Hypotheses (published) on

the aetiology of CKDu in Sri Lanka

Sachie Panawala

Ministry of Science Technology and Research

China-Sri Lanka Collaborative Grant Research Project – Conference 15 March 2016

Galle Face Hotel, Colombo

22 May 2015 – Workshop on an Action Plan to prevent CKDuMinistry of Special Projects

VI on Health and Well-being

What led to formation of hypotheses for CKDu

Histopathological evidence

Insult of kidneys with one or more toxins

20062007

2009

2008

2011

2013

First detection – mid 1990’s

2012

2014

Timeline of development hypotheses

Development of a case definition for CKDu SL

2015

Local Institutes that proposed hypotheses on CKDu

1. University of Peradeniya2. Rajarata University of Sri Lanka3. Ministry of Health4. University of Kelaniya5. University of Sri Jayawardenepura6. University of Colombo7. World Health Organization8. IWMI9. NWSDB

2006

Organophosphates - RJ Peiris-John, JKP Wanigasuriya, AR Wickremasinghe, WP Dissanayake and A Hittarage. Exposure to acetylcholinesterase-inhibiting pesticides and chronic renal failure (2006). Ceylon Medical Journal Vol. 51, No. 1

Pesticides and Fertilizers

2007

Use of ayurvedic medicines - Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R, Hittarage A. Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease.Transactions of the Royal Society of Tropical Medicine and Hygiene 2007; 101: 1013-7.

2007

genetic predisposition- Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R, Hittarage A. Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease.Transactions of the Royal Society of Tropical Medicine and Hygiene 2007; 101: 1013-7.

2007

drinking well water - Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R, Hittarage A. Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease.Transactions of the Royal Society of Tropical Medicine and Hygiene 2007; 101: 1013-7.

2007

snakebites - Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R, Hittarage A. Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease.Transactions of the Royal Society of Tropical Medicine and Hygiene 2007; 101: 1013-7.

2007

fungal toxins (OA) - Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R, Hittarage A. Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease.Transactions of the Royal Society of Tropical Medicine and Hygiene 2007; 101: 1013-7.

2007

bacterial toxins - Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R, Hittarage A. Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease.Transactions of the Royal Society of Tropical Medicine and Hygiene 2007; 101: 1013-7.

2008

Cadmium - J. M. R. S. Bandara , D. M. A. N. Senevirathna, D. M. R. S. B. Dasanayake, V. Herath, J. M. R. P. Bandara, T. Abeysekara, K. H. Rajapaksha (2008) Chronic renal failure among farm families in cascade irrigation systems in Sri Lanka associated with elevated dietary cadmium levels in rice and freshwater fish (tilapia).Geochem Envron & Health 30:3465–78

2009

Fluoride and Aluminium - Illeperuma OA, Dharmagunawardhane HA, HerathKRP (2009) Dissolution of aluminium from substandard utensils under high fluoride stress: A possible risk factor for chronic renal failures in the North- Central province. Journal of the National Science Foundation of Sri Lanka 37:219–222

2011

drinking water in the field - Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R. (2011)Chronic kidney disease of unknown aetiology in Sri Lanka: is cadmium a likely cause?BMC Nephrology 2011; 12: 32-8.

2011

smoking Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R. Chronic kidney disease of unknown aetiology in Sri Lanka: is cadmium a likely cause?BMC Nephrology 2011; 12: 32-8.

being treated for hypertension -

Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R. Chronic kidney disease of unknown aetiology in Sri Lanka: is cadmium a likely cause?BMC Nephrology 2011; 12: 32-8.

2011

cyanobacterial toxins-

Dissananyake DM, Jayasekera JMKB, RatnayakeP, Wickramasinghe W and Radella YA (2011) The Short Term Effect of Cyanobacterial Toxin Extracts on Mice KidneyProceedings of the Peradeniya University Research Sessions, Sri Lanka, Vol. 16, November 2011

2012

prolonged exposure of the kidney to many ionicspecies

Jayasekera, J., Dissnayake DM, Ratnayake P, Wikramasinghe, W, Radella, YA, Palugaswewa, WB. (2012) The effects from concentrated water on reservoirs of high prevalence areas on CKD of unknown origin in Sri Lanka. - In: Proceedings of the Research Symposium on Chronic Kidney Disease of Unknown Aetiology (CKDu), Sri Lanka Medical Association, Colombo, 11 March 2012 (https://issuu.com/slmanews/docs/ckdu_abstract_book)

2012

Exposure to sun, heat stress and dehydration

Dissananayake DM, Jayasekera JMKB, Wimalasiri R, Ratnayake I, Dissanayake S (2012)Renal tubular functions of farmers of high prevalence area for CKDuIn: Proceedings of the Research Symposium on Chronic Kidney Disease of Unknown Aetiology (CKDu), Sri Lanka Medical Association, Colombo, 11 March 2012 (https://issuu.com/slmanews/docs/ckdu_abstract_book)

2012

Chemical Nephrotoxicity aggravated by Arsenic, Heavy metals

Dahanayake KS, Wijewardahana KMRC , Jayasumana MACS, Paranagama P (2012) Presence of high levels of arsenic in internal organs of deceased patients with chronic kidney disease of unknown aetiology (CKDu): three case reports.In: Proceedings of the Research Symposium on Chronic Kidney Disease of Unknown Aetiology (CKDu), Sri Lanka Medical Association, Colombo, 11 March 2012 (https://issuu.com/slmanews/docs/ckdu_abstract_book)

2012

Chemical Nephrotoxicity aggravated by Arsenic, Heavy metals

Fonseka SI , Jayalath K, Amarasinghe M,Mahamithawa AMP, Senanayake VK,Paranagama PA (2012)Hardness and presence of arsenic in aquifers of selected CKDu prevalent and other areas in Sri LankaIn: Proceedings of the Research Symposium on Chronic Kidney Disease of Unknown Aetiology (CKDu), Sri Lanka Medical Association, Colombo, 11 March 2012 (https://issuu.com/slmanews/docs/ckdu_abstract_book)

2012

drinking reservoir water

Jayasekera JMKB, Dissananyake DM,Ratnayake P, Wickramasinghe W,Radella YA, Palugaswewa WBEffect of concentrated water from reservoirs of high prevalence area for CKD of unknown origin in Sri Lanka on miceIn: Proceedings of the Research Symposium on Chronic Kidney Disease of Unknown Aetiology (CKDu), Sri Lanka Medical Association, Colombo, 11 March 2012 (https://issuu.com/slmanews/docs/ckdu_abstract_book)

2012

Multifactoralorigin

Kamani Wanigasuriya (2012) Aetiological factors of Chronic Kidney Disease in the North Central Provinceof Sri Lanka: A review of evidence to-dateJournal of the College of Community Physicians of Sri Lanka Volume 17, No. 01

2013

Chemical Nephrotoxicity aggravated by Chronic repeated dehydration. Responsible chemicals are Arsenic, Heavy metals, Herbicides

(dehydration + heavy metals)

M.A.C.S.Jayasumana, P.A.Paranagama, M.D. Amarasinghe, K.M.R.C.Wijewardane, K.S.Dahanayake, S.I.Fonseka, K.D.L.M.P.Rajakaruna, A.M.P.Mahamithawa,U.D.Samarasinghe,V.K.Senanayake (2013) Possible link of Chronic arsenic toxicity with Chronic Kidney Disease of unknown etiology in Sri Lanka Journal of Natural Sciences Research www.iiste.orgISSN 2224-3186 (Paper) ISSN 2225-0921 (Online) Vol.3, No.1, 2013

2013

As and Cd(more emphasis on Cd)

Nihal Jayatilake, Shanthi Mendis, PalithaMaheepala, Firdosi R Mehta and On behalf of the CKDu National Research Project Team Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing countryBMC Nephrology 2013, 14:180

2013

Low selenium or other micronutrients in the diet

Nihal Jayatilake, Shanthi Mendis, PalithaMaheepala, Firdosi R Mehta and On behalf of the CKDu National Research Project Team Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing countryBMC Nephrology 2013, 14:180

2014

Maternal malnutrition

Myles F. Elledge, Jennifer HoponickRedmon, Keith E. Levine, Rajitha J. Wickremasinghe, Kamani P. Wanigasariya, and Roshini J. Peiris-John. (2014). Chronic Kidney Disease of Unknown Etiology in Sri Lanka: Quest for Understanding and Global Implications. RTI Press Publication No. RB-0007-1405Research Triangle Park, NC: RTI Press.(https://www.rti.org/pubs/rb-0007-1405-elledge.pdf)

2014

Use of NSAIDs Myles F. Elledge, Jennifer HoponickRedmon, Keith E. Levine, Rajitha J. Wickremasinghe, Kamani P. Wanigasariya, and Roshini J. Peiris-John. (2014). Chronic Kidney Disease of Unknown Etiology in Sri Lanka: Quest for Understanding and Global Implications. RTI Press Publication No. RB-0007-1405Research Triangle Park, NC: RTI Press.(https://www.rti.org/pubs/rb-0007-1405-elledge.pdf)

2014

low calcium intake

Myles F. Elledge, Jennifer HoponickRedmon, Keith E. Levine, Rajitha J. Wickremasinghe, Kamani P. Wanigasariya, and Roshini J. Peiris-John. (2014). Chronic Kidney Disease of Unknown Etiology in Sri Lanka: Quest for Understanding and Global Implications. RTI Press Publication No. RB-0007-1405Research Triangle Park, NC: RTI Press.(https://www.rti.org/pubs/rb-0007-1405-elledge.pdf)

2014

chronic undernutrition

Myles F. Elledge, Jennifer HoponickRedmon, Keith E. Levine, Rajitha J. Wickremasinghe, Kamani P. Wanigasariya, and Roshini J. Peiris-John. (2014). Chronic Kidney Disease of Unknown Etiology in Sri Lanka: Quest for Understanding and Global Implications. RTI Press Publication No. RB-0007-1405Research Triangle Park, NC: RTI Press.(https://www.rti.org/pubs/rb-0007-1405-elledge.pdf)

low BMI

2014

Glyphosate, Hard Water and Nephrotoxic Metals

Jayasumana, Channa; Gunatilake, Sarathand Senanayake, Priyantha (2014). Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka?Int J Environ Res Public Health. 2014 Feb; 11(2): 2125–2147.

2014

Oxidative stress Sayanthooran, S., Magana-Arachchi, D.N., Sooriyapathirana, S.D.S.S, Abeysekera, T. and Gunarathne, L. (2014). Oxidative stress markers in chronic kidney disease: gene expression analysis in a Sri Lankan population. In: Proceedings of the second International Symposium on Driving Research Towards Economy: Opportunities and Challenges, Peradeniya, 13-14th November 2014- 31

2015

Landscape hydrogeology

Manthrithilake, Herath (2015) CKDu : Are we shooting the right target? Proceedings: Importance of Groundwater Monitoring in Sri Lanka, 17 July 2015, Colombo(Along with Panabokke, C.R.)

Other Hypotheses Not Yet Published

1. Uranium2. UV irradiation3. Hanta Viral infection 4. Leptospirosis (silent spp)