Commentary on Kovesdy CP, Bleyer AJ, Molnar MZ, et al. Blood pressure and mortality in U.S. veterans with chronic kidney disease: a cohort study. Ann Intern Med. 2013;159(4):233-242. Show
High blood pressure is one of the most important modifiable causes of morbidity and mortality. Overwhelming evidence demonstrates that hypertension is a leading risk factor for stroke and cardiovascular events. Blood pressure control also is critical in slowing the progression of kidney disease and preventing end-stage renal disease. Observational data suggest that lower systolic blood pressure (SBP) goals may improve cardiovascular and renal outcomes across all age groups. However, more recent studies have shown a J-shaped relationship between blood pressure and mortality in patients with advanced chronic kidney disease (CKD) and other high-risk populations. , With the possible exception of patients with proteinuria, , 6
The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group.
randomized controlled trials of lower blood pressure goals in patients with CKD have shown mixed results, and some have reported adverse events when achieving lower blood pressure targets. , 6
The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group.
, , One of the major limitations to many of these trials is that they have not considered discrete combinations of SBP and diastolic blood pressure (DBP). The present population-based study provides insight into some of these gaps in knowledge and will complement the ongoing SPRINT (Systolic Blood Pressure Intervention Trial) randomized trial to establish the benefits or harms of lower blood pressure targets for patients with CKD. What did this study show?Kovesdy et al analyzed data for more than 650,000 US veterans with non–dialysis-dependent CKD; participants had a mean age of 73.8 years and mean estimated glomerular filtration rate of 50.4 mL/min/1.73 m2, and 62.3% had stage 3A CKD. The authors evaluated individual and discrete combinations of SBP and DBP at baseline and their associations with risk of death over time. More than one-third of the participants died during a median follow-up of 5.8 years. A key study finding was that blood pressure combinations of 130-159 to 70-89 mm Hg were associated with the lowest risk for death. Furthermore, blood pressure combinations that included either DBP < 70 mm Hg regardless of SBP value or SBP < 130 mm Hg regardless of DBP value were both associated with increased risk of death. Hence, when SBP and DBP were considered separately, both followed a J-shaped association with risk of death. The authors conclude that low blood pressure can be deleterious and it may be better to target SBP ≥ 130 mm Hg if DBP is ∼70 mm Hg. Observational cohorts such as the present study provide a unique opportunity to evaluate special populations. The elderly population and those with multiple comorbid conditions are rarely recruited in clinical trials but comprise many of the patients we see in daily practice. There are inherent limitations to observational designs, namely bias and unmeasured confounding. Patients who have low DBP may include an over-representation of individuals with significant vascular disease or vascular stiffness. Similarly, patients with SBP < 130 mm Hg may have concurrent systolic heart failure not well characterized in the available data. In these circumstances, it may not be the lower blood pressure, but rather the underlying cause of the patient’s low blood pressure (eg, vascular stiffness or systolic heart failure) that is associated with increased mortality. Another important limitation of the present study is the inability to properly address the impact of blood pressure values in patients with proteinuria. Although individuals with proteinuria are more likely to benefit from lower blood pressure targets, the investigators were limited in their evaluation because of missing urine protein measurements. Finally, the study did not explore the risk of kidney function decline or end-stage renal disease as related to the blood pressure targets. For younger patients, we know that the risk of end-stage renal disease consistently exceeds the risk of mortality across several subgroups, whereas for the elderly, the opposite holds true. , These shortcomings will need to be addressed by ongoing randomized controlled trials. How does this study compare with prior studies?The finding of the present study is consistent with prior studies. The relationship between low SBP or DBP and increased mortality is well documented in both the general and CKD populations, and a J-shaped relationship between blood pressure and mortality has been described in patients with advanced CKD and those receiving hemodialysis. , Although the present study does not explore kidney function decline, it is important to highlight that a recent systematic review of trials examining lower blood pressure targets in CKD identified only 3 studies of patients with nondiabetic CKD. All 3 studies randomly assigned participants to 2 different blood pressure targets and demonstrated no benefit for blood pressure goals < 130/80 mm Hg for the primary outcome of kidney function decline. Additionally, another trial in a diabetic population that included participants with CKD showed similar results. These trials suggested that there was a possible benefit for those with proteinuria. As a result, the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines recommend blood pressure goals < 130/80 mm Hg for patients with albumin excretion rates > 30 mg/24 h (approximately equivalent to albumin-creatinine ratio > 30 mg/g). These guidelines are summarized in Table 1. 14 Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group
An important safety aspect highlighted in all these trials is that patients maintained on lower blood pressure targets required more medications, had more adverse events, and had more frequent visits and monitoring. Table 1Summary of 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD Reproduced from the KDIGO Blood Pressure Work Group 14 Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group
Note: Quality of Evidence: A, high; B, moderate; C, low; D, very low. Level 1 KDIGO “recommends” (most patients should receive the recommended course of action); Level 2 “suggests” (different choices will be appropriate for different patients). Abbreviations: BP, blood pressure; CKD, chronic kidney disease; KDIGO, Kidney Disease: Improving Global Outcomes.
What should clinicians and researchers do?Currently, there is no evidence to support blood pressure targets < 130/80 mm Hg for patients with proteinuria or <140/90 mm Hg in patients without proteinuria. The present study adds to the observational evidence that lower targets may be harmful in high-risk groups such as the elderly, those with CKD, and those with multiple comorbid conditions. This risk appears to be more pronounced at DBP < 70 mm Hg. The results also highlight that it may be preferable for patients to have a less ideal SBP (130-159 mm Hg) so that DBP is maintained at ∼70 mm Hg. This recommendation corresponds to the most current KDIGO guidelines, released in December 2012, which specifically state that for elderly patients with nondialysis CKD, providers should individually “tailor blood pressure treatment regimens.” 14
Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group
It is recommended that providers carefully consider comorbid conditions and gradually escalate treatment with close attention to adverse events, including electrolyte disorders, acute deterioration in kidney function, orthostatic hypotension, and drug side effects. This recommendation is not graded because results from ongoing trials are pending. Treatment to a lower target requires frequent monitoring for symptoms and adverse events, as previously described. Two clinical trials currently are evaluating lower than usual blood pressure targets in patients with CKD: SPRINT (www.sprinttrial.org) and HALT-PKD (haltpkd.org). HALT-PKD is devoted to interventions to slow the progression of polycystic kidney disease. The SPRINT trial randomly assigned more than 9,000 patients to 1 of 2 SBP goals, <120 versus < 140 mm Hg. In SPRINT, the population is enriched for high-risk patients, including those with CKD (glomerular filtration rate < 60 mL/min/1.73 m2) and the elderly (>75 years old). As discussed, these 2 subgroups represent segments of the population that are at higher risk of adverse outcomes and the information to be gained will inform recommended BP targets in these high-risk populations. SPRINT recruited patients without heavy proteinuria (timed urine collection or estimate by urine protein-creatinine ratio < 1 g/d). In this regard, SPRINT will not be able to answer questions regarding potential benefits of blood pressure thresholds for those with heavy proteinuria. Furthermore, future research is needed to determine whether low DBP is reflective of aortic stiffness. Can measurements of aortic stiffness, such as pulse wave velocity, inform treatment goals for those who most often develop low DBP, including elderly patients? An ancillary study to SPRINT is attempting to address whether measures of vascular stiffness will be predictive of outcomes independent of the achieved peripheral SBP. In conclusion, providers and patients must set individualized targets for blood pressure control. These discussions should consider not only the risks of elevated and low SBP and DBP, but also the costs associated with added medications and laboratory testing, along with the potential cardiovascular and renal benefits of blood pressure control. AcknowledgementsSupport: Dr Hung is supported by a Career Development Award ( 2-031-09S ) and Dr Roumie is supported by an investigator-initiated grant ( I01CX000570-01 ) from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Clinical Sciences Research . Financial Disclosure: The authors declare that they have no relevant financial interests. References
Article InfoPublication HistoryPublished online: March 31, 2014 IdentificationDOI: https://doi.org/10.1053/j.ajkd.2014.02.011 CopyrightPublished by Elsevier Inc. ScienceDirectAccess this article on ScienceDirect
Related ArticlesWhat are the 3 early warning signs of kidney disease?Here are three signs that could indicate that you are beginning to experience a decline in kidney function.. Dizziness and Fatigue. One of the first possible signs of weakening kidneys is the experience of overall weakness in yourself and your overall health. ... . Swelling (Edema) ... . Changes in urination.. What does low blood pressure mean with kidney failure?Low blood pressure (hypotension) leads to decreased filtered blood by the kidney and this will result in a failure of clearance of substances by the kidney. If this continues for some time, acute kidney injury can occur.
What blood pressure is too low for CKD?The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a treatment target of less than 140/90 mm Hg in CKD without proteinuria or less than 130/80 mm Hg if there is micro- or macroalbuminuria.
How is kidney function related to blood pressure?The kidneys help filter wastes and extra fluids from blood, using a lot of blood vessels. When the blood vessels become damaged, the nephrons that filter your blood don't receive the oxygen and nutrients they need to function well. This is why high blood pressure is the second leading cause of kidney failure.
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