Disclosures. Objectives 2/28/2018. Chronic Kidney Disease of Unknown Origin: An emerging occupational disease? Sally Moyce, RN PhD March 2018

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1 Chronic Kidney Disease of Unknown Origin: An emerging occupational disease? Sally Moyce, RN PhD March 2018 Disclosures I have no disclosures to report. Objectives 1. Describe differences between Chronic Kidney Disease (CKD) and Chronic Kidney Disease of Unknown Origin (CDKu). 2. Explore the global dimensions of CKDu. 3. Investigate evidence of possible etiology of CKDu. 4. Present an agenda for future research and treatment. 1

2 CKD versus CKDu No history of HTN or DM Middle aged patients (30s 50s) Males > Females Poor, rural areas Predominant occupation: agriculture Tubulo interstitial fibrosis (hisology) Urine: Central America: Low grade proteinuria/albuminuria Sri Lanka: Albumin creatinine ratio 30 mg/dl Global Dimensions of CKDu Global Dimensions of CKDu Mexico and Central America (Mesoamerican Endemic Nephropathy) Honduras: 25 deaths/100,000 persons Nicaragua: 26 deaths/100,000 persons El Salvador: 52 deaths/100,000 persons India Andhra Prakesh: Estimated incidence 15% Sri Lanka 20,000 deaths in the last decade (leading cause of death) Egypt 2

3 Etiology Barriers to identification No standard definition Geographic differences in distribution and detection Delays in diagnosis due to poor access to heath care Differences in measurement of risk factors Likely multi factorial Frequency of measured exposures from systematic review (Lunyera et al, 2015) Occupational Exposures 1. Pesticides 2. Heat strain/volume depletion 3. Strenuous labor 3

4 Agrochemicals/Pesticides Common agricultural occupational exposure Interstitial nephritis related to pesticide exposure Many pesticides known nephrotoxins, especially organochlorine insecticides (e.g. propanil) Some evidence of pesticides in drinking water in affected communities Organochlorines in India Case control study in Delhi (n=300) Median serum levels of OCPs Increased OCP associated with CKDu OCP Healthy Group CKD Group CKDu Group α HCH 0.7( ) 1.26 ( ) 1.68 ( ) Aldrin 1.6 ( ) 1.96 ( ) 2.15 ( ) β endosulfan 1.3 ( ) 0.84 ( ) 2.38 ( ) p, p DDE 2.6 ( ) 1.54 ( ) 2.94 ( ) Ghosh et al (2017) Heat Strain/Volume Depletion Sugarcane harvesting in Central America Chena agriculture in Sri Lanka Increased prevalence in lowland, coastal regions Evapora ve cooling volume deple on decreased kidney perfusion 4

5 Heat Exposure in Central America Comparison of agricultural workers at sea level and 500 meters above sea level Male workers at sea level had higher prevalence of CKDu than those at elevation egfr<60 mil/min/1.73m 2 Sugarcane workers at sea level 18% Coffee plantation workers at 500 masl 2% Prevalence of elevated serum creatinine by sex and age (Peraza et al, 2012) Strenuous Labor in California California Heat Illness Prevention Study (CHIPS, PI Marc Schenker, UC Davis) Investigation of acute kidney injury (AKI) in 300 California farm workers After a single day of work, AKI in 12% of sample AKI related to heat exposure, not volume depletion AKI associated with 4.5 odds ratio for those paid by the piece 5

6 No AKI AKI No Heat Strain Heat Strain No body mass change Gained body mass Lost <1.5% Lost 1.5% Association of heat strain and volume depletion and AKI (Moyce et al, 2017) Association of piece rate work with AKI in California farm workers (Moyce et al, 2017) Multi Factorial Etiology: Occupational? 6

7 Future Research Standardize case definition of CKDu Standardize exposure measurements Workload Heat exposure Volume depletion Agrochemical exposure Heavy metal exposure Focus on AKI and biomarkers pre and post work shift or harvest season Global collaboration among researchers Future Treatment Increase access to health care for early detection and dialysis Safe and fair labor practices Re assignment of financial resources to poorest, rural areas Protection of drinking water Question 1 Barriers to identification of the etiology of CKDu include all of the following EXCEPT: A. Early detection and diagnosis B. Lack of standardized case definition C. Easily traceable exposures D. International attention to problem 7

8 Question 2 The most likely cause of CKDu is A. Pesticides B. Heat strain C. Strenuous labor D. Multiple causes Question 3 The physician suspects CKDu in which of the following patients? A. A 65 year old African American B. A 52 year old diabetic patient C. A 37 year old immigrant farm worker D. A 61 year old subsistence farmer Select References Ghosh, R., Siddarth, M., Singh, N., Tyagi, V., Kare, P. K., Banerjee, B. D.,... & Tripathi, A. K. (2017). Organochlorine pesticide level in patients with chronic kidney disease of unknown etiology and its association with renal function. Environmental health and preventive medicine, 22(1), 49. Lunyera, J., Mohottige, D., Von Isenburg, M., Jeuland, M., Patel, U. D., & Stanifer, J. W. (2015). CKD of uncertain etiology: a systematic review. Clinical Journal of the American Society of Nephrology, CJN Moyce, S., Mitchell, D., Armitage, T., Tancredi, D., Joseph, J., & Schenker, M. (2017). Heat strain, volume depletion and kidney function in California agricultural workers. Occup Environ Med, 74(6), Peraza, S., Wesseling, C., Aragon, A., Leiva, R., García Trabanino, R. A., Torres, C.,... & Hogstedt, C. (2012). Decreased kidney function among agricultural workers in El Salvador. American Journal of Kidney Diseases, 59(4), Valcke, M., Levasseur, M. E., da Silva, A. S., & Wesseling, C. (2017). Pesticide exposures and chronic kidney disease of unknown etiology: an epidemiologic review. Environmental Health, 16(1), 49. 8