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Nephritic Authors

Syndrome
Topics Overview
Overview Overview Nephritic syndrome is one of two clinical patterns seen in
glomerular disease. Nephritic Syndrome is characterised by
Classification
haematuria, proteinuria, hypertension and oligouria. Nephritic
Anatomy and syndrome can be further classified based on light microscopic
Physiology
features:
Signs and
Symptoms
Focal
Differential Diffuse
Diagnosis

Investigations Definition
Glomerular Disease: Disease effecting the glomerulus. Glomerular
Pathophysiology
disease reduces the ability of the kidneys to maintain a balance of
Management certain substances in bloodstream
IgA Nephropathy Nephritic Syndrome: Group of symptoms that occur with some
Post-Infectious disorders that cause swelling and inflammation of the glomeruli in
glomerulonephritis the kidney, or glomerulonephritis. Acute nephritic syndrome is
Lupus Nephritis often caused by an immune response triggered by an infection or
other disease.
Anti-GBM
Nephrotic Syndrome: kidney disease, especially when characterized
« Back to notes by oedema and the loss of protein from the plasma into the urine
due to increased glomerular permeability
Acute Kidney Injury: Characterized by abrupt deterioration in
kidney function, manifested by an increase in serum creatinine
level with or without reduced urine output. The spectrum of injury
ranges from mild to advanced, sometimes requiring renal
replacement therapy. The diagnostic evaluation can be used to
classify acute kidney injury as prerenal, intrinsic renal, or postrenal.
Chronic Kidney Failure: Defined as the presence of kidney damage,
manifested by abnormal albumin excretion or decreased kidney
function, quantified by measured or estimated glomerular filtration
rate (GFR), that persists for more than three months

Classification
The page will focus on four common nephritic syndromes towards
the end:

IgA nephropathy
Lupus Nephritis
Post-infectious Glomerulonephritis
Anti-GBM disease

Anatomy and Physiology

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 functional units of the kidney. There are millions
of nephrons. A 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,
pathophysiology and effect of glomerulonephritis it is important to
learn the layers of the glomerulus + bowman's capsule.

From inside out the layers are (as depicted in the image above):

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

Haematuria
Proteinuria
Oligouria - with signs of salt and water retention
Hypertension

Side note Pyuria can also be conspicuous in nephritic patients,

particularly in inflammatory forms of glomerulonephritis such as
poststreptococcal glomerulonephritis. However, pyuria is never the
sole manifestation of nephritic urine sediment.
Differential Diagnosis
IgA nephropathy and Henoch–Schönlein purpura
Lupus nephritis
Post-infectious GN
Anti-GBM disease
ANCA-associated vasculitis
Mesangiocapillary GN (MCGN)
Investigations
Dipstick urine for haematuria, proteinuria.
Urine microscopy for red blood cell morphology, casts
Amount of proteinuria variable
eGFR
EUC
FBC
Bone profile
LFT
Acute phase markers (CRP, ESR).
Immunological and serological (‘nephritic’) screen
C3, C4
ANA, dsDNA
Antineutrophil cytoplasmic antibody (ANCA) titers
a streptozyme test
HBV and HCV serologies
HIV
Anti-glomerular basement membrane (GBM)
Ultrasound of kidneys.
Renal biopsy

Pathophysiology
To come
Management
Salt and water restriction - It is vital to correctly assess
volume status
Control Blood Pressure
Diuretics
ACE inhibitors or ARBs
Immunosuppressive therapy - tailored to specific type of
nephritic syndrome (based on histology)
Corticosteroids
Cyclophosphamide
Chlorambucil
Calcineurin inhibitors
Azothiopurine
Ritiximab

IgA Nephropathy
Overview The most common primary glomerulonephritis in the
world, affecting an estimated 1.5% of the population. Often presents
with haematuria in the 2nd and 3rd decades. Occurs due to IgA
immune complex deposition in glomerular mesangium and capillary
wall, associated complement 3 activation and IgG binding and
resulting glomerular destruction. Damage results in chronic
microscopic or recurrent macroscopic haematuria, often after acute
URTI or gastroenteritis

Remember Previously considered relatively benign, it is now

recognized that 30– 50% will progress to significant CKD over
time.

Risk Factors
 Liver cirrhosis and other liver disease (due to reduced IgA
removal by Kuppfer cells)
Coeliac disease (excessive IgA production against gliadin
protein in gluten, form gliadin-antigliadin immune complexes,
up to 30% coeliacs develop IgA nephropathy.
HIV (abnormal IgA produced, form immune complexes)
Family history

Clinical Presentation

Painless Haematuria
<2days after URTI of gastrointestinal infection
Usually brown colour
Oligouria or dysuria
Abdominal or flank pain
Fever
Malaise
Myalgia
Hypertension
Purpuric skin rash - IgA nephropathy associated with Henoch–
Schönlein purpura

Side note Recurrent gross haematuria is the hallmark of IgA

nephropathy. Closely related to IgAN is Henoch–Schönlein purpura
(HSP), a condition that occur in children. HSP is a small vessel
systemic vasculitis characterised by IgA deposition in affected
blood vessel, with kidney biopsy findings usually indistinguishable
from IgAN

Pathology and Diagnosis

Light microscopy: Mesangial cell proliferation with matrix

expansion
Immunoflourescence: IgA, IgG and complement 3 protein
deposition on mesangial cells
Electron microscopy: Mesangial/paramesangial electron-
dense deposits of immune complexes

Treatment for IgA nephropathy is only required with persistent

proteinuria, recurrent haematuria, mild to moderate findings on
renal biopsy and evidence of decreased GFR. Isolated haematuria
does not require treatment

ACE inhibitors
Statin
Omega 3 fish oil
Immunosuppresive therapy (usually for high-risk patients) -
Corticosteroirds, cyclophosphamide
Dietary modification
Renal replacement therapy - for end stage kidney disease

Pharmacology Cyclophosphamide

Complications

Chronic Kidney Disease

End stage renal disease
Acute renal failure

Prognosis

IgA nephropathy is benign in majority of patients but up to

30% of patients progress to end stage renal disease within 10
years.
Patients with minimal proteinuria or minimal renal
dysfunction might undergo long-term remission periods

Post-Infectious glomerulonephritis
Overview Post-infectious glomerulonephritis is classically
associated with streptococcal infection, but infection of almost any
cause may be associated with an acute nephritic syndrome and a
diffuse proliferative GN on kidney. Post-infectious
glomerulonephritis is an immune complex-mediated GN that
usually occurs in childhood (age <7 years) following (usually) a
upper respiratory tract infection (Tonsilitis, pharyngitis) but also
impetigo, otitis media and cellulitis 1-2 weeks earlier.
Clinical presentation

Frank haematuria
Oliguria
Oedema
↑BP
Pulmonary oedema
Acute Kidney Injury
Loin Pain (may be bilateral)

Side note The most common Post-infectious glomerulonephritis is

Post-streptococcal glomerulonephritis. Other causes include:
streptococcal pneumococcal, meningococcal, salmonella,
mycobacterial, syphilis. Viruses: influenza B, mumps, rubella,
coxsackie, hepatitis B, EBV, CMV. Fungi: candida, Coccidioides,
Histoplasma. Parasites: malaria, filiariasis, toxoplasmosis, or
schistosomiasis.

Investigations

As summarised above in the investigation section of nephritic

syndrome
Anti-streptolysin O titre
Anti-DNAase B (for group A streptococci)

Pathology/Diagnosis

Light Microscopy - Diffuse proliferative changes with

hypercellularity. Extensive neutrophilic infiltration and red cell
casts. Crescentic change and frank necroses are unusual
Immunoflorecence - IgG and C3 deposition in diffuse granular
pattern in both the mesangium and glomerular capillary walls
Electron Miscroscopy - ‘dome-shaped’, electron-dense deposits
in the subepithelial aspects of the capillary walls, with
endothelial cell swelling

Course of Post-Infectious Glomerulonephritis

Generally is self-limiting. It is associated with a full renal

recovery (even after AKI).
 Resolution usually begins after 7–10 days.

Recurrence is rare.
Urinary abnormalities may persist for many years after
recovery
Proteinuria, ↑ BP, and CKD also occur, so patients should be
offered follow-up

Treatment

Ensure underlying infection has been resolved

Restrict salt and fluid (~500-1000mL/day)
Antihypertensive (Frusomide or ACE inhibitors)
Renal replacment

Lupus Nephritis
Overview Renal involvement is common in systemic lupus
erythematosus (SLE). There are several types of renal disease in SLE
(most commonly, immune complex-mediated glomerular disease),
which are usually differentiated with a renal biopsy

Pathophysiology The pattern of glomerular injury seen in systemic

lupus erythematosus (SLE) (and in other immune complex-mediated
glomerular diseases) is primarily related to the site of formation of
the immune deposits, which are primarily due to anti-double-
stranded DNA antibodies (anti-dsDNA, or anti-DNA)

Classification

Class I disease (minimal mesangial lupus nephritis) is

characterized by mesangial immune deposits that are
identified either by immunofluorescence alone or by
immunofluorescence and electron microscopy
Class II disease (mesangial proliferative lupus nephritis) is
characterized by mesangial hypercellularity or mesangial
matrix expansion on light microscopy.
Class III disease (focal lupus nephritis) is defined by light
microscopic appearance of endocapillary or extracapillary
glomerulonephritis that involves fewer than 50 percent of
glomeruli.
Class IV (diffuse lupus nephritis) is defined by more than 50
percent of glomeruli displaying endocapillary with or without
extracapillary glomerulonephritis.
Class V (lupus membranous nephropathy) is characterized by
diffuse thickening of the glomerular capillary wall on light
microscopy and by subepithelial immune deposits on
immunofluorescence or electron microscopy.
Class VI disease (advanced sclerosing lupus nephritis) is
characterized by global sclerosis involving more than 90
percent of glomeruli.
Anti-GBM
Overview Anti-GBM antibody disease is a disorder in which
circulating antibodies are directed against an antigen intrinsic to
the glomerular basement membrane (GBM), thereby resulting in
acute or rapidly progressive glomerulonephritis that is typically
associated with crescent formation.

Patients with anti-GBM antibody disease usually present with

rapidly progressive glomerulonephritis: acute renal failure, nephritic
urine sediment, and non-nephrotic proteinuria. Pulmonary
involvement (alveolar haemorrhage) is present in 40 to 60 percent
of patients

Diagnosis

Presence of anti-GBM antibodies

Kidney biopsy, unless contraindicated, since demonstration of
linear deposits of IgG (which represent binding of anti-GBM
antibodies to the GBM)

Other investigations

Antineutrophil cytoplasm antibodies

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