Opponent’s comments Free

The heat stress hypothesis is strong because the renal effects of heat (increased body temperature) and dehydration (hyperosmolarity) are clinically, epidemiologically and experimentally consistent with the disease without requiring additional factors. In response to the arguments raised by Dr Campese, the increased frequency of disease along the Pacific coast is consistent with greater mean temperatures in this area (Figure 1) [1]; the reason climate change may partially explain the recent rise in cases is because climate change, while raising mean temperatures slightly, is responsible for the marked increase in heat extremes [2] as we discussed. While not everyone has a high serum uric acid, studies show that the mean uric acid is higher than expected for the kidney function [3] and also strongly correlates with the disease [4]. The fact that some women and children show signs of renal injury is because there will be a gradient with heat stress exposure from high exposure (fieldwork) to lesser exposure. Heat stress-associated renal disease is also associated with fever, leukocyturia and acute interstitial inflammation that later becomes chronic interstitial fibrosis [5, 6].

FIGURE 1

Average temperatures (1951–2010) are greatest along the Pacific Coast in Central America and this correlates with the location of MeN. Adapted from Glaser et al. [1].

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The attractive hypothesis by Dr Campese that dehydration increases tubular reabsorption of toxins and thereby could be primarily an augmenting factor remains possible and has been previously suggested [1, 7, 8], but the primary obstacle is that despite extensive screening no specific toxin has been identified. It has been proposed that it may involve the collective effect of multiple toxins that concentrate into the kidney at levels below classically toxic levels [7], which is a difficult hypothesis to test. If it is a toxin, the exposure must be widespread, for the disease in Central America appears clinically similar to the epidemics occurring elsewhere throughout the world.

Nevertheless, I am reminded of an epidemic of renal failure and visceral gout that killed the vast majority of vultures (raptors) in India and Pakistan and was due to the feeding of cattle with a nonsteroidal (diclofenac); in this situation, the combination of dehydration, uricase deficiency and contamination of livestock meat with an NSAID was the root cause of the epidemic [9]. Therefore, I agree with Dr Campese that we should not view the heat stress hypothesis as proven, and we must continue to look for toxins in both the water and food that could augment the effects of dehydration.

Emily Dickinson wrote a poem entitled ‘Dwell in Possibility’, which we all should. But if we have to dwell in probability, recurrent heat stress is sufficient to explain the epidemic.

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