Nanocrystal-induced Chronic Tubulaonephropathy in Tropical Countries: Diagnosis, Mitigation, and Eradication

Abstract

In tropical countries, a mysterious tubulointerstitial chronic renal disease (CKD), unrelated to diabetes, hypertension, and immunological causes, manifested over the past four decades. Approximately 25,000 primarily middle-aged male farmers succumb annually to this crystal-tubular nephropathy (CTN). Its cause is hypothesised to arise from agrochemical or heavy metal contamination of food or drinking water. Since no causative factor was identified, this CKD due to crystalline tubular-nephropathy (CKD-CTN) was known as CKD of unknown aetiology (CKDu or CKDmfo). However, current data suggest that it is due to natural causes. Clinical manifestation of CKD-CTN occurs following decades of consumption of high-ionic stagnant groundwater, aided by fluoride. In all affected countries, prolonged annual dry seasons lead to the concentration of ions and minerals in groundwater, making water unpalatable, thus less water consumption. In addition, exposure to hot climatic conditions and daily alcohol intake sustains chronic dehydration. These conditions provide a highly conducive environment—a perfect storm—for calcium phosphate (CaPO4) crystal formation in renal tissues. Recent histological and preliminary electron microscopic data reveal CaPO4 crystals and nano-tubes deposition in kidneys. While CaPO4 nano-minerals are unstable, the presence of fluoride ions stabilises and makes them grow. This new concept paves the path for highly cost-effective, simple solutions to protect peasants and eliminate the disease without embarking on expensive medications or interventions. Chronic dehydration-associated renal crystal formation is preventable by consuming potable water. This straightforward solution of providing drinking water to affected communities prevents chronic dehydration, CKD-CTN-associated renal failure and premature deaths. However, it becomes irreversible once the disease is established beyond CKD stage IIIB. Therefore, eradicating CKD-CTN is through prevention—education and increased water consumption, not by treating end-stage renal disease, expanding dialysis centres and renal transplantation services. The straightforward approaches described here will prevent CKD-CTN and save thousands of lives in affected farming communities.