Renal Disease Flashcards
Anatomy of the kidney
From inside-outside: Ureter, renal artery, renal vein Renal calynx Medullary pyramid Cortex Capsule
Where is most of the sodium reabsorbed in the kidney
Ascending lim b of the loop of Henle
Major functions of the kidney
Excretion of metabolic waste products and foreign chemicals
Regulation of fluid and electrolyte balance
Regulation of acid-base balance
Secretion of hormones - erythropoietin, renin, and 1,25 dihydroxycholecalciferol
Causes of major manifestations of glomerular disease
Failure to filter an adequate amount of blood so that waste products are not excreted
Failure to maintain barrier function leading to loss of protein and/or blood cells in the urine
Aetiology of glomerular disease
Syndromes: acute renal failure, nephrotic syndrome, microscopic haematuria
Morphological changes: glomerulonephritis, thrombotic microangiopathy
Aetiologies: SLE, amyloidosis, drugs, infections
What are immune complexes
Immune complexes are composed of a lattice work of antibody and antigen
What effect do immune complexes have on the kidneys
May become deposited in the glomerulus and lead to an inflammatory response (immune complex glomerulonephritis)
Complement activation
Stimulation of inflammatory cells through Fc receptors
Aetiology of immune-complex glomerulonephritis
The antigens in immune complexes may be endogenous (autoantigens) – e.g. SLE or exogenous e.g. derived from infective organisms
May deposit at different rates – rapidly progressive glomerulonephritis vs. slow onset
May deposit at different sites
Glomerular injury is determined by immune complex localization.
How can immune complexes be detected in the kidney
Immunohistochemistry and electron microscopy
Congenital kidney diseases
Bilateral or unilateral agenesis
Ectopic kidney e.g. pelvic
Horseshoe kidney (1:500 to 1:1000) – usually fused at lower pole
Adult Polycystic Kidney Disease
Autosomal dominant (1:400 – 1:1000) 10% of end stage renal failure Cysts arise from all portions of the nephron Renal failure develops from 40-70 years Two genes identified –PKD1 and PKD2
Acquired cystic kidney disease
Cysts commonly arise in kidneys of patients with end stage renal failure on dialysis
Carcinoma may occur (7% at 10 years)
Kidney syndromes
Acute renal failure (acute kidney injury)
Nephrotic syndrome
Isolated urinary abnormalities
Chronic kidney disease
Acute renal failure pathophysiology
Rapid loss of glomerular filtration and tubular function
Abnormal water and electrolyte balance
Reduced GFR manifested as increased serum creatinine and urea
May result in acidosis, hyperkalaemia and water overload
Causes of acute renal failure
Pre-renal: failure of perfusion
Renal: acute tubular injury, acute glomerulonephritis, thrombotic microangiopathy
Post-renal: obstruction to urine flow
Acute tubular injury (acute tubular necrosis)
Commonest cause of acute renal failure
Caused by damage to tubular epithelial cells by ischaemia or toxins e.g. drugs, myoglobin
Common in critically ill patients
Drugs that inhibit vasodilatory protaglandins e.g. NSAIDS predispose
Pathogenesis of acute tubular injury
Ischaemia or toxins:
Cause loss of polarity of epithelium and brush border, causing cell apoptosis and necrosis and sloughing of viable and dead cells causing luminal obstruction.
This causes spreading and dedifferentiation of viable cells and eventual proliferation and differentiation and re-polarization of cells to form a normal epithelium and brush border
Why does acute tubular injury cause failure of glomerular filtration
Blockage of tubules by casts
Leakage of fluid from tubules to interstitium reducing flow
Secondary haemodynamic changes
Acute glomerulonephritis
Acute inflammation of glomeruli leading to reduction in glomerular filtration
Presents with oliguria with urine casts containing red and white blood cells
GN sufficiently severe to cause renal failure is almost always associated with glomerular crescents
Causes of crescentic glomerulonephritis
Immune complex
Anti-GBM disease
Pauci-immune – associated with anti-neutrophil cytoplasm antibodies (ANCA)
Features of immune complex associated crescentic glomerulonephritis
Causes include SLE, IgA nephropathy, post-infectious GN
Immune complexes can be identified by immunohistochemistry or electron microscopy
Anti-GBM disease
Rare disease characterised by antibodies directed against the glomerular basement membrane – may be detected in circulation
Characterised by linear deposition of IgG on the GBM
Antibodies also bind to the alveolar basement membrane and may lead to lung haemorrhage
Pauci-immune crescentic glomerulonephritis
Only scanty deposits of immunoglobulin and complement are present in glomeruli
Usually associated with anti-neutrophil cytoplasm antibodies (ANCA)
These antibodies cause neutrophil activation leading to glomerular necrosis
Typically patients also have vasculitis in other organs – e.g skin rash, lung haemorrhage
Crescentic glomerulonephritis
Leads rapidly to irreversible renal failure
Correct diagnosis and treatment are urgent
Thrombotic microangiopathy
Damage to endothelium of glomeruli, arterioles and arteries leading to thrombosis
Red blood cells may become damaged by fibrin leading to haemolysis – microangiopathic haemolytic anaemia
Syndrome therefore referred to as haemolytic uraemic syndrome (HUS)
Forms of thrombotic microangiopathy
Diarrhoea associated: Caused by bacterial gut infection – usually E. coli
Releases toxin that targets the renal endothelium
Non-diarrhoea associated: Often associated with abnormalities of proteins that control activation of the complement pathway on endothelium
May be familial
Nephrotic syndrome
Breakdown of selectivity of the glomerular filtration barrier leading to massive protein leak
Proteinuria > 3.5g/day
Hypoalbuminaemia
Oedema
Hyperlipidaemia
Primary glomerular disease
Typically interferes with podocyte function
Causes of nephrotic syndrome
Systemic: DM, amyloidosis, SLE
Primary glomerular disease: minimal change disease, focal and segmental glomerulosclerosis, membranous glomerulonephritis
Amyloidosis and the kidneys
Deposition of extracellular proteinaceous material
Stains with Congo red stain and looks green under polarised light
May be derived from many precursor proteins.
Commonest forms in kidney are:
AA: derived from serum amyloid associated protein (SAA)
SAA is an acute phase protein which is increased in chronic inflammatory conditions e.g rheumatoid arthritis, chronic infections.
AL: Derived from immunoglobulin light chains
80% of patients have multiple myeloma.
Minimal change disease
Glomeruli look normal apart from effacement of foot processes on EM
Common cause of nephrotic syndrome in children
Generally responds to immunosupprssion
Focal and segmental glomerulosclerosis
Similar to minimal change disease but glomeruli develop segmental scars
Less likely to respond to immunosuppression
Membranous glomerulonephritis
Associated with immune deposits on the outside of the glomerular basement membrane
Causes of membranous glomerulonephritis
Primary autoimmune – many associated with antibodies to phospholipase A2 receptor
Secondary: SLE, Infection, Drugs, Malignancy
Causes of isolated urinary abnormalities
Microscopic haematuria:
Thin basement membranes
IgA nephropathy
Asymptomatic proteinuria:
May be associated with a wide range of glomerular structural abnormalities or immune complex deposition
Diagnosis often requires renal biopsy
Thin basement membrane
Hereditary defect in type IV collagen
In most cases microscopic haematuria is the only consequence
IgA nephropathy
Commonest form of glomerulonephritis worldwide
Predominant IgA deposition in glomeruli
Often presents with microscopic or macroscopic haematuria
May cause proteinuria, acute renal failure
Up to 30% progress to end stage renal failure
CKD classification
Stage 1 GFR>90 kidney damage with normal GFR
Stage 2 GFR 60-89 mild reduction in GFR
Stage 3 GFR 30-59 moderate decrease in GFR
Stage 4 GFR 15-29 severe reduction in GFR
Stage 5 <15 or dialysis kidney failure
CKD features
Most of the diseases discussed so far, together with hypertension and chronic infection can cause chronic kidney damage
Strongly associated with cardiovascular disease
Some progress to end stage renal failure and require renal replacement therapy
Causes of CKD
Diabetes (19.5%)
Glomerulonephritis (15.3%)
Hypertension & Vascular disease (15%)
Reflux nephropathy (chronic pyelonephritis) (9.5%)
Polycystic kidney disease (9.4%)
Systemic Lupus Erythematosus (SLE)
Systemic autoimmune disease
Affects kidney, skin, joints, heart, serosa and CNS
Commonly deposition of immune complexes in kidney
1:2500
M:F 1:9
Antibodies directed at a range of intracellular and extracellular antigens
Patients typically have anti-nuclear antibodies and antibodies to ds-DNA
Depending on site and intensity of immune complex deposition clinical presentation may be: Isolated urinary abnormalities Acute renal failure Nephrotic syndrome Progressive chronic renal failure
