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