12.1 Indications for acute/chronic dialysis
Treatment options for both end-stage kidney disease (ESKD) and acute kidney injury (AKI) include extracorporeal hemodialysis-based options, and peritoneal dialysis (PD). Important elements in the decision to initiate dialysis include interpreting the signs and symptoms of uremic syndrome ( Table 12.1 ).
Symptoms
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Assessment should include the specific indication(s) for initiating dialysis, the appropriateness of initiating dialysis as opposed to conservative management, the best method of dialysis, and the appropriate timing of initiation of dialysis.
In some cases, the initiation should be done on a trial basis, leaving open the possibility of later withdrawing the patient from dialysis support. An increasingly popular strategy in the chronic setting is active conservative chronic kidney disease (CKD) management, to forestall the need for dialysis. In addition, withholding of dialysis is increasingly a part of the nephrologist’s evaluation in the AKI or ESKD setting. , Examples include patients with profound, irreversible neurological impairment, terminal illness, inability to cooperate with the procedure, and those with markedly impaired functional status. Such a decision requires appropriate input from the patient/healthcare proxy/family members, including the option for them to pursue a second opinion.
12.1.1 Indications for dialysis initiation
Several indications for initiating dialysis are common, and they are similar in acute or chronic renal failure: to alleviate symptoms or signs of uremia, correct abnormalities of electrolyte or acid-base balance, or reverse uncontrolled hypervolemia ( Figure 12.1 ).
Dialysis may be started in severe acute renal failure when no quick recovery is expected, to avoid “impending uremia.” Typical indications for initiating renal replacement therapy (RRT) are related to hyperkalemia, acidemia, volume overload, and symptomatic azotemia.
12.2 Dialysis modalities for acute kidney injury
Guidelines state that intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are complementary therapies, with no clear superiority of one over the other (PD is currently rarely used for AKI). In a recent meta-analysis of 21 studies comparing clinical outcomes among critically ill adults with AKI treated with CRRT, IHD, or sustained low efficiency dialysis (SLED), for example, no modality had a distinct advantage. For clinically stable AKI patients, IHD is the standard modality. For more compromised patients in the intensive care unit (ICU) in whom either hemodialysis (HD) or CRRT is a consideration, continuous therapies do not appear to result in superior key outcomes such as patient survival, ICU length of stay, or ventilator days.
Meta-analyses have compared outcomes without an overall survival benefit to either modality. Several, but not all, analyses of observational data have shown a higher rate of nonrecovery from AKI among survivors treated with IHD. Conventional HD may be assumed to be contraindicated in severely compromised ICU patients (e.g., those with hypotensive circulatory failure, for whom CRRT is the standard modality). In patients with acute brain injury or fulminant hepatic failure, better preservation of cerebral perfusion may be achieved with CRRT.
Recent guidelines from the International Society for Peritoneal Dialysis suggested that PD should be considered a suitable modality for treatment of AKI in all settings, citing studies that demonstrated equivalent survival and possibly a shorter need for RRT with PD compared to other modalities. ,
12.2.1 Appropriateness of dialysis initiation
Whether or not to offer dialysis must be addressed in the AKI patient, just as it is in the ESKD patient. While the vast majority of patients could undergo dialysis with current technology, feasibility must first be addressed. The potential for dialysis recovery should be evaluated. Advance directives must be accommodated. The patient must be informed about the procedure and potential outcomes, including the possible dependence on chronic dialysis. Professional guidelines should be reviewed.
12.2.2 Timing of initiation of dialysis in AKI
The evidence regarding timing of dialysis initiation in sick patients with AKI remains relatively weak, and guidelines remain nonspecific. It is generally accepted that dialysis is urgently indicated when the AKI patient has pericarditis, altered mental status, seizures, severe metabolic derangements, uncontrollable symptomatic hypervolemia, or treatable intoxications.
When the case to initiate dialysis is less compelling, considerations may include the likelihood of recovery and the risks of doing dialysis. Elective initiation of dialysis for AKI may be required when symptoms or laboratory derangements are less severe. Multiple clinical trials have compared an early initiation approach when there is no specific indication, with a delayed approach (i.e., initiating when relevant but nonsevere signs or symptoms) have developed.
In recent years, a few randomized controlled trials have attempted to resolve the issue of initiation of dialysis for AKI with mixed results ( Table 12.2 ).
| Variable a | ELAIN (N = 231) | AKIKI (N = 620) | IDEAL-ICU (N = 488) | STARRT-AKI (N = 3019) |
|---|---|---|---|---|
| Study design | Single-center RCT | Multicenter RCT | Multicenter RCT | Multicenter multinational RCT |
| Early group | Within 8 hr of stage 2 AKI and NGAL > 150 ng/mL; median: 6 hr | Within 6 hr of stage 3 AKI; median: 2 hr | Within 12 hr of stage 3 AKI; median: 7.6 hr | Within 12 hr of stage 2 or 3 AKI; median: 6.1 hr |
| Delayed/standard group (time from eligibility) | Within 12 hr of stage 3 AKI or clinical indication; median: 25.5 hr | After 72 hr in stage 3 AKI or clinical indication; median: 57 hr | After 48 hr in stage 3 AKI or clinical indication; median: 51.5 hr | After 72 hr in AKI or clinical indication; median: 31.1 hr |
| Key exclusions | eGFR < 30 | Severe lab abnormalities | Emergent need for dialysis | eGFR < 20 |
| KRT protocol | Prescribed protocol using CVVHDF | Discretion of site providers, guideline based | Discretion of site providers, guideline based | Recommendations provided based on guidelines |
| Primary outcome | 90-day mortality: 39.3% vs. 54.7% ( P = 0.03) | 60-day mortality: 48.5% vs. 49.7% ( P = 0.79) | 90-day mortality: 57.7% vs. 53.8% ( P = 0.38) | 90-day mortality: 43.9% vs. 43.7%; RR, 1.00 (95% CI, 0.93–1.09) |
| Proportion not requiring KRT | 0% vs. 9.2% | 1.9% vs. 49.0% | 2.8% vs. 38.4% | 3.2% vs. 38.2% |
| Dialysis dependence (among survivors) | At 90 days: 13.4% vs. 15.1% ( P = 0.80) | At 60 days: 1.9% vs. 5.2% ( P = 0.12) | At 90 days: 2.0% vs. 2.7% ( P = 1.00) | At 90 days: 10.4% vs. 6.0%; RR, 1.74 (95% CI, 1.24–2.43) |
| Adverse events | No significant differences | CRBSIs: 10.0% vs. 5.2%; P = 0.03 | Hyperkalemia: 0% vs. 4.1%; P = 0.03 | Any: 23.0% vs. 16.5% ( P < 0.001); no difference in serious adverse events |
Two randomized controlled trials have recently reported data on the timing of RRT in critically ill patients with AKI, while demonstrating the difficulties of such trials. In the Artificial Kidney Initiation in Kidney Injury (AKIKI) multicenter trial from France, 620 patients were initiated either “early” (KDIGO stage 3) or “late” (KDIGO stage 3 and clinical indications), to determine whether late dialysis initiation improved mortality risk. There was no difference in the primary outcome of 60-day all-cause mortality. Importantly, however, half of patients randomized to late initiation did not receive RRT, either recovering kidney function or dying. Nonetheless, a post-hoc analysis indicated that, for patients in the late-start group actually treated with RRT, mortality was higher in comparison with the early group.
In the Standard Versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial, the most definitive study to date, over 3000 AKI patients without a specific indication for dialysis were randomized. Dialysis was initiated in most of the early-initiation patients, but only about two-thirds of the late-initiation patients. Adverse events, continued dialysis dependence, and rehospitalization, but not mortality, were higher in the early-initiation group. In the AKIKI-2 trial, critically ill AKI patients were allowed to be more azotemic before randomization to early or late strategies, with mixed results.
The single-site Early Versus Late Initiation of KRT in Critically Ill Patients With AKI (ELAIN) trial in Germany compared early (KDIGO AKI stage 2) with late (KDIGO AKI stage 3). To diminish the likelihood that enrollees would actually recover kidney function and not need dialysis, clinical AKI criteria were combined with levels of the biomarker NGAL. In the late group, only 5% recovered from AKI without needing dialysis. The early group had a lower 90-day all-cause mortality; the ELAIN trial is the only recent randomized trial to demonstrate mortality benefit.
Few studies have examined initiation of dialysis for AKI in specific settings. For elective initiation of dialysis in cases of AKI after major abdominal surgery, there is a suggestion that early initiation of dialysis might be beneficial to patient mortality.
Finally, a recent meta-analysis showed that mortality did not differ significantly according to whether dialysis was initiated early or delayed in AKI, and suggested initiation only when a specific clinical indication emerges as an acceptable approach.
Taken together, these studies have diminished enthusiasm for aggressive initiation of dialysis for AKI in the absence of a compelling indication.
12.2.3 Withdrawal from dialysis
The principal justification for dialysis is to improve quality of life and to prolong life. However, dialysis in vulnerable patients may be associated with deteriorating physical function, increasing dependence, and deteriorating quality of life. Withdrawal from dialysis may then be appropriately discussed with the patient and family, with emphasis placed on symptom control and addressing end-of-life goals.
12.2.4 Recovery from AKI
The dialysis- or CRRT-dependent AKI patient should be monitored for recovery of kidney function, but the optimal strategy and timing for actually weaning from dialysis remain uncertain.
The obvious clinical clues include increase in urine output (UO) before dialysis (usually detected in the interdialytic interval), slowed postdialytic rise in creatinine (Cr), or a functional test such as responsiveness to diuretics. In the future, renal biomarkers may be shown to be independent predictors of recovery.
12.2.5 Adequacy of conventional hemodialysis in AKI
Assessment of adequacy of IHD is conventionally based on urea kinetic modeling. In the chronic setting, a calculated single-pool Kt/V urea of 1.2 is accepted as the minimal goal for adequate dialysis. Kt/V (urea) (the fractional urea clearance) is regarded as the most clinically valid small-solute measure of dialysis dose at the current time. It is a biochemical outcome measure. Kt/V (urea) refers to clearance of urea in a given time period (Kt = clearance × time), individualized to patient size, with this calculation based on the patient’s total body water volume (V) as estimated from the patient’s weight, leading to the expression Kt/V. In the setting of AKI, however, the volume of distribution of urea may be highly variable. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend delivering a Kt/V of 3.9 per week for IHD. The Veterans Adminstration/National Institutes of Health (VA/NIH) ATN study randomized patients to receive either intensive or less intensive dialysis; for those on intermittent dialysis, the less intensive group were treated 3 times per week, and the more intensive group 6 times per week. Intensive renal support did not improve outcomes. The best evidence, such as from the Acute Renal Failure Trial Network (ATN) Study (VA/NIH), suggests that patients with dialysis-dependent AKI should receive at least 3 HD treatments per week, each with a delivered Kt/V value of 1.2. A simpler approach may be to target a urea reduction ratio (URR = [predialysis BUN—postdialysis BUN] / predialysis BUN) of >0.67.
12.2.6 Continuous renal replacement therapy
The choice of renal replacement modality is commonly determined by the patient’s hemodynamic status. However, CRRT for AKI in gradually undergoing a paradigm shift beyond just those patients too unstable to tolerate conventional HD, to becoming the treatment of choice for all with multiorgan failure. CRRT is an ICU-based therapy intended to be applied on a continuous but short-term basis.
CRRT is the preferred dialysis modality in patients with AKI and hemodynamic instability. A typical indication for CRRT is the need for RRT (fluid overload, uremia, uncorrectable acidosis, hyperkalemia, some intoxications) in a hemodynamically unstable patient. It may also have advantages for the AKI patient with increased intracranial pressure, severe hypo/hypernatremia, or drug intoxications. Typical indications for CRRT are shown in Table 12.3 .
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There are multiple CRRT options, as shown below in Table 12.4 .
| Option | Clearance | Dialysis | Replacement | UF Goals | Clearance |
|---|---|---|---|---|---|
| SCUF | Convection | No | No | Modest | Low |
| CVVH | Convection | No | Yes | Large | Medium |
| CVVHD | Convection and diffusion | Yes | No | Modest | Higher |
| CVVHDF | Convection and diffusion | Yes | Yes | Large | Highest |
Most CRRT is done by continuous veno-venous hemofiltration (CVVH), rather than continuous arterio-venous hemofiltration (CAVH), as CVVH without dialysis or with concomitant dialysis, through a process called continuous veno-venous hemodialysis or hemodiafiltration (CVVHD). Balanced hemofiltration and dialysis with larger volumes of hemofiltration and large volumes of replacement fluid, together with dialysis, can be achieved with CVVHDF (also known as continuous hemodiafiltration) when the hemofiltration rate is set at 20% and the effluent target ranges from 20 to 35 mL/kg/hr. They should be viewed as complementary therapies for the AKI/ESKD population.
CRRT offers several advantages over intermittent HD in critically ill patients: greater hemodynamic stability, increased fluid removal, and continuous solute (uremic toxins, electrolytes) control. CRRT clearance is based on a combination of diffusion (dialysis), convection (ultrafiltration), and to a lesser degree, adsorption by the membrane. It is similar to clearance by intermittent dialysis, although less efficient per unit time.
Compared to HD, blood flow is slower, the throughput of fluid (i.e., administered and removed) is much larger than for HD, and the dialysate rate is slower. Because filter clearance for small solutes is equal to the product of the total effluent (i.e., postfilter fluid) amount and the concentration of solute in that effluent is relative to plasma (i.e., the sieving coefficient)—which reaches 1 for small solutes—clearance adequacy can be measured as actual solute removal. Adequacy is therefore determined by the total effluent fluid rate (replacement fluid, dialysate, net fluid removal), which is recommended to be 25 mL/kg body weight per hour.
The fluids utilized for replacement and dialysate are premixed, sterile, and free of bacterial endotoxins. Depending on the product, they generally contain calcium, magnesium, sodium, potassium, bicarbonate, lactate, and dextrose. An additional fluid replacement option contains phosphate. A few of the options do not contain dextrose; loss of endogenous glucose in the ultrafiltrate may place some critically ill, catabolic patients at risk for euglycemic ketosis during CRRT. Typical replacement and dialysate solutions are shown in Table 12.5 .
| GAMBRO (BAXTER) | NXSTAGE | B. BRAUN | ||
|---|---|---|---|---|
| a PrismaSol BGK/B22K/BK | b PrismaSATE3 BGK/B22K/BK | b RFP 400–456 | b Duosol 4551–4556 | |
| Na + , mEq/L | 140 | 140 | 130–140 | 140–136 |
| K + , mEq/L | 0–4 | 0–2–4 | 0–4 | 0–4 |
| Cl − , mEq/L | 108–113 | 108–120.5 | 108.5–120.5 | 109–117 |
| Lactate, mEq/L | 3 | 3 | 0 | 0 |
| Bicarbonate, mEq/L | 22–32 | 22–32 | 25–35 | 35–25 |
| Ca + + , mEq/L | 0–2.5–3.5 | 0–2.5–3.5 | 0–3 | 3–0 |
| Mg + , mEq/L | 1.0–1.2–1.5 | 1.0–1.2–1.5 | 1–1.5 | 1–1.5 |
| Dextrose, g/dL | 0–1 | 0–1.1 | 1 | 1–0 |
A typical order set for CVVHDF would include blood flow rate 100 to 250 mL/min; dialysate flow rate 1000 to 2000 mL/hr; replacement flow rate 1000 to 2000 mL/hr; and ultrafiltration rate 33 to 66 mL/min.
Replacement fluids may be administered pre- or postfilter. Prefilter administration is associated with decreased filter clotting and increased filter lifespan. (The blood pump will usually have its rate increased to compensate for the added fluid and to achieve sufficient clearances.) Postfilter administration is associated with improved solute clearances.
As a motor-driven system involving flow of fluid, key pressure measurements are determined at four points in the CRRT extracorporeal circuit. Abnormal pressure alarms require clinical correlation. Pressures are used to calculate the transmembrane pressure (TMP) and pressure drop from one end of the filter to the other. Pressure measurements that may require troubleshooting are shown in Figure 12.2 .
12.2.7 Characteristic pressure measurements and common abnormalities
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Access line: Preblood pump; pressure always negative (–50 to –150); high due to catheter clotting, line kinked.
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Filter (prefilter): At postblood pump; always positive (+50 to +150); detects resistance to flow to patient, or clotting.
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Effluent line: Before effluent pump; usually negative but may be positive; –150 to +50; used to calculate TMP.
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Return line: Pressure of return circuit before catheter; high pressure due to catheter clotted/line kinked.
The filtration fraction is the fractional volume of plasma removed from the dialyzed blood in the process of ultrafiltration (i.e., the ratio of the ultrafiltration rate to the plasma flow rate). Filtration fraction is calculated as follows:
12.2.8 Filtration fraction
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FF(%) = (UFR × 100)/Qp
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where Qp = BFR × (1—hct) = filter plasma flow rate in mL/min (FF, filtration fractio; UFR, ultrafiltration rate; Hct, hematocrit)
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Example: BFR = 100 mL/min
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Hct = 30%
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UFR of .21 (21%) = FF 30%
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Experts recommend keeping the filtration fraction below 20% to 30% in order to reduce the risk of premature filter clotting. However, there are limitations of using the filtration fraction as an index of risk of hemofilter clotting, including the rate of administration of prefilter replacement fluids. So the use of end-of-hemofilter hematocrit is an alternative, but needs to be validated.
Removal of medications by CRRT, since it is a form of continuous dialysis, may be significant, and may even exceed that of normal kidney function. Multiple citations are available as guides to drug dosing in CRRT.
Some antimicrobial agents do not require dose modification during CRRT ( Table 12.6 ) .
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CRRT allows for increased volumes of nutritional support but may result in loss of some nutrients.
The CRRT system typically requires anticoagulation, in the form of regional citrate anticoagulation with calcium replacement ( Figure 12.3 ) , or, less commonly, systemic or regional heparin anticoagulation ( Figure 12.4 ).
Citrate infused into the arterial port of the circuit chelates calcium, resulting in anticoagulation of the filter. Replacement parenteral calcium is administered separately. Guidelines now advocate citrate anticoagulation as first-line therapy for CRRT. Trisodium citrate is typically administered prefilter at a fixed ratio between blood and citrate infusions. Replacement calcium is administered systemically. Dosing protocols for using unfractionated heparin vary widely; a typical approach would be a systemic loading dose of 500 to 1000 IU followed by 500 units hourly, and adjusted according to the activated partial thromboplastin time ( Figure 12.4 ).
The results of a recent large randomized trial comparing anticoagulation strategies for CRRT favored citrate compared to heparin anticoagulation, with greater efficacy (filter lifespan) and safety (lower risk of bleeding complications). Several regional citrate anticoagulation protocols are available. CRRT in COVID-19 patients may be complicated by thromboembolic events and disseminated intravascular coagulation. Frequent clotting of CRRT filters and dialysis catheters in many cases has required both systemic heparin and prefilter citrate anticoagulation as well. ,
From the above description of the CRRT procedure, several complications would be predicted. Common complications are shown in Table 12.7 .
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CRRT is intensive and complex therapy. Key quality metrics in CRRT commonly used include delivery of adequate dose of dialysis, adequate fluid removal, actual compared to prescribed dialysis dose, filter life, and preventable significant errors. Strategies have been described to bring process-based metrics to quality improvement of CRRT delivery.
Few studies have evaluated strategies for weaning the AKI patient off of CRRT. Clinical considerations should include evidence of impending renal recovery (UO monitoring, improvement in kidney function tests), as well as goals of care. Increased UO before CRRT cessation is a common predictor.
Between CVVH and CVVHDF, there is little evidence to support one modality over the other in the overall CRRT population. Several studies have addressed both renal recovery and mortality outcomes of CRRT relative to HD in AKI, with no consensus.
While no improvement with CVVH in mortality was shown in a meta-analysis, hemofiltration did increase the clearance of medium to larger molecules.
Data on mortality and other outcomes related to the amount of CRRT delivered are limited. The RENAL study assessed CRRT at two levels of intensity in critically ill patients with AKI (replacement): lower (effluent flow of 25 mL/kg/hr) or higher (40 mL/kg/hr). High intensity (35–48 mL/kg/hr) was not associated with benefit in terms of mortality or renal recovery in a meta-analysis.
A summary of basic reminders for the dialysis prescription is shown in Table 12.8 .
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12.2.9 Sustained low-efficiency dialysis
SLED has been increasingly used recently, related to patient surges exceeding the availability of CRRT machines in the ICU setting. The 2012 KDIGO guidelines for AKI noted that SLED was suitable for hemodynamically unstable patients, but noted the lack of scientific evidence necessary to support it as a modality alternative to CRRT. At some centers, it is employed as a prolonged therapy instead of CRRT.
The same dialysis machines for intermittent HD are used for SLED; alternatively, CRRT machines may be used for this hybrid therapy. A typical SLED prescription would include blood flow 250 to 300 mL/min, dialysate flow 100 to 300 mL/min, a duration of 6 to 12 hours, fluid removal less than 500 mL/hr, and treatment frequency 3 to 6 times per week. Metabolic clearance goals are achieved in less time than with CRRT. There is less need for anticoagulation than with CRRT (i.e., prefilter heparin 1000 u bolus, then 500 u/hr would be typical). Potential advantages of SLED include faster correction of acidemia, less anticoagulation, and uninterrupted therapy (i.e., CRRT patients have the treatments paused not infrequently for radiology, etc.) so that clearance goals are more likely to be met than with CRRT.
Typical parameters for a SLED prescription are shown in Table 12.9 .
| Blood Flow | Dialysate Flow | Duration | UF Rate | Frequency |
|---|---|---|---|---|
| 150–300 mL/min | 100–300 mL/min | 6–12 hr | Up to 500 mL/hr | 3–6 times per week |
SLED and CRRT have demonstrated equivalence in outcomes such as hemodynamic tolerance, fluid removal, ICU stays, renal recovery, pressor requirement, and mortality rates. , Practical disadvantages include cost of supplies, limited flow rates, and dependence on dialysis nursing because conventional HD machines are used.
12.2.10 Peritoneal dialysis for AKI
PD should be considered a suitable modality for treatment of AKI. In fact, potential advantages include simplicity, lower cost, gradual solute removal, no need for anticoagulation, better hemodynamic tolerance, and possibly shorter time to renal recovery. Disadvantages may include catheter-related mechanical problems, risk of peritonitis, lack of adequacy in hypercatabolic or hypoperfused patients, undesirable effects on mechanical ventilation, glucose absorption, and protein loss. The main concern of physicians may be inadequate clearances with PD.
Because of insufficient good-quality clinical data, selection of PD for AKI patients needs to be individualized.
Commercially available PD solutions typically contain significant lactate, which may accumulate in critically ill patients or those with liver failure. Emergent placement of PD catheters should be used where resources and expertise exist.
The appropriate dose of PD in the AKI patient remains uncertain. The application of standard urea kinetic modeling has not been validated for use of PD in AKI. Recent guidelines indicate that targeting a weekly Kt/V urea of 3.5 provides outcomes comparable to those of daily HD in critically ill patients.
Recent meta-analyses have shown that PD is not inferior to other extracorporeal therapies in the management of patients with AKI, and additional experience has been gained during the COVID-19 pandemic, , though the need for prone positioning to improve oxygenation posed a challenge for some COVID-19 patients.
12.3 Dialysis for ESKD
Characteristics of currently available dialysis modalities are shown in Table 12.10 . (adapted from Table 1 ).
| Characteristic | Conventional Hemodialysis | Short Daily Hemodialysis | Nocturnal Hemodialysis | Continuous Ambulatory Peritoneal Dialysis | Automated Peritoneal Dialysis |
|---|---|---|---|---|---|
| Location | In-center | In-center or home | In-center or home | At home | At home |
| Sessions per week | 3 | 5–6 | 5–6 | Daily | Daily |
| Time per session | 4 hr | 2–3 hr | 6–9 hr | 3–5 hr per exchange | 8–9 hr at night |
| Contraindications | No vascular access; CV instability | No vascular access; CV instability; inadequate home support | No vascular access; CV instability; inadequate home support | Abdominal surgeries; nonfunctional membrane; inadequate home support | Abdominal surgeries; nonfunctional membrane; inadequate home support |
Conventional HD is by far the most common modality. Compared to the standard 3 weekly in-center treatments, frequent (6 weekly) treatments appear to reduce long-term mortality and benefit select patients. Longer session times appear to improve hospitalization and mortality rates. HD intensification with extended-duration nocturnal treatments modestly improves overall metabolic profiles of uremic toxins but is more effective in clearing small toxins, and studies suggest improved quality of life and patient survival. Results from recent studies have revealed concerns inherent in the 3-times weekly intermittent HD schedule, which obligates one longer, 3-day interdialytic interval each week. These include increased arrhythmias, hospitalizations, and mortality on the day of the dialysis treatment that follows the longer interdialytic interval.
12.3.1 Timing of dialysis initiation in ESKD
Older studies established a trend for early initiation of dialysis in ESKD. The definition of early and late was based on the degree of renal dysfunction, measured by creatinine clearance (CrCl) or Cr-based estimated glomerular filtration rate (eGFR). More recently there has been much uncertainty about the timing of chronic dialysis initiation (early vs. late start).
Several studies have found that there is no benefit of early initiation of dialysis, and that it may lead to dialysis of patients who might not require it. Furthermore, there is a suggested benefit of a late start based on symptoms or signs of uremia. The results of the Initiating Dialysis Early and Late (IDEAL) study, the only randomized trial to have tested the impact of dialysis initiation at two different levels of kidney function on outcomes, demonstrated no significant difference in survival or other patient-centered outcomes between treatment groups. Another large retrospective analysis concluded that late initiation of dialysis (classified by eGFR at the time of initiation) was associated with a reduced risk of mortality.
These data have challenged the established paradigm of using estimates of glomerular filtration as the primary guide for initiation of maintenance dialysis and illustrate the compelling need for research to optimize the high-risk transition period from CKD to ESKD. That is, the solute and volume control achievable by dialysis may be offset by the potential risks of dialysis. Risk equations for predicting the time frame to needing maintenance kidney replacement therapy have been developed.
12.3.2 Appropriateness of dialysis initiation
The appropriateness of starting dialysis in a particular patient applies especially to the chronic setting, and should be based upon two considerations: expected patient survival with or without dialysis, and quality of life. ,
Elderly patients (>80 years) with significant comorbidities might need to be informed that chronic HD may extend life only 2 to 3 months more than conservative medical management without improving quality of life, although that should be decided individually on a case-by-case basis. ,
12.3.3 Conservative management of the ESKD patient
Conservative (nondialytic) care of the patient with advanced kidney failure is increasingly recognized as an alternative and appropriate approach for certain patients. , Key features while attempting to delay late progression of kidney disease include minimizing ESKD complications and improving symptom burden and life satisfaction. Advanced care planning and shared decision-making should be incorporated.
12.3.4 Dialysis membranes
HD membranes are manufactured with cellulose, modified cellulose, or synthetic polymers. A variety of membrane compositions continue to be tested in order to bring solute removal closer to that of native kidneys.
Dialyzer clearance specifications are determined by the surface area (A) and mass transfer coefficient of a given solute, which is a function of the membrane composition. Ideal features of an HD membrane include nonthrombogenic, selective permeability, biologically compatible, adequate surface area, tight pore size distribution, minimal thickness, and affordability. Noncellulosic membranes are characterized as high flux (i.e., they are better able to remove fluid and moderate-sized molecules).
Solute removal in conventional HD occurs primarily by diffusion. The effectiveness of extracorporeal therapies in general is related to the size of the target substances being removed. While smaller molecules are effectively removed by HD, clearance of “middle molecules” (0.5–60 kD), typically represented by beta2-microglobulin, is less effective ( Figure 12.5 ) .
Middle molecules have been associated with inflammation, cardiovascular events (CVEs), and other ESKD comorbidities. Compared to the previous generation of low-flux dialysis membranes, currently used high-flux membranes provide greater clearance of larger solutes. The clinical benefit of even newer “medium cutoff” dialysis membranes, which help remove larger middle molecules with minimal albumin leak, is under investigation. This device has recently received FDA approval in the United States.
Dialysis membrane biocompatibility refers to specific interactions between the dialysis membrane and the patient’s blood. The material of the dialysis membrane is the major determinant of the biological response to it. Improved, biocompatible membranes elicit less of an inflammatory response. Synthetic membranes have higher biocompatibility than older cellulosic membranes.
Membrane characteristics are shown in Figure 12.6 .
12.3.5 Vascular access for hemodialysis
While the intent of chronic dialysis is to clear uremic toxins from the entire body, quality HD starts with the existence of a reliable access to the patient’s vascular system. There are three main types of vascular access for HD: arteriovenous fistula (AVF), arteriovenous graft (AVG), and central venous catheter (CVC; tunneled or not). (Note that a “hybrid” access called the Hemodialysis Reliable Outflow [HeRO] involves a graft at one end, typically sutured to the brachial artery, and a tunneled central venous segment at the other end; it is designed to allow bypass of a central venous occlusion). The standard types of dialysis access are described below ( Figure 12.7 ).
The “Fistula First” initiative emphasized the AVF as the optimal vascular access type, while reevaluation of this strategy for all patients has increased awareness that this may not always be the best strategy, such as in elderly patients. HD access should be able to provide a blood flow of at least 300 mL/min. Recent recommendations call for a more patient-focused approach to access planning and management.
12.4 Dialysis access planning
Access care decisions involve protocols and an interdisciplinary team but must be individualized in order to determine the best access use for each patient , since there are advantages and disadvantages of all vascular access types. In recent years, there have been shifts from AVGs to fistulas and from distal to upper arm fistula locations. Patients referred to the nephrologist prior to the need for dialysis are more likely to start dialysis with an AV fistula as their permanent access. Unfortunately, the CVC remains the first access used in as many as 75% of patients initiating dialysis in the United States.
Dialysis access planning begins with educating the patient about the basic types of kidney replacement therapy (HD, PD, transplantation). In patients not certain to choose PD or those unlikely to receive a timely kidney transplant, evaluation for an AVF should be initiated, while at the same time CKD management should continue, and the patient should understand that this does not mean dialysis is imminent.
Since fistula maturation (i.e., maturation means the AVF can be cannulated and provide prescribed dialysis) may take at least 1 month, commonly, 3 to 12 months, and may require interventional procedures before use, each patient with progressive and/or an eGFR of 15 to 20 mL/min/1.73 m 2 should therefore begin access planning, including patient education and referral to the access surgery team. (It is important that the patient understand that veins for potential AVF placement should not be used for venipuncture, placement of intravenous catheters, or overlying blood pressure [BP] cuff placement.) Imaging studies to determine the suitability of vessels for AV access creation, such as Doppler ultrasound, may be required.
12.4.1 Access dysfunction/monitoring/surveillance
Access dysfunction occurs in several ways, most importantly resulting in reduction in access flow ( Table 12.11 ).
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Recent guidelines emphasize the primary importance of clinical monitoring strategies such as inspection, palpation, and auscultation in early detection of access dysfunction.
Access recommendations now conclude that evidence supporting technical measures such as access blood flow, pressure monitoring, or imaging for stenosis as surveillance tools is inadequate. , Likewise, guidelines are not to recommend preemptive angioplasty of fistulas or grafts which have stenosis that is not associated with clinical indicators.
Key features of dialysis access surveillance and monitoring are shown in Table 12.12 .
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12.5 Hemodialysis catheters
For both ESKD and (more commonly) AKI requiring urgent HD, the most efficient and achievable access remains the HD catheter. Tunneled dialysis catheters are in fact the most common vascular access used to initiate maintenance dialysis in many patients with ESKD, and may be appropriate in cases of AKI with some likelihood of recovery from longer-term dialysis dependence. The ideal dialysis catheter would deliver adequate blood flow, be resistant to infection and thrombosis, and not cause vascular injury, but currently available catheters are imperfect.
Duration of optimal catheter use to minimize infection risk is shown in Table 12.13 .
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Early complications of catheter insertion are mainly related to insertion, as shown in Table 12.14 .
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Subsequent complications of the HD catheter use are shown in Table 12.15 .
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An additional management challenge is a poorly functioning catheter. The differential diagnosis may include not only thrombotic occlusion, but also growth of a fibrin sheath, malpositioning of the catheter tip, or kinking of the catheter. Mechanical problems are more common shortly after insertion whereas thrombotic occlusion or fibrin sheath formation is more likely 2 weeks or more after catheter insertion. The approach to malfunction is indicated in Figure 12.8 .
Note that evidence does not support the routine use of prophylactic systemic anticoagulation in order to prevent catheter thrombosis episodes.
12.6 Hemodialysis catheter infections
Prophylaxis: Catheter infection may occur via contamination of external or internal tunneled catheter surfaces. In addition to routine surveillance and monitoring, methods to prevent catheter-related bloodstream infections (CRBSIs) include extraluminal strategies and the use of intraluminal antibiotic lock solutions. The approach to prophylaxis is shown in Table 12.16 .
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CRBSIs contribute significantly to morbidity and mortality in HD patients. Common risk factors include impaired immune system, skin colonization with Staphylococcus , prolonged catheter duration, and a history of prior catheter-related bacteremia episodes.
Blood cultures should be drawn as an initial step to confirm the presence of bloodstream infection. Determination that bacteremia is secondary to the HD catheter is likely when there is obvious infection of the external portion of the catheter by the same organism.
Confirmation that the catheter is the culprit in a bacteremic patient, according to recent guidelines, may also be determined by criteria involving cultures obtained from blood samples through the catheter or directly from the catheter tip (at removal), compared to results from a peripheral venous culture.
There are four main options for CVC management (in addition to systemic antibiotic treatment) in the setting of CRBSI, as shown in Table 12.17 .
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Immediate empiric catheter removal may be indicated in the presence of high-grade bacteremia, severe sepsis, metastatic infection, or concurrent exit-site/tunnel infection.
Empiric therapy should include both Gram-positive (vancomycin) and Gram-negative (ceftazidime/aminoglycoside) coverage.
Subsequent antibiotic coverage should be based on identification and antibiotic sensitivity of the offending pathogen.
The KDOQI algorithm for CVC-related infection is shown in Figure 12.9 .
12.7 Anticoagulation in hemodialysis
Anticoagulation is an important part of the dialysis procedure itself. Most common options for anticoagulation are unfractionated heparin and, less commonly, low molecular weight heparin. While there is no need to adjust dosing of unfractionated heparin in ESKD, dosage reduction is necessary for low molecular weight heparin. Other agents are available when heparin is not an option (e.g., in heparin-induced thrombocytopenia). The pharmacokinetic properties of anticoagulants in the setting of ESKD are shown in Table 12.18 .
| Anticoagulant | Chemical Composition | Mechanism | Follow-Up Indicator |
|---|---|---|---|
| Unfractionated heparin | Mixture of glycosaminoglycan chains 5000–30,000 Da; renal excretion 10% | Binds to antithrombin III, inhibits clotting factors IIa and Xa | PTT; anti-Xa heparin assay (therapeutic range 0.3–0.7 U/mL); 1%–5% heparin-induced thrombocytopenia |
| Low molecular weight heparin | Fragments of larger heparins, 4000–8000 Da; renal excretion 40% | Binds to antithrombin III, inhibits clotting factor Xa | Anti-Xa (therapeutic range 0.5–1.2 U/mL, prophylactic 0.2–0.5 U/mL); 0%–3% heparin-induced thrombocytopenia |
| Citrate | Citrate 2.4 mEq/L in dialysate acid concentrate or trisodium citrate solution, 3% (ACD-A solution) | Citrate chelates calcium to disrupt the coagulation cascade | Visual inspection for clots in dialysis circuit; ionized calcium (therapeutic <0.4 mmol/L in the dialyzer) or an activated clotting time of 1.5–2.0 times baseline (180–250 sec) |
The need for systemic anticoagulation is also common in ESKD apart from the dialysis procedure. A common example is atrial fibrillation. The proper use of anticoagulation unrelated to the dialysis procedure in ESKD begins with assessment of bleeding risk ( Table 12.19 ).
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The site of action of oral anticoagulants in the coagulation cascade is noted in Figure 12.10 .
The use of vitamin K antagonists has long been the standard of care in CKD patients at risk for thromboembolic complications, but the risk of bleeding is disproportionately increased. For ESKD patients requiring systemic anticoagulation such as atrial fibrillation, initiation and maintenance of anticoagulation is complex. For example, doses of warfarin required may be 20% lower, and ESKD patients spend less time in the therapeutic INR range. Note that warfarin is considered a risk factor for calcific uremic arteriolopathy (calciphylaxis). Non–vitamin K-dependent oral anticoagulants are increasingly used, primarily for atrial fibrillation, and would be expected to have an improved risk–benefit profile. Apixaban 2.5–5 mg twice daily may be administered in ESKD, but the dosage should be reduced to 2.5 mg twice daily if the patient is over 80 years old or weighs less than 60 kg. Apixaban appears to be associated with reduced mortality and embolic events and is safer than warfarin treatment in dialysis patients. In a recent randomized trial, rivaroxaban reduced fatal/nonfatal CVEs and major bleeding complications compared to a vitamin K antagonist in HD patients with atrial fibrillation.
The pharmacokinetic properties of oral anticoagulants are shown in Table 12.20 .
| OAC | Type | Prodrug | PHARMACOKINETICS | Pharmacodynamics: Binding to Effector | ||
|---|---|---|---|---|---|---|
| Metabolism | Renal Dose Adjustment | Dialyzable | ||||
| Warfarin | Vitamin K–dependent factor inhibitor | No | Extensive metabolism by CYP2C9 | Minor | No | Irreversible |
| Dabigatran | Direct thrombin inhibitor | Yes | Metabolized by esterases, 80% excreted by kidney | Yes | Yes | Reversible |
| Apixaban | Free and clot-bound Xa inhibitor | No | Metabolized in liver by CYP3A4, then excreted in feces and kidney (25%), no active metabolite | Yes for some | Small | Reversible |
| Rivaroxaban | Free and clot-bound Xa inhibitor | No | 66% excreted by kidney, 36% unchanged, minimal in feces | Yes | No | Reversible |
| Edoxaban | Free Xa inhibitor | No | 50% excreted unchanged by the kidney, 10% hydrolyzed by carboxyesterase 1 | Yes | No | Reversible |
12.8 Hemodialysis emergencies
Maintenance HD safety has improved significantly over time and is now considered a routine procedure. Nonetheless, serious complications can occur and require emergency evaluation and management. Some are reviewed below ( Table 12.21 ).
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12.8.1 Dialyzer reactions
Allergic or even anaphylactic reactions may occur in the dialysis patient, usually within the first 5 to 10 minutes (Type A, commonly related to ethylene oxide used as a sterilant, or less commonly to the dialyzer membrane), but in some cases up to 30 minutes after initiation. Dialyzer reactions occurring after 30 minutes and up to 60 minutes after initiation (Type B) are usually less severe and most commonly related to reactions to the dialyzer membrane that are often complement mediated. Less commonly, reactions are related not to the sterilant or membrane, but to heparin or other medications administered, such as iron, rarely erythropoiesis stimulating agents (ESAs), or blood products.
Presentation may include acute bronchial constriction with respiratory distress or chest tightness, vasodilation with hypotension, anxiety, abdominal cramping/diarrhea, or in the worst cases, cardiac arrest.
Dialysis in such severe cases should be terminated without returning blood to the patient; provide aggressive fluids for hypotension, call for emergency assistance, and administer antihistamines, corticosteroids, or epinephrine.
For subsequent episodes, switch to a dialyzer with a non-ethylene oxide sterilizer, such as a gamma ray–sterilized dialyzer; use an alternative dialysis membrane; prime the dialyzer well, and pretreat with antihistamines/steroids as needed.
12.8.2 Dialysis disequilibrium syndrome
Neurological signs and symptoms of dialysis disequilibrium syndrome can include nausea, vomiting, confusion, or seizures during or shortly after the initial dialysis session(s).
Risk factors are very high BUN/Cr, rapid reduction of BUN/Cr by the dialysis treatment, older age, liver disease, abnormal serum sodium, and metabolic acidosis.
Prevention measures for the initial 3 HD treatments include lower blood flow, shortened dialysis sessions, and higher dialysate sodium, or consideration of CRRT.
12.8.3 Venous air embolism
A venous air embolism occurs when air enters the patient’s bloodstream from the extracorporeal circuit due to a loose connection or defect in the components of the blood circuit.
A venous air embolism may cause hypoxia, hypotension, pulmonary hypertension (HTN), or cardiac arrest; if it coexists with a patent foramen ovale, it may enter the arterial circulation and result in ischemic injury, usually cerebral.
In cases of venous air embolisms, stop dialysis, place the patient in the left lateral recumbent position, and treat for hypoxia and hypotension.
12.8.4 Pyrogenic reactions
Symptoms of pyrogenic reactions include fever, chills, hypotension, headache, and myalgias during HD. Such reactions are usually caused by Gram-negative bacteria that produce endotoxins in the dialysate. A pyrogenic reaction may lead to systemic infection and death. The dialysis machine, extracorporeal circuit including dialysis membrane, and water treatment system should be evaluated.
12.8.5 Arrhythmias
Arrhythmias and cardiac arrest account for almost one-third of deaths in ESKD patients, the most common single cause. Furthermore, the risk of sudden cardiac death is highest following the longer interdialytic period. Unlike in the general population, bradyarrhythmias appear to be more common than ventricular arrhythmias. Potential triggering factors include rapid electrolyte changes (potassium, calcium).
12.9 ESKD comorbidities/coexisting conditions
ESKD is a state of multiple comorbidities. Conditions variously included as comorbidities in the incident/prevalent ESKD patient population include HTN, diabetes, ischemic heart disease, congestive heart failure, hyperlipidemia, cerebrovascular disease, anemia, gout, and others.
12.9.1 Ischemic heart disease
Atherosclerosis is accelerated in patients with ESKD, due to both traditional and nontraditional (uremia-related) factors, such as vascular calcification, endothelial dysfunction, inflammation, anemia, and insulin resistance. Changes in ventricular function chronically or temporally related to the dialysis procedure (see Intradialytic Hypotension section below) may be a result of myocardial hypoperfusion. ESKD patients with severe coronary artery disease may require coronary bypass surgery.
12.9.2 Hypertension
HTN affects a majority of ESKD patients. Multiple mechanisms are involved, although the predominant one is sodium and volume excess. HTN contributes to cardiovascular morbidity and mortality in ESKD. Control of extracellular volume is the primary therapeutic strategy. The linear relationship between systolic BP and mortality in the general population is not seen in ESKD. In fact, data suggest a U-shaped relationship, with increased mortality risk at low systolic (<∼110 mmHg) and at high systolic (>165 mmHg).
Control of HTN in ESKD patients, especially if documented in home or ambulatory readings, is associated with improvement in cardiovascular outcomes. Dialysis patients also suffer greater adverse consequences of hypotension than the general population. Trials done in ESKD patients suggest that treatment may be important, but have not led to firmly established BP treatment targets. Guidelines suggest that predialysis BP should be 140/90 and postdialysis BP 130/80, but goals must be individualized.
Medications commonly used are listed in Table 12.22 .
| Medication | Usual Dose Range | Removal With Hemodialysis (%) |
|---|---|---|
| Alpha-blockers | ||
| Doxazosin | 1–16 mg daily | None |
| Prazosin | 1–10 mg twice daily | None |
| Terazosin | 1–20 mg daily | None |
| ACEi | ||
| Benazepril | 5–40 mg daily | 20–50 |
| Enalapril | 2.5–10 mg daily | 35–50 |
| Fosinopril | 10–80 mg daily | None |
| Lisinopril | 2.5–40 mg every 24–48 hr | 50 |
| Perindopril | 2–8 mg daily | 50 |
| Quinapril | 10–20 mg daily | 25 |
| Ramipril | 2.5–10 mg daily | 20–30 |
| Trandolapril | 0.5–4 mg daily | 30 |
| ARBs | ||
| Candesartan | 4–32 mg daily | None |
| Irbesartan | 75–300 mg daily | None |
| Losartan | 50–100 mg daily | None |
| Olmesartan | 10–40 mg daily | None |
| Telmisartan | 40–80 mg daily | None |
| Valsartan | 80–320 mg daily | None |
| Beta-blockers | ||
| Atenolol | 25–100 mg every 24–48 hr | 50–75 |
| Carvedilol | 6.25–25 mg twice daily | None |
| Labetalol | 100–1200 mg twice daily | None |
| Metoprolol | 50–200 mg twice daily | High |
| Nadolol | 40–240 mg daily | 50 |
| Propranolol | 40–160 mg twice daily | None |
| CCBs | ||
| Amlodipine | 2.5–10 mg daily | None |
| Diltiazem CD | 180–360 mg daily | None |
| Felodipine | 2.5–10 mg daily | None |
| Nifedipine XL | 30–120 mg daily | None |
| Verapamil | 180–360 mg daily | None |
| Diuretics | ||
| Bumetanide | 0.5–2 mg twice daily | None |
| Ethacrynic acid | 50–200 mg twice daily * | None |
| Furosemide | 40–160 mg twice daily | None |
| Metolazone | 5–10 mg daily | None |
| MRAs | ||
| Eplerenone | 50–100 mg daily | None |
| Spironolactone | 25–100 mg daily | None |
| Others | ||
| Clonidine (oral) | 0.1–0.4 mg three times daily | 5 |
| Hydralazine | 10–100 mg three times daily | None |
| Minoxidil | 2.5–30 mg daily | Yes |
* Ethacrynic acid is not generally used due to concern for hearing loss.
Drug selection should take into consideration patient comorbidities for which specific agents are also indicated. The approach to drug selection should include factors such as comorbid conditions, adverse effects, pharmacokinetics in ESKD, and effects of the dialysis treatment on BP.
Note that most angiotensin-converting-enzyme inhibitors (ACEi), metoprolol, atenolol, and nadolol are removed by HD.
12.9.3 Chronic fluid overload
Controlling fluid overload in ESKD patients should be viewed as another component of dialysis adequacy. Pulmonary congestion is a predictor of cardiac events and mortality in ESKD. Clinical assessment of fluid overload may be difficult. While fluid overload carries risk, so does the need for excessive ultrafiltration during the dialysis procedure in an ongoing attempt to achieve euvolemia. Fluid removal rates higher than 13 mL/hr/kg body weight are associated with poor outcomes. The use of diuretics between HD treatments to control hypervolemia was initially considered controversial, but they are now being used successfully by many nephrologists.
Dialysis can potentially relieve heart failure. There is no consensus for treatment of systolic heart failure. The benefit of beta-blocker therapy was indicated in a recent observational study showing lower mortality in HD patients with heart failure. Atenolol, metoprolol, nadolol, and bisoprolol are dialyzed off. Some studies have shown increased risk for diabetes, stroke, or hyperkalemia with beta blockade.
12.9.4 Pulmonary hypertension
Pulmonary HTN is a progressive pulmonary circulatory disease that accompanies either left or right ventricular failure and volume overload. It is underrecognized in ESKD patients, though causes and mechanisms of right heart failure have now been well described. However, awareness of right-sided heart failure and pulmonary HTN in the ESKD population is increasing.
Treatment consists of control of HTN, use of beta-blockers, ACEi/angiotensin II receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), correction of anemia, reassessment of target weight, treatment of arrhythmias, and evaluation and treatment of coronary ischemia.
12.9.5 Peripheral artery disease
The prevalence of peripheral artery disease (PAD) is 25% to 35% in incident patients. The risk in prevalent patients is higher in association with intradialytic hypotension (IDH). Predictors include advanced age, male sex, diabetes, current smoking, coronary artery disease, and malnutrition. Presentation includes gangrene, ischemic ulceration, and pain at rest; classic symptoms of claudication are uncommon. Guidelines recommend evaluation for PAD at initiation of chronic dialysis. Calcification of vessels may reduce the success of endovascular therapy. Increased postoperative mortality after surgical revascularization is a risk.
12.9.6 Intradialytic hypotension
Intradialytic hypotension (IDH) is one of the most frequent complications of HD, affecting 10% to 30% or more of treatments, depending on its definition. During an HD treatment, the majority of patients experience some overall decline in BP. Commonly used definitions of IDH include a decrease in systolic BP of 20 mmHg, a nadir systolic BP below 90 mmHg, or any hypotensive event that requires an immediate corrective measure. The ultrafiltration goals for an HD treatment in the United States are commonly up to 3 L (roughly 1 total plasma volume).
The evaluation should begin with a full assessment of the patient’s condition and comorbidities that may contribute to hypotension with HD fluid removal ( Figure 12.11 ).
The mechanism of IDH in the absence of the underlying conditions described above usually involves failed compensations of cardiac output and arteriolar tone for fluid removal. Compensation may be hindered by impaired sympathetic activation. Major risk factors are diabetes, large interdialytic weight gains, and lower body weight.
The most common symptoms of IDH include muscle cramps, nausea, vomiting, and dizziness. Severe episodes may be complicated by loss of residual renal function, hypotensive seizures, stroke events, coronary and cerebral ischemia, vascular access occlusion, and increased mortality risk. Repeated episodes are now known to result in damage to the heart with myocardial fibrosis, central nervous system (CNS) cerebral ischemia, kidneys, and gastrointestinal (GI) tract related to end-organ hypoperfusion. ,
Multiple interventions may be utilized to prevent IDH, but because of inadequate longitudinal trials, treatment is individualized and frequently empiric. Refractory patients should be evaluated for undiagnosed cardiac disease and undergo autonomic testing. Note that the full Trendelenburg position is no longer recommended. Both hyperoncotic (25%) and isooncotic (5%) intravenous albumin have been used in place of isotonic saline for hypotension, but resultant volume expansion appears to be ineffective despite its oncotic properties.
Prevention and treatment of IDH is outlined in Table 12.23 .
| Dialysis-Related Modalities | Extra–Dialysis-Related Modalities |
|---|---|
| Confirm accuracy of blood pressure reading | Adjust antihypertensive dosing and timing |
| Establish an accurate target weight | Limit intradialytic weight gain |
| Reduce ultrafiltration rate | Improve anemia |
| Reduce intradialytic blood flow | Predialysis midodrine |
| IV fluid administration | Predialysis pseudoephedrine |
| Ultrafiltration modeling | Predialysis caffeine consumption |
| Prohibit food consumption during dialysis | Fludrocortisone (extrarenal effect) |
| Oxygen administration | Oral carnitine (if deficient) |
| Increase dialysate calcium | |
| Cool dialysate to 36°C |
12.10 Anemia management
Comorbid anemia occurs in over half of ESKD patients, and a substantial portion of ESKD patients initiate dialysis with very low hemoglobin (Hgb) levels. Anemia at initiation of dialysis is associated with increased fatigue, weakness, and an increased risk of cardiovascular mortality. The multifactorial etiology includes decreased endogenous erythropoietin (EPO) production, functional or absolute iron deficiency, resistance to EPO in uremia related to suppression of hypoxia-inducible factors, and shortened red cell lifespan.
Initial anemia evaluation should be similar to that in the non-ESKD patient, and should consider factors such as the patient’s history, complete blood count (CBC), iron studies, and reticulocyte count ( Table 12.24 ).
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Determination of iron deficiency is of relevance not only as a primary diagnosis, but as a factor in the response to ESAs.
Anemia is treated with ESAs (e.g., epoetin), intravenous iron, and, infrequently, blood transfusions. Note that management in the dialysis facility is usually facilitated by the use of approved protocols. KDOQI Guideline Recommendations for HD Patients are shown in Table 12.25 .
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Concerns regarding toxicity of ESAs began to emerge with their initial regulatory trials. Several adverse effects of ESAs were reported early, when Hgb targets were near normal or normal, including CVEs, malignancy, seizures, exacerbation of HTN, dialysis access thrombosis, and mortality.
Harmful effects were related to the use of large ESA doses and maintaining higher Hgb levels. As a result, clinically acceptable target for Hgb with ESAs are in the range of 10 to 12 g/dL. Several treatments are now available to treat patients with ESKD. Doses are titrated based on the patient’s response to ESA treatment.
ESA hyporesponsiveness is found in up to 20% of HD patients, and is associated with higher ESA requirements, increased major CVEs, and mortality. Causes include iron deficiency, inflammation, hyperparathyroidism, and systemic infection. Rarely, neutralizing antibodies to ESAs will result in severe anemia.
Parenteral iron is also known to raise or help sustain Hgb levels in ESKD.
Current treatment options for anemia management in the ESKD patient are shown in Table 12.26 .
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a Fishbane S, Spinowitz BS, Wisemandle WA, Martin NE. Randomized controlled trial of subcutaneous epoetin alfa-epbx versus epoetin alfa in end-stage renal disease. Kidney Int Rep . 2019 May 22;4(9):1235–1247. doi:10.1016/j.ekir.2019.05.010 .
b Fishbane S, Singh B, Kumbhat S, Wisemandle WA, Martin NE. Intravenous epoetin alfa-epbx versus epoetin alfa for treatment of anemia in end-stage kidney disease. Clin J Am Soc Nephrol . 2018 Aug 7;13(8): 1204–1214. doi:10.2215/CJN.11631017 .
c Sinha SD, Bandi VK, Bheemareddy BR, et al. Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase III trial. BMC Nephrol . 2019 Mar 13;20(1):90. doi:10.1186/s12882-019-1209-1 .
d Chen N, Hao C, Liu B-C, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med . 2019 Sep 12;381(11):1011–1022. doi:10.1056/NEJMoa1901713 .
e Akizawa T, Iwasaki M, Yamaguchi Y, Majikawa Y, Reusch M. Phase 3, randomized, double-blind, active-comparator (darbepoetin alfa) study of oral roxadustat in CKD patients with anemia on hemodialysis in Japan. J Am Soc Nephrol . 2020 Jul;31(7):1628–1639. doi:10.1681/ASN.2019060623 .
f Singh AK, Carroll K, Perkovic V, et al. Daprodustat for the treatment of anemia in patients undergoing dialysis. N Engl J Med . 2021;385(25):2325–2335. doi:10.1056/NEJMoa2113379 .
g Saglimbene VM, Palmer SC, Ruospo M, Natale P, Craig JC, Strippoli GFM. Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease. Cochrane Database Syst Rev . 2017 Aug 7;8(8):CD009904. doi:10.1002/14651858.CD009904.pub2 .
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