Hemodialysis for the non-nephrologist.

Abstract: Hemodialysis is now routinely provided to more than 300,000 patients in the United States. An epidemic of end-stage renal disease will nearly double this number by 2010. Patients undergoing chronic hemodialysis have high morbidity and mortality rates. Given these facts, most medical providers will be involved in the care of patients undergoing hemodialysis and it is thus important to have an understanding of the dialysis procedure and its attendant risks. This review discusses the basic physiology of the dialysis procedure and its associated complications.

Key Words: adequacy, complications, end-stage renal disease, hemodialysis

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In the year 2003, more than 300,000 patients in the United States were receiving chronic hemodialysis. (1) The incidence rates for end-stage renal disease (ESRD) have quadrupled since 1980 and now approach 333 per million. (1) Certain populations such as black Americans have disproportionately higher risks of ESRD, with an incidence of 982 per million in 2002. (2) These higher incidence rates, along with the recent improved survival of ESRD patients, have increased the prevalent population on dialysis by approximately 7 to 9% per year. This has led to estimates that the dialysis population may reach 600,000 patients by the year 2010. (1)

This epidemic of ESRD necessitates that the vast majority of health care providers in all disciplines will be called on to participate in the care of patients who are receiving chronic hemodialysis. It is imperative to have an understanding of the dialysis procedure and its associated complications when caring for these patients.

Epidemiology

Diabetes mellitus remains the most common cause of ESRD and is the main driving factor for the increasing incidence of ESRD, accounting for approximately 40% of cases. (1) Hypertension represents the next most common cause of ESRD and is particularly important in black Americans. (1) Other causes of ESRD include cystic kidney diseases, glomerulonephritis (especially that caused by human immunodeficiency virus), vascular disease, obstructive uropathy, failed renal allografts, and interstitial disease.

End-stage renal disease affects certain racial populations to a greater extent. Data from the 2002 United States Renal Data System (USRDS) indicate that the odds ratio for ESRD for black Americans was 4.45, as compared with white Americans. (2) Native Americans also have a higher risk for ESRD, with an odds ratio of 3.57, as compared with white Americans. (1) The reasons for these differences are multifactorial but include a higher prevalence of diabetes mellitus, obesity, and hypertension in these populations.

The median age of patients initiating hemodialysis has steadily increased from age 54 in 1978 to age 65 in 2002. (2) This shift in median age has been fueled by a rapid rise in the incidence of ESRD in patients above age 75 years. In this age group, incidence rates have grown 93%; in 1980, patients ages 75 years or older accounted for only 8% of patients with ESRD. This number now stands at 25%. (1)

Substantial morbidity and mortality rates accrue from ESRD. Patients with diabetes and ESRD are admitted to the hospital on average 2.3 times per year, and only 27% of these patients will survive 5 years on hemodialysis. (1) The life expectancy of ESRD patients is one fourth to one sixth of the age-matched general population, with cardiovascular disease being the most likely cause of death. (1) Despite these dismal projections, the mortality rate for patients on dialysis has actually decreased by 10% from the peak in 1988 and stands at 248 deaths per 1,000 patient-years. (1)

The average cost of providing dialysis care in the Medicare entitlement program in 2002 was $53,000 per patient, with an overall program cost of 17.0 billion dollars. (1) This represents 6.7% of the total Medicare budget. The cost of ESRD care is rising at an annual rate of 10% (4% after correction for inflation), and, coupled with the increasing prevalence of ESRD, these costs are anticipated to grow at an even faster rate in the future.

Goals of hemodialysis

As renal function deteriorates, a series of potentially life-threatening complications (uremia) develop. These include volume overload, hyperkalemia, metabolic acidosis, anemia, metabolic bone disease, fatigue, encephalopathy, and malnutrition. These symptoms reflect the lack of renal clearance of both small solutes and larger molecular weight compounds (generically termed "uremic toxins"). Although some uremic toxins have been identified (including parathyroid hormone and [[beta].sub.2] microglobulin; for a more complete review, see Reference 3), most toxic substances remain elusive, and our knowledge of the uremic syndrome is far from complete. (4) Symptoms also emanate from the lack of renal production of important homeostatic hormones such as 1,25 (OH)[.sub.2]-vitamin [D.sub.3] (leading to renal osteodystrophy) (5) and erythropoietin (leading to anemia). (6) The goals of hemodialysis are to treat uremic symptoms (through removal of toxic metabolites), correct acid-base and electrolyte disturbances, maintain volume status, and, over the long term, improve quality of life, lower morbidity and mortality rates, and maintain nutritional stability. An ancillary goal of hemodialysis treatment is to provide hormonal therapy with recombinant human erythropoietin and vitamin D compounds to replete the low levels of these hormones seen in renal failure.

To reach these goals, patients with glomerular filtration rates of less than 10 to 15 mL/min undergo thrice-weekly hemodialysis (7) (other options for chronic renal replacement therapy include peritoneal dialysis and renal transplantation, both of which will not be discussed here). Credit for the first human dialysis treatment goes to Georg Haas, who in 1924 provided dialysis to a patient with acute renal failure. (8) This procedure was subsequently refined by Willem Kolff (9) in the 1930s and 1940s and was used sporadically for patients with acute renal failure. Problems with early dialysis therapy included clotting of blood in the extracorporeal circuit and difficulty in obtaining reliable access to the circulation. The availability of purified heparin in 1943 and the development of a Teflon arteriovenous shunt by Belding Scribner and colleagues (10) in 1960 were landmarks that led to the general applicability of hemodialysis to patients with chronic renal failure. On March 9, 1960, Clyde Shields, a 39-year-old machinist with terminal renal failure, became the first chronic hemodialysis patient in the United States. (11) Mr. Shields lived for more than 11 years on chronic hemodialysis before dying from a myocardial infarction at age 50 years.

On October 30, 1972, the national ESRD program, Public Law 92-601, was passed as an amendment to the Medicare Act after only 30 minutes of debate with only one dissenting vote. (12) The senate followed with a 52 to 3 vote. Senator Vance Hartke (D-Indiana) summed up the rationale for the new law: "In what must be the most tragic irony of the 20th century, people are dying because they cannot get access to proper medical care. We have learned how to treat or to cure some of the diseases (that) have plagued mankind for centuries, yet those treatments are not available because of their cost. Mr. President, we can begin to get our priorities straight by undertaking a national effort to bring kidney disease treatment within the reach of all those in need." (11) The bill, signed into law by President Nixon, gave all Americans the right to treatment for ESRD, regardless of age. ESRD was and remains the only medical condition given this status.

The hemodialysis procedure

Broadly speaking, dialysis involves the movement of solutes and solvent (water) across a semipermeable membrane (the dialyzer). Clinically, this occurs when blood is exposed to an extracorporeal semipermeable membrane, on the other side of which a solution of dialysate is flowing. Three major mechanisms govern the movement of molecules in this procedure: diffusion, ultrafiltration, and convection (Table 1).

Diffusion refers to the movement of solute across a semipermeable membrane from a region of higher concentration to a region of lower concentration. This transport is dependent on the physical size of the molecule relative to the size of the pores in the membrane. (13) Obviously, if the size of the molecule exceeds the pore size of the membrane, no transport/removal of the molecule will occur. Dialysis membranes are designed to allow molecules up to 1,500 to 5,000 daltons (Da) to pass easily (high-flux membranes) but exclude progressively larger molecular weight species. (14) Other important molecular characteristics that govern diffusion include the charge and shape of the molecule. (13) Diffusion is the predominant method for removal of small molecular weight species such as electrolytes and is inefficient in the removal of larger-molecular-weight species. (13)

Ultrafiltration refers to the movement of a solvent (plasma water) across a semipermeable membrane through the application of external pressure. (15) In this process, either hydrostatic or osmotic pressure is applied to one side of the membrane and leads to solvent movement. Clinically, during hemodialysis, a negative transmembrane pressure is applied across the dialysis membrane. This hydrostatic pressure forces plasma water from the patient out into the dialysate and is the principal method of volume removal during hemodialysis. (15) One of the most important advances in dialysis technology was the development of volumetric ultrafiltration controls that can precisely determine the amount of fluid that is removed during a dialysis session.

As solvent molecules move along a pressure gradient, the dissolved solute molecules are dragged along (solvent drag) in a process termed convection. (16) Once again, the ease with which solute can be dragged across the dialysis membrane is a function of the size of the molecule relative to the size of the membrane pores. This porosity is reflected by the sieving coefficient of the membrane, which is simply the ratio of the solute concentration on either side of the membrane. For solutes such as sodium and potassium, the sieving coefficient is 1.0 (signifying easy passage across the dialysis membrane), whereas for larger-molecular-weight proteins such as albumin, the sieving coefficient is quite small (0.008). Newer, high-flux dialysis membranes are designed to allow removal of larger molecular weight species through convection. (14,16) Despite the limitations in the removal of larger molecular weight species, convection is the principle method of their dialytic removal.

The traditional hemodialysis circuit is depicted in Figure 1. In this process, blood from the patient flows on one side and dialysate flows on the other side of the dialysis membrane. The dialyzer is the site of the exchange of molecules and is the critical part of the dialysis machine. It consists of thousands of hollow capillary fibers composed of a biocompatible synthetic semipermeable membrane such as polysulfone. These fibers are bundled in the dialyzer to create a large surface area (up to 2 [m.sup.2]) that is efficient at removing solute. Blood flows through these fibers, whereas the outer surfaces are bathed in a dialysis solution. The dialysis machine circuit also includes a rotary blood pump, pressure monitors, air bubble detectors, a pump for heparin dosing, and various other safety monitors. The nephrologist sets a blood flow rate (typically, 250 to 450 mL/min), a dialysate flow rate (typically 500 to 800 mL/min), a fluid removal rate, and a duration of therapy. These parameters are chosen to maximize clearance of uremic toxins and removal of excess volume. The composition of a typical dialysate solution is given in Table 2 and can be varied to maximize clearance of substances such as potassium (for example, the dialysate concentration of potassium can be varied from 1 to 4 mEq/L, depending on the patient's serum potassium level and the need for removal).

[FIGURE OMITTED]

During a dialysis treatment, patients can be exposed to as much as 100 L of dialysate. As the dialyzer membrane acts as a filter and prevents bacteria from entering the blood, the dialysate and water used to prepare the dialysate are not required to be sterile. However, smaller molecular weight contaminants in the water system can pass into the patient and some of these are injurious (for example, copper [hemolysis], aluminum [bone disease, encephalopathy], chloramines [hemolysis], and endotoxin [febrile reactions]). (17) Thus, the water used for the dialysate preparation must undergo a rigorous purification process including reverse osmosis, deionization, and charcoal filtration. The Association for the Advancement of Medical Instrumentation has set minimum standards for water quality for dialysis. (18)

The concept of clearance and dialysis adequacy

Clinically, the removal of solute is measured in terms of clearance. Clearance reflects the volume of blood or plasma that is cleared of a given solute in a unit time. For example, if a patient begins a dialysis treatment with a blood urea nitrogen (BUN) concentration of 100 mg/dL, which falls to 10 mg/dL at the outset of the dialyzer, there is a 90% fall in the concentration of BUN that largely reflects diffusion. Now, if the blood flow rate through the dialyzer was 200 mL/min, then the clearance would be 180 mL of blood per min (0.90 multiplied by 200). Several factors affect clearance and include the blood flow rate, the dialysate flow rate, and the efficiency of the dialyzer (the ability of the membrane to allow the transport of a solute through its pores). The nephrologist alters these variables, as well as the duration of treatment to achieve clearance goals. (19)

What these clearance goals should be and how best to measure them has been the subject of much debate. (20) The ultimate goal is to provide enough clearance of toxic substances to maximize patient benefit in terms of minimizing morbidity and mortality rates. Stated in another way, the nephrologist aims to deliver enough dialysis such that the amount of dialysis delivered is not a factor in the patient's morbidity and mortality. Much of the recent history of dialysis research has focused on two central issues: (1) what solute clearances should be measured and (2) how much removal of a given solute constitutes adequate dialysis therapy.

Typically, BUN has served as the marker of clearance. (21) This is due to several factors, including the ease of measurement, and that BUN levels often correlate with uremic symptoms, which emanate from the metabolism of protein (surrogate marker). BUN levels also reflect protein intake and serve as a marker of nutritional adequacy. (22) Given this, a high BUN level in a patient with ESRD could reflect either excellent nutrition or inadequate dialysis. Alternatively, a low BUN level could reflect poor nutrition or excellent dialysis. Thus, routine laboratory measurements are not accurate in determining the "dose" of dialysis. Instead, two widely used measures of the adequacy of dialysis are calculated from the decrease in the BUN that occurs during the treatment: urea reduction rate (URR) and the KT/V. The URR is simply the percentage reduction in BUN that occurs from pretreatment values to postdialysis values. (23) KT/V is a dimensionless value that assesses three variables: (1) K, the clearance of urea during the treatment, (2) T, the duration of the dialysis session and (3) V, the volume of distribution of urea (roughly equal to total body water). (22) For example, a KT/V of 1.0 indicates that one volume of distribution of urea has been completely cleared of urea.

Two large-scale, randomized trials have assessed the relation between the delivered dose of dialysis (as measured by the KT/V) and survival. The first of these trials, the National Cooperative Dialysis Study, published in 1981, demonstrated that clearance of urea correlated with morbidity (substantiating its role as a surrogate marker for uremia), and that provision of a minimal KT/V (greater than 0.8) was required to ensure good outcomes. (24,25) Subsequently, the HEMO trial published in 2002 refined the goal KT/V by assessing outcomes in groups that were randomly assigned to two clearance goals, a low-dose group with KT/V of 1.32 and a high-dose group with KT/V of 1.71. (26) The HEMO trial demonstrated similar mortality rates in each group. Thus, the recommended goal-delivered dose of dialysis is a KT/V of 1.2 to 1.3 (or a URR of 65 to 70%). An important finding of the HEMO trial was that the provision of increased small solute clearance did not decrease mortality rates, suggesting that once a minimum dose of dialysis is delivered, other factors take on increasing importance in determining the risk of morbidity and mortality (such as blood pressure control, nutritional issues, and control of volume overload). (27) To achieve these adequacy goals, patients typically undergo hemodialysis thrice weekly with durations of treatment varying from 3 to 5 hours. In general, larger patients require longer times to achieve minimal clearance goals. Clearance is monitored for each patient on at least a monthly basis and treatment prescriptions are altered to ensure adequate dialysis.

Clearance is just one measure of the adequacy of dialysis. Adequacy encompasses the overall function of the patient and thus it is important to assess the patient's global well-being to ensure optimal dialysis. Some of the features that suggest inadequate dialysis are listed in Table 3. It is the nephrologist's responsibility to continually monitor for signs of inadequate dialysis and adjust treatment accordingly.

Vascular access

Perhaps one of the greatest challenges in the provision of hemodialysis is obtaining a long-term, reliable, dependable method of repeatedly accessing a patient's blood stream. Several options exist for permanent dialysis access including a native arteriovenous fistula (AVF), an artificial arteriovenous graft (AVG), and a dual lumen tunneled dialysis catheter. (28)

AVF is the preferred method of dialysis access. (28) AVF have the longest lifespan and are associated with the fewest complications. To create the AVF, a surgeon forms an anastomosis between an artery and a vein. The forearm of the nondominant arm is the preferred site (most commonly between the radial artery and the cephalic vein). However, other sites in the proximal arm can also be used (brachial artery and cephalic vein). (29) With this anastomosis, arterial pressure is transmitted to the vein, which dilates and becomes thickened. This process can take up to three months and generally, AVF should not be used for at least 2 months after their creation (thus, patients need to be referred to a surgeon in a timely manner). (28) After maturation, the access can be cannulated repeatedly with dialysis needles to provide blood for the dialysis procedure. Although AVF are the preferred dialysis access, there are several complications that can be attributed to the access. (30) Perhaps the most important of these problems is simply failure of the venous segment to dilate and develop a thick wall. This may occur in up to 30 to 40% of patients and necessitates formation of an alternative access site. (31) Other complications include a steal syndrome, where blood is diverted through the access and away from distal segments of the arm, and stenosis and thrombosis of the AVF. (32)

In the event that an AVF cannot be created, an AVG is the next best option. (28) In this procedure a tubular graft most often composed of polytetrafluoroethylene in interposed between an artery and a vein and tunneled underneath the skin. (33) The most common location is between the brachial artery and the basilic vein. AVG can be used within days to weeks after formation and thus require less advance planning. However, they are plagued by a high complication rate. (34) AVGs typically develop stenotic lesions at the venous anastomosis due to intimal hyperplasia. (35) This leads to increased pressures within the AVG, with prolonged bleeding once the dialysis needles are removed, and eventually will lead to thrombosis of the graft. These stenotic lesions can be treated with either surgical revision or more commonly with percutaneous angioplasty. (36) However, long-term patency rates are poor, and most AVGs do not last for more than a few years. (37) AVGs are also much more prone to infection than are native AVFs. (38) This is probably the result of the presence of artificial graft material that can be seeded with bacteria during cannulation or any time there is bacteremia.

The last hemodialysis access choice is a dual lumen catheter that is implanted surgically into the internal jugular vein (other venous sites can also be used if required). (39) The extravenous segment of the catheter is tunneled under the skin and a polyester cuff is positioned near the exit site to secure the catheter. These catheters should only be used when other access options are not available or when access is needed before there is time for placement and maturation of an AVF or AVG. (28) Hemodialysis catheters are prone to clotting, typically provide low blood flow rates and thus poor clearance, and have a high risk of infection. (39) Infections can occur at the exit site of the catheter, in the tunnel, or in the catheter itself. These infections are often difficult to eradicate without removal of the catheter and can lead to endocarditis and metastatic infection, such as osteomyelitis. (40)

Complications of hemodialysis

Hemodialysis is a complex procedure and has numerous attendant risks and complications associated with it. Broadly, these complications can be divided into treatment-related medical complications and complications that are machine related. There are a larger series of complications that occur in patients with ESRD that are due to long-standing uremia and the lack of renal function. These are reviewed elsewhere. (41)

The most common medical complication seen during hemodialysis is hypotension. (42-45) It occurs in 15 to 40% of dialysis sessions, and patients typically complain of dizziness, nausea, vomiting, sweating, and chest pain. The pathogenesis is complex and involves several interdependent variables. (42-45) Ultrafiltration that occurs during hemodialysis removes volume from the plasma space initially. This decrease in plasma volume is slowly buffered by movement of water from the extracellular space to maintain vascular filling. This refilling of the vascular space is governed by Starling forces and can vary tremendously between patients. For example, patients with a low serum albumin may not be able to move extravascular water into the plasma space very efficiently. Furthermore, during hemodialysis, solute is also preferentially removed from the plasma volume, thus lowering the osmotic forces that tend to maintain vascular volume. With the lowering of intravascular solute levels, plasma water tends to move into the extravascular space, where solute levels are higher. This further increases the risk of hypotension. Other factors that are important in the development of hypotension include autonomic dysfunction, anemia, production of vasodepressors from ischemic tissue (adenosine) during dialysis, cardiac disease, antihypertensive medications, and errors in the estimation of the patient's target dry weight. 42-45 Other factors that must be considered include bleeding and sepsis. To minimize the risk of intradialytic hypotension, dialysis sessions are closely monitored and the ultrafiltration and solute removal rates can be varied to minimize hemodynamic effects. (46) Intradialytic hypertension can also occur but does so much less frequently than hypotension. (47) Causes of a rising blood pressure during hemodialysis include removal of antihypertensive medications and underestimation of the patient's dry weight.

The leading cause of sudden death during dialysis sessions is cardiac arrhythmias, which occur more frequently in patients with preexisting left ventricular hypertrophy and coronary artery disease. (48) The rapid fluctuations in volume, electrolytes, and pH probably are causative. Electrocardiographic monitoring, however, is not routine in hemodialysis units, and thus the true frequency of intradialytic arrhythmias is unknown.

Other common intradialytic complications include muscle cramps, nausea, vomiting, and headaches. (49) The etiology of many of these complaints is unknown. A less common but serious complication is the dialysis disequilibrium syndrome (DDS). (50) Patients can have a range of neurologic symptoms including headaches, nausea, vomiting, disorientation, seizures, obtundation, or even coma. Typically, this syndrome occurs in patients with severe uremia undergoing their first dialysis treatment. Although the exact pathogenesis is unknown, it is believed that rapid removal of extracellular solute leads to movement of water into the central nervous system and the development of cerebral edema. (50) Typically, the first dialysis sessions are optimized to remove solute slowly and prevent the occurrence of DDS. Symptoms of DDS generally improve within 24 to 48 hours, and patients can be treated with mannitol if needed. (50)

Complications may also be directly related to the dialysis machine and the dialysis membrane. The hemodialysis machine is designed for optimal safety, but complications can arise, either due to machine failure or human error. The most important of these complications are air embolism and hemolysis. Air embolism manifests clinically as severe dyspnea, loss of consciousness, seizures, and lower extremity ischemic symptoms. (51) Symptoms will depend on the position of the patient and location of the dialysis access. For example, patients dialyzing through a tunneled catheter may have air enter the right atrium and pass into the lungs and present with dyspnea. Treatment consists of immediate cessation of dialysis, placement of the patient on their left side with their head down, and administration of high oxygen flow rates. In some cases, aspiration of air from the right ventricle with a pulmonary artery catheter is required. (51)

Acute hemolysis occurs rarely during hemodialysis. Most frequently, hemolysis is due to exposure of blood to chloramines that are present in municipal water systems and functions as a bacteriostatic agent. (52) Usually, chloramines are removed by a carbon filter before contact with the patient, but if the carbon filter fails, then chloramines can contaminate the dialysis water supply. Other less common causes of hemolysis include hyperthermic dialysate and kinking of blood tubing sets. (53)

Patients may also have hypersensitivity reactions to the hemodialyzer. (54,55) These may range from simple urticaria to life-threatening anaphylaxis. Often times, the cause is a reaction to ethylene oxide, which is used to sterilize the membrane, and can be treated with the use of irradiated membranes or by thoroughly prewashing the dialyzer before use. (54,55)

Conclusion

Whereas once renal failure signified certain death, the widespread availability of hemodialysis has provided patients with a life-saving and life-sustaining therapy. The procedure has been refined to the point that dialysis is now routinely provided in most communities in the United States. Recent advances promise to bring hemodialysis to the homes of patients, thus freeing patients from the restraints imposed on them by dialysis center schedules. Despite these advances, the longevity of patients on chronic hemodialysis is poor and morbidity is high. Further understanding of the uremic state is clearly needed but tremendous advances have been accomplished since Clyde Shields first began chronic hemodialysis in 1960. Most health care practitioners will participate in the care of patients undergoing hemodialysis, and it is important to have an understanding of this important procedure. It is hoped that the recent gains in improving the survival of patients on hemodialysis can be sustained and increased.

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55. Salem M, Ivanovich PT, Ing TS, et al. Adverse effects of dialyzers manifesting during the dialysis session. Nephrol Dial Transplant. 1994;9(Suppl 2):127-137.

Mitchell H. Rosner, MD

From the Department of Internal Medicine, University of Virginia, Charlottesville, VA.

Dr. Rosner has no disclosures to declare.

Reprint requests to Mitchell Rosner, MD, Division of Nephrology, Department of Medicine, Box 800133, University of Virginia HSC, Charlottesville, VA 22908. Email: [e-mail]

Accepted April 1, 2005.

RELATED ARTICLE: Key Points

* The basic physiology of the dialysis procedure and its associated complications are discussed.

* What is meant by adequate dialysis?

* What are the complications associated with dialysis?

Table 1. Physiological mechanisms involved in solute and solvent removal
during hemodialysis

Mechanism                         Description

Diffusion        Solute moves from side of higher concentration to side
                   of lower concentration across semipermeable membrane.
                 Dependent on size, shape, and charge of molecule.
                 Efficient in removal of small-molecular-weight species
                   such as electrolytes.
Ultrafiltration  Movement of solvent across a semipermeable membrane
                   from a region of high to low pressure (usually
                   hydrostatic).
                 Responsible for the removal of excess total body water.
Convection       As solvent moves down a pressure gradient, dissolved
                   solutes are dragged across the membrane. Removal is
                   dependent on the sieving coefficient of the membrane.
                 Responsible for the removal of both small- and middle-
                   molecular-weight species.

Table 2. Composition of typical hemodialysate

Constituent   Concentration (mEq/L)

Sodium           135-145
Chloride         100-116
Potassium          0-4
Calcium            2.5-3.5
Magnesium          0.5-1.5
Acetate            2-4
Bicarbonate       35-38
Dextrose           0-200 mg/dL

To form the final dialysate, two concentrates. A and B, are pumped into
proportioning systems where they are mixed with water to produce the
final concentrations. The A solution contains all of the electrolytes
and an acid buffer (acetate); the B solution contains bicarbonate.
Bicarbonate can not be stored with the electrolyte mixture, since
insoluble calcium carbonate salts would form.

Table 3. Signs and symptoms indicative of inadequate dialvsis

Malnutrition with low serum albumin, weight loss, anorexia
Nausea, vomiting
Declining functional status
Encephalopathy
Peripheral neuropathy
Pericarditis
Persistent volume overload and hypertension
Low predialysis BUN and/or creatinine
KT/V <1.2 or URR <65%

K, clearance of urea during treatment; T, duration of dialysis session;
V, volume of distribution of urea; URR, urea reduction rate.