Systemic Disease And The Kidney Flashcards

1
Q

What three diseases are encompassed in ANCA vasculitis

A
Granulomatosis with polyangitits 
-wegeners granulomatosis 
Inflammation in the blood vessels small and large in the nose, sinuses, throats, lungs and kidneys, necrotising granulomatous inflammation and vasculitis of small and medium vessels -kidney RPGN with crescent formation 
cANCA 
Macroscopic polyangitis 
Associated with pANCA MPO 
No granulomatous inflammation
Eosinophilic granulomatosis with polyangitis 
Late onset progressive asthma 
High eosinophils
also called churg Strauss 
Nasal polyps 
Pulmonary infiltrates
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2
Q

WHat are the main presentations of kidney disease

A

Nephrotic syndrome
Nephritic syndrome
Abnormal kidney function found incidentally
Unexplained haematuria/proteinuria

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3
Q

What are the complications of diabetes

A
Microvascular
Neuropathy
Retinopathy
Nephropathy
Macrovascular 
Brain -stroke
Heart -CAD
PVD
Renal artery disease
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4
Q

What is diabetic kidney disease

A

Any kidney disease in a patient with diabetes no matter the underlying cause

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5
Q

What is diabetic nephropathy

A

Any kidney disease presumed to be caused by diabetes

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6
Q

What is diabetic glomerulonephropathy

A

Diabetic kidney disease proven with a biopsy changes that are caused by diabetes

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7
Q

How is kidney disease screened for in diabetes

A

eGFR but this being decreased would be a late complication so may be too late
Albuminuria is an early sign - 2 samples 3-6 months apart prefer MSU first thing in the morning
Also need to exclude physiological causes of albuminuria such as vigourous exercise, dehydration, and ill with a high fever
Some patients have deteriorating CKD but no proteinuria and patients can have albuminuria with normalcy renal function.

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8
Q

What other causes if kidney disease are those with diabetes likely to have or could have instead but have similar symptoms to diabetic nephropathy

A

Severed or persistent hypertension
Haematuria
Nephrotic syndrome
Rapidly deteriorating function

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9
Q

What other features would a patient need to have to diagnose diabetic nephropathy

A

Need to have other microvasuclar complication signs

Retinopathy and neuropathy

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10
Q

What is the pathology of diabetic glomerulopathy

A
Mesangial expansion
Inc deposits of ECM 
- mesangium, BM, tubulars-interstitium 
-vascular changes 
-fibrosis -> sclerosis
Kimmelstiel-Wilson nodules on pathology imaging
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11
Q

Risk factors for the development /progression of diabetes nephropathy

A
Modifiable 
-glycaemic control
-BP control 
-lifestyle factors salt intake, smoking 
RAS blockade -proteinuria 
-lipid control
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12
Q

Timeline of changes in those with diabetes to renal function

A

Pre diabetic nephropathy -hyperfiltration 0-5 years
Incipient diabetic nephropathy - dec eGFR, rising proteinuria not vast changes 5-15 years
Overt diabetic nephropathy eGFR drops significantly and proteinuria rises 15 -25 years
ESRF eGFR below 10 transplant, dialyse or palliative care

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13
Q

What are diabetic patients annually screened for

A

ACR
Retinal screening
Foot checks -sensory neuropathy

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14
Q

Diabetic nephropathy management

A
Optimism diabetes control
-diet exercise 
-anti diabetic medication  
Optimise blood pressure control 
-salt restriction 
-weight management 
-antihypertensives 
Treatment or micro albuminuria/proteinuria 
-ACE /ARB even in normal blood pressure 
Smoking cessation 
Other interventions under investigation -none in clinical use yet
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15
Q

What does ANCA stand for

A

Anti neutrophil cytoplasmic antibodies

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16
Q

What are the types of ANCA and what molecules are they against

A

Myeloperoxidase pANCA

cANCA Proteinase 3

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17
Q

How are ANCA detected

A

By direct immune fluorescence
Neutrophil fixed and stained ab in patients blood are tagged mixed together is they are on the neutrophil then that is the +be result and the type of ANCA

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18
Q

What syndrome to patients with vasculitis get

A
Nephritic syndrome
Haematuria proteinuria 
Oedema
Salt and water retention 
Usually AKI
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19
Q

How to treat vasculitis

A
Sooner the better to prevent irreversible loss of kidney function if untreated 80% die in 1-2years 
Immunosuppression 
Little amount necessary to control it 
To induce remission 
-corticosteroids-prednisolone 
Severe
- chemo agent, cyclophosphamide, rituximab, or plasma exchange 
Moderate mild
-mycophenolate mofetti
-methotrexate
To maintain remission 
- corticosteroids
\+
Azathioprine 
Mycophenolate mofetil
Methotrexate 
Rituximab
20
Q

How to ensure it is safe to immunosuppress someone

A

BBV screen HCV/HBV/HIV
Zoster immunity
Pneumocystis jerovicci -prophylactic ab
Adequate cancelling before cyclophosphamide -due to inc infection,cancer risk and infertility

21
Q

What is myeloma

A
Plasma cell cancer 
Plasma cells from B cells 
Plasma cell produce antibodies
Plasma cell too many of one single Ab 
Monoclonal Ab - abnormal
22
Q

Local effects of myeloma

A

Bones
Over expression of RANF receptor activator nuclear factor
Activates osteoclasts =resorbs bone
Cause lytic lesion - pepper pot skull, long bone, axial skeleton
Hypercalaemia

23
Q

Systemic affects of myeloma

A

Anaemia
Replacement of normal cells in the long bones with tumour cells
Inhibition of normal cell production by cytokines
Paraproteins -variety of effects in kidney
Susceptible to infection nor al Ig suppressed

24
Q

How to diagnose myeloma

A
CRAB criteria 
C - calcium- hypercalcaemia 
R - renal failure 
A - anaemia 
B - bone
25
Q

How does myeloma affect the kidneys

A
Hypercalcaemia 
- dehydration 
-directly toxic to the kidney 
Cast nephropathy 
NSAIDS to treat bone pain 
AL Amyloidosis -light chain causing fibrosis in kidneys 
MGUS can cause 
Monoclonal gammopathy of renal significance
26
Q

What determines the renal phenotype

A

Depends on the specific properties of the monoclonal Ig
Concentration of light chain the more light chain the more toxic
The local microenvironment in the kidneys - if you inc hydration and dec the hypercalcaemia help
Kappa -monomeric 40% renal clearance
Lambda - dimeric 20% renal clearance

27
Q

What is the pathogens of cast nephropathy

A

Light chain in freely filter in the kidney through the glomerulus into the renal tubule
The light chains are then reabsorbed in the kidneys by the receptor mediated endocytosis, this has a capacity of 10-30g a day and usually we produce 500mg/day so the kindle can usually handle this but with myeloma you can exceed to 10-30g the PCT can reabsorb so it cannot all be taken back to carries in to the loop of Henle
In the loops of Henle there is Tamm-Horsel protein THP
Combination of THP and LC
This causes cast in the ascending limb in the loop of Henle

28
Q

What promotes cast nephropathy

A
Promoters of THF aggregation 
-dehydration
-hypercalcaemia
-acidosis
- furosemide 
Light chain conc - risk renal damage is directly proportionate the the level of urinary free light chain excretion 
The properties of the light chain 
- some gave more affinity for THP due to different domains
29
Q

What happens once casts are deposited

A

They can cause inflammation in the interstitium
Rapid scarring that is not reversible can occur in 6weeks of the casts occurring
Majority of myeloma patients have some renal Impairment on presentation .

30
Q

Why is the renal disease such bad news in myeloma

A

Is it an independent risk factor fir death
Dec life expectancy presenting with renal impairment
If kidney function can be recovered prognosis is better

31
Q

How to investigate kidneys in myeloma

A

Myeloma screen
Immunoglobulins - results come back quickly may see an inc in a particular IG and dec in the others
Serum electrophoresis
Immunofixation
Urine electrophoresis -
Serum free light chain - determine abnormal light chain -light chain only myeloma, track response to treatment

32
Q

Why is it important to think myeloma

A
Slowest trajectory to diagnosis 
AKI
Bone pain 
High calcium
Non specifically unwell
Anaemia
Fatigue
Weight loss
Fracture
33
Q

Myeloma presentation with kidney damage

A

AKI
- paraprotien myeloma screen
-paraprotein not present and no other solid indication - biopsy
-paraprotein present
<500 - haematology follow up - kidney biopsy if haematology investigations inconclusive
>500 - myeloma cast nephropathy likely, urgent haem work up, kidney biopsy in bone marrow doesn’t indicate myeloma

CKD
Paraprotein absent - indication for biopsy -
Paraprotein present - indication for kidney biopsy
- full hisotological assessment including Congo red stain with examination by polarised light
Immuniflorescence for intact light chain Ig, electron microscopy

34
Q

How are myeloma patients managed

A
Supportive care 
-focus on hydration +urine output
- correct hypercalcaemia- IV fluids + bisphosphonate 
- correct the acidosis
- avoid diuretics 
- avoid nephrotoxic drugs 
Haematology assessment + management 
- bone marrow biopsy
-dexamethosone + bortezomib 
-  chemotherapy
35
Q

What is AL amyloidosis

A

Rarer complications
Low paraprotein abnormal serum free light chain
Proteins misfold to form amyloid fibrils
-deposit in tissues all over body
- symptoms depend on organs affected
Multisystem disorder
Infiltration into tissues
Diagnosed Congo red staining after biopsy
Phrenology bire refringence under polarised light
Macro gloss is -pathognomic
Peroribital bruising no trauma =amyloid

36
Q

Classification criteria of lupus

A
Clinical 
Acute cutaneous lupus 
Chronic cutaneous lupus 
Oral or nasal ulcers 
Non-scarring alopecia 
Synovitis 2 or more joints 
Serositis pleurisy pericarditis 
Renal
Neurological 
Autoimmune haemolytic anaemia 
Leukopenia 
Thrombocytopenia 
Immunologic 
ANA
anti dsDNA
Anti sm 
Antiphosoholipid ab 
Low complement 
Direct Coombs test 

4 criteria and at least 1 from each

37
Q

Common manifestations of lupus

A

Cutaneous
Butterfly rash
Skin photography sensitivity
Discoid lesions

Resp 
Lung pleurisy 
Diffuse alveolar haemorrhage uncommon but severe life threatening
Fibrosis 
Pulmonary embolism 
Broncholitits obliterans 

Cardiac
Uncommon
Commonest -pericarditis +- effusion
Mayo and endocarditis may occur

38
Q

Presentation of lupus nephritis

A
Proteinuria 
Nephrotic 
Low serum albumin oedema 
Life threatening can be nephritic 
There are many presentation as the disease can affect the kidneys in many ways
AKI, CKD, ESRF
39
Q

What is the 6 stage classification for lupus nephritis

A
Class 1 minimal change
2proliferaration 
3 focal nephritis - vasculitis 
4 diffuse
5 membranous 
6 sclerotic
40
Q

Pathophysiology of SLE

A

Auto and Indy production against several different target antigens

Innate susceptibility plus environmental factors can cause autoimmune proliferation

If you are less able to immune regulate and clear dead cells get a bigger inflammation which can lead to autoimmunity if you are less able to immune regulate and clear dead cells get a bigger inflammation which can lead to autoimmunity

Viral infection bacterial infection and UV light can trigger the development of autoimmunity

Autoimmune proliferation can be dendritic activation B-cell proliferation and T-cell activation ->. Which causes auto Ab production such as ANA but most people have this and there is no evidence of disease

Multiple genetic polymorphisms interact with environmental exposures
Threshold environmental stimulation in susceptible individuals
Non susceptible equals lots of triggers but no auto antibodies
Susceptible = a few triggers leads to autoantibody production
Many triggers = full blown disease

41
Q

Treatment of SLE

A

This depends on the severity
Mild cutaneous lupus might be treated with topical steroids & hydrchloroquine
Severe lupus may need remission induction treatment with high-dose steroids cyclophosphamide or rituximab or plasma exchange
Maintenance therapy may be needed with low dose steroids azathioprine or mycophenolate mofetil or rituximab every 6 to 12 months

42
Q

What is good pastures syndrome

A

Rare condition associated with pulmonary haemorrhage and RPGN

43
Q

What is good pastures caused by

A

Anti-GBM ab against type IV collagen

Associated with HLA DR2

44
Q

What is found on renal biopsy

A

Linear IgG deposits along the BM

45
Q

Mx of good pastures syndrome

A

Plasma exchange - plasmapheresis
Steroids
Cyclophosphamide