haematuria/nephritic syndrome Flashcards
mnemonic to remember causes of haematuria
Stone
Haematological / hereditary
Infectious/iatrogenic/idiopathic/immune
Renal
Tumour/trauma
factitious haematuria - some causes
urate crystals in infants, foods/dyes, haemoglobinuria from haemolytic anaemia, myoglobinuria from rhabdo, drug metabolites
extraglom vs glomerular haematuria
extraglom: red/pink, can have clots, usually no protein, rbc morph normal, no casts
glomerular: cola, no clots, can have protein, rbc dysmorphic, can have casts
types of RPGN
type I = anti-GBM (goodpastures); linear on IF
type II = immune complexes e.g. IgA, SLE, PSGN, HSP; granular on IF
type III = ANCA, pauci-immune; nothing on IF
cANCA vs pANCA vasculitides
CAW: cANCA = Wegner’s
PAMC: pANCA = microscopic polyangitis, Churg-Strauss
RPGN also known as what?
crescentic GN - crescent shape proliferation of cells into Bowman’s capsule
causes of haematuria with low C3 vs low C3 AND C4
Low C3 = typically due to activation of the alternate C’ pathway
- APSGN
C3 glomerulopathies including DDD (subtype of MGPN)
Low C3 + C4 = indicates activation of classic pathway due to complex formation
- Lupus nephritis
- MPGN I
- Shunt nephritis + associated with bacterial endocarditis
What would the follows IF stains suggest?
i. IgG and C3 on external side of GBM
ii. IgG and C3 found along GBM + mesangium
iii. IgG1, IgG3, IgA, IgM, C3, C4, C1q
i. IgG and C3 on external side of GBM = APSGN (‘starry sky’)
ii. IgG and C3 found along GBM + mesangium = MPGN type I + II
iii. IgG1, IgG3, IgA, IgM, C3, C4, C1q = ‘full house’ ie. SLE
what are these pathognomonic features of?
i. Crescentic
ii. Tram tracking
iii. Wire loops
iv. Starry sky
v. Subepithelial humps
i. Crescentic = RPGN – ANCA associated, anti-GBM, post strep
ii. Tram tracking = MPGN
iii. Wire loops = lupus class III/ IV
iv. Starry sky = APSGN (granular pattern) on immunofluorescence
v. Subepithelial humps = APSGN on EM
name some synpharyngitic causes of haematuria besides PSGN
• Alports
• Thin basement membrane
• IgA
• HSP nephritis
pathogenesis in goodpasture’s
anti-GBM Abs against alpha3 chain of collagen IV of BM
esp HLA DR15
environmental stress will expose the alpha 3 further
lung Sx first, then kidneys
PSGN vs IgA nephropathy - timeline after infection
IgA = 1-2 DAYS (by definition <5/7 days)
VS. postinfectious GN = 10-14 days post pharyngitis, or 3-6 weeks post skin infection
5 key presentation types of IgA nephropathy
- haematuria
- nephritic
- RPGN
- nephrotic (rare <10%)
- mixed nephrotic/nephritic
HTN treatment in IgA nephropathy vs PSGN
IgA = ACE/ARB
PSGN = frusemide
IgA biopsy findings similar to what disease?
HSP, but IgA isolated to renal disease
ESKD likelihood with IgA nephropathy?
20-30% of children will develop ESKD in 15-20 years after disease onset
genetics of alport’s syndrome
mutation in COL4A3/4/5 causing collagen IV abnormality
- COL4A3 and 4 autosomal (AR - early onset/AD - late onset)
- most COL4A5 which is X-linked
clinical manifestations of alport’s
ALPORT:
anterior lenticonus
persistent haematuria
ototoxicity and SNHL
renal - FSGS, basket weave
Treatment - ACEI, renal transplant
pathognomonic features of Alport’s
anterior lenticonus
basket weave BM pattern on EM
*IF will be non-diagnostic…nothing will light up
thin basement membrane disease associated with what condition and why?
alport’s
also a/w COL4A3 and COL4A4 mutations
in fact, homozygous mutations will result in AR Alport’s
also a/w haematuria and BM thinning
TBMD - gross haematuria present when?
associated with resp illness
when is TMBD termed benign familial haematuria?
isolated haematuria in multiple family members, not associated with other signs of renal disease (proteinuria, renal impairment)
age range of PSGN
2-13, uncommon <3yo
when does ASOT and anti-DNase B rise post strep infection?
ASOT - 3-4 weeks post
anti-DNase B - 6-8 weeks post
PSGN - Abx or not?
doesn’t stop it - but if strep still present, can consider treating to reduce severity
how long does haematuria last after PSGN resolves?
Persistent microscopic haematuria can persist for 1-2 years
criteria for SLE diagnosis
DOPAMINE RASH (4/11):
discoid rash
oral ulcers (painless)
photosensitivity
arthritis
malar rash
immune markers
neurological
ESR
Renal
ANA
serositis
haematological
how many childhood SLE will develop renal disease?
most common manifestation - up to 80%
what is the strongest single genetic factor for SLE
Deficiency of C1q is rare but the strongest single genetic factor
what is the most common type of lupus nephritis?
Class III and IV = mesangial and endocapillary lesions (‘wire loop lesions’)
how may lupus nephritis manifest clinically?
nephrotic (class V) or nephritic (I-II mild, some III and all IV need treatment)
C3 and C4 activity with SLE flare
low C3 during flare, low C4 pre-flare
% of HSP patients who will develop nephritis
50%
when does nephritis manifest with HSP?
usually after rash
what monitoring of BP and urinalysis must there be with HSP?
at diagnosis, then
weekly for first month
fortnightly until end of month 3
then once at 6mo and 12mo
classic symptoms of HSP
Palpable purpura without thrombocytopenia and coagulopathy
Arthritis/arthralgia
Abdominal pain
Kidney disease
pulmonary renal syndrome - examples
ANCA associated vasculitis - Wegner’s
ANCA not associated vasculitis - HSP
Goodpasture’s
SLE
examples of upper tract non-renal tissue causes of haematuria
obstruction: renal vein thrombosis, nephrocalcinosis
idiopathic hypercalcuria
haem: sickle cell
iatrogenic: haemorrhagic cystitis e.g. cyclophos, ifos
pathogenesis of sickle cell nephropathy
esp in renal medulla - hypoxic, acidotic and hypertonic area
increased sickling causes stasis, RBC adhesion, tubular damage and scarring
how to treat hypercalcuria?
- Oral thiazide diuretics – stimulating calcium reabsorption in the proximal and distal tubules
- Potassium citrate – helpful in patients with low urinary citrate excretion and symptomatic dysuria
- Sodium restriction - Urinary calcium excretion parallels sodium excretion
not usually reduced Ca intake
why are patients with IE/infected cardiac shunts at risk of renal disease?
- septic emboli
- drug-induced AI nephritis
- AKI from nephrotoxics e.g. aminoglycosides
- immune complex mediated GN
most common organism associated with IE nephritis
staph aureus in 55%
triad of HUS features
i. Microangiopathic haemolytic anaemia (DAT –ve)
ii. Thrombocytopenia
iii. AKI
DDx for HUS
1) DIC - abnormal coags, prolonged PTT
2) TTP - abnormally low ADAMTS13
3) systemic vasculitis
most common cause of infection induced HUS? worst cause of infection HUS?
- Shiga-toxin producing Escherichia coli (STEC) = most common in Western world
- Shigella dysenteriae type 1 = most common in Asia and South Africa
Worst prognosis = Neuraminidase producing Streptococcus pneumoniae
STEC HUS - which is the most common serotype?
O156:H7
Abx in infective HUS - yay or nay
nay - dead bacteria release more toxin!
pathogenesis of TTP
deficiency of ADAMTS13, protease that cleaves VWF (sticky tape for platelets)
what drugs are associated with causing HUS?
calcineurin inhibitors e.g. cyclosporin, tacro
cytotoxics e.g. cisplastin
pathogenesis of all HUS
- Microvascular injury with endothelial damage > localised thrombosis
— in kidneys: AKI - Progressive platelet aggregation > consumptive thrombocytopenia
- mechanical damage to RBC bumping into clots > microangiopathic anaemia > schistocytes, helmet cells
aetiology of atypical, hereditary HUS
1) complement mediated
2) non-complement mutations A) coagulation pathway B) cobalamin
most common complement-mediated HUS genetic mutations
factor H = 11-30%
CD46 = factor I = C3 = 3-17%
treatment options for hereditary HUS
- plasmapheresis
- eclizumab (C5 inhibitor)
