Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing country

BMC Nephrology

Firdosi R Mehta¹  Palitha Maheepala²  Shanthi Mendis³  Nihal Jayatilake² 

[1] World Health Organization, Colombo, Sri Lanka;Ministry of Health, Colombo, Sri Lanka;Management of Noncommunicable Diseases, World Health Organization, Geneva, Switzerland

关键词: Pesticides;    Lead;    Heavy metals;    Kidney disease of uncertain aetiology;    Chronic kidney disease;    Cadmium;    Arsenic;   

Others  :  1082859
DOI  :  10.1186/1471-2369-14-180

 received in 2013-03-16, accepted in 2013-08-16,  发布年份 2013

【 摘 要 】

Background

This study describes chronic kidney disease of uncertain aetiology (CKDu), which cannot be attributed to diabetes, hypertension or other known aetiologies, that has emerged in the North Central region of Sri Lanka.

Methods

A cross-sectional study was conducted, to determine the prevalence of and risk factors for CKDu. Arsenic, cadmium, lead, selenium, pesticides and other elements were analysed in biological samples from individuals with CKDu and compared with age- and sex-matched controls in the endemic and non-endemic areas. Food, water, soil and agrochemicals from both areas were analysed for heavy metals.

Results

The age-standardised prevalence of CKDu was 12.9% (95% confidence interval [CI] = 11.5% to 14.4%) in males and 16.9% (95% CI = 15.5% to 18.3%) in females. Severe stages of CKDu were more frequent in males (stage 3: males versus females = 23.2% versus 7.4%; stage 4: males versus females = 22.0% versus 7.3%; P < 0.001). The risk was increased in individuals aged >39 years and those who farmed (chena cultivation) (OR [odds ratio] = 1.926, 95% CI = 1.561 to 2.376 and OR = 1.195, 95% CI = 1.007 to 1.418 respectively, P < 0.05). The risk was reduced in individuals who were male or who engaged in paddy cultivation (OR = 0.745, 95% CI = 0.562 to 0.988 and OR = 0.732, 95% CI = 0.542 to 0.988 respectively, P < 0.05). The mean concentration of cadmium in urine was significantly higher in those with CKDu (1.039 μg/g) compared with controls in the endemic and non-endemic areas (0.646 μg/g, P < 0.001 and 0.345 μg/g, P < 0.05) respectively. Urine cadmium sensitivity and specificity were 70% and 68.3% respectively (area under the receiver operating characteristic curve = 0.682, 95% CI = 0.61 to 0.75, cut-off value ≥0.397 μg/g). A significant dose–effect relationship was seen between urine cadmium concentration and CKDu stage (P < 0.05). Urine cadmium and arsenic concentrations in individuals with CKDu were at levels known to cause kidney damage. Food items from the endemic area contained cadmium and lead above reference levels. Serum selenium was <90 μg/l in 63% of those with CKDu and pesticides residues were above reference levels in 31.6% of those with CKDu.

Conclusions

These results indicate chronic exposure of people in the endemic area to low levels of cadmium through the food chain and also to pesticides. Significantly higher urinary excretion of cadmium in individuals with CKDu, and the dose–effect relationship between urine cadmium concentration and CKDu stages suggest that cadmium exposure is a risk factor for the pathogensis of CKDu. Deficiency of selenium and genetic susceptibility seen in individuals with CKDu suggest that they may be predisposing factors for the development of CKDu.

【 授权许可】

   
2013 Jayatilake et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Gooneratne IK, Ranaweera AK, Liyanarachchi NP, Gunawardane N, Lanerolle RD: Epidemiology of chronic kidney disease in a Sri Lankan population. Int J Diabetes Dev Ctries 2008, 28:60-64.
• [2]Nanayakkara S, Komiya T, Ratnatunga N, Senevirathna ST, Harada KH, Hitomi T, Gobe G, Muso E, Abeysekera T, Koizumi A: Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka. Environ Health Prev Med 2012, 17:213-221.
• [3]Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW: Chronic kidney disease: global dimension and perspectives. Lancet 2013, 382(9888):260-272.
• [4]Shah MD, Iqbal M: Diazinon-induced oxidative stress and renal dysfunction in rats. Food Chem Toxicol 2010, 48(12):3345-3353.
• [5]Tripathi S, Srivastav AK: Nephrotoxicity induced by long-term oral administration of different doses of chlorpyrifos. Toxicol Ind Health 2010, 26(7):439-447.
• [6]World Health Organization: Environmental Health Criteria 134: Cadmium Environmental Health Criteria. Geneva: World Health Organization; 1992.
• [7]World Health Organization: Environmental Health Criteria 165: Lead. Geneva: World Health Organization; 1995.
• [8]World Health Organization: Environmental Health Criteria 224: Arsenic and Arsenic Compounds. Geneva: World Health Organization; 2001.
• [9]Sabolić I: Common mechanisms in nephropathy induced by toxic metals. Nephron Physiol 2006, 104:107-114.
• [10]Athuraliya NT, Abeysekera TD, Amerasinghe PH, Kumarasiri R, Bandara P, Karunaratne U, Milton AH, Jones AL: Uncertain etiologies of proteinuric-chronic kidney disease in rural Sri Lanka. Kidney Int 2011, 80:1212-1221.
• [11]Wijewickrama ES, Weerasinghe D, Sumathipala PS, Horadagoda C, Lanarolle RD, Sheriff RM: Epidemiology of chronic kidney disease in a Sri Lankan population: experience of a tertiary care center. Saudi J Kidney Dis Transpl 2011, 22:1289-1293.
• [12]Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R: Chronic kidney disease of unknown aetiology in Sri Lanka: is Cd a likely cause? BMC Nephrol 2011, 12:32. BioMed Central Full Text
• [13]Wanigasuriya KP, Peiris H, Ileperuma N, Peiris-John RJ, Wickremasinghe R: Could ochratoxin A in food commodities be the cause of chronic kidney disease in Sri Lanka? Trans R Soc Trop Med Hyg 2008, 102:726-728.
• [14]Bandara JM, Senevirathna DM, Dasanayake DM, Hearth V, Bndara JMRP, Abeysekera T, Rajapajsha KH: Chronic renal failure among farm families in cascade irrigation systems in Sri Lanka associated with elevated dietary Cd levels in rice and freshwater fish (Tilapia). Environ Geochem Health 2008, 30:465-478.
• [15]Bandara JM, Wijewardena HV, Liyanege J, Upul MA, Bandara JMUA: Chronic renal failure in Sri Lanka caused by elevated dietary cadmium: Trojan horse of the green revolution. Toxicol Lett 2010, 198:33-39.
• [16]Desalegn B, Nanayakkara S, Harada KH, Hitomi T, Chandrajith R, Karunaratne U, Abeysekera T, Koizumi A: Mycotoxin detection in urine samples from patients with chronic kidney disease of uncertain etiology in Sri Lanka. Bull Environ Contam Toxicol 2011, 87:6-10.
• [17]Chandrajith R, Dissanayake CB, Ariyarathna T, Herath HM, Padmasiri JP: Dose-dependent Na and Ca in fluoride-rich drinking water – another major cause of chronic renal failure in tropical arid regions. Sci Total Environ 2011, 409:671-675.
• [18]Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R, Hittarage A: Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease. Trans R Soc Trop Med Hyg 2007, 101:1013-1017.
• [19]Bandara JM, Wijewardena HV, Bandara YM, Jayasooriya RG, Rajapaksha H: Pollution of River Mahaweli and farmlands under irrigation by Cd from agricultural inputs leading to a chronic renal failure epidemic among farmers in NCP, Sri Lanka. Environ Geochem Health 2011, 33:439-453.
• [20]Chandrajith R, Nanayakkara S, Itai , Aturaliya TN, Dissanayake CB, Abeysekera T, Harada K, Watanabe T, Koizumi A: Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: geographic distribution and environmental implications. Environ Geochem Health 2011, 33:267-278.
• [21]World Health Organization: Guidelines for Drinking-Water Quality. 4th edition. Geneva: World Health Organization; 2011.
• [22]Joint FAO/WHO Food Standards Programme, Codex Alimentarius Commission: Twenty-Fourth Session, Geneva, Switzerland, 2–7 July, 2001. Report of the 33rd Session of the Codex Committee of Food Additives and Contaminants. The Hague, The Netherlands, 12–16 March 2001. Rome: Codex Alimentarius Commission; 2001. ALINORM 01/12A
• [23]Joint FAO/WHO Food Standards Programme, Codex Alimentarius Commission: Report of the 28th of the session Joint FAO/WHO Food Standards Programme. Rome, Italy, 4–9 July 2005. Report of the 15th Session of the Codex Committee on Residues of Veterinary Drugs in Food. Washington DC, USA, 26–29 October 2004. Rome: Codex Alimentarius Commission; 2005. ALINORM 05/28/41
• [24]Setting Maximum Levels For Certain Contaminants in Foodstuffs. European Commission Regulation (EC) No 1881/2006. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:364:0005:0024:EN:PDF webcite
• [25]Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J: CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med 2009, 150(9):604-612.
• [26]Millán Adame E, Florea D, Sáez Pérez L, Molina López J, López-González B, Pérez De La Cruz A, Planells Del Pozo E: Deficient selenium status of a healthy adult Spanish population. Nutr Hosp 2012, 27(2):524-528.
• [27]Lipworth L, Mumma MT, Cavanaugh KL, Edwards TL, Ikizler TA, Tarone RE, McLaughlin JK, Blot WJ: Incidence and predictors of end stage renal disease among low-income blacks and whites. PLoS One 2012, 7(10):e48407.
• [28]Järup L: Hazards of heavy metal contamination. Br Med Bull 2003, 68:167-182.
• [29]Noonan CW, Sarasua SM, Campagna D, Kathman SJ, Lybarger JA, Mueller PW: Effects of exposure to low levels of environmental Cd on renal biomarkers. Environ Health Perspect 2002, 110:151-155.
• [30]Järup L, Alfvén T: Low level Cd exposure, renal and bone effects-the OSCAR study. Biometals 2004, 17:505-509.
• [31]Järup L, Akesson A: Current status of Cd as an environmental health problem. Toxicol Appl Pharmacol 2009, 238:201-208.
• [32]Huang M, Choi SJ, Kim DW, Kim NY, Bae HS, Yu SD, Kim DS, Kim H, Choi BS, Yu IJ, Park JD: Evaluation of factors associated with Cd exposure and kidney function in the general population. Environ Toxicol 2011, 10:1002. /tox.20750
• [33]Huang M, Choi SJ, Kim DW, Kim NY, Park CH, Yu SD, Kim DS, Park KS, Song JS, Kim H, Choi BS, Yu IJ, Park JD: Risk assessment of low-level Cd and As on the kidney. J Toxicol Environ Health A 2009, 72:1493-1498.
• [34]Brima EI, Haris PI, Jenkins RO, Polya DA, Gault AG, Harrington CF: Understanding Arsenic metabolism through a comparative study of Arsenic levels in the urine, hair and fingernails of healthy volunteers from three unexposed ethnic groups in the United Kingdom. Toxicol Appl Pharmacol 2006, 216:122-130.
• [35]Navas-Acien A, Umans JG, Howard BV, Goessler W, Francesconi KA, Crainiceanu CM, Silbergeld EK, Guallar E: Urine As concentrations and species excretion patterns in American Indian communities over a 10-year period: the strong heart study. Environ Health Perspect 2009, 117:1428-1433.
• [36]Hsueh YM, Chung CJ, Shiue HS, Chen JB, Chiang SS, Yang MH, Tai CW, Su CT: Urinary As species and CKD in a Taiwanese population: a case–control study. Am J Kidney Dis 2009, 54:859-870.
• [37]Buchet JP, Heilier JF, Bernard A, Lison D, Jin T, Wu X, Kong Q, Nordberg G: Urinary protein excretion in humans exposed to arsenic and cadmium. Int Arch Occup Environ Health 2003, 76:111-120.
• [38]Nordberg GF, Jin T, Hong F, Zhang A, Buchet JP, Bernard A: Biomarkers of cadmium and arsenic interactions. Toxicol Appl Pharmacol 2005, 206:191-197.
• [39]Xiao P, Jia XD, Zhong WJ, Jin XP, Nordberg G: Restorative effects of zinc and selenium on cadmium-induced kidney oxidative damage in rats. Biomed Environ Sci 2002, 15:67-74.
• [40]Thomson CD, Robinson MF, Butler JA, Whanger PD: Long-term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase (EC 1.11 1.9) in blood components of New Zealand women. Br J Nutr 1993, 69:577-588.
• [41]Duffield AJ, Thomson CD, Hill KE, Williams S: An estimation of selenium requirements for New Zealanders. Am J Clin Nutr 1999, 70:896-903.
• [42]Bernhard D, Rossmann A, Henderson B, Kind M, Seubert A, Wick G: Increased serum Cd and strontium levels in young smokers effects on arterial endothelial cell gene transcription. Arterioscler Thromb Vasc Biol 2006, 26:833-838.
• [43]United States Environmental Protection Agency: Fact Sheet: Drinking Water Standard for Arsenic. 815-F-00-015, January 2001. http://water.epa.gov/lawsregs/rulesregs/sdwa/arsenic/regulations_factsheet.cfm webcite
• [44]European Food Safety Authority: Cd dietary EXPOSURE in the European population. EFSA Journal 2012, 10:2551-2588.
• [45]Food and Agriculture Organization of the United Nations/World Health Organization: Evaluation of Certain Contaminants in Food. Seventy-second report of the Joint FAO/WHO Expert Committee on Food Additives. Geneva: World Health Organization; 2011. [WHO Technical Report Series, No. 959]
• [46]Food and Agriculture Organization of the United Nations/World Health Organization: Safety Evaluation of Certain Contaminants in Food. Geneva; Rome: World Health Organization; Food and Agriculture Organization of the United Nations; 2011. [WHO Food Additives Series, No. 63; FAO JECFA Monographs 8]
• [47]Holmgren GGS, Meyer MW, Chaney RL, Daniels RB: Cd, Pb, Zinc, Copper, and Nickel in agricultural soils of the United States of America. J Environ Qual 1993, 22:335-348.
• [48]California Department of Food and Agriculture: Evaluation of Heavy Metals and Dioxin in Inorganic Commercial Fertilizers and California Cropland Soils. Sacramento: California Department of Food and Agriculture; 2004.
• [49]Naturvardsverket: Annual report of the Swedish Environmental Objectives Council 1997. Stockholm: Naturvardsverket; 1997.
• [50]He JY, Ren YF, Wang FJ, Pan XB, Zhu C, Jiang DA: Characterization of cadmium uptake and translocation in a cadmium-sensitive mutant of rice (Oryza sativa L. ssp. japonica). Arch Environ Contam Toxicol 2009, 57:299-306.
• [51]Gagnon C, Vaillancourt G, Pazdernik L: Influence of water hardness on accumulation and elimination of cadmium in two aquatic mosses under laboratory conditions. Arch Environ Contam Toxicol 1998, 34:12-20.
• [52]Sukreeyapongse O, Holm PE, Strobel BW, Panichsakpatana S, Magid J, Hansen HC: pH-dependent release of cadmium, copper, and lead from natural and sludge-amended soils. J Environ Qual 2002, 31:1901-1909.
• [53]Rankin GO, Racine C, Sweeney A, Kraynie A, Anestis DK, Barnett JB: In vitro nephrotoxicity induced by propanil. Environ Toxicol 2008, 23:435-442.
• [54]Stefanovic V, Polenakovic M: Fifty years of research in Balkan endemic nephropathy: where are we now? Nephron Clin Pract 2009, 112:51-56.
• [55]Torres C, Aragón A, González M, López I, Jakobsson K, Elinder CG, Lundberg I, Wesseling C: Decreased kidney function of unknown cause in Nicaragua: a community-based survey. Am J Kidney Dis 2010, 55:485-496.
• [56]Morabia A, Costanza MC: Could Chinese herbal medicine be nephrotoxic? Prev Med 2012, 55:85-86.
• [57]Peraza S, Wesseling C, Aragon A, Leiva R, García-Trabanino RA, Torres C, Jakobsson K, Elinder CG, Hogstedt C: Decreased kidney function among agricultural workers in El Salvador. Am J Kidney Dis 2012, 59:531-540.
• [58]Tellez-Plaza M, Navas-Acien A, Caldwell KL, Menke A, Muntner P, Guallar E: Reduction in cadmium exposure in the United States population, 1988–2008: the contribution of declining smoking rates. Environ Health Perspect 2012, 120:204-209.
• [59]Sato A, Takeda H, Oyanagi W, Nishihara E, Murakami M: Reduction of cadmium uptake in spinach (Spinacia oleracea L.) by soil amendment with animal waste compost. J Hazard Mater 2010, 181:298-304.