 80%
80% long term remission
for frequently relapsing - 2nd line immunosuppression (remember steroid toxicity - steroid dependent and \>4 relapses p/a
31
steroid resistant nephrotic syndrome
**acquired**
* focal segmental glomerulosclerosis (FSGS) - podocyte loss, progressive inflammation and sclerosis
**congenital**
* infant presentations
* NPHS1 - nephrin
* NPHS 2 - podocin
* podocyte loss
32
prognosis of FSGS
50% require renal replacement therapy in 5yrs
33
haematuria in children
* macroscopic/frank - ALWAYS INVESTIGATE
* microscopic - dipstix adequate
* investigate if \> trace on 2 occasions
* haemoglobinuria - stix +ve and microscopy -ve
* associated proteinuria = glomerular disease
34
causes of haematuria
**urinary tract**
* malignancies - sarcomas
* stones
* UTI
* trauma
* urethritis
**renal**
* glomerulonephritis
* tumour - Wilm's (nephroblastoma)
* cysts
**systemic**
* clotting disorders
*
35
investigations in haematuria
**bloods**
* waste accumulation (creatinine)
* electrolytes - may seen hyponatraemia and hyperkalaemia
* FBC - anaemia, haemolysis
* albumin
**urine**
* exclude UTI (culture)
* any overlap w/ nephrotic syndrome
36
what is nephritic syndrome and what are the features
clinical diagnosis - describes glomerulonephritis
* haematuria and proteinuria
* reduced GFR
* oliguria
* fluid overload - raised JVP, oedema
* hypertension
* worsening renal failure → rapidly progressive GN
37
how does glomerulonephritis cause AKI
intrarenal cause of AKI
38
which components are affected in acquired glomerulopathy w/ frank haematuria
epithelial cell (podocyte) - **MCD, FSGS**, lupus
basement membrane - membranous glomerulopathy, MPGN, GS, PIGN
endothelial cell - **PIGN, HUS,** membranoproliferative glomerulonephritis, lupus, ANCA vasculitis
mesangial cell - **HSP/IgA nephropathy**, lupus
39
further investigations to make a diagnosis in nephritic syndrome
radiology - renal USS
chase most likely diagnosis - ASOT, throat swab (strep)
immunology workup - complement C3 and 4, AI diseases (ANA, ANCA)
biopsy
40
acute post infectious glomerulonephritis features
3-7y/o
usually group A strep - beta haemolytic
throat 7-10 days after infection, skin 2-4wks
41
pathogenesis in PIGN
1. nephrogenic antigens on strep
2. bind specific sites in glomerulus, antibodies bind Ag forming circulating complexes → deposits in the kidney
3. humeral and cellular immune response, activates alternative complement pathway
4. AKI
42
prognosis of acute PIGN
self limiting
generally improves 6wks after diagnosis - haematuria and hypertension resolves, normalisation of C3 6-8wks after
not recurrent
43
making diagnosis of acute PIGN
bacterial culture
+ve AOT
low C3
remeber DDx e.g. lupus, MPGN, IgA nephropathy
44
treatment of PIGN
abx
support renal function - electrolyte, acid-base
overload/HT - diuretics
45
how common is IgA nephropathy
most common glomerulonephritis
46
features of IgA nephropathy
1-2 days after URTI
usually older children and adults
* recurrent macroscopic haematuria
* +/- chronic microscopic haematuria
* varying degree of proteinuria
clinical diagnosis
47
pathogenesis of IgA nephropathy
1. increased circulating levels of Gd-IgA1
2. production of anti IgA1 antibodies
3. immune complexes form in the circulation and in situ
4. immune complexes in the mesangium cause local immune activation and injury → matrix production, mesangial proliferation, glomerular sclerosis, interstitial fibrosis
48
diagnosis of IgA nephropathy
clincial picture
-ve AI workup
normal complement
49
treatment of IgA nephropathy
mild disease - ACEi for persistent proteinuria or hypertension
mod-severe - immunosuppression (KDIGO)
50
outcome of IgA nephropathy
variable
25% ERSF by 10yrs post diagnosis - ?outcome better in children
51
age of onset of Henoch Schonlein purpura/IgA related vasculitis
5-15yrs
52
clinical diagnosis of Henoch Schonlein purpura/IgA related vasculitis
mandatory: palpable purpura
one out of:
* abdo pain
* renal involvement
* arthritis or arthralgia
* biopsy - IgA deposition
53
IgA vasculilits
* how common
* what conditions does it overlap with
most common childhood vasculitis
small vessel vasculitis
overlaps w/ IgA nephropathy - IgA vasculitis w/ nephritis
54
features of IgA vasculitis
1-3 days post trigger
* viral URTI in 70%
* streptococcus, drugs
duration of Sx - 4-6wks, ⅓ relapse
nephritis - mesangial cell injury
55
treatment of IgA vasculitis
symptomatic - joints, gut
glucocorticoid therapy - not helpful in mild nephritis, may help w/ GI involvement
immunosuppression - trial in mod-severe renal disease
long term - HT and proteinuria screening
56
what is an AKI
abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes
57
features of AKI
anuira/oliguria \<0.5ml/kg/hr
hypertension w/ fluid overload
rapid rise in plasma creatinine
58
features of AKI in paeds
serum creatinine \>1.5x age specific reference (or previous baseline)
UO \<0.5ml/kg for \>8hrs
59
interpretation fo AKI warning score
AKI 1: measured creatinine \>1.5-2x reference creatinine/ULRI
2: measured creatinine 2-3x
3: serum creatinine \>3x
60
management of AKI
prevention
3M's:
* monitor - paediatric early warning scores (BP), UO, weight
* maintain - good hydration, electrolytes, acid-base
* minimise - drugs (NSAIDS, diuretics)
causes - pre-renal, renal, post-renal
61
pre-renal cause of AKI
perfusion problem
* intravascular depletion resulting in hypoperfusion of glomerulus
* decreasing GFR → AKI
* e.g. gastroenteritis, acute haemorrhage, painful laparonephrectomy syndrome, intravascular depletion, liver disease etc
62
renal causes of AKI
glomerular disease - HUS, glomerulonephritis
tubular injury - acute tubular necrosis (consequence of hypoperfusion, drugs)
interstitial nephritis - NSAIDs, AI
63
post-renal causes of AKI
obstructive uropathies
e.g. pelvis and ureter obstruction, ureteropelvic junctions, bladder stones/tumours, external pressure e.g. constipation, drugs affecting blood emptying in the pelvic floor
64
what is haemolytic uraemic syndrome
haemolysis - packed cell volume \<10%, Hb \<10g/dl and fragmented erythrocyte on blood film
thrombocytopenia - plt \<150x109/L
AKI - serum creatinine \> age related range (\>97th pc), GFR \<80mls/min/1.73m2, proteinuria
65
typical HUS causes
typical - post diarrhoea
* entero-haemorrhagic E coli (EHEC), verotoxin producing E coli (VTEC), shiga toxin (STEC)
* pneumococcal infection
* drugs
66
typical HUS causes
typical - post diarrhoea
* entero-haemorrhagic E coli (EHEC), verotoxin producing E coli (VTEC), shiga toxin (STEC)
* pneumococcal infection
* drugs
67
risk of developing HUS
E coli O157:H7 serotype
period of risk of HUS
* up to 14 days after onset of diarrhoea
* 15% develop HUS
bloody diarrhoea is a medical emergency in children
68
triad of symptoms in HUS
microangiopathic haemolytic anaemia
thrombocytopenia
AKI/acute renal failure
69
consequences of HUS
70
management of bloody diarrhoea and HUS - volume expansion
prevention of oliguric HUS = intravascular volume expansion w/ normal saline
71
management of HUS - 3 M's
monitor:
* 5 kidney functions
* fluid balance - hypertension
* electrolytes
* acidosis
* waste
* hormones - hypertension
maintain:
* IV normal saline and fluid
* renal replacement therapy
minimise:
* no abx/NSAIDs
72
monitoring for LT consequences of AKI
BP
proteinuria
evolution to CKD
73
causes of chronic kidney disease in children
* **congenital anomalies of the kidney and urinary tract** - 55% of CKD
* reflux nephropathy, dysplasia, obstructive uropathy
* **hereditary conditions** - 17%
* cystic kidney disease, cystinosis
* **glomerulonephritis** - 10%
* remember syndromic causes - CAKUT may not be isolated
* turner, trisomy 21, branchio-oto-renal, prune belly syndrome
74
stages of CKD
* normal GFR: 90-120
* CKD 2: 60-89
* CKD 3a: 45-59, b: 30-44
* CKD 4: 15-29
* CKD 5: ESRF
75
presentation of CKD
symptoms variable depending on which function affected
* waste handling: increased urea → decreased appetite, affects cardiac function, affects neuro function → seizures
* water handling: poly/oligouria
* salt balance: hyponatraemia → affects growth, hyperkalaemia → affects cardiac health
* acid-base control → poor growth
* endocrine: red cells → anaemia, BP → hypertensive (high renin drive) OR hypotensive (very polyuric), bone health → metabolic bone disease
* bladder dysfunction
76
UTI in children - definition
clinical signs
**AND**
* bacterial culture from MSSU
* any growth on suprapubic aspiration or catheter
77
presenting signs and symptoms in neonates w/ UTI - most to least common (**systemic symptoms in bold**)
* **fever, vomiting, lethargy, irritability**
* poor feeding, FTT
* abdo pain, jaundice, haematuria, offensive urine
any child can present w/ septic shock 2y to UTI (more common in infants)
78
presenting signs and symptoms in pre-verbal children w/ UTI - - most to least common (**systemic symptoms in bold**)
* **fever**
* **abdo or abdo/loin tenderness, vomiting, poor feeding**
* **lethargy, irritability**, haematuria, offensive urine, FTT
any child can present w/ septic shock 2y to UTI (more common in infants)
79
presenting signs and symptoms in verbal children w/ UTI - most to least common (**systemic symptoms in bold**)
* frequency, dysuria
* dysfunctional voiding, changes to continence, **abdo/loin pain or tenderness**
* **fever, malaise, vomiting,** haematuria, offensive urine, cloudy urine
any child can present w/ septic shock 2y to UTI (more common in infants)
80
obtaining urine specimens
* difficult in pre-toilet trained children
* clean catch or MSSU is gold standard
* ? collection pads and urine bags
* sick infants - catheter samples or suprapubic aspiration
* if acutely unwell, do not delay treatment
81
diagnosing UTI in children
suggestive tests:
* dipstix
* leucocyte esterase activity, nitrites
* unreliable \<2y/o
* microscopy
* pyruria, bacteria
culture \>105 colony forming units/ml (gram -ve bacteria - e coli)
82
why are UTI's worrying in vesico-ureteric reflux
may cause a kidney injury
* not all children w/ reflux get scarring
83
grades of vesico-ureteric reflux
higher grade = more likely to cause/have an associated renal injury
1. reflux partially up ureter
2. all the way up into the calyces but without distending
3. ureteric distension
4. up into fornices and sharp angle in relation to papillae
5. significant tortuosite of the ureters, loss of papillae indentation into the calyces
84
what to look out for in UTI
* screening for children at risk of progressive scarring
* reflux nephropathy
* capture those w/ renal dysplasia
* urological abnormalities
* unstable bladder - voiding dysfunction
85
when to investigate a UTI in children
* all children w/ first time UTI
* upper tract symptoms
* younger
* recurrent
86
investigating a UTI
US - structure (within 6wks)
DMSA (isotope scan) - scarring/function
micturating cysto-urethrogram MAG 3 scan - dynamic (gold standard for looking for reflux)
87
treatment of UTIs
lower tract - 3 days oral abx
upper tract/pyelonephritis - 7-10 days abx (oral if systemically well), possible role of prophylaxis but controversial
prevention - fluids, hygiene, avoiding constipation
manage voiding dysfunction
88
when is prophylaxis used in UTI treatment
abnormal urinary tract:
* grade 3 or above VUR
* obstructive abnormalities e.g. PUJ obstruction, posterior urethral valves
* abnormal bladder
89
factors affecting progression of CKD
* late referral
* hypertension
* proteinuria
* high intake of protein, phosphate and salt
* bone health - PTH, phosphate, vit D
* acidosis
* recurrent UTI
90
blood pressure in children
gold standard - sphymanomometer
* doppler US in children \<5
* oscillometry good for MAP
technique is important - children move about and cuff can deflate, never use cuff too small (bladder needs to cover at leat 80% of arm circumference)
* white coat HT - 24hr ABPM
91
factors affecting BP
sex
age
height specific
92
hypertension in children - definition
3 occasions, ≥95th percentile
borderline ≥90 but \<95th PC
93
management of CKD
depends on which function affected
* modify protein intake
* fluid restriction/free access if oliguric/polyuric
* K restriction in ESRF, Na supplementation if hyponatraemic
* phosphate reduction in diet or binders
* bicarb replacement
* EPO for anaemia
* control BP - ACEi
* monitor bladder function e.g. ocybutynin to relax bladder function
94
how does metabolic bone disease occur with CKD
damaged kidneys → can't excrete phosphate → phosphate elevates in blood
phosphate = potent driver for PTH
damaged kidneys can't activate vit D3 into active form → less calcium absorbed from gut into blood and calcium is also lost from kidneys → hypocalcaemia → drives PTH
95
management of metabolic bone disease
low phosphate diet
phosphate binders
active vit D
if ongoing poor growth - growth hormone
96
cardiovascular risks in renal patients
accelerated atherosclerosis
* traditional risk factors
PLUS
* anaemia/metabolic bone disease (PTH)
97
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