where F = 1.23 (males), 1.04 (females).
Ideal body weight should be used for obese patients, as actual bodyweight would overestimate creatinine clearance, leading to an overdose. Actual bodyweight should be used for heavy muscle-bound patients to prevent under-dosing. Table 8.1 shows some limitations and inaccuracies of the Cockcroft & Gault and MDRD equations.
Table 8.1 Limitations and inaccuracies of the equations.
| Cockcroft & Gault (creatinine clearance, mL/min) | MDRD (eGFR, mL/min/1.73 m2) |
| People in catabolic states | Transplant patients |
| Extensive oedema | Serious comorbidities, e.g. diabetes |
| Certain races | Certain races |
| Rapidly changing renal function | Extremes or rapidly changing renal function |
| Extremes of body weight | Extremes of body weight |
| Pregnant women | Pregnant women |
| Increased creatine consumption | Increased creatine consumption |
| Children | Children |
Principles of drug dosing in renal impairment
Various pharmacokinetic factors are altered in kidney disease, and renal replacement therapy (RRT) can alter the excretion of some medication. Many drugs are renally excreted or have renally excreted metabolites, leading to a need for dosage adjustments in patients with renal impairment.
The main pharmacokinetic parameters that may be altered in CKD are:
- bioavailability
- distribution
- metabolism
- elimination
Bioavailability
Bioavailability is defined as the percentage of an administered drug that reaches the systemic circulation. In the case of oral administration, it is the percentage of the drug that is absorbed across the gastrointestinal membrane. Intravenous drugs have 100% bioavailability, but the bioavailability of drugs administered by other routes may vary considerably with drug, formulation and individual patient. Altered bioavailability can lead to erratic absorption and enhanced adverse drug reactions.
Renal impairment can affect absorption by:
- Altered gastrointestinal motility – Absorption is reduced by nausea, vomiting, diarrhoea, peritonitis or oedema, e.g. reduced availability of furosemide in oedematous patients.
- Increased gastric pH due to increased blood urea nitrogen levels and the majority of CKD patients being on stomach protection, e.g. H2-antagonists (ranitidine) or proton-pump inhibitors (omeprazole, lansoprazole). Some medication is best absorbed in acidic conditions, so if the gastric pH is too high it can lead to reduced absorption e.g. ferrous sulphate.
- Reduced absorption due to insoluble chelate formation, e.g. drug interactions between phosphate binders and iron tablets.
Distribution
After a drug is administered it disperses throughout the body until it reaches equilibrium. This is called the apparent volume of distribution (Vd), which is a ratio of the amount of drug in the body to the amount of the drug in the plasma. Drugs are distributed into areas with the highest blood flow first. A low Vd is seen with highly protein-bound or water-soluble drugs. A high Vd is seen with fat-soluble or un-ionised drugs due to increased tissue penetration.
In renal failure this can be altered by:
- Hydration – Vd of water-soluble drugs is increased if the patient is oedematous or has ascites, and conversely in dehydrated patients the Vd may be reduced.
- Reduced protein binding, due to uraemia changing the shape of binding sites, drugs or waste products competing for binding sites, inadequate nutrition causing low albumin levels, inflammation or dialysis, especially peritoneal dialysis. Highly protein-bound drugs are most affected.
- Changes in tissue binding – This is rarely of clinical importance apart from in the case of digoxin, where the Vd can be reduced by up to 50%, so that patients with CKD stages 3–5 require a reduced loading dose.
Hydration and reduced protein binding are usually only clinically relevant in drugs with narrow therapeutic indexes and low Vd (less than 0.7 L/kg), e.g. theophylline, and can result in an increased Vd and toxicity.
An important example is phenytoin, where binding is reduced if GFR is less than 25 mL/min or if the patient has low albumin levels (< 4.4 g/dL). This causes increased concentrations of free drug. This is critical when interpreting phenytoin drug levels, as the measured level will be falsely low and should be adjusted.
Metabolism
This usually occurs in the liver to make drugs more water-soluble so that they can be more easily excreted. Some drugs are metabolised in the kidney to their active form, e.g. vitamin D, or to renally excreted active metabolites, e.g. morphine and pethidine. This can lead to the adverse effects and toxicity seen with some medication due to accumulation. The metabolic pathways of reduction and hydrolysis are reduced in renal impairment.
In CKD, metabolism can also be increased, as more drug is available for metabolism due to reduced protein binding and uraemic toxins inducing hepatic enzymes.
Elimination
The elimination half-life (T1/2) is the time taken for free drug concentrations in the body to halve. The renal excretion of medication depends on glomerular filtration, active tubular excretion and passive tubular reabsorption. In renal failure, if a drug is renally excreted its T1/2 will be increased. This can affect the dose and frequency of administration of medication: for example, the T1/2 of gentamicin is increased from 1–3 hours to over 24 hours, so it only has to be given every 48 hours to CKD 5 patients.
If a dose adjustment is required, either reduce the dose or increase the dosage interval. The option used will depend on the dosage units available and what would be most convenient for the patient and nursing staff. If high serum drug concentrations are needed quickly then loading doses may be required due to reduced absorption and increased T1/2, as it takes longer to reach steady state (5 × T1/2).
In CKD and haemodialysis some physiological actions can be altered, and this can contribute either to enhanced effects or to increased adverse drug reactions:
- Hypovolaemia or haemodialysis (if the patient has put on too much weight between sessions, requiring rapid removal of excess fluid during dialysis) can lead to an enhanced blood-pressure-lowering effect with antihypertensives.
- Increased risk of hyperkalaemia with angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs), potassium-sparing diuretics and potassium salts.
- Uraemia can cause excess bleeding with antiplatelets or anticoagulants.
- Enhanced CNS sensitivity to centrally acting drugs, e.g. antidepressants, analgesics (especially opioids), medication for neuropathic pain, e.g. gabapentin.
- Electrolyte variations, e.g. digoxin toxicity due to potassium shifts pre and post dialysis.
Patients with CKD are usually prescribed medication for life, but their regime will change according to their individual health state and their position on their (dynamic) care pathway. On starting dialysis, some medications may be stopped (typically sodium bicarbonate). In the initial few weeks following commencement of dialysis, the patient’s antihypertensive medication may also be altered as the patient achieves his or her dry weight (weight without any excess fluid). Patients on haemodialysis may receive some medication in the dialysis unit, e.g. vitamin D or intravenous iron. The type of RRT and the pharmacokinetics of the drug determine the dose of medication required to treat patients with established renal failure on dialysis.
Peritoneal dialysis is a much gentler treatment compared to haemodialysis, Drug removal is by passive diffusion across the peritoneal membrane, so smaller quantities of medication are usually removed.
As haemodialysis is a more aggressive treatment, if a drug is likely to be removed by haemodialysis then it should be given after dialysis. The exception is medication which is given more than three times a day, when it would not be practical to wait until after dialysis to give the drug.
The drugs most likely to be dialysed are those which (Levy et al. 2004):
- have a low molecular weight (less than 500 daltons for haemodialysis, up to 30 000 daltons in haemodiafiltration)
- have low protein binding
- have a small volume of distribution (< 1 L/kg)
- are highly water-soluble
- are renally excreted (if > 50%)
Acute kidney injury
Acute kidney injury (AKI) is defined as a rapid deterioration in renal function, and it can occur over days or weeks. Between 5% and 20% of AKI is drug-related (Ashley 2004), and 2–5% of hospital inpatients will develop AKI, usually due to aminoglycosides or radiocontrast media. In primary care ACE inhibitors, ARBs, non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics are the most common causes. As mentioned in Chapter 6, AKI can be subdivided into pre-renal, intra-renal (intrinsic) and post-renal failure, depending on where the injury occurs.
Table 8.2 Nephrotoxic drugs.
Data from Ashley 2004.
| Diuretics NSAIDS ACE inhibitors and ARBs Calcineurin inhibitors, e.g. ciclosporin, tacrolimus Radiocontrast media Beta-blockers High-dose dopamine Laxatives |
Pre-renal kidney injury
Pre-renal failure is usually due to medication or physiological causes that reduce renal blood flow or cause dehydration. Five per cent of pre-renal failure is due to nephrotoxins. The main drugs implicated are listed in Table 8.2.
Pre-renal kidney injury responds well to the removal of the nephrotoxin and rehydration, and recovery is usually within 24–72 hours once the blood flow is returned to the kidney. If it is not treated quickly enough it can lead to more severe renal impairment, e.g. acute tubular necrosis (ATN). This can happen in primary care mainly in elderly patients who are on an ACE inhibitor and a diuretic and who are unwell and stop eating and drinking for a few days but continue their medication and become dehydrated. When counselling patients on ACE inhibitors or ARBs it is safest to advise them to temporarily discontinue them if they stop drinking for a few days.
Intra-renal kidney injury
Acute damage to the kidney is usually due to a direct nephrotoxic effect on the glomeruli and renal tubules. It can be subdivided into glomerular, hypersensitivity and tubular effects (Table 8.3).
Interstitial nephritis is usually drug-induced, with more than 70 drugs being implicated. Antibiotics, omeprazole and NSAIDs are the most common causes. AKI may occur within two weeks of exposure to the nephrotoxin, or it may be delayed for months. Thirty-five per cent of patients will require dialysis.
ATN is usually due to direct damage to the kidney and causes a reduction in GFR and oliguria or anuria. In some cases it can be prevented by adequate hydration. Contrast-induced nephropathy has an AKI incidence ranging from 0.6% in patients with no renal impairment to 100% in diabetic patients with CKD.
Table 8.3 Nephrotoxic effects of different agents on kidney structure.
Data from Ashley 2004, Ashley & Morlidge 2008.
| Glomerular (immune-mediated) | Hypersensitivity (interstitial nephritis) | Tubular (acute tubular necrosis) |
| Antibiotics, e.g. penicillin, sulphonamides, rifampicin Allopurinol Halothane NSAIDs Gold (2–19% of patients) Penicillamine (30% of patients) Thiazide diuretics | Antibiotics, e.g. cephalosporins, erythromycin, penicillin, aminoglycosides, minocycline, rifampicin, sulphonamides Allopurinol Azathioprine Carbamazepine Cimetidine Clofibrate Diuretics Gold Halothane Interferon NSAIDs Omeprazole Penicillamine Phenytoin | Antibiotics, e.g. aminoglycosides, cephalosporins, colistin, septrin, polymyxin, vancomycin Aciclovir Amphotericin Ciclosporin Cisplatin Lithium Heavy metals Herbal medicines Methyldopa Mushrooms Paracetamol Radiocontrast media Snake venom |
Table 8.4 Causes of post-renal kidney injury.
Data from Ashley 2004.
| Chemotherapy (due to uric acid crystal formation) Methysergide (due to retroperitoneal fibrosis) Sulphonamides Precipitation of poor-solubility drugs, e.g. intravenous aciclovir, methotrexate Anticoagulants (due to blood clot formation) Analgesics |
Post-renal kidney injury
This is usually due to obstruction in the urinary tract preventing outflow of urine. It may be caused by disease processes, e.g. malignancy, or due to drugs that cause crystal formation (Table 8.4).
Removal of the obstruction can lead to polyuria, so fluid balance and monitoring of electrolytes is very important to prevent the patient becoming dehydrated, leading to pre-renal kidney injury (see Chapter 6).
Table 8.5 Other drug-related causes of renal impairment.
Data from Ashley 2004.
| Vasculitis | Systemic lupus erythematous (SLE) | Rhabdomyolysis |
| Amphetamines | High-dose hydralazine | Statins |
| Penicillins | Procainamide | Fibrates |
| Sulphonamides | Isoniazid |
Table 8.6 Treatment of symptoms in AKI.
| Symptom | Treatment |
| Dehydration | Intravenous/oral fluids |
| Fluid overload | High-dose diuretics, RRT |
| Hyperkalaemia | Calcium resonium, glucose/insulin infusions, RRT, dietary potassium restriction |
| Pulmonary oedema | RRT |
| Uraemia | RRT |
| Acidosis | Sodium bicarbonate, RRT |
| Infection | Treat infections aggressively |
| Hyperphosphataemia | Dietary phosphate restriction, phosphate binders |
| Hypocalcaemia | Alfacalcidol and calcium (oral and/or intravenous), but not if the patient has rhabdomyolysis |
Other drug-related causes of renal impairment
These are listed in Table 8.5.
Treatment of the symptoms of AKI
The first step is to remove the nephrotoxin, and then the symptoms should be treated (Table 8.6).
Medication used in CKD
Chronic kidney disease mineral and bone disorder (CKD-MBD)
CKD-MBD (or renal osteodystrophy) is caused by the inability of the kidney to regulate phosphate excretion (due to reduced urinary clearance). This leads to reduced calcium absorption and vitamin D metabolism causing stimulation of parathyroid hormone (PTH) production. This results in an increased incidence of fractures and cardiovascular mortality. Almost all patients with CKD stage 4–5 will have some degree of CKD-MBD. The Renal Association standards recommend phosphate levels of 1.1–1.7 mmol/L for dialysis patients and 0.9–1.5 mmol/L for CKD stage 3B–5. This is achieved by a combination of medication (phosphate binders) and diet. Low phosphate levels in haemodialysis patients should be avoided, as they are often an indication of poor nutrition.
There are many different types of phosphate binders available, and the one chosen depends on the patient’s blood results (mainly calcium levels) and patient tolerability. Binders work by binding phosphate in the gut and forming a complex with it which is then excreted in the faeces. All phosphate binders should be taken at mealtimes. Patients who are not eating do not need to take any, but if they are having a high-phosphate meal (e.g. macaroni cheese) they should take extra.
The different types of phosphate binders are:
- Calcium-based
- Calcium carbonate – e.g. Calcichew, Calcium 500
- Calcium acetate – e.g. Phosex, PhosLo, Renacet, Osvaren (also contains magnesium)
- Calcium carbonate – e.g. Calcichew, Calcium 500
- Heavy-metal-based
- Aluminium hydroxide – e.g. Alucaps
- Lanthanum carbonate – e.g Fosrenol
- Aluminium hydroxide – e.g. Alucaps
- Polymer-based
- Sevelamer carbonate and hydrochloride (e.g. Renvela, Renagel)
Alucaps are cheap and effective but they can have quite serious side effects if the aluminium accumulates, which was mainly a problem in the 1960s when dialysis was first introduced. At that time the water used for haemodialysis was not filtered, so if the aluminium content in the water was high this resulted in high aluminium levels in patients, leading to constipation, anaemia, dementia and renal bone disease. They are now only recommended for short-term use.
Calcium-based binders are the main binders used in many units, although they are also losing favour with many nephrologists due to calcium accumulation leading to vascular calcification and cardiovascular mortality. They remain popular as they are inexpensive and are better tolerated than some of the newer phosphate binders such as sevelamer and lanthanum. Calcium acetate is slightly better than calcium carbonate, because less calcium is absorbed. It is important when prescribing calcium carbonate to ensure that it is not the vitamin D formulation (Calcichew D3) that is used, as renal patients are unable to utilise vitamin D in that form. Calcium-based binders should not be taken at the same time as iron tablets, as they form chelates resulting in reduced absorption.
Sevelamer was the first non-calcium, non-aluminium binder licensed. It now comes in two forms as the carbonate (Renvela) and the hydrochloride (Renagel). The tablets are film-coated and easy to swallow, and the carbonate also comes as sachets. They have the advantage that they may slightly lower cholesterol levels. The disadvantages are cost, tablet burden (9–15 tablets have to be taken every day), gastrointestinal side effects and acidosis, and high doses can cause bowel obstruction in peritoneal dialysis patients. They must be taken with or after food; if taken on an empty stomach they are more likely to make the patient feel nauseous.
Lanthanum carbonate is near barium in the periodic table and is visible on abdominal x-rays. The advantages of lanthanum are that it is a non-calcium, non-aluminium binder, it can reduce tablet burden as it comes in different strengths, and it comes as a chewable tablet and granules. It can also be crushed and sprinkled on food. One of the main disadvantages, apart from cost, is its gastrointestinal effects. If taken on an empty stomach it can cause nausea and vomiting.
Vitamin D is essential for healthy bones. The body gets vitamin D from food and the sun in its inactive form (cholecalciferol). In order for it to become useful to the body it must first be metabolised by both the kidney and the liver to active vitamin D (1,25-dihydroxycholecalciferol). In renal failure this process is reduced, which in turn leads to reduced calcium absorption and increased PTH levels.
The calcium range aimed for is the normal range for CKD stage 3–5 and 2.2–2.5 mmol/L for dialysis patients (Renal Association 2010a).
Treatment options are:
- alfacalcidol (1-alpha-hydroxycholecalciferol)
- calcitriol (1,25-dihydroxycholecalciferol)
- vitamin D analogues, e.g. paricalcitol
These can be given either daily or pulsed (three times a week), and by the intravenous or oral route with no difference in efficacy. Haemodialysis patients may receive pulsed therapy in an attempt to minimise the number of tablets they have to take and to ensure adherence. Hypercalcaemia and hyperphosphataemia are the dose-limiting effects. Phosphate should always be corrected before commencing vitamin D. Care should also be taken not to over-suppress the PTH as this can lead to adynamic bone disease. The Renal Association advises aiming for a PTH of 2–9 times the upper limit of normal for the assay used locally.
One of the newest agents used to treat hyperparathyroidsim is cinacalcet, a calcimimetic. It acts on the calcium-sensing receptors on the parathyroid gland and mimics the effects of calcium, reducing PTH secretion. It can produce a reduction in calcium, phosphate, PTH and alkaline phosphatase. Calcium has to be monitored closely initially and after dose changes, as hypocalcaemia can occur. It has been accepted with restrictions by the National Institute for Health and Clinical Excellence (NICE 2007). It is very expensive and is not effective in everyone but can result in savings on erythropoiesis-stimulating agents (ESAs) and phosphate binders and is safer than an operation (parathyroidectomy), which has a high mortality with an average age of 45 years.
Renal anaemia
According to patients, anaemia is one of the most debilitating symptoms of renal disease. It is mainly caused by a lack of erythropoietin production by the kidney, leading to a reduction in red blood cell production by the bone marrow. NICE (2011a) and the Renal Association (2010b) provide guidelines for use in this area.
Renal anaemia can also be caused by:
- iron deficiency
- increased red blood cell breakdown
- blood loss (due to blood tests, haemodialysis or increased GI losses)
- hyperparathyroidism
- aluminium toxicity
- infection or inflammation
- inadequate dialysis
It is best to avoid blood transfusions in patients on the transplant list, to prevent the production of cytotoxic antibodies which can make getting a suitable donor match difficult. Treatment is with a combination of iron and ESAs. NICE and the Renal Association advise starting an ESA if the haemoglobin is below 11 g/dL or if the patient is symptomatic. The ESAs available in the UK are epoetin alfa, beta, theta and zeta, darbepoetin (Aranesp) and methoxy polyethylene glycol-epoetin beta (Mircera). Biosimilars are available for some of the epoetins. It is important to ensure that your patient remains on the same brand and does not switch between them, as they are not interchangeable.
Iron deficiency limits the efficacy of ESA therapy and is the most common cause of non-response to treatment. Patients can be treated with either oral or intravenous iron. Many studies have shown a decrease in ESA maintenance doses with the pre-emptive use of intravenous iron. Intravenous iron is therefore the optimum form in which to give iron to haemodialysis patients and CKD patients on an ESA.
The IV iron products available in the UK are iron sucrose (Venofer), iron dextran (Cosmofer), ferric carboxymaltose (Ferinject) and iron isomaltoside 1000 (Monofer). A test dose is recommended for all intravenous iron preparations apart from Monofer and Ferinject. The main side effects associated with intravenous iron are gastrointestinal upset, injection-site reactions, anaphylactic reactions and hypotension. In practice the main ones are slightly loose stools on the day the patient receives the iron, a metallic taste during the infusion and injection-site reactions. Use intravenous iron with care in people with allergic-type conditions, e.g. asthma and eczema.
The aim of iron treatment is to obtain:
- ferritin 200–500 ng/mL
- transferrin saturation > 20%
- hypochromic red cells < 6%
The dose of ESA the patient is started on depends on the patient’s weight and haemoglobin. Different hospitals have different supply procedures (supplied by the hospital, shared care or home-delivery schemes run by outside companies). The aim of anaemia treatment is to achieve a haemoglobin of 10–12 g/dL with a rise of 1–2 g/dL every month. There have been a number of studies over the past few years that have shown that if you normalise haemoglobin in dialysis patients it can lead to an increase in mortality and vascular access failure (Singh et al. 2006, Drueke et al. 2006, Renal Association 2010b). Blood pressure (BP) should always be checked prior to administering an ESA injection. Administration should be discussed with medical staff if BP > 170/95 mmHg. However, the ESA should not be withheld on the basis of a single BP measurement, but should be discussed with a clinician who will take responsibility for the treatment of the patient’s hypertension.
The more common side effects of ESAs are:
- hypertension (usually due to the haemoglobin increasing too quickly)
- flu-like symptoms
- thrombosis
- hyperkalaemia
- seizures
Sodium bicarbonate
This is used to correct the acidosis associated with CKD due to reduced excretion of hydrogen ions by the kidney. If left uncorrected it can lead to respiratory problems and hyperkalaemia. Sodium bicarbonate capsules and tablets are used at doses from 500 mg twice a day, up to 2 g four times a day or more.
Hyperkalaemia
Hyperkalaemia is a common problem in CKD, especially once GFR is below 40–60 mL/min, and it can lead to arrhythmias and death if left untreated. It can be treated with a combination of the following (Levy et al. 2004, Ashley 2004):
- removal of potassium-sparing medication, e.g. spironolactone, ACE inhibitors, ARBs, trimethoprim
- dietary potassium (K+) restriction
- treatment of acidosis – sodium bicarbonate
- 50 mL 50% glucose and short-acting insulin 10 units over 5–10 minutes repeated according to response – lowers K+ by 1–2 mmol/L over 30–60 minutes
- 10 mL 10% calcium gluconate over 60 seconds to stabilise cardiac muscle
- calcium resonium – works slowly and can cause severe constipation, so always prescribe with a laxative
- salbutamol nebules (lowers K+ by 0.6–1 mmol/L)
- dialysis
Hypertension
Hypertension can be both cause and effect of renal impairment, and it affects approximately 80–90% of renal patients. It is defined as BP ≥ 140/90 mmHg measured on three separate occasions. Malignant hypertension, defined as BP > 180/110 mmHg with progressive organ damage and papilloedema, must be treated immediately. Guidelines from NICE (2011b) and the Renal Association (2011) are available on the treatment of hypertension.
BP aimed for:
- with proteinuria > 1 g/24 h or diabetic
- Renal Association: < 130/80 mmHg
- without proteinuria
- NICE: < 140/90 mmHg
- Renal Association: < 140/90 mmHg
- NICE: < 140/90 mmHg
The latest update to NICE (2011b) aims for a BP target of < 150/90 mmHg in patients over 80 years of age.
Renal hypertension is mainly due to increased activity of the renin–angiotensin system (RAS) causing sodium and water retention. It must be adequately controlled to limit the rate of decline of kidney function and decrease the risk of cardiovascular mortality. Rarely is it controlled by one drug, and a combination is usually required.
Drug therapies available:
- beta-adrenoceptor blocking drugs
- calcium-channel blockers
- drugs affecting the RAS
- alpha-adrenoceptor blocking drugs
- centrally acting agents
- diuretics
Beta-adrenoceptor blocking drugs
According to NICE (2011b), these should be used in younger patients who are intolerant of ACE inhibitors or ARBs. In renal patients beta-blockade is best achieved with bisoprolol, carvedilol or metoprolol as they are dual or hepatically excreted. In practice most are well tolerated, but always start with a low dose and gradually increase the dose as tolerated. Beta-blockers are best avoided if clinically possible in people with new fistulas as they can decrease the blood flow to the fistula and cause maturation problems. Water-soluble beta-blockers are less likely to cause sleep disturbances but are usually renally excreted, and therefore may accumulate in renal failure – although this is not usually a problem.
Calcium-channel blockers
These are first-line agents in patients > 55 years old and in black African or Caribbean patients (NICE 2011b). One limitation is ankle swelling; this is more frequent with the dihydropyridines such as amlodipine. Diltiazem is sometimes used to reduce proteinuria. Lercanidipine, nicardipine, diltiazem and verapamil may cause an increase in ciclosporin levels, so they should be used with care in transplant patients. Verapamil can also cause constipation.
Drugs affecting the RAS
These are first-line agents for patients < 55 years old and can be subdivided into ACE inhibitors, ARBs and renin inhibitors (e.g. aliskiren) (NICE 2011b). They have cardio- and reno-protective effects. ARBs are less likely to cause the cough associated with ACE inhibitors, because they do not affect bradykinin. ACE inhibitors and ARBs are two of the main treatments for diabetic nephropathy and proteinuria as they can prevent the rate of decline of renal function. They exert their reno-protective effect by reducing proteinuria, increasing GFR and reducing arterial blood pressure. They should be used with caution in patients with renal artery stenosis or dehydration, where they may cause a reduction in GFR. When initiating treatment, especially in haemodialysis patients, start with a small dose at night. Hyperkalaemia and increased creatinine are the dose-limiting factors associated with this class of antihypertensive. An increase in creatinine of 20% should be expected. Urea and electrolytes (U&Es) should be monitored every 1–2 weeks after starting and dose alterations.
Alpha-adrenoceptor blocking drugs
Alpha-blockers are not first-line agents but are used in conjunction with other antihypertensives, as renal patients usually have resistant hypertension. They also have the advantage that they can lower cholesterol levels and help with urinary retention in benign prostatic hyperplasia.
Centrally acting agents
As renal hypertension is so difficult to treat, centrally acting agents may also be used, e.g. moxonidine or methyldopa, but side effects such as tiredness tend to limit the long-term use of the latter. Vasodilatory agents, e.g. hydralazine or minoxidil, are other alternatives, although side effects such as hirsutism may limit the use of minoxidil, and fluid retention and systemic lupus erythematosis (in high doses) that of hydralazine.
Diuretics
Thiazide diuretics such as bendroflumethiazide are ineffective if creatinine clearance is less than 30 mL/min. Metolazone has a role in combination with loop diuretics to help remove fluid in resistant oedema. Metolazone is now unlicensed but can be imported from IDIS.
Loop diuretics – A normal dose of furosemide in CKD can be from 250 mg to 2 g per day. If the oral formulation does not work then intravenous furosemide is indicated, but monitor for signs of deafness, which are usually reversible. Bumetanide can also be used and may be beneficial in patients in whom furosemide is not working. A rough conversion is 1 mg of bumetanide = 40 mg of furosemide.
Prolonged diuretic therapy can also lead to fluid depletion, which can cause AKI, so check the patient’s weight before and during therapy. Monitoring a patient’s weight is the best way to assess fluid balance, as urine collections are notoriously inaccurate.
Related posts:
Managing Chronic Conditions: The Policy Context
Acute Kidney Injury in Hospitalised Patients
General Considerations Related to Treatment Modalities
Optimising Nutrition in People with Chronic Kidney Disease
Supportive and Palliative Care for Patients with Advanced Kidney Disease
A Practical Approach to Chronic Kidney Disease in Primary Care
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