What medication should CKD patients avoid or adjust dosage?
Moliere, the 17th century playwright wrote, ‘Nearly all men die of their remedies, and not of their illnesses.’ This is very pertinent for CKD patients who, a. may need a lot of medication, but b. are more vulnerable to their side-effects.
Why? The kidneys are the body’s dustmen. And, as such, they also remove medication from the body when it has been used (to benefit the patient). For this reason if you are in CKD, some drugs need to be either (1) avoided, or (2) have a lower or less frequent dose.
In this article, we will describe what medication should CKD patients avoid or adjust dosage.
Most of these comments are relevant if your CKD stage is CKD3B-CKD5 (kidney failure).
ACE/ARBs are a ‘double-edged sword’
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are blood pressure tablets that are essential to CKD treatment – as they also reduce protein in the urine. And although not overtly nephrotoxic, under certain clinical circumstances they have the potential for harm.
In patients with bilateral (both sided) renovascular disease (RVD), they can cause a rapid decline in renal function (Acute Kidney Injury, AKI), leading to temporary (and occasionally permanent) dialysis.
In any patient, they can cause hyperkalaemia (high blood potassium) which can affect heart function. If the blood potassium is > 6 mmol/L (normal is 3.5-5.3 mmol/L) then they should not be started; and, if you are on one, it should be stopped, and perhaps restarted at a lower dose.
They should not be used together.
Allopurinol
The dose of allopurinol (for gout) should be reduced by 2/3rd in CKD3A or worse – from 300mg to 100mg OD.
Allopurinol and azathioprine
These should not be co-prescribed. Allopurinol interferes with the breakdown of azathioprine, which may result in potentially fatal low blood counts. Azathioprine used to be used a lot to prevent rejection of a kidney transplant, or autoimmune disease. It is used less now. But older patients may still be on it.
Anticoagulants
Low molecular weight heparin (e.g. Enoxaparin) should be administered at a reduced dose with lower grades of CKD (e.g. 20 mg OD, not 40 mg OD), and avoided in ESRF.
Antimicrobial drugs
Most antibiotics, antifungal and antiviral medications are cleared by the kidneys. Some need to have their dose adjusted:
Antibiotics
A group of hospital prescribed IV antibiotics called aminoglycosides (e.g. gentamicin) and others (e.g. vancomycin and streptomycin) build up in CKD, so the dose (and/or frequency) have to be reduced.
Antifungal drugs
Older antifungal agents, particularly amphotericin B are highly toxic to the kidneys and should be avoided.
Antiviral drugs
Herpes zoster is a common viral infection. It causes chickenpox and shingles. Shingles can make elderly people very unwell. GPs usually start an antiviral agent called aciclovir in shingles, to reduce the duration of the disease, pain, and to prevent ‘postherpetic neuralgia’ (pain after the disease). In CKD, the dose needs to reduced and made less frequent.
If adjustments are not made, aciclovir can become toxic leading to drowsiness, fits and/or other neurological psychiatric disease – some reactions are life-threatening.
Other antiviral drugs should be avoided or have dose reduction in CKD.
Digoxin
This is an anti-arrhythmic drug (mainly used for atrial fibrillation). It requires dose reduction.
Diuretics (water tablets)
Thiazide and loop diuretics are essential drugs in CKD, especially at the later stages (CKD4+). They are commonly used for fluid overload and BP control. Overuse of diuretics use can dehydration causing (prerenal) AKI in vulnerable patients with advanced CKD, CCF, ascites, or other oedematous states (ie. with extra water causing swelling in the body).
Note 1. Diuretics can also cause:
- a low or high sodium in the blood
- a low or high potassium
- a low or high calcium
- worsen diabetes and/or gout.
Hence these minerals and chemicals need to be monitored if you are on a diuretic.
Note 2. Adding a nonsteroidal anti-inflammatory drug (NSAID; see below) to an ACE/ARB (see above) and diuretic can amplify the risk of AKI, and has been described as a ‘triple whammy.’
Erythropoeitin (EPO; and related drugs)
Anaemia treatment with EPO (and related drugs) is often required in patients with CKD4 or worse. It is treated by increasing the amount of EPO produced by the kidneys. This can be done using:
- Erythropoiesis-stimulating agents (ESA), like Darbepoetin alfa (‘Aranesp’; given as an injection once a week)
- Hypoxia-inducible factor–prolyl hydroxylase (HIF-PH) inhibitors, like Roxadustat (given as a tablet three times a week).
But there is a balance between causing the haemoglobin (Hb) to rise, and minimising its adverse effects; e.g. a high haemoglobin can cause high blood pressure, a stroke or causing an arteriovenous fistula (AVF) to clot and stop working. The target Hb in advanced CKD is 110-120 g/L.
Herbal supplements and vitamins
Many herbal supplements contain minerals such as potassium or phosphate that can be damaging for people with chronic kidney disease. In general, herbal and vitamin supplements should be avoided if you have CKD.
Insulin (and other anti-diabetic medication)
Diabetes is a leading cause of CKD and the need for dialysis and/or a kidney transplant. But if you go into CKD3B or worse, insulin (and other diabetes medication) build up, risking hypoglycaemia (low blood sugar) which can be prolonged and serious.
So for some CKD patients, insulin (and other anti-diabetic tablets including sulphonylureas (e.g. gliclazide) and biguanides (e.g. metformin) need to have their doses reduced as GFR falls. In some patients, they may need to be stopped completely.
If you have diabetes and chronic kidney disease, check with your doctor to see if any dosing changes need to be made based on your level of kidney function.
Intravenous contrast dye
Intravenous contrast dyes are used in diagnostic tests such as MRIs, CT scans, and angiograms. These can cause acute kidney injury (AKI). This is called contrast nephropathy. If it happens, it is usually reversible. In a minority short-term dialysis may be required. In a small number of these, long-term dialysis results.
If you are due have one of these tests, talk to the doctor ordering the test or your radiologist (x-ray doctor). Tell all health care professionals responsible for your care about your glomerular filtration rate (GFR) and CKD.
If your kidneys are at risk, as your doctor if you really need that scan or angiogram. Are there alternative tests?
Lithium
Lithium is a very old and very effective for bipolar disease. But it can lead to CKD by causing a chronic interstitial nephritis in some patients. This is why blood levels are monitored if you are on it.
But please do not stop the drug if your develop CKD. Follow the advice of your GP or psychiatrist.
Methotrexate
Methotrexate is a strong drug used for cancer and some autoimmune diseases (e.g. rheumatoid disease). It should be started at a low dose in patients with chronic kidney disease (CKD). It is contraindicated in advanced CKD.
NSAIDs
If you have CKD, some over-the-counter (OTC) and prescription pain medications, including aspirin, ibuprofen (and other nonsteroidal anti-inflammatory drugs (NSAIDs)), are not recommended because they can reduce blood flow to the kidneys, and hence kidney function.
Opiates
Most opiates (e.g. codeine, morphine, fentanyl) build up in the body in CKD and long-term use should be avoided. If this happens, you may become drowsy and very unwell. They can be used in the short-term at normal or reduced dosage, say after an operation.
Upset stomach/antacid medication
This group of over-the-counter medications can disrupt the body’s electrolyte balance if you have chronic kidney disease. Check with your doctor to see if these are safe for you to use.
Sulphonylureas
Summary
We have described what medication should CKD patients avoid or adjust dosage. We hope it has been helpful.
Other resource
This is a good review article: Whittaker, 2018.
Last Reviewed on 19 April 2024