Renal Disease Flashcards
What are the major functions of the kidney?
Excretion of metabolic waste products and foreign chemicals (including drugs).
Regulation of fluid, electrolyte and acid/base balance.
Regulation of blood pressure: Renin
Regulation of calcium and bone metabolism: 1,25 Dihydroxycholecalciferol.
Regulation of haematocrit: Erythropoietin.
Where are the kidneys?
Retroperitoneal.
T12 to L3 on left; right is lower.
Mean length 11cm.
Normal weight 125-170g (male), 115-155g (female)
Receive around 20% of cardiac output.
What is the anatomy of a kidney?
Basic unit is the nephron:
- Glomerulus
- Afferent and efferent arterioles
- Tubules
Approximately one million nephrons per kidney.
Large functional reserve.
Where is blood filtered in the nephron?
Blood is filtered at the glomerulus.
High hydrostatic pressure (60mmHg).
Podocytes create charge-dependent (anionic) and size-dependent barrier.
125 mL/min
Where in the nephron is the filtrate modified?
The filtrate is modified in the tubules
Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
Collecting tubule
Collecting Duct
What is the function of the proximal convoluted tubule?
The Proximal Convoluted Tubule actively resorbs sodium.
Hydrogen exchange to allow carbonate resorption.
Co-transport of amino acids, phosphate, glucose.
Potassium is also reabsorbed.
What is the function of the Loop of Henle?
The Loop of Henle doubles back on itself.
Descending/thin ascending limb permeable to water but not ions or urea; ascending limb actively resorbs sodium and chloride.
Countercurrent Multiplier; aligned with vasa recta.
What is the function of the distal convoluted tubule?
The Distal Convoluted Tubule is impermeable to water.
Regulates pH via active transport (proton/bicarbonate).
Regulates sodium, potassium via active transport (aldosterone).
Regulates calcium (parathyroid hormone, 1,25 dihydroxycholecalciferol).
What is the function of the collecting duct?
Resorbs water (principal cells, antidiuretic hormone).
Regulates pH (intercalated cells, proton excretion).
What is the relationship between immune complexes and the kidney?
Latticework of antibody and antigen: May be endogenous or exogenous antigens.
May deposit in the glomerulus:
- Inflammatory response
- Complement activation
- Stimulation of inflammatory cells
May deposit at different rates.
May deposits at different sites.
What are signs and symptoms of renal disease?
- Haematuria
- Proteinuria
- Uraemia
- Hypertension
- Oliguria/Anuria
- Polyuria
- Oedema
- Colic
What are examples of renal disease syndromes?
Acute renal failure
Nephrotic syndrome
Microscopic haematuria
Isolated Urinary Abnormalities
Chronic Kidney Disease
What are renal morphological changes?
Glomerulonephritis
Thrombotic microangiopathy
What is the aetiology of renal disease?
Congenital
Systemic Lupus Erythematosus
Amyloidosis
Drugs
Infections
What are examples of genitourinary malformations and the kidney?
- Agenesis
- Renal Fusion (e.g. horse-shoe)
- Ectopic Kidney
- Renal Dysplasia
- Pelvi-ureteric Junction Obstruction
- Ureteral Duplication
- Vesicoureteral Reflux
- Posterior urethral Valves
What is adult (dominant) polycystic kidney disease?
1:500
10% of end-stage renal failure.
Presents in adulthood with hypertension, flank pain and haematuria.
PKD1, PKDS2
Berry aneurysm
In which group of people do kidney cysts develop?
Cysts commonly develop in patients with end stage renal disease who are on dialysis:
- Multiple
- Bilateral
- Cortical and Medullary
What is the association between cystic kidneys and malignancy?
Increased risk of development of malignancy.
7% risk at 10 years.
Papillary renal cell carcinoma.
What is acute renal failure?
Rapid deterioration in renal function (hours, days).
Common, often in the setting of pre-existing disease.
Presentation and prognosis variable.
What are causes of acute renal failure?
Pre-Renal: Failure of perfusion.
Renal: Acute tubular injury, acute glomerulonephritis, thrombotic microangiopathy.
Post-Renal: Obstruction.
What is acute tubular injury?
Commonest cause of acute renal failure. Tubular epithelial cells damaged by:
- Ischaemia
- Toxins (contrast, haemoglobin, myoglobin, ethylene glycol)
- Drugs
Common in critical illness.
Drugs that inhibit vasodilatory prostaglandins predispose e.g. NSAIDs.
What are causes of failure of glomerular filtration?
Blockage of tubules by casts
Leakage of tubules to interstitial space
Secondary haemodynamic changes
What is acute tubulo-interstitial nephritis?
Immune injury to tubules and interstitium. Can also be due to infection and drugs:
- NSAIDs
- Antibiotics
- Diuretics
- Allopurinol
- Proton Pump Inhibitors
Heavy interstitial inflammatory infiltrate with tubular injury. Can see eosinophils, granulomas.
What is acute glomerulonephritis?
Acute inflammation of glomeruli. Presents with oliguria with urine casts containing erythrocytes and leucocytes.
When sufficient to cause acute renal failure, there are almost always crescents. Proliferation of cells within Bowman’s space.
What is acute crescentic glomerulonephritis?
Immune Complex.
Anti Glomerular Basement Membrane Disease.
Pauci-immune (anti-neutrophil cytoplasm antibodies).
Leads rapidly to irreversible renal failure.
Correct diagnosis and treatment are urgent.
What is the aetiology of immune complex associated crescentic glomerulonephritis?
Aetiologies include SLE, IgA nephropathy and Post-Infectious Glomerulonephritis.
Immune complexes can be identified and localised with immunohistochemistry and electron microscopy. Final diagnosis depends on specific findings interpreted within the appropriate clinical context.
What is anti-GBM disease?
Rare and severe disease caused by antibodies directed against the glomerular basement membrane.
C-terminal domain of Type IV collagen.
May cross-react with alveolar basement membrane leading to pulmonary haemorrhage.
Antibody may be detected with serology.
Linear deposition of IgG demonstrable on glomerular basement membrane.
What is Pauci-Immune crescentic glomerulonephritis?
Only scanty glomerular immunoglobulin deposits.
Usually ANCA-associated: Trigger neutrophil activation and glomerular necrosis.
Vasculitis elsewhere.
What is thrombotic microangiopathy?
Damage to endothelium in glomeruli, arterioles, arteries leading to thrombosis. Red cells may be damaged by fibrin:
- Microangiopathic haemolytic anaemia
- Haemolytic Uremic Syndrome
What are causes of diarrhoea associated thrombotic microangiopathy?
Bacterial gut infection such as with E. coli.
Toxins released that target renal endothelium.
What are causes of non-diarrhoea associated thrombotic microangiopathy?
- Defects in regulation of complement
- Deficiency in ADAMTS13
- Drugs (calcineurin inhibitors)
- Radiation
- Hypertension
- Scleroderma
- Antiphospholipid Antibody Syndrome (+/- SLE)
What is nephrotic syndrome?
Breakdown in selectivity of glomerular filtration barrier leading to protein leak.
What are the hallmark signs of nephrotic syndrome?
Proteinuria (>3.5g/day)
Hypoalbuminemia
Oedema
Hyperlipidaemia
What are examples of primary glomerular disease, non-immune complex related diseases?
Minimal Change Disease
Focal Segmental Glomerulosclerosis
What are examples of primary renal disease, immune complex mediated diseases?
Membranous Glomerulonephritis
What are examples of systemic diseases resulting in renal disease?
Diabetes mellitus
Amyloidosis
SLE
What is minimal change disease?
Glomeruli look normal by light microscopy.
Effacement of foot processes on electron microscopy.
Common cause of nephrotic syndrome in children.
Generally responds to immunosuppression.
What is focal segmental glomerulosclerosis?
Some glomeruli are partially scarred.
Less likely to respond to immunosuppression.
Must exclude possible other diseases that can produce a similar appearance.
These tend not to be nephrotic.
What is membranous glomerulonephritis?
Associated with immune deposits on outside of glomerular basement membrane - subepithelial.
Common cause of nephrotic syndrome in adults.
Primary disease is autoimmune: Antibody against phospholipase A2 type M receptor (PLA2R) in 75% of cases.
Need to exclude possibility of a secondary disease: Epithelial malignancy, drugs, infections, SLE.
Interpret findings in clinical and serological context.
What is diabetic nephropathy?
30-40% of diabetics
High glucose levels thought to be directly injurious.
Typically starts as microalbuminuria before progression to proteinuria and nephrotic syndrome.
What are the stages of nodular glomerulosclerosis?
Stage 1: Thickening of basement membrane on EM.
Stage 2: Increase in mesangial matrix, without nodules.
Stage 3: Nodular lesions/Kimmelstiel-Wilson.
Stage 4: Advanced glomerulosclerosis.
How does amyloidosis lead to kidney injury?
Deposition of extracellular proteinaceous material exhibiting β-sheet structure.
What are the commonest types of amyloidosis in the kidney?
AA: Derived from serum amyloid associated protein (SAA), an acute phase protein; patients tend to have a chronic inflammatory state.
AL: Derived from immunoglobin light chains; 80% of patients have multiple myeloma.
What are causes of microscopic haematuria?
Thin basement membranes
IgA Nephropathy
What is asymptomatic proteinuria?
May be associated with a broad range of glomerular structural abnormalities or immune complex deposition.
Diagnosis often requires renal biopsy for histology, immunohistochemistry and electron microscopy.
What are causes of thin basement membranes?
Hereditary defect in Type IV collagen synthesis.
Basement membrane <250nm thickness.
Haematuria is only consequence in most cases.
What is Alport’s Syndrome?
X-linked dominant mutations affecting ⍺5 subunit.
Forms exist in which mutation affects ⍺3 or ⍺4 subunit.
Typically progressive, renal failure in middle age.
Often have deafness, ocular disease.
What is IgA nephropathy?
Commonest glomerulonephritis.
IgA predominant mesangial immune complex deposition.
Aetiology not well understood in primary form:
- Secondary forms observed in liver, bowel and skin disease.
- Can be seen with small-vessel vasculitis (Henoch-Schönlein Purpura).
30% develop end stage renal failure.
Oxford Classification (MEST-C).
What is CKD?
Can be caused by a large number of diseases.
Significant cause of morbidity and mortality.
Association with ischaemic heart disease: Hypertension, hyperlipidaemia, calcification of blood vessels.
Association with calcium and phosphate metabolic derangement: Hyperparathyroidism, osteomalacia, osteoporosis.
What is stage 1 CKD?
Kidney injury with normal or elevated GFR
eGFR >90
2.0-3.0% prevalence
What is stage 2 CKD?
Mild reduction in GFR
eGFR 60-89
3.0% prevalence
What is stage 3 CKD?
Moderate reduction in GFR
eGFR 30-59
4.0-8.0% prevalence
What is stage 4 CKD?
Severe reduction in GFR
eGFR 15-29
0.2-0.4% prevalence
What is stage 5 CKD?
End-Stage Renal Failure
eGFR <15
0.2-0.3% prevalence
What are common causes of CKD?
Diabetes – 27.5%
Glomerulonephritis – 14.1%
Polycystic Kidney Disease – 7.4%
Pyelonephritis – 6.5%
Hypertension – 6.8%
Renal Vascular Disease – 5.9%
Other / Uncertain – 31.7%
What are causes of hypertensive nephropathy?
Pathophysiology is not fully understood.
Narrowing of arteries and arterioles leading to scarring and ischaemia of glomeruli.
Hypertension in glomeruli leading to altered haemodynamic environment, stress and segmental scarring.
How do kidneys affected by hypertensive nephropathy look?
Shrunken kidneys with granular cortices.
Histopathology may show “nephrosclerosis”.
Arteriolar hyalinosis, arterial intimal thickening, ischaemic glomerular changes, segmental and global glomerulosclerosis.
What is the association between SLE and renal disease?
SLE is a systemic autoimmune disease.
Affects the kidney, skin, joints, heart, serosal surfaces and the central nervous system. Affects around 1 in 2500 people and is nine times more common in females than in males.
Deposition of immune complexes in the kidney is common.
Antibodies directed at a broad range of intracellular and extracellular antigens.
Anti-nuclear and Anti-dsDNA antibodies are typical.
How may SLE affect presentation of renal disease?
Highly variable disease.
Depending on site, speed and intensity of immune complex deposition, may present as:
- Acute Renal Failure
- Nephrotic Syndrome
- Isolated Urinary Abnormality
- Chronic Kidney Disease
