Biomarkers Suggest Intensive Blood Pressure Treatment Does Not Cause True Kidney Damage in CKD Patients

MedicalResearch.com Interview with:

Michael G. Shlipak, MD, MPH Scientific Director , Kidney Health Research Collaborative (khrc.ucsf.edu/) Professor of Medicine, Epidemiology & Biostatistics University of California, San Francisco Associate Chief of Medicine for Research Development San Francisco VA Medical Center

Dr. Shlipak

Michael G. Shlipak, MD, MPH
Scientific Director , Kidney Health Research Collaborative (khrc.ucsf.edu)
Professor of Medicine, Epidemiology & Biostatistics
University of California, San Francisco
Associate Chief of Medicine for Research Development
San Francisco VA Medical Center

MedicalResearch.com: What is the background for this study?

  • Our study represents major advancements in our understanding of whether kidney tissue damage accompanies the diagnosis of chronic kidney disease during hypertension therapy.
  • The Systolic Blood Pressure Intervention Trial (SPRINT) was a landmark clinical trial that demonstrated that more intensive systolic blood pressure management (target <120 mmHg) reduced rates of major cardiovascular events and mortality compared with standard therapy (<140 mmHg). A recent announcement indicated that the lower systolic blood pressure target also slowed the rate of cognitive decline and dementia incidence.
  • The major concern with intensive blood pressure lowering in SPRINT is the 3-fold incidence of chronic kidney disease, as defined using the clinical standard of serum creatinine levels. This detrimental impact on the kidney was surprising because hypertension is a predominant risk factor for kidney disease, and hypertension therapy should reduce CKD risk.
  • Given the lower blood pressure targets in the recently-updated national hypertension guidelines, there has been substantial concern that guideline implementation of blood pressure targets could cause an epidemic of CKD and the attendant suffering from its downstream consequences of cardiovascular disease, heart failure, and kidney failure.
  • In our study, we compared SPRINT participants who developed CKD with matched controls, using a panel of validated urinary biomarkers of kidney damage. These urine tests can measure actual kidney damage, rather than relying on the creatinine which is an indirect reflection of the kidney’s filtering function.
  • In the group undergoing intensive blood pressure lowering in SPRINT, we found that the new cases of CKD had an overall lowering of the kidney damage biomarkers compared with the controls, contrary to what would have been expected if they were developing “real” CKD.
  • In contrast, the new CKD cases that developed in the standard treatment group did have overall elevations in the urinary biomarkers of kidney damage; 5 of the 9 biomarkers significantly increased relative to the CKD cases in the intensive treatment group. 

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SPRINT Trial: Greater Mean Blood Pressure Reductions Linked To Increased Risk of Kidney Function Decline

MedicalResearch.com Interview with:
Rita Magriço MD

Hospital Garcia de Orta
Almada, Portugal 
 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The SPRINT trial showed that in non-diabetic patients with high cardiovascular risk, intensive systolic blood pressure treatment (<120 mmHg) was associated with lower rates of major cardiovascular events and mortality. However, intensive treatment was unexpectedly associated with increased kidney function decline.

We thought that lowering blood pressure could compromise kidney perfusion, evaluated by mean arterial pressure (MAP). If so, the magnitude of MAP reduction was expected to be associated with kidney function decline. We hypothesized that a greater difference between the baseline MAP and the lowest achieved MAP may be associated with a higher risk of kidney function decline.

Our analysis supports this hypothesis. We discovered that MAP reduction >20 mmHg in patients with a target systolic BP <120 mmHg was associated with higher incidence of kidney function decline. The benefit-risk balance of intensive treatment seemed to be less favourable with greater MAP reduction. Prospective studies evaluating the effect of MAP reduction in addition to hypertension treatment target on kidney function decline and cardiovascular events are warranted.

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Elderly At Greater Risk of Falls With Intensive Blood Pressure Control

MedicalResearch.com Interview with:
Donal J. Sexton, BSc, MD
The Irish Longitudinal Study on Ageing
Trinity College Dublin
Health Research Board Clinical Research Facility Galway
National University of Ireland Galway, Galway, Ireland
Trinity Health Kidney Centre, Tallaght Hospital
Department of Nephrology, Beaumont Hospital, Royal College of Surgeons of Ireland
Dublin, Ireland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In this study we used the inclusion criteria for SPRINT to identify those community dwelling elders who would meet criteria for the trial in clinical practice.

Our data are based on a prospective cohort study composed of participants chosen by a national stratified random sampling mechanism. If SPRINT participants were truly representative of the population, then the participants in the standard care arm of the trial should resemble the population to some extent. If this were true then the injurious falls rate might be similar between the two samples also.

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Ambulatory vs. Office Blood Pressure as Inclusion Criteria for the SPRINT Trial

MedicalResearch.com Interview with:
Alejandro de la Sierra, MD, PhD, FESC, FAHA
Professor of Medicine
Head, Internal Medicine Department
Hospital Mutua Terrassa
University of Barcelona, Spain

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Systolic Blood Pressure Intervention (SPRINT) trial has demonstrated that a strategy of systolic blood pressure (BP) reduction to a goal of 120 mmHg in selected hypertensive patients prevents the development of cardiovascular complications and mortality. The trial used automated office BP measurements. However, ambulatory BP monitoring (ABPM) has demonstrated to be superior to office BP in predicting cardiovascular events and mortality. We aimed to evaluate ambulatory BP values in hypertensive patients from the Spanish ABPM Registry who meet eligibility criteria for the SPRINT trial.

The results indicated that one third of our hypertensive population met such eligibility criteria and that ABPM values were considerably lower than office BP, with 42% of subjects having daytime BP below 130 mmHg and 21% with 24-hour BP below 120 mmHg.

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