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3/8/18 Disclosures u I have no disclosures to report. Chronic Kidney Disease of Unknown Origin: An emerging occupational disease? Sally Moyce, RN PhD March 2018 Objectives 1. Describe differences between Chronic Kidney Disease (CKD) and

  1. 3/8/18 Disclosures u I have no disclosures to report. Chronic Kidney Disease of Unknown Origin: An emerging occupational disease? Sally Moyce, RN PhD March 2018 Objectives 1. Describe differences between Chronic Kidney Disease (CKD) and Chronic Kidney Disease of Unknown Origin (CDKu). Central America India India 2. Explore the global dimensions of CKDu. 3. Investigate evidence regarding a possible etiology of CKDu. Sri Lanka 4. Present an agenda for future research and treatment. Photo credits: La Isla Foundation 1

  2. 3/8/18 Chronic Kidney Disease u Gradual loss of kidney function u Reduced eGFR u Risk factors: u DM u HTN u Obesity u Advanced Age Chronic Kidney Disease of Chronic Kidney Disease of Unknown Origin Unknown Origin ► Histology studies: ► Decline in eGFR leading to kidney failure and Proximal tubular damage (v. glomerular) • death Mild-moderate tubular atrophy • ► High rate of mortality Interstitial inflammation • ► Middle aged patients (30s-50s) ► Urine: ► No history of HTN or DM • Central America: Low grade proteinuria/albuminuria ► Males > Females • Sri Lanka: Persistent albuminuria ► Poor, rural areas Wijkstrom et al., 2013 ► Predominant occupation: agriculture 2

  3. 3/8/18 Global Dimensions of CKDu Global Dimensions of CKDu ► Central America Mortality rates 4x global rates • Honduras: 25 deaths/100,000 • Nicaragua: 26 deaths/100,000 • El Salvador: 52 deaths/100,000 • Global Dimensions of CKDu Etiology ► Sri Lanka ► Barriers to identification ► Potential causes Leading cause of death – 20,000 • Occupational deaths in last decade No standard definition • • Geographic differences in Behavioral Endemic districts • • • distribution and detection Geographical Anuradhapura 15% • • Delays in diagnosis due to • Physiological • Polonnaruwa 20% • poor access to heath care Badulla 23% Differences in measurement • • of risk factors ► India Andhra Pradesh – 15% • Jayatilake et al, 2013 3

  4. 3/8/18 Occupational Exposures 1. Pesticides 2. Heavy metals 3. Heat strain/volume depletion 4. Strenuous labor Frequency of measured exposures from systematic review (Lunyera et al, 2015) Agrochemicals/Pesticides Organochlorines in India ► Common agricultural occupational ► Case-control study in Delhi (n=300) exposure ► Median serum levels of OCPs ► Interstitial nephritis related to pesticide ► Increased OCP associated with CKDu exposure ► Many pesticides known nephrotoxins, especially organochlorine insecticides Median serum levels OCPs (range) (e.g. propanil) OCP Healthy Group CKD Group CKDu Group ► Some evidence of pesticides in α HCH 0.7(0.002-1.66) 1.26 (0.34-3.15) 1.68 (0.12-4.26) drinking water in affected communities Aldrin 1.6 (0.002-2.15) 1.96 (0.002-3.12) 2.15 (0.002-3.18) β -endosulfan 1.3 (0.002-2.65) 0.84 (0.002-1.54) 2.38 (0.65-4.28) Photo: Julie Potyraj p, p -DDE 2.6 (0.002-3.54) 1.54 (0.29-2.64) 2.94 (0.68-4.58) Ghosh et al (2017) 4

  5. 3/8/18 Organochlorines in India Heavy Metals u Heavy metals damaging to kidneys ► Case-control study in Delhi (n=300) u Effect of agrochemicals may be exacerbated by “hard” water ► Median serum levels of OCPs ► Increased OCP associated with CKDu u Linked to tubulo-interstitial disease u Iron-deficiency may increase risk Median serum levels OCPs (range) OCP Healthy Group CKD Group CKDu Group u Increased cadmium levels in CKDu patients in α HCH 0.7(0.002-1.66) 1.26 (0.34-3.15) 1.68 (0.12-4.26) Sri Lanka (Jayatilake et al, 2013) Aldrin 1.6 (0.002-2.15) 1.96 (0.002-3.12) 2.15 (0.002-3.18) β -endosulfan 1.3 (0.002-2.65) 0.84 (0.002-1.54) 2.38 (0.65-4.28) p, p -DDE 2.6 (0.002-3.54) 1.54 (0.29-2.64) 2.94 (0.68-4.58) Ghosh et al (2017) Heat Strain/Volume Depletion Heat Exposure in Central America ► Sugarcane harvesting in Central America ► Chena agriculture in Sri Lanka u Comparison of agricultural workers at sea level and 500 meters above sea level ► Increased prevalence in lowland, coastal regions u Male workers at sea level had higher prevalence of CKDu than those at ► Evaporative cooling → volume depletion → decreased elevation kidney perfusion eGFR<60 mil/min/1.73m 2 Workers at sea level 18% Workers at 500 masl 2% 5

  6. 3/8/18 Strenuous Labor in California California Heat Illness Prevention Study (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 Prevalence of elevated serum creatinine by sex and age (Peraza et al, 2012) 100 Odds of AKI with Heat Strain and Volume Depletion (n=283) 90 Piece-rate 80 Diabetes 70 Female sex 60 Heat strain 50 Yrs in farm work No AKI 40 AKI Age 30 Hypertension 20 Volume depletion 10 Obesity 0 No Heat Heat Strain No body Gained Lost <1.5% Lost ≥1.5% 0 1 2 4 6 8 10 12 Strain mass body mass change Association of piece-rate work with AKI in California farm workers (Moyce et al, 2017) Association of heat strain and volume depletion and AKI (Moyce et al, 2017) 6

  7. 3/8/18 Multi-Factorial Etiology: Occupational? Multi-Factorial Etiology: Other Sources? u Heat exposure + volume depletion + social/economic factors + behavioral factors + family history + environmental risks + ??? Uric acid and chronic kidney disease (Johnson et al, 2013) Future Research Future Treatment ► Standardize case definition of CKDu ► Standardize exposure measurements ► Increase access to health care for early • Workload detection and dialysis • Heat exposure ► Safe and fair labor practices • Volume depletion ► Re-assignment of financial resources to • Agrochemical exposure poorest, rural areas • Heavy metal exposure ► Protection of drinking water ► Focus on AKI and biomarkers pre- and post-work shift or harvest season ► Global collaboration among researchers 7

  8. 3/8/18 Summary Questions? Comments? u CKDu prevalence increasing on global scale u Potential for disease among agricultural workers in United States u Etiology likely multi-factorial but related to heat and volume depletion u Improved worker safety essential to combat disease Sally Moyce, RN PhD Assistant Professor Samuel Merritt University smoyce@samuelmerritt.edu Question 1 Question 2 A barrier to the identification of the etiology of CKDu includes which of The most likely cause of CKDu is the following: Pesticides A. Early detection and diagnosis A. Heat strain B. Lack of standardized case definition B. Strenuous labor C. Easily traceable exposures C. Multiple causes D. International attention to problem D. 8

  9. 3/8/18 Question 3 Select References Ghosh, R., Siddarth, M., Singh, N., Tyagi, V., Kare, P. K., Banerjee, B. D., ... & u 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. u The physician suspects CKDu in which of the following patients who presents with decreased eGFR? Lunyera, J., Mohottige, D., Von Isenburg, M., Jeuland, M., Patel, U. D., & Stanifer, u J. W. (2015). CKD of uncertain etiology: a systematic review. Clinical Journal of the American Society of Nephrology , CJN-07500715. Moyce, S., Mitchell, D., Armitage, T., Tancredi, D., Joseph, J., & Schenker, M. A 65 year old African American u A. (2017). Heat strain, volume depletion and kidney function in California A 52 year old diabetic patient agricultural workers. Occup Environ Med , 74 (6), 402-409. B. Peraza, S., Wesseling, C., Aragon, A., Leiva, R., García-Trabanino, R. A., Torres, u A 37 year old immigrant farm worker C. C., ... & Hogstedt, C. (2012). Decreased kidney function among agricultural workers in El Salvador. American Journal of Kidney Diseases , 59 (4), 531-540. A 61 year old subsistence farmer D. Wijkström, J., Leiva, R., Elinder, C. G., Leiva, S., Trujillo, Z., Trujillo, L., ... & u Wernerson, A. (2013). Clinical and pathological characterization of Mesoamerican nephropathy: a new kidney disease in Central America. American Journal of Kidney Diseases , 62 (5), 908-918. Valcke, M., Levasseur, M. E., da Silva, A. S., & Wesseling, C. (2017). Pesticide u exposures and chronic kidney disease of unknown etiology: an epidemiologic review. Environmental Health , 16 (1), 49. 9

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