Post-transplant erythrocytosis refractory to ACE inhibitors and angiotensin receptor blockers

Abstract

Post-transplant erythrocytosis (PTE) is a condition with elevated haematocrit (hct) in renal allograft recipients. The mainstay of treatment is ACE inhibitors (ACEi) or angiotensin II receptor blockers (ARB), but seldom phlebotomy. PTE must be recognised early to prevent major thromboembolic events. We present a case of PTE that was refractory to blockade of renin-angiotensin system (RAS) by ACEi and ARB and required phlebotomy for control of hct. Our review of medical literature about prevalence and pathophysiology of PTE suggests that approximately 22% of patients with PTE are refractory to ACEi/ARB treatment. There are four plausible pathways that appear to play a role in causing PTE: disruption of erythropoietin regulation, mitogenic effect of the RAS on erythroid lineage, insulin-like growth factor 1 and androgenic stimulation. Presently, there is no unifying hypothesis involving these factors, but refractoriness to ACEi/ARB may represent a distinct subcategory of PTE.

Risk factors and outcomes of post‐transplant erythrocytosis among adult kidney transplant recipients: a systematic review and meta‐analysis

“…Post-transplant erythrocytosis (PTE) is defined by the Kidney Disease Improving Global Outcomes (KDIGO) 2009 as hemoglobin (Hgb) >17 g/dl or a hematoctrit (Hct) >51% for both males and females [1]. The rising of Hct must be persistent over a period of 3 to 6 months and independent of other pathological conditions, such as polycythemia vera, tumors associated with increased erythropoetin (EPO), hypoxia, chronic obstructive pulmonary disease, and obstructive sleep apnea [2,3]. PTE is one of the more common post-transplant hematologic complications which affect 8-26% of kidney transplant (KT) recipients [4].…”

“…PTE is one of the more common post-transplant hematologic complications which affect 8-26% of kidney transplant (KT) recipients [4]. The prevalence varies from study to study because of the different levels of Hct used for diagnosis, length persistence of disease, and gender variation of Hct cut-off values [2,5]. Although the cause has remained unclear, several risk factors have been linked to this complication, and the symptoms are similar to other forms of erythrocytosis, including headache, dizziness, fatigue, dizziness, and malaise [5,6].…”

“…Spontaneous remission occurs in less than 25% of the patients within 2 years from the onset, with a median time of 13 months [2,4,5]. Thus, early detection and prompt management are necessary.…”

“…Persistence of the condition causes worsening kidney function because of chronic rejection, which required treatment with angiotensin converting enzymes (ACEI) and angiotensin II receptor blockers (ARB) or phelbotomy [5] with a goal of maintaining Hct below 51% [1]. Several studies have reported thromboembolic events, such as stroke, pulmonary embolism, thrombosis of digital or brachial arteries, and cardiovascular disease, as a sequela of PTE because of an increased blood viscosity [2,5]. However, outcome of PTE is controversial and is also an aim of this study.…”

“…Thirty-nine studies from July 1982 to January 2021 were included (7,099 KT recipients). The following factors were associated with PTE development: male gender (pooled RR = 1.62 [1.38, 1.91], I 2 = 39%), deceased-donor KT (pooled RR = 1.18 [1.03, 1.35], I 2 = 32%), history of smoking (pooled RR = 1.36 [1.11, 1.67], I 2 = 13%), underlying polycystic kidney disease (PKD) (pooled RR=1.56 [1.21,2.01], I 2 =44%), and pretransplant dialysis (pooled RR=1.6 [1.02, 2.51], I 2 =46%). However, PTE was not associated with outcomes of interest, including overall mortality, death-censored graft failure, and thromboembolism.…”