Treatment Options for End Stage Renal Disease

Prim Care Clin Office Pract 35 (2008) 407–432

Treatment Options for End Stage Renal Disease Paul W. Crawford, MD, FACPa,b,*, Edgar V. Lerma, MD, FACP, FASN, FAHAc,d a

Feinberg School of Medicine, Northwestern University, Chicago, IL, USA b Evergreen Park Dialysis Unit, 9730 S. Western Avenue, Suite 326, Evergreen Park, IL 60805, USA c Section of Nephrology, Department of Medicine, University of Illinois at Chicago College of Medicine, 820 S. Wood Street, Chicago, IL 60612-4325, USA d Associates in Nephrology, SC, 210 South Desplaines Street, Chicago, IL 60661, USA

Currently, more than 480,000 United States citizens are receiving dialysis [1]. More than 314,000 are receiving hemodialysis, more than 25,000 are receiving peritoneal dialysis, and another 143,000 have had transplants [1]. Significantly, 16.8% of the population has chronic kidney disease (CKD) [2]. The latest National Health and Nutrition Study revealed an increasing incidence of kidney disease among aging baby boomers, as the incidence of diabetes mellitus and hypertension rises. Because of this trend, a greater proportion of a primary care physician’s practice will involve patients with CKD, and consequently, end stage renal disease (ESRD) or CKD patients receiving dialysis [3]. Unfortunately, far too many of these CKD patients are referred to a nephrologist very late. More often than not, the opportunity for secondary preventive intervention, with the goal of avoiding renal replacement therapy, is lost [4]. When should a patient with CKD be referred to a nephrologist? The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend a referral to a nephrologist when the glomerular filtration rate (GFR) is less than 30 mL per minute per 1.73 m2 [5]. A more aggressive approach is to encourage referral when the * Corresponding author. Evergreen Park Dialysis Unit, 9730 S. Western Ave., Suite 326, Evergreen Park, IL 60805. E-mail address: [email protected] (P.W. Crawford). 0095-4543/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2008.05.003 primarycare.theclinics.com

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GFR is less than 60 mL per minute per 1.73 m2. As a cautionary note, a consultation when the GFR is greater than 60 is warranted in the presence of rapidly declining GFR with or without hematuria or proteinuria. Late referral to the nephrologist is considered by most clinicians to be ‘‘when management pf patients with chronic kidney disease could have been significantly improved by earlier contact with the nephrology team,’’ and surprisingly, it is extremely common in the United States. In most cases, it is when one is referred within 3 months or less before start of dialysis therapy [6]. With an early referral, the patient and family are given the advantage of participating in educational classes concerning CKD, as well as of receiving oneon-one counseling with a multidisciplinary kidney care team, including a nurse practitioner, physician, dietitian, and social worker. These team interventions (informed selection of dialysis modality, timely placement of appropriate dialysis access, as well as preemptive transplant) are paramount in helping the patient and family overcome many of the fears and myths associated with dialysis, as well as to arm them with skills needed to cope with the CKD, its complications, or ESRD diagnosis and treatment [7]. Similarly, other benefits associated with early referral include nonemergent initiation of dialysis, lower morbidity and improved rehabilitation, less frequent and shorter hospital stays, lower cost, and improved survival [8]. Moreover, many CKD patients are able to remain stable (within the same CKD stage), or improve CKD stage with aggressive intervention. The National Kidney Foundation classifies CKD stages into stages 1 through 5, as illustrated in Table 1. Unfortunately, many patients with ESRD have been threatened with dialysis by primary care providers or family members. Though well intentioned, the use of the threat of dialysis as a tool for motivating compliance with prescribed treatments and medications ultimately results in a patient who fears the treatment (dialysis) more than the disease (ESRD), with all the accompanying complications. All too often, this leads to patients with CKD Stage 5 refusing renal replacement therapy for a prolonged time (more than a year in some cases) or even never consenting to this life-saving treatment. Table 1 National Kidney Foundation stages of chronic kidney disease Stage

Description

GFR (mL/min/1.73 m2)

1 2 3 4 5

Kidney damage with normal or [ GFR Kidney damage with mild Y GFR Moderate Y GFR Severe Y GFR Kidney failure

R 90 60–89 30–59 15–29 !15 (or dialysis)

Chronic kidney disease is defined as either kidney damage or GFR less than 60 mL per minute per 1.73 m2 for greater than or equal to 3 months. Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. From National Kidney Foundation. KDOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 Suppl 1):S46; with permission.

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It is ironic that, given our current armamentarium, our success in managing comorbidities associated with CKD Stage 5, such as anemia, hypertension, metabolic acidosis, and secondary hyperparathyroidism with hyperphosphatemia leads our patients to question whether dialysis can improve their quality of life. With diligent management of these comorbidities, patients no longer need suffer from symptoms of fatigue, weakness, loss of mental alertness, lethargy, severe pruritus, recurrent chronic heart failure, shortness of breath, and inability to perform activities of daily living (ADLs). Instead, they are able to work, walk miles on a treadmill, golf, bowl, swim, dance and perform all ADLs without difficulty, despite having a GFR of less than 15 mL per minute. Indications for renal replacement therapy ESRD is always a diagnosis of exclusion; it is only after all exams have ruled out all reversible causes for renal failure that a diagnosis of ESRD should be made. No assumptions can be made in the work-up. A comprehensive, meticulous work-up includes an extensive history and physical, laboratory exams, renal ultrasound, chest X-Ray, and CT scan and MRI when indicated. Previous medical records must be reviewed. The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative guidelines define CKD as: 1. Kidney damage for greater than or equal to 3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR and manifest by either: Pathologic abnormalities; or Markers of kidney damage, including abnormalities in the composition of blood or urine, or abnormalities in imaging tests 2. GFR less than 60 mL per minute per 1.73 m2 for greater than or equal to 3 months, with or without kidney damage (Table 2) [9].

Table 2 KDOQI criteria for initiation of renal replacement therapy Criteria for initiation of renal replacement therapy Prior approach Diabetics Nondiabetics Transplant Current approach All patients Patients with symptomatic severe left ventricular dysfunction, symptomatic uremia, uncontrollable hyperkalemia or metabolic acidosis Transplant

GFR !15 mL/min !10 mL/min Not candidate until on dialysis GFR !15 mL/min 15–20 mL/min

!20 mL/min

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According to KDOQI guidelines, hemodialysis is also indicated when the GFR has not yet decreased to or below 15 mL per minute per 1.73 m2, in the presence of [9]: Intractable extracellular fluid volume overload Hyperkalemia Hyperphosphatemia Hypercalcemia or hypocalcemia Metabolic acidosis Anemia Neurologic dysfunction (eg, neuropathy, encephalopathy) Pleuritis or pericarditis Otherwise unexplained decline in functioning or wellbeing Gastrointestinal dysfunction (eg, nausea, vomiting, gastroduodenitis) Weight loss or other evidence of malnutrition Hypertension

diarrhea,

After the diagnosis of ESRD is determined, a decision concerning the most appropriate mode of renal replacement for the patient must be made. The various modes of dialysis must be very carefully discussed with patients and families as a life saving treatment for those with ESRD who, without this opportunity to receive treatment, will die prematurely of uremic complications. If the primary care provider is unable to dedicate the time for this often very lengthy, emotional discussion, then it is best left to the nephrology team. Options for renal replacement therapy for ESRD Kidney Transplantation a. Deceased donor b. Living donor Peritoneal Dialysis a. Continuous ambulatory peritoneal dialysis (CAPD) b. Continuous cycler peritoneal dialysis (CCPD) c. Nocturnal intermittent peritoneal dialysis (NIPD) d. NIPD-wet day e. Tidal peritoneal dialysis Hemodialysis (HD) a. Conventional: 3 to 5 hours, 3 times per week i. In-center HD ii. Home HD iii. Nocturnal home HD iv. Nocturnal in-center HD (not widely available) b. Daily home HD (day or nocturnal) c. Day or nocturnal 8–10 hour HD

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Variations of the above referenced renal replacement therapies are being attempted in an effort to improve outcomes, such as reduction of morbidity, mortality, and hospitalization days, in accordance with current ongoing demonstration projects. Goals of renal replacement therapy include: Prolongation of life Reversal of symptoms of uremia Return the patient to their prior lifestyle/activities of daily living Maintenance of a positive nitrogen balance and an adequate energy intake Minimization of patient inconvenience Maximization of quality of life

Selection of renal replacement therapy mode The nephrologist has great influence over the patient’s selection of peritoneal versus hemodialysis. The nephrologist’s preferences are greatly dependent upon their training, orientation, and practice location. A significant percentage of Nephrology Fellows come into practice with no prior experience in peritoneal dialysis. Subsequently, these nephrologists are much less likely influence a patient to choose peritoneal dialysis because of a lack of confidence in their ability to successfully manage peritoneal dialysis patients and staff. Lack of experienced and adequately trained staff can be, and often is, a major deterrent to a nephrologist recommending CAPD, even when they believe this to be the best option for the patient. Fear of insecure, inexperienced staff can also make an already apprehensive and fearful new ESRD patient even more anxious and reluctant to take on the responsibility of self-care (Table 3).

Table 3 Considerations when determining mode of renal replacement therapy Consideration Access

Hemo

CAPD

Desired: arteriovenous Tenckhoff catheter; no (AV) fistula AV access Alternate: catheter Frequency/duration 3 times per week/4 hrs Four exchanges daily per session Patient manual Not a factor Partner is dexterity recommended Patient intellectual Not a factor Partner is capacity recommended Family support An advantage Necessary

CCPD Tenckhoff catheter; no AV access Cycler at night Partner is recommended Partner is recommended Necessary

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Hemodialysis History Georg Haas performed the first human hemodialysis in 1924 in Giessen, Germany. Using collodian tubes arranged in parallel cylinders, blood came in contact with exchange fluid. Since that time, there have been numerous breakthroughs with various membranes, including cellophane, cellulose acetate, and cupraphane, all in the search for more biocompatible dialysis membranes and ultimately, disposable kidneys. In 1946, Gordon Murray created a dialyzerda coil design on steel framed and used his invention on a patient in acute renal failure, performing the first successful dialysis in North America. Many patients start dialysis with the perception that their kidneys are going to recover and that dialysis is ‘‘only temporary.’’ This is despite counseling to the contrary by multiple care providers that their kidney disease is irreversible and that they will need renal replacement therapy for the rest of their life. Such denial is common in patients starting renal replacement therapy and is to be expected for the first 6 to 12 months of dialysis. This is true even for the patient who has received early, in depth education about the need for renal replacement therapy. Contraindications to hemodialysis Hemodialysis contraindications include hemodynamic instability, hypotension, unstable cardiac rhythm and patient refusal. Vascular access Vascular access has been called the Achilles heel of dialysis. Without adequate access to the circulation, it is impossible to achieve adequate dialysis results. Blood flow of between 200 mL to 500 mL per minute is required for adults, depending on their size. For patients needing chronic hemodialysis, creation of an arteriovenous (AV) fistula (connecting an artery to a vein using a surgical anastomosis of the native vessels) in an upper extremity is imperative. Early identification of patients requiring AV access Patients in CKD Stage 4 should have vein mapping with ultrasound. After mapping has identified that the patient has adequate size vessels for the creation of a native AV fistula, a surgical referral for creation of an AV fistula should be made. Only a native AV fistula should be placed. The decision to place any other form of access should be reviewed with the nephrology team, patient, and family. Some surgeons believe an AV graft using artificial veins (PTFE) are also fistulas. However, the nephrologists must not relegate the decision of appropriate AV access placement to the vascular surgeon.

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The selection and order of preference for placement of AV fistula are a wrist (radial-cephalic) primary AV fistula or and elbow (brachial-cephalic) primary AV fistula. If unable to establish AV access with the preceeding methods, then use an artificial vein graft of synthetic material or a transposed brachial-basilic vein fistula. Typical longevity of an AV fistula is 80% over a 3-year period as compared with 50% over 3 years for an AV-PTFE graft. Location of an AV graft should be determined by the anatomic size of vessels, as shown by vein mapping, the surgeon’s skills, and the anticipated duration of dialysis, as noted in the KDOQI guidelines. After an AV fistula is placed, a period of 4 to 16 weeks is required until adequate venous enlargement and thickening of vessel walls results in a fistula suitable for cannulation (Figs. 1 and 2). The implications, potential complications, and risks associated with catheter placement must be weighed carefully to avoid increased morbidity and mortality. Unfortunately, there are instances wherein the patient may require hemodialysis on a rather emergent manner, such as in cases of acute poinsonings or intoxications, acute renal failure with uremic signs and symptoms at presentation, or in situations where the patient has not been adequately prepared for hemodialysis, such that no AV access has been placed. In these situations, the use of double lumen, noncuffed, nontunneled, short (9 cm–13 cm) hemodialysis catheters have been the preferred method for vascular access. Such catheters can be inserted into the jugular, subclavian, or femoral veins, via a modified Seldinger guidewire technique. Because they are noncuffed, they are considered temporary and they can be inserted at the bedside under sterile conditions. Radiologic imaging guidance is not commonly required during their placements. The subclavian route is discouraged because of increased risk of subclavian stenosis and thrombosis. For femorally inserted catheters, a length of 18 cm or less is recommended to minimize recirculation.

Fig. 1. Primary radiocephalic arteriovenous fistula. A side-to-side anastomosis becomes a functional artery side-to-venous-end anastomosis by ligation of the distal venous limb close to the AV anastomosis (L1) or more distally (L2). Abbreviations: A, radial artery; V, cephalic antebrachial vein. (From Feehally J, Johnson R. Comprehensive Clinical Nephrology, 2nd Edition. New York: Mosby, an imprint of Elsevier; 2003. p. 930; with permission.)

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Fig. 2. Arteriovenous polytetrafluoroethylene graft in the forearm. (From Feehally J, Johnson R. Comprehensive Clinical Nephrology, 2nd Edition. New York: Mosby, an imprint of Elsevier; 2003. p. 931; with permission.)

Internal jugular catheters can be left in place for 2 to 3 weeks, while femoral catheters should be removed after one use in ambulatory patients, or 3 to 7 days in those who are bed-ridden. The most common complications that arise from such catheters are infections. At times, such temporary catheters have to be changed to the less thrombogenic, permanent, cuffed catheters that can be used for longer periods, such as up to 6 months. For these purposes, the double lumen silastic/silicone, cuffed catheters are used. Because of their larger size, fluoroscopy is usually required for placement. The majority of such catheters are loss to bacteremia. Thrombosis, stenosis, and infection of the catheters are also common complications. In comparing AV fistulas or grafts to catheters, the latter usually require an increase in hemodialysis duration of treatment by approximately 20% to achieve equivalent urea removal with the former [10]. In fact, using ultrasound dilution techniques, there is an estimated 20% to 30% decrease in blood flow (based on blood pump reading) when using a catheter as opposed to an AV access. Hemodialysis basics The basic unit of an artificial kidney is a semipermeable membrane made up of several thousand hollow fibers with a surface area of from 0.5 m2 to

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2.0 m2. Arranged in parallel, these fibers provide separation of the patient’s blood and dialysate fluid. Blood from the patient circulates through the dialyser and is returned to the patient with the assistance of a pump and tubing. Dialysate makes just a single pass through the dialyzer (Fig. 3A). There are several types of extracorporeal therapy: hemodialysis, hemofiltration, hemodiafiltration, and hemoperfusion. For the purpose of management of chronic renal failure in the outpatient setting, this discussion will be limited to that of hemodialysis. There are several variants of hemodialysis. These include: Conventional hemodialysis, which uses a conventional low flux (small pore size) membrane. The primary mechanism of solute removal is diffusion. High efficiency hemodialysis, which uses a low flux membrane with higher efficiency for removal of small solutes (eg, use a large surface area membrane). High flux hemodialysis, which uses a high flux (large pore size) membrane that is more efficient in removing large solutes. Hemodialysis machines have several key components (Fig. 3B), such as: Blood pumpddelivers blood to the artificial kidney at a constant rate of approximately 500 mL per minute. Monitorsdensures pressure inside blood circuit is not excessive. Detectordmonitors leakage of red blood cells from the blood circuitry component into the dialysate compartment. Air detector/shut off devicedprevents air from entering the patient. Dialysate pumpddelivers dialysate to the artificial kidney. A proportioning systemdassures proper dilution of the dialysate concentrate. Heaterdwarms the dialysate to approximately body temperature. Ultrafiltration controllerdprecisely regulates fluid removal. Conductivity monitordchecks dialysate ion concentrations (Fig. 4). With all the above devices, the artificial kidney can safely and reliably exchange water and solute in the physiologic ranges necessary to maintain chemical homeostasis as well as hemodynamic stability. Water transport and solute clearance Ultrafiltration coefficients are used to measure effectiveness of water transport across the dialysis membrane. Ultrafiltration coefficients are usually 2 mL to 5 mL per hour per mm Hg, with conventional membranes and 15 mL to 60 mL per hour per mm Hg with high flux membranes [11]. Stable patients may tolerate 5-L ultrafiltration or fluid removal over the 4-hour dialysis treatment, with close monitoring of vital signs.

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Mass transfer coefficient (Ko) and membrane surface area (A) determine solute transport of dialysis membranes, expressed as mass transfer-area coefficient Ko A as molecular size increases and diffusive clearance of solutes decreases. Therefore, small molecules, such as urea, are readily cleared at rates much higher than normal glomerulus of the kidney. However, 4 hours of dialysis 3 times per week cannot replace 24 hours, 7 days-a-week of clearance at the rate of 168 hours per week. Dialysate composition Dialysate sodium at or above plasma sodium prevents hemolysis from abrupt decrease in plasma sodium. Potassium often is kept low to decrease plasma potassium. Bicarbonate concentrate is usually high to correct acidosis. Today, acetate is seldom used in the United States because of problems with transient hypoxemia, metabolic acidosis, intradialytic hypotension, and cardiac arrhythmia. Calcium concentration in dialysate may vary depending on individual needs of the patient. Magnesium is usually low for ESRD patients who tend to be hypermagnesemic. For all patients, to avoid hypoglycemia, the glucose in the bicarbonate bath is usually kept at 200 mg/dL.

Complications of hemodialysis Hemodialysis today is a relatively safe procedure; however, complications do occur. Hypotension The most common complication of hemodialysis is hypotension. This can be either intradialytic or after dialysis. Etiology of hypotension Dialysis-related hypotension is attributed to changes in body volume. Both the amount of fluid removed and the rapidity of the removal from the intravascular space can affect the development of hypotension, as can

= Fig. 3A. Diagram of a hemodialysis circuit. Labels point to blood removed for cleansing, arterial pressure monitor, blood pump, heparin pump to prevent clotting, dialyzer, inflow pressure monitor, air detector clamp, venous pressure monitor, air trap and air detector, and clean blood returned to body. (From the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Treatment Methods for Kidney Failure Hemodialysis (KU-152). Available at http://kidney.niddk.nih.gov/kudiseases/pubs/choosingtreatment/index.htm.) Fig. 3B. Blood circuit for hemodialysis. (a) The blood circuit. (b) The pressure profile in the blood circuit with an arteriovenous fistula as the vascular access. (From Feehally J, Johnson R. Comprehensive Clinical Nephrology, 2nd Edition. New York: Mosby, an imprint of Elsevier; 2003. p. 955. with permission.)

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Fig. 4. Design of a modern hollow-fiber dialyzer. (From Feehally J, Johnson R. Comprehensive Clinical Nephrology, 2nd Edition. New York: Mosby, an imprint of Elsevier; 2003. p. 953; with permission.)

changes in serum osmolality and sympathetic tone. Patients taking oral antihypertensive medication before dialysis can experience intradialytic hypotension. In addition, patients eating while being dialyzed can experience hypotension secondary to splanchnic pooling. Management of intradialytic and post dialysis hypotension Treatment of hypotension may include: Normal saline infusion Recumbency Discontinuing ultrafiltration Increasing dry weight Decreasing the temperature of the dialysate

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Sodium modeling during hemodialysis Isolated ultrafiltration Withhold antihypertensive medications before dialysis Midodrine, an oral selective a1-agonist has been used in some cases with satisfactory results. The use of salt-poor albumin has been shown not to demonstrate any advantage over normal saline infusion, and may actually be more costly. Hypertension Hypertension during or immediately after dialysis is another common complication, and it is primarily volume-dependent in its etiology. There are patients, with so-called ‘‘dialysis-resistant hypertension,’’ whose blood pressures remain elevated despite adequate fluid removal. Such patients tend to have underlying long-standing hypertension and often have excessive interdialytic weight gains. They may have a hyperactive renin angiotensin system in response to fluid removal [12]. Use of erythropoietin has also been associated with a 20% to 30% incidence of new onset of hypertension, or exacerbation. Cardiac arrhythmia Cardiac arrhythmias can occur in any patient, but are most often seen in patients on multiple cardiac medications and when a low K bath is being used. The numbers of patients with cardiovascular disease and arrhythmia developing ESRD are continuing to rise and warrant close attention [13]. Arrhythmia prevention Preventive measures may entail use of bicarbonate dialysate with close monitoring of the potassium and calcium levels in the patient’s serum and the dialysate. The use of zero potassium dialysate is arrhymogenic in itself and should not be used, especially if the patient is on maintenance digoxin. Steal syndrome Steal syndrome is commonly seen in patients with radiocephalic arteriovenous fistulas or grafts, where blood flow to the involved hand is diverted and diminished. These patients should be evaluated for signs and symptoms of ischemia, such as subjective coldness and paresthesia, objective reduction in skin temperature, or intact sensory or motor functions. Neurologic changes and muscle wasting tend to occur in severe cases. Mild ischemia can be treated with analgesics or by wearing a glove. Those that do not respond to conservative measures may require surgical intervention with banding or access correction or even ligation.

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Muscle cramps Muscle cramps are common when a patient drops below their dry weight or when they undergo ultrafiltration that is too rapid. Peripheral arterial disease (PAD) is common in kidney patients with CKD and can produce muscle cramps [14]. As expected, they tend to occur toward the latter part of the dialysis session, tending to involve the lower extremities, most commonly. This is also the reason for a significant proportion of patients discontinuing dialysis treatment session prematurely. Muscle cramp management Large intradialytic weight gain can be avoided with fluid restrictions of 1,000 cc to 1,500 cc plus urine volume per 24 hours, a task that requires extreme self-discipline for some patients whose thirst center is overactive. In the past, quinine sulfate, given 2-hours before dialysis, was favored by many physicians. The United States Food and Drug Administration currently regards quinine sulfate as both unsafe and ineffective for prevention of muscle cramps. Oxazepam has been used by some physicians with varying rates of success. The value of sodium modeling in relieving muscle cramps has been shown in at least one study [15]. Evaluation for PAD with Ankle Brachial Index (ABI) may indicate presence of PAD that requires further treatment and evaluation. Restless leg syndrome Patients usually complain of crawling sensations on both lower extremities, which seem to occur during periods of inactivity (while the patient is sleeping or seated). Sometimes it is perceived as pain. Prompt relief is usually obtained by moving the legs, hence, the term ‘‘restless legs.’’ Many patients have difficulty sleeping and can have a poor quality of life. Use of certain antidepressants (eg, tricyclic antidepressants, selective serotonin reuptake inhibitors, and lithium) can exacerbate the symptom. Restless leg syndrome has to be differentiated from peripheral neuropathy, which tends to be more constant and is not relieved by movement. Gabapentin has been shown to be effective and can also help with the insomnia. Recently, ropinirole, a dopamine agonist approved for use in Parkinson’s disease, has shown to be a promising agent [16]. Disequilibrium syndrome This syndrome may occur when too much fluid is removed over too short a time period. Disequilibrium syndrome may manifest as a range of symptoms, including headache, nausea, vomiting, altered mental status, seizure, coma, and death.

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Disequilibrium syndrome management Fortunately, disequilibrium syndrome is much less common in patients who are referred to a nephrologist for timely initiation of dialysis. Early referral coupled with improved technology has made this syndrome much rarer than in the past. Anaphylaxis Anaphylactic reactions may manifest with burning or heat over the access site or throughout the body, chest or abdominal pain, difficulty breathing, hypotension or hypertension, fever, chills, pruritis, emesis, urticaria, flushing, and even cardiopulmonary arrest. The typical onset of symptoms is usually within the first 5 minutes of initiating dialysis, although it may be delayed by up to 20 minutes. Fortunately, improved technology has decreased the incidence and frequency of anaphylactic reactions to the dialysis membrane. Modern membranes are much more biocompatible. Using bicarbonate dialysis rather than acetate dialysis has also decreased the occurrence of anaphylaxis. Thorough rinsing of the dialyzer before use, helping to remove any noxious materials or contaminants that became attached to the membrane during manufacturing, has also reduced the occurrence of anaphylaxis. Eliminating the reuse of dialyzers prevents patient exposure to contamination of membranes by chemicals used during sterilization and reprocessing and reduces the risk of anaphylaxis caused by sensitivity to these chemicals. Postdialysis syndrome An ill-defined, washed-out feeling or malaise during or after hemodialysis is seen in approximately one third of patients [17]. It has been attributed to several factors: decreased cardiac output, peripheral vascular disease, depression, deconditioning, electrolyte abnormalities, hypotension, and myopathy, among others. Infectious complications Patients with ESRD primarily die from cardiovascular events. However, infections are the second most common cause of death [18,19] Temporary dialysis catheters are the source for most infections. AV fistulas carry the least risk of infection. Staphylococcus aureus and Staphylococcus epidermidis are the bacterial culprits most frequently found. Frequent infection control in services and follow-up training to staff are required policy for all dialysis units, whether hemodialysis or peritoneal dialysis units. Hepatitis B was prevalent in the 1970s. Currently Hepatitis C is more prevalent and increasing risk for liver failure and cirrhosis in ESRD

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patients. Unfortunately, the mode of transmission is not yet established. Screening for Hepatitis B is mandatory and patients presenting or developing this condition require isolation. Vaccination for Hepatitis B, Flu, and pneumonia are offered to appropriate patients. Patients are considered candidates for the vaccines unless a specific contraindication, such as established antibody levels for Hepatitis B, is present (Table 4). Role of water treatment in hemodialysis complications Water treatment is the most critical component of hemodialysis. Fortunately, it is also the most monitored, regulated, and precisely accurate segment of dialysis. Purification of water from municipalities is critical because of inherent levels of contaminants, as well as hardness that varies from location and water source. Inadequate removal of calcium, aluminum, bacteria, chloramine, and other water components that may be either naturally occurring or as a result of contamination can lead to deadly consequences. There is no room for error in proportioning systems whose function is to maintain proper osmolality, electrolyte content, and pH balance. Improper

Table 4 Vaccination table for patients with ESRD Vaccine Anthrax DTaP/Tdap/Td Hib Hepatitis A Hepatitis B Influenza (TIV) Influenza (LAIV) Japanese Encephalitis MMR Meningococcal Pneumococcal Polio (IPV) Rabies Rotavirus Smallpox Typhoid Varicella Yellow Fever

Recommended

May use if otherwise indicated

Contraindicated

a

X Xa Xa Xa X X X Xa Xa Xa X Xa Xa Xb Xa Xa Xa Xa

a No specific Advisory Committee on Immunization Practices recommendation for this vaccine exists for renal dialysis patients and patients with chronic renal disease. b Children with primary immunodeficiency disorders and both children and adults who have received hematopoietic, hepatic, or renal transplants are at risk for severe or prolonged rotavirus gastroenteritis and can shed rotavirus for prolonged periods. (Data from Advisory Committee on Immunization Practices, unpublished data.)

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temperature range can lead to hemolysis. Air leak detectors ensure against air embolism that can arise from a defective blood circuit.

Peritoneal dialysis Peritoneal dialysis is the author’s first choice for renal replacement therapy for a patient with ESRD if a kidney transplant is not possible or available. Peritoneal dialysis was initially used only to treat patients who were in acute kidney failure. Typically used exclusively in intensive care units (ICU), a hard plastic catheter was placed into the peritoneal cavity, allowing the infusion of peritoneal dialysis fluid. The dialysis fluid was supplied in 2-liter glass bottles. The ICU nurse would perform exchanges every 1 to 2 hours, documenting hourly volume of intake and output, and calculating a positive or negative fluid balance. This was a very laborious task for nursing staff, often requiring a one-to-one patient-to-staff ratio (hardly available in today’s nursing shortage era). By the mid-1970s, continuous ambulatory peritoneal dialysis was introduced. Currently, more than 25,000 patients with ESRD are on peritoneal dialysis. Fundamentals of peritoneal dialysis Peritoneal dialysis involves an exchange of solutes and fluids across the peritoneal membrane, which serves as the dialysis surface, via diffusion and convective transport regulate solute movement. Urea, creatinine, and potassium move into the peritoneal cavity dialysate across the peritoneal membrane, while bicarbonate and calcium move in the opposite direction. The concentration gradient between dialysate and blood facilitates small molecule movement. Convection is also responsible for solute movement across the peritoneal membrane. Patients perform the exchanges at home on a daily basis and have follow-up at the dialysis center or home therapy center twice monthly. Peritoneal dialysis patients are typically seen by the nephrologist once a month and by the staff twice a month for social, dietary, and financial needs. Monthly laboratory work is required at a minimum; more frequent laboratory work may be required (Fig. 5). A high concentration of glucose in the peritoneal dialysis fluid is used as solute driving fluid removal, creating an osmotic gradient for ultrafiltration of fluid, and providing a dwell time that is not prolonged. Crucial to effective exchanges and fluid removal are peritoneal blood flow, dialysate volume, and the integrity of the peritoneal membrane (Table 5). The peritoneal dialysis catheter is inserted by a surgeon or nephrologist as an out-patient procedure. Most catheters are double-cuffed, curled tip Tenckhoff catheters. Other types of catheters are available, but they are infrequently used.

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Fig. 5. Diagram of a patient receiving peritoneal dialysis. Dialysis solution in a plastic bag drips through the catheter into the abdominal cavity. CAPD is the most common form of peritoneal dialysis. (From the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Kidney Failure: Choosing a Treatment That’s Right for You (KU-50). Available at: http:// kidney.niddk.nih.gov/kudiseases/pubs/choosingtreatment/index.htm.)

Table 5 Peritoneal dialysate fluid composition Peritoneal dialysate fluid composition Sodium Potassium Calcium Lactate Magnesium Glucose Osmolality pH

132 mEq/L 0 mEq/L 3.5 mEq/L 40 mEq/L 0.5 mEq/L 1.5 g/dL, 2.5 g/dL, or 4.25 g/dL 346, 396, 485 5.2

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Continuous ambulatory peritoneal dialysis CAPD uses 9 L to 10 L of peritoneal dialysis fluid per day, usually in 2-L to 3-L bags. Four to six exchanges are typically performed over a period of 24 hours. The peritoneal dialysis fluid is infused into the peritoneal cavity via catheter. The fluid remains in the cavity for 4 to 6 hours, is then drained out, removing water and solutes, including urea and creatinine. The number of exchanges and the volume of the peritoneal dialysis fluid bags are determined by patient size, peritoneal membrane permeability, and residual kidney function (Fig. 6). Automated continuous cycling peritoneal dialysis While the mechanism of dialysis is the same, patients on CCPD use a cycler. A cycler is a small bedside device that is programmed to set volumes of infusion, dwell times and drain times. After programming, the device automatically performs exchanges while the patient is either asleep or resting. Because the process is automated, the patient is able to rest without interruption, with the exception of an alarm that sounds as a result of a problem detected by the cycler (Fig. 7).

Fig. 6. Flush-before-fill strategy used with Y transfer sets. (A) A small volume of fresh dialysis solution is drained directly into the drainage container (either before or just after drainage of the abdomen). This washes away any bacteria that may have been introduced in the limb of the Y leading to the new bag at the time of connection. (B) Fresh solution is introduced through the rinsed connector. (From NIH Publication No. 01-4688, May 2001. Available at: http://www. intelihealth.com/IH/ihtIH/WSIHW000/23,847/25,944/273,441.html?d¼dmtContent#works.)

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Benefits of self care using CAPD or CCPD Self discipline Ownership of disease and self-management Responsibility Family involvement Overcomes denial Residual renal function preservation Better quality of life Lower morbidity and mortality Adequacy of peritoneal dialysis is measured through determination of KT/V where K equals urea clearance, T equals per unit time, and V equals total body water. The combination of creatinine clearance of peritoneum and residual renal function should reach a weekly KT/V of 2. Failure to achieve the guideline level of 2 may result in uremic symptoms, decreased protein intake, and increased mortality (Table 6). Complications of peritoneal dialysis Peritonitis is the most common complication of peritoneal dialysis. This complication is usually discovered when the patient reports a cloudy drainage bag. A diagnosis of peritonitis is confirmed through a positive gram stain, cell count, and sensitivity culture, as well as signs and symptoms of peritoneal inflammation. Empiric treatment is started to treat gram-positive or gram-negative organisms by instillation of intraperitoneal antibiotics.

Objective criteria for rationing dialysis? In the early days of dialysis in the United States, dialysis was only offered at university teaching centers. It was considered a high risk, experimental, but life saving procedure. Dialysis was only offered to those with ESRD who were accepted by the ‘‘God Committees’’ as eligible for dialysis. Criteria were very limiting; for example, patients had to be under the age of 55 and could not be diabetic. I will never forget having to inform a 55year-old father of two children that the committee voted he was not eligible for dialysis. Never again do I wish to see a committee decide who may be treated and who is essentially given a death sentence. Yet some 35 years later, this pendulum of death appears to be resurfacing in the medical

= Fig. 7. Example of a system used for cycler-assisted peritoneal dialysis. Solution is heated before use and weighed after use. The last bag of solution may have a different concentration to last throughout the day. (From NIH Publication No. 01-4688, May 2001. Available at: http:// www.intelihealth.com/IH/ihtIH/WSIHW000/23,847/25,944/273,441.html?d¼dmtContent# works.)

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Table 6 Common laboratory parameters measured in patients receiving dialysis Measure

Expected level

KT/V Hemoglobin Parathyroid hormone Phosphorus HbA1c Albumin Calcium Tsat Ferritin Blood pressure Low-density lipoprotein Standardized mortality rate

R1.2 (Hemodialysis) R 2 (Peritoneal dialysis) 11 g/dL –12 g/dL 150–300 4.5–5.5 %7.0 R4.0 8,5–10.0 O20% !500 130/80 !100 !18%

community, as use of medical resources based on costs is becoming more prevalent. The role of the medical field is to ‘‘do no harm.’’ To accomplish this health care providers must always weigh benefits against the risk for any procedure, including dialysis and transplant. For patients who cannot maintain adequate perfusion of vital organs secondary to hypotension resulting from hemodialysis, the risk of dialysis outweighs the benefits. In a patient for whom previous abdominal surgery has resulted in multiple adhesions obstructing inflow and drainage of peritoneal dialysis fluid, or for those who develop sclerosing peritonitis, the risk of peritoneal dialysis outweighs the benefits. Dialysis, even when benefits outweigh the risk, is contraindicated if the patient cannot understand the procedure and give informed consent, and do not have family or a guardian who can do so on their behalf. Other patients perceive, even when the benefit is evident to the physician, that the procedure is torturous and not beneficial to them. Those patients should not be coerced to undergo dialysis, despite the ultimately grave outcome. The author is not a proponent of socialized medicine systems that refuse dialysis to patients over a certain age, or that deny dialysis to patients with certain diseases, or that block access to dialysis based on ability to pay for treatment, or that refuse treatment based on race, gender or ethnic group. Ultimately, the decision of who should or should not receive dialysis must be made by an informed, educated patient and family, in conjunction with the medical care team that includes the nephrologist, primary care physician, nurses, social workers, and spiritual leader. Kidney transplantation Much literature has been published attesting to the survival benefits of patients who have undergone renal transplantation as compared with those

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on dialysis. Comparisons on rates of mortality have been made between those patients who are on the waiting list (for renal transplant) and those who are already transplant recipients. From these studies, the question arose of whether transplantation of these patients before initiation of dialysis (preemptive transplantation) would translate into significantly improved outcomes. Several studies published recently [20–23], show significantly improved patient and allograft survival in those with preemptive transplants as opposed to those who were on dialysis for a period of time before transplantation. There have been lower rates of delayed graft function or acute rejection episodes (biopsy-confirmed) associated with preemptive transplantation. Interestingly, preemptive transplant recipients have better socioeconomic and demographic features [24] that were also correlated with better outcomes. Examples of these include younger age, white race, higher degree

Box 1. Initial evaluation of the potential renal transplant recipient Complete history and physical examination (includes detailed surgical and psychosocial history) Blood type, complete blood count, blood urea nitrogen, creatinine, electrolytes, calcium, phosphorous, albumin, liver function tests, prothrombin time, and partial thromboplastin time Serologic testing for HIV, cytomegalovirus, varicella virus, herpes simplex virus, Epstein Barr virus, hepatitis virus A, B, and C, rapid plasma reagin, and fluorescent treponemal antibody Urinalysis and urine or bladder-wash culture Purified protein derivitive Chest X-ray and electrocardiogram In men: testicular examination and, in those over the age of 50, measurement of prostate specific antigen and a digital rectal examination. In women: breast examination and, in those over the age of 40, mammography. The age for mammography should be lowered to 35 if there is a history of breast cancer in the premenopausal years in a first-degree relative. HLA antigen typing and a panel reactive antibody assay to detect for previous sensitization Chest radiography Renal ultrasonography (post-void residual is optional) Two-dimensional echocardiography Thallium scintigraphy or dobutamine stress echocardiography

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of education, and employment. They also had fewer HLA antigen mismatches. It is therefore reasonable to recommend possibly avoiding dialysis with early preemptive transplantation in certain situations. This should be considered, especially in younger individuals with very minimal comorbidities, if at all. The role of hemodialysis versus peritoneal dialysis as before-transplant dialysis modality in predicting outcomes remains controversial. Studies have also shown that successful renal transplantation significantly improves quality of life and decreases the risk of mortality as compared with maintenance dialysis. However, because of the donor organ shortage, there is an ever increasing number of candidates waiting on the transplant list, and wait times are also increasing. Some groups are trying to find ways to alleviate this donor shortage, such as specialists in xenotransplantation, proponents of paired-exchange transplantation, as well as good Samaritan or altruistic transplantation. The Consensus Conference [25] (United Network for Organ Sharing) currently recommends that adult candidates for renal transplant should have progressive renal disease and a GFR less than 18 mL per minute for them to be placed on the cadaveric renal transplant waiting list. The evaluation of both potential renal transplant donor and recipient tends to be tedious and exhaustive (Box 1). Before a patient is accepted for renal transplantation, one has to take into consideration, certain contraindications (Box 2). Advanced age, history of

Box 2. Contraindications to renal transplantation Relative Active infection Coronary heart disease Active hepatitis Active peptic ulcer disease Cerebrovascular disease Proven habitual medical noncompliance HIV infection (Although most centers exclude patients who are HIV positive; in certain cases, those considered to have well-controlled HIV infection are still eligible for solid organ transplantation) Absolute Untreated current infection Active malignancy with short life expectancy Chronic illness with life expectancy of less than 1 year Poorly controlled psychosis Active substance abuse

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previous transplantation, as well as underlying kidney disease diagnosis, are not contraindications to renal transplantation. Certain renal diseases, such as focal segmental glomerulosclerosis and IgA nephropathy, have high recurrence rates in the transplanted organ, yet are not considered as contraindications. Unfortunately, there is still a large proportion of patients who are referred for actual renal transplantation who are eventually excluded. Reasons for exclusion are varied, and include medical contraindication, patient decision, obesity, death, and insurance or financial reasons [26]. The most common medical reasons were heart disease, malignancy, and noncompliance. References [1] U.S. Renal Data System, USRDS 2007 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda (MD); 2007. [2] Saydah S, Eberhardt M, Rios-Burrows, et al. Prevalence of Chronic Kidney Disease and Associated Risk FactorsdUS 1999–2004. MWR 2007;56(8):161–5. [3] Wetterhall SF, Olson DR, DeStefano F, et al. Trends in diabetes and diabetic complications, 1980–1987. Diabetes Care 1992;15:960–7 [Abstract]. [4] Levin A. Consequences of later referral on patient outcomes. Nephrol Dial Transplant 2000; 15(Suppl 3):8–13. [5] National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Part 4. Definition and Classification of Stages of Chronic Kidney Disease. Available at: http://www.kidney.org/Professionals/ Kdoqi/guidelines_ckd/p4_class_g2.htm. Accessed July 22, 2008. [6] Stevens LA, Levey AS. Chronic kidney disease: staging and principles of management. In: Greenberg A, editor. Primer on kidney diseases. 4th edition. Philadelphia: National Kidney Foundation; 2005. p. 461. [7] Crawford PW. Changing Trends in Referral Source of ESRD Patients in a Nephrology Practice Between 1995 and 2005 [Abstract]. Presented at the National Kidney Foundation 2006 Spring Clinical Meeting. Chicago, April 19–23, 2006. [8] Kausz AT, Pereira BJ. Late referral to nephrologists of patients with chronic kidney disease. In: Rose BD, editor. UpToDate. Wellesley (MA): UpToDate; 2008. [9] National Kidney Foundation. NKF K/DOQI Clinical Practice Guidelines and Clinical Practice Recommendations. 2006 Updates. Available at: http://www.kidney.org/ Professionals/kdoqi/guideline_upHD_PD_VA/hd_rec1.htm. Accessed July 22, 2008. [10] Schwab SJ. Acute hemodialysis vascular access. In: Rose BD, editor. UpToDate. Waltham (MA): UpToDate; 2008. [11] Cheung AK. Hemodialysis and hemofiltration. In: Greenberg A, editor. Primer on kidney diseases. 4th edition. Philadelphia: National Kidney Foundation; 2005. p. 467. [12] Rahman M, Dixit A, Donley V, et al. Factors associated with inadequate blood pressure control in hypertensive hemodialysis patients. Am J Kidney Dis 1999;33:498–506. [13] Keith DS, Nichols GA, Gullion CM, et al. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004;164:659–63. [14] Jaar BG, Plantinga LC, Astor BC, et al. Novel and traditional cardiovascular risk factors for peripheral arterial disease in incident-dialysis patients. Adv Chronic Kidney Dis 2007;14:304–13. [15] Sandowski RH, Allred EN, Jabs K. Sodium modeling ameliorates intradialytic and interdialytic symptoms in young hemodialysis patients. J Am Soc Nephrol 1993;4:1192–8.

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[16] Pellecchia MT, Vitale C, Sabatini M, et al. Ropinirole as a treatment of restless legs syndrome in patients on chronic hemodialysis: an open randomized crossover trial versus levodopa sustained release. Clin Neuropharmacol 2004;27:178–81. [17] Parfrey PS, Vavasour HM, Henry S, et al. Clinical features and severity of nonspecific symptoms in dialysis patients. Nephron 1998;50:121–8. [18] Bloembergen WE, Stannard DC, Port FK, et al. Relationship of dose of hemodialysis and cause-specific mortality. Kidney Int 1996;50:557–65 [Medline]. [19] US Renal Data System: USRDS 2000 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, MD, National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2000. [20] Kasiske BL, Snyder JJ, Matas AJ, et al. Preemptive kidney transplantation: the advantaged and the disadvantaged. J Am Soc Nephrol 2002;13:1358–64. [21] Meier-Kriesche HU, Port FK, Ojo AO, et al. Effect of waiting time on renal transplant outcome. Kidney Int 2000;58:1311–7. [22] Mange KC, Joffe MM, Feldman HI. Effect of use or non-use of long-term dialysis on the subsequent survival of renal transplants from living donors. N Engl J Med 2001;344:726–31. [23] Gill JS, Tonelli M, Johnson N, et al. Why do preemptive kidney transplant recipients have an allograft survival advantage? Transplantation 2004;78:873–9. [24] Butkus DE, Dottes AL, Meydrech EF, et al. Effect of poverty and other socioeconomic variables on renal allograft survival. Transplantation 2001;72:261–6. [25] Consensus conference on standardized listing criteria for renal transplant candidates. Transplantation 1998;66:962–7. [26] Holley JL, Monaghan J, Byer B, et al. An examination of the renal transplant evaluation process focusing on cost and the reasons for patient exclusion. Am J Kidney Dis 1998;32(4): 567–74.