Hepatorenal Acute Kidney Injury and the Importance of Raising Mean Arterial Pressure.

BACKGROUND: The efficacy of vasoconstrictors in hepatorenal syndrome (HRS) is variable. We hypothesized that the effectiveness of vasoconstrictor therapy in improving kidney function ultimately relates to the magnitude of the achieved mean arterial pressure (MAP) increase. METHODS: A retrospective study was conducted to identify cirrhotic individuals treated with vasoconstrictors for acute kidney injury (AKI) presumably caused by HRS to examine the relationship between change in MAP and change in serum creatinine (sCr) using multivariate mixed linear regression. RESULTS: Among 73 patients treated with midodrine/octreotide, change in MAP inversely correlated with change in sCr (p = 0.0005). The quartile with the greatest increase in MAP (+15.9 to +29.4 mm Hg) was associated with a subsequent absolute decrease in sCr. The strength of the correlation increased when the analysis was restricted to those who met the HRS criteria (n = 27, p = 0.002), where the third (+5.3 to +15.6 mm Hg) and fourth (+15.9 to +20.9 mm Hg) quartiles of MAP change were associated with a decrease in sCr. A similar but stronger correlation was found among 14 patients treated with norepinephrine either after failing midodrine/octreotide (n = 10) or de novo (n = 4; p = 0.002), where a rise in MAP of +19.2 to 25 mm Hg was associated with a larger reduction in sCr. Associations remained significant after adjustment for baseline parameters. CONCLUSIONS: The magnitude of MAP rise during HRS therapy with midodrine/octreotide or norepinephrine correlated with a reduction in sCr concentration. Our results suggest that achieving a pre-specified target of MAP increase might improve renal outcomes in hepatorenal AKI.

Intravenous conivaptan for the treatment of hyponatraemia caused by the syndrome of inappropriate secretion of antidiuretic hormone in hospitalized patients: a single-centre experience.

BACKGROUND: Intravenous conivaptan is a novel therapeutic agent indicated for the treatment of euvolaemic and hypervolaemic hyponatraemia. However, there is paucity of reported clinical experience using conivaptan for the treatment of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Moreover, while there is reasonable concern for overcorrection, no pre-treatment variables are known to be helpful to identify patients at risk for rapid correction. METHODS: We searched our records for hospitalized patients treated with intravenous conivaptan for moderate to severe hyponatraemia due to SIADH, with a starting serum sodium <130 mmol/L, between 2006 and 2009 (n = 18), to examine its efficacy as aquaretic, and to search for pre-treatment variables that could predict degree of response. RESULTS: Twenty-four hours after initiation of therapy, all patients had at least a 3-mmol/L increase in serum sodium, with 66.7% (12/18) of the patients having an absolute increase >or=4 mmol/L, and a median increase in serum sodium of 7 mmol/L (range: 3-16 mmol/L). Concomitantly, urine osmolality decreased in all patients with a mean reduction of 45.9 +/- 28.8% from baseline. Lower serum sodium, lower blood urea nitrogen and higher estimated glomerular filtration rate at baseline had a significant correlation with the magnitude of the absolute increase in serum sodium 24 hours after initiation of therapy. CONCLUSIONS: We conclude that intravenous conivaptan is an effective aquaretic to treat hyponatraemia caused by SIADH, as evidenced by a simultaneous increase in serum sodium and decrease in urine osmolality. Baseline values of serum sodium, blood urea nitrogen and estimated glomerular filtration rate may help predicting the magnitude of response to therapy.