Environment, Smoking, Obesity, and the Kidney

Environmental Nephrotoxins

The most common causes of poisoning AKI are chemicals, plants, and snake envenomation, especially in developing countries. For heavy metals, please see Chapter 222 .

Nephrotoxins may be pesticides, mainly paraquat and glyphosate surfactant herbicide, other chemicals (paraphenylene-diamine dye, potassium permanganate, and oxalic acid) and toxic plants as well as snake envenomation (Russell's viper, hump-nosed pit viper, saw-scaled vipers, green pit viper, sea snakes, and Bothrops and Crotalus species). Many different pathophysiologic mechanisms overlap to generate renal injury after ischemia-reperfusion injury, although pesticides and natural toxins have a very diverse range of dose-dependent mechanisms leading to AKI.

AKI following paraquat intoxication is attributed mainly to increase reactive oxygen species (ROS) generation and inflammation, whereas glyphosate surfactant causes adenosine triphosphate (ATP) depletion via uncoupling of oxidative phosphorylation, cytochrome C activation, and macromolecular oxidation.

Exposure to organic solvents has been suggested to cause or exacerbate renal disease. Cellular toxicity appears to derive largely from metabolic activation within cells of free radical toxic metabolites with initiation of lipid peroxidation reactions causing deleterious effect on cellular membrane structure and function. Moreover, nephrotoxins themselves may become covalently bound to cellular components, ultimately leading to nephron damage. However, methodologic concerns regarding previous studies preclude firm conclusions. The results from a recent nationwide population-based study do not support the hypothesis of an adverse effect of organic solvents on renal failure development, although detrimental effects from subclasses of solvents on specific renal diseases cannot be ruled out.

Mycotoxins such as ochratoxin A, aflatoxin B, and the immunosuppressive agent cyclosporine may be nephrotoxic, and clinical syndromes have been documented. Ochratoxin A is a ubiquitous nephrotoxic and carcinogenic mycotoxin considered to be involved in the cause of Balkan endemic nephropathy. The occurrence of this human fatal disease that appears in regions of Bosnia, Herzegovina, Bulgaria, Croatia, Rumania, Serbia, and Montenegro correlates with very high incidence of otherwise rare urothelial tumors of the renal pelvis, and ureters. Although Ochratoxin A was found more frequently and/or in higher concentration in food and blood of inhabitants in regions with Balkan endemic nephropathy than in other regions, the involvement of Ochratoxin A in the development of Balkan endemic nephropathy is still open.

Acute ethylene glycol intoxication is a medical emergency that, if not diagnosed correctly and treated aggressively, will lead to serious neurologic, cardiopulmonary, and renal dysfunction, and may result in death. Ethylene glycol toxicity is characterized by severe metabolic acidosis with high anion and osmolal gaps, and calcium oxalate crystals in the urine. Early recognition of ethylene glycol intoxication and rapid, aggressive use of large amounts of sodium bicarbonate, ethanol infusion, and hemodialysis may improve survival.

Conclusion

Acute renal damage by environmental nephrotoxins should require admittance to the intensive care unit (ICU). Clinicians need to be aware of this possibility because correct diagnosis and management are critical to prevent and manage renal damage.