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Background <p>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.</p> Methods <p>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 (<i>n</i> = 32) were screened for antibodies against known human pathogenic viruses using the VirScan<sup>TM</sup>-Pipeline. Kidney biopsies (<i>n</i> = 19) were analyzed for the presence of viral pathogens using a PAN-Hanta-PCR and next-generation sequencing (NGS).</p> Results <p>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&#xa0;ml/min/1.73m<sup>2</sup> eGFR per year and their eGFR was &lt; 90&#xa0;ml/min/1.73m<sup>2</sup> 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.</p> Conclusion <p>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.</p> Trial registration <p>Not applicable.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年10月22日

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  • Nilantha Pushpakumara,
  • Paul Freund,
  • Shakila Premarathne,
  • Pasan Hewavitharane,
  • Naduni Erandika,
  • Dulanjali Herath,
  • Thilini Weerakoon,
  • Sulochana Wijethunga,
  • Neelakanthi Ratnatunga,
  • Abdul Wazil,
  • Christopher M. Skopnik,
  • Diana Metzke,
  • Julia Melchert,
  • Tobias Bleicker,
  • Kerstin Amman,
  • Christoph Daniel,
  • Victor M. Corman,
  • Terry C. Jones,
  • Sabrina Weiss,
  • Kai-Uwe Eckardt,
  • Philipp Enghard,
  • Nishantha Nanayakkara

摘要

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.