Renal Disease

Question 1

Anatomy of the kidney

Answer 1

From inside-outside:
Ureter, renal artery, renal vein 
Renal calynx
Medullary pyramid 
Cortex
Capsule

Question 2

Where is most of the sodium reabsorbed in the kidney

Answer 2

Ascending lim b of the loop of Henle

Question 3

Major functions of the kidney

Answer 3

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

Question 4

Causes of major manifestations of glomerular disease

Answer 4

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

Question 5

Aetiology of glomerular disease

Answer 5

Syndromes: acute renal failure, nephrotic syndrome, microscopic haematuria
Morphological changes: glomerulonephritis, thrombotic microangiopathy
Aetiologies: SLE, amyloidosis, drugs, infections

Question 6

What are immune complexes

Answer 6

Immune complexes are composed of a lattice work of antibody and antigen

Question 7

What effect do immune complexes have on the kidneys

Answer 7

May become deposited in the glomerulus and lead to an inflammatory response (immune complex glomerulonephritis)
Complement activation
Stimulation of inflammatory cells through Fc receptors

Question 8

Aetiology of immune-complex glomerulonephritis

Answer 8

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.

Question 9

How can immune complexes be detected in the kidney

Answer 9

Immunohistochemistry and electron microscopy

Question 10

Congenital kidney diseases

Answer 10

Bilateral or unilateral agenesis
Ectopic kidney e.g. pelvic
Horseshoe kidney (1:500 to 1:1000) – usually fused at lower pole

Question 11

Adult Polycystic Kidney Disease

Answer 11

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

Question 12

Acquired cystic kidney disease

Answer 12

Cysts commonly arise in kidneys of patients with end stage renal failure on dialysis
Carcinoma may occur (7% at 10 years)

Question 13

Kidney syndromes

Answer 13

Acute renal failure (acute kidney injury)
Nephrotic syndrome
Isolated urinary abnormalities
Chronic kidney disease

Question 14

Acute renal failure pathophysiology

Answer 14

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

Question 15

Causes of acute renal failure

Answer 15

Pre-renal: failure of perfusion
Renal: acute tubular injury, acute glomerulonephritis, thrombotic microangiopathy
Post-renal: obstruction to urine flow

Question 16

Acute tubular injury (acute tubular necrosis)

Answer 16

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

Question 17

Pathogenesis of acute tubular injury

Answer 17

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

Question 18

Why does acute tubular injury cause failure of glomerular filtration

Answer 18

Blockage of tubules by casts
Leakage of fluid from tubules to interstitium reducing flow
Secondary haemodynamic changes

Question 19

Acute glomerulonephritis

Answer 19

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

Question 20

Causes of crescentic glomerulonephritis

Answer 20

Immune complex
Anti-GBM disease
Pauci-immune – associated with anti-neutrophil cytoplasm antibodies (ANCA)

Question 21

Features of immune complex associated crescentic glomerulonephritis

Answer 21

Causes include SLE, IgA nephropathy, post-infectious GN

Immune complexes can be identified by immunohistochemistry or electron microscopy

Question 22

Anti-GBM disease

Answer 22

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

Question 23

Pauci-immune crescentic glomerulonephritis

Answer 23

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

Question 24

Crescentic glomerulonephritis

Answer 24

Leads rapidly to irreversible renal failure

Correct diagnosis and treatment are urgent

Question 25

Thrombotic microangiopathy

Answer 25

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)

Question 26

Forms of thrombotic microangiopathy

Answer 26

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

Question 27

Nephrotic syndrome

Answer 27

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

Question 28

Causes of nephrotic syndrome

Answer 28

Systemic: DM, amyloidosis, SLE Primary glomerular disease: minimal change disease, focal and segmental glomerulosclerosis, membranous glomerulonephritis

Question 29

Amyloidosis and the kidneys

Answer 29

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.

Question 30

Minimal change disease

Answer 30

Glomeruli look normal apart from effacement of foot processes on EM Common cause of nephrotic syndrome in children Generally responds to immunosupprssion

Question 31

Focal and segmental glomerulosclerosis

Answer 31

Similar to minimal change disease but glomeruli develop segmental scars Less likely to respond to immunosuppression

Question 32

Membranous glomerulonephritis

Answer 32

Associated with immune deposits on the outside of the glomerular basement membrane

Question 33

Causes of membranous glomerulonephritis

Answer 33

Primary autoimmune – many associated with antibodies to phospholipase A2 receptor Secondary: SLE, Infection, Drugs, Malignancy

Question 34

Causes of isolated urinary abnormalities

Answer 34

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

Question 35

Thin basement membrane

Answer 35

Hereditary defect in type IV collagen | In most cases microscopic haematuria is the only consequence

Question 36

IgA nephropathy

Answer 36

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

Question 37

CKD classification

Answer 37

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

Question 38

CKD features

Answer 38

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

Question 39

Causes of CKD

Answer 39

Diabetes (19.5%) Glomerulonephritis (15.3%) Hypertension & Vascular disease (15%) Reflux nephropathy (chronic pyelonephritis) (9.5%) Polycystic kidney disease (9.4%)

Question 40

Systemic Lupus Erythematosus (SLE)

Answer 40

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 ```