Subtyping CKD Patients by Consensus Clustering: The Chronic Renal Insufficiency Cohort (CRIC) Study
- 18 January 2021
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 32 (3), 639-653
- https://doi.org/10.1681/asn.2020030239
Abstract
Background CKD is a heterogeneous condition with multiple underlying causes, risk factors, and outcomes. Subtyping CKD with multidimensional patient data holds the key to precision medicine. Consensus clustering may reveal CKD subgroups with different risk profiles of adverse outcomes. Methods We used unsupervised consensus clustering on 72 baseline characteristics among 2696 participants in the prospective Chronic Renal Insufficiency Cohort (CRIC) study to identify novel CKD subgroups that best represent the data pattern. Calculation of the standardized difference of each parameter used the cutoff of ±0.3 to show subgroup features. CKD subgroup associations were examined with the clinical end points of kidney failure, the composite outcome of cardiovascular diseases, and death. Results The algorithm revealed three unique CKD subgroups that best represented patients’ baseline characteristics. Patients with relatively favorable levels of bone density and cardiac and kidney function markers, with lower prevalence of diabetes and obesity, and who used fewer medications formed cluster 1 (n=1203). Patients with higher prevalence of diabetes and obesity and who used more medications formed cluster 2 (n=1098). Patients with less favorable levels of bone mineral density, poor cardiac and kidney function markers, and inflammation delineated cluster 3 (n=395). These three subgroups, when linked with future clinical end points, were associated with different risks of CKD progression, cardiovascular disease, and death. Furthermore, patient heterogeneity among predefined subgroups with similar baseline kidney function emerged. Conclusions Consensus clustering synthesized the patterns of baseline clinical and laboratory measures and revealed distinct CKD subgroups, which were associated with markedly different risks of important clinical outcomes. Further examination of patient subgroups and associated biomarkers may provide next steps toward precision medicine.Keywords
Funding Information
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902, U24DK060990)
- National Center for Advancing Translational Sciences (UL1TR000003)
- National Center for Advancing Translational Sciences (UL1TR-000424)
- National Center for Advancing Translational Sciences (M01 RR-16500)
- Clinical and Translational Science Collaborative of Cleveland
- National Center for Advancing Translational Sciences (UL1TR000439)
- National Center for Advancing Translational Sciences (UL1TR000433)
- National Center for Research Resources (UL1RR029879)
- Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases (P20 GM109036)
- National Center for Research Resources (UL1 RR-024131)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119199)
- American Philosophical Society (Daland Fellowship in Clinical Investigation)
This publication has 37 references indexed in Scilit:
- ForewordKidney International Supplements, 2012
- CKD in Hispanics: Baseline Characteristics From the CRIC (Chronic Renal Insufficiency Cohort) and Hispanic-CRIC StudiesAmerican Journal of Kidney Diseases, 2011
- Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney diseaseKidney International, 2011
- Chronic Kidney Disease Associated With Environmental Toxins and ExposuresAdvances in Chronic Kidney Disease, 2010
- Pathologic Classification of Diabetic NephropathyJournal of the American Society of Nephrology, 2010
- Chronic Renal Insufficiency Cohort (CRIC) StudyClinical Journal of the American Society of Nephrology, 2009
- Inflammation and wasting in chronic kidney disease: Partners in crimeKidney International, 2006
- Pathophysiology of Hypertensive Renal DamageHypertension, 2004
- The Chronic Renal Insufficiency Cohort (CRIC) StudyJournal of the American Society of Nephrology, 2003
- Development and Progression of Renal Disease in Pima Indians with Non-Insulin-Dependent Diabetes MellitusThe New England Journal of Medicine, 1996