Erythrocytosis and CKD: A Review

Erythrocytosis or polycythemia is defined as an increase in red blood cell concentration above the age- and sex-specific normal levels. Unlike anemia that is very common in chronic kidney disease (CKD) patients, erythrocytosis is less frequent but requires specific understanding by healthcare professionals in order to provide the best care. Erythrocytosis, especially when undiagnosed and untreated, can lead to serious thrombotic events and higher mortality. Classical causes of erythrocytosis associated with CKD include cystic kidney diseases, kidney or other erythropoietin-secreting neoplasms, high-altitude renal syndrome, overdosage of erythropoietin-stimulating agents, androgen therapy, heavy smoking, chronic lung disease, obstructive sleep apnea, IgA nephropathy, post-kidney transplant erythrocytosis, renal artery stenosis and congenital etiologies. After ruling out the common acquired causes of erythrocytosis, and/or in the presence of suggestive parameters, primary erythrocytosis or polycythemia vera (PV) should be considered and patients screened for JAK2V617F somatic mutation. The newest entity inducing erythrocytosis is linked to the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors that hypothetically activate hypoxia-inducible factor 2-alpha (HIF-2α), and in some cases unmask PV. This review focusses on the pathogenesis, renal manifestations and management of PV, the pathophysiology of erythrocytosis induced by SGLT2 inhibitors and the relevance of timely JAK2 mutation screening in these patients.