Contributions
Abstract: S159
Type: Oral Presentation
Session title: Population based studies in myeloid disorders
Background
The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are acquired stem-cell diseases. The molecular basis for MPNs includes the JAK2V617F, CALR -and MPL-mutations. MPNs evolve from clonal hematopoiesis of indeterminate potential (CHIP), which is characterized by an age-dependent acquisition of mutations. In recent years, chronic inflammation has been increasingly recognized as an important pathogenetic mechanism for MPN development – which may even in the CHIP phase be important for clonal evolution and development of comorbidities. Several studies have described a progressive reduction in estimated glomerular filtration rate (eGFR) among MPN patients, hence termed MPN-related nephropathy. However, no studies have focused upon the impact of CHIP mutations on eGFR.
Aims
We investigated the association between CHIP mutations and elevated blood counts on eGFR in a Danish general population study.
Methods
In total, 19,958 participants were included from the General Suburban Population Study, with 645 (3.2%) participants being positive for either the JAK2V617F (N=613) or CALR (N=32) mutation. All participants with MPN or other hematological malignancy at baseline were excluded from the analysis. eGFR (mL/min pr. 1.73m2) was calculated by the EPI-CKD formula using plasma-creatinine levels and adjusted for age and gender as recommended for use. Neutrophil/lymphocyte – ratio (NLR) and thrombocyte/lymphocyte– ratio (PLR) were calculated as proxies for chronic inflammation. A composite binary variable for cytosis was calculated, including hemoglobin concentration, hematocrit, erythrocyte, thrombocyte, leukocyte, neutrophil, eosinophil, basophil, and lymphocyte cell counts adjusted for gender. We assessed the impact of CHIP (JAK2V617F or CALR) on eGFR using inverse-probability weighting (IPW) regression analysis to estimate potential outcome mean (95%CI) differences. The IPW regression was adjusted for age, gender, blood pressure, BMI, smoking status, ischemic heart disease, NLR, and PLR.
Results
Using IPW-regression analysis, CHIP (JAK2V617F & CALR) had an adjusted mean (95%CI) difference in eGFR of -0.3 (-1.5 - -0.86), p=0.6 with a -0.39% (-1.8% - 1%) reduction in eGFR compared with non-mutated participants. JAK2V617F positive individuals had an adjusted mean(95%CI) difference in eGFR of -0.2 (-1.4 - -0.1), p=0.7 with a -0.2 % (-1.6% - 1.1%) reduction in eGFR compared with non-mutated participants. CALR positive individuals, had an adjusted mean(95%CI) difference in eGFR of -9 (-13.7 - -4.3), p <0.0001 with a -10.3% (-15.6% - -4.9%) reduction in eGFR compared with non-mutated participants. Cytosis in the general population was associated with an adjusted mean(95%CI) difference in eGFR of -0.5 (-0.9 - -0.04), p=0.03 with a -0.5% (-1% - -0.04%) reduction in eGFR compared with participants with no cytosis. CHIP participants had a significantly elevated NLR and PLR compared to non-mutated participants with a mean (95%CI) difference of 0.1 (0.03 – 0.17), p=0.008 and 9.8 (5.6 – 13.7), p=3.8x10-6, respectively. NLR was negatively associated with eGFR among CHIP individuals with coefficient (95%CI) -2.2 (-3,6 - -0.78), adjusted R2=0.04, p=0.002).
Conclusion
This study shows that CHIP CALR-mutations in a general population study associate with a significant reduction in eGFR as a proxy for renal function. Furthermore, cytosis is associated with a significant decrease in eGFR. Chronic inflammation and MPN-associated mutations may contribute to a decrease in eGFR even in the very early stage of MPN-development.
Keyword(s): Epidemiology, Mutation status, Myeloproliferative disorder, Renal
Abstract: S159
Type: Oral Presentation
Session title: Population based studies in myeloid disorders
Background
The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are acquired stem-cell diseases. The molecular basis for MPNs includes the JAK2V617F, CALR -and MPL-mutations. MPNs evolve from clonal hematopoiesis of indeterminate potential (CHIP), which is characterized by an age-dependent acquisition of mutations. In recent years, chronic inflammation has been increasingly recognized as an important pathogenetic mechanism for MPN development – which may even in the CHIP phase be important for clonal evolution and development of comorbidities. Several studies have described a progressive reduction in estimated glomerular filtration rate (eGFR) among MPN patients, hence termed MPN-related nephropathy. However, no studies have focused upon the impact of CHIP mutations on eGFR.
Aims
We investigated the association between CHIP mutations and elevated blood counts on eGFR in a Danish general population study.
Methods
In total, 19,958 participants were included from the General Suburban Population Study, with 645 (3.2%) participants being positive for either the JAK2V617F (N=613) or CALR (N=32) mutation. All participants with MPN or other hematological malignancy at baseline were excluded from the analysis. eGFR (mL/min pr. 1.73m2) was calculated by the EPI-CKD formula using plasma-creatinine levels and adjusted for age and gender as recommended for use. Neutrophil/lymphocyte – ratio (NLR) and thrombocyte/lymphocyte– ratio (PLR) were calculated as proxies for chronic inflammation. A composite binary variable for cytosis was calculated, including hemoglobin concentration, hematocrit, erythrocyte, thrombocyte, leukocyte, neutrophil, eosinophil, basophil, and lymphocyte cell counts adjusted for gender. We assessed the impact of CHIP (JAK2V617F or CALR) on eGFR using inverse-probability weighting (IPW) regression analysis to estimate potential outcome mean (95%CI) differences. The IPW regression was adjusted for age, gender, blood pressure, BMI, smoking status, ischemic heart disease, NLR, and PLR.
Results
Using IPW-regression analysis, CHIP (JAK2V617F & CALR) had an adjusted mean (95%CI) difference in eGFR of -0.3 (-1.5 - -0.86), p=0.6 with a -0.39% (-1.8% - 1%) reduction in eGFR compared with non-mutated participants. JAK2V617F positive individuals had an adjusted mean(95%CI) difference in eGFR of -0.2 (-1.4 - -0.1), p=0.7 with a -0.2 % (-1.6% - 1.1%) reduction in eGFR compared with non-mutated participants. CALR positive individuals, had an adjusted mean(95%CI) difference in eGFR of -9 (-13.7 - -4.3), p <0.0001 with a -10.3% (-15.6% - -4.9%) reduction in eGFR compared with non-mutated participants. Cytosis in the general population was associated with an adjusted mean(95%CI) difference in eGFR of -0.5 (-0.9 - -0.04), p=0.03 with a -0.5% (-1% - -0.04%) reduction in eGFR compared with participants with no cytosis. CHIP participants had a significantly elevated NLR and PLR compared to non-mutated participants with a mean (95%CI) difference of 0.1 (0.03 – 0.17), p=0.008 and 9.8 (5.6 – 13.7), p=3.8x10-6, respectively. NLR was negatively associated with eGFR among CHIP individuals with coefficient (95%CI) -2.2 (-3,6 - -0.78), adjusted R2=0.04, p=0.002).
Conclusion
This study shows that CHIP CALR-mutations in a general population study associate with a significant reduction in eGFR as a proxy for renal function. Furthermore, cytosis is associated with a significant decrease in eGFR. Chronic inflammation and MPN-associated mutations may contribute to a decrease in eGFR even in the very early stage of MPN-development.
Keyword(s): Epidemiology, Mutation status, Myeloproliferative disorder, Renal