Abstract

A new form of chronic tubulointerstitial kidney disease (CKD) not related to diabetes or hypertension appeared during the past four decades in several peri-equatorial and predominantly agricultural countries. Commonalities include underground stagnation of drinking water with prolonged contact with rocks, harsh climatic conditions with protracted dry seasons, and rampant poverty and malnutrition. In general, the cause is unknown, and the disease is therefore named CKD of unknown aetiology (CKDu). Since it is likely caused by a combination of factors, a better term would be CKD of multifactorial origin (CKDmfo). Middle-aged malnourished men with more than 10 years of exposure to environmental hazards are the most vulnerable. Over 30 factors have been proposed as causative, including agrochemicals and heavy metals, but none has been properly tested nor proven as causative, and unlikely to be the cause of CKDmfo/CKDu. Conditions such as, having favourable climatic patterns, adequate hydration, and less poverty and malnutrition seem to prevent the disease. With the right in vivo conditions, chemical species such as calcium, phosphate, oxalate, and fluoride form intra-renal nanomineral particles initiating the CKDmfo. This article examines the key potential chemical components causing CKDmfo together with the risk factors and vulnerabilities predisposing individuals to this disease. Research findings suggest that in addition to drinking water from stagnant sources that contain high ionic components, more than 10 years of exposure to environmental nephrotoxins and micronutrient malnutrition are needed to contract this fatal disease.

Highlights

  • The prevalence of common chronic diseases is increasing worldwide, including type 2 diabetes (T2D), metabolic syndrome, obesity, and chronic kidney disease (CKD) [1]

  • This review focuses on CKD of multifactorial origin” (CKDmfo) in Sri Lanka, based on the data collected over two decades

  • Kidneys are essential for maintaining normal calcium, phosphorus, and magnesium homeostasis, which are disrupted in the presence of renal failure

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Summary

Introduction

The prevalence of common chronic diseases is increasing worldwide, including type 2 diabetes (T2D), metabolic syndrome, obesity, and chronic kidney disease (CKD) [1]. These diseases significantly increase morbidities and premature deaths [2]. Data points toward a combination of multiple factors and conditions causing this fatal disease, and a more accurate term would be “CKD of multifactorial origin” (CKDmfo). Because the cause remains unknown, the disease is called “CKD of unknown origin” (CKDu) [4,5,6]. Human behaviour and types of food consumed are comparable in affected and non-affected regions; differences include the quality of water, degree of hydration and amount of water consumed, poverty, and malnutrition

Demographics Associated with CKDmfo
Geographical Distribution of CKDmfo
Diagnosis of CKDmfo
Urinary Biomarkers for CKDmfo
Prognosis of CKDmfo
Summary of Proposed Causes of CKDmfo
Physiology of Renal Filtration Unit
CKDmfo
Toxic Tubular Nephropathy
1.10. Factors that Lead to Prolongation of the Disease
Extenuating Factors Affecting CKDmfo
CKDmfo and Chronic Exposure to Nephrotoxins
Sources of Water Contamination with Nephrotoxins
Mechanisms Initiating Tubular Inflammation and Fibrosis Leading to CKDmfo
Relationship of Drinking Water and CKDmfo
Contribution of Agrochemicals and Pollution to CKDmfo
Fluoride in Drinking Water and CKDmfo
Excess Fluoride Intake from Water
Dental and Skeletal Fluorosis and CKDmfo
Observations and New Concepts
Geographical and Other Similarities of CKDmfo-Affected Regions and Countries
Effects of Diet and Malnutrition
Ion Interactions and In Vivo Formation of Apatite
Nanominerals Causing Pathology
Other Factors to Consider
Explanations of Why Wet Zonal Regions are Spared of CKDmfo
Findings
Discussion
Conclusions
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