Harnessing Evolution and Biomimetics to Enhance Planetary Health: Kidney Insights

Abstract

Planetary health encompasses the understanding that the long-term well-being of humanity is intrinsically linked to the health of global ecological systems. Unfortunately, current practices often overlook this principle, leading to a human-oriented (anthropocentric) worldview that has resulted in heightened greenhouse gas emissions, increased heat stress, lack of access to clean water, and pollution, threatening both the environment and health and survival of Homo sapiens and countless other species. One significant consequence of these environmental changes is the exacerbation of inflammatory and oxidative stressors, which not only contributes to common lifestyle diseases but also accelerates the aging process. We advocate for a shift away from our current anthropocentric frameworks to an approach that focuses on nature's solutions that developed from natural selection over the eons. This approach, which encompasses the field of biomimicry, may provide insights that can help protect against an inflammatory phenotype to mitigate physiological and cellular senescence and provide a buffer against environmental stressors. Gaining insights from how animals have developed ingenious approaches to combat adversity through the evolutionary process of natural selection not only provides solutions for climate change but also confronts the rising burden of lifestyle diseases that accumulate with age.

Figure 1

Kidneys are particularly vulnerable to a rapidly changing environment. It can be hypothesized that the rising global incidence of kidney disease reflects the effects of climate change. As such, kidney disease may be considered the “black lungs” of climate change. Scientific research has shown that various factors—including the consumption of ultra-processed foods, insufficient access to clean water, viral pandemics, exposure to toxins, heat stress, air pollution, psychosocial stress, and urbanization—contribute to the growing global burden of kidney disease.

Figure 2

Nature offers a wealth of ingenious solutions that may enhance health and address climate challenges. Natural products and their structural analogs have historically played a significant role in pharmacotherapy, contributing not only to the treatment of cancer and infectious diseases but also to the advancement of treatment of CKD, as indicated in green. Derived from the venom of the Gila monster, GLP-1 receptor agonists are used to manage diabetes and obesity. Found in the venom of the Brazilian viper, bradykinin-potentiating peptides form the basis of therapeutic strategies for CKD. Originating from phlorizin, discovered in the bark of apple trees during the 1830s, SGLT2 inhibitors are now key in CKD management.^, Cyclosporin and rapamycin, sourced from fungus and bacterium, are critical for success in transplantation. Found in the death cap mushroom, the orellanine toxin is selectively harmful to kidney cells but has been harnessed in treating metastatic kidney cancer, despite the risk of kidney function loss. Furthermore, nature provides insights into understanding disease mechanisms and developing innovative treatment strategies, as indicated in blue. Hibernating bears are metabolic marvels that offer insights into protection against osteoporosis, muscle wasting, type 2 diabetes, thromboembolism, obesity, and arteriosclerosis. With the highest recorded BP in the animal kingdom (300/180 mm Hg), giraffes exhibit no damage to their kidneys, heart, or brain, thanks to a protective genetic mutation that has been successfully transferred to mice. Bats have become models for healthy aging, showcasing remarkable defenses against chronic inflammation and viral infections. Burmese Pythons undergo significant organ growth after feeding, attributed to an enriched NRF2-mediated oxidative stress response. Tree shrews are an unassuming species that thrive on nectar from brewery-scented palm trees; they demonstrate intriguing resilience to high alcohol content. Sharks are renowned for their ability to self-heal and regenerate skin. The sluggish Greenland shark (Somniosus microcephalus) has an average lifespan of at least 250 years but can potentially reach a lifespan over 500 years. It was recently reported that genes duplicated in this shark form a functionally connected network enriched for DNA repair function. Adapted to deep-sea diving, seals possess mechanisms to protect their kidneys from oxygen deprivation. Despite the risks of fatty liver and blood glucose spikes from their high-sugar diet, hummingbirds demonstrate remarkable metabolic resilience, leading to insights into diabetes management. Komodo dragons exhibit strong immunity in bacterium-laden environments, and a synthetic molecule derived from their blood is being explored as a potential antibiotic. Sleeping only approximately 2 hours a day, elephants also display resilience to cancer, possessing an incredible 40 copies of the p⁵³ gene, providing them with superior cancer protection. Naked mole rats are unique for their insensitivity to pain, exceptional cancer resistance, and maintenance of youthful vascular health. Hippos secrete a reddish fluid once mistaken for blood—this natural UV-blocking compound protects their skin from the harsh African sun. Adapted to desert environments, camels endure extreme temperature fluctuations and demonstrate efficient water conservation. Their milk is rich in vitamin C, lactobacilli, and immunoglobulins, offering protective benefits by activating the Nrf2 pathway. Nephrologists can also glean lessons from animal species that exhibit susceptibility to disease, highlighted in red. The significantly higher risk of CKD in nondomesticated felids offers insights into dietary risk factors, particularly the consumption of red meat, enhancing our understanding of CKD susceptibility and prevention strategies. ACE, angiotensin-converting enzyme; GLP-1, glucagon-like peptide-1; Nrf2, nuclear factor erythroid two–related factor 2; SGLT2, sodium-glucose cotransporter-2.

Figure 3

Gut microbiome at the interface between exposome and diseasome. Environmental stressors including an unbalanced diet, sedentary lifestyle, air pollution, and heat stress may mediate lifestyle diseases partly by disturbing the gut microbiome. A disrupted gut microbiome, reflected by a decreased a-diversity, a shift from Bacteroides to Firmicutes predominance, and suppressed carbohydrate fermentation, may compromise the gut epithelial barrier and gut epithelial mitochondrial bioenergetics and disturb bidirectional communication with the host, the latter involving immune, endocrine, humoral, and neural signals.^, Pathophysiological pathways are complex, but mounting evidence identifies oxidative stress and inflammation as central drivers. IBD, inflammatory bowel disease.