Usefulness of Spironolactone for the Prevention of Acute Kidney Injury in Critically Ill Patients With Invasive Mechanical Ventilation

Acute kidney injury (AKI) is a common multifactorial syndrome in hospitalized patients. Patients in critical care units have the highest risk of developing AKI, which is related to an increase in morbidity and doubles in-hospital mortality (10.2% vs. 25.6%) and at 90 days (16.6% vs. 33.7%).

The frequency of this condition reaches 39.3% of the critically ill patients hospitalized in the Intensive Care Units (ICU). Most cases occur early, 91% of cases occur within the first 5 days of entry. There are numerous studies in the literature investigating risk factors related to the development of AKI in critically ill patients hospitalized in critical care units. Some of those who have been associated with severe AKI and need for renal replacement therapy are: invasive mechanical ventilation, septic shock, cardiogenic shock and hepato-renal syndrome; In addition, the presence of multiple organic faults (by Sequential Organ Failure Assessment scale) is closely related to the development of AKI, and the risk seems to increase in parallel with the number of organic failures. The pathophysiological relationship between invasive mechanical ventilation and the development of AKI is well known, both for direct and indirect effects, therefore patients with invasive ventilatory support represent a special risk group.

In a recently published study evaluating the long-term prognosis of a cohort of patients who developed AKI with dialysis requirement, 62% of mortality was reported at 3.5 years, with an average survival of 8.1 to 8.9 months since the moment of dialytic requirement; almost 6% of patients in the study remained on renal replacement therapy at 3.5 years of follow-up, while 42% had micro or macroalbuminuria. (Microalbuminuria 32% and macroalbuminuria 9.9%), with a reduction in estimated glomerular flitration rate of 38 ± 29 ml/min/1.73 m2 in the 3.5 years of follow-up.

One of the major problems in the diagnosis and treatment of AKI is the difficulty in identifying it timely. From the moment of AKI occurs, the increase in the creatinine can be up to 72 h. For this reason, there is an intense search for biomarkers that allow the timely diagnosis of AKI. Several biomarkers for the early detection of AKI have been identified. These include: neutrophil gelatinase-associated lipocalin (NGAL), a protein of the lipocalin family, present in neutrophil secondary granules. Upon renal damage this protein is released from the affected epithelium early. Studies that have evaluated its usefulness as a marker of renal damage have been performed mainly in children, and its usefulness in critically ill patients has been debated. Another biomarker that has been used for the detection of renal damage is the transmembrane glycoprotein Kim-1, which releases its extracellular ectodomain by the action of proteases. Under normal conditions, Kim-1 expression is very low and increases significantly when there is tubular damage, such as occurs during AKI. A characteristic feature of this molecule is that it is expressed only in injured renal tissue. Although the induction of Kim-1 after an AKI episode is important, unfortunately this protein has not been shown to be useful as an early biomarker of AKI. Recently, our group identified a new, non-invasive, and reliable biomarker to detect AKI earlier by measuring the concentration of the 72 kilodaltons heat shock protein (HSP72). Similar to Kim-1, this protein is practically not expressed under normal conditions, but is induced in the tubular epithelium after an episode of AKI. In addition to being a highly sensitive and early biomarker, it was able to stratify different degrees of renal injury and to monitor the efficacy of a renoprotective maneuver in animals undergoing ischemia/reperfusion. In addition, we have also observed that in critically ill patients, the detection of HSP72 in urine specimens made it possible to detect AKI 48 h before diagnosis of creatinine elevation or reduction of urinary flow.

Aldosterone and kidney injury in hum There are limited number of studies aimed to evaluate the prevention of AKI with the use of any particular strategy, regard with the use of spironolactone either. However, in a study published by Dr. Brown's group in the United States aimed for decreasing the frequency of postoperative atrial fibrillation (AF) by decreasing the concentration of cytokines and inflammation that has been linked to the development of fibrillation (147 patients), ramipril (151 patients) or spironolactone 25 mg/day (147 patients) were randomly assigned to the study group. Of the secondary objectives of the study, serum K and creatinine levels were considered among other measurements. The frequency of AF in the postoperative period was similar. It should be noted that when analyzing other values such as blood pressure there were no differences between groups, despite being critically ill patients, thus the administration of these drugs did not affect AF. The need for amine use in the postoperative period was similar in the placebo group and the treatment groups. In the postoperative period, an increase in potassium levels was observed in the spironolactone group, but only in one case was necessary to suspend the treatment. The most important aspect of this study is that those patients with spironolactone or ramipril had a lower elevation of creatinine levels compared to the placebo group, which was interpreted as a prevention of renal damage independent of hemodynamic factors. Other observed results were that the group receiving spironolactone had a shorter hospital stay and a reduction in the time of invasive mechanical ventilation.