Pharmacology of CKD Flashcards
What is the 7 step process clinically?
- Identify the patient’s problem
- Specify the therapeutic objective
- Select a drug on the basis of comparative efficacy, safety, cost and suitability
- Discuss choice of medication with patient (and carer) and make a shared decision about treatment
- Write a correct prescription
- Counsel the patient on appropriate use of the medicine
- Make appropriate arrangements for follow up (Monitor/stop the treatment)
Case history = 59M Routine check up revealed: High BP = 170/110 Normal HR = 72bpm Proteinuria Creatinine = 140 umol/L = high Urea = 11mmol/L = high
The GP requested an ambulatory blood pressure monitor (ABPM), a renal ultrasound, and repeat blood tests. The ABPM gives a mean reading of 165/110, the creatinine and urea are unchanged, and the renal ultrasound shows unobstructed, slightly small kidneys
Write what the possible diagnoses are and calculate his eGFR?
Differential diagnosis =
Stage 2 hypertension
Chronic kidney disease (CKD)
eGFR if white = 48 ml/min or if black = 58 ml/mol
What are the therapeutic objectives?
Reduce BP to reduce cardiovascular risk (BP is also elevated due to CKD)
To slow pregression of CKD
What treatment would the GP initiate at this point?
For hypertension =
Aged >55 = Amlopidine (L-type calcium channel blocker)
Target should be lower than normal due to CKD e.g. (130/70)
For CKD =
Tight BP control (to slow CKD progression - regardless of cause)
For CVD risk =
Conservative measures (smoking cessation, reduce salt intake, exercise)
Atorvastatin as risk >10% (13% - 31% depending on ethnicity)
Statins to reduce cholesterol
Case history - follow-up
Reffered to nephrology services and is now diagnosed by CKD secondary to hypertension - no other causes identified
Amlodipine = controlling his BP well, BUT he has significant proteinuria
What treatments should the nephrologist initiate for the proteinuria and what treatment might need to be stopped?
Proteinuria is a marker of glomerular dysfunction AND damaging in its own right (presence of protein also causes problems) - e.g. pasta blocking the holes in a colander
Drug interventions to improve proteinuria =
Continue to reduce BP - e.g. ACEi OR angiotensin receptor blockers (ARB)
ACE also gets rid of bradykinin, which is a vasodilator, therefore ACEi would have greater effects on lowering his BP
OR
Sodium-glucose co-transporter-2 (SGLT-2) inhibitors (e.g. dapagliflozin) - prevent reabsorption of glucose = good for T2DM and lowering HbA1c; but for CKD it aids sodium reabsorption = favourable effects on hydrostatic pressure in the glomerulus
Lifestyle factors = careful monitoring of salt intake
Stop Amlodipine if the ACEi reduces his BP too low!
What is the difference between prescribing antihypertensives for solely hypertension VS prescribing hypertensives for hypertension and CKD?
Any antihypertensive does the job for only treating hypertension
More selective about antihypertensive choice for CKD, because certain antihypertensives have added benefits e.g. the ACEi also reduces proteinuria along side reducing BP, so it is faobured over the amlodipine
Would you treat this patient with aspirin?
Yes or no - both are justified
Although most likely not unless his CVD risk ishigher, because according to NICE guidelines for CKD state:
Consider prescribing aspirin in people with a high risk of stroke or myocardial infarction
There is limited evidence of benefit even in people with multiple risk factors and there is a risk of harm
In general, we tend to avoid aspirin for primary prevention
Why is aspirin considered as a treatment?
Aspirin given for CVD - as nly a small dose is required for its affect on the platelets thatare found in the hepatic portal vein, conincidentally where the aspirin is found at its highest concentration
Platelets also do not have a nucleus, and aspirin binds to the COX enzyme found in platelets irreversibly, that platelet is destroyed forever
So due to the very small dose required, it doesnt have a detramental affect on the kidneys or systemically when its being cleared out
Case history - follow-up
Few months later - mild dysuria
GP diagnoses him with a UTI and he is started on trimethoprim (antibiotic) while a urine sample is sent to the lab and routine lood tests are done
Lab reports show he has E. coli that is insenstive to Trimethoprim
Routine blood tests show creatinine has increased (145 –> 280), and urea is unchanged (13 mmol/L)
Use an eGFR calculator to work out what his GFR is currently?
eGFR = if white is 21mls/min OR if black is 26mLs/min
His use of trimethoprim invalidates the GFR calculator. Why is this, and do you think his GFR has in fact changed?
Trimethoprim inhibits the active secretion of creatinine
So the decrease in clearance of creatinine = increase in amount in the blood - so the 280 could be false
You wouldn’t know whether it is due to his CKD getting worse or the antibiotic
So the equation to calculate GFR is now invalid
Maybe put him on another antibiotic etc.
How is GFR calculated?
Using creatinine because it is freely filtered - and not rebabsorbed or secreted
Case history - follow-up
GP prescribes him a new antibiotic but 1 week later he presents to A&E feeling worse
Dysuria still present - but now also has loin pain and fever
Has been taking ibuprofen for the last few days
USS shows perinephric fat stranding and pyelonephritis is diagnosed
Treated with Gentamicin
Creatinine is now 450, urea 27
What is his GFR now and which of his drugs are contributing to the worsening GFR and how?
egFR = if white 12mls/min or if black 15mls/min
Ibuprofen - main drug contributing to hiw new, poorer GFR
Ibuprofen = NSAID = inhibits the COX enzyme, and so blocks the synthesis of prostaglandin (PG)
PGs are immportant in the kidneys to regulate renal blood flow - with inuprofen renal blood flow decreases so GFR decreases
ACEi = reduces perfusion pressure in glomerulus by lowering BP, exacerbated by sepsis
Sepsis also contributes to the acute injury
You are the admitting doctor on the medical ward and making a plan for his medication. What would you do about the ibuprofen, ACEi, and gentamicin?
Stop ACEi temporarily - as they usually slightly worsen GFR by changing the flow in the glomerulus, which is fine normally but during an acute injury that rapidly deteriorates kidney function, it is good to stop the ACEi temporarily
Ibuprofen = NSAID = unsuitable as its the major cause of the rapid GFR deterioration
Paracetamol does not work by blocking COX because it is not an NSAID, therefore very suitable alternative to ibuprofen as it still provides pain relief
Gentamicin can be continued - but reduce frequency / dosage according to his blood gentamicin levels OR choose an alternative antibiotic
What are the take home messages?
There are two things to consider when prescribing for a patient with reduced renal function:
- Does this drug I’m prescribing damage the kidney and so worsen the kidney injury
(eg NSAIDs such as ibuprofen) - Is the drug I’m prescribing eliminated by the kidney, and so will it accumulate in the blood if kidney function is impaired, and then lead to side effects? (eg morphine, metformin)
