Update and Management

of Glomerular Diseases

Certificate Course on Renal Medicine 2021

9th September 2021

Dr. Elaine Ho
Associate Consultant
Tseung Kwan O Hospital
interstitium
 What is glomerulonephritis
• Inflammation of the glomeruli 腎小球炎

abnormal one
normal
ivery severe inflammation
tubules surrounding glomeruli
deep red glomeruli
 Glomerular injury

eg RBC

[Molecules normally not Impaired

filtered] pass into the glomeruli
urine and are excreted function

Decrease
Hematuria Proteinuria
GFR
with increase Cr
 Clinical presentation
1. Proteinuria
2. Hematuria microscopic hematuria (not be seen by pure eye)

3. Hypertension
4. Nephrotic syndrome
5. Nephritic syndrome
6. Acute kidney injury dramatic increase Cr and decreased GFR

7. Rapidly progressive renal failure

8. Chronic kidney disease/ ESRD
 foam in urine just like beating egg white

Clinical Presentation: Proteinuria

Clinical Presentation: Hematuria
Dysmorphic RBC

for aggressive GN
if normal shape rather benign or mild form

Red cell cast

 nephrotic: collection of symptoms
nephritic: disease

Clinical Presentation: Nephrotic/ Nephritic

Nephrotic Nephritic
Hypertension N/↑ ↑↑
Edema leg swelling Severe Mild to moderate
Hematuria N/+ +++
Proteinuria +++~++++ (>3-3.5g/d) +~++
Serum albumin ↓↓ N/↓
Hyperlipidemia ↑↑ N/↑
Renal function Normal Abnormal
Different types of glomerulonephritis
• Onset
o Acute vs chronic
• Clinical presentation
o Nephrotic vs nephritic
• Etiology
o Primary: IgA nephropathy, minimal change disease,
membranous GN, membranoproliferative GN, anti GBM
disease…… glomerular basement membrane

o Secondary: DM nephropathy, lupus nephritis, myeloma kidney,

ANCA related/ vasculitis/ HIV associated nephropathy……
 Spectrum of glomerulonephritis
lupus can happen for the whole spectrum

Lupus nephritis

IgA nephropathy
minimal change nephropathy
severe nephrotic syndrome
poor bp control with dysmorphi RBC
MCD/ FSGS DMN
ANCA related GN
Post Anti GBM disease
Membranous
Nephrotic GN infectious Nephritic
GN
 Injury to amyloidosis  Inflammation
podocyte MCGN  Reactive cell
 Change proliferation
architecture  Break GBM
 Scaring Haematuria  Crescent
 Deposition formation
of matrix or Proteinuria
other
element
 Investigation
• History nsaid related GN?

o Recent infection, medications, family history

o Associated symptoms swelling? lupus for skin rash and joint pain and photosensitivity

• Physical examination BP very important

• Urinalysis
• Quantify proteinuria
• Blood test
o RFT
o Clues for secondary causes
hep B and C associating GN
for dm nephropathy e.g. FBS, autoimmune markers, hepatitis status primary GN need steroid need to consider whether hep is
active state— need to check first

• Radiological test
o KUB, USG kidney r/o obstructive cause
and can measure kidney size to differentiate AKI or CKD

• Renal biopsy small kidney size

biopsy may not be feasible risk of hemorrhage high
 Renal biopsy
1. Light microscopy
4 pathology part
glomeruli
tublues
vessel
interstitial

2. Direct immunofluorescence
antoinmmune disease for antibody stain

3. Electronic microscopy
for the comprehend of renal report
further magnify
for electron dense deposition
 Management
• General
o Low salt diet
o Control BP, aim at BP <130/80mmHg
• Angiotensin converting enzyme inhibitor (e.g. perindopril, lisinopril, ramipril,
renitec…)
• Angiotensin II receptor blocker (e.g. losartan, telmisartan, candesartan,
irbesartan…)
** anti-proteinuric
• Diuretic
• Specific
o Steroid for primary GN
o Immunosuppressant
• Dialysis support e.g severe AKI , late presentation of ESRD
Case study
 Case 1
• 24 years old male

• Presented with headache, malaise, sore throat

• Fever 2 days ago
• Episode of gross hematuria, no dysuria
• Mild ankle edema
• BP 156/90
• Urine RBC +++, protein ++
• Bilateral ankle pitting edema

• Proteinuria 2g/d
• sCr 100 mmol/L
• Serum albumin 35g/L normal
renal function

• USG kidney: normal

What is the likely diagnosis? nephritic

 Renal bx
Mesangial cell proliferation
Increase mesangial matrix
No crescent formation
10% interstitial fibrosis
No vasculitis

Mesangial deposit of IgA, C3

 IgA nephropathy
• The most common primary glomerulonephritis in the world
• 2nd to 3rd decades
• Male > female
r/o infection, stone disease, UTI first

• Asymptomatic, microscopic hematuria, mild proteinuria

• Gross hematuria associated with upper respiratory tract
infection (synpharyngetic hematuria)

• RFT is usually normal, but occasionally may present as acute

kidney injury due to ATN secondary to gross hematuria

• Diagnosed by renal biopsy (IgA +/- C3 deposits in mesangium

on immunofluorescence)
 IgAN pathogenesis
• Abnormal galactosylated IgA1
deposit in the mesangium of
glomerulus
• IgA binding of mesangial Fc
receptors
 activate mesangial cell
 produce platelet-derived and other
growth factors and cytokines
 resulting in mesangial cell
proliferation and matrix synthesis
 inflammatory cell recruitment
 local injury in the glomeruli
 IgA nephrology
• Slowly progressive
• By 20 years, 20-50% have end stage renal disease

• Poor prognosis
o Impaired renal function
o Heavy proteinuria
o Hypertension chronic changes noted

o Tubulointerstitial fibrosis and glomerulosclerosis on biopsy

o Rapidly progressive crescentic IgAN
 Management of IgA nephropathy
• Aggressive control of BP and proteinuria
• ACEI/ ARB anti hypertensive med

• ?fish oil
do no harm

immunosuppresant

• If heavy proteinuria  steroid +/- MMF

• If crescent GN  high dose steroid + cyclophosphamide, then
azathioprine

• IgAN can recur in transplant kidney, usually insidious onset

need regular f/u and BP control strict
 IgAN versus Post infectious GN
IgAN Post infectious GN
Pathogenesis Abnormal galactosylated Immune complex mediated
IgA1 deposition GN take time to develop around 2-3 weeks

Clinical Nephrotic/Nephritic Nephritic

presentation synpharyngetic hematuria Symptoms onset at least 2-3
weeks after URTI
Histology Mesangial proliferation Diffuse proliferative changes
IF: IgA +/- C3 with hypercellularity
IF: IgG
Prognosis Prognosis Variable Usually self limiting
 Case 2
• 15 years old female

• Facial puffiness,
• bilateral lower limb edema,
• weight gain
 nephrotic

• BP 110/76
• Urine RBC -ve, protein ++++
• Bilateral ankle pitting edema

• Proteinuria 3.5g/d
• sCr 86 mmol/L
• Serum albumin 24g/L low

• USG kidney: normal

 Renal biopsy

minimal change disease

IF staining and light microscopy normal
Podocytes effacement
seen in EM
 Minimal change disease
• The most common cause of nephrotic syndrome in children
• ~25% of cases in adult
• Male = female

• Prognosis is excellent
 Minimal change disease
• Pathogenesis is uncertain
• Impaired T-lymphocyte activity
• Disorder of podocyte function
• Foot processes effacement
 Loss of net membrane negative charge
 Proteinuria
 Treatment of MCD
• Usually remit rapidly to corticosteroid therapy
• Prednisolone 1mg/kg/d for 4-6 weeks, then taper off in 12 weeks

• Can recur after stopping treatment  restart treatment

• Certain sub-groups will experience recurrent relapses
o Frequent relapsing: 2 relapses in 6 months
o Steroid dependent: relapse during or within 2 weeks of steroid withdrawal
o Steroid resistant
 Exclude focal segmental glomerulosclerosis (FSGS)
 Focal Segmental Glomerulosclerosis (FSGS)
• FSGS is a histological description rather than a disease

• Focal: affecting some but not all glomeruli

• Segmental: affecting part but not all of a glomerular tuft

• Mesangial matrix expansion and glomerular sclerosis

*** renal biopsy with limited glomeruli may be misinterpreted as

minimal change disease ***
if sample not enough
FSGS would be missed
 FSGS
• Primary cause

• Secondary causes
o Reduced nephron number
o Any causes of GN with scarring
o HIV associated: collapsing glomerulopathy
o Drug related: e.g. pamidronate
 Treatment of FSGS
• Primary FSGS fair prognosis
proteinuria may be remained and some may progress to CKD

o Prolonged course of steroid

o Consider adding other immunosuppressant, e.g. cyclosporin,
cyclophosphamide, chlorambucil
• Secondary FSGS
o Treat underlying causes

• Prognosis is usually fair

 Case 3
• 43 years old female

• Facial rash especially after outdoor activities

• Both hand small joints pain
• Frothy urine for few weeks
• No gross hematuria
• Did not take OTC medications or NSAID
 nephrotic and nephritic

• BP 150/90
• Malar rash
• No active arthritis
• Urine RBC +++ protein +++

• Urine microscopy: dysmorphic RBC 5%

• Proteinuria 4g/d
• sCr 230mmol/L
• Serum albumin 22g/L
• ANA +ve, anti ds DNA >300, C3 0.35 (reduced)
 Renal biopsy
• Diffuse proliferative GN
• IF: positive staining for IgG,
IgA, IgM, C3, C1q, kappa
and lambda chain full home

 Class IV lupus nephritis

 ISN/ RPS 2003 classification of lupus nephritis

Class I Normal light microscopy (but mesangial deposits in EM)

Class II Mesangial proliferation (hypercellularity)
Class III Focal involvement: affecting <50% of glomeruli
Class IV Diffuse involvement: affecting >50% of glomeruli
Segmental (IV-S) or Global (IV-G)

Class V Membranous GN (subepithelial deposit)

Class VI Advanced sclerosis with >90% glomeruli sclerosis

NB
1. Class III and IV can be further subclassified as active or chronic
 e.g. Class IV-G (A) is active global diffuse proliferative lesion
2. Class III and IV can mixed with V, i.e. Class III+V, Class IV+V
 Treatment
• Induction therapy • For resistant disease
o Prednisolone 1mg/kg/d for 4-8 weeks, o Rituximab
then taper down
o Pulse methylprednisolone
o Cyclophosphamide mensus
bladder toxicity
problem
• Multi-targeted therapy
• intravenous or oral o Steroid + MMF + Tacrolimus
• Monitor WCC
o Mycophenolate mofetil • Study drugs
o B Cell- activating factor (BAFF)
• Maintenance therapy • Belimumab
o Prednisolone o Co-stimulatory blockage with
o Azathioprine CTLA4-Ig
o Cyclosporine • Abatacept
 Case 4
• 64 years old male

• Diagnosed T2DM 5 years ago, defaulted followed-up

• Presented with frothy urine, bilateral LL edema and SOB for
recent 2 months
• No fever
• No chest pain
• BP 160/95
• Urine RBC –ve, protein ++++
• Fundi: both eye non proliferative DM retinopathy
• Bilateral LL pitting edema upto knee

• Proteinuria 3.5g/d
• sCr 280mmol/L
• Serum albumin 26g/L
• USG kidney: renal parenchymal disease
 in DM nephropathy features
Renal biopsy
• Kimmelstiel-Wilson nodules
• Hyalinosis of arterioles (both
afferent and efferent)
• Interstitial fibrosis

Renal biopsy is usually not required to establish a diagnosis of DMN

Consider if: consider apart from DM nephropathy, any oyher possible GN
1. Absence of retinopathy
2. Dysmorphic RBC or red cell cast in urine aggressive GN feastures
3. Rapidly increasing proteinuria or sudden worsening of RFT
 DM nephropathy
• DMN is the most common underlying cause of ESRD
in Europe/USA, also in HK

YW Ho, et al. HKJN 2013

Interventions to slow down progression of DMN

Target
BP control <130/80
Inhibition of RAS Proteinuria <0.3g/d
Glycemic control HbA1c <7%
Control dyslipidemia LDL-C <2.6mmol/L
 control BP

Renoprotective effect of ACEI/ARB

• Angiotensin converting enzyme inhibitor (ACEI)
o E.g. Captopril, Renitec, Lisinopril, Perindopril, Ramipril
• Angiotensin II receptor blocker (ARB)
o E.g. Irbersatan, Losartan, Candesartan, Valsartan, Telmisartan

• Interfering renin-angiotensin system

• ↓ efferent arteriolar pressure  ↓ intraglomerular pressure

** antiproteinuric effect  slow down progression of DMN

may speed up renal function worsening as the BP would be toooooolow

** combination of ACEI + ARB is NOT recommended

 Anti diabetic agents with renoprotective effect
• Sodium-glucose cotransporter-2 inhibitor (SGLT2i)
o E.g. Canaglifozin, empagliflozin, dapaglifozin

o Mechanism
• Inhibit glucose absorption in proximal tubule  Glucosuria  Weight loss and
improve glycemic control

o Benefit
• Reduce cardiovascular events (EMPA-REG OUTCOMES/ CANVAS/ DECLARE-TIMI58)
• Delay progression of renal failure

o Renal dose adjustment

• Not recommended with eGFR <45-60ml/min/1.73m2
• Contraindicated with eGFR <30ml/min/1.73m2
** transient decline in RFT upto 20%

o Potential side effects: euglycemic DKA, genitourinary tract infection, risk of Fournier’s
gangrene, risk of bone fracture and amputation (Canaglifozin)
 Take home message
• Take a comprehensive history
• Urinalysis
o Hematuria/ proteinuria
• Exclude secondary causes
• Renal biopsy is arranged to confirm diagnosis and
guide treatment

• Early referral to nephrologist

Welcome for questions