Kidneys in Systemic Disease Flashcards
Give some systemic diseases affecting the kidney
Diabetes mellitus
Cardiovascular disease:
- Cardiac failure
- Atheroembolism
- Hypertension
- Atherosclerosis
Infection:
- Sepsis
- Post-infective GN
- Infective endocarditis
Inflammation in blood vessels:
- SLE
- Vasculitis
- Scleroderma and other connective tissue diseases
- Cryoglobulinaemia
HUS/TTP
Myeloma
Amyloidosis
Drugs
- Aminoglycosides
- ACE inhibitors
- Penicillamine, gold
- NSAIDs
- Radiocontrast
What type of damage to drugs cause to the kidney?
Acute interstitial nephritis
What is the pathology of diabetic nephropathy?
- Hyperfiltration
- Silent sub-clinical phase
- Pathological increase of GFR
- Hyperfiltration due to osmotic effect of glucose - Microalbuminuria
- [20-200ug/d]
- Check diabetics every year for this - Clinical nephropathy
- Proteinuria > 0.5g/d
- Decline in kidney function
- Brisk rise in proteinuria - Established renal failure
How does diabetic nephropathy in type 1 and type 2 differ in terms of rate of progression?
Doesn’t
Nephropathy due to chronic increase in blood glucose.
Progression seems to be the same
What is the long term risks of diabetic nephropathy for Type 1 and type 2 diabetic patients?
Type 1
- 4% develop nephropathy within 10 years
- 5% develop nephropathy within 25 years
Type 2
- 10% nephropathy by 5 years
- 30% nephropathy by 20 years
What percentage of those with diabetic nephropathy will progress to ESRF?
30%
What is the commonest single cause of ESRF?
Diabetic nephropathy
How does GFR stage Chronic Kidney Disease?
Stage 1 = GFR >90 Stage 2 = GFR 60-89 Stage 3 = GFR 30-59 Stage 4 = GFR 15-29 Stage 5 = GFR
What is a common cause of renal failure in older patients?
Renal vascular disease
Describe the pathology of atheroembolic diasease
Eosinophilia -> allergic reaction to cholesterol
Peripheral rash in legs
Common if on warfarin
Vascular procedures can precipitate by disturbing cholesterol triggering eosinophilia
What is vasculitis?
Inflammatory reaction in the wall of any blood vessel
Defined by size of vessel involved
Can affect single or multiple organs
Wide spectrum of clinical presentations
Describe the type of vasculitis and causes
Aorta/ large artery
- Takayasu
- Giant cell arteritis
Medium artery
- Polyarteritis nodosa
- Kawasaki disease
Small vessel
- Wegener’s granulomatosis
- Microscopic polyarteritis
- Churg-strauss syndrome
What us wegener’s granulomatosis also called?
Granulomatous polyarteritis
What is Churg-Strauss syndrome?
Autoimmune condition -> vasculitis of medium-sized blood vessels in persons with a history of airway allergic hypersensitivity (atopy).
Usually manifests in three stages.
- Early (prodromal) stage:
- –Marked by airway inflammation; almost all patients experience asthma and/or allergic rhinitis.
- Second stage
- –Characterized by hypereosinophilia, which causes tissue damage, most commonly to the lungs and the digestive tract.
- Third stage
- –Vasculitis, which can eventually lead to cell death and can be life-threatening.
What is the most common pANCA target?
By far the most common p-ANCA target is myeloperoxidase (MPO), a neutrophil granule protein whose primary role in normal metabolic processes is generation of oxygen radicals.
When the condition is a vasculitis, the target is usually MPO.
What is Wegener’s granulomatosis?
Granulomatous inflammation in respiratory tract
Focal necrotising glomerulonephrotos with crescents
Slightly more common in males
Affects all age groups, most common 40-60
How does Wegener’s granulomatosis effect the respiratory tract?
Upper respiratory tract
- Epistaxis
- Nasal deformity
- Sinusitis
- Deafness
Lower respiratory tract
- Cough
- Dyspnoea
- Haemoptysis
- Pulmonary haemorrhage
Apart from the lungs what other organs does wegener’s granulomatosis effect?
Kidney - gomerulonephritis
Joints - arthralgia, myalgia
Eyes- scleritis
Heart - pericarditis
Systemic - fever, weight loss, vasculitic skin rash
What is microscopic polyarteritis?
Similar clinical spectrum to Wegener’s granulomatosis
Can present with systemic disease, renal and pulmonary involvement
More commonly renal limited disease
How can you diagnose vasculitis?
Urine
-Blood/protein
Renal function
-Raised urea/creatinine
Biochemistry
-Raised alk phos, CRP, low albumin
Haematology
-Anaemia, thrombocytosis, leukocytosis
Immunology
- Hyperglobulinaemia
- Positive ANCA
Renal biopsy
What are the two types of ANCA seen in vasculitis?
c-ANCA
p-ANCA
What ELISA matches to immunostaining?
p-ANCA -> myeloperoxidase
c-ANCA -> Proteinase 3
What do different ANCA results mean?
Wegener’s granulomatosis >90% c-ANCA
Microscopic polyarteritis usually p-ANCA
Churg-Strauss may be neither
ANCA can be false positive
-e.g. inflammatory bowel disease
What is infective endocarditis and what causes it typically?
A result of bacterial (or fungal) infection on cardiac valves
Typical infections:
- Staphylococcus aureus
- Viridans streptococci
- Enterococci
How can infective endocarditis lead to secondary glomerulonephritis +/- small vessel vasculitis?
Immune complex formation
How is glomerulonephritis in infective endocarditis spotted?
Renal involvement suggested by:
- Abnormal urea/creatinine
- Haematuria, red cell casts
- Reduced complement levels
Renal disease shouls recover when underlying infection is treated
What is multiple myeloma?
A monoclonal proliferation of plasma cells producing an excess of immunoglobulins and light chains
Common in the elderly
What are the clinical features of multiple myeloma?
- Markedly elevated ESR
- Anaemia
- Weight loss
- Pathological fractures
- Infections
- Back pain/ Cord compression
How is multiple myeloma diagnosed?
Bone marrow aspirate > 10% clonal plasma cells
Serum paraprotein +/- immunoparesis
Urinary Bence-Jones protein (BJP)
Skeletal survey
-lytic lesions
How can myeloma result in renal failure?
Cast nephropathy
-“Myeloma kidney”
Light chain nephropathy
Amyloidosis
Hypercalcaemia
Hyperuricaemia
How is cast nephropathy seen?
Light microscopy
-Tubule will be filled with material
Anti-lambda immunochemistry
What can you see for light chain disease on light microscopy and immunoflourescence?
Light chain disease = TBM Ig deposition
LM = PAS stain IF = anti-kappa
What symptoms should make you suspect a systemic disease with renal involvement?
Fever, malaise, weight loss
Arthralgia, myalgia
Skin rash (vasculitic)
Gritty eyes
Breathlessness, haemoptysis, epistaxis
Haematuria, oedema
What signs should make you suspect a systemic disease with renal involvement?
Hands
-Spinter haemorrages, purpura, Rayneud’s
Face
-Scleritis, uveitis, nasal cartilage deformity, retinal vasculitis, hypertensive retinopathy
Skin
-Vasculitic rash, scleroderma
CVS
-Hypertension, murmur
Chest:
-Crepitations, haemoptysis
Locomotor
-Joint swelling, tenderness
CNS
-Stroke, encephalopathy
What investigations would make you suspect a systemic disease with renal involvement?
Urine
- Blood/protein on urinalysis
- microscopy - red cell casts
Blood
- Elevated urea/creatinine
- Raised CRP
- Thrombocytosis, anaemia
- Raised alkaline phosphate
If suspecting a systemic disease with real involvement what investigations should you carry out?
Blood:
- ANCA (anti-MPO/anti-PR3 antibodies
- ANA, dsDNA antibodies
- Complement levels C3, C4
- Blood cultures
Radiology
- CXR
- USS abdomen (renal size)
- CT thorax (pulmonary granulomas, interstitial disease)
- Echocardiography
Biopsy
-Kidney, nasal mucous, lung, skin
