Early ultrastructural changes in biopsies from patients with symptomatic CKDu (Sym-CKDu)

Christoph Daniel, Prof.1 ; Philipp Enghard, PD2 ; Neelakanthi Ratnatunga, Prof.3  ; Sulochana Wijetunge, Prof. 3 ; Wazil AWM, MD7 ; Christian Zwiener, Prof. 4 ; Johannes A.C. Barth, Prof.5 ; Rohana Chandrajith, Prof.6 ; Monika Klewer1 ; Kai-Uwe Eckhardt, Prof.2 , Kerstin Amann, Prof.1 ; Paul Freund, MD2 , Shakila Premarathne8 , W.D.R.N. Pushpakumara, MD8 , Nishantha Nanayakkara, MD7* 

1 Institute of Pathology, Department of Nephropathology, Friedrich-Alexander Universität (FAU) Erlangen-Nuremberg Krankenhausstr. 8-10, 91054 Erlangen, Germany.

2 Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany.

3 Department of Pathology, Faculty of Medicine, University of Peradeniya, Sri Lanka.

4 Environmental Analytical Chemistry, Department of Geosciences, Eberhard-Karls- University Tübingen, Schnarrenbergstr. 94-96, D-72076 Tübingen, Germany.

5 Department of Geography and Geosciences, Friedrich-Alexander-Universtiät Erlangen- Nuremberg (FAU), GeoZentrum Nordbayern, Schlossgarten 5, 91054 Erlangen, Germany.

6 Department of Geology, Faculty of Science, University of Peradeniya, Sri Lanka.

7 Nephrology and Kidney Transplant Unit, National Hospital, Kandy, Sri Lanka.

8 Centre for Research, National Hospital Kandy, Sri Lanka.




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.



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 to 100 biopsies from German patients with 20 different kidney diseases.



Of the Sri Lankan patients, most were men (12/13), frequently employed in agriculture (50%), and showed symptoms such as feverish feeling (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 two biopsies which showed additional signs of diabetes. Most glomeruli showed only mild changes, such as podocyte foot process effacement on EM. 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.



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 compared to the controls.


Keywords: CKDu, ultrastructure, kidney, lysosomal alteration, mitochondrial swelling


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