Investigators - Clinical/Translational - mehrotra

Rajnish Mehrotra, MD

Project 1: Comparative Effectiveness of Dialysis Modalities

Even though maintenance dialysis is a life-saving therapy, it imposes significant burden of treatment on individuals with end-stage renal disease. This burden differs by dialysis modality and hence, each has a substantial, but different, effect on patients’ lifestyles. Moreover, care innovations have led to a significantly more diverse ways to deliver maintenance dialysis such as nocturnal in-center hemodialysis, frequent diurnal in-center hemodialysis, or frequent home hemodialysis. In order to inform patient and providers to make an informed decision about selection of dialysis therapies, this project is leveraging data from a large dialysis provider of over 150,000 dialysis patients newly diagnosed to have end-stage renal disease between 2007-2011 to study the comparative effectiveness of the newer dialysis modalities with conventional therapies (thrice-weekly in-center hemodialysis and peritoneal dialysis). A large variety of outcomes are being examined and include all-cause mortality, racial disparities, hospitalizations, anemia management, blood pressure control, and mineral metabolism. In order to account for the non-random allocation of patients to dialysis modalities, as is the case in clinical practice, this project will uses causal inference modeling to account for baseline and time-varying differences in patient- and facility-level characteristics to generate valid estimates of outcomes attributable to each dialysis modality. The importance of this project is highlighted by the fact that it is the only kidney-disease related topic listed by the Institute of Medicine among the top 100 national priorities for comparative effectiveness research in the United States.  

Project 2: Biological Determinants of Peritoneal Dialysis

The success of peritoneal dialysis to generate sufficient ultrafiltration and maintain fluid balance in patients with end-stage renal disease treated with this modality depends upon the peritoneal solute transfer rate.  There is an over two-fold variability in peritoneal solute transfer rate in patients starting treatment with peritoneal dialysis and most of the variability cannot be explained by demographic, or clinical differences between individuals. Moreover, in a significant fraction of patients exposed to conventional peritoneal dialysis solutions, the peritoneal solute transfer rate changes over time and most of the variability in this change over time also cannot be predicted. There is preliminary evidence to suggest that common genetic variants account for a significant fraction in variability in both the baseline and subsequent change in peritoneal solute transfer rate over time. This is the central hypothesis being tested in this project and will be tested by collecting genotypic and phenotypic data from up to 5000 subjects four different cohorts from around the world: (1) PDOPPS is a prospective multicenter international cohort study of patients undergoing peritoneal dialysis in five different countries in the world; in this current project, bio-samples will be collected and longitudinal measurement of ultrafiltration capacity performed in about 2400 subjects enrolled in the United States, Canada, and the United Kingdom; (2) PD-CRAFT is a prospective longitudinal observational cohort study in the United Kingdom that will enroll 1600 subjects; 1200 of these individuals have already been enrolled; (3) collaborative relationship with investigators in Europe will provide bio-samples for up to 800 subjects from Belgium, Netherlands, Spain, and the United Kingdom, and (4) up to 200 subjects enrolled in the bio-repository at the Kidney Research Institute. This project will not only identify the common genetic variants associated with peritoneal function but has the potential to enhance our understanding of vascular biology and neo-angiogenesis.   

Project 2: TODD Trial

Hemodialysis (HD) patients have a high burden of disease and treatment; this is compounded by a very high prevalence of comorbid depression that is strongly and independently associated with poor patient-reported outcomes and difficulty in adherence with complex treatment regiments. Yet many HD patients with comorbid depression are reluctant to accept the diagnosis and/or treatment for the condition.

Successful completion of this study, developed in partnership with patients, caregivers, and numerous stakeholders, will generate the first high-level evidence on the ability of the healthcare team to engage HD patients in the treatment of comorbid depression and the comparative efficacy of the two most common treatment options considered by patients with the condition. Each of these two treatments can also be readily integrated into current models for care delivery for HD patients, further enhancing the significance of our proposal.

Current Funding

R01 DK095668 (Mehrotra, PI)
NIH/NIDDK
Comparative Effectiveness of Dialysis Modalities

R01 DK099165 (Mehrotra, PI)
NIH/NIDDK
Biological Determinants of Peritoneal Dialysis

U01 DK082179 (Himmelfarb, PI)
NIH/NIDDK
Vascular Structure and Function in Arterio-venous Fistula Maturation

U01 DK099923 (Ikizler/Himmelfarb, PI)
NIH/NIDDK
Anti-Inflammatory Interventions in Maintenance Hemodialysis Patients

R21 AG047036 (Molnar, PI)
Comparative Effectiveness of Home Hemodialysis versus Kidney Transplant

Past Funding

K23 RR018298 (Mehrotra, PI)
NIH (7/1/08-6/30/10)
Cardiovascular Disease and Diabetic Nephropathy
The major goals of this project were to explore the association between chronic kidney disease and acuity of coronary heart disease.

UCSF Department of Medicine Cohort Award
University of California San Francisco (1/1/13-12/31/14)
Comprehensive Pediatric and Adult Kidney Transplant Cohort
The major goals of this project are to establish a biorepository and clinical database of all adult and pediatric kidney transplant recipients at UCSF Medical Center. (Relinquished on departure from UCSF.)

Publications

PubMed provides a list of Dr. Mehrotra's research publications

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