Skip to main content
Top
Published in: Environmental Health and Preventive Medicine 3/2012

01-05-2012 | Regular Article

Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka

Authors: Shanika Nanayakkara, Toshiyuki Komiya, Neelakanthi Ratnatunga, S. T. M. L. D. Senevirathna, Kouji H. Harada, Toshiaki Hitomi, Glenda Gobe, Eri Muso, Tilak Abeysekera, Akio Koizumi

Published in: Environmental Health and Preventive Medicine | Issue 3/2012

Login to get access

Abstract

Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.
Appendix
Available only for authorised users
Literature
1.
go back to reference Manns B, Hemmelgarn B, Tonelli M, Au F, Chiasson TC, Dong J, Klarenbach S. Population based screening for chronic kidney disease: cost effectiveness study. BMJ. 2010;341:c5869.PubMedCrossRef Manns B, Hemmelgarn B, Tonelli M, Au F, Chiasson TC, Dong J, Klarenbach S. Population based screening for chronic kidney disease: cost effectiveness study. BMJ. 2010;341:c5869.PubMedCrossRef
2.
go back to reference Soderland P, Lovekar S, Weiner DE, Brooks DR, Kaufman JS. Chronic kidney disease associated with environmental toxins and exposures. Adv Chronic Kidney Dis. 2010;17:254–64.PubMedCrossRef Soderland P, Lovekar S, Weiner DE, Brooks DR, Kaufman JS. Chronic kidney disease associated with environmental toxins and exposures. Adv Chronic Kidney Dis. 2010;17:254–64.PubMedCrossRef
3.
go back to reference Chandrajith R, Nanayakkara S, Itai K, 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;33:267–78.PubMedCrossRef Chandrajith R, Nanayakkara S, Itai K, 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;33:267–78.PubMedCrossRef
4.
go back to reference 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;101:1013–7.PubMedCrossRef 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;101:1013–7.PubMedCrossRef
5.
go back to reference Kawano S, Nakagawa H, Okumura Y, Tsujikawa K. A mortality study of patients with Itai–itai disease. Environ Res. 1986;40:98–102.PubMedCrossRef Kawano S, Nakagawa H, Okumura Y, Tsujikawa K. A mortality study of patients with Itai–itai disease. Environ Res. 1986;40:98–102.PubMedCrossRef
6.
go back to reference Bandara JM, Senevirathna DM, Dasanayake DM, Herath V, Abeysekara T, Rajapaksha KH. 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). Environ Geochem Health. 2008;30:465–78.PubMedCrossRef Bandara JM, Senevirathna DM, Dasanayake DM, Herath V, Abeysekara T, Rajapaksha KH. 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). Environ Geochem Health. 2008;30:465–78.PubMedCrossRef
7.
go back to reference Bandara JM, Wijewardena HV, Liyanege J, Upul MA. Chronic renal failure in Sri Lanka caused by elevated dietary cadmium: Trojan horse of the green revolution. Toxicol Lett. 2010;198:33–9.CrossRef Bandara JM, Wijewardena HV, Liyanege J, Upul MA. Chronic renal failure in Sri Lanka caused by elevated dietary cadmium: Trojan horse of the green revolution. Toxicol Lett. 2010;198:33–9.CrossRef
8.
go back to reference Khajehdehi P, Junaid SM, Salinas-Madrigal L, Schmitz PG, Bastani B. Percutaneous renal biopsy in the 1990s: safety, value, and implications for early hospital discharge. Am J Kidney Dis. 1999;34:92–7.PubMedCrossRef Khajehdehi P, Junaid SM, Salinas-Madrigal L, Schmitz PG, Bastani B. Percutaneous renal biopsy in the 1990s: safety, value, and implications for early hospital discharge. Am J Kidney Dis. 1999;34:92–7.PubMedCrossRef
9.
go back to reference Howie A. Renal Biopsy. Medicine Renal 1. 2003;31:29–31. Howie A. Renal Biopsy. Medicine Renal 1. 2003;31:29–31.
11.
go back to reference Kooman JP. Estimation of renal function in patients with chronic kidney disease. J Magn Reson Imaging. 2009;30:1341–6.PubMedCrossRef Kooman JP. Estimation of renal function in patients with chronic kidney disease. J Magn Reson Imaging. 2009;30:1341–6.PubMedCrossRef
12.
go back to reference Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Hayry PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Yamaguchi Y, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999;55:713–23.PubMedCrossRef Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Hayry PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Yamaguchi Y, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999;55:713–23.PubMedCrossRef
13.
go back to reference Rivera F, Lopez-Gomez JM, Perez-Garcia R. Clinicopathologic correlations of renal pathology in Spain. Kidney Int. 2004;66:898–904.PubMedCrossRef Rivera F, Lopez-Gomez JM, Perez-Garcia R. Clinicopathologic correlations of renal pathology in Spain. Kidney Int. 2004;66:898–904.PubMedCrossRef
14.
go back to reference Briganti EM, Dowling J, Finlay M, Hill PA, Jones CL, Kincaid-Smith PS, Sinclair R, McNeil JJ, Atkins RC. The incidence of biopsy-proven glomerulonephritis in Australia. Nephrol Dial Transplant. 2001;16:1364–7.CrossRef Briganti EM, Dowling J, Finlay M, Hill PA, Jones CL, Kincaid-Smith PS, Sinclair R, McNeil JJ, Atkins RC. The incidence of biopsy-proven glomerulonephritis in Australia. Nephrol Dial Transplant. 2001;16:1364–7.CrossRef
15.
go back to reference Hughson MD, Johnson K, Young RJ, Hoy WE, Bertram JF. Glomerular size and glomerulosclerosis: relationships to disease categories, glomerular solidification, and ischemic obsolescence. Am J Kidney Dis. 2002;39:679–88.PubMedCrossRef Hughson MD, Johnson K, Young RJ, Hoy WE, Bertram JF. Glomerular size and glomerulosclerosis: relationships to disease categories, glomerular solidification, and ischemic obsolescence. Am J Kidney Dis. 2002;39:679–88.PubMedCrossRef
16.
go back to reference Hoy WE, Hughson MD, Singh GR, Douglas-Denton R, Bertram JF. Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension. Kidney Int. 2006;70:104–10.PubMedCrossRef Hoy WE, Hughson MD, Singh GR, Douglas-Denton R, Bertram JF. Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension. Kidney Int. 2006;70:104–10.PubMedCrossRef
17.
go back to reference Sterzel RB, Schulze-Lohoff E, Marx M. Cytokines and mesangial cells. Kidney Int Suppl. 1993;39:S26–31.PubMed Sterzel RB, Schulze-Lohoff E, Marx M. Cytokines and mesangial cells. Kidney Int Suppl. 1993;39:S26–31.PubMed
18.
go back to reference Speirs RS. Cells involved in hypersensitivity and immunity. Blood. 1963;22:363–7.PubMed Speirs RS. Cells involved in hypersensitivity and immunity. Blood. 1963;22:363–7.PubMed
19.
go back to reference Neusser MA, Lindenmeyer MT, Moll AG, Segerer S, Edenhofer I, Sen K, Stiehl DP, Kretzler M, Grone HJ, Schlondorff D, Cohen CD. Human nephrosclerosis triggers a hypoxia-related glomerulopathy. Am J Pathol. 2010;176:594–607.PubMedCrossRef Neusser MA, Lindenmeyer MT, Moll AG, Segerer S, Edenhofer I, Sen K, Stiehl DP, Kretzler M, Grone HJ, Schlondorff D, Cohen CD. Human nephrosclerosis triggers a hypoxia-related glomerulopathy. Am J Pathol. 2010;176:594–607.PubMedCrossRef
21.
go back to reference Caetano ER, Zatz R, Saldanha LB, Praxedes JN. Hypertensive nephrosclerosis as a relevant cause of chronic renal failure. Hypertension. 2001;38:171–6.PubMed Caetano ER, Zatz R, Saldanha LB, Praxedes JN. Hypertensive nephrosclerosis as a relevant cause of chronic renal failure. Hypertension. 2001;38:171–6.PubMed
22.
go back to reference Nanayakkara S, Senevirathna STMLD, Karunaratne U, Chandrajith R, Harada KH, Hitomi T, Watanabe T, Abeysekera T, Aturaliya TNC, Koizumi A, Consortium CKDoUA (2011) Evidence of tubular damage in the very early stage of chronic kidney disease of uncertain etiology in the North Central Province of Sri Lanka: a cross sectional study. Environ Health Prev Med (in press). Nanayakkara S, Senevirathna STMLD, Karunaratne U, Chandrajith R, Harada KH, Hitomi T, Watanabe T, Abeysekera T, Aturaliya TNC, Koizumi A, Consortium CKDoUA (2011) Evidence of tubular damage in the very early stage of chronic kidney disease of uncertain etiology in the North Central Province of Sri Lanka: a cross sectional study. Environ Health Prev Med (in press).
23.
go back to reference Kido T, Nordberg GF, Roels HA. Cadmium-induced renal effects. In: Clinical nephrotoxins: renal injury from drugs and chemicals. 3rd ed, chap 35. New York: Springer Science+Business Media, pp 785–811. Kido T, Nordberg GF, Roels HA. Cadmium-induced renal effects. In: Clinical nephrotoxins: renal injury from drugs and chemicals. 3rd ed, chap 35. New York: Springer Science+Business Media, pp 785–811.
24.
go back to reference Nogawa K, Yamada Y, Honda R, Ishizaki M, Tsuritani I, Kawano S, Kato T. The relationship between itai–itai disease among inhabitants of the Jinzu River basin and cadmium in rice. Toxicol Lett. 1983;17:263–6.PubMedCrossRef Nogawa K, Yamada Y, Honda R, Ishizaki M, Tsuritani I, Kawano S, Kato T. The relationship between itai–itai disease among inhabitants of the Jinzu River basin and cadmium in rice. Toxicol Lett. 1983;17:263–6.PubMedCrossRef
25.
go back to reference Bonnell JA, Ross JH, King E. Renal lesions in experimental cadmium poisoning. Br J Ind Med. 1960;17:69–80.PubMed Bonnell JA, Ross JH, King E. Renal lesions in experimental cadmium poisoning. Br J Ind Med. 1960;17:69–80.PubMed
26.
go back to reference Bamias G, Boletis J. Balkan nephropathy: evolution of our knowledge. Am J Kidney Dis. 2008;52:606–16.PubMedCrossRef Bamias G, Boletis J. Balkan nephropathy: evolution of our knowledge. Am J Kidney Dis. 2008;52:606–16.PubMedCrossRef
27.
go back to reference Schiller A, Gusbeth-Tatomir P, Pavlovic N, Ferluga D, Spasovski G, Covic A. Balkan endemic nephropathy: a still unsolved puzzle. J Nephrol. 2008;21:673–80.PubMed Schiller A, Gusbeth-Tatomir P, Pavlovic N, Ferluga D, Spasovski G, Covic A. Balkan endemic nephropathy: a still unsolved puzzle. J Nephrol. 2008;21:673–80.PubMed
28.
go back to reference Shaohua Z, Ananda S, Ruxia Y, Liang R, Xiaorui C, Liang L. Fatal renal failure due to the Chinese herb “GuanMu Tong” (Aristolochia manshuriensis): autopsy findings and review of literature. Forensic Sci Int. 2010;199:e5–7.PubMedCrossRef Shaohua Z, Ananda S, Ruxia Y, Liang R, Xiaorui C, Liang L. Fatal renal failure due to the Chinese herb “GuanMu Tong” (Aristolochia manshuriensis): autopsy findings and review of literature. Forensic Sci Int. 2010;199:e5–7.PubMedCrossRef
29.
go back to reference de Jonge H, Vanrenterghem Y. Aristolochic acid: the common culprit of Chinese herbs nephropathy and Balkan endemic nephropathy. Nephrol Dial Transplant. 2008;23:39–41.PubMedCrossRef de Jonge H, Vanrenterghem Y. Aristolochic acid: the common culprit of Chinese herbs nephropathy and Balkan endemic nephropathy. Nephrol Dial Transplant. 2008;23:39–41.PubMedCrossRef
30.
31.
go back to reference Krogh P, Elling F, Gyrd-Hansen N, Hald B, Larsen AE, Lillehoj EB, Madsen A, Mortensen HP, Ravnskov U. Experimental porcine nephropathy: changes of renal function and structure perorally induced by crystalline ochratoxin A. Acta Pathol Microbiol Scand A. 1976;84:429–34.PubMed Krogh P, Elling F, Gyrd-Hansen N, Hald B, Larsen AE, Lillehoj EB, Madsen A, Mortensen HP, Ravnskov U. Experimental porcine nephropathy: changes of renal function and structure perorally induced by crystalline ochratoxin A. Acta Pathol Microbiol Scand A. 1976;84:429–34.PubMed
32.
go back to reference Desalegn B, Nanayakkara S, Harada KH, Hitomi T, Chandrajith R, Karunaratne U, Abeysekera T, Koizumi A, Consortium CKDoUE. 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.PubMedCrossRef Desalegn B, Nanayakkara S, Harada KH, Hitomi T, Chandrajith R, Karunaratne U, Abeysekera T, Koizumi A, Consortium CKDoUE. 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.PubMedCrossRef
33.
go back to reference Yang CC, Wu ML, Deng JF. Prolonged hemolysis and methemoglobinemia following organic copper fungicide ingestion. Vet Hum Toxicol. 2004;46:321–3.PubMed Yang CC, Wu ML, Deng JF. Prolonged hemolysis and methemoglobinemia following organic copper fungicide ingestion. Vet Hum Toxicol. 2004;46:321–3.PubMed
34.
go back to reference Schuurman M, van Waardenburg D, Da Costa J, Niemarkt H, Leroy P. Severe hemolysis and methemoglobinemia following fava beans ingestion in glucose-6-phosphatase dehydrogenase deficiency: case report and literature review. Eur J Pediatr. 2009;168:779–82.PubMedCrossRef Schuurman M, van Waardenburg D, Da Costa J, Niemarkt H, Leroy P. Severe hemolysis and methemoglobinemia following fava beans ingestion in glucose-6-phosphatase dehydrogenase deficiency: case report and literature review. Eur J Pediatr. 2009;168:779–82.PubMedCrossRef
35.
go back to reference Srinivas R, Agarwal R, Jairam A, Sakhuja V. Intravascular haemolysis due to glucose-6-phosphate dehydrogenase deficiency in a patient with aluminium phosphide poisoning. Emerg Med J. 2007;24:67–8.PubMedCrossRef Srinivas R, Agarwal R, Jairam A, Sakhuja V. Intravascular haemolysis due to glucose-6-phosphate dehydrogenase deficiency in a patient with aluminium phosphide poisoning. Emerg Med J. 2007;24:67–8.PubMedCrossRef
36.
go back to reference Xiong X, Liu J, He W, Xia T, He P, Chen X, Yang K, Wang A. Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children. Environ Res. 2007;103:112–6.PubMedCrossRef Xiong X, Liu J, He W, Xia T, He P, Chen X, Yang K, Wang A. Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children. Environ Res. 2007;103:112–6.PubMedCrossRef
Metadata
Title
Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka
Authors
Shanika Nanayakkara
Toshiyuki Komiya
Neelakanthi Ratnatunga
S. T. M. L. D. Senevirathna
Kouji H. Harada
Toshiaki Hitomi
Glenda Gobe
Eri Muso
Tilak Abeysekera
Akio Koizumi
Publication date
01-05-2012
Publisher
Springer Japan
Published in
Environmental Health and Preventive Medicine / Issue 3/2012
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI
https://doi.org/10.1007/s12199-011-0243-9

Other articles of this Issue 3/2012

Environmental Health and Preventive Medicine 3/2012 Go to the issue