Pietro Ravani

The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2013. This years update includes 2 new recommendations. First, among nonhypertensive or stage 1 hypertensive individuals, the use of resistance or weight training exercise does not adversely influence blood pressure (BP) (Grade D). Thus, such patients need not avoid this type of exercise for fear of increasing BP. Second, and separately, for very elderly patients with isolated systolic hypertension (age 80 years or older), the target for systolic BP should be < 150 mm Hg (Grade C) rather than < 140 mm Hg as recommended for younger patients. We also discuss 2 additional topics at length (the pharmacological treatment of mild hypertension and the possibility of a diastolic J curve in hypertensive patients with coronary artery disease). In light of several methodological limitations, a recent systematic review of 4 trials in patients with stage 1 uncomplicated hypertension did not lead to changes in management recommendations. In addition, because of a lack of prospective randomized data assessing diastolic BP thresholds in patients with coronary artery disease and hypertension, no recommendation to set a selective diastolic cut point for such patients could be affirmed. However, both of these issues will be examined on an ongoing basis, in particular as new evidence emerges.

Associations between Hemodialysis Access Type and Clinical Outcomes: A Systematic Review

Clinical practice guidelines recommend an arteriovenous fistula as the preferred vascular access for hemodialysis, but quantitative associations between vascular access type and various clinical outcomes remain controversial. We performed a systematic review of cohort studies to evaluate the associations between type of vascular access (arteriovenous fistula, arteriovenous graft, and central venous catheter) and risk for death, infection, and major cardiovascular events. We searched MEDLINE, EMBASE, and article reference lists and extracted data describing study design, participants, vascular access type, clinical outcomes, and risk for bias. We identified 3965 citations, of which 67 (62 cohort studies comprising 586,337 participants) met our inclusion criteria. In a random effects meta-analysis, compared with persons with fistulas, those individuals using catheters had higher risks for all-cause mortality (risk ratio=1.53, 95% CI=1.41-1.67), fatal infections (2.12, 1.79-2.52), and cardiovascular events (1.38, 1.24-1.54). Similarly, compared with persons with grafts, those individuals using catheters had higher risks for mortality (1.38, 1.25-1.52), fatal infections (1.49, 1.15-1.93), and cardiovascular events (1.26, 1.11-1.43). Compared with persons with fistulas, those individuals with grafts had increased all-cause mortality (1.18, 1.09-1.27) and fatal infection (1.36, 1.17-1.58), but we did not detect a difference in the risk for cardiovascular events (1.07, 0.95-1.21). The risk for bias, especially selection bias, was high. In conclusion, persons using catheters for hemodialysis seem to have the highest risks for death, infections, and cardiovascular events compared with other vascular access types, and patients with usable fistulas have the lowest risk.

Temporal Risk Profile for Infectious and Noninfectious Complications of Hemodialysis Access

Vascular access complications are a major cause of morbidity in patients undergoing hemodialysis, and determining how the risks of different complications vary over the life of an access may benefit the design of prevention strategies. We used data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) to assess the temporal profiles of risks for infectious and noninfectious complications of fistulas, grafts, and tunneled catheters in incident hemodialysis patients. We used longitudinal data to model time from access placement or successful treatment of a previous complication to subsequent complication and considered multiple accesses per patient and repeated access complications using baseline and time-varying covariates to obtain adjusted estimates. Of the 7769 incident patients identified, 7140 received at least one permanent access. During a median follow-up of 14 months (interquartile range, 7-22 months), 10,452 noninfectious and 1131 infectious events (including 551 hospitalizations for sepsis) occurred in 112,085 patient-months. The hazards for both complication types declined over time in all access types: They were 5-10 times greater in the first 3-6 months than in later periods after access placement or a remedial access-related procedure. The hazards declined more quickly with fistulas than with grafts and catheters (P<0.001; Weibull regression). These data indicate that risks for noninfectious and infectious complications of the hemodialysis access decline over time with all access types and suggest that prevention strategies should target the first 6 months after access placement or a remedial access-related procedure.

Renal Denervation Therapy for the Treatment of Resistant Hypertension: A Position Statement by the Canadian Hypertension Education Program

Renal denervation is a novel catheter-based, percutaneous procedure using radiofrequency energy to ablate nerves within the renal arteries. This procedure might help to significantly lower blood pressure (BP) in patients with resistant hypertension, defined as BP > 140/90 mm Hg (> 130/80 mm Hg for those with diabetes) despite use of ≥ 3 optimally dosed antihypertensive agents, ideally including 1 diuretic agent. The Canadian Hypertension Education Program Recommendations Task Force reviewed the current evidence on safety and efficacy of this procedure. Eleven studies on renal denervation were examined and most of the evidence evaluating renal denervation was derived from the Symplicity studies. In patients with systolic BP ≥ 160 mm Hg (≥ 150 mm Hg for patients with type 2 diabetes) despite use of ≥ 3 antihypertensive agents, bilateral renal denervation was associated with significantly lower BP (-22/11 to -34/13 mm Hg) at 6 months with a low periprocedural complication rate. Few patients underwent 24-hour ambulatory BP monitoring and ambulatory BP monitoring showed more modest BP lowering (0 to -11/7 mm Hg). Although early results on short-term safety and blood pressure-lowering are encouraging, there are no long-term efficacy and safety data, or hard cardiovascular end point data. The discrepancy between office BP reductions and 24-hour ambulatory BP monitor reductions needs to be further investigated. Until more data are available, renal sympathetic denervation should be considered as a treatment option of last resort for patients with resistant hypertension who have exhausted all other available medical management options.

Clinical trials in minimal change disease

Minimal change disease (MCD) is a pathological condition characterized by subtle glomerular lesions causing massive and reversible proteinuria that is usually steroid sensitive. Recurrence of symptoms of active disease following successful treatment (including proteinuria, oedema and oliguria) and steroid toxicity requires the use of other drugs to attain or maintain remission. Unresolved MCD is considered the initial step in the pathological pathway leading to focal and segmental glomerulosclerosis (FSGS). Historically, cyclophosphamide, chlorambucil, mycophenolate and calcineurin inhibitors have been utilized with success in MCD; however, the chronic nature of the disease and the toxicity of long-term use of these medications has pushed the development of new therapies. Synthetic corticotropin (adrenocorticotropic hormone) and anti-CD20 monoclonal antibodies, for example, are currently under investigation in clinical trials. In addition, these new interventions have dramatically impacted our understanding of the mechanisms of the disease. Phase II-IV clinical trials targeting new mechanisms and/or molecules are in progress. The list is long and includes drugs blocking the adaptive immune system (abatacept and anti-CD40 antibodies), as well as retinoids and the sialic acid precursor N-acetyl-D-mannosamine (ManNAc), two agents that affect the sieving properties of the glomerular basement membrane. Other drugs are being tested against FSGS and, if successful, could also be utilized against MCD. Clinical trials currently in progress should furnish a proper solution to what appears to be a solvable problem.