RENAL - KIDNEY DISEASE Flashcards
1
Q
What are the functions of the kidneys?
A
Elimination of metabolic waste
Water homeostasis
Electrolyte homeostasis
Acid base homeostasis
Blood pressure control
Synthesising vitamin D, EPO and renin
Excretion of drugs and drug metabolites
2
Q
Explain why there is a non-linear relationship between serum creatinine and kidney function?
A
Kidney function needs to drop by 50% before creatinine levels become abnormal I.e. its no sensitive to small changes in function
3
Q
What is eGFR calculated from?
A
Creatinine, age, gender ethnicity
4
Q
Why do we use eGFR for chronic kidney disease not acute?
A
Because its the best measure for use when stable renal function
5
Q
How do we classify CKD?
A
EGFR <60 or kidney damage
Must be present for over 3 months
6
Q
What is the staging for CKD?
A
EGFR stages
g1 - >90
G2 - 60-89
G3a - 45-59
G3b - 30-44
G4 - 15-29
G5 - <15
Or ACR categories. <3 is A1, 3-30 is A2 and >30 is A3
7
Q
What’s the eGFR threshold for symptoms?
A
<30
8
Q
Do you always see urine volume decrease in kidney disease?
A
No. In slowly progressive kidney disease can see urine volume actually increase, as failing tubular function leads to a salt and water wasting state. This is because the concentrating ability in the tubules fails
9
Q
What are the risk factors for CKD?
A
Age, hypertension, diabetes, smoking, poor socioeconomic status, use of nephrotoxic medications
10
Q
What are some causes of CKD?
A
Diabetes or hypertension
Atherosclerosis
Immune mediated diseases e.g. membranous nephropathy, IgA nephropathy and SLE
Drugs
Infectious diseases e.g. HIV, HBV, TB, HCV
Polycystic kidneys
Obstructions e.g. tumours or stone
11
Q
Normally CKD is asymptomatic but what signs and symptoms may suggest it?
A
Pruritus
Loss of appetite
Nausea
Oedema
Muscle cramps
Peripheral neuropathy
Pallor
Hypertension
12
Q
How do we investigate CKD?
A
EGFR from U&E blood test - 2 tests required 3 months apart
Urine dipstick for proteinuria and haematuria
Renal ultrasound
13
Q
What must eGFR be for a diagnosis of CKD?
A
<60 (or proteinuria)
14
Q
Why can anaemia occur in CKD?
A
EPO deficiency
But it can also be from a number of other causes… increased blood loss, bone marrow toxins, haematuria deficiency, increased red cell destruction, ACEi use
15
Q
How much does CKD increase the risk of cardiovascular disease?
A
16 fold
16
Q
Why can CKD cause pruritus?
A
Accumulation of nitrogenous waste products of protein catabolism
Iron deficiency
Hyperparathyroidism
Hypercalcaemia and hyperphosphataemia
17
Q
What are some complications of CKD?
A
Cardiovascular disease
Hypertension
Oedema
Electrolyte abnormalities
Metabolic acidosis
Mineral-bone disease
Anaemia
Uraemia
Altered drug metabolism
18
Q
What are some general measures for managing CKD?
A
Treat any modifiable underlying cause
Address CVD risk factors e,g, smoking cessation, exercise, weight loss
Avoid nephrotoxic drugs
Immunise against influenza and pneumococcus
19
Q
How do we correct hyperkalaemia in CKD?
A
FAR
Force K+ into cells - 20 ml 10% dextrose and 10-20 units of insulin. Or sodium bicarbonate. Or beta 2 agonist like salbutamol
Antagonise K+ - 10ml 10% calcium gluconate
Remove K+ - sodium-calcium resonium or dialysis as a last resort
20
Q
Which drugs must be stopped in CKD?
A
Contrast media
ACEi/ ARBs
NSAIDs
Diuretics
Anti-microbials - Aminoglycosides, sulfamethoxazole, penicillins, rifampicin, amphoterecin, aciclovir
Anti convulsants - lamotrigine, valproate, phenytoin
Lithium
Anaesthetic agents - methoxyflurane and enflurane
Ethylene glycol
21
Q
What causes renal bone disease?
A
We get low active vitamin D which is essential in calcium absorption from the intestines and kidneys
Secondary hyperparathyroidism occurs due to parathyroid glands reacting to low serum calcium and high serum phosphate - this increases osteoclast activity = absorption of calcium from bone
22
Q
How quick does AKI come on?
A
Hours - days
23
Q
How to we measure AKI?
A
Using creatinine and urine output
24
Q
What are the creatinine and urine output values for stage 1 AKI?
Stage 2?
Stage 3?
A
Stage 1 - 50-100% creatinine increase. Or <0.5ml/kg/hour for 6 hours urine
Stage 2 - 100-200% creatinine increase. Or <0.5ml/kg/hour for 12 hours urine
Stage 3 - >200% creatinine increase or <0.3ml/kg/hour for 24 hours or anuria for 12 hours or needs dialysis
25
What are the risk factors for AKI?
Older age
Diabetes
Hypertension
Heart disease
Liver disease
CKD
Meds - diuretics, ACEi/ARB, NSAID, gentamicin, vancomycin, chemotherapy
26
What are pre-renal causes of AKI?
Perfusion failure e.g hypovolemia, hypotension, low cardiac output or blockage of renal artery
Medications
27
What are common intra-renal causes of AKI?
Diseases that affect the kidney tissue e.g. vascular is, SLE, multiple myeloma, interstitial nephritis
28
What are post-renal causes of AKI?
Obstruction to urinary system e.g, stones, tumours, blocked catheters
29
What are the main complications of AKI?
Death
Infections
Anaemia
Metabolic acidosis
Hypertension
CKD
Altered drug metabolism
Oedema
Electrolyte abnormalities
30
What are the clinical signs of nephrotic syndrome?
Heavy proteinuria (>3.5g/day) which also leads to hypoalbuminaemia
Peripheral oedema due to salt and water retention
Hyperlipidaemia and lipiduria
Loss of antithrombin III (and protein S and C)
Loss of thyroglobulin and vitamin D
Marked peripheral pitting oedema, pleural effusion, pericardial effusion and ascites
Hypercoagulability
Hypertension (not s marked as nephritic)
Frothy urine
31
What are the causes of nephrotic syndrome?
When the glomerular filtration barrier is damaged leading to increased protein leak
focal segmental glomerulosclerosis
membranous glomerulonephritis
minimal change disease
diabetic nephropathy
Amyloidosis
32
What are the complications of nephrotic syndrome?
Thromboembolism
Infections
Hyperlipidaemia
Malnutrition
CKD and occasionally AKI
33
Why can nephrotic syndrome cause thromboembolism?
increased excretion of antithrombotic factors by the affected kidneys and increased production of pro-thrombotic factors by the liver.
34
How do we treat nephrotic syndrome?
Loop diuretics
Salt restriction
ACEi or ARBs to reduce proteinuria
Thrombo-prophylaxis
Treat underlying cause
35
Why can nephrotic syndrome cause Hyperlipidaemia?
Due to increased synthesis of lipoproteins as a direct consequence of low plasma albumin
36
What are some primary causes of nephrotic syndrome?
Minimal change nephropathy
Congenital nephrotic syndrome
Focal segmental glomerular sclerosis
Membranous nephropathy
37
What are some secondary causes of nephrotic syndrome?
Amyloidosis
Diabetic nephropathy
38
What are the clinical features of minimal change disease?
Most common in children, particularly boys
Proteinuria is highly selective where albumin, but not higher molecular weight proteins are lost in urine
Oedema is usual and in children presents mostly around the face
Accounts for 25% of adult nephrotic syndromes
Doesn’t lead to CKD
Minimal changes on light microscopy but electron microscopy shows fusion of the foot processes of podocytes
Treated with high dose prednisolone
39
What’s the pathophysiology of minimal change disease?
Effacement of foot processes in glomeruli
40
What’s the pathophysiology of congenital nephrotic syndrome?
An autosomal recessive lay inherited disorder due to mutations in the gene coding for nephron. This loss of function results in massive proteinuria shortly after birth
41
What is focal segmental glomerulosclerosis?
Progressive glomerular scarring that can occur in all ages
Present as massive, non-selective proteinuria, haematuria, hypertension and renal impairment
42
What is amyloidosis?
a group of rare, serious conditions caused by a build-up of an abnormal, insoluble protein called amyloid in organs and tissues throughout the body
Can affect the kidneys, manifesting as nephrotic syndrome
43
Outline the pathology of diabetic nephropathy?
glucose will non-enzymatically combine with proteins and lipids to form pro-inflammatory molecules (non-enzymatic glycation). These molecules cause inflammation of efferent arteriole leading to arteriosclerosis. Overall effect is thickening of arteriole which increases the pressure proximal to the arteriole which causes an increase in GFR. Mesangial cells respond by secreting transforming growth factor beta = extracellular matrix release = fibrosis (glomerulosclerosis) = drops GFR
44
What are the clinical features of nephritic syndrome?
Proteinuria <3G a day. May have frothy urine
Haematuria (macroscopic or microscopic) - Cola coloured urine
Sterile pyuria (raised WCC in urine but no growth on cultures)
Hypertension
Temporary oliguria or uraemia
Azotemia
Oedema - liver can compensate for quite a bit of this so less marked than in nephrotic syndrome
45
What are some of the causes of nephritic syndrome?
Anything that damages the glomerular endothelium and causes inflammation or is immune mediated
Rapidly progressive GN
IgA nephropathy
Henoch-schonein purpura
Alport syndrome
Haemolytic uraemic syndrome (HUS)
SLE
Anti-GBM GN
ANCA vasculitis
46
What is post-streptococcal glomerulonephritis?
Occurs in childhood
Acute nephritis 1-3 weeks after a group A streptococcal infection (streptococcal throat infection, otitis media or cellulitis)
Caused by immune complex deposition in glomeruli (type 3 hypersensitivity)
Presents with flu-like sympotms, haematuria, proteinuria, hypertension and oliguria
47
What is IgA nephropathy?
The most common form of glomerulonephritis worldwide
Presents with asymptomatic haematuria and (classically) 12-72 hours after an upper RTI
Associated with HSP, coeliac disease and alcohol cirrhosis
48
What age group does IgA nephropathy tend to present in?
Teens-late thirties
49
What is Alports syndrome?
A rare hereditary nephritis characterised by chronic kidney disease, hearing loss and eye abnormalities
X-linked dominant inherited disease due to a defect in type IV collagen = abnormal GBM
50
What is the mortality from patients with AKI?
About 50%
51
Is pre-renal, renal or post-renal the most common cause of kidney failure?
Pre-renal
52
What is the surgical triad for common cause of hospital acquired AKI?
Post-operative volume depletion
Infection
Nephrotoxic drugs
53
Which drugs are nephrotoxic?
ACEi and ARB - cause efferent vasodilation
NSAIDs - cause afferent vasodilation
PPIs - cause interstitial nephritis
Aminoglycosides
Contrast mediums
54
What is acute uraemia?
A rise in blood urea and other products of metabolism which is often but not invariably accompanied by oliguria
55
What is oliguria?
A volume of urine below which at maximum urinary concentration the body cannot excrete the products of metabolism
A decrease in urine output relative to fluid input of <0.5mg/kg/h for 12 hours
56
What would you see on ECG in hyperkalaemia?
Tenting of T waves
Widening of QRS
Disappearance of p waves
Sine wave pattern
57
What clinical methods are used to assess intravascular fluid volume?
Body weight
Skin turgor
Postural bp
Mucous membranes
JVP
Lung bases
58
What does absolute anuria mean until proven otherwise?
Urinary tract obstruction
59
What is RIFLE classification?
Risk - GFR decreases >25%
Injury - GFR decreases >50%
Failure - GFR decreases >75%
Loss - dialysis dependant >4 weeks
End stage kidney disease - dialysis dependant >3 months
60
What is oliguria?
<400mls/day or <0.5ml/kg/hour
61
What is anuria?
No urine output I.e. <50mls/day
62
What do we think when we see macroscopic haematuria compared to microscopic?
Macroscopic usually indicates bleeding within the urinary tract
Microscopic more commonly indicates glomerular haematuria
63
What are the common sites of obstruction in post renal renal failure?
Bilateral pelvicoureteric junction
Bilateral ureteric junction
bladder outflow
Urethra
64
Which hormones does the kidney produce?
1,25 dihydroxy D3
EPO
Renin
65
What are some symptoms and signs of uraemia?
Anorexia
Change in taste
Nausea
Vomiting
Pruritis
Neuropathy
Pericarditis
Confusion
Encephalopathy
Coma
66
What are some common symptoms of hypovolemia seen in an AKI?
Thirst, orthostatic symptoms and postural hypotension
67
What is secondary glomerulonephritis?
When the kidney damage is as a result of another disease process
68
Why do patients with nephrotic syndrome have an increased risk of infection?
Due to losses of immunoglobulins and immune mediators in the urine
69
What’s the difference between the oedema seen in nephrotic syndrome and the oedema in nephritic syndrome?
In nephrotic syndrome low oncotic pressure due to hypoalbuminaemia and high hydrostatic pressure from fluid retention
in nephritic syndrome oliguria causes na+ and water retention
70
What are the main 2 causes of nephrotic syndrome in children?
Minimal change disease
Focal segmental glomerulosclerosis
71
What are the main causes of nephrotic syndrome in adults?
Membranous glomerulonephritis
Focal segmental glomerulosclerosis
Diabetic nephropathy
SLE, amyloidosis, Hep B C and HIV
72
What is steroid responsive nephrotic syndrome?
Because most children with nephrotic syndrome will have MC disease and most will respond to steroids, you can treat without a biopsy - this is what we call steroid responsive nephrotic syndrome
73
What is relapsing nephrotic syndrome?
When children relapse on steroid withdrawal
74
What is steroid dependant nephrotic syndrome?
Children who need continuous steroid therapy
75
What is steroid resistant nephrotic syndrome and what is the likely cause?
Children who’s nephrotic syndrome does not respond to steroids
They need a biopsy
Usually caused by inherited abnormalities of podocyte proteins or quite often focal segmental glomerulosclerosis
76
What is the most common cause of nephritic syndrome in children?
Post-streptococcal glomerulonephritis
77
What’s the most common cause of nephritic syndrome in adults?
IgA nephropathy
78
Briefly outline the pathophysiology of post-streptococcal glomerulonephritis?
Streptococcal antigens deposit in the glomerulus forming immune complexes and causing inflammation
79
What is Henoch-Schonlein purpura?
an inflammation of the small blood vessels of the skin, joints, bowels and kidneys.
It can cause nephritic syndrome
Presents with a rash on extensor surfaces, polyarthtisi, abdominal pain, GI haemorrhage
80
Why is the histology crescentic in rapidly progressive glomerulonephritis?
Because sudden breaks in the glomerular basement membrane allow an influx of inflammatory cells
81
How does anti-GBM antibody disease present?
Rapid renal function decline and pulmonary haemorrhage (SOB and haemoptysis)
82
What’s the classical presentation of IgA nephropathy?
Visible haematuria 1-2 days following an upper resp tract infection
83
What lesions are commonly seen histologically in diabetic nephropathy?
kimmelsteil wilson lesions
84
What are the 3 types of amyloidosis?
AL (primary)
AA (secondary)
Familial ATTR amyloidosis
85
What are some secondary causes of nephrotic syndrome?
Diabetes
Lupus
Amyloidosis
Malaria
Hep B and C
HIV
SLE
Drugs - gold, NSAIDs, heroin, lithium
Malignancies - lymphoma and leukaemia
86
What can cause pre-renal azotemia?
Absolute fluid loss e.g. haemorrhage, vomiting, diarrhoea, severe burns
Relative fluid loss - congestive heart failure causing low CO, hypotension, NSAID use, ACEi ARB use, cyclosporine use
87
What causes azotemia?
High serum levels of nitrogen and creatinine
88
What can cause intra-renal azotemia?
Acute tubular necrosis
vascular causes e.g. vasculitis
Acute tubulointerstitial nephritis
Glomerulonephritis (aka nephritic syndrome)
89
What are the 3 types of ATN?
Ischemic-Induced Acute Tubular Necrosis e.g. MI or haemorrhage
Nephrotoxic-Induced Acute Tubular Necrosis (aminoglycosides, myoglobin secondary to rhabdomyolysis, radiocontrast agents, lead)
Sepsis-Induced Acute Tubular Necrosis.
90
What are some nephrotoxins that can cause acute tubular necrosis?
Aminoglycosides
Heavy metals
Myoglobin
Uric acid in tumour lysis syndrome
91
What is acute tubulointerstitial nephritis?
What can cause it
inflammation that affects the tubules of the kidneys and the interstitium
Hypersensitivity reaction to drugs such as penicillins, NSAIDs or PPIs.
It can also be caused by infections e.g. pyelonephritis
92
What can cause a post-renal AKI?
BPH
Tumours
Stones
93
Is pre-renal AKI reversible?
Yes but prolonged can lead to ischaemic intra-renal AKI
94
How can you investigate pre-renal causes of AKI?
Check fluid status of patient
Calculate fractional excretion of Na+ and urea
95
How can you investigate intra-renal causes of AKI/
Urinanalysis
Urine microscopic sensitivity
Urine casts
Renal ultrasound
Urine creatinine ratio and albumin creatinine ratio
(Think about intra causing inflammation = WBC casts. Alternatively glomerulonephritis causing haematuria)
96
How can we investigate post renal causes of AKI/
Bladder scan for urinary retention
Check catheter to see if its blocked/kinked
Imaging to check for obstruction
97
What are the indications for acute dialysis?
Acidosis (refractory)
Electrolyte imbalance (refractory severe hyperkalaemia)
Intoxication (Salicyclic acid, Lithium, Isopropanol, Magnesium laxatives, Ethylene glycol)
Overload with fluid
Uraemic complications e.g. pericarditis, platelet dysfunction
98
What should you be thinking when you see a raised MCV and raised GGT?
Alcohol!
99
Why can hypertension cause kidney failure?
We get thickening of vessel walls and luminal narrowing of the small arteries and arterioles which leads to chronic ischaemia and gradual loss of nephrons
100
Outline how atherosclerotic renal disease can cause secondary hypertension?
Hypoperfusion of the kidney causes renin release -> angiotensin 2 release -> aldosterone release -> increased blood volume due to sodium and water retention -> hypertension
101
What is interstitial nephritis?
A type 1 hypersensitivity reaction usually in response to antibiotics, NSAIDs or diuretics
102
Outline the investigations for renal failure?
Urinanalysis and cultures
ABG - for acidosis
VBG - hyperkalaemia, raised urea and creatinine
CXR, AXR and ultrasound
Renal biopsy
ECG to look for hyperkalaemia
103
What is hydronephrosis?
The swelling of the kidneys due to a build up of urine - indicates a backward pressure
104
Why should you treat complications of AKI before the cause?
Because the complications will kill you faster
105
Outline management for AKI?
Protect myocardium from hyperkalaemia - calcium gluconate
Remove K+ - insulin and dextrose
Diuretics for pulmonary oedema
Bicarbonate for any acidosis (or dialysis if refractory)
Then treat underlying cause
106
What are the indications for dialysis?
Complications of uraemia e.g. encephalopathy
Refractory hyperkalaemia
Refractory fluid overload
Anuria
107
Why is the BUN: creatinine ratio so important to look at?
As acutely urea will go up faster than creatinine (larger ratio)
But chronically creatinine will be higher than urea (smaller ratio)
108
What GFR is end-stage renal failure?
<15ml/min
109
What are the 3 most common causes of CKD?
DM
Hypertension
Glomerulonephritis
110
What are come manifestations of CKD?
Peripheral neuropathy, restless leg syndrome, fatigue - urea affects nervous system
Taste perception
Accelerated atherogenesis!!!
Renal osteodystrophy and bone cysts
Electrolyte imbalances
Anaemia of chronic disease (EPO)
Bruise easily (impaired platelet function due to uraemia)
111
What do most CKD patients die of and why?
Heart disease due to accelerated atherosclerosis
112
Why does CKD cause renal osteodystrophy?
reduces absorption of calcium due to failure of hydroxylation of 25-dehydroxycholecalciferol. This low calcium level leads to hyperparathyroidism.
113
How can we reduce the risk of heart disease in CKD patients?
We prescribe all CKD patients statins
BP control, blood sugar control etc
114
What is a renal diet?
low in sodium, phosphorous, and protein. Some patients may also need to monitor potassium and calcium too
115
What’s a normal potassium range?
3.5-5.0mmol/l
116
What is mild hyperkalaemia? And what is severe?
5-6mmol/l is mild
>6mmol/l is severe (or a lower level but with ECG changes)
117
What are the main causes of hyperkalaemia?
Renal failure
Drugs - combination of ACEi, K+ sparing diuretics and NSAIDs
Increased K+ release - acidosis, haemolysis, cytotoxic drugs, rhabdomyolysis
118
What do we worry about when hyperkalaemia is accompanied by acidosis?
Ventricular tachyarrythmias
119
Although its usually asymptomatic, what symptoms can be seen with hyperkalaemia?
Muscle weakness and flaccid paralysis
120
How do you treat severe hyperkalaemia?
Protect the myocardium from K+ - 10ml 10% calcium glauconate IV
Remove K+ from the blood using 10 units actrapid insulin (check blood glucose!) and 50ml 50% dextrose IV.
You may give calcium resonium
you may also give 2.5mg salbutamol as this will also help drive K+ into cells
121
Outline who we screen for CKD and how?
Those taking medicines that can adversely affect kidney function such as lithium or NSAIDs should have their GFR monitored at least annually
122
How does screening for CKD happen after an AKI?
You should monitor patients for at least 3 years even if eGFR has returned to baseline
123
What are some symptoms that suggest CKD rather than AKI?
Fatigue
Weight loss
Anorexia
Nocturia
Pruritus
124
How does hypertension cause CKD?
Hypertension causes renal artery walls to thicken. Narrow lumen = ischaemic injury to nephrons glomerulus = immune cells secrete growth factors = mesangial cells regress to mesangioblasts which secrete extracellular matrix = glomerulosclerosis (scarring) which diminishes the ability to filter the blood
125
How does diabetes cause CKD?
Non-enzymatic glycation = stiff and narrow efferent arterioles (hyaline arteriosclerosis) = increased pressure in glomerulus = hyperfiltration = mesangial cell expansion (glomerulosclerosis) = diminishes ability to filter blood
126
What electrolyte imbalances are present in CKD?
Hyperkalaemia
Hypocalcaemia
127
Which types of drugs are typically excreted directly via the kidneys?
Hydrophilic (hydrophobic must first undergo biotransformation before)
128
How does urinary pH impact excretion?
Drug ionisation changes depending on the alkaline or acidic environment. Increased excretion of weakly acidic drugs occurs with basic urine and vice versa.
129
What can impact kidney drug excretion?
Renal disorders
Age - kidney function naturally declines with ages
Pathologies that impact renal blood flow or urine flow e.g. congestive HF
130
Why are ACEi contraindicated in patients with bilateral renal artery stenosis?
due to risk of azotemia resulting from preferential efferent arteriolar vasodilation in the renal glomerulus.
131
What are the main causes of oedema?
Medication
Pregnancy
Underlying disease e.g. kidney disease, liver cirrhosis, congestive heart failure
132
What are the main causes of proteinuria?
Glomeruli disease
Urine infections
First warning of eclampsia in pregnancy
Intense exercise
Stress
Fever
Prolonged exposure to cold temperatures
133
What’s the structure of immunoglobulins?
they are heterodimic proteins composed of 2 heavy and 2 light chains. They are separated functionally into variable domains that bind antigens and constant domains that specify effector functions e.g. activating complement of binding to Fc receptors.
134
What are the 5 main classes of heavy chain C domains of immunoglobulins?
IgM, IgG, IgA, IgD, IgE
135
What’s the function of IgM?
They are membrane bound and found on the surface of immature and mature B cells.
They are the first antibody produced in primary response to an antigen
They are efficient in binding antigens with many repeating epitopes and activate the complement
Responsible for early stages of immunity
136
What’s the function of IgG?
The most abundant class with 4 isotopes.
They have the highest opsonisation and neutralisation activities
137
What’s the function of IgA?
expressed in mucosal tissues and secretions
Forms dimmers after secretion
First lune of defence against infection by microorganism
138
What’s the function of IgD?
Membrane bound immunoglobulin on the surface of matur B cels with no biological effector function known
139
What’s the function of IgE?
Found mainly in tissues
Associated with hypersensitivity reactions and defend against parasite infections
140
What’s the function of Th1 cells? What cytokines do they release?
They drive activation of monocytes, macrophages and cytotoxic T lymphocytes.
they have a key role in protection against intracellular pathogens
Release INF gamma and TNF alpha
141
What’s the function of Th2 cells? What cytokines do they release?
Drive antibody responses and promote eosinophil granulocyte functions
Protect against extracellular parasites and immune responses that underlie allergic disease
Secrete IL-4, IL-5 and IL-13
142
What’s the function of Th17 cells? What cytokines do they release?
Drive inflammatory responses, especially via recruitment of neutrophil granulocytes
Protect against fungal infections and have a role in chronic inflammatory diseases
Secrete IL-17
143
What’s the function of T follicular helper cells? What cytokines do they release?
helping B cells produce antibody against foreign pathogens.
Secrete IL-21
144
What’s the function of T regulatory cells? What cytokines do they release?
maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases
Secrete IL-10 and TGF-beta
145
What is the function of cytotoxic CD8 T cells?
They kill virus infected cells following recognition of viral peptide HLA class 1 complexes.
146
What are the 3 mechanisms that CD8 T lymphocytes can kill?
Cytotoxic granule proteins e.g. perforin
Toxic cytokines
Death inducing surface molecules
147
What’s the most common cause of AKI?
Infections and nephrotoxic drugs
148
What’s the definition of nephrotoxic drugs?
Any drugs who act directly on the kidneys
149
What are the diagnostic criteria for AKI?
A 50% or greater rise in serum creatinine known or presumed to have occurred within the past 7 days.
A fall in urine output to less than 0.5mL/kg/hour for more than 6 hours.
150
What’s the diagnostic criteria for a CKD?
CKD is a reduction in kidney function or structural damage present for more than 3 months
It includes all individuals with markers of kidney damage or those with an eGFR of less than 60ml/min/1.73m2 on at least 2 occasions 3 months apart
151
Why do we use eGFR for CKD and not AKI?
eGFR calculations assume that the level of creatinine in the blood is stable over days or longer
152
What are the 2 reasons that CKD can cause hypocalcaemia?
increased serum phosphorus and decreased renal production of 1,25 (OH)2 vitamin D.
153
Outline BUN:Cr, FENA and urine osmolality in pre-renal AKI?
BUN:Cr ratio >20:1 - this is because the functioning units of the kidney have not been affected so they can still excrete creatinine and retain urea as normal
Fractional excretion of sodium (FENA) <1% and urine osmolality >500 (very conc) - because urine urea is low and sodium and water follow the urea into the blood
154
Outline BUN:Cr, FENA and urine osmolality in intra-renal AKI?
BUN:Cr ratio will be <15:1 as urea can’t be reabsorbed and creatinine can’t be excreted (tubular cells damaged).
FENA is >2% and osmolality <350. The low GFR stimulates RAAS but kidney tubules can’t respond to aldosterone. Na+ and water follow urea into urine.
Doesn’t respond to fluid challenge
155
Outline BUN:Cr, FENA and urine osmolality in post-renal AKI?
Early stages - will resemble pre-renal AKI as kidney tubules are functioning BUN:Cr >20:1
In later stages it will resemble intra-renal AKI as kidney tubules are no longer functioning BUN:Cr <15:1
156
How do you rule out post-renal causes?
Renal ultrasound (alternatively CT, bladder scan etc)
157
What are the 3 ways in which glomerulonephritis can present?
asymptomatic urinary abnormalities
acute nephritis (nephritic syndrome)
rapidly progressive glomerulonephritis.
158
Which chromosome is most likely affected in autosomal dominant Polycystic kidney disease?
Chromosome 16
159
How can we measure renal plasma flow?
By measuring para aminohippuric acid
160
What proportion of renal flow is the GFR usually?
20%
161
What is a nephrostomy?
a thin, plastic tube (catheter) that is inserted through the skin on your back, and into a kidney - drains the kidney
162
Why are the kidneys and lungs commonly affected at the same time?
They both have plenty of basement membranes
163
When are ACEi Reno-protective?
In patients with renal disease and diabetes
164
What are the contraindications for ACEi?
hyperkalemia, renal artery stenosis, pregnancy, or prior adverse reaction to an ACEI including angioedema.
165
What can increase serum urea?
High protein diet
Increased catabolism e.g. surgery, infection, trauma
Steroid therapy
Renal disease
166
What can decrease serum urea?
Hepatic dysfunction
Physiological increased filtration e.g. pregnancy
Low protein diet
Reduced catabolism e.g. old age
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What form of investigation is diagnostic for kidney injury?
Renal biopsy
168
What associated sympotms are present with a obstruction in post-renal failure?
Vomiting
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How do you treat hyperphosphataemia
Phosphate binders e.g. calcium carbonate or calcium acetate
170
How do you treat uraemic encephalopathy?
Renal replacement therapy
171
Whats the classic picture of pulmonary oedema on x-ray?
Bat wing distribution of a heterogeneous opacity
Fluid filled fissure
Kerley B lines
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At what mean arterial pressure does perfusion to the kidney stop?
65mmHg
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How does acute interstitial nephritis present?
fever, rash, arthralgia
eosinophilia
mild renal impairment
hypertension
174
When should you refer to a nephrologist concerning an eGFR?
referring to a nephrologist from primary care if eGFR falls below 30 or progressively by > 15 in a year
175
Whats the difference between Contrast media nephrotoxicity and contrast-induced nephropathy?
Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within 3 days of the intravascular administration of contrast media. Contrast-induced nephropathy occurs 2 -5 days after administration.
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How can you prevent contrast induced nephropathy?
intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure
And stop metformin for a minimum of 48 hours and until the renal function has been shown to be normal - prevents lactic acidosis
177
Whats the most commonly isolated organism in peritonitis associated with peritoneal dialysis?
Staphylococcus epidermidis
178
On biopsy, what does a sample for post-streptococcal glomerulonephritis show?
IgG, IgM and C3 immune complex deposition
Endothelial proliferation with neutrophils
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Whats the most common type of glomerulonephritis in adults?
Membranous glomerulonephritis
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How does membranous glomerulonephritis present?
Nephrotic syndrome or proteinuria
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What can cause membranous glomerulonephritis?
Causes
idiopathic: due to anti-phospholipase A2 antibodies
infections: hepatitis B, malaria, syphilis
malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia
drugs: gold, penicillamine, NSAIDs
autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid
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How do you manage membranous glomerulonephritis?
ACEi or ARB to reduce proteinuria
Anticoagulation for high risk patients
Severe and progressive disease - corticosteroids and cyclophosphamide
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Whats the prognosis for membranous glomerulonephritis?
one-third: spontaneous remission
one-third: remain proteinuric
one-third: develop ESRF
184
What are the complications of nephrotic syndrome?
Increased risk of thromboembolism
Increased risk of acute coronary syndrome, stroke etc
CKD
Infections
Hypocalcaemia
185
Why can nephrotic syndrome increase the risk of thromboembolism?
increased excretion of antithrombotic factors by the affected kidneys and increased production of pro-thrombotic factors by the liver.
186
Why is there an increased risk of acute coronary syndrome and or stroke in nephrotic syndrome?
Due to the hyperlipidaemia
187
Why does nephrotic syndrome cause hyperlipidaemia?
increased hepatic lipogenesis, a non-specific reaction to falling oncotic pressure secondary to hypoalbuminemia.
188
Why does nephrotic syndrome increase risk of infections?
As immunoglobulin are lost in the urine
189
Why does nephrotic syndrome put you at risk for hypocalcaemia?
As vitamin D and binding protein are lost in the urine
190
What are the 3 main things that can cause nephritic syndrome?
Small vessel vasculitis
Immune complex deposition
Anti-GBM autoantibodies
191
What are examples of how immune complex deposition can cause nephritic syndrome?
SLE
Post-streptococcal glomerulonephritis
IgA nephropathy
Cryoglobulinaemia
192
What is ANCA-associated vasculitis?
An umbrella term for
- Microscopic polyangiitis (MPA)
- Granulomatosis with polyangiitis (GPA): previously known as Wegener’s granulomatosis
- Eosinophilic granulomatosis with polyangiitis (EGPA): previously known as Churg-Strauss syndrome
193
What is ANCA?
Anti-neutrophil cytoplasmic antibody (autoantibodies that target self antigens leading to a vasculitis
194
What is anti-GBM disease?
a rare small-vessel vasculitis that results from the formation of GBM antibodies that target type IV collagen within the basement membrane. This results in linear deposition of IgG in the glomerular capillaries.
195
Whats the aetiology of nephrotic syndrome?
Structural damage = loss of negative charge at the GBM means the loss of the selectivity of permeability
=massive non-selective loss of protein
196
Whats the aetiology of nephritic syndrome?
Inflammation of glomerulus = cytokine release = leaky capillaries = leakage of proteins and RBC
197
What does ‘diffuse’ mean?
Affecting >50% of glomeruli
198
What does ‘focal’ mean?
Affecting <50% of glomeruli
199
What does ‘global’ mean?
Entire glomerulus is affected
200
What does ‘segmental’ mean?
Only part of the glomerulus is affected
201
What does ‘proliferative’ mean?
An increased number of cells in glomerulus
202
What does ‘membranous’ mean?
Thickening of GBM
203
What does ‘sclerosis’ mean?
Scarring of glomerulus
204
What are examples of mixed nephrotic and nephritic syndrome causes?
Membranoproliferative GN
Poststreptococcal GN
205
What is rapidly progressive glomerulonephritis?
A nephritic syndrome which rapidly progresses to renal failure in days/weeks
It can be caused by ANCA–associated small-vessel vasculitis, lupus nephritis and anti-GBM disease
It may be associated with pulmonary haemorrhage
206
What is seen on renal biopsy in rapidly progressive GN?
Crescents - breaks in the GBM allow an influx of inflammatory cells
207
Whats the treatment for rapidly progressive glomerulonephritis?
Corticosteroids
Cyclophosphamide
Plasma exchange
208
What is seen on renal biopsy in IgA nephropathy?
Mesangial hypercellularity
Positive immunofluoresence for IgA and C3
209
How is IgA nephropathy treated?
ACEi/ARBs to reduce proteinuria
If after 3-6 months of this there is persistent haematuria… Corticosteroids
210
What is Henoch-schonlein purpura?
(A systemic variant of IgA nephropathy)
IgA deposition in skin, joints, gut and kidneys
Presents with a purpuric rash on extensor surfaces, poly arthritis, abdominal pain (GI bleeding) and nephritic syndrome
211
What is found on renal biopsy in Henoch-schonlein purpura?
Mesangial hypercellularity
Positive immunofluoroscence for IgA and C3
212
What does Alport syndrome look like on renal biopsy?
Longitudinal splitting of laminate dense of GBM = basket weave appearance (on electron microscopy)
213
How is Alport syndrome managed?
ACEi/ARBs may slow progression of disease but most patients require dialysis or transplant
214
What is membranoproliferative glomerulonephritis?
A mixed nephritic/nephrotic syndrome
Due to either immune complex deposition secondary to autoimmune conditions, infections of Cryoglobulinaemia. OR due to C3 glomerulopathy
Effacement of foot processes of pdodocytes with electron dense deposits on electron misciospy
215
What is a C3 glomerulopathy?
A genetic or acquired defect in the C3 complement pathway
216
How can a recent streptococcal infection be confirmed?
Positive anti-streptolysin O titres
217
What is seen on renal biopsy for PSGN?
Acute, diffuse, proliferative glomerulonephritis
Immunofluorescence shows a granular starry sky appearance
218
What is minimal change disease?
A nephrotic syndrome that’s usually idiopathic but may be due to drugs, paraneoplastic or infectious mononucleosis
Typically affects children
Causes a highly selective proteinuria - mainly albumin and transferrin leak
219
Whats seen on renal biopsy in minimal change disease?
No changes on light microscopy but effacement of foot processes of podocytes on electron microscopy
220
How is minimal change disease managed?
Steroids
221
What is focal segmental glomerulosclerosis?
A cause of nephrotic syndrome
Scarring of GBM that can be idiopathic or secondary to HIV/heroine/lymphoma/other forms of GN
High recurrence rate even after renal transplant
222
What is seen on renal biopsy in focal segmental glomerulosclerosis?
Focal and segmental sclerosis
Effacement of foot processes of podocytes on electron miscioscpy
223
What is membranous glomerulonephritis?
The most common cause of nephrotic syndrome
May be primary to anti-phospholipase A2 antibodies or secondary to infections/malignancy/drugs/autoimmune conditions
224
Whats seen on renal biopsy in membranous glomerulonephritis?
Spike and dome pattern on electron microscopy - deposition of antibodies between podocytes and basal membrane
225
How is membranous glomerulonephritis managed?
Ponticelli regime - IV methylprednisolone, prednisolone tablets, cyclophosphamide tablets
226
Whats the most common cause of end-stage renal failure?
Diabetic nephropathy
227
What is seen on renal biopsy in amyloidosos?
Nodular glomerulosclerosis with apple green birefringence due to amyloid deposition with Congo red stain
228
What are the main causes of focal segmental glomerulosclerosis?
FSG is caused (mostly) by the 4H's
- Huh? - idiopathic
- Hurt kidney - secondary to other nephropathies
- HIV
- Heroin
229
What casts are seen on acute tubular necrosis?
Brown granular casts
