Kidneys in Systemic Disease Flashcards
Why are the kidneys a particular target for any systemic diseases?
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
Name common systemic diseases which can effect the kidney
- Diabetes mellitus
- Myeloma
- Amyloidosis
- Hemolytic uremic syndrome (HUS) is a condition that affects the blood and blood vessels.
What are the CVS diseases which can effect the kidneys?
- Cardiac failure
- Atheroembolism
- Hypertension
- Atherosclerosis
What are infectious diseases which can effect the kidneys?
- Sepsis
- Post-infectious glomerulonephritis
- Infective endocarditis
What are the diseases which causes inflammation of blood vessels can effect the kidneys?
Systemic lupus erythematosus (SLE)
Vasculitis
Scleroderma and other connective tissue diseases
Cryoglobulinaemia (blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins)
What drugs can effect the kidneys?
- Aminoglycosides
- NSAIDs
- ACE inhibitors
- Radiocontrast
- Penicillamine, gold
What is diabetic nephropathy?
Divided into five stages of deterioration, with the final one being ESRD.
What are the stages of diabetic nephropathy?
- Silent sub-clinical phase: hyperfiltration + increased GFR due to increase glomerular blood flow (glomerular hypertension)
- Microalnuminuria filtered through tubule
- Clinical nephropathy (macroproteinuria which can be detected in the urine)
- Established renal failure (less proteinuria as kidneys have failed)
Describe the long term risk in Type I diabetes in diabetic nephropathy
4% with Type 1 DM will develop nephropathy within 10 years
25% with Type 1 DM will develop nephropathy within 25 years
Describe the long term risk in Type II diabetes in diabetic nephropathy
10% with Type 2 DM will have nephropathy by 5 years
30% with Type 2 DM will have nephropathy by 20 years
What are the features of diabetic nephropathy?
Diabetic nephropathy develops over many years
Type I and Type II patients are equally at risk
Increasing proteinuria is usually associated with declining GFR
Diabetic nephropathy is the single commonest cause of ESRF leading to the need for dialysis or transplantation
What is the classification of chronic kidney disease?
NKF Kidney Disease Outcomes Quality Initiative (NKF KDOQI)
Describe the different stages of NKF Kidney Disease Outcomes Quality Initiative (NKF KDOQI) for chronic kidney disease
Stage 1: kidney damage / normal or high GFR (GFR > 90)
Stage 2: kidney damage / mild reduction in GFR (GFR 60-89)
Stage 3: moderately impaired (GFR 30-59)
Stage 4: severely impaired (GFR 15 - 29)
Stage 5: advanced or on dialysis (GFR <15)
What is the relationship between CVS disease and chronic kidney disease?
More likely to die of CVS disease than requiring dialysis
Hypertension, congestive heart failure or ischaemic heart disease, LV hypertrophy (caused by hypertension)
In over 65s, what is the most common cause of renal failure?
Reno-vascular disease
In under 65s, what is the most common cause of end-stage kidney disease?
Diabetes
What are the features of atheroembolic disease (common cause of renal failure in elderly)?
Eosinophilia
Peripheral Skin lesions
Treatment:
Warfarin Therapy
Vascular Procedures
Name two types of vasculitis of aorta/large arteries
Takayasu arteritis
Giant cell arteritis
Name two types of vasculitis of medium arteries
Polyarteritis nodosa
Kawasaki disease
Name three types of vasculitis of small vessels
Wegener’s granulomatosis (or granulomatous polyarteritis)
Microscopic polyarteritis
Churg-Strauss syndrome
What are the features of Wegener’s granulomatosis (or granulomatous polyarteritis)?
- Granulomatous inflammation in resp. tract
- Focal necrotising glomerulonephritis with crescents
- Slightly more common in males
- Affects all age groups, most common 40-60yrs
What are the symptoms of Wegener’s granulomatosis?
Upper resp. tract:
• Epistaxis, nasal deformity, sinusitis, deafness
Lower resp. tract:
• Cough, dyspnoea, haemoptysis
• Pulmonary haemorrhage
What is the effect of Wegener’s granulomatosis on the kidneys?
Glomerulonephritis
What are other body manifestations of Wegener’s granulomatosis?
- 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
What is the diagnosis in vasculitis?
- Urine - blood/protein
- Renal function - raised urea/creatinine
- Biochemistry - raised alk phos, CRP, low albumin
- Haematology - anaemia, thrombocytosis, leukocytosis
- Immunology - hyperglobulinaemia and positive ANCA
- Renal biopsy
What is an important investigation for vasculitis?
Detection of Antineutrophil cytoplasmic antibodies (ANCA)
What are two methods of detection of ANCA?
- P-ANCA acting on myeloperoxidase antibodies in ELISA
* C-ANCA acting on proteinase 3 in ELISA
Describe the results of ANCA for Wegener’s granlomatosis
> 90% C-ANCA
Describe the results of ANCA for microscopic polyarteritis
P-ANCA
What is infective endocarditis?
Bacterial (or fungal) infection on cardiac valves
What bacteria typically cause infective endocarditis?
Staphylococcus aureus
Viridans streptococci
Enterococci
How does infective endocarditis affect the kidneys?
Leads to glomerulonephritis ± small vessel vasculitis due to immune complex formation
Chronic inflammation -> chronic activation of immune system -> immune complexes deposited in renal tubule causing inflammation
How does glomerulonephritis present in infective endocarditis?
- Abnormal urea/creatinine
- Haematuria, red cell casts
- Reduced complement levels
Renal disease should recover when underlying infection treated
What is multiple myeloma?
Cancer of plasma cells, a type of white blood cell typically responsible for producing antibodies
A monoclonal proliferation of plasma cells producing an excess of immunoglobulins and light chains (of the Ig)
What are the clinical features of multiple myeloma?
- Markedly elevated ESR
- Anaemia
- Weight loss
- Fractures
- Infections
- Back Pain /Cord compression
How is multiple myeloma diagnosed?
- Bone marrow aspirate >10% clonal plasma cells
- Serum paraprotein ± immunoparesis (hypogammaglobulinemia)
- Urinary Bence-Jones protein (BJP) - immunoglobulin light chain found in the urine
- Skeletal survey - lytic lesions (destruction of bone)
How does multiple myeloma cause renal failure?
- Cast nephropathy - ‘myeloma kidney’ (renal failure resulting from urinary excretion of monoclonal immunoglobulin light chains or Bence Jones proteins)
- Light chain nephropathy
- Amyloidosis
- Hypercalcaemia
- Hyperuricaemia
What is amyloidosis?
Build-up of an abnormal protein called amyloid in organs and tissues throughout the body. The build-up of amyloid proteins (deposits) can make it difficult for the organs and tissues to work properly.
With what symptoms should renal involvement be suspected. with systemic disease?
Fever, malaise, weight loss, arthralgia, myalgia, skin rash (vasculitic), gritty eyes, breathlessness, haemoptysis, epistaxis, haematuria, oedema
With what signs should renal involvement be suspected. with systemic disease?
Hands:
Splinter haemorrhages, purpura, Raynaud’s disease
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 is Raynaud’s disease?
Affects fingers and toes — to feel numb and cold in response to cold temperatures or stress.
In Raynaud’s disease, smaller arteries that supply blood to your skin narrow, limiting blood circulation to affected areas (vasospasm).
What is uveitis?
Inflammation of the uvea — the middle layer of the eye that consists of the iris, ciliary body and choroid.
What are the initial investigations are used to determine renal involvement?
Urine:
• Blood/protein on urinalysis
• Microscopy - red cell casts
Blood: • Elevated urea/creatinine • Raised CRP • Thrombocytosis, anaemia • Raised alkaline phosphatase
What further blood tests are used to determine renal involvement?
- ANCA (anti-MPO/anti-PR3 antibodies)
- ANA, dsDNA antibodies
- Complement levels C3, C4
- Blood cultures
What further radiological tests are used to determine renal involvement?
- CXR
- USS abdomen
- Renal size
- CT thorax
- Pulmonary granulomas, interstitital disease
- Echocardiography
What further biopsy tests are used to determine renal involvement?
- Kidney
- Nasal mucosa
- Lung
- Skin
