Genetic and environmental risk factors for chronic kidney disease
Authors: Gregorio T. Obrador, Ulla T. Schultheiss, Matthias Kretzler, Robyn G. Langham, Masaomi Nangaku, Roberto Pecoits-Filho, Carol Pollock, Jerome Rossert, Ricardo Correa-Rotter, Peter Stenvinkel, Robert Walker, Chih-Wei Yang, Caroline S. Fox, Anna Köttgen
Journal: Kidney International Supplements (2017)

In order to change the current state of chronic kidney disease knowledge and therapeutics, a fundamental improvement in the understanding of genetic and environmental causes of chronic kidney disease is essential. This article first provides an overview of the existing knowledge gaps in our understanding of the genetic and environmental causes of chronic kidney disease, as well as their interactions. The second part of the article formulates goals that should be achieved in order to close these gaps, along with suggested timelines and stakeholders that are to be involved. A better understanding of genetic and environmental factors and their interactions that influence kidney function in healthy and diseased conditions can provide novel insights into renal physiology and pathophysiology and result in the identification of novel therapeutic or preventive targets to tackle the global public health care problem of chronic kidney disease. In order to change the current state of chronic kidney disease knowledge and therapeutics, a fundamental improvement in the understanding of genetic and environmental causes of chronic kidney disease is essential. This article first provides an overview of the existing knowledge gaps in our understanding of the genetic and environmental causes of chronic kidney disease, as well as their interactions. The second part of the article formulates goals that should be achieved in order to close these gaps, along with suggested timelines and stakeholders that are to be involved. A better understanding of genetic and environmental factors and their interactions that influence kidney function in healthy and diseased conditions can provide novel insights into renal physiology and pathophysiology and result in the identification of novel therapeutic or preventive targets to tackle the global public health care problem of chronic kidney disease. Understanding genetic and environmental factors influencing kidney function in healthy and diseased conditions and the interaction between genetic susceptibility factors and the environment can provide important insights into renal physiology and pathophysiology. It can reveal previously unknown or unexpected mechanisms, and consequently, research of genetic and environmental factors associated with chronic kidney disease (CKD) has the potential to identify novel therapeutic or preventive targets. In order to identify knowledge gaps and propose and prioritize activities in CKD research, the International Society of Nephrology (ISN) held a meeting of international experts in CKD research in July 2016. The main recommendations and overview of the ISN CKD roadmap were published in The Lancet.1Levin A, Tonelli M, Bonventre J, et al. Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy [e-pub ahead of print]. Lancet. http://dx.doi.org/10.1016/S0140-6736(17)30788-2. Accessed May 1, 2017.Google Scholar This review builds on the concepts in the main article and provides a more detailed summary of the current knowledge and knowledge gaps, including a detailed discussion of environmental risk factors, consideration of issues related to understanding genetic risk factors, and suggestions on methods to improve our knowledge of genetic and environmental risk factors of CKD. Important advances in human genetics in the past decade include the sequencing of the human genome, determination of patterns of genetic variation in human populations around the globe, improvements in high-throughput genotyping and massively parallel sequencing technologies, and advances in statistical genetics and bioinformatics. These resources together have led to the discovery of many novel risk genes and disease-associated genetic variants.2Manolio T.A. 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They have been used successfully in nephrology to identify genetic variants associated with important CKD etiologies as well as with kidney function in healthy and diseased conditions and to detect mutations that cause monogenic kidney diseases.6O'Seaghdha C.M. Fox C.S. Genome-wide association studies of chronic kidney disease: what have we learned?.Nat Rev Nephrol. 2011; 8: 89-99Crossref PubMed Scopus (57) Google Scholar, 7Vivante A. Hildebrandt F. Exploring the genetic basis of early-onset chronic kidney disease.Nat Rev Nephrol. 2016; 12: 133-146Crossref PubMed Scopus (198) Google Scholar, 8Wuttke M. Kottgen A. Insights into kidney diseases from genome-wide association studies.Nat Rev Nephrol. 2016; 12: 549-562Crossref PubMed Scopus (71) Google Scholar Several hundred genes are currently known to contain mutations that can cause single-gene disorders with a kidney phenotype, as well as dozens of genetic loci in which common genetic variants are associated with kidney function in the normal range and with complex kidney diseases.8Wuttke M. Kottgen A. Insights into kidney diseases from genome-wide association studies.Nat Rev Nephrol. 2016; 12: 549-562Crossref PubMed Scopus (71) Google Scholar Although it is now possible to efficiently discover new disease genes as a basis for the translation of gene discovery into improved CKD prevention and treatment, important gaps in understanding the mechanism of action of the genetic components of CKD remain, hindering translational efforts. First, there is limited education and awareness of the value and importance of genetic research. This is true not only for the lay public but also for clinicians, researchers, and patients. Lack of education can pose a particular challenge in clinical genetics, especially with respect to the initiation and type of genetic testing, assessment of the pathogenicity of detected genetic variants, and patient counseling. Moreover, realistic expectations and timelines for the clinical translation of genetic findings are often not well communicated. Second, despite the fact that some indigenous populations of non-European ancestry show especially high rates of kidney disease, much of the genetic research so far has been carried out in patients and study populations of European ancestry. Previous studies have supported the existence of region-specific genetic risk factors for CKD.9Genovese G. Friedman D.J. 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Rehm H.L. et al.Genetic misdiagnoses and the potential for health disparities.N Engl J Med. 2016; 375: 655-665Crossref PubMed Scopus (425) Google Scholar Third, genetic research, especially of but not limited to rare diseases, can reach its full potential only through widespread data sharing. This practice is currently limited and often occurs in unstandardized formats. However, comprehensive and current inventories of existing genetic datasets as well as their findability and accessibility are prerequisites to maximize the use of existing genetic evidence. Fourth, the limited existence of tools for functional genomics research in nephrology is a major roadblock for the identification of causal genes and variants, improved mechanistic insights, and clinical translation.13Fox C.S. Hall J.L. Arnett D.K. et al.Future translational applications from the contemporary genomics era: a scientific statement from the American Heart Association.Circulation. 2015; 131: 1715-1736Crossref PubMed Scopus (34) Google Scholar A variety of environmental factors have been associated with the development of CKD (Table 1).14Soderland P. Lovekar S. Weiner D.E. Brooks D.R. Kaufman J.S. Chronic kidney disease associated with environmental toxins and exposures.Adv Chronic Kidney Dis. 2010; 17: 254-264Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar, 15Weaver V.M. Fadrowski J.J. Jaar B.G. Global dimensions of chronic kidney disease of unknown etiology (CKDu): a modern era environmental and/or occupational nephropathy?.BMC Nephrol. 2015; 16: 145Crossref PubMed Scopus (108) Google Scholar Several of these factors have been implicated as potential causes of CKD in so-called CKD hotspots, which are defined as countries, regions, communities, or ethnicities with higher than an average incidence of CKD16Martin-Cleary C. Ortiz A. CKD hotspots around the world: where, why and what the lessons are. A CKJ review series.Clin Kidney J. 2014; 7: 519-523Crossref PubMed Scopus (46) Google Scholar (Figure 117Abraham G. Varughese S. Thandavan T. et al.Chronic kidney disease hotspots in developing countries in South Asia.Clin Kidney J. 2016; 9: 135-141Crossref PubMed Scopus (82) Google Scholar). In most CKD hotspots, CKD is not due to traditional causes such as diabetes or hypertension.15Weaver V.M. Fadrowski J.J. Jaar B.G. Global dimensions of chronic kidney disease of unknown etiology (CKDu): a modern era environmental and/or occupational nephropathy?.BMC Nephrol. 2015; 16: 145Crossref PubMed Scopus (108) Google Scholar, 18Lunyera J. Mohottige D. Isenburg M.V. et al.CKD of uncertain etiology: a systematic review.Clin J Am Soc Nephrol. 2016; 11: 379-385Crossref PubMed Scopus (114) Google Scholar Despite the suspected causative role of environmental factors, a cause-effect relationship has not been demonstrated in most regions, and thus, CKD of unknown etiology (CKDu) and infections remain the leading causes of CKD in the majority of CKD hotspots15Weaver V.M. Fadrowski J.J. Jaar B.G. Global dimensions of chronic kidney disease of unknown etiology (CKDu): a modern era environmental and/or occupational nephropathy?.BMC Nephrol. 2015; 16: 145Crossref PubMed Scopus (108) Google Scholar, 18Lunyera J. Mohottige D. 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Rajagopalan B. et al.Climate change and the emergent epidemic of CKD from heat stress in rural communities: the case for heat stress nephropathy.Clin J Am Soc Nephrol. 2016; 11: 1472-1483Crossref PubMed Scopus (226) Google Scholar, 24Paula Santos U. Zanetta D.M. Terra-Filho M. Burdmann E.A. Burnt sugarcane harvesting is associated with acute renal dysfunction.Kidney Int. 2015; 87: 792-799Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 25Roncal Jimenez C.A. Ishimoto T. Lanaspa M.A. et al.Fructokinase activity mediates dehydration-induced renal injury.Kidney Int. 2014; 86: 294-302Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 26Garcia-Trabanino R. Jarquin E. Wesseling C. et al.Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador–A cross-shift study of workers at risk of Mesoamerican nephropathy.Environ Res. 2015; 142: 746-755Crossref PubMed Scopus (183) Google Scholar, 27Roncal-Jimenez C. Garcia-Trabanino R. Barregard L. et al.Heat stress nephropathy from exercise-induced uric acid crystalluria: a perspective on Mesoamerican nephropathy.Am J Kidney Dis. 2016; 67: 20-30Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar, 28Wesseling C. Aragon A. Gonzalez M. et al.Kidney function in sugarcane cutters in Nicaragua–A longitudinal study of workers at risk of Mesoamerican nephropathy.Environ Res. 2016; 147: 125-132Crossref PubMed Scopus (96) Google Scholar, 29Garcia-Arroyo F.E. Cristobal M. Arellano-Buendia A.S. et al.Rehydration with soft drink-like beverages exacerbates dehydration and worsens dehydration-associated renal injury.Am J Physiol Regul Integr Comp Physiol. 2016; 311: R57-R65Crossref PubMed Scopus (56) Google Scholar, 30Wimalawansa S.J. Escalating chronic kidney diseases of multi-factorial origin in Sri Lanka: causes, solutions, and recommendations.Environ Health Prev Med. 2014; 19: 375-394Crossref PubMed Scopus (52) Google Scholar, 31Jayasumana C. Paranagama P. Agampodi S. et al.Drinking well water and occupational exposure to herbicides is associated with chronic kidney disease, in Padavi-Sripura, Sri Lanka.Environ Health. 2015; 14: 6Crossref PubMed Scopus (126) Google Scholar, 32Wanigasuriya K. Update on uncertain etiology of chronic kidney disease in Sri Lanka's north-central dry zone.MEDICC Rev. 2014; 16: 61-65PubMed Google Scholar, 33Yaxley J. Litfin T. Non-steroidal anti-inflammatories and the development of analgesic nephropathy: a systematic review.Ren Fail. 2016; 38: 1328-1334Crossref PubMed Scopus (8) Google Scholar, 34Stanifer J.W. Muiru A. Jafar T.H. Patel U.D. Chronic kidney disease in low- and middle-income countries.Nephrol Dial Transplant. 2016; 31: 868-874Crossref PubMed Scopus (132) Google Scholar, 35Jha V, Rathi M. Natural medicines causing acute kidney injury. Semin Nephrol. 28:416–428.Google Scholar, 36Jha V. Prasad N. CKD and Infectious diseases in Asia Pacific: challenges and opportunities.Am J Kidney Dis. 2016; 68: 148-160Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 37Yang H.Y. Hung C.C. Liu S.H. et al.Overlooked risk for chronic kidney disease after leptospiral infection: a population-based survey and epidemiological cohort evidence.PLoS Negl Trop Dis. 2015; 9: e0004105Google Scholar, 38Freedman B.I. APOL1 and nephropathy progression in populations of African ancestry.Semin Nephrol. 2013; 33: 425-432Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar, 39Freedman B.I. Skorecki K. Gene-gene and gene-environment interactions in apolipoprotein L1 gene-associated nephropathy.Clin J Am Soc Nephrol. 2014; 9: 2006-2013Crossref PubMed Scopus (78) Google Scholar, 40Naicker S. Rahmanian S. Kopp J.B. HIV and chronic kidney disease.Clin Nephrol. 2015; 83: 32-38Crossref PubMed Scopus (59) Google Scholar).Table 1Environmental factors potentially associated with the development of chronic kidney diseaseFactorHeavy metals (lead, cadmium, arsenic, mercury, uranium)Environmental chemicalsAgricultural chemicalsIndustrial waste productsAristolochic acidOccupational exposuresNonsteroidal antiinflammatory drugsCounterfeit drugsTraditional herbal medicinesInfectionsIllegal alcohol consumptionSugary beveragesSalty foodCKD, chronic kidney disease. Open table in a new tab Table 2Environmental and occupational factors that are associated with kidney damageHeavy metals14Soderland P. Lovekar S. Weiner D.E. Brooks D.R. Kaufman J.S. Chronic kidney disease associated with environmental toxins and exposures.Adv Chronic Kidney Dis. 2010; 17: 254-264Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar, 15Weaver V.M. Fadrowski J.J. Jaar B.G. Global dimensions of chronic kidney disease of unknown etiology (CKDu): a modern era environmental and/or occupational nephropathy?.BMC Nephrol. 2015; 16: 145Crossref PubMed Scopus (108) Google ScholarLead•Potential sources include lead paint (pre-1977), water from lead pipes, leaded gasoline, adulterated alcohol (moonshine), food contaminated during processing, and contamination of water, soil, and air in areas close to lead smelters, old mines, or garages.•Acute toxicity manifests with Fanconi-type syndrome and chronic toxicity with gout, hypertension, and CKD due to tubulointerstitial nephritis.•Body lead burden can be measured by X-ray fluorescence or chelation tests and measurement of urinary lead excretion (normal values are uncertain for the latter test).•Treatment consists of minimizing exposure and chelation therapy; however, chelation does not remove lead from bone, which may be a continued source of lead.Cadmium•Potential sources include tobacco smoke, certain foods (seafood, cereals, and vegetables), nickel-cadmium batteries, fuel combustion, industrial and household waste, sewage, Indian medicinal herbs, and residence in contaminated areas.•Clinically manifests with Fanconi-type syndrome, nephrolithiasis, and hypercalciuria.•Itai-itai disease in Japan is due to the ingestion of rice contaminated with cadmium from the water of the Jinzu River; clinical manifestations include anemia, osteomalacia, severe bone pain ("itai" means "ouch" in Japanese), and progressive CKD. High levels of cadmium in soil and rice and a simultaneous increase in the urinary levels of cadmium have also been reported in inhabitants of the Mae Sot District, Tak Province, Thailand.•Treatment consists of supportive care and elimination of exposure.Arsenic•Potential sources include food contaminated by pesticides, seafood, groundwater, traditional remedies, and wood preservation products.•Clinically manifests with CKD, and there is a good correlation between serum levels and worsening renal function.•Treatment consists of supportive care and elimination of exposure.Mercury•Potential sources include fish contamination from water, fuel combustion, contaminated water, whitening creams, dental amalgam (controversial), and cereals (treated with ethyl mercury as pesticide).•A typical example from the1950s is Minamata disease in Japan, where the local food supply (mainly fish) was contaminated by the water of Minamata Bay due to mercury-containing waste from a chemical factory.•Acute toxicity manifests with acute tubular necrosis and potential residual tubulointerstitial nephritis and chronic toxicity because of the damage to the proximal tubule or nephrotic syndrome due to either membranous glomerulonephritis or minimal change disease.•Treatment consists of elimination of exposure, as mercury-induced nephropathy is often reversible.Uranium•Contaminated food or groundwater, uranium mining, dermal exposure in children playing in contaminated areas.•Clinically manifests with Fanconi-type features due to proximal tubule damage, including low molecular weight proteinuria.•Treatment consists of elimination of the exposure.Other toxins•Exposure to AA has been associated with the development of chronic tubulointerstitial nephritis and urothelial cancer. BEN is deemed to be caused by AA consumption through contaminated wheat; several Chinese herbal medications contain AA, and thus, Chinese herb nephropathy is considered to be a form of AAN. Replacement of one substance (Stephania) by Aristolochia in Chinese herbal weight loss pills was the cause of the outbreak of kidney failure and urothelial cancer seen in women visiting a clinic in Brussels in the early 1990s. More cases of AAN due to consumption of Chinese herb remedies have been reported in other countries, particularly in China and Taiwan.20Debelle F.D. Vanherweghem J.L. Nortier J.L. Aristolochic acid nephropathy: a worldwide problem.Kidney Int. 2008; 74: 158-169Abstract Full Text Full Text PDF PubMed Scopus (575) Google Scholar•Exposure to environmental chemicals used for daily consumer activities (dietary intake of food, domestic and commercial food preparation, household maintenance procedures) or medical treatment (routine medical and dental care) may lead to kidney damage; however, further research is needed to clarify the mechanism and long-term effects of these exposures.21Kataria A. Trasande L. Trachtman H. The effects of environmental chemicals on renal function.Nat Rev Nephrol. 2015; 11: 610-625Crossref PubMed Scopus (130) Google Scholar•Exposure to certain industrial chemicals has been associated with the development of kidney damage.14Soderland P. Lovekar S. Weiner D.E. Brooks D.R. Kaufman J.S. Chronic kidney disease associated with environmental toxins and exposures.Adv Chronic Kidney Dis. 2010; 17: 254-264Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar•Exposure to occupational chemicals and toxic substances other than metals, such as methylene chloride, carbon tetrachloride, trichloroethylene, toluene, and arsine gas, may lead to acute tubular necrosis, although CKD has rarely been reported; exposure to occupational solvents accelerates the progression of underlying kidney disease even if the primary lesion is unrelated to the exposure.14Soderland P. Lovekar S. Weiner D.E. Brooks D.R. Kaufman J.S. Chronic kidney disease associated with environmental toxins and exposures.Adv Chronic Kidney Dis. 2010; 17: 254-264Abstract Full Text Full Text PDF PubMed Scopus (167) Google ScholarOccupational exposures•MeN mainly affects agricultural workers and is probably related to repeated episodes of AKI secondary to dehydration and volume depletion, heat stress, and rhabdomyolysis associated with extreme labor; hyperuricemia and uric acid crystalluria may contribute to the pathogenesis of heat stress nephropathy; consumption of NSAIDs, illegal alcohol, and fructose-containing beverages may also play a role; exposure to pesticides and other agrochemicals, heavy metals, and toxic pollutants are other potential risk factors.22Correa-Rotter R. Wesseling C. Johnson R.J. CKD of unknown origin in Central America: the case for a Mesoamerican nephropathy.Am J Kidney Dis. 2014; 63: 506-520Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar, 23Glaser J. Lemery J. Rajagopalan B. et al.Climate change and the emergent epidemic of CKD from heat stress in rural communities: the case for heat stress nephropathy.Clin J Am Soc Nephrol. 2016; 11: 1472-1483Crossref PubMed Scopus (226) Google Scholar, 24Paula Santos U. Zanetta D.M. Terra-Filho M. Burdmann E.A. Burnt sugarcane harvesting is associated with acute renal dysfunction.Kidney Int. 2015; 87: 792-799Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 25Roncal Jimenez C.A. Ishimoto T. Lanaspa M.A. et al.Fructokinase activity mediates dehydration-induced renal injury.Kidney Int. 2014; 86: 294-302Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 26Garcia-Trabanino R. Jarquin E. Wesseling C. et al.Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador–A cross-shift study of workers at risk of Mesoamerican nephropathy.Environ Res. 2015; 142: 746-755Crossref PubMed Scopus (183) Google Scholar, 27Roncal-Jimenez C. Garcia-Trabanino R. Barregard L. et al.Heat stress nephropathy from exercise-induced uric acid crystalluria: a perspective on Mesoamerican nephropathy.Am J Kidney Dis. 2016; 67: 20-30Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar, 28Wesseling C. Aragon A. Gonzalez M. et al.Kidney function in sugarcane cutters in Nicaragua–A longitudinal study of workers at risk of Mesoamerican nephropathy.Environ Res. 2016; 147: 125-132Crossref PubMed Scopus (96) Google Scholar, 29Garcia-Arroyo F.E. Cristobal M. Arellano-Buendia A.S. et al.Rehydration with soft drink-like beverages exacerbates dehydration and worsens dehydration-associated renal injury.Am J Physiol Regul Integr Comp Physiol. 2016; 311: R57-R65Crossref PubMed Scopus (56) Google Scholar•In Sri Lanka, India (two coastal districts of Andhra Pradesh), and Pakistan, contamination of water and/or food by industrial chemicals, agrochemicals, and heavy metals has been suspected but not confirmed.17Abraham G. Varughese S. Thandavan T. et al.Chronic kidney disease hotspots in developing countries in South Asia.Clin Kidney J. 2016; 9: 135-141Crossref PubMed Scopus (82) Google Scholar, 30Wimalawansa S.J. Escalating chronic kidney diseases of multi-factorial origin in Sri Lanka: causes, solutions, and recommendations.Environ Health Prev Med. 2014; 19: 375-394Crossref PubMed Scopus (52) Google Scholar, 31Jayasumana C. Paranagama P. Agampodi S. et al.Drinking well water and occupational exposure to herbicides is associated with chronic kidney disease, in Padavi-Sripura, Sri Lanka.Environ Health. 2015; 14: 6Crossref PubMed Scopus (126) Google Scholar, 32Wanigasuriya K. Update on uncertain etiology of chronic kidney disease in Sri Lanka's north-central dry zone.MEDICC Rev. 2014; 16: 61-65PubMed Google ScholarMedications•Analgesic abuse has been associated with AKI, reduced GFR, and probably CKD, although the latter is controversial.33Yaxley J. Litfin T. Non-steroidal anti-inflammatories and the development of analgesic nephropathy: a systematic review.Ren Fail. 2016; 38: 1328-1334Crossref PubMed Scopus (8) Google Scholar•Counterfeit medications may account for 10%–60% of the drugs available in the market of some LMICs and are potential hazards for developing CKD and for patients who already have CKD.34Stanifer J.W. Muiru A. Jafar T.H. Patel U.D. Chronic kidney disease in low- and middle-income countries.Nephrol Dial Transplant. 2016; 31: 868-874Crossref PubMed Scopus (132) Google ScholarHerbal remedies•Herbal remedies are often used in rural populations in Asia and Africa and have become popular in developed countries. Unfortunately, they are still available legally in many countries and can be bought via the Internet.20Debelle F.D. Vanherweghem J.L. Nortier J.L. Aristolochic acid nephropathy: a worldwide problem.Kidney Int. 2008; 74: 158-169Abstract Full Text Full Text PDF PubMed Scopus (575) Google Scholar, 35Jha V, Rathi M. Natural medicines causing acute kidney injury. Semin Nephrol. 28:416–428.Google Scholar•Herbal remedies have been associated with the development of AKI, CKD, renal papillary necrosis, nephrolithiasis, tubular and electrolyte disturbances, hypertension, and urothelial cancer.20Debelle F.D. Vanherweghem J.L. Nortier J.L. Aristolochic acid nephropathy: a worldwide problem.Kidney Int. 2008; 74: 158-169Abstract Full Text Full Text PDF PubMed Scopus (575) Google Scholar, 35Jha V, Rathi M. Natural medicines causing acute kidney injury. Semin Nephrol. 28:416–428.Google ScholarInfections•Infections are still prevalent in many LMICs due to insufficient access to safe water, poor sanitary conditions, and high concentrations of disease-transmitting vectors.36Jha V. Prasad N. CKD and Infectious diseases in Asia Pacific: challenges and opportunities.Am J Kidney Dis. 2016; 68: 148-160Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar•Potential renal pathogens include schistosomiasis, filariasis, leishmaniasis, toxoplasmosis, onchocerciasis, malaria, leptospirosis, tuberculosis and other mycobacterial diseases (e.g., leprosy), rickettsial diseases (e.g., typhus), hemorrhagic fevers, and viral vector-borne diseases (e.g., hantavirus, dengue fever, and yellow fever).14Soderland P. Lovekar S. Weiner D.E. Brooks D.R. Kaufman J.S. Chronic kidney disease associated with environmental toxins and exposures.Adv Chronic Kidney Dis. 2010; 17: 254-264Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar, 36Jha V. Prasad N. CKD and Infectious diseases in Asia Pacific: challenges and opportunities.Am J Kidney Dis. 2016; 68: 148-160Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 37Yang H.Y. Hung C.C. Liu S.H. et al.Overlooked risk for chronic kidney disease after leptospiral infection: a population-based survey and epidemiological cohort evidence.PLoS Negl Trop Dis. 2015; 9: e0004105Google Scholar•Enteric and diarrheal diseases (e.g., Escherichia coli, Shigella dysenteriae, and typhoid) may lead to AKI and CKD.34Stanifer J.W. Muiru A. Jafar T.H. Patel U.D. Chronic kidney disease in low- and middle-income countries.Nephrol Dial Transplant. 2016; 31: 868-874Crossref PubMed Scopus (132) Google Scholar, 36Jha V. Prasad N. CKD and Infectious diseases in Asia Pacific: challenges and opportunities.Am J Kidney Dis. 2016; 68: 148-160Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar•HIV-associated nephropathy is epidemic in Sub-Saharan Africa and highly prevalent in African Americans (potential role of high-risk alleles in APOL1 and MYH9).38Freedman B.I. APOL1 and nephropathy progression in populations of African ancestry.Semin Nephrol. 2013; 33: 425-432Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar,