Blood Pressure Targets on the Operating Table: What the HISTAP Debate Reveals About Kidney Injury

When a large randomized clinical trial fails to deliver the answer clinicians hoped for, the most productive response is rarely silence. It is the argument that follows. In intensive care medicine, few debates illustrate this better than the exchange now unfolding around the HISTAP trial, a multicenter randomized clinical trial that tested whether pushing blood pressure targets higher during major surgery could protect the kidneys of high-risk patients. The trial, published in Intensive Care Medicine, compared a higher blood pressure target against a standard target in hypertensive patients undergoing elective major abdominal surgery, and its findings have now prompted a formal correspondence and an author reply that dig into two of the most contested issues in perioperative medicine: how acute kidney injury is defined, and how the cumulative burden of low blood pressure should be measured.

The HISTAP trial, conducted by Cecconi and colleagues across multiple centers, enrolled hypertensive patients judged to be at high risk because they were undergoing elective major abdominal surgery. These are patients whose chronic hypertension has already remodeled their renal autoregulation, shifting the pressure range over which the kidneys can maintain stable blood flow. The trial asked a deceptively simple question: if these patients are managed to a higher intraoperative blood pressure target rather than a standard one, do they suffer less postoperative organ dysfunction, particularly acute kidney injury? The design reflects a long-standing hypothesis in anesthesiology and critical care, namely that the routine blood pressure targets used for the general surgical population may be dangerously low for patients whose physiology has adapted to chronically elevated pressures.

The correspondence, authored by Cirenei, Kipnis and Tavernier, and the reply from the HISTAP investigators, led by Messina, Cortegiani, Samuelli and Cecconi, zero in on two methodological fault lines. The first concerns the diagnostic criteria used to identify acute kidney injury in the trial. The second concerns the concept of cumulative exposure to hypotension, a metric that has gained enormous traction in anesthesia research over the past decade. Both issues matter because they determine not only how the HISTAP results should be read, but also how future trials of blood pressure management should be designed and interpreted.

Acute kidney injury is currently diagnosed in clinical research according to consensus criteria, most prominently the KDIGO framework, which combines two physiological signals: a rise in serum creatinine relative to a baseline value, and a reduction in urine output over defined time windows. Each signal has well-known weaknesses. Serum creatinine is a lagging and noisy indicator, influenced by muscle mass, fluid loading, and the kinetics of creatinine distribution rather than by injury itself. Urine output is highly sensitive but nonspecific, fluctuating with hydration, surgical stress hormones, and anesthetic technique. When a trial reports that one blood pressure strategy reduced acute kidney injury, the specific criteria and thresholds used to make that diagnosis become central to the claim, because different definitions can classify the same patient differently and shift the apparent incidence of injury substantially.

This is precisely why the correspondents raised the role of AKI criteria in interpreting HISTAP. If the trial’s primary renal endpoint hinged on creatinine-based staging, then the timing of postoperative creatinine measurements, the choice of baseline, and the use of diuretics or fluid boluses could all modulate how many patients crossed the diagnostic threshold. If urine output criteria contributed, then intraoperative fluid management becomes a potential confounder, since a higher blood pressure target typically requires more vasopressor support and often more fluid, either of which can alter urine flow independently of any genuine renoprotective effect. The author reply addresses these concerns directly, defending the trial’s handling of its renal endpoints and explaining how the definitions were applied consistently across both randomized groups, which is the essential condition for an unbiased comparison even if no single definition of kidney injury is perfect.

The second axis of the debate, cumulative exposure to hypotension, touches on one of the most influential ideas in modern perioperative monitoring. Rather than asking whether blood pressure ever dipped below a threshold, researchers increasingly quantify the total dose of hypotension a patient experiences: the area under the curve below a mean arterial pressure limit, the minutes spent below that limit, or weighted combinations that give more importance to deeper and longer excursions. This dose-based framing emerged from large observational analyses showing that the probability of postoperative kidney and myocardial injury rises steeply and roughly linearly with the integrated burden of low pressure, suggesting that the kidney experiences hypotension cumulatively rather than episodically.

Applied to HISTAP, the logic of cumulative exposure raises a subtle interpretive problem. A trial that assigns patients to a higher or lower blood pressure target does not thereby assign them to a fixed dose of hypotension. Individual patients in both arms will spend varying amounts of time below any given pressure threshold, depending on surgical events, blood loss, anesthetic depth, vasopressor responsiveness, and baseline vascular stiffness. The correspondents argued that characterizing the actual hypotension exposure achieved in each arm, and its overlap between arms, is necessary to understand whether the trial truly tested the hypothesis that less hypotension means less kidney injury, or whether it merely tested a management protocol whose physiological effect was diluted by overlap between the groups. The trial authors’ reply engages with this point, situating the randomized target within the reality of intraoperative hemodynamic variability and explaining how the protocol was implemented at the bedside.

Underlying this technical exchange is a broader truth about randomized trials in perioperative medicine that has begun to reshape the field. Trials of physiological targets are not tests of a drug with a fixed dose; they are tests of a management strategy executed by many anesthesiologists across many operating rooms, against the backdrop of human hemodynamic variability. The effect of such strategies on hard outcomes like acute kidney injury depends on the separation actually achieved between the assigned targets, the sensitivity and specificity of the outcome definitions, and the baseline risk of the enrolled population. HISTAP’s focus on hypertensive patients was itself a deliberate attempt to enrich the population for renal vulnerability, on the theory that chronically hypertensive kidneys have a rightward-shifted autoregulatory curve and therefore stand to benefit most from higher pressure targets.

The scientific stakes of this debate are considerable. Major abdominal surgery is performed millions of times each year worldwide, and postoperative acute kidney injury is among the most common and consequential surgical complications, associated with longer hospital stays, progression to chronic kidney disease, and increased mortality. If a simple, titratable intervention such as raising the intraoperative mean arterial pressure target could reliably reduce that burden, the practice change would be immediate and global. Conversely, if the benefit is small, confined to specific subgroups, or contingent on how kidney injury is measured, then blanket adoption of higher targets could expose patients to unnecessary vasopressor load, with its own risks of vasoconstrictive ischemia in the gut and extremities. The correspondence and reply are, in effect, a public calibration of how much confidence the evidence can bear.

What makes this exchange worth attention beyond the subspecialty is its demonstration of how clinical science refines itself in the open. The HISTAP investigators did not dismiss the methodological critique; they answered it in the same journal, walking readers through the trial’s definitional choices and the behavior of its hemodynamic data. The correspondents, for their part, framed their concerns as interpretive guidance rather than rejection, pointing toward the analyses that would make the trial’s message sharper. For clinicians managing high-risk surgical patients, the practical takeaway is that blood pressure targets are not one-size-fits-all numbers but hypotheses to be tested against each patient’s chronic baseline, and that the dose of hypotension, integrated over time, may matter as much as any single threshold. For researchers, the message is that the next generation of perioperative trials should predefine renal criteria with care, report achieved hypotension exposure transparently, and treat the gap between assigned targets and delivered physiology as a first-class result rather than an afterthought. The HISTAP debate, playing out in the correspondence pages of Intensive Care Medicine, is exactly the kind of disciplined argument that turns a trial result into durable clinical knowledge.

Subject of Research: Interpretation of the HISTAP randomized trial on intraoperative blood pressure targets, acute kidney injury criteria, and cumulative hypotension exposure in high-risk surgical patients

Article Title: Interpreting the HISTAP trial: the role of AKI criteria and cumulative exposure to hypotension. Author’s reply

Article References: Messina, A., Cortegiani, A., Samuelli, N., & Cecconi, M. (2026). Interpreting the HISTAP trial: the role of AKI criteria and cumulative exposure to hypotension. Author’s reply. Intensive Care Medicine. https://doi.org/10.1007/s00134-026-08639-4

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08639-4

Keywords: HISTAP trial, acute kidney injury, blood pressure targets, hypotension, major abdominal surgery, KDIGO criteria, mean arterial pressure, perioperative medicine, intensive care, renal autoregulation, randomized clinical trial, hypertension