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Chronic kidney disease of unknown origin occurs in young sugar cane workers in Central American countries and Mexico (Mesoamerican Nephropathy). Occupational heat stress from high physical workload in hot climate is a key etiology and pathophysiologic pathways need further investigation. We examined whether (repeated) episodes of subclinical rhabdomyolysis contribute to kidney injury and tested the validity of our observations in animal experiments.
We determined serum myoglobulin (ng/ml), serum creatine kinase (CK, Units/L) and serum creatinine (Scr mg/dl) in 109 sugar cane cutters, 19-78 years, before and after a working shift of 8-12 hours during sugar cane harvest in Acatlán of Perez Figueroa, Mexico. We also studied subclinical rhabdomyolysis induced in rats with daily intramuscular injections of 2 ml/kg of 50% glycerol for 1 month (GLY group, n=4). Control rats (n=4) were injected with 0.9% saline. Kidney histology was studied at the end of the experiment and kidney function was followed for additional 4 weeks.
Results (mean ± SE). In the patients, there were significant cross-shift increments (p<0.0001, paired t tests) of serum myoglobulin (Pre=33.2±1.42; Post=60.0±5.02), CK (figure 1A) and Scr (Figure 1B), correlating with each other (p<0.0001). In rats, daily subclinical rhabdomyolysis shown by mild increments in CK (GLY group Pre=59±2; Post=73±2, p=0.004 on day 5) was associated with tubulointerstitial fibrosis in the kidney (Figure 1D, PAS stain) and with increase in Scr that returned to normal after 4 weeks (Figure 1C).
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A single working shift in sugar cane harvesters is associated with subclinical rhabdomyolysis. Repeated episodes of mild rhabdomyolysis in rats result in tubulointerstitial fibrosis and reversible deterioration of kidney function. Daily subclinical rhabdomyolysis should be studied as a possible important cofactor of Mesoamerican nephropathy.