The Kidneys in Systemic Disease Flashcards
The kidney is a particular target for many systemic diseases, why?
The kidney receives more blood flow per unit volume than any other organ in the body
The glomeruli may filter proteins which are then reabsorbed by the tubule epithelial cells
The glomeruli may trap proteins or immune complexes
The kidney metabolises or excretes certain drugs, which may be toxic to the kidney
what are systemic diseases that affect the kidneys?
Diabetes mellitus
Cardiovascular disease - Cardiac failure, Atheroembolism, Hypertension, Atherosclerosis
Infection - Sepsis, Post-infectious GN, Infective endocarditis
Inflammation in blood vessels - SLE, Vasculitis, Scleroderma and other connective tissue diseases, Cryoglobulinaemia
HUS / TTP
Myeloma
Amyloidosis
Drugs - Aminoglycosides, NSAIDs, ACE inhibitors, Radiocontrast, Penicillamine, gold
what is shown here?
Diabetic Nephropathy
Describe the Natural history of diabetic nephropathy - Development of proteinuria and decline in GFR?
- Silent sub-clinical phase, Hyperfiltration, Increased GFR
- Microalbuminuria [20 - 200ug/d]
- Clinical nephropathy [proteinuria > 0.5g/d]
- Established renal failure
what is the long term risk of diabetic nephropathy in type 1 and type 2 patients?
- 4% with Type 1 DM will develop nephropathy within 10 years
- 25% with Type 1 DM will develop nephropathy within 25 years
- 10% with Type 2 DM will have nephropathy by 5 years
- 30% with Type 2 DM will have nephropathy by 20 years
- 30% of those with diabetic nephropathy will progress to ESRF
- Substantial associated increase in mortality
What is the commonest single cause of ESRF?
diabetes
Is the incidence of ESRD due to Diabetes increasing or decreasing?
increasing
Diabetic nephropathy summary:
- Diabetic nephropathy develops over many _____
- Type I and Type II patients are ______ at risk
- Increasing _________ is usually associated with declining GFR
- Diabetic nephropathy is the single commonest cause of ____ leading to the need for ______ or transplantation
years
equally
proteinuria
ESRF
dialysis
what is the classification of chronic kidney disease based on?
Classification based on kidney function - Glomerular Filtration Rate ( GFR )
chronic kidney disease has a relationship with ____________ disease
cardiovascular
what other things are common causes of renal failure in older patients?
Reno-vascular Disease
Atheroembolic Disease
Systemic diseases – Case history
71 year old female
3/52 fever, anorexia, malaise, rigors
On examination temp 37.5-38 oC
BP 130/80
No cardiac murmurs
No organomegaly
Invesitgations:
Hb 101 g/l
WCC 15.4 x 109/l
Plat 608 x 109/l
ESR 105 mm/h
Na 134 mmol/l
K 3.6 mmol/l
Creatinine 195 umol/l
Urea 7.3 mmol/l
Albumin 28 g/l
Alk phos 360 u/l
Sigmoidoscopy Normal
Ba enema Normal
ERCP Normal
CT thorax/abdo Small pleural effusions
what is the intial management?
Treatment with antibiotics
However, no improvement, remained pyrexial
invesitgations/course:
Urinalysis - blood +++ , protein ++
pANCA positive, raised anti MPO antibodies
Renal biopsy - Focal necrotising GN
Diagnosis - Microscopic polyarteritis
Treatment - Cyclophosphamide, prednisolone
Outcome - Creatinine 120 umol/l after 3/12
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
Nomenclature of vasculitis - Aorta/large artery
Takayasu arteritis
Giant cell arteritis
Nomenclature of vasculitis - medium artery
Polyarteritis nodosa
Kawasaki disease
Nomenclature of vasculitis - Small vessel
Wegener’s granulomatosis
Microscopic polyarteritis
Churg-Strauss syndrome
What is Wegener’s granulomatosis and who does it occur in?
Granulomatous inflammation in respiratory tract
Focal necrotising glomerulonephritis with crescents
Slightly more common in males
Affects all age groups, most common 40-60 y
haracterized by inflammation in various tissues, including blood vessels (vasculitis), but primarily parts of the respiratory tract and the kidneys
Where does Wegener’s granulomatosis and what is its effects?
Upper respiratory tract - Epistaxis, nasal deformity, sinusitis, deafness
Lower respiratory tract - Cough, dyspnoea, haemoptysis; Pulmonary haemorrhage
Kidney - glomerulonephritis
Joints - arthralgia, myalgia
Eyes - scleritis
Heart - pericarditis (inflammation of the pericardium)
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
a form of necrotizing small vessel vasculitis that most often affects venules, capillaries, arterioles, and small arteries, although it occasionally involves medium-sized arteries
how is a diagnosis in vasculitis done?
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 is ANCA?
Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against antigens found in the cytoplasmic granules of neutrophils and monocytes. ANCA testing is usually performed to help diagnose or exclude Wegener’s granulomatosis and microscopic polyangiitis
what is Infective endocarditis?
infection of the endocardium
what causes infective endocarditis?
Endocarditis: a result of bacterial (or fungal) infection on cardiac valves
Typical infections:
- Staphylococcus aureus
- Viridans streptococci
- Enterococci
How does infective endocrditis affect the kidneys?
Leads to glomerulonephritis ± small vessel vasculitis due to immune complex formation
Glomerulonephritis in infective endocarditis - renal involvement is suggested by what?
Abnormal urea/creatinine
Haematuria, red cell casts
Reduced complement levels
Renal disease should recover when underlying infection treated
what is a multiple myeloma?
A monoclonal proliferation of plasma cells producing an excess of immunoglobulins and light chains
a cancer that forms in a type of white blood cell called a plasma cell
who is multiple myeloma common in?
common in eldery
what are the clinical features of a multiple myeloma?
Markedly elevated ESR
Anaemia
Weight loss
Fractures
–nfections
Back Pain/Cord compression
how is a multiple myeloma diagnosed?
Bone marrow aspirate >10% clonal plasma cells
Serum paraprotein ± immunoparesis
Urinary Bence-Jones protein (BJP)
Skeletal survey - lytic lesions
how is renal failure present in a myeloma?
Cast nephropathy - ‘myeloma kidney’
Light chain nephropathy
Amyloidosis
Hypercalcaemia
Hyperuricaemia
What is shown here?
Cast nephropathy
is the formation of plugs (urinary casts) in the kidney tubules from free immunoglobulin light chains leading to kidney failure in the context of multiple myeloma. It is the most common cause of kidney injury in myeloma
What is shown here?
Light chain disease: TBM Ig deposition
Light chain deposition disease (LCDD) is a rare blood cell disease which is characterized by deposition of fragments of infection-fighting immunoglobulins, called light chains (LCs), in the body. LCs are normally cleared by the kidneys, but in LCDD, these light chain deposits damage organs and cause disease
What is shown here?
Amyloid
a rare disease that occurs when an abnormal protein, called amyloid, builds up in your organs and interferes with their normal function
When to suspect a systemic disease with renal involvement?
Is this common and what may be seen in the histry
Relatively rare but frequently missed
Outcome depends on prompt diagnosis and treatment
History: Fever, malaise, weight loss, arthralgia, myalgia, skin rash (vasculitic), gritty eyes, breathlessness, haemoptysis, epistaxis, haematuria, oedema
When to suspect a systemic disease with renal involvement?
what ssigns would you suspect on the hands, face and skin?
Hands - Splinter haemorrhages, purpura, Raynaud’s
Face - Scleritis, uveitis, nasal cartilage deformity, retinal vasculitis, hypertensive retinopathy
Skin - Vasculitic rash, scleroderma
When to suspect a systemic disease with renal involvement?
what CVS, chest, locomotor and CNS signs would you suspect?
CVS - Hypertension, murmur
Chest - Crepitations, haemoptysis
Locomotor - Joint swelling, tenderness
CNS - Stroke, encephalopathy
When to suspect a systemic disease with renal involvement?
what initial investigations would you do?
Urine:
- Blood/protein on urinalysis
- Microscopy - red cell casts
Blood:
- Elevated urea/creatinine
- Raised CRP
- Thrombocytosis, anaemia
- Raised alkaline phosphatase
what furthe rinvestigations may be done?
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, interstitital disease
Echocardiography
Biopsy:
Kidney
Nasal mucosa
Lung
Skin
In conclusion:
Systemic diseases are a rare but potentially _______ cause of renal disease
Need to consider when systemic symptoms±signs are present with abnormal urinalysis ± impaired renal function
Early treatment _________ renal function
treatable
preserves
