High human cytomegalovirus DNAemia early post-transplantation associates with irreversible and progressive loss of renal function - a retrospective study

Abstract

Transplant recipients are prone to viral infections, which could affect renal transplantation outcome. Our aim was to assess the effects of early human cytomegalovirus (CMV) DNAemia on transplant renal function. A total of 264 (age 50.9 ± 13.5; male 55%) renal transplantation recipients undergoing preemptive anti-CMV therapy were retrospectively categorized based on early (<3 months post-Tx) CMV peak viral load (PVL); PVL ≤ 536, PVL536-6310, or PVL > 6310 International Units/ml (IU/ml). Estimated glomerular filtration rate (eGFR) was analyzed between 1 and 36 months post-transplantation with Kruskal-Wallis test, linear regression, and a linear mixed-effects model. CMV infection was detectable in 113 (43%) recipients within 49 [38-67] days. Subjects with PVL > 6310 had statistically significant ~5-13 ml/min lower eGFR between 3 and 36 months compared to PVL ≤ 536 and PVL536-6310. eGFR declined from 46.1 to 40.7 ml/min/1.73 m (-12%) over 3 years, and the annual decrease for pronounced infection with high PVL was 2.0 ml/min/1.73 m faster than for noninfected or mildly infected subjects. In conclusion, high CMV DNAemia early after renal transplantation was associated with significant loss of renal function, from which subjects did not recover. The severity of infection (high PVL early post-transplantation), more than the infection per se, was related to irreversible and progressive loss of renal function.

Epidemiology, risk factors, and outcomes associated with cytomegalovirus in adult kidney transplant recipients: A systematic literature review of real‐world evidence

“…An additional eight studies meeting inclusion criteria were identified from the manual review of bibliographies of published SLRs. Ultimately, 86 5,6,14‐97 citations representing 81 unique studies 5,6,14‐92 including 69 803 participants met the inclusion criteria.…”

Less renal allograft fibrosis with valganciclovir prophylaxis for cytomegalovirus compared to high-dose valacyclovir: a parallel group, open-label, randomized controlled trial

“…Management of infectious diseases is a critical component of care of solid organ transplant recipients. Both cytomegalovirus (CMV) disease and asymptomatic CMV replication results in increased mortality and graft loss rates [ 1 – 5 ]. These impacts are driven mainly by the cellular and immunological effects of CMV including alloimmune response upregulation by innate immune mechanisms and/or cross-reactivity of CMV-specific T cells with donor MHC-peptide complexes [ 1 , 6 – 9 ].…”

Standard ganciclovir dosing results in slow decline of cytomegalovirus viral loads

“…The CMV viral load was measured in plasma, using a previously described method. 28 Briefly, 190 μL of clinical sample was collected and nucleic acids were extracted using the MagNA Pure LC Total Nucleic Acid Isolation Kit (Roche Diagnostics, Mannheim, Germany). An in-house CMV PCR (LLOQ 536 IU/mL) was prepared using the 2X TaqMan Universal Mastermix (Life Technologies, Carlsbad, CA, USA) and performed on an Applied Biosystems 7500 (Life Technologies).…”