Clinical outcomes in patients who need acute renal replacement therapy in the intensive care unit

Desenlaces clínicos de pacientes con requerimiento de terapia de reemplazo renal aguda en unidad de cuidado intensivo

Intensive care units (ICUs) have changed the overall focus of various diseases, increasing the treatment pos sibilities and decreasing the associated mortality and comorbidity. One of the diseases with the greatest change over the last few years has been acute kidney injury (AKI) with the need for renal replacement therapy (RRT). It is estimated that up to 21.6% of patients admitted to the hospital have AKI, with 10% of these cases requiring RRT ¹. Wald et al. reported an increased incidence of acute kidney injury with the need for RRT comparing the five-year periods of 1996-2000 and 2006-2010, at 0.8% and 3.0%, respectively, with the 90-day need for chronic RRT at 25% in ICU patients ².

Anywhere from 13-78% of AKI cases in the ICU have medical causes, and surgical conditions account for 16 to 30% of the cases ³, with 5.6% of all of these requiring RRT. The 28, 90 and 365-day mortality in this context is 51, 60 and 64%, respectively ⁴, with wide variances between studies ⁵. Furthermore, kidney function and the need for chronic dialysis have been the focus of ongoing research. Wald et al. reported that, in 21,234 patients, 90-day RRT dependence was 27.2% ².

Many factors are associated with the clinical outcomes and a predisposition to needing dialysis in the ICU. The most frequently reported factors are high blood pressure, diabetes, heart failure, chronic kidney disease ^6,7, and the chronic use of medications such as acetylsalicylic acid (ASA), angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), diuretics, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (PPIs) ^8,9. The type of RRT and timing of its initiation are also included, with a substantial dispar ity in the results of different studies in this regard ¹⁰.

Moreover, there are different definitions of kidney recovery, specifically in this type of patient, based on dif ferent creatinine or glomerular filtration rate (GFR) cut-off points ¹¹. Pannu et al. showed that a greater than 25% deterioration in kidney function from the baseline GFR is the point at which the risk of other outcomes such as death and the need for chronic RRT increases ¹², this being the starting point for evaluating the composite outcome of major adverse kidney events (MAKE) in patients with AKI¹³. The objective of the current study was to determine the clinical outcomes of patients needing acute dialysis using MAKE assessment in 90-day and one-year follow-up.

This study found a relationship between the compound outcome of MAKE and diabetes, APACHE II, timing of RRT initiation and anuria at 90 days and one year, when the modality of RRT was added, with similar results on the logistic regression. In addition, arterial hypertension, NSAIDs, obstructive uropathy, anuria, metabolic acidosis, hypercalcemia and uremic encephalopathy were associated with chronic RRT therapy at 90 days, with an association with NSAIDs, anuria, metabolic acidosis and uremic en cephalopathy persisting at one year.

The results evidence the complexity and worse prognosis of patients who require RRT due to AKI in the ICU. Inpatient mortality was 73.77% at 90 days and 74.5% at one year. Compared with other studies reporting mortality between 41 and 65%, ours had greater inpatient mortality. However, we had a lower mortality between the follow up periods ^15-19, also associated with the severity of the clinical condition. Other authors described an association with a positive fluid balance, metabolic acidosis, late initiation of therapy and continuous therapy, similar to the findings of this study, although they did not maintain these findings in the multivariate analysis ¹⁵. There are likely to be differences in mortality, mainly related to sociodemographic variables, given the origin of the patients admitted to our institution, compared with international studies.

One of the important points in this study is the evalu ation of the MAKE compound outcome, which in recent years has been proposed as the best way to characterize the results in patients with AKI. Few studies have evaluated this outcome in the ICU. De Corte et al. ¹⁵ analyzed MAKE in 1,292 patients, 86 and 87.5% of whom developed this outcome at 90 days and one year of follow up, respectively, these being higher results than those of our study (77.04% for MAKE at 90 days and 76.22% for MAKE at one year). The most significant associations included kidney stage 3 on ICU admission, oligo/anuria, and the severity of the clinical condition on admission ¹⁵, similar to our study. M. Meersch et al. followed the patients who participated in the ELAIN study, with MAKE analysis at the 12 month follow up, finding that 64.9% of the patients who received early therapy developed MAKE at one year compared with 89.1% of the patients who began therapy late ²⁰. Although there is some concordance with our findings, the differences in the definition of the timing of therapy should be noted. The STARRT-AKI study evaluated the results of early vs. late implementation of RRT, with secondary analysis of the MAKE components at 90 days, finding no differences ²¹. As can be seen, a large proportion of the compound outcome is due to inpatient mortality, as found in the studies men tioned as well as our own. It is clear that MAKE evaluation provides important information regarding these patients' outcomes; however, looking at its individual components also supplies other relevant data, as done in our study.

Within the renal outcomes, 65.62% had full recovery of renal function, 21.87% had partial recovery and 12.5% were dialysis-dependent at 90 days, with similar results after one year. Compared with similar studies, there was a lower per centage of RRT requirement compared with the FINNAKI study ²² (18.9%) and a greater percentage compared with the RENAL ²³ and IVOIRE ²⁴ studies (5.6% and 1.4%, respectively). At one-year follow up, there was a similar need for RRT in the studies by Meersch et al. ²⁰ and Conroy et al. ¹⁹, coinciding in the association of this outcome with oligo/anuria and worse kidney function on admission ¹⁵. An association was found between worse kidney function on admission (kidney stage 3b) and the need for chronic dialysis, just as in studies by other authors ^15,25-27.

The bivariate analysis showed an association between the type of therapy and timing of initiation, and MAKE and mortality. Regarding the continuous therapy outcomes, these could be explained by the implementation of this therapy in patients with greater hemodynamic instability, reflecting a worse clinical condition at a given time. Most randomized studies have not shown any differences when evaluating the therapy modality, mentioning the great equality between the various study arms compared with ours ^28,29. Further more, an association has not been found between dialysis dependence and the modality of treatment, a situation which some authors have presented in their papers, noting that the vast majority of these are observational studies ^30-32. In Schneider et al.'s systematic review ³³, this hetero geneity is mainly found in observational studies, in which differences are found in clinical outcomes, as opposed to randomized studies.

Regarding the timing of initiation, we found worse results in MAKE and mortality in the group with late initiation, with no effect found on kidney outcomes. These findings differ partially from the randomized studies of recent years. We share findings with the ELAIN study ³⁴ with, however, a clear difference in the definition of early initiation, which makes comparison difficult. On the other hand, in other randomized studies with 28 and 90-day follow up and a similar initiation criterion to ours, there is no similarity in the findings, which could be partially explained by the dif ference in the number of patients in the treatment initiation groups compared with these papers ^21,35-37. While there are differences in the findings with regard to mortality, there is consistency in the kidney outcomes, corroborated by vari ous meta-analyses ^38-40.

The strengths include: a broad analysis of the condi tions associated with clinical outcomes not included in other publications, as well as 90-day and one-year follow up. The MAKE evaluation is a more comprehensive way of analyzing the effects of treatment in this type of patient. The limitations include retrospective data collection, a sample from a single institution, the different number of patients according to the type and timing of RRT, the low number of patients in follow up, and not including other sociodemographic and nutritional variables which could be determining factors in mortality.

In conclusion, the APACHE II score, high blood pressure, NSAIDs, obstructive uropathy, metabolic acidosis, anuria, hypercalcemia and uremic encephalopathy were associated with the need for RRT at 90 days. Mortality was greater in patients with late-starting or continuous RRT. Anuria, a higher APACHE II score, and continuous or late-starting RRT are more frequent in patients who develop MAKE.