Chronic Kidney Disease Management – Advance Practice Nurse Pharmacology Credit
The purpose of this activity is to enable the learner to review the management of patients with chronic kidney disease. The learner will garner a better understanding of how to manage complications occurring during dialysis, better comprehend the pharmacokinetics and pharmacodynamics in patients with chronic kidney disease and finally a brief review of the role that nurses (both dialysis and non-dialysis nurses) play in caring for patients with chronic kidney disease.
At the end of this learning activity, the learner will be able to:
- Recognize the side effect profile of common oral hypoglycemic medications used in patients with chronic kidney disease
- Define the etiology and treatment of intradialytic hypotension
- Describe the volume of distribution of drugs and how it affects drug plasma concentrations
- List the 3 types of allergic reactions to dialyzers
- Identify the cause of dialysis disequilibrium syndrome?
Chronic kidney disease (CKD) is defined as kidney damage or a glomerular filtration rate < 60 ml/min/1.73 m2 for 3 months or more regardless of the original cause (KDIGO, 2013). Patients with CKD can be extremely challenging to manage medically given their multiple comorbid conditions and the potential for serious consequences if mistakes are made in their care. Common comorbidities that affect patients with CKD include hypertension, diabetes, dyslipidemia and anemia. In patients with CKD, it is very common to experience deleterious effects from standard medications used to treat the very same comorbidities in other patient populations. Therefore, it is imperative to provide appropriate care to these patients taking into account all their comorbidities.
When discussing the care of CKD patients with multiple comorbidities this patient population can be divided into two groups; patients with CKD and patients with end stage renal disease (ESRD). Nurses and other health care practitioners caring for patients with CKD most be cognizant about the perils of applying standard therapy to this patient group.
Hypertension Management and Case Study
Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) are commonly used together in the management of hypertension in patients with CKD. There is, however, a greater incidence of acute kidney injury and adverse cardiac events. Common adverse events reported with ACE inhibitors and ARBs include cough and angioedema with ACE inhibitors and anaphylaxis and hyperkalemia with either drug class.
You are a nurse for a primary care physician who is seeing a 23 old year old recently diagnosed with CKD and is also hypertensive. He was started on Lisinopril 3 weeks ago and since then has reported a chronic nonproductive cough. He denies any other signs and symptoms of a cold. He reports no other complaints and is dismissive of the cough but continues to clear his throat during your assessment.
Discussion for Case Study:
ACE inhibitors are one of the most commonly prescribed anti hypertensives. A dry cough is a well reported side effect to ACE inhibitors. Once the patient was educated that this may be a side effect he reported that the cough was progressively getting worse and would occasionally wake him up at night. The physician discontinued the ACE inhibitor and prescribed a ARB. The patient was seen in clinic 4 weeks later and he denied the presence of any side effects.
Often recently diagnosed patients are overwhelmed by a recent life altering diagnosis and may tend to brush off what they perceive as small complaints. It is important to remain a patient advocate even when the patient may be overwhelmed. One could argue that the patient is at an even greater need for you during these times.
Diabetes Management and Case Study
In ESRD patients with diabetes, Metformin is an effective agent oral hypoglycemic which may be used in patients with CKD but should be discontinued when the Glomerular Filtration Rate (GFR) falls below 30 ml/min due to the risk of lactic acidosis with accumulation due to impaired renal clearance. It is important to note that Metformin is not completely cleared by the dialyzer.
In the older patient with diabetes, sulfonylureas (such as glipizide, glyburide and Amaryl) and thiazolidinediones (such as Pioglitazone [Actos] and Rosiglitazone [Avandia] should be used cautiously because of the concern of severe hypoglycemia with the sulfonylureas and the risk of exacerbating the symptoms of heart failure with thiazolidinediones (Gangji, Cukierman, Gerstein, Goldsmith, & Clase, 2007). Of all the sulfonylureas, glyburide appears to have the highest risk of hypoglycemia especially in the setting of kidney impairment. Other sulfonylureas such as glipizide and gliclazide which are metabolized through the liver could be continued at standard doses without adjustments in patients with CKD. In spite of the use of oral hypoglycemic agents, insulin may be needed for effective glycemic control.
You are a dialysis nurse working at an outpatient clinic and part of your clinic’s policy is to review each patient’s medication list each month. Ms. C. is a 38-year-old female with a history of CKD, HTN and Diabetes. She recently went to visit her parents and while she was there she felt dizzy at a family function. Her glucose level was checked by her mom who noted that blood glucose was 478. Her mom insisted she see the family doctor who had been taking care of her before she left for college. He noted that she had been taken off Metformin which she had previously been on and instead was on glipizide. He then added Metformin 1000mg po daily. Of note she neglected telling him she was now diagnosed with ESRD. She has been taking the Metformin and glipizide for a total of 3 weeks.
Case Study Discussion:
Promptly inform the nephrologist on call regarding the Metformin prescribed, ask the patient what her blood glucose trends have been. The patient in this case had not been checking her blood glucose levels at home. Her blood glucose level in the clinic today is 82. The nephrologist promptly ordered a discontinue order on her Metformin and increased her dose of glipizide. He also added a HbA1C level lab draw.
Managing complications occurring during dialysis
With hemodialysis, there are specific complications that occur acutely during the dialysis process which the nurses caring for dialysis patients must be cognizant of including; hypotension, cramps, nausea and vomiting, headache, chest pain, back pain, itching, fever and chills. This article will focus on a few commonly occurring complications during dialysis.
Often times dialysis nurses are expected to manage these acute dialysis complications independently given the acuity and frequency of their occurrence. As such, they are expected to be well versed in managing these complications.
Hypotension occurs in 25-55% of hemodialysis treatments. Variations in blood pressure are caused by a decrease in blood volume induced by the process of ultrafiltration coupled with the fact that patients with ESRD tend to have abnormal compensatory response systems to fluid removal. In addition, most of these patients have underlying cardiovascular disease. Ultimately the process of ultrafiltration surpasses all the mechanisms activated to prevent a clinically significant drop in blood pressure (Santos et al., 2012).
According to Liu et al. (2015), hypotension during hemodialysis is most common amongst patients with diabetes mellitus. They also report that patients with arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) may develop high-output cardiac failure due to shunting of blood through the dialysis access.
Acetate which was previously used as a buffer in dialysate solutions was linked to dialysis-associated hypotension due to its cardio-depressive effect. As expected since the introduction of bicarbonate-containing dialysate, the incidence of hypotension during dialysis has decreased (Liu et al., 2015). Repetitive episodes of intra-dialysis hypotension have been associated with asymptomatic myocardial ischemia which then induces myocardial stunning and eventually irreversible cardiac death.
Dialysis-associated hypotension should be managed acutely by discontinuing ultrafiltration, administration of 100-250 ml of isotonic saline, 10 ml of 23% saturated hypertonic saline, administration of a low salt albumin solution. Other methods proposed for limiting the occurrence of hypotension during dialysis include; careful evaluation and monitoring of the patient’s dry weight. The estimated dry weight is defined as the patient’s baseline weight without the weight of the fluid accumulated in between dialysis treatment sessions. The corresponding measure in a non ESRD patient will be the weight the patient weighs after urinating. Ultrafiltration modeling can be performed in patients at risk for intra dialysis hypotension where fluid is removed at the beginning rather than at the end of the dialysis treatment (Liu et al., 2015). Cooling of the dialysate during dialysis, refraining from eating heavy meals during and immediately before dialysis treatments are also being used to prevent hypotension.
A common pharmacological intervention used to combat hypotension is Midodrine which is a selective alpha 1 adrenergic agent administered orally. However, there is limited evidence to support its efficacy. As a matter of fact, the Food and Drug Administration (FDA) recently considered reversing the drugs approval due to the drug’s manufacturer’s failure to fulfill its obligation to perform post marketing studies to show clinical effectiveness. (Dhruva et al., 2010).
Finally, decreasing inter-dialysis weight gain, promoting greater sodium to water restriction and correcting severe anemia have all been beneficial in the management of hypotension occurring during dialysis.
Muscle cramps occur in 5-20% of dialysis treatments, their etiology remains unclear. Changes in perfusion to muscles due to extremely rapid volume removal often precipitate dialysis associated cramps. Often times, greater than 10-12 ml/kg/hr could be removed from dialysis patients based on their estimated dry weights (Liu et al., 2015).
Cramps can be treated by decreasing the ultrafiltration rate either by decreasing the volume to be removed during dialysis or increasing the time of dialysis. Another method is ultrafiltration profiling, the use of sodium modeling profiles and the administration of hypertonic saline have been reported as beneficial. In non-diabetic patients, using D50W solution has been shown to be helpful particularly towards the end of the dialysis session, especially since glucose is metabolized without the effects of hyperosmolality and intravascular volume expansion. Diazepam has also been shown to be effective in treating dialysis associated muscle cramps but it may also cause hypotension. Quinine is also very effective in preventing muscle cramps if administered 1-2 hours prior to the hemodialysis session. However, a significant side effect is the risk of thrombocytopenia. Vitamin E and L-Carnitine have also been shown to be weakly effective.
Dialysis disequilibrium syndrome (DDS) is a syndrome characterized by a variety of acute neurologic symptoms which could range from benign to very severe. DDS usually affects dialysis patients when they first start dialysis and it is thought to be caused by cerebral edema. Tsai, Chen, & Tsao (2015) describe DDS as the clinical phenomenon of acute neurological dysfunction which is attributed to dialysis treatment related cerebral edema.
Risk factors for DDS include; CKD as a reason for initiating dialysis rather than Acute Kidney Injury (AKI), first dialysis treatment, very high urea concentrations in the blood prior to initiating dialysis, older age and pediatric patients, Other neurologic disease (such as seizures, stroke) as well as prior cerebral edema from other causes (such as hyponatremia and meningitis) (Zepeda-Orozco & Quigley, 2012).
Clinical manifestations of DDS include nausea, vomiting, headache, restlessness, blurred vision, asterixis (which is the tremor of the hand when the wrist is extended due to inability to actively maintain position secondary to metabolic encephalopathy), confusion, seizures, comas or death.
The best course for management of DDS is to establish slow urea removal either by reducing the duration of the first few dialysis sessions or by alternating ultrafiltration with hemodialysis. Also starting with a low blood flow rate and slowing building up to the target blood flow rate during sessions has been shown to be beneficial.
Allergic reactions to the dialyzer
Although uncommon, anaphylactic reactions to the dialyzer can occur especially on the first use. Reactions will be divided into three types in this article.
- Type 1 reactions are attributed to an IgE mediated hypersensitivity reaction to ethylene oxide which is used in the sterilization of new dialyzers. Type 1 reactions usually occur within a few minutes and may progress to full anaphylaxis if the offending stimulus is not removed (i.e. stopping the dialysis treatment). Treatment is usually with epinephrine and steroids. Dialysis should be stopped immediately and the patient’s blood should not be returned.
- Type 2 reactions occur from complement activation and cytokine release. This reaction usually occur several minutes (usually 20-40 minutes) into the dialysis treatment and will typically resolve with continued dialysis. They usually present as nonspecific symptoms such as chest and back pain.
- Type 3 reactions are pyogenic reactions which can occur at any time. They usually occur from endotoxin or bacterial contamination. Treatment is to stop hemodialysis immediately if hypotension is present and collect blood cultures then administer antibiotics and antipyretics.
Complications in patients undergoing peritoneal dialysis
Most common complications occurring with peritoneal dialysis includes peritonitis, catheter associated infections (non-peritonitis infections), metabolic disturbances and residual uremia. Peritonitis usually occurs secondary to lack of sterile technique during one of the peritoneal fluid exchange procedures. Clinically, peritonitis is diagnosed by an elevated peritoneal fluid white blood cell count greater or equal to 100/uL (with at least 50% of those being neutrophils). Of note, the bacterial count cut off is lower than that established for the diagnosis of spontaneous bacterial peritonitis because the peritoneal dialysis solution contains sugars in the form of dextrose. The clinical presentation is usually a cloudy dialysate fluid with abdominal pain and fever. The common organism involved are gram positive cocci and other skin flora. Treatment is either with intraperitoneal or oral antibiotics and most patients can be managed on an outpatient basis. If the infection does not respond to antibiotic therapy, the dialysis catheter may have to be removed. In catheter associated infections not related to peritonitis, management may be limited to silver nitrate administration or antibiotic therapy and on rare occasions the catheter may have to be removed.
Peritoneal dialysis patients are prone to multiple metabolic complications. For example, albumin and other proteins could be lost across the peritoneal membrane. There is a smaller chance of potassium and phosphorus accumulation with peritoneal dialysis than there is with hemodialysis.
Pharmacokinetics and pharmacodynamics in patients with CKD
Drugs that are primarily eliminated by the kidneys, have a narrow therapeutic index or have active metabolites that are primarily eliminated by the kidneys, should be closely monitored for adverse side effects. These dose adjustments are necessary to avoid toxicity in patients with CKD.
Medication errors are a huge factor contributing to morbidity in patients in general especially in patients with CKD given that a large proportion of medication errors occur due to dosing errors (prescribing standard doses to patients who should be receiving reduced doses) or prescribing errors account (prescribing medications to ESRD patients which should never be prescribed).
Most drug doses have to be adjusted in dialysis patients. In this section we will focus on understanding why and how doses must be adjusted in patients with CKD and patients with dialysis. First we must understand the bioavailability of drugs which is defined as the percentage of a drug which reaches the blood stream. Note that bioavailability is 100% in iv administration of drugs.
In patients with ESRD multiple factors affect drug availability including decreased gastrointestinal absorption, co administering drugs with phosphate binders which form complexes making them insoluble and therefore non absorbable. Impaired plasma protein binding resulting in more free drug available for metabolism through the liver. Uremia has been shown to alter drug pharmacokinetics and pharmacodynamics.
The volume of distribution of a drug is not an actual physical volume but rather it is a theoretical volume obtained from the ratio between the dose of a drug present within the body and the plasma concentration. The ratio is calculated once the concentration of the drug within the tissues and plasma have reached equilibrium. Therefore, lipid soluble drugs tend to have a higher volume of distribution while lipid insoluble drugs have a low volume of distribution.
ESRD patients with uremia may have decreased protein binding of drugs thereby affecting the amount of free (active) drug available. Also, drug metabolism by non-hepatic oxidation is delayed in patients with renal disease there by affecting the plasma concentration.
Drug monitoring and therapeutic drug ranges:
There are a few drug classes which have a narrow therapeutic range making it necessary for clinicians to monitor drug ranges due to the risk of drug toxicity. Antibiotics are a commonly used drug class and we will review a few drug classes and how their metabolism is affected in patients with CKD. Often times patients undergoing dialysis have poor vascular access options therefore dialysis nurses are asked to draw multiple labs especially labs checking for specific drug levels. It is important to understand when these drugs may be drawn. Often times the clinicians requesting the labs are not nephrologists and in such cases dialysis nurses should be able to educate and properly communicate with non-dialysis specialized personnel. This article will focus on 2 common examples.
Aminoglycosides e.g. Gentamicin (peak of 5-8 mg/L and a trough of 0.5-2 mg/L). The peak is usually drawn 30 min after a 30 – 45min infusion. The trough is usually drawn immediately prior to the dose. Both are drawn around the third dose.
Digoxin has a therapeutic dose range of 0.8-2.0 ng/mL and the lab is usually checked 5-7 days after the first dose in patients with normal renal function and 15-20 days in anephric patients. The lab sample should be drawn 12 hours after the maintenance dose is administered in all patients.
Most drug dosing has to be adjusted in patients with ESRD and some drugs may be avoided all together. In today’s healthcare climate laden with polypharmacy and over prescription, it is critical the nurses understand which drugs place their patients at increased risk for experiencing toxic side effects. We will examine a few common drugs and review how the doses change depending on the GFR.
Acetaminophen can be administered at normal doses and administered as often as every 4 hours in patients with a GFR > 50 mL/min. In patients with a GFR between 10-50 mL/min the standard 4 hour doses should be administered at 6 hour intervals. And in patients with a GFR < 10mL/min, the standard dose should be administered at 8 hour intervals. Patients on hemodialysis and peritoneal dialysis, should receive their dose reduced to q8h intervals as well.
Acetazolamide is a carbonic anhydrase inhibitor which is commonly used as a diuretic or for the treatment of glaucoma. In patients with a GFR > 50mL/min the standard dose should be administered every 6 hours. If the GFR is between 10-50 mL/min, the dose should be prolonged to q12h and if the GFR is less than 10 mL/min, the dose should be prolonged to q24h. In patients receiving both hemodialysis and peritoneal dialysis the dose should as be administered q24h.
Acetylsalicylic acid (Aspirin) can be administered q4h in patients with a GFR > 50 mL/min. The dose should be prolonged to q4-6h in patients with a GFR between 10 – 50 mL/min. In patients with a GFR with a GFR < 10 mL/min, it should be completely avoided. Patients on both hemodialysis and peritoneal dialysis may receive standard doses as patients with a normal GFR because it is appropriately cleared during dialysis.
When administering Atenolol in patients with CKD the dose must be decreased by 50% in patients with a GFR between 10 – 50 mL/min. In patients with a GFR < 10 mL/min, the dose should be decreased to 33% of the daily dose administered every 24 hours.
Cefazolin is normally administered q8h in patients with GFR > 50 mL/min. In patients with a GFR between 10 -50 mL/min, the dose should be prolonged to q12h. If the GFR is < 10mL/min, the dose should be halved and administered q24-48h. In hemodialysis patients, the dose should be weight based at 15-20 mg/kg after hemodialysis.
Chlorthalidone a thiazide diuretic should be completely avoided in patients with a GFR less than 50 mL/min including patients on dialysis.
Digoxin dose should be decreased by 10 – 25% of the standard dose administered to patients with a normal GFR. And in patients with a GFR < 10 mL/min the dose is decreased to 10-25% and the timing is prolonged to q 24-48h.
Rivaroxaban (Xarelto) and Triamterene should be avoided in patients with a GFR < 50 mL/min including dialysis patients.
Caring for the dialysis patient for non-dialysis nurses
Hemodialysis access can be either short term access of long term access. There are 3 options for long term hemodialysis access and they are; arteriovenous fistulas (AVF), arteriovenous grafts (AVG) and a tunneled venous catheter. Note that these are listed in the order of decreasing preference.
When considering options for short term dialysis access, the focus is to provide an access which can be used immediately and has minimal complications in the short term. Ideally an arteriovenous fistula should be placed at least 6 months prior to the initiation of dialysis. A dialysis graft should be placed 3- 6 weeks prior to the initiation of dialysis. A peritoneal dialysis catheter should be placed at least 2 weeks prior to the initiation of peritoneal dialysis (NKF, 2006).
Note that not all venous access catheters are equal. Specific catheters must be used when intending to perform dialysis. Dialysis catheters tend to have larger lumens to withstand the high blood flow rates. An ideal access has to be able to withstand flow rates of up to 600 ml/minute (NKF, 2006). The basic dialysis catheter has at least 2 ports; the red and the blue port. The red port removes blood away from the patient and the blue port corresponds to the venous return port. Some catheters include a third port which is used for lab draws which some dialysis patients may require as frequently as once a week.
The dialysis access has been termed by some as “the patient’s life line” and as such patients are very protective of their access. Dialysis nurses are skilled at assessing the dialysis access for potential complications but sometimes non dialysis nurses are taking care of patients and are faced with the ordeal of assessing a patient’s dialysis access. Assessing dialysis access will be discussed by reviewing the following case studies.
Case Study I
You are medical/surgical nurse working in a hospital setting and you have a newly assigned patient. Mrs. T. is a 55-year-old female admitted congestive heart failure. This is her 3rd admission in the past 6 weeks. She recently had her arteriovenous fistula on her left forearm fail and had an arteriovenous graft placed 4 weeks ago on her right upper arm. She also has a tunneled dialysis catheter on her right chest. Upon physical assessment you notice that all the accesses are uncovered and the access on her left forearm has pus oozing out of an open wound over laying the access. Upon questioning, the patient reports that she was picking at the scabs on her AVF access when she noticed pus oozing out about a week ago. She also reports that her catheter exit site was occasionally itchy which is why the dressing fell off.
Discussion for Case Study:
The first reaction is to page for the on call dialysis nurse but your hospital doesn’t have a dialysis unit in house and the on call contracted nurse reports that she will be available in 6 – 8 hours after she is done with her current assignment but asks if you can place a dressing on the dialysis catheter currently being used in order to prevent a potential catheter infection given that the patient has an active source of infection. Also, your ICU does not provide Continuous Renal Replacement Therapy (CCRT) so none of the nurses in the ICU have any experience with dialysis accesses.
The focus of your assessment is to first identify which access is currently being used and which ones have failed. In this case, the AVF has failed and now appears infected with pus oozing out. The AVG has never been used and is currently maturing. It was only placed 4 weeks ago and according to the National Kidney Foundation (NKF) guidelines, the graft needs a minimum of 6 weeks to mature. Next is the dialysis access catheter which is the only access currently being used.
Most non dialysis nurses may never need to assess a dialysis catheter but if you need to, it is a fairly simple process. First gather supplies for a dressing change which include masks, gloves, gauze, tape, cleansing solution, e.g. betadine, chlorhexidine etc. It is important to NOT open the catheter hubs. All you need to do is clean the catheter site and apply a dressing to the catheter exit site. When assessing the catheter exit site look for redness, discharge, drainage, swelling and other signs of infection. Be sure to assess the site as well as the skin overlaying the catheter tract for signs of infection. This is a semi sterile procedure; you do not need sterile gloves but both you and the patient should wear masks. Using sterile technique, cleanse the site and apply a sterile dressing over the catheter exit site. Some may choose to apply triple antibiotic over the site prior to applying the dressing. Also, some practitioner’s advocate cleansing the catheter hubs and applying a sterile gauze dressing over them as well. Reapplying the dressing in this manner allows you to keep the site sterile at least until the dialysis nurse gets there. Often, most patients are taught how to replace their dressings so depending on the patient’s cognitive status they may be a great resource and may need minimal assistance.
Next focus on assessing the AVG; feel for a thrill and using a stethoscope listen for a bruit. Also assess for signs of infection. Finally, assess the AVF looking for a bruit and thrill as well as signs of infection. Then using sterile technique, place a dressing over the wound in order to contain the source of the infection.
Notice how the AVF was addressed last since we knew it was infected. It is an important concept to always address the most infected wound or site last. Next contact the physician and report your findings regarding all 3 dialysis access sites and perform orders as ordered.
In this case, the patient was seen by the dialysis nurse in 4 hours, and wound care nursing was consulted by the nephrologist. The patient continued to receive dialysis via her catheter and she received antibiotics prophylactically and never became septic all thanks to proactive nursing.
Case Study II
Mr. P. is a 45-year-old male with a right forearm AVF admitted for pneumonia and respiratory failure necessitating intubation. You are an ICU nurse caring for this patient who is currently extubated. He gets dialysis on MWF and you are working on a Sunday. You cared for him the previous day and this morning you are performing your nursing physical assessment. You notice a faint thrill but do not hear a bruit. What do you do next?
Case Study Discussion:
Always err on the side of caution. In this case the bruit is more reliable than the thrill and more than likely you may be pressing too hard and feeling your own pulse. Promptly report the findings to the nephology team as well as the ICU team.
The patient was sent for angiography and was noted to have a thrombus in the AVF. He was scheduled for a thrombectomy with interventional radiology later that day and received his regularly scheduled dialysis session the next day.
Emotional toll of CKD and ESRD
Caring for patients undergoing dialysis comes with special challenges for physicians, mid-level providers as well as nurses and other allied healthcare providers including social workers and hemodialysis technicians. The challenges faced by the patients undergoing dialysis are very unique because initiating dialysis is usually reserved for patients with end stage renal disease (ESRD). Implying that the majority of patients initiating dialysis usually remain on dialysis indefinitely or until they get a kidney transplant which may take years.
It has been well reported that patients with CKD are at increased risk for depression compared to other patients group with chronic diseases (Palmer et al., 2013). In addition, they reported that depression in patients with CKD has been linked to poorer outcomes. Bautovich, Katz Smith, Loo, & Harvey (2014) reported that one in five patients with ESRD will suffer from depression. The challenge making the diagnosis in this patient group is the fact that depression is confounded by the overlap in symptoms with multiple comorbidities.
Nutritional restriction imposed by the disease processes is bound to cause some degree of emotional distress. Not being able to drink as much water as one pleases can be frustrating in and of if itself. Not to mention the innumerable dietary restrictions.
CKD patients, especially those on dialysis, face many challenges and often times have limited emotional support systems because their families may experience caregiver burn out or they may be reclusive in forming relationships given the chronicity of their disease. However, as nurses caring for patients with dialysis we could always show empathy because our smiling faces and kind words may be the only ones a patient sees and hears on any given day.