Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease

Abstract

BACKGROUND In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.)

Relationship between low blood pressure and renal/cardiovascular outcomes in Japanese patients with chronic kidney disease under nephrologist care: the Gonryo study

“…As for the optimal blood pressure (BP) in CKD patients, the recommended target systolic BP (SBP)/diastolic BP (DBP) is \140/90 mmHg for those without albuminuria and \130/80 mmHg for those with urine albumin excretion rates [30 mg/24 h, according to the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines [3]. The recommendations were derived from previous data such as those from the MDRD (Modification of Diet in Renal Disease) study and the AASK (AfricanAmerican Study of Kidney Disease and Hypertension), which demonstrated that aggressive BP control to lower BP targets was associated with a lower risk of CKD progression, especially in patients with proteinuria [4,5]. However, the lower limit of the optimal BP target range for patients with CKD remains unclear.…”

Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis

“…Current guidelines recommend a blood pressure target below 130/80 mm Hg for patients with chronic kidney disease, [8][9][10] but this recommendation is mostly based on observational studies and a single randomized trial (the Modification of Diet in Renal Disease [MDRD] study) that focused on kidney protection. 11 Subsequent trials of different targets in people with chronic kidney disease have yielded inconsistent results, 12,13,14 leading to criticism by the recent Canadian Hypertension Education Program guideline (which suggested a less aggressive target) of other guidelines, with suggestions that their blood pressure recommendations went beyond the available evidence. This criticism has been supported by a recent systematic review (no meta-analysis was performed) that focused on 3 trials and reported inconclusive results overall but raised the possibility that proteinuria was an effect modifier.…”

Metalloproteinases: key and common mediators of multiple GPCRs and candidate therapeutic targets in models of hypertensive cardiac disease

“…In the USA, up to 75% of the adult patients with diabetes have hypertension and renovascular disease [5,6]. The chronic activation of the renin-angiotensin system results in sympathetic activation further impairing cardiovascular and renal functions.…”

“…Indeed, antihypertensive drugs targeting signaling by one or more GPCRs such as angiotensinconverting enzyme (ACE) inhibitors, angiotensin receptor blockers and β-blockers are prescribed to treat and prevent cardiovascular complications including microvascular complications of retinopathy and progression of nephropathy in diabetic patients. Similar to diabetes [5] and obesity [7], chronic stress (e.g. due to job strain, social environment or emotional distress) [6,[8][9][10][11][12] and genetic predisposition [2,13] can cause various degrees of hypertension and cardiac disease.…”

“…The detrimental cardiovascular effects of high catecholamine levels are well established in humans as well as many disease models including rodents. Genetic predisposition plays a major role in disease development and, therefore, in the responses to antihypertensive treatments [2,5,13,14]. This has been well studied in North America where multiple ethnic groups coexist and are at risk of cardiovascular disease associated with metabolic syndrome.…”