Dr. Sharanya Ramesh
Supervisor(s): Sofia Ahmed, Lesley Inker
Award: KRESCENT Post-Doctoral Fellowship
Institution: Tufts Medical Center, Boston, MA
Year: 2025-2027
Project Title: Revisiting GFR Equations: Role of Sex and Sex Hormones in Kidney Function
Topic(s): Chronic Kidney Disease, Clinical research
Biography
Dr. Sharanya Ramesh, MD PhD, is a postdoctoral research fellow at Tufts Medical Center. She completed her MD/PhD at the University of Calgary, where she developed a research program to study the role of sex hormones in cardiovascular risk in chronic kidney disease. She completed her internal medicine residency at the University of Toronto and returned to Calgary for her clinical fellowship in nephrology. Her research is driven by an interest in sex-based physiological differences. At Tufts Medical Center, under the mentorship of Dr. Lesley Inker, a leading expert in glomerular filtration rate (GFR) estimation, and Dr. Sofia Ahmed, a world-renowned expert in sex and gender research, Dr. Ramesh is exploring the interplay between sex hormones and GFR estimating equations. Beyond GFR methodology, Dr. Ramesh’s broader research interests include the intersection of healthy aging, menopause, and the risk factors contributing to the onset and progression of kidney disease, as well as outcomes in CKD.
Lay Summary
Why One Size Doesn’t Fit All: Sex Differences in Kidney Function
Background: In Canada, one in ten people have kidney disease. Kidney disease is related to high rates of death and disability with large costs to the healthcare system. Interestingly, women are more likely to have kidney disease compared to men however, they are less likely to progress to kidney failure. The reasons for these differences are not well understood. Differences between men and women in accuracy of the tests used to diagnose kidney disease or differences in how kidney disease progresses based between the sexes. Kidney disease is diagnosed using a measure called glomerular filtration rate or GFR. GFR is a measure of how well the kidneys filter blood and is calculated using a blood test called creatinine. Creatinine is a marker of GFR but is also affected by factors that are not related to kidney function, such as muscle mass and can be affected by sex hormones (estrogen and testosterone). Sex hormones differ between men and women and change with aging (menopause) and health conditions like obesity, diabetes, or polycystic ovarian syndrome (PCOS). As these non-GFR factors differ between men and women, creatinine levels differ between men and women. To account for such differences a GFR value is derived from a formula that accounts for factors (such as age or sex) that cause the differences in creatinine not related to kidney function. The value of GFR that is derived from this formula is therefore an estimate and can be prone to errors and many different formulae have been published to estimated GFR. GFR is used widely in medical practice- it is used to diagnose kidney disease, determine appropriate doses of medications such as antibiotics or chemotherapy, and to make decisions on what treatment should be used for kidney disease. Inaccuracies in GFR can lead to inappropriate diagnosis, giving lower (less effective) or higher (more toxic) doses of medication, or misuse of healthcare resources and patient time.
Purpose: Although we know that there are differences in kidney disease in men and women, whether these differences are due to the tests we use to diagnose kidney disease is poorly understood. In particular, the role of sex hormones (estrogen and testosterone) in creatinine levels and GFR estimation has not been studied. Additionally, whether the accuracy of the GFR formula is different in younger versus older men and women individuals.
Methods: My study will address these knowledge gap through three different projects. 1. I will start by reviewing published studies of equations that estimate GFR and determine the way they account for sex differences in these equations. Understanding the way these equations account for sex and how it differs across different equations may shed some light on the drivers of differences in GFR estimation between men and women. 2. I will analyze the accuracy of GFR estimation based on age and sex (younger versus older men and women) and explore the relationship between sex hormones (estrogen and testosterone) and GFR estimation. 3. I will investigate the relationship between creatinine and sex hormones in men and women based on age and menopausal status.
Anticipated outcomes: We hope to identify instances in which GFR estimation is not accurate and identify additional blood tests that might make kidney function estimation more accurate in these groups. Patient engagement: We will involve patient partners in all aspects of this research including data analyses and presentations to ensure lived experiences are taken into consideration.
Conclusion and relevance to the community: Medical knowledge has been historically derived from studies conducted predominantly in men and is foundational for clinical care. However, we are uncovering substantial biological and clinical differences based on sex that can be overlooked by the “one-size-fits-all” approach in medicine. This can lead to significant errors in diagnosis, management and resource allocation. A prominent example is heart disease, where landmark studies conducted in men have led to misdiagnosis and suboptimal treatment when applied to women. These consequences may extend to kidney disease. Investing in women’s health research is a scientific necessity and an economic opportunity as recent analyses suggest that doubling such investments could yield a return of up to 174,000% in investments. This proposal aims to bridge key knowledge gaps in kidney care and sex differences.