Abstract: FR-PO1011
Kidney Involvement in Primary Myelofibrosis and Possible Role of the JAK-STAT Pathway
Session Information
- Onco-Nephrology: Basic
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Gil, Miguel, University of Florida, Gainesville, Florida, United States
- Bejjanki, Harini, University of Florida, Gainesville, Florida, United States
- Bozorgmehri, Shahab, University of Florida, Gainesville, Florida, United States
- Sayeski, Peter, University of Florida, Gainesville, Florida, United States
- Mohandas, Rajesh, University of Florida, Gainesville, Florida, United States
Background
Isolated case reports have described a connection between primary myelofibrosis (PMF) and kidney disease. Activation of JAK-STAT pathways, commonly seen in PMF, leads to worsening kidney function in rodent models. Hence, we hypothesized that JAK-STAT activation in PMF may be associated with kidney disease.
Methods
We used the integrated data repository to identify all adult patients with PMF evaluated at an academic hospital between 1/1/2007 and 11/20/2017. We recruited a control group matched for age, sex, and presence or absence of diabetes mellitus. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Paired t-test was used to compare continuous variables and McNemar's test for categorical variables. Change in renal function over time was compared using mixed-effects model. A p-value < 0.05 was considered significant.
Results
Most patients with PMF(n=46) were Caucasian (93%), male (57%) and older (mean age of 66 ± 11 years). 70% had hypertension and 18% diabetes. Cytogenetic analysis showed more than half had a Jak2 mutation (67%). There were no differences in baseline renal function or prevalence of CKD between patients with PMF and matched controls. Proteinuria on dipstick was more common in PMF than controls (50 % vs. 18%, p=0.03). Patients with PMF and Jak 2 mutation were more likely to have proteinuria at baseline (73%) compared without Jak 2 mutations (22%) or controls (18%) Overall p<0.005. A mixed effects model showed no changes in eGFR over time. However, patients with PMF had higher blood urea nitrogen (BUN) levels at follow-up than matched controls (22±9 vs. 18±12 mg/dl, p=0.001) and a significant increase in BUN (3.3±9.8 vs. 0.5±8.2 mg/dl, p=0.03) from baseline.
Conclusion
Patients with PMF were more likely to have proteinuria, higher BUN at follow-up and a significant increase in BUN compared to controls matched for age, gender, and diabetes. Proteinuria was more likely in those with Jak2 mutations. Our results suggest that PMF is associated with kidney dysfunction and highlights the need for more thorough assessment of renal function in these patients. Identifying the molecular basis of these clinical observations could help improve outcomes in PMF and give us novel insights into the pathogenesis of kidney disease.