Nutrition & drug dosing in dialysis patient

1. 1
PABITRA THAPA
B-PHARM, MBA
Product Manager
Asian Pharmaceuticals
Kathmandu, Nepal
January 20, 2018

2. 2
Nutrition of patient undergoing dialysis.
Dialysis and CKD Overview
Dialysis is a process that uses a man-made membrane to filter out toxins, waste products, and excess fluid
from the blood when kidney function is impaired. Dialysis treatment also balances the body´s calcium,
phosphorus and potassium levels. Dialysis treatment extends life expectancy significantly, but it alone is
not enough to manage advanced CKD,so it is used in conjunction with dietary restrictions and medication
to slow down the progression of CKD. (Munuais-ja maksaliitto 2013.)
Removal of excess fluid through dialysis is also known as ultrafiltration. The level of ultrafiltration is
dependent on the patient´s fluid load. Fluid load is determined by weighing the patient before dialysis
treatment to determine a post-dialysis target weight. Ideally, the weight gain between dialysis treatments is
a maximum of 2 kilograms.
Dialysis is the most widely utilized treatment for end-stage CKD. However,it requires extensive
modifications and restrictions to a patient´s lifestyle and often interferes with daily activities. (Pessoa &
Linhares 2015.) Long-term compliance with dietary restrictions, medications and treatment schedules can
cause stress to hemodialysis patients. Further, hemodialysis is a time- and energy-consuming treatment,
which can potentially cause social isolation, dependency on others, financial stress and strained family
relationships (Seah- Tan- Srinivas- Wu - Griva 2013).
CKD is a long-term health condition brought on by damage to both kidneys, which is usually irreversible,
and which can be triggered by severalcauses. The most common causes are diabetes mellitus,
hypertension, smoking, cardiovascular disease, advanced age, chronic use of non-steroidal anti-
inflammatory drugs, and obesity.
In addition to CKD,two other reasons a patient may need dialysis are glomerulonephritis and interstitial
nephritis. The glomeruli are parts of the kidney that filter excess fluid and waste products from urine and
glomerulonephritis is an inflammation of the glomeruli that is treated with dialysis. Interstitial nephritis is
a swelling between the kidney tubules, which causes the kidneys to function less efficiently, and can be
acute or chronic. Interstitial nephritis may also be treated with dialysis. (Munuais-ja maksaliitto 2013.)
Renal Diet Overview
The main goal of the renal diet is to manage the levels of circulating waste products and minerals, between
dialysis treatments. To achieve this, patients undergoing dialysis treatment are instructed to limit their
intake of vegetables, fruits, legumes, nuts, whole grains and dairy, because these foods contain high
amounts of potassium and phosphate, which can cause excess strain to already-failing kidneys. Further,
fluid intake is generally restricted in order to control interdialytic weight gain.
However,this diet is complicated to manage and can cause various problems. Prohibition of various foods
can lead to monotony of diet and malnutrition. Moreover, loss of appetite is common in dialysis patients
and contributes to undernutrition. Furthermore, limiting consumption of many everyday foods makes it
difficult for patients to adequately satisfy their energy and protein needs.
Tracking patient´s nutritional status is necessary to identify possible problems early during hemodialysis
treatment. Regular blood tests to check on albumin, phosphorus, acidosis, and C-reactive protein are part
of a patient´s treatment plan. Patients are always weighed before each dialysis treatment to determine how
much fluid can be removed safely. BMI is calculated monthly and creatinine is checked from a blood
sample monthly as well. Patients meet with a licensed nutritionist once or twice a year.Food cravings and
thirst are a common issue for dialysis patients

3. 3
Fluid and salt
Healthy kidneys can regulate fluid balance by excreting excess water and salt from the body. But patients
with CKD are unable to adequately regulate their fluid balance, due to their kidney failure. Because any
excess fluid retention in the body causes hypertension, shortness of breath and nausea, patients on
hemodialysis are put on fluid restrictions. To determine how much fluid can be safely consumed per day, a
patient´s 5 urine output is measured. The daily fluid allowance is usually the amount of urine output per
day plus 500-750 ml of fluid depending on kidney function. As a result of their kidney disease and the
resulting fluid restriction, many patients on hemodialysis urinate very little or not at all. Sodium intake is
also restricted for patients on a renal diet. Sodium intake can increase thirst for patients on a renal diet,
because sodium affects receptors located in the brain called osmoreceptors, which regulate the feeling of
thirst. Excessive thirst makes it difficult to adhere to the fluid restrictions discussed above. Current
recommendation of salt for patients on hemodialysis is less than 5 grams a day or 2000mg of sodium.To
manage thirst, use of ice cubes,small sips and sour flavoured candy were common among dialysis
patients.
Protein
Kidney disease is associated with impaired protein metabolism. Therefore,protein consumption is often
restricted. Only 1.2g/kg/day of protein is typically recommended for dialysis patients. About 50% of the
protein should come from sources that are of high biological value such as chicken, fish, eggs .
When patients are unable to ingest sufficient protein through their regular food consumption, they may
seek to supplement their protein intake through the use of oral protein supplements. However,oral protein
supplements can be hard on dialysis patients´ digestion and can cause unwanted side effects like nausea.
For patients who wish to avoid oral protein supplements or parenteralprotein supplementation, egg whites
seem to be a good choice of protein because of their low phosphate-to-protein ratio. Further, egg whites
seem to be easily digested by patients receiving hemodialysis treatment who frequently suffer from
gastrointestinal discomfort. (Taylor et al. 2011.) Patients on dialysis should carefully monitor the amount
of protein they consume because excess intake of protein can cause strain on the kidneys. Regular blood
tests for albumin serum levels are necessary for all dialysis patients. Albumin is a protein found in animal
sources such 6 as milk, eggs and meat. Lowered serum albumin is associated with higher mortality rate
among patients receiving dialysis treatments.
Phosphorus
Patients with CKD gradually lose the ability to remove excess phosphorus from their blood. This can
result in renal osteodystrophy, which happens when impaired kidneys fail to maintain calcium and
phosphorus levels in the blood causing damage to veins, arteries, lungs and soft tissues of the body. Renal
osteodystrophy affects nearly all people receiving dialysis treatment. Phosphorous restrictions are used to
prevent and slow down the progression of renal osteodystrophy. Dialysis patients should limit their daily
phosphorus intake to 800- 1000mg. The amount is adjusted according to patient´s weight and gender.
Many foods that contain high amounts of phosphorus also contain high amounts of protein, so many
scientific societies recommend lowered protein intake in order to reduce the amount of phosphorus
consumed. One gram of protein has about 15mg of phosphorus and about 30% to 70% of it is absorbed in
the intestine. (GonzalesParra et al. 2012.)
Potassium
Healthy kidneys are able to maintain normal potassium levels by excreting excess potassium through
urine. But people with CKD have impaired kidney function, which causes accumulation of potassium in
their blood and increases the risk of hyperkalemia. Hyperkalemia causes abnormal heart rhythms which
increases the risk of sudden death.In CKD patients, hemodialysis treatment is not enough to control

4. 4
potassium levels and dietary restriction on potassium consumption is always necessary. The average daily
limit for potassium intake for a hemodialysis patient is 2000-2500mg. (Munuais-ja maksaliitto 2013.)
Prevention of Anemia
Anemia is common among dialysis patients and it appears to be more common in those who suffer from
malnutrition or protein energy wasting. Symptoms of anemia include fatigue, weakness,dizziness,
headache,low immunity, breathless or shortness of breath, chest pain, low appetite and pale.
Anemia of chronic kidney disease is one of the complications of kidney failure. The main reason
for anemia among chronic disease patients is the reduced production of erythropoietin (EPO) by the
kidneys. EPO prompts the bone marrow to make red blood cells. When the kidney’s function is
decreasing, the amount of EPO produced will be reduced. Other factors causing anemia among dialysis
patients are:
1. Reduced red blood cell lifespan due to accumulated urea toxic
2. Malnutrition
3. Lack of iron
4. Lack of folate and other vitamins
5. Blood loss during haemodialysis
Adequate intake of protein, iron, vitamin C, vitamin B 12 and folate are important in preventing and
treating anemia as these nutrients are the important elements in making new red blood cells.
Conclusion
To evaluate the amount of food intake and food preference, the patient's diet history should be
taken. The patient's age, gender, social environment, economic, psychological, and educational
status and history of the disease should be considered due to nutrition effect. Also, including
weekends, during the 3-7 days whole foods is recorded by the patient along with the amount.
Daily intake of calories and nutrients of the patients are calculated with information from those
records. In addition, laboratory values and SGA as a scoring tool are very important for preparing
a appropriate diet for HD patients.
The hemodialysis therapy should be dealt with by a multidisciplinary team, as recommended for other
high risk populations (Morais 2005). A part of medical nutrition therapy is to provide nutrition education
and periodic counseling by dietitians. For effective intervention, dietitians should present a guide for
educating HD patients about individual nutritional needs. This guide should provide information about
food sources,nutrients and usage exchange food lists. Adapting to patients requirements of intakes should
be based on their laboratory values. Patients may be predisposed to receiving lower than recommended
amounts of energy and macro-nutrients to the diet and patients who received information or counseling
about their diet must be followed up closely by renal dietitians (Mahan 2012).
If a patient has diabetes, the control of blood sugar is required with a specialized diet therapy. Due to high
serum glucose levels, osmolality increases,water and potassium are pulled out of cells. There are the
relationship between glycemic control and survival of hemodialysis patients (Mahan 2012). Poor glycemic
control causes to macrovascular complications and generation of advanced glycation end products
(AGEs)( Ricks 2012). The diet for diabetes management can be modified for a patient on dialysis.
References:
Munuais-ja maksaliitto. 2013. Munuaispotilaan opas. http://www.muma.fi/munuaispotilaan_opas/munuaispotilaan_opas.
Accessed 30.1.2017
Taylor, L., Kalantar-Zadeh, K., Markewich, T., Colman, S., Benner, D., Sim, J., Kovesdy, C. (2011). Dietaryegg whites for
phosphorus control inmaintenance hemodialysis patients. Journal ofRenalCare. 37 (1), 16-24.
Gonzalez-Parra, E., Gracia-Iguacel, C., Egido, J., Ortiz, A. (2012) Phosphorus and nu-tritioninchronic kidneydisease. International
Journal of Nephrology. 2012, 1-5

5. 5
Drug Dosing Consideration for Patients on Dialysis
The pharmacokinetics of a drug may be altered in patients with renal impairment who require dialysis.
Some drugs are contraindicated. The drug’s clearance and therapeutic index determine if a dose
adjustment is needed. A lower dose or less frequent dosing may be required.We should start at a low dose
and increase gradually. If possible give once-daily drugs after dialysis.
Renal impairment reduces the clearance of some drugs.4
When prescribing for patients on dialysis, it is
essential to consult a reference guide to determine if the drug is subject to renal clearance and requires a
dose adjustment.
Dose adjustments can be made by reducing the dose, increasing the interval between doses or a
combination of the two. The approach to take is determined by the relative importance of stable serum
drug concentrations (for instance to maintain the antimicrobial effect of penicillins), the adverse effects of
peak concentrations after intermittent doses, and patient convenience.
Suggested resources for drug dosing in dialysis
Australian Medicines Handbook (https://amhonline.amh.net.au)
Therapeutic Guidelines: Antibiotic. Version 15 (www.tg.org.au)
MIMS Australia (http://mims.com.au)
Bailie and Mason’s 2014 Dialysis ofDrugs (http://renalpharmacyconsultants.com/publications)
Oxford Handbook ofDialysis. 3rd ed. Oxford: Oxford University Press; 2009.
The Renal Drug Handbook. 4th ed. London: Radcliffe Publishing; 2014.
Pharmacokinetics
The two main considerations that determine if a particular drug requires dose reduction in dialysis patients are renal
clearance and therapeutic index. Other factors that may affect dosing include clearance by dialysis, increased
availability of highly protein-bound drugs due to hypoalbuminaemia,altered volume of distribution and the presence
of comorbid hepatic dysfunction.
Clearance
We should Consider the magnitude of the renal component of total clearance of the drug and any active metabolites.
For drugs subject to significant renal clearance, the marked decrease in glomerular filtration rate seen in patients on
dialysis results in an increase in half-life and drug accumulation with repeated dosing in the absence of dose
adjustment. These changes also apply to renally cleared drug metabolites which may be active or toxic.
The increased half-life also prolongs the time to achieve a steady-state which,in clinical practice, means a longer
period is required before judging that the maximum effect of a particular dose has been achieved. The starting dose
should be low and caution is required before increasing drug doses.Given the longer time to steady state,a loading
dose can be considered if giving a renally adjusted dose could lead to a delay in reaching a therapeutic serum
concentration (for instance, if treating a severe infection). In practice, loading doses are rarely used.
Therapeutic index
A drug with a wide therapeutic index may be safely given without a dose reduction knowing that, although the drug
concentration will be higher, this is unlikely to result in harm. However, drugs with narrow therapeutic indices may
require substantialdose reductions.
Dialysis and drug clearance
Patients on dialysis are subject to extracorporeal clearance of small molecules, including many drugs.The extent to
which dialysis removes a particular drug from plasma is dependent on its water solubility, molecular weight, protein
binding and volume of distribution.3 Many reference sources contain lists of drugs cleared by dialysis.

6. 6
Haemodialysis can pose a challenge as it is intermittent and has the potential for relatively rapid drug clearance. In
practice this is most important when prescribing once-daily drugs,especially antibiotics. It may be best to give them
after dialysis. Dose timing is typically left unchanged for drugs dosed more frequently, as complex dosing regimens
may reduce adherence to therapy. In peritoneal dialysis, timing is not important as the clearance of small molecules
is slower and more even than in haemodialysis.
Commonly prescribed drugs
Many drugs are not renally cleared. Specific examples of commonly used drugs include proton pump inhibitors,
statins,corticosteroids and calcium channel blockers. They are unlikely to need a dose adjustment in patients on
dialysis.
Analgesics
Patients on dialysis may have comorbid pain, but its treatment is often suboptimal.Paracetamol is the preferred simple analgesic.
It is safe and can be used without dose modification.
Although nephrotoxicity might be considered of little importance, non-steroidal anti-inflammatory drugs (NSAIDs) should be
avoided as they may cause sodium retention, hypertension and gastrointestinal toxicity. Due to theincreased risk of myocardial
infarction seen in the general population, cyclo-oxygenase-2 inhibitors isnot recommend in dialysis patients as they are already at
markedly higher baseline cardiovascular risk.Topical NSAIDs appear to be safe as systemicabsorption is minimal.
Many opioids, or their active metabolites, are renally cleared (Table). Codeine and morphine have active, renally excreted
metabolites so they are not recommended because of theincreased risk of toxicity. Hydromorphoneis our preferred oral opioid
for treating severe pain. It is five to seven times more potent than morphine so starting doses are correspondingly low (0.5–1 mg
orally 6-hourly).Its active metabolite hydromorphone-3-glucuronide can accumulate, but is substantially cleared by haemodialysis
and is less likely to cause adverse effects than morphine metabolites.Oxycodone may be used, although thesustained-release
formulations should be used only with caution due to the risk of accumulation and toxicity. Fentanyland buprenorphineboth
undergo hepatic clearance and can be used when theoral route is not suitable.Whichever opioid is chosen, it is important to use
small starting doses and closely monitor up-titration to avoid toxicity.
Neuropathic pain is common in patients on dialysis.Amitriptyline is hepatically metabolised and does not accumulate. However, it has
numerous adverse effects including anticholinergic effects and postural hypotension which may limit its use in patients with multiple
comorbidities. Gabapentin and pregabalin are effective andmay also treat uraemic pruritis. However, they are extensively renally cleared
and marked dose reductions are necessary to avoid sedation, ataxia and dizziness. Doses should be taken after dialysis.

7. 7
Opioid-induced constipation
In surveys,over half of the patients on dialysis report constipation.Prevention of opioid-induced constipation is
particularly important in patients on peritoneal dialysis as constipation may markedly reduce its effectiveness.
Lactulose, docusate,senna and bisacodylare all suitable treatments.
Antimicrobials
Many antibiotics require dose adjustment in patients receiving dialysis. Quinolones, sulfamethoxazole with
trimethoprim, glycopeptides and aminoglycosides all require significant dose reductions.Trimethoprim should be
avoided in patients due to the risk of hyperkalaemia and bone marrow suppression.2
Nitrofurantoin is primarily
renally excreted, and relies on urinary concentration to achieve its effect. It is rarely associated with neurotoxicity
and life-threatening pulmonary toxicity.Despite recent support for extending its use in chronic kidney disease,it
should be avoided in patients on dialysis.Cephalosporins and penicillins have wider therapeutic indices and vary in
the need for dose adjustment.Once-daily doses should be prescribed after haemodialysis.
The antiviral drug aciclovir and its prodrugs,famciclovir and valaciclovir, are extensively renally excreted. These
drugs accumulate rapidly in patients on dialysis and may cause severe neurological toxicity.They should only be
prescribed after discussion with the treating nephrologist and with appropriate dose reduction and close clinical
follow-up.
Anticoagulants
Despite controversy surrounding its use for stroke prevention in dialysis patients with atrial fibrillation, warfarin
remains the anticoagulant of choice for those with venous thromboembolism or other indications for anticoagulation.
The dose is adjusted according to the INR in the usualmanner. Close monitoring and avoidance of supratherapeutic
INRs is particularly important as patients on dialysis have increased rates of bleeding with warfarin.Low-molecular-
weight heparins are renally excreted and they are rarely used for anticoagulation as their effect is difficult to
predict.Unfractionated heparin is preferred for acute treatment of venous thromboembolism in patients on dialysis.
The newer oral anticoagulants (such as dabigatran and rivaroxaban) are contraindicated. They all undergo a degree of
renal clearance which makes them unsuitable for patients on dialysis.
Drugs for diabetes
Patients with diabetes who need dialysis have reduced insulin clearance, so they may be more liable to
hypoglycaemia with both insulin and insulin secretagogues (sulfonylureas).These patients may also be at increased
risk of hypoglycaemia unawareness due to comorbid illnesses and co-prescribed drugs.
Gliclazide and glipizide are the preferred sulfonylureas as they have short half-lives and no active metabolites. All
sulfonylureas should be started at low doses and up-titrated carefully. The dipeptidyl peptidase-4 inhibitors vary in
their suitability for use in dialysis so the product information should be reviewed before prescribing.Metformin is
contraindicated due to the risk of lactic acidosis.Although not renally excreted, thiazolidinediones are associated
with fluid retention and are not recommended.The sodium-glucose co-transporterinhibitors are contraindicated in
dialysis patients as they depend on the glomerular filtration of glucose for their effect.
Conclusion: In general, commence with a low dose,observe closely for adverse effects and increase the dose only
after a timely interval. Put simply: ‘start low and go slow’.
References:
1. ClaytonP, McDonald S, HurstK, editors.ANZDATARegistry AnnualReport2013. Adelaide: Australia and New Zealand Dialysis and Transplant
Registry; 2013.www.anzdata.org.au/anzdata/AnzdataReport/36thReport/ANZDATA_36th_Annual%20_Report.pdf [cited 2016 Jan4]
2. Manley HJ, Drayer DK, MutherRS. Medication-relatedproblemtypeand appearancerate in ambulatory hemodialysis patients. BMC
Nephrol 2003;4:10. 10.1186/1471-2369-4-10 [PMC freearticle][PubMed][Cross Ref]
3. Weir MR, Fink JC. Safety ofmedicaltherapy in patients withchronic kidney diseaseand end-stagerenal disease. CurrOpinNephrol
Hypertens 2014;23:306-13.10.1097/01.mnh.0000444912.40418.45 [PubMed][Cross Ref]

8. 8
4. Faull R, LeeL. Prescribing in renal disease. Aust Prescr 2007;30:17-20.
5. Meijers BK, Bammens B, Verbeke K, Evenepoel P.Areview ofalbumin binding in CKD. Am J Kidney Dis 2008;51:839-50.
10.1053/j.ajkd.2007.12.035 [PubMed][Cross Ref]
6. Katzung BG, Masters SB, Trevor AJ. Basic& clinical pharmacology. LANGEBasicScience. 12thed. McGraw-Hill Education; 2012