Lack of evidence for viral etiology in symptomatic chronic kidney disease of unknown etiology (CKDu) in Sri Lanka

Pushpakumara N, Freund P, Premarathne S, Hewavitharane P, Erandika N, Herath D, Weerakoon T, Wijethunga S, Ratnatunga N, Wazil A, Skopnik CM, Metzke D, Melchert J, Bleicker T, Amann KU, Daniel C, Corman VM, Jones TC, Weiss S, Eckardt KU, Enghard P, Nanayakkara N (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

BMC Nephrology BMC

Book Volume: 26

Article Number: 578

Journal Issue: 1

DOI: 10.1186/s12882-025-04527-z

Abstract

Background: Chronic kidney disease of unknown etiology (CKDu) is a major health problem in Sri Lanka. A transient symptomatic episode, characterized by fever, dysuria, and arthralgias, accompanied by kidney dysfunction, has been reported in endemic areas of CKDu. Sym-CKDu has shown with histological features consistent with acute interstitial nephritis and is considered a potential initiating event of CKDu. Among various potential etiologies, viral infections such as Hantavirus, Cytomegalovirus (CMV), and Epstein-Barr virus (EBV) have been implicated in the causation of CKDu. Methods: Here, we performed a prospective observational cohort study of symptomatic patients presenting with at least three of symptoms - i.e. arthralgia, myalgia, fever, back pain or feeling unwell an outpatient clinic in a CKDu-endemic region of Sri Lanka. Between June 2018 and November 2021, a cohort of 151 patients presenting with a feverish syndrome to an outpatient clinic in a CKDu endemic region in Sri Lanka were included in this study, and 85 patients returned for follow-up. serum creatinine, CRP, cystatin C and dipstick proteinuria were determined. Serum samples (n = 32) were screened for antibodies against known human pathogenic viruses using the VirScanTM-Pipeline. Kidney biopsies (n = 19) were analyzed for the presence of viral pathogens using a PAN-Hanta-PCR and next-generation sequencing (NGS). Results: The prevalence of reduced eGFR at initial presentation was high, especially in men. After a median follow-up of 2.3 years, 16 patients had lost ≥ 4 ml/min/1.73m2 eGFR per year and their eGFR was < 90 ml/min/1.73m2 at the last follow-up. Patients who experienced a loss of eGFR clustered geographically. Virome screening did not identify any antibody reactivity in the group with loss of eGFR. NGS evaluation and Hanta-PCR of 19 kidneys biopsies did not detect viral pathogens. Conclusion: A significant proportion of patients in a CKDu endemic region presenting with a feverish syndrome developed a substantial loss of eGFR over the following years. No evidence of a viral etiology was found. Trial registration: Not applicable.

Authors with CRIS profile

Kerstin Ute Amann Professur für Nephropathologie Christoph Daniel Department of Nephropathology

Involved external institutions

Kandy Teaching Hospital LK Sri Lanka (LK) University of Peradeniya LK Sri Lanka (LK) Charité - Universitätsmedizin Berlin DE Germany (DE)

How to cite

APA:

Pushpakumara, N., Freund, P., Premarathne, S., Hewavitharane, P., Erandika, N., Herath, D.,... Nanayakkara, N. (2025). Lack of evidence for viral etiology in symptomatic chronic kidney disease of unknown etiology (CKDu) in Sri Lanka. BMC Nephrology, 26(1). https://doi.org/10.1186/s12882-025-04527-z

MLA:

Pushpakumara, Nilantha, et al. "Lack of evidence for viral etiology in symptomatic chronic kidney disease of unknown etiology (CKDu) in Sri Lanka." BMC Nephrology 26.1 (2025).

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