Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

Abstract

Drug-induced hematological cytopenia is common in kidney transplantation. Various cytopenia including leucopenia (neutropenia), thrombocytopenia, and anemia can occur in kidney transplant recipients. Persistent severe leucopenia or neutropenia can lead to opportunistic infections of various etiologies. On the contrary, reducing or stopping immunosuppressive medications in these events can provoke a rejection. Transplant clinicians are often faced with the delicate dilemma of balancing cytopenia and rejection from adjustments of immunosuppressive regimen. Differentials of drug-induced cytopenia are wide. Identification of culprit medication and subsequent modification is also challenging. In this review, we will discuss individual drug implicated in causing cytopenia and correlate it with corresponding literature evidence.

Q134R: Small chemical compound with NFAT inhibitory properties improves behavioral performance and synapse function in mouse models of amyloid pathology

“…Although CNIs often show benefits in rodent models of AD‐like pathology when given acutely (over a few days, or weeks), chronic treatment with these drugs (e.g., over months or years) causes systemic immunosuppression in otherwise healthy subjects, characterized, in part, by a drop in lymphocyte counts and other white blood cell changes (Gallo et al, 2006; Khalil et al, 2018; Koprak et al, 1996). Chronic lymphopenia could offset possible neurologic benefits achieved by long‐term CN inhibition.…”

“…As a potential therapeutic strategy for managing neurodegenerative disorders, it is notable that Q134R had no apparent direct effects on CN activity in vitro or in vivo , suggesting that Q134R acts downstream of CN activation. These observations suggest that Q134R could be used to target key CN‐mediated deleterious processes without triggering many of the adverse effects commonly ascribed to commercial CN inhibitors (Farouk & Rein, 2020; Khalil et al, 2018) (see additional discussion below).…”

“…At the endpoint, one brain hemisphere was formalin-fixed for immunolabeling, while the other hemisphere from some mice was used for the preparation of in situ brain slices for hippocampal electrophysiology (Figure 6). (Gallo et al, 2006;Khalil et al, 2018;Koprak et al, 1996). Of the peripheral cell types that were assessed during treatment, only red blood cells showed a significant change over time (~16% reduction with Q134R over 3 months).…”

“…A noted limitation of CN inhibitors (CNIs) for treating neurologic disorders is the risk of numerous and major adverse effects, which can include renal‐ and neuro‐dysfunction, as well as progressive lymphopenia (Farouk & Rein, 2020; Khalil et al, 2018). Although CN inhibitor toxicity is less likely to occur at “maintenance” doses commonly used in human solid organ transplant patients, the concerns raised suggest that alternative CN‐related targets may provide a safer approach for clinical applications beyond allograft transplant cases and autoimmune disorders.…”

The Living-Related Kidney Transplant Program in Brunei Darussalam: Lessons Learnt from a Nascent National Program in a Small, Muslim, and Asian Country

“…To maintain self-sufficiency and governance, we have an active research unit that had churned out several review articles on transplantation between 2017 and 2019. is was to enable the team to acquaint themselves with transplant literature and keep abreast with the latest transplant developments. Review articles have been published on aspirin usage in kidney transplants [27], hematological cytopenia in kidney transplants [28], use of fluoroquinolone in BK virus nephropathy [29], cigarette smoking in kidney transplants [30], and dual kidney transplantations [31]. Another recent local-driven study in 2017 showed that lack of donors (71%), lack of awareness of the program (21.2%), and unwillingness to take risks (26.5%) were the main barriers to the progress of the program [32].…”