Early Ultrastructural Changes in Biopsies From Patients With Symptomatic CKD of Uncertain Etiology

Christoph Daniel; Philipp Enghard; Neelakanthi Ratnatunga; Sulochana Wijetunge; A W M Wazil; Christian Zwiener; Johannes A C Barth; Rohana Chandrajith; Monika Klewer; Kai-Uwe Eckhardt; Kerstin Amann; Paul Freund; Shakila Premarathne; W D R N Pushpakumara; Nishantha Nanayakkara

doi:10.1016/j.ekir.2022.12.022

Early Ultrastructural Changes in Biopsies From Patients With Symptomatic CKD of Uncertain Etiology

Kidney Int Rep. 2022 Dec 31;8(3):642-657. doi: 10.1016/j.ekir.2022.12.022. eCollection 2023 Mar.

Authors

Affiliations

¹ Department of Nephropathology, Institute of Pathology, Friedrich-Alexander Universität, Erlangen-Nuremberg, Erlangen, Germany.
² Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany.
³ Department of Pathology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
⁴ Nephrology and Kidney Transplant Unit, National Hospital, Kandy, Sri Lanka.
⁵ Environmental Analytical Chemistry, Department of Geosciences, Eberhard-Karls-University Tübingen, Tübingen, Germany.
⁶ Department of Geography and Geosciences, Friedrich-Alexander-Universtiät Erlangen-Nuremberg, GeoZentrum Nordbayern, Erlangen, Germany.
⁷ Department of Geology, Faculty of Science, University of Peradeniya, Peradeniya, Sri Lanka.
⁸ Center for Research, National Hospital Kandy, Kandy, Sri Lanka.

Abstract

Introduction: Although the investigation of chronic kidney disease of uncertain etiology (CKDu) has identified many possible influencing factors in recent years, the exact pathomechanism of this disease remains unclear.

Methods: In this study, we collected 13 renal biopsies from patients with symptomatic CKDu (Sym-CKDu) from Sri Lanka with well-documented clinical and socioeconomic factors. We performed light microscopy and electron microscopic evaluation for ultrastructural analysis, which was compared with 100 biopsies from German patients with 20 different kidney diseases.

Results: Of the 13 Sri Lankan patients, 12 were men (92.3%), frequently employed in agriculture (50%), and experienced symptoms such as feeling feverish (83.3%), dysuria (83.3%), and arthralgia (66.6%). Light microscopic evaluation using activity and chronicity score revealed that cases represented early stages of CKDu except for 2 biopsies, which showed additional signs of diabetes. Most glomeruli showed only mild changes, such as podocyte foot process effacement on electron microscopy. We found a spectrum of early tubulointerstitial changes including partial loss of brush border in proximal tubules, detachment of tubular cells, enlarged vacuoles, and mitochondrial swelling associated with loss of cristae and dysmorphic lysosomes with electron-dense aggregates. None of these changes occurred exclusively in Sym-CKDu; however, they were significantly more frequent in these cases than in the control cohort.

Conclusion: In conclusion, our findings confirm the predominant and early alterations of tubular structure in CKDu that can occur without significant glomerular changes. The ultrastructural changes do not provide concrete evidence of the cause of CKDu but were significantly more frequent in Sym-CKDu than in the controls.

Keywords: chronic kidney disease of uncertain etiology (CKDu); lysosomal alteration; mitochondrial swelling; renal biopsy; transmission electron microscopy; tubular injury.