Renal Replacement Therapy

Tingting Li

Anitha Vijayan

The principal strategy regarding acute kidney injury (AKI), particularly in the intensive care setting, is prevention. Once AKI occurs, the presentation and course are variable and treatment is generally supportive. The optimal time to initiate renal replacement therapy (RRT) remains unknown.

INDICATIONS

Conventional indications for RRT include metabolic acidosis, hyperkalemia, volume overload, and severe uremic symptoms refractory to medical management.Other indications include certain intoxications of certain substances (ethylene glycol, methanol, lithium, etc.), where either the substance or the toxic metabolite will be cleared with dialysis.

Acidosis

Refractory metabolic acidosis is an acute indication for dialytic therapy in the severely ill patient. Progressive acidemia can develop as the kidneys lose their ability to reclaim bicarbonate and excrete organic acids. More commonly in the intensive care setting, tissue hypoperfusion with multiorgan system failure results in severe lactic acidosis. Aggressive alkali therapy can encounter problems with volume overload, metabolic alkalosis, and hypocalcemia. Initiation of RRT would obviate the concern over volume overload and could restore the blood pH to its physiologic range.

Hyperkalemia

Hyperkalemia can be rapidly fatal and need to be addressed promptly. Temporizing measures include intravenous calcium to stabilize the myocardial cell membrane, as well as insulin (with dextrose 50% in water), sodium bicarbonate, and inhaled beta-agonists to promote an intracellular shift in potassium. Elimination of potassium from the body can be achieved with ion-exchange resins, but this effect is unpredictable and inefficient. In the volume-depleted patient, aggressive fluid resuscitation can enhance sodium delivery to the distal nephron. The reabsorption of sodium makes the lumen electronegative, promoting secretion of potassium via the potassium channel (see Chapter 24 for further discussion).

When these efforts are unsuccessful, urgent RRT becomes necessary. Intermittent hemodialysis (IHD) with higher blood flow and dialysate flow rates is very effective in lowering potassium rapidly and is the preferred modality of choice. The patients are
dialyzed using a 0 or 1 mEq/L potassium concentration in the dialysate. However, in a critically ill hypotensive patient with or without pressors, continuous renal replacement therapy (CRRT) with high flow rates (>35 mL/kg/hr) of replacement fluid and dialysate with 0 potassium concentration can also be utilized to lower potassium levels.

Volume Overload

Volume overload is another frequently encountered problem in the critical care setting. There is evidence that in patients with AKI, fluid overload is an independent risk factor for mortality. Although randomized trials studying the use of diuretics in AKI have not demonstrated any survival advantage, improvement in renal recovery, or avoidance of dialytic therapy, it is not unreasonable to offer a trial of high-dose loop diuretic (160 to 200 mg of furosemide) in the setting of fluid overload. Respiratory compromise with pulmonary edema and/or significant soft tissue edema that impairs the barrier defense of the skin is the most common subjective criteria for initiating renal replacement in the oliguric patient.

Uremia

With progressive renal dysfunction, there is an impaired ability to excrete nitrogenous wastes and glycosylated end products. Blood urea nitrogen (BUN) level is generally used as a surrogate marker for uremic toxin accumulation. Unfortunately, many signs and symptoms commonly found in the uremic syndrome do not always correlate with BUN levels, and therefore there is no established objective cutoff beyond which dialytic therapy is recommended. Rather, acute indications for initiating urgent RRT center on the presence of specific clinical findings, namely uremic encephalopathy and uremic pericarditis. The latter possesses a high risk of converting into hemorrhagic pericarditis with cardiac tamponade.

TIMING OF INITIATION OF RRT

The optimal timing for initiation of RRT is undefined at this time. A few studies have shown a survival advantage with early initiation (definition varies greatly among studies; most used BUN <60 vs. >60).However, all the studies have significant design flaws and no definitive conclusions can be drawn.

MODALITIES

Once the decision has been made to initiate RRT, one needs to select a modality. The available modalities are IHD, CRRT, sustained low-efficiency dialysis (SLED), or peritoneal dialysis. The choice depends on the availability of therapies at the institution, physician preference, the patient’s hemodynamic status, and the presence of comorbid conditions. Intermittent modalities generally cause greater fluctuations in blood pressure and produce greater fluid shifts in a short amount of time. Continuous modalities allow for the same solute clearance and fluid removal, but spread out during a 24-hour period, and thus are favored in hemodynamically unstable patients such as those with sepsis or fulminant hepatic failure.

In the United States, CRRT is performed in approximately 30% of adult patients with AKI and has almost completely replaced peritoneal dialysis in the intensive care unit (ICU) setting. However, although CRRT has some potential benefits over IHD,
as seen in randomized trials, CRRT has not shown improved survival over IHD in critically ill patients. Likewise, randomized trials have not shown a difference in time to renal recovery or length of ICU or hospital stay between groups treated with IHD versus CRRT.

In the recent years, the use of SLED or extended daily dialysis (EDD) has risen and is mainly driven by its convenience, safety, excellent control of electrolytes and volume status, and lower cost compared to CRRT. Treatments are intermittent but with longer duration (8 to 10 hours/session), lower blood and dialysate flow rate, lower small solute, and fluid removal than IHD (and higher blood and dialysate flow rate, small solute and fluid removal than CRRT). SLED is often performed 5 to 6 times per week, usually during the night. It is an excellent modality for those patients who are prone to hemodynamic instability, provides “down time” for procedures, and at the same time does not compromise the dialysis dose. SLED usually requires little or no anticoagulation, demands less nursing care, and is a good alternative to CRRT in the ICU. Randomized, controlled studies have suggested similar safety and effectiveness compared to CRRT and IHD.

Table 44.1 lists the advantages and disadvantages of the different modalities of dialysis.

TABLE 44.1 Renal Replacement Modalities

Modality	Advantages	Disadvantages
IHD	High-efficiency transport of solutes when rapid clearance of toxins or electrolytes is required Allows time for off-unit testing	Hemodynamic intolerance secondary to fluid shifts “Saw-tooth” pattern of metabolic control between sessions
CRRT	Gentler hemodynamic shifts than IHD Steady solute control	Continuous need for specialized nursing Requires continuous anticoagulation (heparin vs. citrate)
SLED	All of the advantages of CRRT Provides “down time” for off-unit testing Less nursing care than CRRT Less expensive than CRRT Anticoagulation generally not necessary	Requires almost daily treatments Less “middle molecule” removal than CRRT
Peritoneal dialysis	Gentler hemodynamic shifts than IHD	Requires invasion of peritoneal cavity, which may not be possible in postoperative patients Less predictable fluid removal rates
CRRT, continuous renal replacement therapy; IHD, intermittent hemodialysis; SLED, sustained low-efficiency dialysis.

DIALYSISDOSE

The ideal dose of dialytic therapy in critically ill patients has not yet been conclusively determined. Evidence from end-stage, dialysis-dependent patients suggests that a thrice-weekly regimen should be performed with a urea reduction of approximately 70% per session. However, in the acutely ill intensive care population, these calculations are not always equivalent. The actual urea clearances are approximately 25% lower than what would be expected in a stable chronic dialysis patient, and thus it has been proposed that additional benefit may be derived from higher treatment doses, more frequent treatments, or greater hemofiltration.

In IHD, a few small studies had shown a survival advantage in critically ill patients who receive either a higher delivered dialysis dose three times per week or undergo daily dialysis. In contrast, the VA/NIH Acute Renal Failure Trial Network (ATN) study, a large multicenter, prospective, randomized trial, did not find a decrease in mortality or increase in renal recovery with more frequent dialysis (six times per week vs. three times). We recommend IHD be provided three time a week, targeting the urea reduction ratio of >70%, or Kt/V of 1.2 to 1.4 per treatment.

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