APPROACH TO NEPHROTIC AND

NEPHRITIC SYNDROME

Wan Ahmad Syahril M.D., MMed

Nephrology IIUM
Normal Renal tissue
“More Than Meets The Eye”
 Clinical Presentation Of Glomerular
Diseases

5 Clinical Syndromes:

1. Isolated haematuria and/or proteinuria

2. Nephritic syndrome
3. Nephrotic syndrome
4. Rapidly progressive glomerulonephritis
5. Chronic kidney disease
Approach to Oedema
 Isolated Haematuria and/or Proteinuria

Definition
• Haematuria ≥ 3 RBC/hpf or 10 x 106 cells/L
• Proteinuria > 150 mg/day

Frequently asymptomatic
• Incidental finding during health screening e.g. to obtain life
insurance, pre employment examination, prior to joining military

• Incidence varies according to screening practice

• Common – affects up to 13% of population1
• Incidence increases with age2

• 1Mohr DN et al. JAMA 1986;256:224-229

• 2Iseki K et al. Kidney Int 1996; 49:800-805
 Isolated Haematuria

• EXCLUDE urological causes

• Glomerular haematuria – red cell cast and
dysmorphic RBCs
 Red Blood Cells in the urine
- URINE PHASE CONTRAST EXAMINATION

Monomorphic Dysmorphic
 Isolated haematuria – Glomerular
( “NEPHRO”)

• Common causes – IgA nephropathy, thin

basement membrane disease

• Less common – Hereditary nephritis e.g.

Alport’s disease
 Haematuria – Differential Diagnoses
• Acquired glomerular and Tubulointerstitial dz
- Primary
- Secondary to systemic disease (pericarditis)
• Hereditary renal disease - Alport’s syndrome
– APKD
• Infection ( Mycobacteria and Schistosoma )
• Renal Papillary Necrosis
- Sickle cell disease / Analgesic abuse
 Isolated Haematuria - Management
Approach to management
• Isolated glomerular haematuria without proteinuria
or renal insufficiency may not warrant a renal biopsy

Long term follow-up

• Not completely benign course with increased risk of
ESRD with HR 32.4 (Incidence 19.6/ 100 000 person
year)
Richards NT et al. Nephrol Dial Transplant 1994;9:1255-1259.
2A Vivante et al. JAMA. 2011;306(7):729-736
 Proteinuria :

• Nephrotic range ( >3.5gm/day)

• Non-nephrotic range ( <3.5gm/day)

• Non-nephrotic range proteinuria:

Consider:
a. non glomerular causes – overflow proteinuria
and tubular proteinuria
b. non persistent proteinuria – functional
proteinuria (fever, exercise) and orthostatic
c. persistent non-nephrotic proteinuria – renal
biopsy if proteinuria ≥ 1 g/d
EVALUATION OF
ASYMPTOMATIC
PROTEINURIA
 Nephrotic Syndrome

Definition
• • Proteinuria > 3.5 g/day
• • Hypoalbuminaemia
• • Oedema
• • Hyperlipidaemia

• Mechanism
• Due to increased glomerular permeability and
loss of protein in the urine
 Isolated Proteinuria

• Nephrotic range proteinuria (> 3.5 g/d) :

characteristic of glomerular disease
Mechanism of Oedema
 DIFFERENTIAL DIAGNOSES OF NEPHROTIC
SYNDROME

• ALWAYS LOOK FOR SECONDARY CAUSES !

NEPHROTIC
SYNDROME
EVALUATIONS
FLOW

(From AAFP)
APPROACH TO THE MANAGEMENT OF
NEPHROTIC SYNDROME

1. General Management
2. Specific Management
• DON’T FORGET
Fluid and Salt
control !!

• Iv. Infusion in
severe oedema
 Summary of Management of Edema

• Primary Na retention (overfill)

–Diuretics (appropriate dosage, frequency,
sequential)
–Albumin probably does not add much

• Hypovolemia (underfill)
–Albumin may have a role in augmenting
diuresis
 Groups After Starting Steroid
Treatment

1) Steroid Sensitive NS
2) Steroid Dependent NS
(Relapsed after tapering steroid)
3) Steroid Resistant NS
(not responding to high dose steroid
after 4mths)
 Secondary Nephrotic Syndrome

• E.g. Diabetic Nephropathy

• Treat the Underlying disease
• May Not require Steroids
 Antiproteinuric drugs in Nephrosis
• Aim : proteinuria reduction to levels below 0.5 g/d.
• The exceptions are MCD and SSNS where complete
remission defines the disease.
• ACE-I or ARB may reduce proteinuria by up to 40–50%
(dose dependent), esp with good salt restriction.

• The combination of ACEi + ARBs = additive

antiproteinuric activity, BUT with conflicting evidence
of risk vs benefit

• Since ACE-I and ARBs lower GFR, a 10–20% increase in

SCr is often observed.
CAUTION with ACEi / ARBs
 SPECIFIC TREATMENTS

• Depending on
the Aetiology

• Renal Biopsy to
confirm the
diagnosis
• Steroids
• Diuretics
• Statins
• ACE
inhibitors
 Nephrotic Syndrome - Complications

• Hypercoagulability
• Risk of infection

• AKI in Nephrotic Syndrome–

- volume depletion,
- ATN,
- interstitial oedema,
- renal vein thrombosis,
- secondary to drug therapy
• Prophylactic
low-dose
anticoagulation
• Mandatory
LMWH /
Warfarin if
thrombosis
 Risk of Infection
• high clinical vigilance for infection
• Parenteral antibiotics
• Vaccination with live vaccines
(measles,mumps, rubella, varicella, rotavirus,
yellow fever) is contraindicated while on
immunosuppressive or cytotoxic agents

• (should be deferred until prednisolone dose is ~ 20

mg/d and/or immunosuppressive agents have been
stopped for at least 1–3 months.)
 Hyperlipidemia
• Increased risk of CV events
• Dietary restriction + Statins are well tolerated
and effective although Not proven to reduce
CV events in nephrotic syndrome.

• Drug – drug interaction : increased risk of

myalgia/myositis when combined with
calcineurin inhibitors.
DON’T FORGET
TO LOOK FOR
SECONDARY
CAUSES !
 WORSENING RENAL FUNCTION IN
NEPHROTIC SYNDROME

• Causes ??
Rapidly Progressing Glomerulonephritis

• Clinical :
- Rapid loss of renal function >50 % within 3
months

• Pathological findings :
- extensive Crescent formation usually
involving more than 50percent of glomeruli
RPGN – biopsy : crescents
 RPGN types :
• Type I with linear deposits of immunoglobulin
G (IgG) - (anti- GBM disease)
• Type II with granular deposits of
immunoglobulin (immune-complex mediated)
• Type III with few or no immune deposits
(pauci-immune) - Antineutrophil cytoplasmic
antibody (ANCA–associated )
• Type IV combinations of types I and III
• Type V ANCA-negative pauci-immune
renal vasculitis (5-10%)
RPGN – differential diagnoses
Thank You