Blood Pressure Targets in Chronic Kidney Disease: An Update on the Evidence

Dominique Guerrot; Jelmer K. Humalda


Curr Opin Nephrol Hypertens. 2020;29(3):327-332. 

In This Article

Evidence for Blood Presure Targets to Reduce Kidney Disease Progression in Patients With Chronic Kidney Disease

Although intensive BP lowering is associated with an increase in the risk of acute GFR decline,[13,28–31] optimal management of hypertension is recommended as a major goal for nephroprotection.[32] This largely relies on the concept of 'hypertensive nephropathy', in which a chronic nonsevere hypertension is, per se, considered as the cause of kidney parenchymal disease. Actually, accumulating evidence challenges this classical concept, which is key in defining whether BP targets in CKD should, or should not, be driven by renal outcomes.

A recent study describing a long-term follow-up of 609 patients with essential hypertension without CKD at baseline showed that a large majority (91%) of these patients did not present a significant decrease in GFR with time.[33] In the 9% patients with decreased kidney function at follow-up, the GFR decrease did generally not follow a progressive pattern but was driven by episodes of AKI without return to baseline, which is opposite to the pathophysiological model of hypertensive nephropathy.

If hypertension was to be a leading and 'dose-dependent' cause of CKD, then a genetically-driven increase in BP should result in a long-term increase in the risk of CKD. A genome-wide association study defined a genetic risk score based on 29 genetic polymorphisms individually associated with BP. As expected, this score was strongly associated with hypertension and demonstrated clear associations with left ventricular hypertrophy, stroke, and coronary artery disease. Importantly, the score was not associated with the onset of albuminuria or decreased kidney function.[34]

Moreover, in the concept of hypertensive nephropathy was valid, lower BP targets in hypertensive patients with normal kidney function at baseline should reduce the onset of CKD, and lower BP targets should also limit progression of CKD in patients with CKD (Figure 1). The MDRD study was the first RCT to analyze the consequences on GFR decline of two different BP targets.[28] This study compared a mean BP target less than 92 mmHg (approximately 125/80 mmHg) to less than 107 mmHg (approximately 140/90 mmHg). A post-hoc analysis showed a significant interaction on the decline of GFR between the BP target and proteinuria, with a significant benefit for proteinuria more than 3 g/day, moderate between 1 and 3 g/day, and absent less than 1 g/day. This result motivated the recommendation of K-DOQI and JNC6 to target BP less than 125/75 mmHg in patients with CKD with proteinuria above 1 g/day. These recommendations were secondarily withdrawn, because of doubts about the strength of the data and in particular the fact that only post-hoc analyzes had led to these conclusions. The AASK study included African-American patients with stage 3 and 4 CKD. It compared two BP targets (128/78 vs. 141/85 mm Hg on average), but also three different antihypertensive classes. Patients with diabetes with proteinuria more than 2.5 g/g were excluded.[35] AASK showed no difference between the two targets on GFR evolution at 4 years, including in a post-hoc analysis of subgroups defined by proteinuria more than 0.22 g/g and on an extended follow-up of the study cohort.[36] However, the same group in a recent meta-analysis of MDRD and AASK studies found that in a subpopulation of patients with CKD with proteinuria more than 0.44 g/day the more intensive BP target was associated with a hazard ratio of 0.79 (CI, 0.63–0.91) of ESRD.[19]

The REIN-2 study compared a DBP target of less than 90 mmHg to an intensive target (<130/80 mmHg). Patients included had nondiabetic proteinuric nephropathy. This study did not show any difference regarding the risk of ESRD.[37] The SPRINT study, within the initial follow-up, was also negative on the evolution of eGFR.[13] In patients with normal kidney function at baseline, intensive BP management was associated with a 3.54-fold (CI, 2.50–5.02) increase in the risk of incident CKD.[38] Magrico et al.[39] evaluated the risk-benefit of intensive treatment in SPRINT, focusing on the balance between cardiovascular events or death and kidney function decline. In patients without CKD larger reductions in MAP were associated with increased incidence of kidney function decline. In a propensity score analysis, MAP reduction less than 20 mm Hg presented a number needed to treat (NNT) (cardiovascular events or death) of 44 and a number needed to harm (NNH; kidney function decline) of 65; MAP reduction between 20 and less than 40 mm Hg presented an NNT of 42 and an NNH of 35; and MAP reduction more than 40 mm Hg presented an NNT of 95 and an NNH of 16. Intensive treatment therefore appeared as less favorable when a larger reduction in MAP from baseline was needed to attain the BP target.

Despite slight discrepancies, possibly related to the heterogeneity of populations included and of follow-up, the conclusions of most major trials do not show a significant effect of an intensive BP target compared to a standard target in terms of renal function. Accordingly, a meta-analysis including the nine major RCT available to date concluded that there is no significant benefit on kidney function associated with an intensive strategy in reducing BP.[40] Furthermore, the increased prescription of renin–angiotensin system blockers would have been expected to improve renal outcomes in the intensive treatment arms, independently of the direct effects of BP. Overall, excluding severe hypertension, the current evidence does not support the classical concept of hypertensive nephropathy.