Post on 18-Oct-2020
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GLOMERULONEPHRITIS
AND NEPHROTIC
SYNDROMEDR. A.O SHITU
INTRODUCTION
Glomerulonephritis comprises a specific set of renal
diseases in which an immunologic mechanism triggers
inflammation and/or proliferation of glomerular tissue,
that can result in damage to the basement membrane,
mesangium, podocytes or capillary endothelium
It can be simply defined as inflammation of the
glomerular capillaries
It encompasses a wide range of disease with different
lesions and several unique clinical features and changes
to urinalysis
STRUCTURE OF THE GLOMERULUS
The glomerulus consist of an anastomosing network of capillaries
invested by two layers of epithelium
Visceral epithelium composed of podocytes and lines the capillary walls
Parietal epithelium which lines the Bowmans capsule
The glomerular capillary wall is the filtration unit and consist of
Fenestrated endothelial cells
Glomerular basement membrane
Podocytes which is adherent to the GBM and has foot processes separated by filtration slits
The glomerular tuft is supported by mesangial cells lying between
the capillaries
MECHANISM OF GLOMERULAR
INJURY
Immune mechanisms underlie most types of primary glomerular
disease and many of the secondary glomerular disease
Antibodies, complement and cell-mediated immunity are involved
2 forms of antibody-associated injury have been established
1. Injury resulting from deposition of soluble antigen-antibody complexes
in the glomerulus
2. Injury by antibodies reacting in situ within the glomerulus either with
Fixed insoluble (intrinsic) glomerular antigens
Planted molecules within the glomerulus
This immune deposition and reaction can occur in the
subendothelial or subepithelial regions of the glomerulus
AETIOLOGY
PRIMARY GLOMERULAR DISEASE
Minimal-change disease
Focal segmental glomerulosclerosis
Membrane nephropathy
MembranoproliferativeGN
IgA nephropathy
HEREDITARY DISORDERS
Alport syndrome
Fabry disease
Podocyte/slit diaphragm protein
mutation
GLOMERULOPATHIES SECONDARY TO SYSTEMIC DISEASE
INFECTIONS
BACTERIAL: post-streptococcal, endocarditis, syphilis, tuberculosis, mycoplasma
VIRAL: HIV, HBV, HCV, EBV, CMV, VZV
PROTOZOAL: toxoplasmosis, malaria
HELMINTHS: schisostomaisis, trypanosmiasis, filariasis
MEDICATION: NSAIDS, pamidronate, rifampicin, gold, lithium, interferon alpha
ALLERGENS: immunization, pollens, serum sickness, vaccines, bee stings
SYSTEM ILLNESSES: SLE, rheumatoid arthritis, amyloidosis, vasculitidies
NEOPLASIA: solid tumours, haematological malignancies (lymphoma
and leukaemia), multiple myeloma
METABOLIC DISEASES: diabetes mellitus, hypothyroidism, graves disease
Graft vs host disease following bone marrow transplantation
MISCELLANOUS: pregnancy related, chronic allograft failure, obesity
MANIFESTATION OF GN
The manifestation is dependent on the pattern of disease. Which
can be
NON-PROLIFERATIVE
Minimal change disease
FSGS
Membranous GN
PROLIFERATIVE
IgA nephropathy
Post-infectious (post-streptococcal)
Membranoproliferative
Rapidly progressive glomerulonephritis
These patterns lead to several distinct syndromes
Nephritic syndrome : haematuria, non-nephrotic proteinuria (1-2g/24hr),
hypertension, fluid retention, and rise serum creatinine
Rapidly progressive glomerulonephritis: if the serum creatinine rises within days. Also called cresentic glomerulonephritis.
Nephrotic syndrome: proteinuria (3.5g/24hrs), hypertension,
hyperlipidaemia, hypoalbuminaemia, edema
Isolated asymptomatic haematuria or proteinuria
Infectious disease can give a range of presentations from nephrotic
to nephritic
Its also important to consider if the GN is acute or chronic
NEPHROTIC SYNDROME
This a clinical syndrome characterized by the triad of
1. Proteinuria (urine protein >3.5g/24hrs)
2. Hypoalbuminaemia (serum albumin <25g/L)
3. Oedema/anasaca
Hyperlipidaemia (total cholesterol >10mmol/L) is often present
Nephrotic syndrome is not a diagnosis, it only explains the
combination of clinical features. Thus the underlying cause should
always be sought
It can be due to a primary renal disease or secondary to a number of systemic disorders
AETIOLOGY PRIMARY CAUSES
Minimal change disease
FSGS
Membranous nephropathy
Hereditary nephropathies (podocyte/slit diaphragm protein mutation)
SECONDARY CAUSES
Infections: HBV, HCV, HIV
Systemic lupus erythermatous
Metabolic disorders: DM, amyloidosis
Malignancy: in the form of paraneoplastic syndrome
Drug related: NSAIDs, penicillamine, anti-TNF, gold
Others: allergic, GVHD
PATHOPHYSIOLOGY
Injury to the podocytes with the disruption of the glomerular filtration
barrier is the key pathology
Damage to the endothelial surface, GBM, podocytes are also seen
Leakage of albumin alone can occur as a result of the loss of the
negative charges in the glomerular membrane
With greater injury there is leakage of all plasma proteins as the is
more than just loss of the negative charge but the is a generalized
defect in permeability
Proteinuria of more than 85% albumin is said to be selective proteinuria
MINIMAL CHANGE DISEASE MEMBRANOUS GN
METABOLIC CONSEQUENCES OF
PROTEINURIA
Oedema and fluid retention
Hypoalbuminaemia
Hyperlipidaemia and bone abnormalities
Infection
Hypercoagulability
Hypovolemia
Hypocalcaemia
OEDEMA AND FLUID RETENTION
UNDERFILL HYPOTHESIS
Hypoalbuminaemia lowering the plasma colloid osmotic pressure,
leading to increased transcapillary filtration of water throughout the
body
With reduction in plasma volume there is secondary increase of sodium
and water retention by the kidneys
OVERFILL HYPOTHESIS
Renal sodium retention occurs as a result of proteinuria
Filtered plasminogen is converted to plasmin and this enhance
reabsorption of sodium and water from the cortical collecting ducts
INFECTION
They susceptible to streptococcus pneumoniae, haemophilus
influenzae, E.coli
Can manifest as sepsis, cellulitis, pneumonia, and peritonitis
The reason for infection include
Urinary immunoglobulin loss
Oedema as a culture medium
Protein deficiency
Decreased perfusion of the spleen
therapy
HYPERLIPIDAEMIA
Regarded as feature of nephrotic syndrome
Hypoproteinaemia leads to reactive hepatic protein synthesis
including lipoproteins
Reduced plasma levels of lipoprotein lipase leads to reduced lipid
catabolism
HYPERCOAGULABILITY
Venous thrombosis and pulmonary embolism are well documented
complications of nephrotic syndrome
The urinary loss of anticoagulant plasma protein including
Antithrombin III
Plasminogen
The simultaneous increase in clotting factors esp. factors I, VII, VIII, X
CLINICAL FEATURES
Generalised oedema/ anasaca, which usually starts at the face
and progresses to involve the entire body
Passage of frothy urine
Evidence of complications e.g infection, thromboembolism
Evidence of underlying cause in secondary nephrotic syndrome. E.g
DM
On examination
Oedema, ascites, pleural efflusion
Hypertension
INVESTIGATION
URINALYSIS
Proteinuria of +++ or more, maybe some haematuria
URINE PROTEIN ESTIMATION
24Hrs urine collection with >3.5g/24hrs
Spot urine collection, using urine protein creatinine ratio of >2g/g
URINE SEDIMENT EXAMINATION
Oval fat bodies and also fatty casts
SERUM ALBUMIN <2.5g/L
TEST FOR AETIOLOGY: Serology for infections(HBV, HCV, HIV), ANA for lupus
USS
RENAL BIOPSY
INDICATION IN CHILDREN
Congenital nephrotic syndrome
Less than 8yrs at onset
Steriod resistance
Frequent relapses or steroid
dependency
Significant nephritic manifestions
INDICATION IN ADULTS
Nephrotic syndrome of unknown
origin
Primary nephrotic syndrome e.g
minimal change and FSGS
Systemic lupus erythermatous
TREATMENT
Reduce oedema:
loop diuretics e.g furosemide are used, high dose are often used. Given intravenously.
The patients weight and urine output monitored.
Restrict fluid and salt intake
Reduce proteinuria: ACE-I or ARB
Reduce risk of complications
Anticoagulation
Statins for hyperlipidaemia
Vaccination and treat infections
Specific treatment for primary disease: steroid and immunosuppression
Treat underlying cause in secondary disease
SUMMARY
GN is the inflammation of the glomerular apparatus usually cause by
abnormal immune reactions
It can be primary involving the kidneys only, or secondary following a systemic disease
Presentation is in the form of clinical syndromes
Nephrotic syndrome being the triad of proteinuria,
hypoalbuminaemia and generalized edema
Podocyte injury and dysfunction are responsible for nephrotic
syndrome
Management involves finding the cause (and treating if possible)
and supportive management