Study data suggest acute kidney injury predicts adverse outcomes in patients hospitalized for acute severe hypertension; editorialists question validity of study conclusions

Among patients hospitalized with acute severe hypertension, those who experience acute kidney injury (AKI) are more likely to also experience adverse cardiovascular outcomes, and even small declines in renal function are independently associated with an increased risk of death, according to study findings. Researchers reviewed data from the Studying the Treatment of Acute Hypertension (STAT) registry. STAT is a U.S.-based, retrospective observational study of patients (n=1,566) with acute...

Among patients hospitalized with acute severe hypertension, those who experience acute kidney injury (AKI) are more likely to also experience adverse cardiovascular outcomes, and even small declines in renal function are independently associated with an increased risk of death, according to study findings.

Researchers reviewed data from the Studying the Treatment of Acute Hypertension (STAT) registry. STAT is a U.S.-based, retrospective observational study of patients (n=1,566) with acute severe hypertension (>=1 blood pressure [BP] measurement with systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg) who were treated in emergency or critical care settings with intravenous antihypertensive therapy. The purpose of the current analysis was to assess risk among patients with acute severe hypertension and AKI and the risks of death and cardiovascular endpoints with AKI and chronic kidney disease (CKD).

At admission, 79% of the cohort had at least mild kidney disease, including 32% with mild CKD (estimated glomerular filtration rate [eGFR] at baseline 60-89 mL/min/1.73 m2), 23% with moderate CKD (baseline eGFR, 30-59 mL/min/1.73 m2), and 11% with severe CKD (eGFR <30 mL/min/1.73 m2), and an additional 11% who were dialysis-dependent. Patients with CKD at baseline were more likely to develop heart failure (HF; P<.0001), non-ST-elevation myocardial infarction (P=.003), and AKI (P<.007).

Changes in kidney function were categorized according to RIFLE criteria, with a decline from baseline <25% characterized as no change, a decline of 25% to 50% characterized as risk, a decline of 50% to 75% characterized as injury, and a decline >75% characterized as renal failure. Of the STAT cohort, 15% experienced a decline in kidney function of 25% to 50%, 4.2% experienced a decline of 50% to 75%, and 3.6% experienced a decline >75%.

The study authors reported that patients who experienced more severe degrees of AKI were significantly more likely to experience HF and cardiac arrest (P<.0001 for both) and had significantly higher 90-day mortality rates (P=.003).

In a multivariable model, any acute loss of kidney function during hospitalization was independently associated with an increased risk of death (OR, 1.05 per 10 mL/min/1.73 m2 decline; P=.03). Other independent predictors of mortality included older age (P<.0001), male sex (P=.016), white versus black race (P=.003), and worse kidney function at baseline (P=.003). (Szczech LA, et al. Circulation 2010;121:2183-2191.)

In an accompanying editorial, Drs. Glenn Chertow and Tara Chang with the Division of Nephrology at Stanford University School of Medicine cited concerns about the study that prompted them to question the authors' conclusions regarding the risks associated with AKI and CKD in patients with acute severe hypertension.

In particular, the editorialists noted that eGFR was calculated with the Modification of Diet in Renal Disease study equation, which tends to underestimate true GFR in ranges exceeding 25 mL/min/1.73 m2 to 55 mL/min/1.73 m2, and determination of CKD was based on a single baseline measurement (ie, without establishing chronicity). Consequently, the potential misclassification (and overestimation) of CKD in the study cohort might have reduced the apparent risk associated with CKD, while inflating the risk associated with AKI.

Moreover, they explained, the researchers calculated acute changes in kidney function as the maximum decline measured in GFR relative to baseline (regardless of length of stay or number of creatinine measurements collected), which probably maximized the prevalence of AKI.

Further, Drs. Chertow and Chang questioned whether subjects included in STAT had truly acute (vs chronic) severe hypertension, and expressed concern regarding the lack of detail provided about in-hospital testing and evaluation of cardiovascular and cerebrovascular outcomes. (Circulation 2010;121:2160-2161.)

STAT was supported by a grant from The Medicines Co.