ABSTRACT
Influenza and pneumococcal infections occurring in individuals with glomerular disease are preventable
contributors to excess healthcare utilization, morbidity, and mortality, and occur at a rate approximately 30 times
higher among individuals with glomerular diseases compared to the general US population. Vaccination is a
powerful and cost-effective method to reduce infectious burden, however, vaccine immunogenicity and
effectiveness have not been adequately studied in this high-risk patient population. Vaccination may not yield
protective or sustained immune responses in individuals with glomerular disease as a result of exposure to
immunosuppressive medications, altered immune cell function, and urinary loss of immunoglobulin and
complement factors. As a result, there remain pressing questions regarding whether these antibodies confer in-
vivo protection from influenza and pneumococcal infection. Evidence gaps that need to be addressed in
preparation for pragmatic trials focused on infection-prevention measures in this population include frequency of
administration of recommended vaccines, pervasiveness of infectious complications, and rates of influenza and
pneumococcal vaccine seroconversion and seroprotection. Prior studies have been limited by small sample size,
insufficiently characterized cohorts, and the use of assays that measure non-opsonic, and thus potentially non-
functional, antibodies.
The objective of this proposal is to describe the association of influenza and pneumococcal vaccination with
influenza and pneumococcal infections and describe functional vaccine immunogenicity in patients with
glomerular disease. Three projects have been proposed to achieve this objective: an analysis of influenza and
pneumococcal vaccine use and effectiveness in a nationwide healthcare claims database (MarketScan®), a
study examining vaccine immunogenicity in the multicenter NIDDK-sponsored Cure Glomerulonephropathy
(CureGN) study, and creation of a multicenter cohort to examine 23-valent pneumococcal vaccine
immunogenicity in children with nephrotic syndrome. The primary hypothesis is that, independent of kidney
function, rates of influenza and pneumococcal infection and suboptimal vaccine response will be higher in
individuals with active glomerular disease, greater immunosuppression exposure, greater proteinuria, and
younger age. Dr. Glenn’s career development goals include gaining advanced training in statistical methods and
epidemiologic study design, with a focus on the analysis of longitudinal datasets, healthcare claims data, and
multicenter vaccine immunogenicity studies. Dr. Glenn will receive mentorship from Dr. Amy Mottl and Dr. Ronald
Falk, both experts in the field of glomerular kidney disease. Additionally, Dr. Glenn will have a scientific advisory
committee comprised of experts in vaccine immunogenicity, infectious disease, healthcare claims data analysis,
and epidemiology. This work will inform the development of an R01 application in which Dr. Glenn leads a
pragmatic trial investigating pneumococcal vaccination strategies among children with nephrotic syndrome.