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Dieter BP, Daratha KB, McPherson SM, Short R, Alicic RZ, Tuttle KR: Association of Acute Kidney Injury with Cardiovascular Events and Death in Systolic Blood Pressure Intervention Trial. Am J Nephrol 2019;49:359–367   

The landmark SPRINT trial [1] of intensive vs standard anti-hypertensive therapy in older, non-diabetic subjects at a high-risk of cardiovascular disease (CVD) demonstrated an overall clear-cut benefit in terms of avoidance of CVD events and all-cause mortality when the systolic arterial blood pressure (SBP) was reduced to 120mmHg or less. However, the cost of these benefits was an increase in acute kidney injury (AKI) events to about double in the intensive SBP group (4.4%) compared to the standard SBP group (2.6%). Whether these AKI events have long term sequelae remains an open question.

Dieter and colleagues addressed this issue by conducting a post-hoc analysis of the SPRINT data. Hypotensive episodes and AKI were frequently observed in the intrusive SBP group. In addition, there was an increased frequency of a decline in eGFR from baseline of >30% in the intensive SBP group, even after adjusting for clinical risk factors. Among patients with chronic kidney disease (CKD) at baseline the intensive SBP group did not experience any slowing of progression.

Importantly, the risk of developing a CVD event or all cause mortal event was higher in those subjects experiencing an episode of AKI, even after adjustment for co-variates, although the magnitude of this risk was attenuated by such an adjustment. Thus, the theoretical advantages of a lower blood pressure in preventing CVD events or death was entirely lost in association with the development of AKI. Fortunately. AKI was rather uncommon in the intensive SBP group (4.4%), and the development of AKI did not abrogate the overall beneficial effects seen in the SPRINT trial as a whole.

This analysis is hypothesis-generating rather than a proof that the AKI events are causally related to the enhanced risk of CVD events and death. But when combined with other observational data, this analysis creates a clear conundrum: namely, is the lowering of SBP to 120mmHg or less and the attendant increase in risk of AKI worthwhile? The episodes of AKI are usually minor and reversible, and we still do not understand the mechanisms underlying a connection between a brief episode of AKI and a longer term enhancement of CVD risk. In addition, we do not have very precise tools to predict which patients are more likely to exhibit AKI when SBP is reduced to around 120mmHg. In an accompanying Editorial, Thomas and Schold stressed the need for vigilance in trying to avoid AKI when initiating therapy for hypertension whenever possible, and to encourage appropriate close monitoring of patients during intensive blood pressure control. [2] The SPRINT trial was conducted in subjects without diabetes but who were at a high risk of CVD. Do these findings also apply to individuals (mainly younger) who are at much lower risk of CVD? These are important questions, yet to be answered. The US Hypertension guidelines, drawing extensively from the SPRINT trial, adopted a goal of <130mmHg for SBP in management of hypertensive patients, and we do not know whether this intermediate goal between intensive and standard approaches to therapy will minimize the risks of AKI and simultaneously optimize the benefits of blood pressure control on CVD events. Stay tuned! This is an evolving story and some answers may be forthcoming in the not too distant future.

References

1. SPRINT Research Group, Wright et al., A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015;373:2103–2116

2. Thomas G, Schold JD, Blood Pressure Control, Acute Kidney Injury, and Cardiovascular Events: Separating the Chaff from the Wheat. Am J Nephrol 2019;49:356–358

Quoted Karger Article

Association of Acute Kidney Injury with Cardiovascular Events and Death in Systolic Blood Pressure Intervention Trial

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