Armando

Hasudungan
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Nephrotic Authors
Armando HF
Syndrome
Topics
Overview

Classification

Kidney and
Glomerular
Anatomy

Signs and
Symptoms

Differential
Diagnosis

Investigations

Pathophysiology

Minimal Change
Disease

Focal Segmental
Glomerulosclerosis

Membranous
Glomerulonephritis

Diabetic
Nephropathy

Complications
Prognosis
References
Watch Video Nephrotic Syndrome - Overview
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« Back to notes

Watch Video Nephrotic Syndrome Types

Overview
Overview Nephrotic syndrome is a relatively rare but important
manifestation of kidney disease. Nephrotic syndrome classically
presents with heavy proteinuria, minimal hematuria,
hypoalbuminemia, hypercholesterolemia, edema, and hypertension.
In general, all patients with hypercholesterolemia secondary to
nephrotic syndrome should be treated with lipid-lowering agents
because they are at increased risk for cardiovascular disease.
Nephrotic syndrome has serious complications and must be part of
the differential diagnosis for any patient presenting with new onset
edema. All patients should be referred to a nephrologist for further
investigation, which often include a renal biopsy.

Remember Classic tetrad of Nephrotic syndrome is proteinuria

(>3g/24hr), hypoalbuminemia, hypercholesterolemia an oedema.
Glomerulonephritis is inflammation of the glomerulus. There are two
broad types Nephritic glomerulonephritis and nephrotic
glormerulonephritis
Remember Glomerulonephritis is divided into two broad groups:

Nephritic glomerulonephritis (Basement

membrane/endothelium injury causing Haematuria)
Nephrotic glomerulonephritis (Podocyte injury causing
proteinuria)

Nephrotic Syndrome

Nephrotic Glomerulonephritis is a renal condition affecting the

podocytes. This causes a leaky glomeruli leading to proteinuria
and subsequent hyperlipidemia, hypoalbuminemia and oedema
Classification
The page will focus on four common nephrotic syndromes towards
the end:

Minimal Change Disease

Focal Segmental Disease
Membranous Glomerulonephritis
Diabetic Nephropathy

Side note Most common cause of chronic kidney disease and

nephrotic syndrome is Diabetic nephropathy

Kidney and Glomerular Anatomy

The kidneys are retroperitoneal organs (at the back of abdomen) and
lies between T11 and L3, the left kidney lying slightly higher than the
right kidney.

The kidney is surrounding by an outer membrane called the renal

capsule. The outer layer of the kidney is the renal cortex where most
of the nephrons are situated. The inner layer is the renal medulla
which contain renal pyramids. The renal pyramids drain urine into
the minor - major calyces before draining to the renal pelvis then the
ureter.

Arterial blood supply

Abdominal Aorta → Renal arteries

The renal artery branches into smaller and smaller arteries
until finally becoming afferent arterioles which supply
individual glomeruli
Anatomy Layers of the glomerulus

The Nephrons are the functional units of the kidney. There are
millions. The nephron is made up of:

Bowman's capsule - afferent arteriole enters the bowmans

capsule and forms t and efferent exits
Proximal convoluted tubule
Loop of Henle (descending and ascending)
Distal convoluted tubule
Collecting ducts

The glomerulus is a network of blood vessels that are located within

the bowman's capsule. To understand the cause, pathophyiology and
effect of glomerulonephritis it is important to learn the layers of the
glomerulus + bowman's capsule
From inside out the layers are:

Endothelial cells of the blood vessels

Glomerular basement membrane
Podocytes
Bowman's space
Parietal cells.
In the center of the glomerulus are the mesangial cells which
help in regulating blood flow the glomeruli.

Signs and Symptoms

Clinical Presentation

Classic tetrad of nephrotic syndrome

Examination

Oedema

Periorbital oedema
Peripheral edema
Ascites

Hypoalbuminemia
 Tiredness
Leuconychia

Dyslipidemia

Eruptive xanthomata
Xanthelasmata

Breathlessness with chest pain (Pulmonary Oedema and pleural

effusion)

Frothy Urine

Differential Diagnosis
This section will mainly focus on the Primary Aetiology + Diabetic
Nephropathy

Primary Aetiology of Nephrotic Syndrome

Minimal Change Disease

Membranous Glomerulonephritis
Focal Segmental Glomerulosclerosis
Secondary Aetiology Nephrotic Syndrome

Diabetic Nephropathy
Amyloidosis
Systemic lupus erythematosus
Infections - HIV, Hep B, Hep C
Drugs - Gold, Antimicrobial agents
Cancer - Multiple Myeloma, lymphoma

Other causes of bilateral swollen legs (because one of the classic

presentations of nephrotic syndrome is oedema)

Heart failure
 Lymphoedemea
Hypoalbuminaemia
Hepatic failure

Investigations
General

Urine Dipstick
Mid-Stream Urine - microscopy
Full blood count
EUC
LFT
Plasma Ca2+

Check for other systemic diseases and causes of nephrotic syndrome

CRP
Glucose
Serum Immunoglobulins
Urine Immunoglobulins
Autoimmune screen (ANA, dsDNA, C3, C4)
Hepatititis B & C
HIV

Chest Xray - if breathless (effusion)

Abdominal or renal ultrasound

Renal biopsy to perform microscopy, immunofluorescence and

Electromicrography
Pathophysiology

Nephrotic Glomerulonephritis is a renal condition affecting the

podocytes. This causes a leaky glomeruli leading to proteinuria and
subsequent hyperlipidemia, hypoalbuminemia and oedema

Pathophysiology - General
Minimal Change Disease
Overview Minimal change disease (MCD), sometimes known as nil
lesion, causes 70–90% of nephrotic syndrome in childhood but only
10–15% of nephrotic syndrome in adults. Minimal change disease
usually presents as a primary renal disease but can be associated
with several other conditions, including Hodgkin’s disease, allergies,
or use of nonsteroidal anti-inflammatory agents.

Clinical Presentation

Children
Anorexia
GI disturbance
Infections
Irritability
Oedema (peritorbital, genital)
Ascites
Oliguria

Minimal Change Disease The most common presentation of MCNS is

oedema. MCNS is characterised by oedema, selective proteinuria,
hypoalbuminaeia, hypercholesterolaemia, and a normal glomerular
filtration rate. Renal Biopsy: The only abnormality is diffuse
effacement and fusion of epithelial cell fot processes.

Renal Biopsy

Light Microscopy: nil

Immunoflourescence: occasional IgG in the mesangium
Electron microscopy: consistently demonstrates an effacement
of 177 the foot process supporting the epithelial podocytes
with weakening of slit-pore membranes.
Management

Prednisone - First line

Cyclophosphamide - If steroid toxicity and relapsing nephrotic
syndrome

Side note After initial treatment, proteinuria <0.3 g/day is defined as

complete remission; a reduction of baseline proteinuria by >50%
with a final value <3 g/day is defined as partial remission.
Remember 90% 0f patients experience a frequently relapsing or
steroid-dependent course with steroid toxicity. These patients are
candidates for treatment with second line drugs - cyclophosphamide
or tacrolimus

Complications

Infections (including spontaneous peritonitis)

Thrombosis - due to haemoconcenration and loss of proteins
such as antithrombin III, leading to a procoagulant state.
Hypovolaemia - due to loss of plasma water into the tissues
with consequent fall in circulating blood volume.
Relapse of Minimal Change Disease in Adulthood

Side note Relapses occur in 70–75% of children after the first

remission, and early relapse predicts multiple subsequent relapses
Focal Segmental Glomerulosclerosis
Focal segmental glomerulosclerosis (FSGS) refers to a pattern of
renal injury characterised by segmental glomerular scars that involve
some but not all glomeruli; the clinical findings of FSGS largely
manifest as proteinuria. When the secondary causes of FSGS are
eliminated, the remaining patients are considered to have primary
FSGS.

Side note The incidence of this disease is increasing, and it now

represents up to one-third of cases of nephrotic syndrome in adults

Renal Biopsy

Light Microsopy: focal and segmental glomerular sclerosis or

consolidation
Immunoflorecence: usually show no staining for
immunoglobulins or complement
Electron Microscopy:

Management

ACE inhibitors
Angiotensin II receptor blockers
Membranous Glomerulonephritis
Membranous glomerulonephritis (MGN), or membranous
nephropathy, accounts for approximately 30% of cases of nephrotic
syndrome in adults, with a peak incidence between the ages of 30
and 50 years and a male to female ratio of 2:1.

Remember Membranous glomerulonephritisis is rare in childhood

and the most common cause of nephrotic syndrome in the elderly

Renal Biopsy

Light Microscopy: Diffuse global capillary wall thickening in the

absence of significant glomerular hypercellularity
Electron Microscopy: Uniform thickening of the basement
membrane along the peripheral capillary loops is seen by light
microscopy on renal biopsy
Immunofluorescence demonstrates diffuse granular deposits of
IgG and C3, and electron microscopy typically reveals electron-
dense subepithelial deposits.

Diabetic Nephropathy
Overview Type II Diabetes Mellitus is the leading cause of Chronic
Kidney Disease. It is classified as a secondary nephrotic syndrome.
~10% have nephropathy at diagnosis and up to half will go on to

develop it over the next 20yrs. 20% of people with Type II diabetes
will develop end stage kidney disease. Everyone with Diabetes should
be screened yearly for microalbuminuria.

Clinical features - Nephrotic Syndrome with signs and symptoms of

diabetes (hyperglycemia)

Pathological features Diabetic nephropathy is defined by

characteristic structural and functional changes. The predominant
structural changes include

Mesangial expansion
Glomerular basement membrane thickening
Glomerular sclerosis
Podocytopathy

Staging
Isolated glomerular basement membrane thickening. There is
Class no evidence of mesangial expansion, increased mesangial
I matrix, or global glomerulosclerosis involving >50 percent of
glomeruli.
Class
Mild (class IIa) or severe (class IIb) mesangial expansion.
II
At least one Kimmelstiel-Wilson lesion (nodular intercapillary
Class
glomerulosclerosis) is observed on biopsy and there is <50
III
percent global glomerulosclerosis.
Class Advanced diabetic sclerosis. There is >50 percent global
IV glomerulosclerosis.
Pathogenesis

Management and Prognosis Microalbuminuria is reversible if caught

early and managed vigorously.

Tight glycemic control

Right BP control with ACE/ARBs
Manage CV risk factors

More info on Chronic Kidney Disease

Complications Prognosis
Complications

Thromboembolism
Infection - due to loss of immunoglobulins and complement
Hyperlipidemia
Loss of vitamin D leading to bone disease
Acute renal failure
Chronic renal failure

References
UpToDate
Best Practice

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