Chronic Kidney Disease: Lower Blood Pressure May Equal Higher Mortality

Dr. Csaba P. Kovesdy, MD Professor of Medicine University of Tennessee Health Science Center Chief of Nephrology Memphis Veterans Affairs Medical CentMedicalResearch.com: Interview Invitation
Dr. Csaba P. Kovesdy, MD
Professor of Medicine
University of Tennessee Health Science Center
Chief of Nephrology
Memphis Veterans Affairs Medical Center

Medical Research: What are the main findings of the study?

Dr. Kovesdy: We applied the structure of a clinical trial of hypertension management to our cohort of >600,000 patients with prevalent Chronic Kidney Disease (CKD). We first identified patients with baseline uncontrolled hypertension (using the definition applied by the SPRINT trial), then isolated the ones who had a decline in their baseline systolic blood pressure to two different levels (<120 and 120-139 mmHg) in response to a concomitant increase in prescribed antihypertensives, similar to what would happen in a trial examining two different systolic blood pressure targets. We then matched patients in the two groups to end up with identical baseline characteristics, similar to a randomized trial. When we examined the all-cause mortality of these two groups, we found that the group with follow-up systolic blood pressure of <120 had a 70% higher mortality.
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Chronic Kidney Disease: Novel variants of APOL1 gene may play a role in susceptibility

MedicalResearch.com Interview with:

Dr. Wen-Ya Ko, Ph.D. Postdoctoral Fellow, First author of the paper  Department of Genetics School of Medicine University of Pennsylvania 426 Clinical Research Building 415 Curie Boulevard Philadelphia, PA 19104-6145Dr. Wen-Ya Ko, Ph.D.
Postdoctoral Fellow, First author of the paper

Department of Genetics
School of Medicine
University of Pennsylvania
426 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104-6145

Dr. Sarah Tishkoff, Ph.D., Senior author of the paper  David and Lyn Silfen University Professor Departments of Genetics and Biology School of Medicine School of Arts and Sciences University of PennsylvaniaDr. Sarah Tishkoff, Ph.D., Senior author of the paper

David and Lyn Silfen University Professor
Departments of Genetics and Biology
School of Medicine
School of Arts and Sciences
University of Pennsylvania

MedicalResearch.com: What are the main findings of the study?



Answer: In humans the APOL1 gene codes for Apolipoprotein L1, a major component of the trypanolytic factor in serum.  The APOL1 gene harbors two risk alleles (G1 and G2) associated with chronic kidney disease (CKD) among individuals of recent African ancestry. We studied APOL1 across genetically and geographically diverse ethnic groups in Africa. We have discovered a number of novel variants at the APOL1 functional domains that are required to lyse trypanosome parasites inside human blood vessels.

We further identified signatures of natural selection influencing the pattern of variation on chromosomes carrying some of these variants. In particular, we have identified a haplotype (a cluster of genetic variants linked along a short region of a chromosome), termed G3, that has evolved adaptively in the Fulani population who have been practicing cattle herding which has been historically documented as early as in the medieval ages (but which could have begun thousands of years earlier).  Many of the novel variants discovered in this study are candidates to play a role conferring protection against trypanosomiasis and/or to play a role in susceptibility of CKD in humans.
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