2 Renal Flashcards
(133 cards)
1
Q
Functions of the kidney:
A
1 Excretion of water-soluble (Glomerular filtration & Tubular secretion)
2 ECF volume & BP (Salt, water excretion) & vasoacitive hormones)
3 Control of acid-base balance
(ECF volume, vasoactive hormones, sympathetic nervous system)
4 Hydroxylation of vitamin D
5 Control of RBC production
1
Q
Cr is produced at a constant rate from?
A
Muscle turnover
2
Q
6 measurements of kidney function
A
- Glomerular filtration rate (endogenous markers: Cr & Cystatin C, exogenous markers: Inulin)
- Tubular secretion(rare)
- ECF and BP
- Acid-base balance – serum [HCO3]
- Vit D hydroxylation – PTH measurement
- RBC production – Hb measurement
3
Q
Cr production rate depends on…
A
Muscle mass therefore age, gender, ethnicity
4
Q
Cr is secreted solely by
A
Glomerular filtration
5
Q
What to think about with trimethoprim and cr?
A
Creatinine is a tiny bit excreted by tubular secretion. Important in very bad function. Simetadine and Trimethoprim inhibit tubular secretion.
6
Q
CrCl is estimated using…. Formula…
A
Cockcroft and Gault
7
Q
eGFR is calculated using the … Formula
A
MDRD
8
Q
For CrCl use which type of body weight?
A
Ideal body weight
9
Q
MDRD is less accurate for
A
Patients at extremes of weight
11
Q
Other tests of kidney function 8
A
- Haematuria (blood in urine)
- Proteinuria (albumin/total protein)
- Abnormal cells or debris in the urine
- Laboratory measurement
- Acidification tests
- Radiology
- Microscopy
- Dipstick
11
Q
Causes of chronic kidney disease
A
Diabetes Hypertension Glomerulonephritis Reflux nephropathy Polycystic disease Previous AKI Others: including nephrotoxicity
12
Q
Causes of AKI?
A
Pre-renal – reduction in renal perfusion
(Hypovolaemia/sepsis/cardiogenic)
Renal – intrinsic kidney disease
• Prolonged pre-renal causing ‘acute tubular necrosis
• Specific causes e.g. vasculitis, glomerulonephritis, drugs
Post-renal – obstruction to urine flow.
(e.g. Prostatic bladder/malignancy)
13
Q
Presentation of kidney disease
A
• CKD is often asymptomatic until stage 4 or even 5
• Late presentation of CKD5 = poor outcome
• So screening of at-risk populations is encouraged
• Anaemia is a common presenting problem
(Exclude alternative causes e.g. deficiency states, bone marrow disorders, haemolysis)
• Symptoms in advanced CKD often non-specific: fatigue, lethargy, loss of appetite, nausea, vomiting, nocturia and polyuria, muscle cramps, restless legs
14
Q
Four treatments for kidney failure
A
1Conservative’ – drug treatment to minimise further loss of kidney function (antihypertensives, NaHCO3), plus symptomatic treatment (ESAs; antiemetics, etc)
2 Peritoneal dialysis
3 Haemodialysis
4 Kidney transplantation
15
Q
Burden of dialysis 6
A
- Fluid/salt/potassium restriction
- Phosphate binders to reduce GI absorption of PO4
- Travel (to centre/restricted abroad)
- Continued symptoms
- Access problems
- Infectious problems
16
Q
Why be careful with ACEI?
A
Restrict blood flow to the kidney, appears as failure… Is it?? I don’t know :/
17
Q
MDRD is suitable for… And not suitable for…
A
Normalised GFR (ml/min/1.73m2) is appropriate for estimating how abnormal the kidney function is, but NOT for drug dose adjustment • At any given level of normalised GFR, bigger people would get smaller doses and smaller people larger doses.
18
Q
Common maintenance drugs…
A
- BP-lowering drug treatment
- Lipid-lowering drug treatment
- Glucose-lowering drug treatment
- Phosphate binders
- Vitamin D analogues
- Sodium bicarbonate supplements
- Erythropoiesis stimulating agents
- Anti-platelet agents
- Water-soluble vitamin supplements
19
Q
Criteria for acute kidney injury
A
Serum creatinine rises by ≥ 26µmol/L within 48 hours
- Serum creatinine rises ≥ 1.5 fold from the reference value, which is known or presumed to have occurred within one week
- urine output is < 0.5ml/kg/hr for >6 consecutive hours
20
Q
Three drugs that reduce blood flow to the kidneys
A
Diuretic, NSAIDs, ACEi
21
Q
5 drugs that contribute to intrinsic renal impairment in AKI
A
NSAIDs PPIs Antivirals Antibiotics (Direct toxic effect - ahminoglycosides)
22
Q
2 drugs contributing to post-renal AKI
A
Methotrexate and aciclovir
23
Q
Two normal responses of the kidney you reduced blood flow? What two drug classes are implicated?
A
Kidneys normal response to a reduction in renal blood flow is :
• Vasodilation of afferent blood vessels – prostaglandins
• Vasoconstriction of efferent blood vessels – renin angiotensin system
Therefore ACEi and NSAIDs prevent body from achieving normal response
24
Consider acute nephrotoxic drug action
* C - Contrast media
* A - Angiotensin converting enzyme inhibitor
* N - Non steroidal anti-inflammatory drugs
* D - Diuretics
* A - Angiotensin II receptor blockers
25
Role of the pharmacist in AKI (6)
* Preventing AKI – Education / Risk assessment
* Recognising AKI
* Identify possible drug causes
* Stop nephrotoxic drugs
* Review drugs that may worsen biochemistry e.g. cause hyperkalaemia
* Review doses of other medication that may accumulate
26
Some general info on CDK
* Abnormal kidney function and/or structure
* Common, frequently unrecognised
* Often co-exists with other conditions
* Diabetes, Cardiovascular disease
* Risk of developing increases with age
* Often asymptomatic – 30% of patients with advanced kidney disease are referred late
* Treatment can prevent or delay progression of CKD and reduce or prevent development of complication
27
Nine complications of CKD
* Anaemia
* Hyperphosphataemia
* Renal Bone Disease
* Oedema
* Hypertension
* Itching
* Nausea
* Electrolyte Imbalances
* Restless Legs/Cramps
28
How do we treat anaemia in AKI?
erythropoietin (SC or IV) and iron (IV) - sometimes straight into the dialysis machine
29
How to treat hyperphosphatemia?
Phosphate binders
30
What vitamin supplement is mainly used in kidney disease?
Alfacalcidol
31
How to treat itching? (2)
Antihistamines and moisturisers
32
How to treat cramps?
Quinine and stretching
33
How to treat restless legs
Clonazepam
34
Phosphate binders may chelate other drugs such as (2)
quinolone antibiotics, levothyroxine
35
Four effects on adsorption
* Reduced compliance (due to uremic symptoms/polypharmacy)
* Gastric oedema
* Phosphate binders (bind quinolones, levothyroxine)
* PPI and H2 receptor antagonists reduce gastric acidity
36
Effects on distribution
• Low albumin reduces the amount of protein binding
• Uraemia causes displacement from protein binding sites
> Increased free drug... Therapeutic drug monitoring
37
Which drugs should be theraputic monitored... 5
* Low albumin reduces the amount of protein binding
* Uraemia causes displacement from protein binding sites
* Increased free drug -
* Phenytoin Sodium valporate
* Diazepam Warfarin
* Digoxin
* Therapeutic drug monitoring.... Due to their changes free levels as a result of reduced protein binding in renal disease
38
Effects of metabolism on CDK
* Vitamin D – Kidney hydroxylation at 1-alfa position
* In CKD need to give activated vitamin D
* Insulin
39
Effects on excretion
* Significant for drugs which are >25% excreted unchanged in the urine
* Remember metabolites
* Drugs with a narrow therapeutic index
40
Five drugs to consider due to half life changes as renally excreted
* Aciclovir – Half life extended from 3-20 hours
* Gabapentin – 100% excreted in kidneys
* Methotrexate – 80-90% excreted in urine
* Digoxin 76-85% excreted unchanged in urine
* Opiates –morphine
* Half life of 6 glucoronide increased from 3-5 hours to 50hours
41
Haemodialsysis or haemofitration require anticoagulants?
Dialysis
42
Ideal renal drug (7) features
* Less than 25% excreted in the urine
* No active metabolites
* Disposition unaffected by fluid balance changes
* Disposition unaffected by protein binding
* Disposition unaffected by tissue sensitivity
* Wide therapeutic index
* Not nephrotoxic
43
Decrease dose or decrease frequency in kidney disease?
Antibiotics – where you want to maintain peak increase dose interval
* Decreasing dose smoother profile e.g. allopurinol
* Consider formulations available
* Consider renal replacement therapy
* Example
* Digoxin reduce loading dose and reduce maintenance dose
* Meropenem give od post dialysis
44
Pharmacists role in CLD
Stop nephrotoxic drugs if patient has function
* Review drugs that may worsen biochemistry e.g. cause hyperkalaemia, increase sodium
* Advice on minimum volumes for IV's if patient fluid restricted
* Review doses of other medication that may accumulate
* eGFR or cockcroft and gault
* Consider adjusting medication around dialysis
* Patient education
* Supply of hospital only medication
45
Pharmacists role in transplants
• Avoid nephrotoxic drugs • Ensure medication is adjusted for level of renal function • Ensure transplant medication is continued • Ensure appropriate brand is supplied • Consider drug interactions • Macrolides • Antifungals
46
Four OTC problems in renal patients
* Caution antacids
* Na, Ca, Mg, Al content
* Caution Cough/Cold remedies
* Sympathomimetics
* Products with electrolytes in them
* Na - Andrews Liver Salts
* K - Losalt
* Citrate - Cystemme (UTI symptom relief)
* Travel medicine
47
Reduction in renal blood flow (perrennial cause of AKI) results in (2)
Ischemia and tubular necrosis
48
Increased production if wastes by... (3) Can result in pre renal cause for AKI
Waste products such as urea
| By infection, upper GI bleeding, steroid therapy
49
Interstitial nephritis is ...
Interstitial damage mediated by hypersensitivity reaction to neurotoxins, results in inflammation affecting those cells lying between the nephrons
50
Most common cause Intra-renal AKI?
Actute tubular necrosis, where the proximal tubule is highly active and therefore more susceptible to ischaemia or toxins... Common cause of this is renal hypo fusion.
51
Post renal causes of AKI result from... Such as... 4
Obstruction to the urinary tract
| Urinary stones, constipation, neoplasm, benign prostatic hypertrophy?
52
Cockroft-Gault not appropriate for use in....
ARF in a patient with previously normal function as serum cr rises by only 10-20 micromol/l per day.
AND
paediatrics or highly muscle developed patients (athletes)
AND
pt with extensive burns
AND
pt with fluid overload
53
How to assess cr clearance in AKI...
24 hour urine collection
54
ACR
Albumin:creatinine ratio
| NICE recommends using this to retention protein in urea rather than other methods
55
Proteininuria is an important indicator or...
Kidney disease and the risk of its progression
57
Functions of the kidney
Excretion of water-soluble waste products: Glomerular filtration, tubular secretion
58
MDRD eqution
Does not require body weight as an input variable, provides a normalised estimate
59
What will happen to the C&G and MDRD estimate is a person puts on weight
C&G will stay the same because the rise in serum creatinine will be cancelled out by the rise in weight.
60
eGFR
= % Kidney function
61
Tests for kidney function
Blood in the urine
62
Causes of chronic kidney disease
Diabetes, hypertension, glomerularphritis, reflux nephropathym polycycstic disease, previous acute KI, nephrotoxicity
63
Clinical presentation of chronic kidney disease
Often asymptomatic until stage 4 or 5, sos creeping of at risk populations is encouraged. Anaemia is a common presenting problem.
64
Treatments for kidney failure
Conservative - drug treatment to minimise further loss of kidney function (antihypertensives, NaHCO3), plus symptomatic treatment (anti emetics etc)
65
Burdens of dialysis
Fluid restriction, restriction of salt intake, restriction of potassium intake, phosphate binders to reduce GI absorption of PO4, travel, restriction in travel within the UK (and abroad), continued symptoms, access problems, infectious problems
66
Normalised GFR
appropriate for estimating ho normal the kidney function is, but not for dose adjustment
67
Acute kidney injury
Clinically, characterised by a rapid reduction in kidney function resulting in a failure to maintain fluid, electrolyte and acid-base homeostasis.
68
5-20%
Estimated amount of critically ill patients that experience an episode of AKI.
69
more than or equal to 26micromol/L within 48 hours
Amount serum creatinine has to rise by to indicate AKI (within 48 hours)
70
more than or equal to 1.5 fold from the reference value, occurring within one week
Amount serum creatinine has to rise by to indicate AKI (within one week)
71
less than 0.5ml/kg/hr for >6 consecutive hours
Urine output amount to indicate AKI
72
Affect on distribution in kidney failure
Low albumin decreases amount of protein binding
73
Vitamin D
Is hydroxylated in the kidney at the 1 alpha position to it's activated form. So in kidney failure need to give the activated form, e.g. alficalcidol, not calcichew D3
74
Excretion in kidney failure
Is significant for drugs which are >25% excreted unchanged in urine, and drugs with a narrow therapeutic index.
75
Aciclovir
Half life is extended from 3 to 20 hours in kidney failure
76
Gabapentin
100 % excreted in the kidneys
77
Methotrexate
80-90% excreted unchanged
78
Digoxin
76-85% excreted unchanged in urine
79
Opiates - morphine
half life of 6 glucuronide increased from 3-5 hours to 50 hours.
80
Properties of the ideal renal failure drug
less than 25% excreted in urine, no active metabolites, disposition unaffected by fluid balance changes, disposition unaffected by protein binding, disposition unaffected by tissue sensitivity, wide therapeutic index, not nephrotoxic.
81
Cockcroft - gault is not appropriate for use in
acute renal failure with previously normal renal function/paediatrics/extensive burns/fluid overload
82
How to measure renal func in AKI
24h urine sample
83
variables in MDRD
age sex ethnicity and serum creatanin
84
test to detect proteininurea
ACR (albumin creatanin ratio)
85
Normally the kidney ..... K
filters
86
with decreasing GFR K levels
rise (unless dietary intake reduced)
87
Diet avoiding K
avoid orange juice, nuts, crisps, baked beans
88
Medication that causes K retention (caution in renal failure)
spironoloctone
| ACE-I
89
Used to treat high K levels?
Push K back into cells:
Calcium glucuronate
Then: 50% dextrose + insulin infusion
OR salbutamol neb/IV
OR NaHCO3 (sodium bicarb)
AND K resin exchange mechanism OR dialysis
90
Problems resulting from high K
fatal arrhythmias
91
K resin exchange mechanism
Calcium resonium
92
Function of bicarbonate
buffer H ions
93
Bicarbonate is regenerated where?
in the tubular cells - then passed back into plasma
94
Renal failure effect on bicarb
```
reduced regeneration
(and the reduced GFR means kidneys don't filter other potential buffers such as phosphate - accumulates - acidosis)
```
95
Result of low bicarbonate
hypokaleamia (low K) & hypernatraemia (high Na)
| fluid overload
96
Treatments for decreased bicarb
oral bicarbonate (contravertial - alkalinisation)
OR
titrate contiunous line against plasma pH
97
As GFR decreases phosphate ... and calcium ....
phosphate accumulates
| calcium decreases
98
Renal bone disease
mixture of oesteomalacia & hyperparathyroidism
| *as a result of accumulated phosphate and Ca decrease
99
Phosphate binders can cause
HYPERcalcaemia > renal damage
100
Essential to maintain normal fluid volume
sodium reabsorption in the tubule (back into the blood stream) - this ability is lost in kidney damage - fluid overlaod
101
Haemodialysis
& 3 disadvantages
several hours 3/week via fisula into vein
Risk of infection/ischemia of the hand, pt feels worse between sessions,
102
At what CrCl is dialysis needed
<15
103
Peritoneal dialysis
Catheter puts solution in, diffuses over membrane 6 hours, drain and replace.
Can be done at home. More stable condition.
Risk of infection - scarring
Weight gain as glucose moves
Constipation can reduce efficacy
104
Haemofiltration
In ICU - continuous against semipermiable membrane but putting in replacement fluid to prevent deydration
105
Factors to consider for medication & dialysis
Excreted or metabolised?
Severity of renal fuction?
Stop nephrotoxics
Does it matter if the drug accumulates? (narrow therapeutic index)
Is the drug cleared by peritoneal/heamofilration? - alter dose
Heamodialysis - alter timeing?
106
How phosphate binders work?
Form insoluble non-absorbable complexes
107
4 phosphate binders
```
Aluminium hydroxide (tox problems)
Calcium carbonate (corrects concurrent hypocalciumia but needs high dose)
Calcium acetate (lower doses)
Sevelamer (decreases likelyhood of hypercacimia - expensive)
```
108
Problems with dihydropyridine CCBs (nifedipine)
less cardiac depression BUT only dilate efferent arterioles which may result in glomerular damage
109
If using ACEi to lower BP
monitor potassium (as they are potassium sparing)
110
Choice of betablockers
Atenolol - well tolerated but requires adjustment in renal failure
Metoprolol - not need for adjustment
111
Should not use CCBs with
b blockers
112
ACEi have advantage that
they may reduce thirst
113
Choices for oedema
Furosemide (limited to a loop diuretic)
+/-
Metazolone works synergistically with furosemide
114
Thiazides are not used becuase
ineffective in renal failure
115
Potassium sparing diuretics are not used because
hyperkalemia risk
116
Hydroxylation of vitamin D occurs
at alpha one position - in the kidney
| Impairment in renal failure > defective bone militarization > oesteomalacia
117
When using Alfacacidol monitor
serum calcium
| + correct hyperphosphatemia before initiating therapy (or results in soft tissue calcification)
118
Anaemia is noticable when GFR <
30ml/min (shorten RBC survival, bone marrow supression, poor dietary uptake of folate/iron)
119
Treat aneamia with
EPO +/- iron ( may want to check ferratin stores to see if iron is being absorbed and if not administer IV)
120
80% of AKI is
pre-renal
121
MDRD tends to over/underestimate
underestimate
122
Cockroft Gault tends to under/overestimate
overestimate
123
MDRD assumes
levels constant over past few days... therefore do not use to assess AKI
124
Itching as a result of
uremic symptoms (high K & low K may contribute)
- Micropercipitation of divalent ions elevated by PTH & increase in dermal mast cell activity.
elcetrolyte correction may help but might not improve until dialyis
125
Nausea and loss of appetite a result of
uremic symptoms
126
Muscle weakness and cramp due to
toxin build
| or sudden drop in electrolytes from dialysis
127
Ankle swelling caused by
fluid build up - (also maybe amlodipine)
128
Nocturia caused by
kidney not concentrating urine enough and not producing ADH for nighttime
129
instead of weigh MDRD uses
standardised body s.a
130
HCO3
bicarbonate
131
PO4
Phosphate
132
PTH levels increase from
low calcium (PTH increases production of Ca through bone reacbsorption)
133
How to treat high PTH
activated vitamin D
