Does Reduction in Immunosuppression in Viremic Patients Prevent BK Virus Nephropathy in De Novo Renal Transplant Recipients? A Prospective Study

Alméras, Cyrielle; Foulongne, Vincent; Garrigue, Valérie; Szwarc, Ilan; Vetromile, Fernando; Segondy, Michel; Mourad, Georges

doi:10.1097/tp.0b013e31816a33d4

Cited by 102 publications

(94 citation statements)

References 26 publications

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“…The BK polyomavirus has been proven to be one of the major viral complications in renal allografts [Andrews et al, 1988;Randhawa et al, 1999Randhawa et al, , 2005Hirsch and Steiger, 2003]. At present there is no efficient antiviral therapy available and the treatment of reactivated BKV infection is limited to reducing the immunosuppressive regimen [Almeras et al, 2008;Saad et al, 2008]. In about one-quarter to one-third of kidney transplant (KTx) patients, the virus was found in the urine, about 10-15% of BKV-infected patients reveal viremia and about 5% of BKV-infected patients develop BKVassociated nephropathy [Hirsch et al, 2002;Viscount et al, 2007].…”

Section: Introductionmentioning

confidence: 99%

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Krautkrämer

Klein

Sommerer

et al. 2008

Journal of Medical Virology

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The reactivation and replication of the BK polyomavirus (BKV) leading to BKV-associated nephropathy (BKVAN) is one of the major complications in renal transplantation patients. BKV isolates were classified into four subtypes (I-IV) based on genotype variations within the VP1-coding region. The type-specific amino acid differences cluster within the BC-loop of the major capsid protein VP1. As demonstrated in vitro, mutations in this region also play a role in the infectivity, attachment and stability of viral particles. Therefore, we analyzed the prevalence of BC-loop mutations in isolates of kidney transplant patients and compared their viral load in the urine. The VP1 subtyping regions of BKV isolates obtained from urine samples of 45 renal transplant patients were sequenced. The phylogenetic analysis of these sequences revealed that subtype I (66.67%) is the most prevalent genotype. The remaining isolates belong to subtype IV (33.33%). A high frequency of changes to specific amino acids within the BC-loop was identified among the BKV isolates from renal transplant patients. Patients with BKVAN exhibited a higher viral replication than patients without nephropathy. Although titers of isolates of subtype I were higher than titers of subtype IV isolates, the difference did not reach statistical significance. In addition, amino acid changes in the BC-loop did not influence the viral load and the incidence of BKVAN. These in vivo results demonstrate that high replication rates which serve as a predictive marker for BKVAN are not caused by altered receptor binding or affinity via mutated BC-loops.

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Section: Introductionmentioning

confidence: 99%

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Krautkrämer

Klein

Sommerer

et al. 2008

Journal of Medical Virology

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“…Since PyVAN is preceded by BKV-viruria and viremia (4,5), several groups have used BKV-viremia as a surrogate marker of PyVAN to reduce immunosuppression (6)(7)(8)(9)(10). This preemptive approach has emerged as effective and safe to clear BKV-viremia without functional impairment in most cases (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Reducing Immunosuppression Preserves Allograft Function in Presumptive and Definitive Polyomavirus-Associated Nephropathy

Schaub

Hirsch

Dickenmann

et al. 2010

American Journal of Transplantation

220

217

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Early detection of polyomavirus BK (BKV) viremia and reduction of immunosuppression is recommended forBased on subsequent allograft biopsy results and peak BKV-viremia, patients were assigned to three groups: (i) definitive PyVAN (n = 13), (ii) presumptive PyVAN defined by plasma BKV-loads of ≥4 log 10 copies/ml (n = 17) and (iii) low BKV-viremia (n = 8). Clearance of BKV-viremia was achieved in 35/38 patients (92%) and subsequent clinical rejection occurred in 3/35 patients (8.6%), both without any difference among the groups. Patients with definitive Py-VAN had higher peak plasma BKV-loads and required longer time for clearance (8.8 vs. 4.6 vs. 2.9 months; p = 0.001). However, allograft function remained stable from baseline to last follow-up at 34 months (range 18-60) in all three groups with median serum creatinine of 1.6 mg/dl, 1.6 mg/dl and 1.3 mg/dl, respectively. We conclude that screening for BKV-replication and reduction of immunosuppression is an effective strategy to preserve medium-term allograft function even in patients developing definitive PyVAN.

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“…In our studies using BKV VP1 mRNA levels, we found the incidence of BKV replication to be 10% at 1 month, 20% at 3 months, 30% at 6 months which plateaued at 12 month post-transplantation. Similarly other studies identified viruria rates of 19% to 49% within the first year post-transplantation using DNA based assays [9,10]. Hirsch and colleagues detected BKV replication using decoy cells in the urine in 30% of their study population [11].…”

Section: Natural History Of Bkv Replicationmentioning

confidence: 99%

“…In another study of 123 patients, 13 developed viremia in which 2 had evidence of BKVN and the remaining 11 did not. With reduction in immunosuppression, 10 of 11 patients without BKVN had clearance of viremia by median of 5 months follow up [10]. Schaub and colleagues evaluated the impact of a three step protocol for reduction in immunosuppression in patients with viremia, presumptive BKVN and biopsy confirmed BKVN.…”

Section: Preemptive Reduction In Immunosuppressive Therapiesmentioning

confidence: 99%

BK Virus Infection in Renal Allograft Recipients

Dadhania¹

2012

Current Concepts in Kidney Transplantation

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Does Reduction in Immunosuppression in Viremic Patients Prevent BK Virus Nephropathy in De Novo Renal Transplant Recipients? A Prospective Study

Abstract: Reduction of IS is probably an effective therapeutic option to clear viremia and prevent BKVN in viremic renal transplant patients.

Cited by 102 publications

References 26 publications

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Reducing Immunosuppression Preserves Allograft Function in Presumptive and Definitive Polyomavirus-Associated Nephropathy

BK Virus Infection in Renal Allograft Recipients

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