Dr. Nadia Zalunardo (biography and disclosures)
What I did before
The most common cause of death among individuals with chronic kidney disease (CKD) is cardiovascular disease. For most people with CKD, the risk of cardiovascular death exceeds the risk of developing end stage kidney disease (ESKD). Hence, interventions aimed at reducing cardiovascular event rates are important in CKD. This includes treatment of hypertension.
The initial enthusiasm for targeting lower blood pressure (BP) in general was supported by compelling prospective observational studies. In a large meta-analysis of data from over 1 million people with no known vascular disease, the risk of death from vascular disease (e.g. stroke, ischemic heart disease) decreased continuously with decreasing BP. This relationship held even at BP levels considered within the “normotensive range” (i.e. down to at least 115/75 mmHg), and among all age groups studied (ages 40 – 89).1 Among individuals with CKD, other observational studies have shown that lower BP is associated with a lower risk of progression to ESKD (e.g. dialysis).2
A recent collaborative meta-analysis of randomized controlled trials (RCTs) of BP lowering included >30,000 individuals with reduced estimated glomerular filtration rate (eGFR). Compared with placebo, blood pressure lowering regimens reduced the risk of major cardiovascular events in CKD.3
What is less clear is just how low the BP target should be in CKD. Until fairly recently, various practice guidelines recommended a target BP of <130/80 mmHg for all individuals with CKD.4 This recommendation was based on interpretation of available RCT evidence. This used to be my practice for most patients with CKD.
What changed my practice
First, while the observational data associating lower BP with lower cardiovascular and renal event rates is compelling, it cannot be assumed that lowering the BP to the same levels by pharmacological means will yield the same results. RCTs of specific BP targets are required to determine whether more intensive BP lowering (defined in this article as <130/80 mmHg) is beneficial.
Unfortunately, there are limited data upon which to base BP target recommendations in CKD at this time. For example, no RCT has shown in a primary analysis that more intensive BP lowering is of benefit in nondiabetic CKD. Recently, existing RCTs were examined in a systematic review and meta-analysis.5 There was no effect of more intensive BP lowering on cardiovascular outcomes or death, but the number of events available for analysis was relatively small, limiting the statistical power of this analysis. For prevention of ESKD, more intensive BP lowering (i.e. <130/80 compared to <140/90) may benefit individuals with proteinuria in particular; however, this evidence comes mainly from subgroup or post hoc analyses of existing RCTs. Thus, the optimal BP in nondiabetic CKD remains somewhat uncertain.6
What I do now
It is important to recognize that the subject of BP targets in CKD is still an area of active study. Recommendations will almost certainly be further refined as evidence from ongoing RCTs becomes available.
Currently, I follow the Canadian Hypertension Education Program (CHEP) 2014 guidelines for BP treatment in CKD for most patients.7 These include:
- Lifestyle intervention. In particular, the importance of dietary sodium restriction to < 2 grams/day should be emphasized in CKD. This may necessitate instructing patients on how to read food labels.
- For nondiabetic CKD, target BP < 140/90 mmHg. Although some Nephrologists may advise a lower target BP in certain patients with proteinuria, the evidence supporting this is limited and this is an area that requires further study. If you are unsure what BP target is most suitable for your patient, or if you are not sure what is causing the proteinuria, a Nephrology referral should be considered for advice.
- For diabetic CKD, target BP < 130/80 mmHg. The recommendation for the lower target for diabetics compared to nondiabetics is mainly for stroke risk reduction rather than prevention of ESKD. In my practice, I inquire about medication side effects as not all diabetics will tolerate this BP target.
The very elderly (≥ 80 years) are at increased risk of side effects from antihypertensives, such as orthostatic hypotension. Furthermore, the very elderly were not included in many of the RCTs of BP lowering, and in the RCTs that did focus on the elderly, the achieved BPs were not as low as in the studies of younger individuals; hence the target BPs established in younger people are not necessarily generalizable to the very elderly. In my practice, I most often use the systolic BP target of <150 mmHg, which is recommended by CHEP for the very elderly.7 A general summary of recommendations from CHEP is provided in the Table.
Frequently Asked Questions regarding angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) use in CKD:
1. How much decrease in eGFR is acceptable after starting ACEi or an ARB?
A decrease in eGFR is commonly observed after starting an ACEi or ARB, and a decline of less than 30% is generally considered acceptable. Patients treated with ACEi or ARB should have lab tests to check for decreases in eGFR (and hyperkalemia) within about 2 weeks of starting the medication. Decreases in eGFR by 30% or more necessitate a dose reduction or discontinuation of the medication.8 A follow-up measurement of kidney function should be arranged to ensure a return of kidney function to baseline.
2. At what eGFR level should ACEi or ARB be avoided?
There is no absolute eGFR level at which ACEi or ARB must be avoided. However, individuals with more advanced CKD (i.e. eGFR <30 mL/min/1.73m2) are at increased risk of acute kidney injury and hyperkalemia after starting these medications. Hence, beginning treatment at low dose, and monitoring of kidney function (and potassium levels) are essential.
3. In patients with CKD who do NOT have diabetes or proteinuria, is there a preference for ACEi (or ARB) over other antihypertensive agents to prevent CKD progression?
There is controversy in the literature on this subject. Two meta-analyses on this topic arrived at different conclusions. In one, the risk of CKD progression was reduced by the use of ACEi regardless of proteinuria levels.9 In the other, those with proteinuria < 500 mg/day seemed to have little benefit from an ACEi compared to other antihypertensive agents.10
In practice, it is reasonable to use an ACEi (or ARB) as a first line agent in most individuals with nondiabetic CKD provided it is well tolerated (i.e. follow patients for development of adverse effects such symptoms, decreased eGFR and hyperkalemia).
- Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002; 360(9349):1903-13. (View with CPSBC or UBC)
- Perry HM, Miller JP, Fornoff JR, Baty JD, Sambhi MP, Rutan G, Moskowitz DW, Carmody SE.Early Predictors of 15-Year End-Stage Renal Disease in Hypertensive Patients. Hypertension. 1995; 25: 587-594.(View with CPSBC or UBC)
- Blood Pressure Lowering Treatment Trialists’ Collaboration. Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials. BMJ 2013;347:f5680 (View with CPSBC or UBC)
- Canadian Hypertension Education Program. The 2011 Canadian Hypertension Education Program Recommendations for the Management of Hypertension: Blood Pressure Measurement, Diagnosis, Assessment of Risk, and Therapy. Canadian Journal of Cardiology. 2011;27(4):415-433. (View with CPSBC or UBC)
- Lv J, Ehteshami P, Sarnak MJ, Tighiouart H, Jun M, Ninomiya T, Foote C, Rodgers A, Zhang H, Wang H, Strippoli GF, Perkovic V. Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis. CMAJ. 2013;185(11):949-57. (View with CPSBC or UBC)
- Hildebrand AM, Garg AX. Blood pressure targets in chronic kidney disease: does proteinuria dictate how low we go? CMAJ. 2013;185(11):941-2. (View with CPSBC or UBC)
- Canadian Hypertension Education Program. The 2014 Canadian Hypertension Education Program Recommendations for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Canadian Journal of Cardiology. 2014;30(5): 485-501. (View with CPSBC or UBC)
- National Kidney Foundation. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004; 43: S1–S290. (View with CPSBC or UBC)
- Jafar TH, Stark PC, Schmid CH, et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med. 2003;139(4):244-252. (View with CPSBC or UBC)
- Kent DM, Jafar TH, Hayward RA, et al. Progression risk, urinary protein excretion, and treatment effects of angiotensin converting enzyme inhibitors in nondiabetic kidney disease. J Am Soc Nephrol. 2007;18(6):1959-1965. (View article)
Table: Summary of CHEP Recommendations for BP targets in CKD, 2014 7
|Diabetic CKD||<130/80||ACEi or ARB preferred if any abnormal albuminuria (including “microalbuminuria”)Lower BP target than for nondiabetic CKD is recommended mainly for stroke risk reduction|
|Nondiabetic CKD||<140/90||ACEi or ARB preferred if urine ACR > 30 mg/mmol|
|Very Elderly (80 and older)||Systolic BP < 150 mmHg||Be aware of increased risk of medication side effects such as orthostatic hypotension|