Faddi G. Saleh Velez, MD

Qureshi AI, Huang W, Lobanova I, Hanley DF, Hsu CY, Malhotra K, Steiner T, Suarez JI, Toyoda K, Yamamoto H, on behalf of Antihypertensive Treatment of Cerebral Hemorrhage 2 Trial Investigators. Systolic Blood Pressure Reduction and Acute Kidney Injury in Intracerebral Hemorrhage. Stroke. 2020;51:3030–3038.

Since the National Institute of Neurological Disorders and Stroke (NINDS) trial in 1995, the rapid management of acute stroke became the cornerstone for all emergency departments and stroke units around the globe. Further scientific progress led to the broadening of the therapeutic window with the later inclusion of endovascular therapies up to 24 hours; therefore, the use of advanced imaging that requires contrast administration exponentially increased and, with it, the concern of contrast-related acute kidney injury (AKI), mainly in patients with an already affected kidney function. In 2017, Brinjikji et al. published a systematic review and meta-analysis concluding that initial contrast administration had no statistically significant association with an increase in risk of AKI in stroke patients independently of pre-existent kidney disease (odds ratio [OR]=0.63; 95% confidence interval [CI] 0.34–1.12). However, little attention has been placed on the risk of kidney injury in patients with intracerebral hemorrhage (ICH) in which aggressive blood pressure management is performed.

The role of intensive systolic blood pressure reduction (goal <140 mmHg) in acute ICH differed in the past years. The 2015 American Heart Association (AHA) guidelines deemed this intervention as safe (class I; level of evidence A). However, the recent 2017 update considers this intervention as a class III (Harm) recommendation.

The current article analyzed the effects of intensive systolic blood pressure control (goal of 110 — 139 mmHg) initiated within the first 4.5 hours from symptoms onset in 1000 individuals with intracerebral hemorrhages that presented with an initial systolic blood pressure greater than 180 mmHg. Authors investigated the risk and predictors for developing AKI through serial serum creatinine assessment. The data is derived from the ATACH 2 trial that evaluated the efficacy of intensive systolic blood pressure reduction vs. standard of care reduction (140 – 179 mmHg) in ICH patients. The authors identified 149 subjects (14.9%) that developed AKI, being mild AKI the most incident event in 13.2% of the cases, and 65 individuals who developed renal adverse events (RAEs) defined as any untoward event or complication, not previously identified, related to the renal system.

There was an impact on length of stay at the intensive care unit in patients who developed either AKI or RAEs; nonetheless, length of hospitalization stay was not different. Notably, the number of patients that died within 90 days were higher in the AKI group when compared to non-AKI group. These results remained significant after adjusting for confounders such as age, Glasgow coma score, hematoma volume, presence or absence intraventricular hemorrhage (OR=2.9; 95% CI 1.6–5.5). Likewise, disability at 90 days was higher in AKI patients compared with non-AKI (OR=2.7; 95% CI 1.7–4.1). Interestingly, higher doses of nicardipine were associated with increased risk of developing AKI and RAEs. Similarly, the size of the hematoma (volume) was directly related to increased incidence of AKI.

Although these results are significant, larger studies are necessary to identify whether the increase in mortality and disability are directly associated with the development of AKI, or rather just a marker of more severe ICH. Study findings should be carefully taken into consideration, and SBP reduction should be managed individually based on patient’s condition, volume, and location of the hematoma, among many other aspects- particularly because the same study group ascertained that after adjusting these results by known prognostic markers in patients with ICH, the effect of AKI and non-AKI in mortality and disability remained significantly even. Despite the results seen in this trial, the real question of how to give priority to the neurons over the nephrons. Future studies aimed to identify strategies that can be applied to reduce the risk of developing AKI while allowing safe reductions in systolic blood pressure in patients with ICH.