David M Charytan1, Scott D Solomon2, Peter Ivanovich3, Giuseppe Remuzzi4, Mark E Cooper5, Janet B McGill6, Hans-Henrik Parving7, Patrick Parfrey8, Ajay K Singh9, Emmanuel A Burdmann10, Andrew S Levey11, Dick de Zeeuw12, Kai-Uwe Eckardt13, John J V McMurray14, Brian Claggett2, Eldrin F Lewis2, Marc A Pfeffer2. 1. Renal Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA. Electronic address: dcharytan@partners.org. 2. Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA. 3. Renal Division, Northwestern University, Chicago, IL. 4. Nephrology and Dialysis Unit, Azienda Ospedaliera Papa Giovanni XXIII, IRCCS-Instituto di Ricerche Farmacologiche Mario Negri, Bergamo and Department of Biomedical and Clinical Sciences, Milan, Italy. 5. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia. 6. Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO. 7. Department of Medical Endocrinology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark. 8. Division of Nephrology, Health Sciences Centre, St. John's, NF, Canada. 9. Renal Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA. 10. Division of Nephrology, University of Sao Paulo Medical School, Sao Paulo, Brazil. 11. Nephrology Division, Tufts University School of Medicine, Boston, MA. 12. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, the Netherlands. 13. Department of Nephrology Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany. 14. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.
Abstract
BACKGROUND: How cardiovascular (CV) events affect progression to end-stage renal disease (ESRD), particularly in the setting of type 2 diabetes, remains uncertain. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 4,022 patients with type 2 diabetes, anemia, and chronic kidney disease from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). PREDICTOR: Postrandomization CV events. OUTCOMES: ESRD (defined as initiation of dialysis for >30 days, kidney transplantation, or refusal or nonavailability of renal replacement therapy) and post-ESRD mortality within 30 days and during overall follow-up after an intercurrent CV event. LIMITATIONS: Population limited to clinical trial participants with diabetes and anemia. RESULTS: 155 of 652 (23.8%) ESRD cases occurred after an intercurrent CV event; 110 (16.9%) cases followed heart failure, 28 (4.3%) followed myocardial infarction, 12 (1.84%) followed stroke, and 5 (0.77%) followed multiple CV events. ESRD rate was higher within 30 days in individuals with an intercurrent CV event compared with those without an intercurrent event (HR, 22.2; 95% CI, 17.0-29.0). Compared to no intercurrent CV events, relative risks for ESRD were higher after the occurrence of heart failure overall (HR, 3.4; 95% CI, 2.7-4.2) and at 30 days (HR, 20.1; 95% CI, 14.5-27.9) than after myocardial infarction or stroke (P<0.001). Compared with individuals without pre-ESRD events, those with ESRD following intercurrent CV events were older, were more likely to have prior CV disease, and had higher (24.4 vs 23.1mL/min/1.73m2; P=0.01) baseline estimated glomerular filtration rates (eGFRs) and higher eGFRs at last measurement before ESRD (18.6 vs 15.2mL/min/1.73m2; P<0.001), whereas race, sex, and medication use were similar. Post-ESRD mortality was similar (P=0.3) with and without preceding CV events. CONCLUSIONS: Most ESRD cases occurred in individuals without intercurrent CV events who had lower eGFRs than individuals with intercurrent CV events, but similar post-ESRD mortality. Nevertheless, intercurrent CV events, particularly heart failure, are strongly associated with risk for ESRD. These findings underscore the need for kidney-specific therapies in addition to treatment of CV risk factors to lower ESRD incidence in diabetes.
BACKGROUND: How cardiovascular (CV) events affect progression to end-stage renal disease (ESRD), particularly in the setting of type 2 diabetes, remains uncertain. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 4,022 patients with type 2 diabetes, anemia, and chronic kidney disease from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). PREDICTOR: Postrandomization CV events. OUTCOMES: ESRD (defined as initiation of dialysis for >30 days, kidney transplantation, or refusal or nonavailability of renal replacement therapy) and post-ESRD mortality within 30 days and during overall follow-up after an intercurrent CV event. LIMITATIONS: Population limited to clinical trial participants with diabetes and anemia. RESULTS: 155 of 652 (23.8%) ESRD cases occurred after an intercurrent CV event; 110 (16.9%) cases followed heart failure, 28 (4.3%) followed myocardial infarction, 12 (1.84%) followed stroke, and 5 (0.77%) followed multiple CV events. ESRD rate was higher within 30 days in individuals with an intercurrent CV event compared with those without an intercurrent event (HR, 22.2; 95% CI, 17.0-29.0). Compared to no intercurrent CV events, relative risks for ESRD were higher after the occurrence of heart failure overall (HR, 3.4; 95% CI, 2.7-4.2) and at 30 days (HR, 20.1; 95% CI, 14.5-27.9) than after myocardial infarction or stroke (P<0.001). Compared with individuals without pre-ESRD events, those with ESRD following intercurrent CV events were older, were more likely to have prior CV disease, and had higher (24.4 vs 23.1mL/min/1.73m2; P=0.01) baseline estimated glomerular filtration rates (eGFRs) and higher eGFRs at last measurement before ESRD (18.6 vs 15.2mL/min/1.73m2; P<0.001), whereas race, sex, and medication use were similar. Post-ESRD mortality was similar (P=0.3) with and without preceding CV events. CONCLUSIONS: Most ESRD cases occurred in individuals without intercurrent CV events who had lower eGFRs than individuals with intercurrent CV events, but similar post-ESRD mortality. Nevertheless, intercurrent CV events, particularly heart failure, are strongly associated with risk for ESRD. These findings underscore the need for kidney-specific therapies in addition to treatment of CV risk factors to lower ESRD incidence in diabetes.
Authors: Junichi Ishigami; Logan T Cowan; Ryan T Demmer; Morgan E Grams; Pamela L Lutsey; Juan-Jesus Carrero; Josef Coresh; Kunihiro Matsushita Journal: J Am Soc Nephrol Date: 2020-01-09 Impact factor: 10.121
Authors: Elaine Ku; Wei Yang; Charles E McCulloch; Harold I Feldman; Alan S Go; James Lash; Nisha Bansal; Jiang He; Ed Horwitz; Ana C Ricardo; Tariq Shafi; James Sondheimer; Raymond R Townsend; Sushrut S Waikar; Chi-Yuan Hsu Journal: Am J Kidney Dis Date: 2019-11-12 Impact factor: 8.860