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

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. 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 VirScan TM -Pipeline. Kidney biopsies ( n = 19) were analyzed for the presence of viral pathogens using a PAN-Hanta-PCR and next-generation sequencing (NGS). 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/1.73m 2 eGFR per year and their eGFR was < 90 ml/min/1.73m 2 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. 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. Not applicable.