Critical analysis of valganciclovir dosing and renal function on the development of cytomegalovirus infection in kidney transplantation

Salas, Maria Aurora Posadas; Taber, David J.; Chua, Elizabeth L.; Pilch, Nicole A.; Chavin, Kenneth D.; Thomas, Beje

doi:10.1111/tid.12133

Cited by 24 publications

(9 citation statements)

References 12 publications

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“…Renal function was significantly lower in patients developing CMV viraemia (P < 0.001) but was not identified as a risk factor, which is in line with results of another retrospective analysis in CMV high-risk patients [ 9 ] and a post hoc analysis of a randomized trial [ 10 ]. In the latter one, patients never achieving a creatinine clearance >60 mL/min were at greater risk for CMV development [ 10 ].…”

Section: Discussionsupporting

confidence: 80%

“…D+/R− patients were ∼13-times more likely to develop CMV viraemia. Posadas Salas et al [ 10 ] found that ∼50% of patients received the recommended dose, the other half received lower or higher doses than appropriate, which confirms the difficulty of appropriate dosing in renal transplant patients. Given the good results on outcome, with only 4.3% hospitalizations due to CMV infections, the obvious underdosing had no detrimental effects on outcome.…”

Section: Discussionmentioning

confidence: 98%

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High frequency of valganciclovir underdosing for cytomegalovirus prophylaxis after renal transplantation

Rissling

Naik

Brakemeier

et al. 2018

Clinical Kidney Journal

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BackgroundThe correct valganciclovir dose for cytomegalovirus (CMV) prophylaxis depends on renal function estimated by the Cockcroft–Gault (CG) estimated creatinine clearance (CG-CrCl) formula. Patients with delayed or rapidly changing graft function after transplantation (tx) will need dose adjustments.MethodsWe performed a retrospective investigation of valganciclovir dosing in renal transplant patients receiving CMV prophylaxis between August 2003 and August 2011, and analysed valganciclovir dosing, CG-CrCl, CMV viraemia (CMV-PCR <750 copies/mL), leucopenia (<3500/µL) and neutropenia (<1500/µL) in the first year post-transplant. On Days 30 and 60 post-transplant, dosing pattern in relation to estimated creatinine clearance was analysed regarding CMV viraemia, leucopenia and neutropenia.ResultsSix hundred and thirty-five patients received valganciclovir prophylaxis that lasted 129 ± 68 days with a mean dose of 248 ± 152 mg/day of whom 112/635 (17.7%) developed CMV viraemia, 166/635 (26.1%) leucopenia and 48/635 (7.6%) neutropenia. CMV resistance within 1 year post-transplant was detected in three patients. Only 137/609 (22.6%) patients received the recommended dose, while n = 426 (70.3%) were underdosed and n = 43 (7.1%) were overdosed at Day 30 post-tx. Risk factors for CMV viraemia were donor positive D (+)/receptor negative R (−) status and short prophylaxis duration, but not low valganciclovir dose. Risk factors for developing leucopenia were D+/R− status and low renal function. No significant differences in dosing frequency were observed in patients developing neutropenia or not (P = 0.584).ConclusionMost patients do not receive the recommended valganciclovir dose. Despite obvious underdosing in a large proportion of patients, effective prophylaxis was maintained and it was not associated as a risk factor for CMV viraemia or leucopenia.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 98%

High frequency of valganciclovir underdosing for cytomegalovirus prophylaxis after renal transplantation

Rissling

Naik

Brakemeier

et al. 2018

Clinical Kidney Journal

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“…Therefore, patients weighing <65 kg should not be given 1800 mg of VGCV. On the other hand, it was reported that patients weighing >80 kg and with creatinine clearance <60 mL/min were given a subtherapeutic dose of VGCV when adjusted according to their renal function in kidney transplantation . Thus, not only the renal adjustments of VGCV dosing based on estimated creatinine clearance calculated using ideal body weight, but also dosing based on actual body weight exerts a decisive influence on the incidence of AEs of VGCV.…”

Section: Discussionmentioning

confidence: 99%

Occurrence of adverse events caused by valganciclovir as pre‐emptive therapy for cytomegalovirus infection after allogeneic stem cell transplantation is reduced by low‐dose administration

Takahata

Hashino

Nishio

et al. 2015

Transplant Infectious Dis

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Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV.

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“…Use of more potent induction and/or maintenance immunosuppressive agents and routine prophylaxis using oral GCV are thought to contribute to the development of a GCV-resistant CMV strain. In addition, underdosing of GCV when using estimated GFR or using the ideal body weight in the Cockcroft-Gault formula when calculating CrCl in obese patients is likely to result in a subtherapeutic level of GCV [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Use of Leflunomide in Renal Transplant Recipients with Ganciclovir-Resistant/Refractory Cytomegalovirus Infection: A Case Series from the University of Chicago

Chon

Kadambi

et al. 2015

Case Rep Nephrol Dial

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Introduction: Although antiviral prophylaxis for cytomegalovirus (CMV) is widely used, CMV infection remains common in renal transplant recipients with adverse consequences. Methods: We report 5 cases of renal transplant recipients with resistant CMV infection who were successfully managed with leflunomide at the University of Chicago Medical Center. Results: Five renal transplant recipients (2 simultaneous pancreas/kidney transplants, 3 deceased donor kidney transplants) were diagnosed with GCV-resistant CMV infection from 2003 to 2011. Of the 4 patients who had resistance genotype testing, 3 showed a UL97 mutation and 1 patient had a clinically resistant CMV infection. All patients received CMV prophylaxis with valganciclovir for 3 months. The number of days from the date of transplant to viremia ranged from 38 to 458 days (median 219). All 5 patients received other antiviral agents (e.g. ganciclovir, foscarnet), and in 4 patients, viremia was cleared before leflunomide was initiated as consolidation (or maintenance) therapy. Conclusion: Leflunomide was well tolerated and successful in preventing recurrence of viremia in renal transplant recipients with resistant CMV infection. The beneficial effect of leflunomide in this setting warrants further investigation.

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Critical analysis of valganciclovir dosing and renal function on the development of cytomegalovirus infection in kidney transplantation

Cited by 24 publications

References 12 publications

High frequency of valganciclovir underdosing for cytomegalovirus prophylaxis after renal transplantation

High frequency of valganciclovir underdosing for cytomegalovirus prophylaxis after renal transplantation

Occurrence of adverse events caused by valganciclovir as pre‐emptive therapy for cytomegalovirus infection after allogeneic stem cell transplantation is reduced by low‐dose administration

Use of Leflunomide in Renal Transplant Recipients with Ganciclovir-Resistant/Refractory Cytomegalovirus Infection: A Case Series from the University of Chicago

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