CKD of Uncertain Etiology: A Systematic Review

Clin J Am Soc Nephrol. 2016 Mar 7;11(3):379-85. doi: 10.2215/CJN.07500715. Epub 2015 Dec 28.


Background and objectives: Epidemics of CKD of uncertain etiology (CKDu) are emerging around the world. Highlighting common risk factors for CKD of uncertain etiology across various regions and populations may be important for health policy and public health responses.

Design, setting, participants, & measurements: We searched PubMed, Embase, Scopus and Web of Science databases to identify published studies on CKDu. The search was generated in January of 2015; no language or date limits were used. We used a vote-counting method to evaluate exposures across all studies.

Results: We identified 1607 articles, of which 26 met inclusion criteria. Eighteen (69%) were conducted in known CKDu-endemic countries: Sri Lanka (38%), Nicaragua (19%), and El Salvador (12%). The other studies were from India, Japan, Australia, Mexico, Sweden, Tunisia, Tanzania, and the United States. Heavy metals, heat stress, and dietary exposures were reported across all geographic regions. In south Asia, family history, agrochemical use, and heavy metal exposures were reported most frequently, whereas altitude and temperature were reported only in studies from Central America. Across all regions, CKDu was most frequently associated with a family history of CKDu, agricultural occupation, men, middle age, snake bite, and heavy metal exposure.

Conclusions: Studies examining etiologies of CKDu have reported many exposures that are heterogeneous and vary by region. To identify etiologies of CKDu, designing consistent and comparative multisite studies across high-risk populations may help elucidate the importance of region-specific versus global risk factors.

Keywords: chronic kidney disease; global health; humans; low- and middle-income countries; nephrotoxicity; occupations; public health; renal insufficiency, chronic; risk factors; temperature.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Age Factors
  • Agricultural Workers' Diseases / epidemiology
  • Diet / adverse effects
  • Environmental Exposure / adverse effects
  • Farmers
  • Female
  • Genetic Predisposition to Disease
  • Global Health*
  • Heavy Metal Poisoning
  • Humans
  • Male
  • Occupational Exposure / adverse effects
  • Pedigree
  • Poisoning / epidemiology
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / epidemiology*
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Snake Bites / epidemiology