Increased Serum CD55 and CD59 During Occupational Heat Stress are Associated with Incident Kidney Injury

Occupational heat exposure is strongly associated with chronic kidney disease of nontraditional cause (CKDnt) among agricultural workers in tropical regions. Efforts which reduce heat stress have been shown to protect agricultural workers against kidney injury in this context. The mechanism of injury connecting heat exposure and kidney disease is an area of active investigation. Current evidence suggests inflammation may play a role, but little is known about the role of the complement system in these inflammatory processes. CD55 and CD59 are membrane-bound complement regulatory proteins whose levels increase during inflammation to protect host cells against complement-mediated injury. This increase is reflected in serum levels of both proteins. In this study, we investigated how serum CD55 and CD59 levels change under conditions of occupational heat stress and whether these changes are associated with kidney injury in these conditions.  

We followed sugarcane cutters in Nicaragua, a group known to experience high levels of occupational heat stress and with high incidence of CKDnt, across two harvest seasons. During the first (“baseline”) harvest season usual occupational practices were in place, while during the second season a rest-shade-hydration intervention was implemented to prevent heat stress. Both harvests were on the same plantation, but the individuals followed during each harvest differed. We assessed each participant for development of incident kidney injury (IKI), defined as an increase in serum creatinine of 0.3mg/dL or more from their pre-harvest to their end-harvest measurement. We measured serum CD55 and CD59 using the Olink platform in each participant before and after each harvest. 

A total of 272 sugarcane cutters were included in this study. Serum levels of both CD55 and CD59 significantly increased from pre-harvest to post-harvest across the baseline harvest (n = 140; p < 0.0001 for CD55; p = 0.0004 for CD59) but not the harvest with improved heat prevention measures in place (n = 132; p = 0.35 for CD55, p = 0.05 for a cross-harvest decrease in CD59; Figure 1A). The degree of rise in both CD55 and CD59 was significantly greater across the baseline harvest than the improved heat prevention harvest (p = 0.002 for CD55, p < 0.0001 for CD59; Figure 1B). Sugarcane cutters who developed IKI across either harvest (n = 27) had significantly greater increases in both CD55 and CD59 compared to individuals who did not develop IKI (p < 0.0001 for CD55 and for CD59; Figure 2).

Figure 1. Change in serum CD55 and CD59 from pre-to post-harvest among sugarcane cutters. Levels of CD55 and CD59 are shown pre- and post-harvest across the baseline harvest (A) and the harvest with improved heat prevention measures in place (B). (C) Comparison of the change in CD55 and CD59 levels between harvests.

Figure 2. Change in serum CD55 and CD59 from pre-to post-harvest among sugarcane cutters who developed incident kidney injury, defined as a rise in serum creatinine of 0.3mg/dL across the harvest, compared to those without incident kidney injury.

There is evidence of increased complement regulatory activity arising during occupational heat stress, which is mitigated when occupational heat stress is prevented. The association between markers of increased complement regulatory activity and IKI suggest that complement may contribute to kidney injury in this context. Further investigation into the role of the complement system in occupational heat stress-related kidney disease may help clarify its role in disease pathogenesis and provide potential future therapeutic targets.