CKDu in Sri Lanka

Last updated

Chronic kidney disease of unknown etiology (CKDu) is an increasing health concern in Sri Lanka. [1] CKDu is recognized as chronic kidney disease without the usual associated causative factors. [2] The first cases of CKDu were reported in Sri Lanka's North Central Province (NCP). Chronic kidney disease (listed under diseases of the urinary tract), was identified as the 8th leading cause of in-hospital mortality in Sri Lanka, and the leading cause of death in Anuradhapura and Polonnaruwa in 2016. [1] This rise in mortality coincided with the increasing cases of CKDu seen across the country. [1] Studies have shown an estimated 70,000 CKDu patients in high risk areas. [3] Various possible causes for CKDu in Sri Lankans have been investigated, including poisoning from metals, cyanobacteria toxins, agrochemicals, and heat stress, but no definite causes have been identified. [4]

Contents

There have been several other geographic areas in which CKDu has emerged, such as Africa, Central America (see Mesoamerican nephropathy), and Asia. [5] Due to similar signs and symptoms of CKDu in these areas, CKDu is also referred to as Chronic Interstitial Nephritis in Agricultural Communities. [6]

Geographic distribution

CKDu is most common in Sri Lanka's NCP, [7] but cases also have been identified in some parts of Eastern, Central, and North Western provinces. [8] The affected villages are located in the dry zone of the country where it rains only a few months a year. [9]

Demographics

A combination of poverty and lack of access to healthcare has made clinical diagnosis of CKDu difficult. [4] The majority of patients are of low socioeconomic status and live in agricultural areas, or are involved in farming. [1] Although it also occurs in females and youth, the majority of CKDu patients are males between 17 and 70 years of age. [2] [10] High numbers of CKDu cases are individuals in their most productive working age (30 – 60 years), creating a negative economic impact in affected areas. [10] [2] Within the NCP and its bordering villages, a 15-20% prevalence of CKDu has been reported. [9]

Timeline

1990 - CKDu first reported in Sri Lanka's dry zones. [3]

2009 - Sri Lanka's Ministry of Health and The World Health Organization conducted a study to determine the etiology of CKDu [1] with the goal of developing preventative strategies. [7]

2016 - A case definition for CKDu was developed and published by Sri Lanka's Ministry of Health to help identify CKDu in Sri Lanka. [1]

Disease overview

CKDu is characterized by a lack of common risk factors (e.g. diabetes and hypertension) [5] normally associated with Chronic Kidney Disease. [2] This disease manifests itself as asymptomatic at first, with a slow progression until later stages, when it becomes irreversible. [10] The most common symptoms include: fatigue, panting, lack of appetite, nausea, and anemia. [2] CKDu typically results in death due to low access to dialysis and organ transplant technology. [4] Annual deaths are estimated at 1,400 based on medical and clinical observations. [3] Affected kidneys exhibit a toxic etiology called tubulointerstitial nephritis. [5]

Possible causes

The concentration of CKDu cases in the NCP suggests multiple risk factors - including a combination of nephrotoxins - that may be responsible for the prevalence of this disease. [10] Potential causes include dehydrating working conditions, genetic susceptibility, and various lifestyle factors. [10] Although one single causative factor has not been identified as the source of CKDu, occupational and environmental causes have been identified as the main reason for the prevalence of the disease. [5] Possible environmental exposures include:

Drinking water

The lack of surface water in the dry zone of Sri Lanka has led many people in the NCP to rely mainly on groundwater in dug and tube wells. [2] An estimated 87% of the population in dry zone regions use and consume groundwater. [9] Elevated fluoride levels and distribution patterns in potable water have been detected in the drinking water of CKDu prevalent areas. [10] Fluoride is an important causal component of CKDu due to its tendency to accumulate in the kidneys. [5] Additionally, studies have shown that there may be a possible link between water hardness, fluoride concentration, and CKDu prevalence. [5] Therefore, drinking water quality might be a significant contributing factor to the disease; several villages that have implemented drinking water regulations seemed to have lower cases of CKDu. [3]

Exposure to metals

The widespread use of agrochemicals in Sri Lanka has led some researchers to study various heavy metals found within these chemicals as potential causes of CKDu in afflicted regions. [7] The significant differences in between wet and dry cycles in the dry zone can influence the bioavailability of heavy metals. [10] People can be exposed to these metals through water and diet. [7] Heavy metals can induce the synthesis of Metallothionein proteins, which are responsible for metal detoxification in the body. [11] Heavy metal-induced oxidative stress plays a role in renal toxicity [12] and injury to the proximal tubules. [13] It is possible that a combination of reactions between heavy metals and water hardness might be contributing to the prevalence of CKDu. [4] Specific metals of concern include:

Mitigation considerations

Due to the unknown etiology of CKDu, funding for the clinical care of affected populations and continued research is important. [4] Some preventative suggestions based on proposed risk factors for CKDu include drinking only treated and spring water, [5] regulated safety protocol for agrochemicals, [4] and improved work practices to prevent dehydration. [4]

Related Research Articles

<span class="mw-page-title-main">Kidney stone disease</span> Formation of mineral stones in the urinary tract

Kidney stone disease, also known as renal calculus disease, nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material develops in the urinary tract. Renal calculi typically form in the kidney and leave the body in the urine stream. A small calculus may pass without causing symptoms. If a stone grows to more than 5 millimeters, it can cause blockage of the ureter, resulting in sharp and severe pain in the lower back that often radiates downward to the groin. A calculus may also result in blood in the urine, vomiting, or painful urination. About half of people who have had a renal calculus are likely to have another within ten years.

<span class="mw-page-title-main">Drinking water</span> Water safe for consumption

Drinking water or potable water is water that is safe for ingestion, either when drunk directly in liquid form or consumed indirectly through food preparation. It is often supplied through taps, in which case it is also called tap water.

<span class="mw-page-title-main">Kidney failure</span> Disease where the kidneys fail to adequately filter waste products from the blood

Kidney failure, also known as end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible. Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications of acute and chronic failure include uremia, hyperkalemia, and volume overload. Complications of chronic failure also include heart disease, high blood pressure, and anaemia.

<span class="mw-page-title-main">Kidney disease</span> Damage to or disease of a kidney

Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option.

<span class="mw-page-title-main">Chronic kidney disease</span> Abnormal kidney structure or gradual loss of kidney function

Chronic kidney disease (CKD) is a type of long-term kidney disease, in which either there is a gradual loss of kidney function which occurs over a period of months to years, or an abnormal kidney structure. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications can relate to hormonal dysfunction of the kidneys and include high blood pressure, bone disease, and anemia. Additionally CKD patients have markedly increased cardiovascular complications with increased risks of death and hospitalization. CKD can lead to kidney failure requiring kidney dialysis or kidney transplantation.

<span class="mw-page-title-main">Water fluoridation</span> Addition of fluoride to a water supply to reduce tooth decay

Water fluoridation is the addition of fluoride to a public water supply to reduce tooth decay. Fluoridated water contains fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding fluoride. Fluoridated water operates on tooth surfaces: in the mouth, it creates low levels of fluoride in saliva, which reduces the rate at which tooth enamel demineralizes and increases the rate at which it remineralizes in the early stages of cavities. Typically a fluoridated compound is added to drinking water, a process that in the U.S. costs an average of about $1.32 per person-year. Defluoridation is needed when the naturally occurring fluoride level exceeds recommended limits. In 2011, the World Health Organization suggested a level of fluoride from 0.5 to 1.5 mg/L, depending on climate, local environment, and other sources of fluoride. In 2024, the Department of Health and Human Services' National Toxicology Program found that water fluoridation levels above 1.5 mg/L are associated with lower IQ in children. In 2024, U.S. court rulings have raised concerns about the potential health risks of water fluoridation, including findings by the EPA and new risk assessments that suggest the benefits may be waning. Bottled water typically has unknown fluoride levels.

<span class="mw-page-title-main">Goodpasture syndrome</span> Rare autoimmune disease

Goodpasture syndrome (GPS), also known as anti–glomerular basement membrane disease, is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs, glomerulonephritis, and kidney failure. It is thought to attack the alpha-3 subunit of type IV collagen, which has therefore been referred to as Goodpasture's antigen. Goodpasture syndrome may quickly result in permanent lung and kidney damage, often leading to death. It is treated with medications that suppress the immune system such as corticosteroids and cyclophosphamide, and with plasmapheresis, in which the antibodies are removed from the blood. Due to the GPS's rapid progression, the significant difficulty of treating the disease is identifying it early and making the appropriate response before severe damage occurs to the kidneys and or lungs. Consequently, the standard treatment plan of corticosteroids, cyclophosphamide, and plasmapheresis is vigorous and fast-acting, including high plasma volume exchange and an intensive dose of corticosteroid and cyclophosphamide based on the patient's body weight in kilograms.

Fluoride toxicity is a condition in which there are elevated levels of the fluoride ion in the body. Although fluoride is safe for dental health at low concentrations, sustained consumption of large amounts of soluble fluoride salts is dangerous. Referring to a common salt of fluoride, sodium fluoride (NaF), the lethal dose for most adult humans is estimated at 5 to 10 g. Ingestion of fluoride can produce gastrointestinal discomfort at doses at least 15 to 20 times lower than lethal doses. Although it is helpful topically for dental health in low dosage, chronic ingestion of fluoride in large amounts interferes with bone formation. In this way, the most widespread examples of fluoride poisoning arise from consumption of ground water that is abnormally fluoride-rich.

<span class="mw-page-title-main">Pyelonephritis</span> Inflammation of the kidney

Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications may include pus around the kidney, sepsis, or kidney failure.

Cadmium is a naturally occurring toxic metal with common exposure in industrial workplaces, plant soils, and from smoking. Due to its low permissible exposure in humans, overexposure may occur even in situations where only trace quantities of cadmium are found. Cadmium is used extensively in electroplating, although the nature of the operation does not generally lead to overexposure. Cadmium is also found in some industrial paints and may represent a hazard when sprayed. Operations involving removal of cadmium paints by scraping or blasting may pose a significant hazard. The primary use of cadmium is in the manufacturing of NiCd rechargeable batteries. The primary source for cadmium is as a byproduct of refining zinc metal. Exposures to cadmium are addressed in specific standards for the general industry, shipyard employment, the construction industry, and the agricultural industry.

<span class="mw-page-title-main">Dental fluorosis</span> Tooth enamel discoloration due to excessive fluoride ingestion

Dental fluorosis is a common disorder, characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation.

<span class="mw-page-title-main">Osteitis fibrosa cystica</span> Medical condition

Osteitis fibrosa cystica is a skeletal disorder resulting in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue, and the formation of cyst-like brown tumors in and around the bone. Osteitis fibrosis cystica (OFC), also known as osteitis fibrosa, osteodystrophia fibrosa, and von Recklinghausen's disease of bone, is caused by hyperparathyroidism, which is a surplus of parathyroid hormone from over-active parathyroid glands. This surplus stimulates the activity of osteoclasts, cells that break down bone, in a process known as osteoclastic bone resorption. The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy. Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream, causing both elevated blood calcium levels, and the structural changes which weaken the bone. The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss.

Chandre Dharma-wardana is a Sri Lankan-born academic and scientist. A former president of Vidyodaya Campus, he is currently a professor of theoretical physics at the Université de Montréal. He has retired and continues as a principal research scientist at the National Research Council of Canada.

<span class="mw-page-title-main">Arsenic contamination of groundwater</span> Form of water pollution

Arsenic contamination of groundwater is a form of groundwater pollution which is often due to naturally occurring high concentrations of arsenic in deeper levels of groundwater. It is a high-profile problem due to the use of deep tube wells for water supply in the Ganges Delta, causing serious arsenic poisoning to large numbers of people. A 2007 study found that over 137 million people in more than 70 countries are probably affected by arsenic poisoning of drinking water. The problem became a serious health concern after mass poisoning of water in Bangladesh. Arsenic contamination of ground water is found in many countries throughout the world, including the US.

In epidemiology, environmental diseases are diseases that can be directly attributed to environmental factors. Apart from the true monogenic genetic disorders, which are rare, environment is a major determinant of the development of disease. Diet, exposure to toxins, pathogens, radiation, and chemicals found in almost all personal care products and household cleaners, stress, racism, and physical and mental abuse are causes of a large segment of non-hereditary disease. If a disease process is concluded to be the result of a combination of genetic and environmental factor influences, its etiological origin can be referred to as having a multifactorial pattern.

Mesoamerican nephropathy (MeN) is an endemic, non-diabetic, non-hypertensive chronic kidney disease (CKD) characterized by reduced glomerular filtration rate (GFR) with mild or no proteinuria and no features of known primary glomerular diseases. MeN is prevalent in agricultural communities along the Pacific Ocean coastal lowlands Mesoamerica, including southern Mexico, Guatemala, El Salvador, Nicaragua, Honduras and Costa Rica. Although most cases have been described among agricultural workers, MeN has also been described in other occupations, including miners, brick manufacturers, and fishermen. A common denominator among these occupations is that they are outdoor workers who reside in rural areas in hot and humid climates.

<span class="mw-page-title-main">Groundwater pollution</span> Ground released seep into groundwater

Groundwater pollution occurs when pollutants are released to the ground and make their way into groundwater. This type of water pollution can also occur naturally due to the presence of a minor and unwanted constituent, contaminant, or impurity in the groundwater, in which case it is more likely referred to as contamination rather than pollution. Groundwater pollution can occur from on-site sanitation systems, landfill leachate, effluent from wastewater treatment plants, leaking sewers, petrol filling stations, hydraulic fracturing (fracking) or from over application of fertilizers in agriculture. Pollution can also occur from naturally occurring contaminants, such as arsenic or fluoride. Using polluted groundwater causes hazards to public health through poisoning or the spread of disease.

Professor Wendy Elizabeth Hoy AO is a Fellow of the Australian Academy of Science (FAA), the Director of the Centre for Chronic Disease at the University of Queensland, Australia, and was appointed an Officer of the Order of Australia (AO) in 2010 and elected as a member of the Australian Academy of Science in 2015. Hoy's research has involved developing new types of kidney imaging and improving health and lives for indigenous populations, in Australia, Sri Lanka and the USA.

Uddanam nephropathy is a chronic kidney disease (CKD) that is endemic in the Uddanam region of Andhra Pradesh in India. Nephropathy on an endemic scale was first reported in Andhra Pradesh in the 1990s. In 2015, over 34,000 cases of kidney disease were recorded in the region, and it was estimated that at least 4,500 people had died from it in the last ten years. Its cause has not been found yet, and according to the WHO, it is "the least understood and the least publicized" nephropathy of unknown origin.

Padaviya is a historic town in the Anuradhapura District of the North Central Province, Sri Lanka.

References

  1. 1 2 3 4 5 6 Wijewickrama, Eranga S.; Gunawardena, Nalika; Jayasinghe, Saroj; Herath, Chula (2019-04-03). "CKD of Unknown Etiology (CKDu) in Sri Lanka: A Multilevel Clinical Case Definition for Surveillance and Epidemiological Studies". Kidney International Reports. 4 (6): 781–785. doi:10.1016/j.ekir.2019.03.020. ISSN   2468-0249. PMC   6551535 . PMID   31194108.
  2. 1 2 3 4 5 6 Cooray, Titus; Wei, Yuansong; Zhong, Hui; Zheng, Libing; Weragoda, Sujithra K.; Weerasooriya, Rohan (2019-03-29). "Assessment of Groundwater Quality in CKDu Affected Areas of Sri Lanka: Implications for Drinking Water Treatment". International Journal of Environmental Research and Public Health. 16 (10): 1698. doi: 10.3390/ijerph16101698 . PMC   6572134 . PMID   31091829.
  3. 1 2 3 4 Edirisinghe, E. A. N. V.; Manthrithilake, H.; Pitawala, H. M. T. G. A.; Dharmagunawardhane, H. A.; Wijayawardane, R. L. (2018-05-04). "Geochemical and isotopic evidences from groundwater and surface water for understanding of natural contamination in chronic kidney disease of unknown etiology (CKDu) endemic zones in Sri Lanka". Isotopes in Environmental and Health Studies. 54 (3): 244–261. Bibcode:2018IEHS...54..244E. doi:10.1080/10256016.2017.1377704. ISSN   1025-6016. PMID   28948847. S2CID   4548414.
  4. 1 2 3 4 5 6 7 Weaver, Virginia M.; Fadrowski, Jeffrey J.; Jaar, Bernard G. (2015-08-19). "Global dimensions of chronic kidney disease of unknown etiology (CKDu): a modern era environmental and/or occupational nephropathy?". BMC Nephrology. 16 (1): 145. doi: 10.1186/s12882-015-0105-6 . ISSN   1471-2369. PMC   4539684 . PMID   26282933.
  5. 1 2 3 4 5 6 7 8 9 10 11 Wasana, Hewa M. S.; Aluthpatabendi, Dharshani; Kularatne, W. M. T. D.; Wijekoon, Pushpa; Weerasooriya, Rohan; Bandara, Jayasundera (2016-02-01). "Drinking water quality and chronic kidney disease of unknown etiology (CKDu): synergic effects of fluoride, cadmium and hardness of water". Environmental Geochemistry and Health. 38 (1): 157–168. Bibcode:2016EnvGH..38..157W. doi:10.1007/s10653-015-9699-7. ISSN   1573-2983. PMID   25859936. S2CID   25173484.
  6. ↑ Agampodi, S. B.; Amarasinghe, G. S.; Naotunna, P. G. C. R.; Jayasumana, C. S.; Siribaddana, S. H. (2018-05-16). "Early renal damage among children living in the region of highest burden of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka". BMC Nephrology. 19 (1): 115. doi: 10.1186/s12882-018-0911-8 . ISSN   1471-2369. PMC   5956963 . PMID   29769043.
  7. 1 2 3 4 Redmon, Jennifer Hoponick; Elledge, Myles F.; Womack, Donna S.; Wickremashinghe, Rajitha; Wanigasuriya, Kamani P.; Peiris-John, Roshini J.; Lunyera, Joseph; Smith, Kristin; Raymer, James H.; Levine, Keith E. (2014-07-28). "Additional perspectives on chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka – lessons learned from the WHO CKDu population prevalence study". BMC Nephrology. 15 (1): 125. doi: 10.1186/1471-2369-15-125 . ISSN   1471-2369. PMC   4120717 . PMID   25069485.
  8. ↑ Edirisinghe, E. A. N. V.; Manthrithilake, H.; Pitawala, H. M. T. G. A.; Dharmagunawardhane, H. A.; Wijayawardane, R. L. (2018-05-04). "Geochemical and isotopic evidences from groundwater and surface water for understanding of natural contamination in chronic kidney disease of unknown etiology (CKDu) endemic zones in Sri Lanka". Isotopes in Environmental and Health Studies. 54 (3): 244–261. Bibcode:2018IEHS...54..244E. doi:10.1080/10256016.2017.1377704. ISSN   1025-6016. PMID   28948847. S2CID   4548414.
  9. 1 2 3 Balasooriya, Shyamalie; Munasinghe, Harshaka; Herath, A. T.; Diyabalanage, Saranga; Ileperuma, O. A.; Manthrithilake, Herath; Daniel, Christoph; Amann, Kerstin; Zwiener, Christian; Barth, Johannes A. C.; Chandrajith, Rohana (2019-12-17). "Possible links between groundwater geochemistry and chronic kidney disease of unknown etiology (CKDu): an investigation from the Ginnoruwa region in Sri Lanka". Exposure and Health. 12 (4): 823–834. doi:10.1007/s12403-019-00340-w. ISSN   2451-9685. S2CID   212893543.
  10. 1 2 3 4 5 6 7 8 Levine, Keith E.; Redmon, Jennifer Hoponick; Elledge, Myles F.; Wanigasuriya, Kamani P.; Smith, Kristin; Munoz, Breda; Waduge, Vajira A.; Periris-John, Roshini J.; Sathiakumar, Nalini; Harrington, James M.; Womack, Donna S. (2016-09-03). "Quest to identify geochemical risk factors associated with chronic kidney disease of unknown etiology (CKDu) in an endemic region of Sri Lanka—a multimedia laboratory analysis of biological, food, and environmental samples". Environmental Monitoring and Assessment. 188 (10): 548. Bibcode:2016EMnAs.188..548L. doi:10.1007/s10661-016-5524-8. ISSN   1573-2959. PMID   27591985. S2CID   5721251.
  11. ↑ Robles-Osorio, Ma Ludivina; Sabath-Silva, Elizabeth; Sabath, Ernesto (2015-04-21). "Arsenic-mediated nephrotoxicity". Renal Failure. 37 (4): 542–547. doi: 10.3109/0886022X.2015.1013419 . ISSN   0886-022X. PMID   25703706. S2CID   24239987.
  12. ↑ Shaikh, Zahir A.; Vu, Thanhtam T.; Zaman, Khalequz (1998-10-20). "Oxidative Stress as a Mechanism of Chronic Cadmium-Induced Hepatotoxicity and Renal Toxicity and Protection by Antioxidants". Toxicology and Applied Pharmacology. 154 (3): 256–263. doi:10.1006/taap.1998.8586. PMID   9931285.
  13. ↑ Prozialeck, W.C.; Vaidya, V.S.; Liu, J.; Waalkes, M.P.; Edwards, J.R.; Lamar, P.C.; Bernard, A.M.; Dumont, X.; Bonventre, J.V. (2007-10-02). "Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity". Kidney International. 72 (8): 985–993. doi:10.1038/sj.ki.5002467. PMC   2747605 . PMID   17687258.
  14. ↑ "LankaWeb – Presence of Arsenic in pesticides used in Sri Lanka" . Retrieved 2020-12-09.
  15. 1 2 Ileperuma, O.A.; Dharmagunawardhane, H.A.; Herath, K.P.R.P (2009-09-26). "Dissolution of aluminium from sub-standard utensils under high fluoride stress: a possible risk factor for chronic renal failure in the North-Central Province". Journal of the National Science Foundation of Sri Lanka. 37 (3): 219. doi: 10.4038/jnsfsr.v37i3.1217 . ISSN   2362-0161.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.