geoenvironmental factors related to chronic kidney disease ... · geoenvironmental factors related...
TRANSCRIPT
Geoenvironmental factors related to
Chronic Kidney Disease of uncertain
aetiology in Sri Lanka
Professor Rohana Chandrajith Professor in Geology
University of Peradeniya [email protected]
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.