Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in 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 b...
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MDPI AG
2022-06-01
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| author | 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 |
| author_facet | 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 |
| author_sort | S. H. Nandana P. Gunawickrama |
| collection | DOAJ |
| description | 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, <i>p</i> < 0.01). Both MT1A and MT2A remained metal-responsive as associations emerged between MT2A and human MT inducer Cr (in EC: r = 0.54, <i>p</i> < 0.05, n = 14), and between MT1A and MT2A (in EC pooled with G1–G5: r = 0.58, <i>p</i> < 0.001, n = 110). Human MT (hMT)-inducers, namely Zn, Cu, As, Pb, and Ni; Σ hMT-inducers; 14 more non-inducer metals; and Σ MT-binding metals remained higher (<i>p</i> < 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. |
| first_indexed | 2024-03-09T23:59:08Z |
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| last_indexed | 2024-03-09T23:59:08Z |
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| spelling | doaj.art-34b32c2be8334d5185cb956304b4b3722023-11-23T16:19:39ZengMDPI AGDiseases2079-97212022-06-011023410.3390/diseases10020034Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri LankaS. H. Nandana P. Gunawickrama0A. Rajith N. Silva1P. G. Chandra L. Nanayakkara2K. B. Suneetha Gunawickrama3J. M. Kithsiri B. Jayasekara4Naduviladath V. Chandrasekharan5Institute for Combinatorial Advance Research and Education, General Sir John Kotelawala Defence University, Ratmalana 10390, Sri LankaDepartment of Basic Sciences, Faculty of Allied Health Sciences, General Sir John Kotelawala Defence University, Boralesgamuwa 10290, Sri LankaDepartment of Anatomy, Faculty of Medicine, University of Ruhuna, Galle 80000, Sri LankaDepartment of Zoology, Faculty of Science, University of Ruhuna, Matara 81000, Sri LankaDepartment of Medical Laboratory Sciences, Faculty of Allied Health Sciences, General Sir John Kotelawala Defence University, Boralesgamuwa 10290, Sri LankaDepartment of Chemistry, Faculty of Science, University of Colombo, Colombo 00300, Sri LankaChronic 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, <i>p</i> < 0.01). Both MT1A and MT2A remained metal-responsive as associations emerged between MT2A and human MT inducer Cr (in EC: r = 0.54, <i>p</i> < 0.05, n = 14), and between MT1A and MT2A (in EC pooled with G1–G5: r = 0.58, <i>p</i> < 0.001, n = 110). Human MT (hMT)-inducers, namely Zn, Cu, As, Pb, and Ni; Σ hMT-inducers; 14 more non-inducer metals; and Σ MT-binding metals remained higher (<i>p</i> < 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.https://www.mdpi.com/2079-9721/10/2/34chronic kidney disease of unknown etiology (CKDu) in Sri LankaCKDproteinuriaeGFRUACRmetallothionein 1A |
| spellingShingle | 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 Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka Diseases chronic kidney disease of unknown etiology (CKDu) in Sri Lanka CKD proteinuria eGFR UACR metallothionein 1A |
| title | Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka |
| title_full | Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka |
| title_fullStr | Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka |
| title_full_unstemmed | Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka |
| title_short | Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka |
| title_sort | metals and metallothionein expression in relation to progression of chronic kidney disease of unknown etiology ckdu in sri lanka |
| topic | chronic kidney disease of unknown etiology (CKDu) in Sri Lanka CKD proteinuria eGFR UACR metallothionein 1A |
| url | https://www.mdpi.com/2079-9721/10/2/34 |
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