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. 

MedicalResearch.com: What are the main findings?

  • Using a panel of 9 urine biomarkers of kidney damage, we found that the diagnosis of chronic kidney disease (CKD) during intensive hypertension treatment was not associated with true kidney tissue damage and thus may not represent real disease.
  • These findings have important implications for the monitoring of kidney health during blood pressure lowering and for our understanding of the overall risk/benefit trade-off from blood pressure lowering to the new guideline targets of systolic blood pressure <130 mmHg. 

MedicalResearch.com: What should readers take away from your report? 

  • These findings suggest that the chronic kidney disease during intensive blood pressure management is typically not accompanied by true kidney damage. Rather, the diagnosis likely reflects benign reductions in kidney blood flow.
  • These findings highlight the major limitations of our current clinical standards to diagnose and monitor kidney disease and the need for new measures that quantify actual damage within the kidney.
  • For clinicians and their patients, these findings should be reassuring that creatinine elevations are common during intensive blood pressure lowering but they usually do not represent true kidney disease. 

MedicalResearch.com: How many people are on intensive hypertension treatment? 

  • In the US, it is estimated that 60 million people are treated for hypertension. The term “intensive treatment” comes from the trial arm of systolic blood pressure <120 mmHg. This is now guideline-concordant therapy, as the goal is <130 mmHg in the clinic, which corresponds to <120 when measured in an idealized, clinical trial setting.

MedicalResearch.com: How many on this treatment are diagnosed with CKD? How many people could be affected by this finding with respect to the new guideline targets? 

  • In our study, about 4% of those being treated to <120 mmHg developed new CKD. If we assume that 50 million persons with hypertension do not already have CKD, then 4% would be 2 million new cases. In addition, many more individuals may have their creatinine levels rise during treatment, which may prompt them to discontinue beneficial blood pressure reduction.

MedicalResearch.com: What recommendations do you have for future research as a result of this study? 

  • Response: Future research is needed to validate these findings and reconsider how we diagnose kidney disease in the setting of hemodynamic shifts. In addition, future studies should investigate whether urinary biomarkers of kidney damage can predict and distinguish the subset of individuals with real kidney damage accompanying creatinine increases during blood pressure reduction.

No relevant disclosures to this study.

Citation:

Zhang WR, Craven TE, Malhotra R, Cheung AK, Chonchol M, Drawz P, et al. Kidney Damage Biomarkers and Incident Chronic Kidney Disease During Blood Pressure ReductionA Case–Control Study. Ann Intern Med. [Epub ahead of print ] doi: 10.7326/M18-1037

Oct 23, 2018 @ 1:02 pm

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