Lack of evidence for viral etiology in symptomatic chronic kidney disease of unknown etiology (CKDu) in Sri Lanka
Nilantha Pushpakumara1,2 , Paul Freund3,4, Shakila Premarathne1,2 , Pasan Hewavitharane1,2 , Naduni Erandika1,2 , Dulanjali Herath1,2 , Thilini Weerakoon1,2, Sulochana Wijethunga5 , Neelakanthi Ratnatunga5 , Abdul Wazil2 , Christopher M. Skopnik3,4, Diana Metzke3,4, Julia Melchert6,7, Tobias Bleicker6,7, Kerstin Amman8 , Christoph Daniel8 , Victor M. Corman6,7, Terry C. Jones6,7, Sabrina Weiss6,9, Kai-Uwe Eckardt3 , Philipp Enghard3,4 and Nishantha Nanayakkara1,2
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.
Keywords
Chronic Kidney Disease of Unknown Etiology (CKDu), Symptomatic CKDu (Sym-CKDu), Virus infections, Feverish syndrome, Virome screening, Serum creatinine, eGFR (estimated glomerular filtration rate)
