Hepatorenal syndrome: one size does not fit all

Renal perfusion relies upon cardiac output, renal blood fl ow, and autoregulation. HRS infl uences cardiac output and systemic vascular resistance, and establishing a pressure gradient across the glomerulus ensures renal blood fl ow and glomerular fi ltration rate [2,3]. In fl uid responsive patients, volume resuscitation is a key component of HRS management. Th e traditional target mean arterial pressure (MAP) of 65 mmHg to ensure renal perfusion assumes that ‘one size fi ts all’ in HRS. Th e kidneys are in the abdominal compartment, and intraabdominal pressure varies among individuals. Th e pressure of the compartment during disease states that cause ascites decreases renal perfusion pressure and should be overcome, especially when autoregulation is impaired [4]. In other words, the arbitrary suggestion of increasing the MAP by 10 mmHg (Table 6 in [1]) may not be enough (or may be too much). Titrating norepinephrine to a baseline MAP of 65 mmHg plus the intraabdominal pressure [4] and administering terlipressin or vasopressin (which may constrict the eff erent glomerular arteriole [5]) may be an eff ective hemodynamic strategy to ensure renal perfusion pressure. Although this recommendation may not be based on grade A evidence, it is physiologically sound (establishes a pressure gradient) and may inspire further studies of hemodynamic management in patients with HRS.

We read with interest the Acute Dialysis Quality Initiative (ADQI) VIII consensus statements on the treatment of patients with hepatorenal syndrome (HRS) and acute kidney injury [1]. While we appreciate the authors' discussion, we question the hemodynamic recommen dations and suggest further areas of study (Section III in [1]).
Renal perfusion relies upon cardiac output, renal blood fl ow, and autoregulation. HRS infl uences cardiac output and systemic vascular resistance, and establishing a pressure gradient across the glomerulus ensures renal blood fl ow and glomerular fi ltration rate [2,3]. In fl uid responsive patients, volume resuscitation is a key component of HRS management.
Th e traditional target mean arterial pressure (MAP) of 65 mmHg to ensure renal perfusion assumes that 'one size fi ts all' in HRS. Th e kidneys are in the abdominal compartment, and intraabdominal pressure varies among individuals. Th e pressure of the compartment during disease states that cause ascites decreases renal perfusion pressure and should be overcome, especially when autoregulation is impaired [4]. In other words, the arbitrary suggestion of increasing the MAP by 10 mmHg ( Table 6 in [1]) may not be enough (or may be too much).
Titrating norepinephrine to a baseline MAP of 65 mmHg plus the intraabdominal pressure [4] and administering terlipressin or vasopressin (which may constrict the eff erent glomerular arteriole [5]) may be an eff ective hemodynamic strategy to ensure renal perfusion pressure. Although this recommendation may not be based on grade A evidence, it is physiologically sound (establishes a pressure gradient) and may inspire further studies of hemodynamic management in patients with HRS.

Andrew Davenport, Mitra K Nadim and John A Kellum, for the authors
We thank Drs Parikh and Moitra for their letter concerning our paper reviewing the medical management of HRS [1]. We agree that the hemodynamic alterations of advanced liver disease are complex. Early in the course of cirrhosis the eff ects of increased splanchnic vasodilatation, primarily due to local nitric oxide synthesis, have limited systemic manifestations. As liver disease progresses, however, systemic vasodilatation develops despite increased visceral sympathetic tone, reninangiotensin-aldosterone activation, endothelin and vasopressin release, leading to a loss of renal autoregulation [6], increasing the risk of 'pre-renal' acute kidney injury [7].
Terlipressin, a potent vasoconstrictor, particularly for the mesenteric circulation, increases renal perfusion pressure. However, the optimum renal perfusion pressure for patients with cirrhosis is unknown [1]. Following coronary artery surgery, renal auto-regulation is impaired and glomerular fi ltration rates are higher, with a mean arterial pressure of 70 mmHg [8]. Patients with cirrhosis diff er in that they may have ascites and right atrial dilatation. Studies in patients with heart failure with elevated right atrial pressures have shown that intraabdominal pressures even as low as 8 mmHg adversely aff ect renal function [9]. In patients with cirrhosis, ascitic drainage can be shown to have an almost immediate dynamic eff ect on renal perfusion, with changes in intrarenal pressure demonstrated with color Doppler assessment of intra-renal blood fl ow. Further prospective studies are thus required to determine whether there is an optimal target renal perfusion pressure for patients with HRS treated with terlipressin, but these will also need to include assessment of intraabdominal pressure.