Renal replacement therapies

Introduction

Acute kidney injury (AKI) occurs commonly in cancer patients and independently increases morbidity and mortality. ^, Despite impressive gains in the understanding of the basic pathophysiologic principles underlying kidney injury, there are no therapeutic options to prevent or ameliorate AKI; treatment consists of supportive care and avoidance of nephrotoxic agents, such as radiocontrast and nonsteroidal antiinflammatory agents.

Patients with cancer are at risk for the development of AKI from causes similar to all hospitalized patients, such as radiocontrast administration, hypotension, antibiotics, infections, and sepsis. Unique causes of AKI in these patients include chemotherapy exposure, tumor lysis syndrome, hematopoietic stem cell transplantation, irradiation, and direct effects of malignancy. In a cross-sectional analysis of prospectively collected data on 3358 patients admitted to a large United States cancer center, 12% developed AKI based on the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage renal disease [ESRD]) creatinine criteria, of whom 4% received dialysis. ^, In a multivariate analysis, the development of AKI was associated with a significantly increased odds of death (odds ratio [OR] 4.72; 95% confidence interval [CI], 3.3–6.7).

At a certain point in the course of AKI, use of renal replacement therapy (RRT) may be considered. Although the literature is sparse and somewhat contradictory, most studies show that in patients started on RRT for AKI, survival is significantly lower for those with cancer compared with those without cancer; survival is particularly poor with hematologic malignancies. In a retrospective study of 309 cancer patients with AKI (based on criteria proposed by Bellomo et al.), an increased risk of mortality was associated with age greater than 60 years, dysfunction of more than two organs, impaired performance status, and uncontrolled cancer. ^, In another analysis, the risk of mortality in 345 patients with hematologic cancer and AKI (based on RIFLE criteria) was significantly associated with septic shock, mechanical ventilation, and allogeneic stem cell transplantation. Patients with all three risk factors had a mortality rate of 86%. Based on such findings, it is somewhat controversial whether initiating RRT in patients with multiple organ dysfunction and uncontrolled cancer is appropriate because RRT is unlikely to change the ultimate outcome. This concern has triggered an interest in “palliative nephrology.” For such patients, it may be reasonable to offer a time limited trial of RRT and discontinue treatment if there is no significant improvement in clinical status. Currently, there are no strict guidelines that define what is a reasonable time limit. The Renal Physicians Association, however, has published general guidelines on shared decision making in the appropriate initiation and withdrawal from dialysis.

Although AKI occurs in patients in all hospital units, the highest frequency is in intensive care units (ICUs) and the majority of research described in this chapter relates to critically ill patients. Several critical issues regarding the use of RRT remain controversial and are outlined in Box 32.1 .

Initiation of renal replacement therapy (timing)

The classic “indications” for initiating RRT in a patient with AKI are listed in Box 32.2 . It is misleading to refer to these clinical conditions as indications because it implies that RRT should only be started when such criteria are present. Reliance on these criteria could delay appropriate therapy, resulting in serious adverse events in patients. Rather, the conditions listed should necessitate emergent RRT, unless palliative care measures are planned.

In the case of lesser degrees of kidney injury, the timing of RRT remains a contentious issue. On the one hand, early initiation would avoid the development of any serious complication of AKI; however, the early use of RRT could expose patients to the potential harm of RRT, when it might have been unnecessary ( Box 32.3 ).

Two retrospective studies divided patients into “early versus late” groups based on the median blood urea nitrogen (BUN) concentration when RRT was started and found a survival advantage in the early dialysis group. ^, In addition, a metaanalysis also reported a benefit to earlier initiation of RRT. Unfortunately, the overall data quality is poor and does not determine when RRT should actually be started.

More recently, two randomized controlled trials on the timing of RRT initiation have been published. In the multicenter trial reported by the AKIKI (Artificial Kidney Initiation in Kidney Injury) study group, 620 patients with Kidney Disease Improving Global Outcomes (KDIGO) stage 3 AKI (≥ threefold increase in baseline serum creatinine or urinary output < 0.3 mL/kg/h for ≥ 24 hours) were randomized to early RRT (at enrollment) or delayed RRT (development of hyperkalemia, severe metabolic acidosis, hypervolemia refractory to diuretics, BUN ≥ 112 mg/dL, or oliguria ≥ 72 hours). ^, There was no difference between the early and delayed groups in the primary endpoint of 60 day mortality (48.5% vs. 49.7%, respectively). Importantly, 49% of the delayed group never received RRT, and diuresis, a marker of improved kidney function, occurred significantly earlier. The rate of catheter-related blood stream infections was significantly higher in the early strategy group.

The ELAIN study (Effect of Early vs. Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury) randomized 231 patients at a single center with KDIGO stage 2 AKI (≥ twofold increase in baseline serum creatinine or urinary output < 0.5 mL/kg/h for ≥ 12 hours) to either early RRT (within 8 hours of diagnosis of KDIGO stage 2 AKI) or delayed RRT (within 12 hours of developing KDIGO stage 3 AKI). Patients in the early group compared with the delayed group had improved survival at 90 days (39.3% vs. 54.7%, respectively). In addition, more patients in the early group recovered kidney function at 90 days compared with the delayed group.

These discordant results are not unexpected. Both studies had a small number of patients, numerous confounders, enrolled patients at different stages of kidney dysfunction, and relied on arbitrary indications for RRT. The two trials also differed in the population studied, where most patients in AKIKI were medical as opposed to those in ELAIN, who were mainly surgical. Whether this difference makes one trial more applicable to cancer patients than the other is unknown. Therefore initiation of RRT should be individualized to each patient, taking into consideration several factors, including fluid balance, severity of multiple organ dysfunction, urinary output, age, and comorbid conditions.