Renal post-mortem findings in myeloproliferative and myelodysplastic/myeloproliferative neoplasms

Abstract

Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematological disorders presenting with an increased proliferation in one or several hematological cell lines. Renal manifestations of MPN have not been fully characterized so far. To morphologically assess the potential renal involvement in MPN patients, we analyzed histomorphological findings of a post-mortem cohort (n = 57) with a disease history of Philadelphia-negative MPN including polycythaemia vera, primary myelofibrosis, essential thrombocythemia, or chronic myelomonocytic leukemia (CMML). Seven (12.2%) patients presented with a pattern of diffuse glomerulosclerosis not attributable to diabetic or hypertensive nephropathy. Weak C4d staining suggestive for chronic thrombotic microangiopathy (TMA) was observed in 4/7 cases. Glomerulonephritis was excluded by light microscopy and immunohistochemistry. Patients with a pattern of diffuse glomerulosclerosis did not differ from the rest of the cohort regarding MPN subtype, disease duration, age, or sex. No significant proteinuria had been observed before death. Further findings attributed to MPNs were extramedullary hematopoiesis (n = 5; 8.8%) and tumor involvement in advanced disease (n = 4; 7.0%). Other common findings included arteriolosclerosis (n = 18; 31.6%) and signs of shock (n = 8; 14.0%). To our knowledge, this study is so far the largest investigating renal findings in MPN patients. There may be a causal relationship between idiopathic diffuse glomerular sclerosis and MPN, although its clinical significance and pathophysiology remain uncertain with TMA probably being relevant in a subgroup of cases. Our findings demonstrate the spectrum of renal findings in MPN from early to terminal disease of which hematologists should be aware of in daily clinical practice.

Clonal haematopoiesis of indeterminate potential and impaired kidney function—A Danish general population study with 11 years follow‐up

“…Renal biopsies were not available to investigate the prevalence of histopathological characteristics associated with MPN-related glomerulopathy. [23][24][25] Although, the CHIP definition in some studies is defined as the absence of haematological malignancy with a VAF larger than 2%, 6 we defined CHIP as the absence of haematological malignancy with the presence of the somatic mutations JAK2V617F…”

“…Finally, the longitudinal eGFR study were real‐life heterogeneous data with more measurements in hospitalised patients than in non‐hospitalised patients and with different indications of eGFR measurements during follow‐up. Renal biopsies were not available to investigate the prevalence of histopathological characteristics associated with MPN‐related glomerulopathy 23–25 . Although, the CHIP definition in some studies is defined as the absence of haematological malignancy with a VAF larger than 2%, 6 we defined CHIP as the absence of haematological malignancy with the presence of the somatic mutations JAK2V617F and CALR , irrespective of the VAF for two main reasons: first, the VAF cut‐off of 2% is arbitrary reflecting analytical capabilities across different platforms.…”

“…Renal biopsies were not available to investigate the prevalence of histopathological characteristics associated with MPN‐related glomerulopathy. 23 , 24 , 25 Although, the CHIP definition in some studies is defined as the absence of haematological malignancy with a VAF larger than 2%, 6 we defined CHIP as the absence of haematological malignancy with the presence of the somatic mutations JAK2V617F and CALR , irrespective of the VAF for two main reasons: first, the VAF cut‐off of 2% is arbitrary reflecting analytical capabilities across different platforms. Second, little is known about the clinical impact of clones <2%.…”

“…In addition, in patients with MPN, moderate to severe chronic kidney disease (CKD) is associated with thrombosis, 19,20 disease severity 20 and reduced survival 21 . CKD in MPN may be caused by an underlying glomerulonephritis 22 such as focal segmental glomerulosclerosis, mesangial sclerosis and hypercellularity and renal interstitial extramedullary haematopoiesis 23–25 . Clonal myelopoiesis has just recently been associated with CKD in the UK Biobank using whole exome sequencing but without measurement of CALR mutations 26 .…”

“… 21 CKD in MPN may be caused by an underlying glomerulonephritis 22 such as focal segmental glomerulosclerosis, mesangial sclerosis and hypercellularity and renal interstitial extramedullary haematopoiesis. 23 , 24 , 25 Clonal myelopoiesis has just recently been associated with CKD in the UK Biobank using whole exome sequencing but without measurement of CALR mutations. 26 Although only supported by a single case‐report, CALR may be associated with MPN nephropathy, 23 as calreticulin is involved in fibrosis.…”