Polyomavirus exerts detrimental effects on renal function in patients after lung transplantation

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Highlights

Abstract

Introduction

Chronic kidney disease (CKD) is associated with significant morbidity and mortality after lung transplantation (LTX). Calcineurin inhibitor (CNI) nephrotoxicity is the leading cause of CKD. After kidney transplantation, polyomavirus-associated nephropathy (PyVAN) is a well-recognized problem. This study aims to evaluate the role of polyomavirus in patients after LTX.

Methods

From January 2017 to January 2020, all lung transplant recipients who performed follow-up visits in our center were included in the study and retrospectively assessed. We measured renal function (creatinine levels before and after transplantation), JCPyV, and BKPyV load by polymerase chain reaction (PCR) in serum and urine samples after transplantation.

Results

In total, 104 consecutive patients (59 males, 56.7%) with a mean age of 49.6 ± 11.1 years were identified. JCPyV was found in urine of 36 patients (34.6%) and serum of 3 patients (2.9%). BKPyV was found in urine of 40 patients (38.5%) and serum of 4 patients (3.8%), respectively. Urine evidence for JCPyV (p < 0.001, coefficient: +21.44) and BKPyV (p < 0.001, coefficient: +29.65) correlated highly with further kidney function decline.

Conclusion

Kidney function deterioration is associated with JCPyV and BKPyV viruria in patients after LTX. This might indicate a role of PyVAN in lung transplant recipients.

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.

Section snippets

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.

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    These authors contributed equally to this work.

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