IgA NEPHROPATHY
DEFINITION: nephritic syndrome defined by the presence of
mesangial IgA immune deposits (Berger’s disease)
An otherwise healthy 22-year-old Japanese- EPIDEMIOLOGY: commonest cause of GN worldwide,
predominantly affect young people following URTI
American man presents with visible PATHOGENESIS: galactose deficient IgA1 expose N-
haematuria accompanied by flank pain. He acetylgalactosamine in the hinge region of the antibody that is
recognised by IgG and IgA1 leading to generation of immune
has a 2-day history of sore throat, fever, complexes. These immune complexes deposit in the renal
chills, malaise, and headache. Physical mesangium, which results in the release of various mediators that
are toxic to the kidneys leading to renal impairment
examination reveals erythema and ASSOC CONDITIONS: alcoholic cirrhosis, coeliac, HSP
inflammation of the uvula and pharynx, CLINICAL FEAT: young male, recurrent episodes of macroscopic
haematuria, typically associated with a recent respiratory tract
enlarged tonsils with patchy greyish-white infection (typically 1-2 days)
exudates, and tender anterior cervical INVESTIGATIONS: urinalysis (haematuria, proteinuria usually
<2-3 g/ day), urine microscopy (dysmorphic erythrocytes and
lymphadenopathy. The rest of the rarely red cell casts), basic biochem and eGFR (usually normal in
examination is normal. Urinalysis shows cases of isolated invisible haematuria, risk of reduced eGFR
cola-coloured urine with haematuria and 3+ increase w/ increasing proteinuria), normal USS/ CT KUB/
complement, biopsy
protein. What is the likely diagnosis? BIOPSY: diffuse mesangial IgA deposition, use Oxford MEST-C to
score biopsies, ther are 5 domains
MANAGEMENT: isolated haematuria, no or min proteinuria
and normal GFR (no treatment needed, follow-up to check renal
function, lifestyle modification), persistent proteinuria, a
normal or only slightly reduced GFR (initially ACEi, control BP
and reduce proteinuria), active disease e.g., falling GFR or
failure to respond to ACEi (immunosuppression or
corticosteroids- avoid in pt at risk of complications)
PROGNOSIS: good prognosis (frank haematuria)< poor prognosis
(male, proteinuria >2g/day, smoking, hyperlipidaemia, ACE
genotype DD), 25% develop ESRF
MEMBRANOUS NEPHROPATHY
DEFINITION: immunologically mediated disease o the GBM
often associated with nephrotic syndrome
EPIDEMIOLOGY: most common cause of GN in adults
A 48-year-old man presents to his family PATHOPHYS: inflammation of the GBM triggered by immune
complex deposits -> increase permeability, proteinuria ->
doctor with a recent lower-extremity swelling nephrotic syndrome. GBM damaged by immune complex
that is gradually worsening. Over the last deposits; sandwiched b/w epithelial cells of podocytes.
Autoantibodies target GBM (2 major antigen targets on
few weeks, he has also noticed puffiness podocytes: M-type phospholipase A2 receptor, neural
under his eyes. A urinalysis demonstrates endopeptidase)
significant proteinuria, and a 24-hour urine PRIMARY: idiopathic, assoc with HLA e.g., HLA-DQA1
SECONDARY: infections (hep B, malaria, syphilis),
collection confirms proteinuria of 12 g. He malignancy (prostate, lung, lymphoma, leukaemia), drugs
has no history of diabetes mellitus, (gold, penicillamine, NSAIDs), autoimmune diseases (SLE,
macroscopic haematuria, or hypertension. thyroiditis, rheumatoid), anti-phospholipase A2 antibodies
PRESENTATION: asymptomatic, proteinuria,
What is the likely diagnosis? hypoalbuminemia, oedema, hyperlipidaemia, lipiduria,
hypercoagulability
INVESTIGATIONS: urinalysis (proteinuria, bland sediment,
lipid droplets occasionally), protein : creatinine ratio (>3.5 in
nephrotic syndrome), serum urea or creatinine normal or
elevated, creatinine clearance normal or decreased, serum
albumin usually low (<30 g/L), serum (assay for a.b,), kidney
biopsy
BIOPSY: light (diffuse thickening of basement membrane),
electron (‘spike and dome’ GB matrix on top of subepithelial
deposits; effacement of podocytes)
MANAGEMENT: ACEi or ARB (reduce proteinuria and improve
prognosis), immunosuppression (in severe or progressive
disease, corticosteroid + another agent e.g.,
cyclophosphamide), consider anticoagulation for high-risk
patients, statin for hyperlipidaemia, furosemide +/-
hydrochlorothiazide for oedema, low salt and low protein diet
PROGNOSIS: 1/3 rule (spontaneous remission, remain
proteinuric, and develop ESRF), good prognosis (female,
young age at presentation, asymptomatic proteinuria)
A 5-year-old boy presents with a short MINIMAL CHANGE DISEASE
history of facial oedema that has now DEFINITION: most common form of nephrotic syndrome
affecting children
progressed to total body swelling involving EPIDEMIOLOGY: children age >1 year but <8 years
the face, abdomen, scrotum, and feet. Other PATHOPHYSIOLOGY: t-cell and cytokine-mediated damage
symptoms include nausea, vomiting, and to the GBM -> polyanion loss. The resultant reduction of
electrostatic charge -> increased glomerular permeability to
, serum albumin. Foot processed of podocytes damaged,
flattened (AKA effacement) -> lose function as a barrier ->
albumin permeates, bigger proteins cannot get through.
CAUSES: idiopathic in majority, drugs (NSAIDs, rifampicin),
Hodgkin’s, thymoma, infectious mononucleosis, infections
(e.g., syphilis)
RISK FACTORS: recent infection, immunisation, NSAIDs,
Hodgkin’s
FEATURES: nephrotic syndrome, normotension (HTN is rare),
abdominal pain. The parents report that the highly selective proteinuria (intermediate-sized proteins such
as albumin and transferrin leak), hypoalbuminemia, oedema,
child had a viral illness with fever a few days hyperlipidaemia
before the development of the swelling. On INVESTIGATIONS: in children (diagnosis presumptive in
examination, he has facial oedema, ascites, presence of nephrotic syndrome), adults (renal biopsy),
proteinuria, protein: creatinine >2, serum albumin <30g/L,
scrotal oedema, and pitting oedema of both elevated triglyceride and cholesterol, increase Hb and
legs up to the knees. What is the likely haematocrit, increased platelet
diagnosis? BIOPSY: light (normal glomeruli), electron (effacement of
foot processes, fusion of podocytes)
MANAGEMENT: oral corticosteroids (usually rapid response),
cyclophosphamide if steroid resistant, low salt diet, fluid
restriction, consider albumin and furosemide if severe
PROGNOSIS: 1/3 (just have one episode, infrequent relapse,
frequent relapse which stop before adulthood)
REMISSION: resolution of oedema and proteinuria and
normal albumin levels
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
DEFINITION: chronic pathological process caused by injury to
podocytes in the renal glomeruli
PATHOLOGY: histologic findings of glomerular damage, not
distinct disease. Affects part of some glomeruli of nephron;
damage, scarring -> proteinuria. Foot processed of podocytes
damaged -> plasma proteins, lipids permeate glomerular filter.
A 42-year-old white man with no previous Proteins, lipids trapped -> build up inside glomeruli -> hyalinosis -
medical history presents to his primary care > scar tissue
PRIMARY: circulating factors damages podocytes, loss of foot
physician with progressively increasing processes
oedema of both lower extremities. There is SECONDARY: adaptive response to renal injury usually
associated with less significant proteinuria and renal impairment.
no family history of renal failure. The patient This is a combination of glomerular hypertrophy and
has pitting pedal oedema rated as 3+ (5 mm hyperfiltration. Causes include sickle cell, HIV, renal
oedema, pit formed on palpation is deep and hyperfiltration
CAUSES: idiopathic, secondary to other renal pathology, HIV,
lasts >1 minute). Urinalysis reveals marked heroin, Alport’s, sickle cell, kidney transplant
proteinuria (3+). What is the likely PRESENTATION: nephrotic syndrome (proteinuria,
hypoalbuminemia, oedema, hyperlipidaemia), renal insufficiency,
diagnosis? HTN, haematuria
INVESTIGATIONS: serum urea and creatinine elevated, GFR
decreased, urinalysis with microscopy (proteinuria, oval fat
bodies, fatty casts), urine protein: creatinine <1 to >3, serum
albumin low, increased cholesterol and LDL, biopsy, 24-hour urine
protein
BIPOSY: light (segmental sclerosis, hyalinosis of glomeruli),
electron (effacement of foot processes)
MANAGEMENT: asymptomatic with proteinuria <3g/24h
(ACEi or ARB, sodium restriction, low fat diet, exercise, statin if
high lipid levels), symptomatic or proteinuria >3g/24hr
(prednisolone, ACEi or ARB, consider statin, furosemide +/-
thiazide for oedema, ciclosporin if steroid-dependent (but not for
pt with CC >60mL/min/1.73m2), secondary (treat underlying
cause, ACEi or ARB + sodium restriction, consider statin,
furosemide +/- thiazide diuretic, immunosuppressants)
PROGNOSIS: untreated FSGS has <10% chance of spontaneous
remission, has worst prognosis of primary glomerular disease-
causing nephrotic syndrome
A 6 year old has a sore throat and has been POST-STREPTOCOCCAL GLOMERULONEPHRITIS
DEFINITION: a glomerular condition mediated by an immunological
given antibiotics. 3 weeks later, he presents response to a group A strep infection. Type III hypersensitivity reaction
feeling feverish with nausea and vomiting EPIDEMIOLOGY: occurs 7-14 days following infection (usually strep
pyogenes), most affected age group are children 5-12 years, with
and tea-coloured urine. Urine dipstick increased risk also in >60 years, boys > girls
confirms haematuria and protein. Blood PATHOPHYSIOLOGY: 2 strep antigens triggering sequence of
immunological glomerular injury (NAPIr, SPE B). Throat or skin GAS
pressure is 100/60. What is the most likely infection -> production of antibodies against strep antigens ->
nephritogenic strep antigens become lodged in GBM -> anti-strep a.b.
diagnosis? bind to form immune complexes -> activation of complement and
inflammation -> damage to glomerulus -> clinical feat of PSGN (in situ
immune complexes formation). Extent of damage to endothelial cell
barrier correlates with the degree of haematuria and decline in GFR.
Subepithelial ‘humps’ or deposits trigger inflammation leading to
epithelial cell damage -> allows proteins to filter more freely into
urine. No of these deposits correlate with degree of proteinuria
PRESENTATION: 1-3 weeks for pharyngitis, 3-6 weeks for skin
infection, acute nephritic syndrome (generalised oedema, HTN, gross
haematuria, oliguria), asymptomatic with incidental microscopic
, haematuria, headache, malaise
INVESTIGATIONS: urinalysis (haematuria- tea or cola coloured,
proteinuria usually mild), variable decline of eGFR, elevated creatinine,
culture (GAS- only +ve in 25% due to delay from initial GAS infection),
serology (streptozyme test= ASO, AHase, ASKase, anti-DNase B, anti-
NAD), complement (low C3 levels), renal biopsy
BIOPSY: light (diffuse glomerular cellular infiltration and endocapillary
proliferation), electron (immune complexes localised to subepithelial
deposits, dome-shaped ‘humps’) immunofluorescence (diffuse glanular
deposits of C3 and IgG, ‘starry sky’ appearance)
MANAGEMENT: prevent and manage any complications from fluid
overload, salt and water restriction, diuretic, monitor BP (loop
diuretics), monitor renal function, antibiotics if persistent infection, if
severe hypertensive encephalopathy (tx with anti-hypertensives)
REFERRAL: refractory fluid overload, refraction HTN, evidence of
serious renal impairment
PROGNOSIS: good prognosis, especially in children, usually self-
limiting. COMPLICATIONS: short-term (pulmonary oedema,
hypertensive encephalopathy, severe AKI requiring dialysis), long-term
(HTN, proteinuria, renal insufficiency)
RAPIDLY PROGRESSIVE GN
A 35-year-old man with no past medical DEFINITION: rapid loss of renal function associated with the
history presents to the emergency formation of epithelial crescents in the majority ot glomeruli
CAUSES: Goodpasture’s syndrome, Wegener’s granulomatosis,
department after he noted cola-coloured SLE, microscopic polyarteritis
urine. He denies pain or fever associated PATHOPHYSIOLOGY: inflammation of kidney’s glomeruli ->
crescent- shape proliferation of cells in the Bowman’s capsule ->
with the blood in the urine, but has had a renal failure within weeks/ months. Inflammation damages GBM -
sore throat for the past 3 days, which is > inflammatory mediators, complement proteins, fibrin and
monocytes pass into Bowman’s space -> expansion of parietal
getting better. He has not had a similar layer of cells into thick, crescent-moon shape -> may undergo
episode previously. Examination reveals a sclerosis/ scarring
TYPES: primary (idiopathic), secondary type I (anti-GBM
non-blanching purpuric rash over both his antibodies, typically circulating autoAb against type IV collagen),
legs. What is the likely diagnosis? secondary type II (immune complexes, post-strep GN, SLE, IgA
nephropathy, HSP, cryoglobulinemia), secondary type III (ANCA,
C-ANCA e.g., granulomatosis with polyangiitis, P-ANCA e.g.,
eosinophilic granulomatosis with polyangiitis)
FEATURES: nephritic syndrome (haematuria with red cell casts,
proteinuria, HTN, oliguria), features specific to underlying cause
(e.g., haemoptysis with Goodpasture’s, vasculitic rash or sinusitis
with GWP)
INVESTIGATION: urinalysis (proteinuria), kidney biopsy
BIOPSY: light (crescent-shaped glomeruli),
immunofluorescence (type I: linear bodies, antibodies bind to
collagen of GBM, type II: glanular, immune complex deposition in
subendothelium, type III: negative- pauci-immune, associated
with ANCA)
MANAGEMENT: pulse methylpred then pred/ cyclophosphamide/
rituximab/ plasmapheresis, plasma exchange to remove antigen
and/ or antibody, RRT if renal failure irreversible
PROGNOSIS: poor if initial serum creatinine >600 µmol/L
DIABETIC NEPHROPATHY
DEFINITION: albuminuria and progressive reduction in the
eGFR in the setting of a long duration of diabetes.
PATHOLOGY: excess glucose in blood overrides renal
threshold for glucose -> glycosuria. Non-enzymatic glycation
of proteins -> GBM thicken -> hyaline arteriosclerosis -> this
plus arteriole dilatation increases pressure in the glomerulus -
> increased GFR (first stage). Thickening of GBM ->
glomerulus expands, filtration slits widen -> increased
permeability. High-pressure state -> supportive mesangial
cells secrete more structural matrix -> Kimmelsteil- Wilson
A 50-year-old man with a 15-year history of nodules. Damage glomeruli -> decreased GFR (second stage)
type 2 diabetes presents with oedema, RISK FACTORS: FHx, poor control of diabetes, development
fatigue, and impaired sensation in the lower of diabetes at a younger age, poor control of HTN, obesity
FEATURES: asymptomatic in early DN, susceptible to lower
extremities. He is found to have proteinuria, UTI, HTN, signs of retinopathy, oedema
a reduced estimated glomerular filtration INVESTIGATION: proteinuria, ACR (albuminuria, to confirm, 2
of 3 specimens should be collected within 3-6 months should
rate (eGFR), anaemia, background diabetic be abnormal), serum creatinine with GFR estimation (may be
retinopathy, and peripheral neuropathy. elevated to normal in CKD 1-2 and reduced in CKD 3-5, kidney
What is the likely diagnosis? US (initially large if diabetes uncontrolled but usually normal
once DN supervenes with increased echogenicity)
SCREENING: all diabetic pt should be screened annually
using urinary ACR, should be early morning specimen, ACR
>2.5= microalbuminuria, repeat test if an abnormal ACR is
obtained but within max of 3-4 months
MANAGEMENT: diabetic protein restriction, tight glycaemic
control, aim for BP <130/80 mmHg, ACEi or ARB (start if
urinary ACR 3mg/mmol or more, not dual therapy,), statin in
dyslipidaemia, smoking cessation, glycaemic control, if BP not
controlled <130/80 to 140/90 by ACEi/ ARB (add CCB and/ or
thiazide-like diuretic and/ or beta-blocker)
A 38-year-old white woman presents to the LUPUS NEPHRITIS
DEFINITION: a severe manifestation of SLE that can result in
