In a recent systematic review and meta-analysis published in AJKD, Huang and colleagues discuss the association of prehypertension with an increased incidence of End Stage Renal Disease (ESRD). The study clearly shows an increased risk of developing ESRD with both low-range (blood pressure 120-129/80-84 mmHg) as well as high-range prehypertension (blood pressure 130-139/85-89 mmHg). These findings might have wide public health implications. In this interview, corresponding author Dr. Dingli Xu (DX) discusses the important findings of his research with Dr. Jean Francis (eAJKD) guest contributor.
eAJKD: What inspired you to study this important topic?
DX: The increasing incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) represents a major worldwide public health problem. CKD affects 10–15% of the adult population worldwide. Individuals with CKD have a reduced life expectancy, and those with ESRD have mortality rates that are 20-fold higher than those of age- and sex-matched individuals with normal kidney function. Hence, the treatment of the risk factors of CKD should be a public health priority.
Many cross-sectional studies have shown that prehypertension, particularly high-range prehypertension, is associated with CKD and ESRD. However, it is difficult to establish the detrimental effects of prehypertension on the kidneys from cross-sectional studies because CKD itself can elevate BP. Some prospective cohort studies have indicated that prehypertension is related to the incidence of ESRD, while other studies have shown that the association was not statistically significant. Some of the reasons for the differences in the results among these studies may be the low incidence rate of ESRD, the small sample size, and the short-term follow-up.
These inconsistent results convinced us that meta-analysis of prospective cohort studies that examined the association of prehypertension with ESRD may help clarify this issue.
eAJKD: From a clinical standpoint, how should the findings of this study be implemented while caring for patients with prehypertension, with or without kidney disease?
DX: First, considering the robust evidence of an association between prehypertension and the risk of ESRD shown in our study, it is preferable to consider earlier interventions for prehypertension to prevent CKD among the general population. Today, lifestyle intervention is the primary treatment for prehypertension in the general population. However, high-risk subpopulations with prehypertension, especially high-range prehypertension, are needed to be selected for future controlled trials of pharmacologic treatment.
Second, the BP target for patients with CKD is inconsistent among different guidelines. JNC 7 recommends that patients with diabetes or kidney disease, the BP goal is <130/80 mm Hg. However, the 2014 Hypertension Guidelines do not recommend this goal. The KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for Management of Blood Pressure in Chronic Kidney Disease acknowledges that no single BP target is optimal for all patients with CKD, and encourages individualization of treatment depending on age, severity of albuminuria, and comorbidities. These differences are mainly due to the fact that available evidence is inconclusive to demonstrate a BP target of less than 130/80 mm Hg improves clinical outcomes more than a target of less than 140/90 mm Hg in adults with CKD. In our study, we found a robust and significant association between prehypertension and the incidence of ESRD. Thus, controlled trials with large samples and long follow-up periods are required to determine the lower BP target in patients with CKD with or without severe proteinuria. We believe that lifestyle intervention and periodic screening of BP should be recommended early for CKD patients with prehypertension.
eAJKD: How would you reconcile the findings in your study with the new recommendations from the 2014 Hypertension Guidelines that were published recently? They have pushed the initiation of medical intervention to higher blood pressure thresholds.
DX: There is a great gap to be covered between epidemiologic studies and randomized controlled studies in prehypertension.
In our study, we found that prehypertension elevates the risk of ESRD after adjusting for multiple cardiovascular risk factors. Another meta-analysis by our group also showed that the situation is similar for cardiovascular disease (CVD). These findings reaffirm the importance of the definition of “prehypertension,” rather than a systolic BP of 120 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg being considered “normal.”
However, whether treatment of prehypertension can reduce the risk of target organ damage is controversial. Based on the lack of prospective, randomized trials in prehypertensive patients, professional societies do not recommend drug treatment, even in high-range prehypertension. We think that this is why the 2014 Hypertension Guidelines pushed the initiation of medical intervention to higher blood pressure thresholds.
Prehypertensive individuals are at a high risk to progress to sustained hypertension, CVD, and kidney disease. For treatment, we emphasize that lifestyle intervention, but not medical intervention, is the mainstay for prehypertension. However, high-risk subpopulations with prehypertension are needed for future controlled trials of pharmacologic treatment.
eAJKD: Could you please elaborate on potential mechanisms linking prehypertension to the development of ESRD?
DX: The mechanisms linking prehypertension and development of ESRD are complicated and not yet fully elucidated. They may include:
First, we think that prehypertension, similar to hypertension, can cause renal arteriosclerosis. This is supported by the Hisayama Study from Japan.
Second, individuals with prehypertension are more likely to progress into clinical hypertension and further cause kidney damage.
Third, it had been reported that metabolic syndrome is associated with prehypertension. This combination may cause progressive CKD.