Tacrolimus dose reduction as an effective therapeutic approach to the patients with active BK virus replication and nephrotoxicity
Karel Krejčí1, Tomáš Tichý2, Pavel Sauer3, Josef Zadražil1, Ester Kurašová1, Jakub Štěpán1, Kamil Žamboch1, Jiří Orság1, František Mrázek4.
13rd Department of Internal Medicine - Nephrology, Rheumatology and Endocrinology, University Hospital and Faculty of Medicine UP Olomouc, Olomouc, Czech Republic; 2Department of Clinical and Molecular Pathology, University Hospital and Faculty of Medicine UP Olomouc, Olomouc, Czech Republic; 3Department of Microbiology, University Hospital and Faculty of Medicine UP Olomouc, Olomouc, Czech Republic; 4Department of Immunology, University Hospital and Faculty of Medicine UP Olomouc, Olomouc, Czech Republic
Background: BK viral nephropathy (BKVN) affects a significant proportion of kidney grafts in the early post-transplant period and often leads to functional failure of these grafts. The intensity of immunosuppressive therapy plays a significant role in the activation of BK viral (BKV) replication.
Methods: 457 per-protocol biopsies of kidney grafts were performed in a group of 161 newly transplanted patients. The incidence of histological signs of tacrolimus nephrotoxicity as a manifestation of excessive immunosuppression was calculated using the Calcineurin Inhibitor Nephrotoxicity Score (CINS). In case of detection of simultaneous toxicity and substantial BKV replication, the dose of tacrolimus and/or mycophenolate was reduced and the effect on the inhibition of BKV activation and regression of toxic changes were compared. In parallel, we studied the effect of pre-emptive reduction of tacrolimus dose on the development of BKV replication in isolated detections of toxicity during the subsequent period.
Results: The reduction of tacrolimus and mycophenolate dose in patients with histological evidence of toxicity and significant BKV replication was associated with an early and significant decrease in the BKV plasma load compared to isolated mycophenolate reduction (P = 0.023), significant decrease in CINS (P = 0.001) and better functional parameters at the end of this one-year follow-up (P = 0.024). A pre-emptive dose reduction of tacrolimus in case of toxicity evidence led to a marked reduction in the incidence of substantial BKV viremia during the subsequent period.
Conclusions: The reduction of tacrolimus and mycophenolate dose in patients with histologically verified tacrolimus nephrotoxicity represents a more effective approach to attenuate significant BKV replication than a single-dose reduction of mycophenolate, including the regression of toxic changes. Pre-emptive tacrolimus dose reduction in case of toxicity signs is associated with a lower incidence of significant BKV replication during the first year after transplantation, without increasing the risk of acute rejection.
Supported by MH CZ – DRO (FNOl, 00098892) and by grant IGA_LF_2022_03.
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