BP target in those with kidney disease

 

New guidelines for blood pressure management in those with chronic kidney disease (CKD), from Kidney Disease: Improving Global Outcomes (KDIGO), an update of their 2012 guidelines: see https://kdigo.org/wp-content/uploads/2016/10/KDIGO_BP_Exec_Summary_final.pdf for the executive summary, or their 92-page full guidelines at https://kdigo.org/wp-content/uploads/2016/10/KDIGO-2021-BP-GL.pdf 

 

Details: 

-- the goal for this working group was to assess blood pressure measurement as well as blood pressure targets in CKD patients (though they still have chapters on lifestyle interventions, blood pressure management in those with kidney transplants, children, as per below) 

 

-- blood pressure measurements: 

    -- they note that routine (casual) office-based blood pressure was not used in the large randomized controlled trials assessing the deleterious effects of hypertension, so the results of these study-based measurements (referred to as standardized measurements, since they were done in a consistent manner) should not be generalized to the office-based measurements 

    -- and, the relationship between office-based and standardized measurements of blood pressure is highly variable, both in patients with and without CKD (eg, see http://gmodestmedblogs.blogspot.com/2020/10/hypertension-office-bp-not-correlate.html ), and even in the SPRINT study (see http://gmodestmedblogs.blogspot.com/2017/06/monitor-bp-effects-by-abpm-sprint-trial.html ) 

    -- they de-emphasize the specifics of how standardized measurements are done, but the emphasis should be on standardization not the type of equipment used 

        -- they do include the  potential importance of the office-based automated oscillometric device (see http://gmodestmedblogs.blogspot.com/2019/02/automated-office-bp-as-good-as-abpm.html )

    -- and, I would add, several studies have found poor relationship between office-based measurement and clinical outcomes (e.g. see http://gmodestmedblogs.blogspot.com/2018/04/ambulatory-blood-pressure-monitoring.html  or http://gmodestmedblogs.blogspot.com/2018/02/ambulatory-blood-pressure-monitoring.html ) 

        -- though they do comment that these studies are mostly observational, and that 24-hour ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) are important 

 

-- lifestyle interventions: 

    -- sodium intake: though there is limited information specific to the CKD population, they do endorse consuming less than 2 g of sodium a day, including in children, though noting that participant adherence to this guideline is not met with much patient adherence and in fact with questionable effectiveness (see http://gmodestmedblogs.blogspot.com/2016/05/blood-pressure-and-low-sodium-diet.html ) 

        -- of note, sodium restriction may be inappropriate in those with sodium wasting nephropathy 

    -- physical activity: beneficial for blood pressure lowering, physical fitness/strength, weight loss, and lowering the risk of diabetes/dysglycemia; they reiterate a goal of at least 150 minutes per week of moderate-intensity physical activity, similar to their own guidelines for diabetes management in CKD 

        -- this recommendation should be individualized according to the patient’s cognitive and physical conditions 

        -- there may be benefits from lesser degrees of physical activity 

    -- weight loss and reducing alcohol consumption have been shown to be beneficial in the general population, though those specific interventions in patients with CKD has not been studied  

 

-- Blood pressure management in those having CKD with or without diabetes but not receiving dialysis or having had renal transplant: 

    -- target blood pressure: systolic blood pressure goal <120 mmHg, a goal lower than 130/80 that they recommended in their 2012 recommendations 

        -- this goal is largely based on the SPRINT study showing cardioprotection, survival, and cognitive benefits of this lower goal (see http://gmodestmedblogs.blogspot.com/2015/11/tighter-blood-pressure-control-sprint.html , where the mean achieved SBP was 121 vs 136 mmHg)

            -- they note that this recommendation is based on only one study (SPRINT), though they feel it is a high-quality one with a predefined subgroup of patients with CKD. Several meta-analyses have suggested proportional reduction in cardiovascular events with better BP control, and this was independent of CKD 

            -- they do emphasize individualization for this goal, including consideration of the patient’s characteristics, tolerability, and preferences 

            -- also, there are certain populations that have not been studied adeqauately: diabetes (which was unfortunately excluded explicitly in the SPRINT trial, though those with impaired glucose metabolism did derive similar benefits as those without), those with advanced CKD (stage IV and V), those with proteinuria >1g/d, those with baseline SBP 120-129 mmHg, those either <50yo or >90yo, or those with “white coat” or severe hypertension 

                -- they emphasized that the lack of studies for some groups of patients does not necessarily mean that these patients should not have a lower goal, just that studies really should be done 

            -- there is concern about lowering the diastolic blood pressure (DBP) too far, especially in those with coronary artery disease (since coronary perfusion depends on the DBP).  In the SPRINT study those with the lowest baseline DBP had similar cardiovascular and survival benefits from intensive reduction of the SBP 

        -- medications: 

            -- those with SBP >20mmHg above target: they suggest combination therapy (though they do note that there are no RCTs comparing different drug combinations in CKD) 

            -- there is limited evidence on specific anti-hypertensive agents to treat hypertension in those with CKD. They reference a network meta-analysis suggesting that ACE inhibitors and ARBs reduce the risk of kidney failure and other major cardiovascular events in those with CKD, in those with or without diabetes and albuminuria. And that ACE inhibitors but not ARBs reduce the odds of all-cause death (see htn metanal CKD better with ACE vs ARB  AmJKidDis2016 in dropbox, or doi.org/10.1053/j.ajkd.2015.10.011) 

                -- however, to my reading of this meta-analysis, these authors actually do not address the specific issue of albuminuria, and prior studies have suggested that these renin/angiotensin antagonists are specifically helpful in those with albuminuria. Their assessment of the studies in the meta-analysis suggest that outcomes are significantly better with ACE inhibitors over ARBs 

                -- and, these updated KDIGO guidelines (both the executive summary and the full report) are a bit unclear about the role of renin/angiotensin antagonists in those with CKD but without proteinuria.

 

-- blood pressure management in those with kidney transplant 

    -- no completed RCTs, so no specific guidelines 

    -- they suggest a BP goal of 130/80, as per their 2012 recommendations. They do note that in SPRINT there was a modest incidence of acute kidney injury in those in the SBP <120 mmHg wing, that the loss of renal autoregulation of arteriolar blood flow with the denervated transplant could aggravate this effect, and that the priority of this working group was preserving allograft survival. Hence the higher goal seemed acceptable to them.

    -- based on several RCTs, they recommend dihydropyridine CCBs or ARBs, which have been shown to decrease graft loss (ARBs first-line if proteinuria, CCBs if women trying to conceive or pregnant) 

 

--BP management in children with CKD 

    --no trials on office-based vs standardized BP measurement. But they suggest annual ABPM if possible, supplemented by standardized auscultatory office BP every 3-6 months 

    -- goal BP should be <50^th percentile of normal children with corresponding age, sex and height 

    -- first-line therapy: ARBs or ACE-I, since they lower proteinuria (no comment on those without proteinuria) 

 

Commentary: 

-- the bottom-line recommendation is that they propose a systolic blood pressure target <120 mmHg for most people with chronic kidney disease not receiving dialysis, the exception being children and kidney transplant recipients 

-- much of this relies on the SPRINT trial (see http://gmodestmedblogs.blogspot.com/2015/11/tighter-blood-pressure-control-sprint.html or http://gmodestmedblogs.blogspot.com/2016/05/sprint-trial-elderly-subgroup-study-of.html ), though there were concerns about SPRINT's methodology (as noted in http://gmodestmedblogs.blogspot.com/2018/03/adding-yet-another-bp-med-helps-alot.html ) 

-- ABPM is considered the standard of care by the USPSTF with a grade A recommendation (see http://gmodestmedblogs.blogspot.com/2015/01/uspstf-recs-on-ambulatory-blood.html ), as well as in the UK’s NICE guidelines 

-- the approach in the KDIGO recommendations above is a standardized one but is not a validated one, see their figure 2 for how blood pressure can be assessed in the office with 19 pointers, none of which have been clinically validated in big studies that I am aware of 

-- starting combination therapy in those with systolic blood pressure >20mmHg above target (ie SBP >140mmHg): I have significant concerns about this recommendation. In general patients have been living with high blood pressure for some time. I am concerned about the potential effects of long-standing hypertension on local microvascular remodeling (where lowering the blood pressure too aggressively may deprive distal tissues of their needed blood supply), the exaggerated responses of some patients to single agents (which I have seen quite frequently) raising the possibility of dramatic and possibly deleterious decreases in blood pressure by using 2 agents at once, and that a trial of a single medication followed with close follow-up and augmentation seems to be much safer without any clear downside. Even asymptomatic patients with very high SBPs could potentially have bad outcomes, and follow-up in a few days after starting medication still seems reasonable. (There have been several studies of rapid, aggressive blood pressure management with such agents as rapid acting nifedipine or some others no longer used, which can lead to strokes) 

 

--of note, a recent Chinese study found results similar to those found in the SPRINT trial (see http://gmodestmedblogs.blogspot.com/2021/09/hypertension-lower-target-blood.html), noting:

    --impressive 30+% reductions of cardiovascular clinical outcomes with achieved systolic blood pressures of 128mmHg vs 135mmHg

    --no adverse renal outcomes with the lower pressure, in those with baseline CKD or not

    --their standardized office-base blood pressure was as good as a home-based one in clinical outcomes

    --unlike SPRINT, diabetics were included, with similar benefits to the lower blood pressure

    --outcomes in those with low diastolic blood pressure (<61mmHg) or high pulse pressures (>60 mmHg) were similar to the overall population enrolled

 

Limitations: 

-- a lot of these recommendations are based on expert opinion, lacking clear-cut studies to demonstrate their conclusions. This is always problematic for those of us treating patients. many of the recommendations are probably quite reasonable extensions of other studies on those without CKD, but experts certainly can be wrong. And this has happened lots of times in the past

 

So, I do think it is reasonable to have a lower goal blood pressure overall, though I would make sure that the patients are asymptomatic at that lower goal (no postural symptoms or falls reported), and would also check orthostatic blood pressures to make sure they do not bottom-out....

    --even those who are asymptomatic but have very low BP on standing should probably have higher goal sitting pressures, since they may well become dehydrated at some point (diarrhea, sweating in the heat) and have a tragic fall)

 

geoff

 

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