Polyomavirus exerts detrimental effects on renal function in patients after lung transplantation
Introduction
Chronic kidney disease (CKD) is a common and significant comorbidity in lung transplant recipients. End-stage kidney disease incidence after lung transplantation (LTX) reaches 4–16% [1], [2], [3]. Though in many cases multifactorial, calcineurin inhibitors (CNI) frequently cause nephrotoxicity [3], [4], [5]. Further comorbidities, such as diabetes mellitus (DM) and arterial hypertension (AH), can contribute to renal impairment after LTX [1].
In renal transplant recipients, polyomavirus-associated nephropathy (PyVAN) is a recognized problem and leads to renal function deterioration [6]. JC virus (JCPyV), BK virus (BKPyV), and SV40 are nonenveloped DNA polyomaviruses (PyV). Serological positivity is prevalent among adults [7, 8]. Initial infection is typically acquired during childhood by the oral-fecal or respiratory route and can lead to mild respiratory infections. More than 80% of adults are positive for JCPyV and BKPyV serologically. After infection, they typically persist in the urothelium. Upon immunosuppression, PyV are capable of escaping immunosurveillance, reactivate, and thereby damage the urothelium and cause hemorrhagic cystitis [9] or PyVAN.
Untreated PyVAN in kidney transplant recipients can lead to loss of allograft function and is reported in up to 10% of kidney transplant recipients [6]. However, few earlier studies revealed the occurrence of PyV in non-renal solid organ recipients (NRSOR). Still, none of them showed an association between renal function and PyV load in urine or serum [10], [11], [12], [13].
The presence of JCPyV and BKPyV viruria and DNAemia and the worsening of renal function in patients after LTX with high immunosuppression indicates the occurrence of PyVAN after LTX. Nevertheless, only very few cases confirmed PyVAN by kidney biopsy in NRSOR [14, 15].
This study aims to further assess the role of PyV reactivation in patients after LTX.
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Study cohort and design
The study was performed at the university hospital of Munich (Ludwig-Maximilian University, LMU), southern Germany. Our transplant program performed 251 LTX during the study period (83.6 ± 25.1 transplantations per year, 3-year follow-up, Jan 2017 - Jan 2020). Patients are followed up in our center.
Patients with inadequate or missing sample collection as well as concomitant kidney transplantation (KTX) or other specific causes for kidney failure were excluded from further analysis, as depicted
Study cohort
In total, 104 lung transplant patients were included in the study. Urine and serum samples were collected from all patients at time point 2 (t2: 25.3 months ± 33.2 months) after LTX during the observation period, as shown in Fig. 1b.
Underlying diseases of the study cohort were: ILD (n = 66, 63.5%), COPD (n = 25, 24.0%), CF (n = 8, 7.7%), pH (n = 5, 4.8%). Demographic characteristics of included patients are depicted in Table 1 and supplementary Table S1. Excluded patient characteristics are
Discussion
JCPyV and BKPyV viruria are prevalent in patients after LTX. Both are associated with subsequent kidney function deterioration in our cohort. To our knowledge, this is the first study that shows an association between JCPyV and BKPyV viruria with kidney function deterioration after LTX.
Our results are in line with previous studies where BKPyV viruria was shown in a significant proportion of patients with LTX [10], [11], [12]. However, in these studies, no impact on renal function was detected
Summary
Our data demonstrate that JCPyV and BKPyV are prevalent in lung transplant recipients. Kidney dysfunction and the occurrence of PyV load in patients with high immunosuppression indicate possible presence of PyVAN in lung transplanted patients. Evidence of PyV in urine and serum are associated with adverse effects on renal function, although histologic proof of PyVAN is rare. Our data show that the occurrence of JCPyV in addition to BKPyV in urine after LTX is a risk factor for deterioration of
Declaration of Competing Interest
The authors have no conflict of interest to disclose.
References (34)
Predictors of renal function following lung or heart-lung transplantation
Kidney Int.
(2002)The incidence of renal failure in one hundred consecutive heart-lung transplant recipients
Am. J. Kidney Dis.
(1995)- et al.
Nephrotoxicity of immunosuppressive drugs: long-term consequences and challenges for the future
Am. J. Kidney Dis.
(2000) Does polyomavirus infection induce renal failure in cardiac transplant recipients?
Transplant. Proc.
(2000)BK virus in heart transplant recipients: a prospective study
J. Heart Lung Transplant.
(2011)Nomenclature for kidney function and disease: report of a kidney disease: improving global outcomes (KDIGO) consensus Conference
Kidney Int.,
(2020)- et al.
Definition and classification of kidney diseases
Am. J. Kidney Dis.
(2013) A randomized trial of everolimus-based quadruple therapy vs standard triple therapy early after lung transplantation
Am. J. Transplant.
(2019)Safety and efficacy of steroid pulse therapy for acute loss of FEV1 in lung transplant recipients after exclusion of acute cellular rejection
Transplant Proc
(2020)Renal replacement therapy for diabetic end-stage renal disease: data from 10 registries in Europe (1991-2000)
Kidney Int.
(2005)
BK and JC virus infections in healthy patients compared to kidney transplant recipients in Tunisia
Microb. Pathog.
Renal Function Impairment in Kidney Transplantation: importance of Early BK Virus Detection
Transplant. Proc.
Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction
Am. J. Transplant.
The impact of infection on chronic allograft dysfunction and allograft survival after solid organ transplantation
Am. J. Transplant.
Preemptive therapy for systemic and pulmonary human cytomegalovirus infection in lung transplant recipients
Am. J. Transplant.
Kidney function in cyclosporine-treated paediatric pulmonary transplant recipients
Transplantation
Cyclosporine nephrotoxicity in lung transplant recipients
Transplantation
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These authors contributed equally to this work.