Geoenvironmental factors related to

Chronic Kidney Disease of uncertain

aetiology in Sri Lanka

Professor Rohana Chandrajith Professor in Geology

University of Peradeniya rohanac@pdn.ac.lk

Geology may appear remote from human

health.

Rocks are the fundamental building blocks of

the Earth’s surface, full of important minerals

/chemical elements.

Rocks are broken down by weathering

processes to form the soils on which crops and

animals are raised.

Drinking water travels through rocks and soils

as part of the water cycle.

GRADE OF GEOLOGICAL MATERIALS? TOTAL (the “in situ” grade of an element)

BIOAVAILABLE

(fraction available for assimilation by live organisms)

ABSOLUTELY BIOAVAILABLE (fraction actually assimalable by a specific living organism)

TOTAL INITIAL CONTENT

BIOAVAILABLE ABSOLUTELY BIOAVAILABLE

NOT BIOAVAILABLE NOT ASSIMILABLE FOR A

SPECIFIC ORGANISM

But most importantly ….

CKDu Distribution

Geology & Geomorphology

DRY ZONE

Low Rain Fall & Strong Drought Periods

High Amount of TDS in the Groundwater

>85% Depend on the Dug wells & Tube wells

Hydrogeochemistry Health

Water Sources- Anuradhapura District

Lapegue, J., (2001). Chemical risks associated to the consumption of groundwater: The specificity of chronic renal failure in eastern areas of Sri Lanka. Technical report of Action Contre la Faim.

“The areas chosen for study were Gomarankadawela, Kebitigollewa and Padaviya-Siripura. Among the suspected causes linked to the geochemistry of the groundwater were (a) Sulphides and pH (deep and shallow groundwater), (b) Pb (deep and shallow water), (c) Cd (only in deep water). Even though no direct cause for the CRF could be identified, the combination of high rates of sulphide and acidic conditions needs to be more thoroughly investigated”.

(Lapegue, 2001)

CKDu- HISTORICAL BACKGROUND

Chronic Kidney Disease in Sri Lanka

Fluoride

Pesticides

Lead

Al/F association

Cadmium

Arsenic

EnvironmentEnvironment

suspected nephrotoxic environmental factors

Natural (geological)

Anthropogenic Algal toxins

According to the WRB data, 45% of

wells exceed the WHO maximum

permissible level of 1.5 mg/L.

CKD Regions CKD Regions CKD Regions

Almost all identified CKD areas falls into the high fluoride zone.

Our Studies……….

Measured with ICP-MS

Types of Samples

•Drinking water

•Soil (paddy, garden, forest)

•Tank sediments

•Rice

•Rhizome-vegetables growing in aquatic environments

HW- Huruluwewa; NK- Nikawewa; GK- Giradurukotte (n=45x3)

Summary statistics for Na/Ca ratio values in endemic and non-endemic CKDu regions.

Na/Ca Giradurukotte Nikawewa Medawachchiya Padaviya Huruluwewa Wellawaya

endemic endemic endemic endemic nonendemic nonendemic

min 0.1 0.2 0.2 0.1 10.0 14.8

max 18.9 42.4 2.9 7.8 207.6 2300

median 1.14 3.37 1.62 1.96 13.33 188

mean 3.3 6.6 1.6 2.3 33.6 469.1

SD 4.3 8.1 0.9 2.0 48.3 21.4

Table 2: Cd and other heavy metals in rice (in mg/kg dry wt.) collected from different regions of Sri

Lanka (NWP-North Western Province; UP-Uva Province; NCP-North Central Province; CP- Central

Province; WP- Western Province)

Sampling location Region Cd Al Cr Mn Ni Cu Zn

Nikawewa/NWP CKDu 0.005 3.23 0.08 8.43 0.12 1.50 5.40

Nikawewa/NWP CKDu 0.007 2.18 0.50 6.38 0.71 3.76 7.57

Nikawewa/NWP CKDu <0.005 1.39 0.05 7.46 0.17 1.66 8.18

Nikawewa/NWP CKDu <0.005 2.52 <0.01 13.23 0.25 2.16 11.98

Giradurukotte/UP CKDu 0.076 2.17 0.06 14.36 0.52 2.48 13.95

Giradurukotte/UP CKDu <0.005 0.96 <0.01 3.37 0.05 0.66 3.11

Huruluwewa/NCP nonCKDu 0.017 10.82 0.16 13.61 0.24 2.54 11.77

Kubukwewa/NWP nonCKDu 0.010 0.31 0.24 10.01 0.09 2.17 9.07

Veyangoda/WP nonCKDu 0.006 13.97 0.03 19.85 0.31 2.86 13.73

Huruluwewa/NCP nonCKDu 0.035 1.93 <0.01 14.92 0.45 3.03 14.27

Peradeniya/CP nonCKDu <0.005 4.67 0.36 16.50 0.22 2.65 15.60

Average(n=11)1 0.02 4.0 0.14 11.6 0.29 2.3 10.4

Bangladesh rice (n=6) 0.012 10.9 NA 16.3 NA 7.7 102

Japanese rice (n=6) 0.019 0.22 0.34 1.71 0.05 0.63 4.14

LOQ (mg/kg)2 0.015 0.424 0.044 0.042 0.024 0.020 0.187

LOD (mg/kg)3 0.005 0.13 0.01 0.01 0.01 0.01 0.06 1LOD Value is allocated when concentration in a sample is lower than LOD. LOD values are used for calculation of average. 2Lower Limit of Quantification (LOQ), based on 10 x (Standard Deviation of blank samples); 3Lower Limit of Detection (LOD), based on 3 x (Standard Deviation of blank samples)

7Li 24Mg 43Ca 51V 53Cr 55Mn 57Fe 59Co

GK 0.00613 25.14 31.87 0.0155 0.00172 0.0041 0.685 0.0003

MW 0.00148 8.01 8.60 0.0037 0.00051 0.0010 0.167 0.0001

HW 0.01960 62.10 55.70 0.0491 0.00692 0.0415 1.340 0.0009 60Ni 63Cu 66Zn 69Ga 75As 82Se 85Rb 88Sr

GK 0.00330 0.0051 0.4832 0.0256 0.00072 0.00289 0.00320 0.6143

MW 0.00120 0.0011 0.0032 0.0022 0.00003 0.00042 0.00016 0.1270

HW 0.01010 0.0409 7.2500 0.2260 0.00150 0.00880 0.01830 1.8000

Water (in mg/L) (Mean, Min & Max)

95Mo 111Cd 118Sn 121Sb 133Cs 137Ba 208Pb

GK 0.00123 0.00012 0.000637 0.00129 0.00018 0.49233 0.00066

MW 0.00002 0.00001 0.000005 0.00001 0.00009 0.05350 0.00013

HW 0.00348 0.00159 0.001900 0.00480 0.00058 3.97000 0.00439

Geochemistry of paddy soils of Sri Lanka (total content)

Trace Element Geochemistry of Soils of Sri Lanka

Soils Various 7.2 (0.1-55) Peaty and bog soils 13 (2-36) Acid sulphate soils (Vietnam) 6-41

Acid sulphate soils (Canada) 1.5-45

Soils near sulphide deposits 126 (2-8000)

Arsenic concentrations in soils……………………..

(after Smedley and Kinniburgh, 2002)

As and CKDu

21

Comparison of Means for Total Urinary Arsenic Concentrations

Sri Lanka CKDu cases Controls

Our study (2013) 50.25 μg/gCr 39.37 μg/gCr

France 11.85 μg/gCr A. Saoudi et al. (2012)

Canada 15.00 μg/gCr Health Canada 2010

US 7.47 μg/gCr Caldwell et al. (2009)

Bangladesh 495 μg/L Chowdhury et al. (2000)

West Bengal,

India 180 μg/L Chowdhury et al. (2000)

Taiwan CKD group Healthy control

Hsueh et al. (2009) 31.95 μg/gCr 20.71 μg/gCr

United

Kingdom

Black African Asian White Brima et al. (2006)

7.2 μg/gCr 20.6 μg/gCr 24.5 μg/gCr

22

Speciation of Arsenic Compounds in Urine

Control mean (n=154)

Case mean (n=176)

ArsenoBetaine (ng/mL) 33.04 25.5

DMA (ng/mL) 7.83 6.39

As (III) (ng/mL) 0.71 0.39

MMA (ng/mL) 0.57 0.56

As (V) (ng/mL) 0.22 0.14

Total As (ng/mL) 42.36 32.99

UCr (g/L) 1.19 0.72

Arsenobetaine (ug/g-Cr) 28.96 40.2

DMA (ug/g-Cr) 7.05 9.43

As (III) (ug/g-Cr) 0.82 0.77

MMA (ug/g-Cr) 0.54 0.92

As (V) (ug/g-Cr) 0.28 0.35

Total As (ug/g-Cr) 37.65 51.66

A total of 330 urine samples were duplicated and analyzed at two independent laboratories for total As and As speciation.

As speciation results revealed that 75–80% of total urinary As in both cases and controls was in the form of arsenobetaine

Pedigrees of the families with chronic kidney disease of uncertain etiology (CKDue)

An integrative study of the genetic, social and environmental determinants of chronic kidney disease characterized by tubulointerstitial damages in the North Central Region of Sri Lanka Journal of Occupational Health

None of 18 metals measured in urine, including Cd, As and Pb, showed significantly higher concentrations in cases compared with controls. As speciation results showed that 75–80% of total urinary As was in the form of arsenobetaine, which is non-toxic to humans. The GWAS yielded a genome-wide significant association with CKDu for a single nucleotide polymorphism (SNP; rs6066043; P=5.23×10-9 in quantitative trait locus analysis; P=3.73×10-8 in dichotomous analysis) in SLC13A3 (sodium-dependent dicarboxylate transporter member 3).

Genetic susceptibility was identified as the major risk factor for CKDu.

Thank you for your attention! Thank you for your attention!

“If you want to learn about the health of a population, look at the air they breathe, the water they drink, and

the places where they live.”

- Hippocrates, 5th Century BC

Number of samples Cadmium in rice AM (ASD) (µg/kg)

Daily intake of cadmium via rice (μg/day)* AM (ASD)

Girandurukotte 5 15.052 (3.406) 5.720 (1.294)

Nikawewa 5 7.279 (4.598) 2.766 (1.747)

Category AM (ASD) (μg/g Cr)

GM (GSD) (μg/g Cr)

Range

CKD patients (M =8, F =10) 0.788 (0.549) 0.636 (1.963) 0.213-2.116

Unaffected relatives (M =6, F =12) 0.571 (0.289) 0.501 (1.721) 0.219-1.206

Controls from Kandy (M =8) 0.390 (0.172) 0.353 (1.651) 0.135-0.640

*The estimated daily rice consumption by the adult population in the NCP is 0.38 kg/day. Notes: There are no significant differences in cadmium excretion among the three groups

(P>0.05 by ANOVA).

Mean daily cadmium intakes via rice in the endemic regions

Cadmium concentrations in urine samples

Abbreviations: AM, arithmetic mean; ASD, arithmetic standard deviation; GM, geometric mean; GSD, geometric standard deviation; CKD, chronic kidney disease; Cr, creatinine; M, males; F, females.