Quantifying a rare disease in administrative data: The example of calciphylaxis

Sagar U. Nigwekar, Craig A. Solid, Elizabeth Ankers, Rajeev Malhotra, William Eggert, Alexander Turchin, Ravi I. Thadhani, Charles A. Herzog

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76 Scopus citations


BACKGROUND: Calciphylaxis, a rare disease seen in chronic dialysis patients, is associated with significant morbidity and mortality. As is the case with other rare diseases, the precise epidemiology of calciphylaxis remains unknown. Absence of a unique International Classification of Diseases (ICD) code impedes its identification in large administrative databases such as the United States Renal Data System (USRDS) and hinders patient-oriented research. This study was designed to develop an algorithm to accurately identify cases of calciphylaxis and to examine its incidence and mortality. DESIGN, PARTICIPANTS, AND MAIN MEASURES: Along with many other diagnoses, calciphylaxis is included in ICD-9 code 275.49, Other Disorders of Calcium Metabolism. Since calciphylaxis is the only disorder listed under this code that requires a skin biopsy for diagnosis, we theorized that simultaneous application of code 275.49 and skin biopsy procedure codes would accurately identify calciphylaxis cases. This novel algorithm was developed using the Partners Research Patient Data Registry (RPDR) (n=11,451 chronic hemodialysis patients over study period January 2002 to December 2011) using natural language processing and review of medical and pathology records (the gold-standard strategy). We then applied this algorithm to the USRDS to investigate calciphylaxis incidence and mortality. KEY RESULTS: Comparison of our novel research strategy against the gold standard yielded: sensitivity 89.2 %, specificity 99.9 %, positive likelihood ratio 3,382.3, negative likelihood ratio 0.11, and area under the curve 0.96. Application of the algorithm to the USRDS identified 649 incident calciphylaxis cases over the study period. Although calciphylaxis is rare, its incidence has been increasing, with a major inflection point during 2006-2007, which corresponded with specific addition of calciphylaxis under code 275.49 in October 2006. Calciphylaxis incidence continued to rise even after limiting the study period to 2007 onwards (from 3.7 to 5.7 per 10,000 chronic hemodialysis patients; r=0.91, p=0.02). Mortality rates among calciphylaxis patients were noted to be 2.5-3 times higher than average mortality rates for chronic hemodialysis patients. CONCLUSIONS: By developing and successfully applying a novel algorithm, we observed a significant increase in calciphylaxis incidence. Because calciphylaxis is associated with extremely high mortality, our study provides valuable information for future patient-oriented calciphylaxis research, and also serves as a template for investigating other rare diseases.

Original languageEnglish (US)
Pages (from-to)S724-S731
JournalJournal of general internal medicine
Issue numberSUPPL. 3
StatePublished - Aug 2014
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements: Conception and design: Sagar Nigwekar, Ravi Thadhani, Charles Herzog Analysis and interpretation of data: Sagar Nigwekar, Craig Solid, William Eggert, Rajeev Malhotra, Alexander Turchin, Elizabeth Ankers, Ravi Thadhani, Charles Herzog Drafting of the article: Sagar Nigwekar, Elizabeth Ankers Critical revision of the article: Craig Solid, William Eggert, Elizabeth Ankers, Rajeev Malhotra, Alexander Turchin, Ravi Thadhani, Charles Herzog Final approval of the article: Sagar Nigwekar, Craig Solid, William Eggert, Elizabeth Ankers, Rajeev Malhotra, Alexander Turchin, Ravi Thadhani, Charles Herzog Administrative, technical and logistic support: Sagar Nigwekar, Elizabeth Ankers, Rajeev Malhotra Collection and assembly of data: Sagar Nigwekar, Alexander Turchin, Craig Solid, William Eggert, Rajeev Malhotra, Ravi Thadhani, Charles Herzog Sagar Nigwekar is supported by the Clinical Scientist in Nephrology Fellowship award from the American Kidney Fund and by Sanofi-Aventis Fellowship award. Ravi Thadhani is supported by National Institute of Health grants DK094872 and DK094486. Dr Herzog served as the director of the USRDS Cardiovascular Special Study Center through February 2014 and was supported by Contract No. HHSN267200715003C (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland). Rajeev Malhotra was supported by the American Heart Association Fellow-to-Faculty Award #11FTF7290032 and is supported by the National Heart, Lung, and Blood Institute (K08HL111210). Portion of this work was presented as an oral abstract at the American Society of Nephrology’s annual conference in Atlanta, GA in November 2013. The authors would like to thank Thadhani Lab members for constructive input on this manuscript and Massachusetts General Hospital’s Multi-disciplinary Calciphylaxis Team for accurate identification of calciphylaxis cases in the RPDR. Authors would also like to thank Julia Wenger for statistical analysis help while revising this manuscript.

Funding Information:
Alexander Turchin reports receiving grant support from Merck, Sharp and Dohme, Inc., serves on the scientific Advisory Board of Monarch Medical Technologies, and is a consultant to GNS Healthcare. Ravi Thadhani is a consultant to Fresenius Medical Care North America and has received a research grant from Abbott Laboratories. Charles Herzog is a consultant to Abbott Laboratories, Abbvie, and Amgen. He also reports having received lecture honoraria from Fresenius Medical Care North America.


  • calciphylaxis
  • dialysis
  • renal disease
  • research design


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