Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka
S. H. Nandana P. Gunawickrama,
A. Rajith N. Silva,
P. G. Chandra L. Nanayakkara,
K. B. Suneetha Gunawickrama,
J. M. Kithsiri B. Jayasekara,
Naduviladath V. Chandrasekharan
Affiliations
S. H. Nandana P. Gunawickrama
Institute for Combinatorial Advance Research and Education, General Sir John Kotelawala Defence University, Ratmalana 10390, Sri Lanka
A. Rajith N. Silva
Department of Basic Sciences, Faculty of Allied Health Sciences, General Sir John Kotelawala Defence University, Boralesgamuwa 10290, Sri Lanka
P. G. Chandra L. Nanayakkara
Department of Anatomy, Faculty of Medicine, University of Ruhuna, Galle 80000, Sri Lanka
K. B. Suneetha Gunawickrama
Department of Zoology, Faculty of Science, University of Ruhuna, Matara 81000, Sri Lanka
J. M. Kithsiri B. Jayasekara
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, General Sir John Kotelawala Defence University, Boralesgamuwa 10290, Sri Lanka
Naduviladath V. Chandrasekharan
Department of Chemistry, Faculty of Science, University of Colombo, Colombo 00300, Sri Lanka
Chronic kidney disease of unknown etiology was investigated for metal relations in an endemic area by a cross-sectional study with CKD stages G1, G2, G3a, G3b, G4, G5 (ESRD), and endemic and nonendemic controls (EC and NEC) as groups. Subjects with the medical diagnosis were classified into groups by eGFR (SCr, CKD-EPI) and UACR of the study. It determined 24 metals/metalloids in plasma (ICPMS) and metallothionein (MT) mRNA in blood (RT-PCR). MT1A at G3b and MT2A throughout G2–G5 showed increased transcription compared to NEC (ANOVA, p p p p < 0.05) in EC as compared to NEC. Declining eGFR or CKD progression increased the burden of Be, Mg, Al, V, Co, Ni, Rb, Cs, Ba, Mn, Zn, Sr, Σ hMT-inducers, and Σ MT-binding metals in plasma, suggesting an MT role in the disease. MT1A/2A mRNA followed UACR (PCA, Dendrogram: similarity, 57.7%). The study provides evidence that proteinuric chronic renal failure may increase plasma metal levels where blood MT2A could be a marker.
