Chronic kidney disease (CKD) is a common, debilitating public health issue, affecting 38 million adults in the U.S. CKD is associated with many adverse outcomes and has been associated with a higher risk of hospitalization for infection, as well as increased mortality from infection. The risk factors that lead patients with CKD to be at increased risk for infection are unknown. In patients with end stage renal disease on dialysis, metabolic acidosis leads to impaired neutrophil function, and secondary hyperparathyroidism leads to impaired phagocytosis. The etiology of CKD may affect risk for infection as patients with diabetes have an increased risk for infection compared to the general population. No longitudinal studies have investigated modifiable risk factors for infection among patients with CKD. We therefore propose to highlight potential causal associations between acid-base status, secondary hyperparathyroidism, etiology of CKD and risk for infection requiring hospitalization among patients with CKD.
In Aims 1 a and 1b we will conduct a cohort study to examine the association between acid-base status as well as secondary hyperparathyroidism and incidence of infection requiring hospitalization among patients with CKD. We will focus on four infections: pneumonia, urinary tract infection, bacteremia, and cellulitis. We will utilize the Partners Research Patient Data Registry (RPDR), a central data warehouse with ~ 40,000 patients with an eGFR <60 mL/min/1.73m2 between 2010 to present. Information on relevant covariates is also available in the RPDR. We will use outpatient serum bicarbonate and parathyroid hormone (PTH) levels divided into categories to compare the risk of infection requiring hospitalization.
In Aim 1 a we hypothesize that patients with CKD with lower serum bicarbonate levels will have an increased incidence of infection requiring hospitalization and in Aim 1b we hypothesize that patients with CKD with higher PTH levels will have an increased incidence of infection requiring hospitalization.
In Aim 2 we will examine the association between etiology of CKD, established by renal biopsy or imaging, and incidence of infection requiring hospitalization among patients with CKD. We will utilize a cohort of ~1,400 patients in the RPDR database over a planned eleven-year study period who have undergone renal biopsy. We hypothesize that patients with CKD and diabetic nephropathy will have an independently higher risk of infection requiring hospitalization than patients with CKD from hypertension or polycystic kidney disease. Collectively, these studies could have a major impact on how we screen, manage, and treat patients with CKD who have factors that could change their risk profile for infection requiring hospitalization.
Chronic kidney disease (CKD) is a growing, major public health issue affecting 38 million adults in the U.S. which has recently been associated with a higher risk for hospitalization for infection as well as increased mortality from infection; however, the risk factors that lead patients with CKD to be at increased risk for infection are unknown. In this proposal, we will longitudinally examine whether acid-base status, secondary hyperparathyroidism, and etiology of CKD affect risk for infection requiring hospitalization among patients with CKD. Collectively, these studies could have a major impact on how we screen, manage, and treat patients with CKD who have factors that could change their risk profile for infection requiring hospitalization.
