#4295 spectrum of glomerular and vascular kidney pathology associated with myeloproliferative neoplasms

Abstract Background and Aims Myeloproliferative neoplasms (MPN) are chronic blood disorders defined by an overproduction of clonal, differentiated hematopoietic cells. A high prevalence of chronic kidney disease (CKD) is described in patients with MPN. The glomerular histological pattern of MPN-related kidney disease, MPN-related glomerulopathy (MPN-RG), may not account for the entirety of CKD risk in this population, as it appears to be rare and has mostly been reported in patients with myelofibrosis. The inflammatory and prothrombotic state of clonal blood cells has been linked to a systemic vasculopathy in MPN patients, characterized by thromboses and microvascular disease. Thus, we put forward the hypothesis that intrarenal vessel injury may occur during MPN, and that vascular nephrosclerosis may be a common histological pattern in MPN patients presenting with kidney disease. Method We conducted an exhaustive, retrospective, multicenter study of MPN kidney biopsies in four kidney pathology units. All adult patients with a history of MPN who underwent a kidney biopsy were included. We performed a systematic histological review of glomerular and vascular compartments. MPN-RG was defined as mesangial expansion and negative glomerular immunofluorescence studies, with at least one of the following: mesangial hypercellularity, or features of chronic glomerular thrombotic microangiopathy. Hematopoietic cells were detected using anti-glycophorin C, anti-myeloperoxidase, and anti-factor VIII immunohistochemistry (IHC). Chronic vascular lesions were evaluated using the Banff aah and cv lesion definitions and compared to matched adult native kidney biopsies. We used multivariable logistic regression models to assess determinants of vascular lesions, using the number of antihypertensive drugs as a proxy for hypertension severity. Results We included 47 MPN patients who underwent a kidney biopsy, including 16 patients with chronic myeloid leukemia, 14 with polycythemia vera, 10 with essential thrombocythemia and 7 with primary myelofibrosis. 14 cases (29.8%) met our definition of MPN-RG. MPN-RG was strongly associated with myelofibrosis (primary or secondary, P = 0.021) and poorer ESRD-free survival (P = 0.007). Positive IHC for circulating cells in the glomerular capillaries was not associated with glomerular injury but was positively correlated with blood leukocyte count (P = 0.004). Thirty-three patients (75.0%) had moderate-to-severe arteriosclerosis; 39 patients (84.8%) had moderate-to-severe arteriolar hyalinosis. Multivariable models including 188 control kidney biopsies revealed an association between MPN and chronic kidney vascular damage, which was independent of established risk factors such as age, diabetes mellitus and hypertension (Table 1 and Table 2). Conclusion We demonstrate the strong association between MPN-RG and myelofibrosis and confirm its poor renal prognosis. We argue that the finding of glomerular intracapillary hematopoietic cells should not be considered in the diagnosis of MPN-RG. Most notably, our results show that MPN represent a novel, independent risk factor for vascular nephrosclerosis, and establish a new link between MPN and CKD. These findings raise new hypotheses regarding the pathophysiology of vascular nephrosclerosis in the general population.