Chronic Kidney Disease Flashcards
1
Q
If you detect a one-off finding of eGFR below 60 on a blood test, what are 4 things that need to be done?
A
- If otherwise well, repeat U+E in 2 weeks to check for resolution or deterioration
- Check urine for protein (ACR), haematuria (indicating renal disease) and dipped or sent for an MSU to rule out a UTI
- History to cover other medications that can trigger drop in eGFR and any recent illnesses that may have caused dehydration such as diarrhoea
2
Q
What are 4 causes of a drop in eGFR?
A
- Acute/ secondary to dehydration (e.g. diarrhoea)
- Infection
- Nephrotoxic medications
- CKD
3
Q
What are 6 criteria that can lead someone to be diagnosed with CKD?
A
- Markers of kidney damage such as proteinuria (urinary albumin:creatinine ratio [ACR] greater than 3 mg/mmol)
- urine sediment abnormalities
- electrolyte and other abnormalities due to tubular disorders
- abnormalities detected by histology
- structural abnormalities detected by imaging and a history of kidney transplantation, and/or
- A persistent reduction in renal function shown by a serum estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2.
4
Q
Over what urinary ACR would CKD be diagnosed?
A
3 mg/mmol
5
Q
What is the definition and minimum time frame of CKD?
A
Presence of abnormal kidney structure or function for >3 months
6
Q
What are the 2 things that are used for classification of CKD?
A
- eGFR: G1-5
- Albuminuria: A1-3
7
Q
What are the stages of chronic kidney disease as defined by eGFR?
A
- stage 1: >90
- stage 2: 60-89
- stage 3a: 45-59
- stage 3b: 30-44
- stage 4: 15-29
- stage 5: <15
8
Q
Where is CKD generally managed and what are 7 exceptions?
A
Generally managed in primary care. Exceptions:
- uncontrolled hypertension: on 4 agents at therapeutic doses
- Polycystic kidneys, other rare of genetic causes
- Suspected renal artery stenosis
- Accelerated progression: drop of 25% in eGFR over 1 year AND hange in CKD category or drop of 15ml/min/1.73m2
- Renal anaemia
- Urinary ACR of >70mg/mmol (non-diabetic)
- ACR>30mg/mmol associated with haematuria
- eGFR<30
9
Q
Should a statin be offered in CKD?
A
If eGFR<60, yes - offer statin to all these people regardless of QRISK score, as those with CKD 20x more likely to die from cariovascular disease than end stage renal failure
10
Q
What regime of statin should patients with eGFR<60 be started on?
A
Atorvastatin 20mg, recheck in 3months
Aim for reduction in non-HDL cholesterol of 40% and titrate up
11
Q
What are the blood pressure targets in CKD?
A
Based on protein levels
- If ACR <70mg/mmol aim for less than 140/90
- if >70 aim for <130/80
Make sure not too low, as once systolic <120 and diastolic <60 mortality and morbidity start to rise as eGFR decreases, and risk of end-stage renal failure increases
12
Q
What is the recommended antihypertensive management in CKD?
A
If blood pressure within target, still recommend ACEi or AiiRA to reduce reduce progression of kidney disease IF ACR >30mg/mmol
13
Q
What safety netting is needed when starting an ACEi? 3 things.
A
- Check U+E within 14 days to check for acute renal failure or renal artery stenosis (drop in eGFR, creatinine and/or potassium)
- BP: check it’s not too low and titrate ACEi up to best tolerated dose, checking bloods with each increase
- Advise to stop ACEi if used solely for CKD if diarrhoea/vomiting as can cause volume depletion, reducing flow to kidneys and may cause AKI
14
Q
What are 5 things to warn a patient about with CKD regarding preventing AKI?
A
- Check U+Es 14 days after starting ACEi - check for drop in eGFR, creatinine and/or potassium
- Warn to stop if diarrhoea and vomiting due to dehydration risk if taking ACEi just for CKD
- Stop taking if you have a high fever
- Don’t use NSAIDs, not even topical
- Yearly influenza immunisations
15
Q
What are 4 things that are used to calculate eGFR?
A
- Creatinine
- Age
- Gender
- Ethnicity
16
Q
What are 3 scenarios when eGFR isn’t valid?
A
- <18 years
- Pregnancy
- Acute kidney injury (renal function changing rapidly)
17
Q
What is an additional factor that can affect eGFR (other than creatinine, agen, gender, ethnicity)?
A
Extreme body mass: high or low, e.g. very obese and body builders
18
Q
Why is serum creatinine no longer used to measure kidney function on its own?
A
When kidney function first declines, little change in serum creatinine so kidney disease could be missed
19
Q
How is proteinuria now measured?
A
Using urinary albumin: creatinine ratio
20
Q
What should patients be told before their ACR is calculate from a urine sample?
A
Should be told not to eat meat within 12 hours of having sample taken
21
Q
What is the definition and time frame of chronic kidney disease?
A
Presence of abnormal kidney structure or function for >3 months
22
Q
What are the boundaries for the 3 ACR categories in chronic kidney disease?
A
- A1: <3 [low]
- A2: 3-30
- A3: >30 [high]
23
Q
What increases as ACR increases in CKD?
A
Risk of poor CKD outcome increases
24
Q
How are eGFR and ACR used together to classify chronic kidney disease?
A
e.g. GFR of 35ml/min - CKD stage G3b, ACR or 20mg/mmol = A2
So: G3b A2, fall within high risk category (red area of table) for progression of chronic kidney disease
25
What proportion of the UK population is likely to have chronic kidney disease?
10% - relatively common
majority have 1, 2 o 3, small percentage 4 or 5
26
What is Stage 5 chronic kidney disease?
eGFR \<15, **end stage renal failure**
Kidneys no longer sufficient to sustain life or health
Need haemodialysis, peritoneal dialysis, or transplantation
If too frail, palliative care
27
What are 6 key groups to think that chronic kidney disease may occur in?
1. Hypertension
2. Diabetes
3. Multiple drugs especially NSAIDs
4. Elderly
5. Smokers - current o previous
6. Poor education
28
What are the 2 commonest causes of chronic kidney disease in the UK?
Diabetes and renovascular disease
29
What are 2 examples of rarer causes of chronic kidney disease?
1. Genetic e.g. autosomal dominant polycystic kidneys
2. Vasculitis
3. Glomulonephritis
30
How does chronic kidney disease relate to socioeconomic status?
Association between CKD and lower socio-economic status
31
What are 7 overall causes of chronic kidney disease?
1. Systemic disease
2. Immune mediated diseases
3. Infectious diseases
4. Genetic diseases
5. Arterial disease
6. Obstruction
7. Drugs
32
What are 4 examples of systemic disease that can cause chronic kidney disease?
1. Diabetes
2. Hypertension
3. SLE
4. Vasculitis
33
What are 3 immune-mediated causes of chronic kidney disease?
1. Membranous nephropathy
2. IgA nephropathy
3. Myeloma
34
What are 4 infectious diseases that can cause chronic kidney disease?
1. HIV
2. HBV
3. HCV
4. TB
35
What are 2 examples of genetic diseases which can cause chronic kidney disease?
1. Polycystic kidneys
2. Cystinosis
36
What are 2 examples of arterial disease that can cause chronic kidney disease?
1. Atherosclerosis
2. Fibromuscular dysplasia (impaired blood flow to kidneys)
37
What are 4 causes of obstruction that can cause chronic kidney disease?
1. Tumours
2. Benign prostate
3. Stones
4. Fibrosis
38
What are 2 examples of drugs which can cause chronic kidney disease?
1. NSAIDs
2. Calcineurin inhibitors e.g. tacrolimus and cyclosporin
39
In what proportion of patients with diabetes (type 1 and 2) does renal disease occur?
40%
40
What is diabetic nephorpathy usually seen in association with?
Associated with poor diabetes control and hypertension
In association with retinopathy, neuropathy - other diabetic complications
41
What is the pathology behind diabetic nephropathy? 5 elements
1. Thickening of basement membrane
2. Activation of renin-angiotensin system
3. Mesangial expansion
4. Glomerulosclerosis
5. Proteinuria
42
What is the mechanism behind mesangial expansion?
* Hyperglycaemia stimulates increased matrix production by mesangial cells
* Stimulation of TGF-ß release
43
What is the mechanism of glomerulosclerosis in diabetes?
Intraglomerular hypertension or ischaemic damage
44
What causes proteinuria in diabetes?
Due to damage to the glomerulus; increases tubular damage and fibrosis
45
What can be seen on histology of kidneys in a diabetic patient with expansion of tissue in the glomerulus?
Kimmelstiel-Wilson nodules - amorphous pink material, loss of normal functioning glomerulus cells, los of open capillary loops
46
What are 3 key stages of the natural history of diabetic nephropathy?
1. Onset of diabetes: raised GFR, reversible albuminuria, increased kidney size
2. 5-15 years: increased glomerular basement membrane thickness, mesangial expansion. Rising BP, microalbuminuria
3. 15-27 years: Inevitable decline in renal function, overt proteinuria, rise in creatinine and falling rGFR
47
What are 3 renal features likely to be seen at the onset of diabetes?
1. Increased eGFR
2. Reversible albuminuria
3. Increased kidney size
48
What are 4 renal features likely to be seen 5-15 years after diagnosis of diabetes?
1. Development of microalbuminuria in assoication with rising BP
2. Rising BP
3. Increased glomerular basement membrane thickness
4. Mesangial expansion
49
What are 4 renal features seen in diabetes 15-27 years after onset, **without treatment**?
1. Overt proteinuria
2. Rise in creatinine
3. Falling eGFR
4. Inevitable decline over next 7-10 years, reaching ESRF
50
What are 2 things that can be done in diabetes to reverse or prevent renal changes?
1. Early improvement of diabetic control
2. Early BP control
51
What are 4 features of diabetic nephropathy?
1. \>10 years diabetes
2. other microvascular complications (retinopathy, neuropathy)
3. Progressive increase in urine protein excretion over years
4. No evidence of other probable cause (no haemturia, no symptoms of obstruction, negative immunology and serology tests)
52
How is diabetic nephropathy diagnosed?
Has all the typical features in history → presumed diagnosis of diabetic nephropathy (without renal biopsy)
if doesn't meet all criteria, may need further investigations such as a renal biopsy
53
What is a common cause of glomerular disease which leads to CKD?
IgA nephropathy
54
What happens histologically in IgA nephropathy?
* **Mesangial proliferation** of glomerulus (inrceased number of mesangial cells)
* **IgA** deposited in glomerulus
55
What are 2 ways that patients may present with IgA nephropathy?
1. Usually present with incidental finding of haematuria (non-visible) and proteinuria
2. May also present with visible haematuria and associated upper respiratory tract infections
56
What are 2 key kidney biopsy changes seen after a period of time with chronic glomerular disease?
1. Glomeruli replaced with amorphous pink sclerotic material with a few scattered cells between
2. Damage to tubules; atrophied, deposition of fibrous material and scarring in between
57
What is an infective disease that can cause typical glomerular disease? What is this called?
HIV: HIV associated collapsing glomerulopathy
58
How can HIV lead to HIV-associated collapsing glomerulonephropathy?
HIV virus directly infecting kidney cells causing nephropathy
59
How could HIV indirectly cause kidney damage?
Acute and chronic kidney damage due to HIV drugs
60
What is the inheritance pattern of polycystic kidey disease?
Autosomal dominant
61
What is one of the commonest genetic causes of chronic kidney disease?
Autosomal dominant polycystic kidney disease
62
When and how does screening occur for polycystic kidney disease?
Early 20s by USS
If negative in early 20s, can be confident pt doesn't have disease
63
What are the 2 main genes affected in autosomal dominant polycystic kidney disease?
PKD1 and PKD2
64
Is there specific treatment available for polycystic kidney disease?
No specific treatment currently available
Drugs therapy currently in trials (Tolvaptan) - to slow down development of renal cysts
65
How can vascular disease impact on renal function?
Can often cause renal artery stenosis; seen in patients with atherosclerotic vascular disease elsewhere e.g. CVD, cerebral vascular disease, peripheral vascular disease
66
What is the screening test for vascular disease causing renal artery stenosis?
MR angiogram (sometimes conventional angiography)
see loss of lumen in right renal artery, small kidney due to ischaemia
67
What are 2 types of tumours that can cause CKD by obstruction?
1. **Intrinsic**: obstruct ureteric orifices. can develop in bladder or ureter, obstructing ureter or orifice, causing hydronephrosis in kidney
2. **Extrinsic**: colonic carcinoma with retroperitoneal spread or in women - cervical carcinoma, spread to obstruct ureters. Prostate cancer in men
68
What can cause fibrosis that may lead to obstruction, in turn leading to CKD?
Can be in relation to previous inflammation/ ifection, can cause obstruction in ureters or urethra
69
What can obstruction of the renal tract lead to if left untreated?
Hydronephrotic kidney - dilation and replacement of renal tissue with large, cystic areas and loss of functioning renal tissue
70
What are 4 initial tests to perform when investigating possible CKD?
1. **Urinalysis** - haematuria and proteinuria
2. **Urinary protein loss** - ACR or protein: creatinine ratio
3. **Urine culture** to exclude infection
4. **Immunology and serology** - ANA, ANCA, serum and urine free light chains and/or protein electrophoresis - myeloma or MGUS, HBV, HCV, HIV
71
When is it particularly important to perform immunology and serology tests in suspected CKD?
when history, examination or risk factors suggest systemic disease may be present
72
Why would you test for anti-nuclear antibodies (ANA) in suspected CKD?
systemic lupus erythematosus
73
Why should you test for serum anti-neutrophil cytoplasm antibodies (ANCA) in suspected CKD?
Small vessel vasculitis
74
Why would you look for serum and urine free light chains and/or protein electrophoresis?
Looking for monoclonal bands, for myeloma or MGUS (mono-glonal gammopathy of undetermined significance)
75
What are 4 elements of the immunology and serology you would perform in suspected CKD?
1. ANA - SLE
2. ANCA - small vessel vasculitis
3. Serum and urine free light chains/ protein electrophoresis
4. HBV, HCV, HIV
76
In addition to the initial investigations for suspected CKD, what are 2 further investigations that may be performed?
1. Renal imaging: ultrasoun, CT-KUB, radioisotope renogram, MRA
2. Renal biopsy
77
What are 4 types of renal imaging that you may do in suspected CKD?
1. Ultrasound
2. CT-KUB
3. Radioisotope renogram
4. Magnetic resonance angiography
78
Why might you perform an ultrasound for renal imaging in suspected CKD? 3 reasons
1. Important in pts with lower urinary tract symptoms or other reasons to suspect obstruction e.g. history of stones
2. Important if biopsy considered
3. Screening for polycystic kidneys
79
Why might a CT-KUB be useful renal imaging in suspected CKD?
To look for stones
80
Why might a radioisotope renogram be used as renal imaging in suspected CKD?
will show differential function of left and right kidneys and show functional excretion (or obstruction)
81
Why might you perform magnetic resonance angiography (MRA) in suspected CKD?
to look at renal vessels
82
What are 2 reasons why you might perform a renal biopsy in chronic CKD?
1. If glomerulonephritis suspected
2. If renal function deteriorating without a cause identified by other investigations
83
How safe is renal biopsy? What is the risk of bleeding?
Relatively safe but not risk free; should not be done if evidence of infection or obstruction
Approx 4% risk of bleeding if done in large centres
84
What are 2 instances when you should not perform renal biopsy?
1. Infection
2. Obstruction
85
What are 3 nephrotoxic drugs that patients who are taking should be screened for CKD?
1. NSAIDs
2. Calcineurin inhibitors (tacrolimus/ ciclosporin)
3. Lithium
86
How are patients taking nephrotoxic drugs screened and how often?
* ACR and eGFR
* done at least annually
87
What are 10 groups of people who should be tested for CKD?
1. Diabetes
2. Hypertension
3. Episode of acute kidney injury
4. Cardiovascular disease: IHD, chronic heart failure, peripheral vascular disease, cerebral vascular disease
5. Structural renal tract disease
6. Recurrent calculi
7. Prostatic hypertrophy
8. Multisystem diseases with potential kidney involvement e.g. SLE, vasculitis
9. FH of ESRF or hereditary kidney disease e.g. adult PKD
10. opportunistic detection of haematuria
88
What are 6 things to do if abnormal eGFR is found?
1. Take history
2. Examination - evidence of bladder outflow obstruction in men
3. BP
4. Urinalysis - haematuria, proteinuria
5. ACR - spot urine sample
6. Repeat eGFR after \>2 weeks to exclude AKI/ rapidly deteriorating renal function
89
How often should eGFR be performed and why if a diagnosis of CKD is suspected?
If abnormal eGFR found, repeat after \>2 weeks to exclude AKI/ rapidly deteriorating renal function
3x eGFR over at least 90 days to see rate of progression
90
How often should you monitor CKD? How can you tell?
Between once (milder) and 4 times (ESRF)
Use NICE table based on CKD stage classification (eGFR and ACR)
e.g. G3b-A2: twice a year
91
What are 6 things that NICE's recommendation for how often to monitor CKD doesn't take into account?
1. Underlying cause of CKD
2. Past patterns of eGFR and ACR - if already deteriorating, monitor more closely
3. Comorbidities e.g. HF
4. Changes to treatment e.g. introduction of RAS blockage, NSAID, diuretics - needs increased monitoring
5. Intercurrent illness
6. Conservative management - G4 and G5 less monitoring if want conservative mgmt
92
What are 6 groups of patients with CKD who need an ultrasound scan?
1. Accelerated progression of CKD
2. Visible or persistent invisible haematuria - looking for malignancy
3. Sx of urinary tract obstruction
4. FH of PKD and aged \>20y
5. GFR\<30
6. Require a renal biopsy
93
What should you do before arranging a renal ultrasound for people with a family history of inherited kidney disease?
Advise about the implications of an abnormal result before scan arranged
94
What are 7 situations when you would refer CKD to a nephrologist?
1. GFR\<30
2. ACR \>70 - unless konwn to be caused by diabetes and already appropriately treated
3. ACR \>30 and associated with haematuria
4. Rare or genetic cause known or suspected
5. Sustained decrease in GFR in 12 months
1. **\>25%** reduction **and** change in GFR **category** (e.g. G3a to 3b)
2. **\>15** reduction in 12 months
6. poorly controlled hypertension requiring at least 4 drugs at therapeutic doses
7. Suspected renal artery stenosis
95
What are 10 risk factors for CKD progression?
1. Cardiovascular disease
2. Proteinuria
3. AKI
4. HTN/ poorly controlled
5. Diabetes
6. Smoking
7. Ethnicity of family origin: African, Afro-Caribbean, Asian
8. Chronic NSAID use
9. Urinary outflow tract obstruction
96
What are 5 important things to tell patients diagnosed with CKD?
1. Implications
2. Risk of progression
3. Self-management - lifestyle measures e.g. healthy eating, exercise
4. Treatment including risks/ benefits e.g. ACEi/ARBs
5. Dialysis/ transplantation if appropriate, with appropriate counselling (esp if likely to need soon)
97
How can progression of CKD be preventing?
Identify and treat modifiable risk factors
98
What are 6 modifiable risk factors that can be identified and treated to prevent progression of CKD?
1. Proteinuria - ACEi/ARB
2. Hypertension - as per NICE
3. Smoking- cessation
4. Control of underlying disease - diabetes, lupus
5. Caution with NSAID use
6. Refer to urology if outflow obstruction/ structural abnormalities
99
What is one of the major complications of CKD?
Cardiovascular disease - people with worse renal function have increased risk of CV disease
Also increase in risk with age
100
What is a key risk factor within CKD for the development of cardiovascular disease, independent of any other risk factor?
Presence of **albuminuria**: even with stage 1/2
also increases risk of progression of CKD
101
What are 2 things that the present of albuminuria in CKD increases risk of?
1. Cardiovascular disease
2. Progression of CKD
102
What are 3 ways to manage the risk of cardiovascular disease associated with CKD?
1. Hypertension mgmt
2. Lipid management: atorvastatin 20mg OD if eGFR \<60 or albuminuria
3. Antiplatelet agents for secondary prevention / lipid management
103
What is the typical statin drug and dose to manage risk of cardiovascular disease in CKD?
atorvastatin 20mg OD
104
What are 8 possible complications of CKD?
1. Uraemia
2. Oedema
3. Hypernatraemia
4. Hyperkalaemia
5. Metabolic acidosis
6. Secondary hyperparathyroidism
7. Hypocalcaemia
8. Anaemia
105
What are 5 signs of failure of fluid homeostasis in chronic kidney disease?
1. Inability to concentrate urine
2. Loss of diurnal rhythm - nocturia, many x a night
3. Dilutional hyponatraemia - can't excrete water load
4. Oedema - pulmonary and pitting
5. Hypertension
106
What are 3 ways to treat the reduced water excretion in CKD?
1. Loop diuretics - furosemide, bumetanide
2. Salt restriction
3. Fluid restriction (in some cases)
107
What are 4 key investigations to perofrm in emergency pulmonary oedema?
1. ABG
2. ECG
3. CXR
4. Pulse oximetry
108
What is the management of emergency pulmonary oedema due to CKD? 5 elements
* **100% oxygen** via facemask _if_ hypoxaemia
* **Furosemide, nitrates**
* Salt restriction, fluid restriction
* Consider **CPAP** or **NIV** if acidotic or poor response to furosemide and nitrates
* Refer to **senior medical staff** and **intensive care** for consideration of *_IV inotropes_* (e.g. dobutamine) or *_invasive ventilation_*
109
When is the only time you should give inotropes to treat emergency pulmonary oedema secondary to CKD?
If **hypotension** and evidence of **reduced organ perfusion**
110
Why can sodium become deranged in CKD?
Loss of nephrons reduces ability to excrete salt and water
111
What can deranged sodium due to CKD cause? 2 things
1. Hypertension and fluid overload
2. must be within normal range for normal neurological function
112
What can high or low sodium lead to in terms of neurological function?
Confusion, fits and coma
113
What is the treatment of hypernatraemia secondary to CKD?
Salt restriction
114
When does severe hyperkalaemia occur in CKD?
When GFR \<10ml/min - enormous functional reserve to excrete potassium
115
What are 4 things that can cause hyperkalaemia in CKD?
1. Excessive load of potassium (e.g. dietary)
2. Interference with potassium excretion - acidosis associated with volume contraction
3. Diabetic nephropathy can interfere with excretion
4. Use of medication e.g. ACEi and ARBs
116
What does hyperkalaemia cause that makes it so dangerous?
Alterations in membrane excitability → cardiac arrhythmias, block of AV node
117
What are 4 key ECG changes due to hyperkalaemia?
1. Tall T waves
2. Long QRS interval
3. Long PR interval (AV nodal block)
4. Cardiac arrest
118
What are the 3 goals of treating **severe** hyperkalaemia?
1. Restoring normal cardiac conduction - IV calcium gluconate
2. Rapid temporary reduction in serum potassium - IV insulin (ActRapid) in glucose and B2 agonists
3. Increased potassium excretion - calcium resonium/ polystyrene sulfonate, loop diuretic
119
How can normal cardiac conduction be restored in severe hyperkalaemia (\>8.0)?
IV calcium gluconate 10ml 10%
120
What are the 2 ways to bring about a rapid temporary reduction in serum potassium in severe hyperkalaemia caused by CKD?
1. IV insulin with glucose: 6-10 units Actrapid in 50ml 50% glucose
2. B2 agonists (salbutamol) can help
121
What are 2 ways to increase potassium excretion in severe hyperkalaemia caused by CKD?
1. Oral/rectal calcium resonium/ calcium polystyrene sulfonate
2. Loop diuretic (±IV fluid)
122
What are 5 steps to take if hyperkalaemia is less severe, secondary to CKD?
1. Dietary restriction of potassium
2. Correction of acidosis (may be driving the hyperkalaemia)
3. Review medication that may be making it worse: ACEi, ARB, aldosterone
123
What are 3 medications that could make hyperkalaemia worse?
1. ACEi
2. ARB
3. Aldosterone
124
What normally maintains acid-base balance in the body?
Bicarbonate-carbonic acid buffer system- protons that accumulate are buffered by bicarbonate to form carbonic acid, dissociates to CO2 and water. CO2 removes through lungs
125
What are 5 symptoms of metabolic acidosis?
1. Increased respiratory drive - feel breathless
2. Chest pain
3. Confusion
4. Bone pain
5. Demineralisation of bone (bone buffering) - long term, to buffer hydrogen ions
126
What is the management of chronic metabolic acidosis secondary to CKD?
* Oral sodium bicarbonate - under specialist guidance only
127
What is the risk of managing chronic metabolic acidosis with sodium bicarbonate?
significant amount of sodium - over-correction can also cause problem i.e. hypertension and fluid retension
128
What is the management of acute metabolic acidosis?
1. Sodium bicarbonate - aim to raise pH to **7.1-7.2** (arrhythmias less likely)
2. Treat underlying cause e.g. treat DKA
129
What is the target pH range when treating acute metabolic acidosis with sodium bicarbonate? Why?
7.1 - 7.2 (lower risk of arrhythmias)
130
What is the vitamin D metabolism system in the body?
* 7-dehydrocholesterol is converted to cholecalciferol (D3) with sunlight
* or D2 and D3 can be absorbed in inactivated form from diet
* Cholecalciferol and ergocalciferol are chaperoned around blood by vitamin D binding protein (DBP)
* In **liver**, will D3 undergo 25-hydroxylation to form **25-hydroxy-D3**
* This is returned to the blood and then onto the **kidney** where taken up by **proximal tubular epithelium**
* 1-alpha-hydroxylase enzyme responsible for 1-alpha-hydroxylation of **25-hydroxycholecalciferol** to form **1, 25-dihydroxycholecalciferol** i.e. _active form_ of vitamin D (the rate limiting step)
* activated vit D enters blood, effect on target organs including gut, promoting calcium absorption (chaperoned by DBP again)
131
What detects low calcium and what action does this result in?
* Low calcium detected by parathyroid glands where calcium detecting receptors are located on chief cells
* Parathyroid glands therefore produce parathyroid hormone
132
What are the 2 key effects of parathyroid hormone release by the parathyroid glands when calcium is low?
1. Kidney: promotes **conversion of 25-vitamin D3 to 1, 25-vitamin D3** which **increases intestinal aborption** of calcium to raise serum calcium
2. Bone: **increases bone resorption** to increase serum calcium - negative feedback effect on parathyoid glands, reduces PTH secretion
133
Why does kidney damage in CKD affect calcium homeostasis?
* Low calcium detected by parthyroid chief cells; **kidneys unable to respond** by increasing activation of vitamin D3
* major effect is on bone with demineralisation and release of calcium to increase serum calcium, with negative feedback on parathyroid glands
* **demineralised bones, increased rigidity**
134
Can parathyroid hormone work directly on the gut?
No - works directly on bone to increase bone resorption but needs to act on kidney to produce activated vit D form (by alpha hydroxylation) which can work on the gut
135
What are 4 possible effects of persistent secondary hyperparathyoidism (due to CKD)?
1. Brown tumour - cystic degeneration of bone
2. Resoprtion of pharalanges
3. Rugger Jersey spine with demineralisation
4. Ectopic calcification: calcification in arteries of leg, soft tissue calcification around joints (painful)
136
What causes the calcification in arteries and soft tissue calcification of renal failure?
Persistent hyperparathyroidism and hyperphosphateamia causes activation of fibroblasts
137
What are 5 elements of the treatment for bone disease and ectopic calcification secondary to hyperparathyroidism in renal disease (CKD)?
1. Replace activated vitamin D (1, 25-dihydroxycholecalciferol) with **alpha-calcidol** or **calcitriol**
2. Phosphoate dietary restriction
3. Phosphate binders (calcium based or non-calcium based)
* to reduce phosphate absorption from gut
4. Calcimimetics - if uncontrolled, e.g. **cinacalcet** to reduce parathyoid hormone secretion
5. Parathyroidectomy - if all else fails
138
How can kidney disease lead to anaemia?
Erythropoietin produced by kidney in response to low oxygen delivery, this controls red cell production in the bone marrow
These enter circulation and restore oxygen delivery
Kidney can't produce EPO in some cases of CKD, so anaemia can't be corrected
139
What are 4 key risks of renal anaemia in CKD?
1. Impaired quality of life - reduced exercise capacity, cognition
2. Transfusion requirement - iron overload, blood-borne infection risks
3. Increased risk of left ventricular hypertrophy
4. Increased CVD risk due to LVH
140
What are 3 possible treatments for renal anaemia in CKD?
1. **Recombinant erythropoietin** and **erythropoiesis stimulating agents**
2. Iron supplementation if necessary
3. Folic acid supplementation if necessary
141
Why is it important that vitamin B12 levels are normal when treating renal anaemia?
stores must be adequate for EPO to be effective
142
What is the major risk of EPO therapy?
Hypertension
143
What are 5 advantages of EPO stimulating agents (ESA) over transfusion in renal anaemia?
1. Avoids risk of infection (HBV, HCV, HIV, new variant CJD)
2. Redued risk of reactions due to antibodies against red cell surface proteins
3. Sensitation and problems with transplant matching avoided
4. Iron overload voided
5. Not using a scarce resource
144
What are 5 mechanisms that can cause hypertension when EPO therapy given in renal anaemia, that can all combine?
1. Sodium retention
2. Volume expansion
3. RAS-over activation
4. sympathetic nervous system activity
5. endothelial dysfunction
145
Why is it particularly dangerous for EPO therapy to cause hypertension in renal anaemia?
Can accelearte decline of kideny functinon and further contributes to cardiovascular risk (stroke, MI, heart failure)
146
How is hypertension managed in CKD? 2 things
* RAS blockage: ACEi, ARB, diuretics; or calcium channel blockers
* salt restriction
147
What are 4 things that can be retained due to reduced removal of waste products/drugs in CKD?
1. Creatinine - rises only after significant renal damage
2. retention of nitrogenous waste - uraemia
3. retention of urate
4. retention of phosphate
148
What can retention of creatinine, nitrgenous waste, phosphate and urate result in? 5 symptoms
1. loss of appetite
2. nausea
3. vomiting
4. pericarditis
5. other serositis
149
What is the treatment for uraemia in CKD?
Dialysis or transplantation
no good alternative - protein restriction not recommended, may result in protein malnutrition
150
What are 5 examples of drugs for which toxicity risk is increased by CKD? What are the associated effects of each?
1. Insulin - hypoglycaemia
2. Opiates - narcosis
3. Antibiotics - encephalopathy
4. Sedatives - respiratory arrest
5. Digoxin - cardiac arrhythmia
151
How can increased toxicity of drugs be avoided in CKD? 4 things
1. modify prescription according to renal function; see BNF
2. online summary of product characteristics for drug freely available
3. renal drug handbook
4. pharmacist advice
152
What type of anaemia is usually caused by CKD?
Normocytic normochromic
153
What is the effect of chronic kidney disease on phosphate? What does this cause?
Kidneys normally exccrete phosphate → hyperphosphataemia
Drags calcium from bones, contributing to osteomalacia
154
What are 3 types of phosphate binders to reduce hyperphosphataemia in chronic kidney disease?
1. aluminium-based: less commonly used now
2. Calcium-based
3. Sevelamer: increasingly used
155
What are the 4 treatments for hyperphosphataemia of chronic kidney disease?
1. Reduced dietary intake of phosphate
2. Phosphate binders
3. Vitamin D: alfacalcidol, calcitriol
4. Parathyroidectomy in some cases
156
What are 2 problems with the calcium-based phosphate binders?
1. Hypercalcaemia
2. Vascular calcification
157
How does sevelamer work to treat hyperphosphataemia?
* It is a non-calcium based binder
* **Binds to dietary phosphate to prevent its absorption**
* Also other beneifical effects: reduces uric acid levels, improves lipid profiles of patients with CKD
158
What are 4 bone clinical manifestations due to reduced renal activation of vit D in CKD?
1. **Osteitis fibrosa cystica,** aka hyperparathyroid bone disease
2. **Adynamic** - reduction in cellular activity (both osteoblasts and osteoclasts), may be due to overtreatment with vit D
3. **Osteomalacia**
4. **Osteosclerosis**
5. **Osteoporosis**
159
At what eGFR does renal anaemia usually become apparent in CKD?
\<35
160
What are 6 other causes of anaemia in renal failure in addition to reduced EPO production?
1. reduced erythropoiesis due to toxic effects of uraemia on bone marrow
2. reduced absorption of iron
3. anorexia/nausea due to uraemia
4. reduced red cell survival, esp in haemodialysis
5. blood loss due to capillary fragility and poor platelet function
6. stress ulceration leading to chronic blood loss
161
What is the target haemoglobin level in CKD?
10-12 g/dl (100-120)
162
What are 2 examples of erythropoiesis stimulating agents (ESAs)?
EPO and darbopoetin
163
What is the first line drug to treat hypertension in CKD? What type of disease are they particularly useful in?
**ACE inhibitors** - proteinuric renal disease (e.g. diabetic nephropathy)
164
How do ACE inhibitors work to treat HTN in CKD and what can be seen following their administration?
reduce filtration pressure
see a small **fall** in GFR and **rise** in creatinine
165
What degree of fall in eGFR and rise in creatinine following administration of ACE inhibitors is deemed acceptable?
* fall in eGFR up to 25%
* rise in creatinine up to 30%
166
In addition to ACE inhibitors, what is also a useful anti-hypertension in patients with CKD and when?
Furosemide - when GFR falls \<45
167
What is the added benefit of using furosemide in CKD?
added benefit of lowering serum potassium
168
What kind of doses of furosemide are usually required in CKD?
high
169
When might you temporarily stop furosemide in CKD, when it's being used to treat hypertension?
If patient becomes at risk of dehydration e.g. gastroenteritis
170
What define CKD stage 1?
GFR \>90, with some sign of kidney damage on other tests
