The Synergistic Relationship Between Estimated GFR and Microalbuminuria in Predicting Long-term Progression to ESRD or Death in Patients With Diabetes: Results From the Kidney Early Evaluation Program (KEEP)

American Journal of Kidney Diseases (Impact Factor: 5.9). 04/2013; 61(4):S12–S23. DOI: 10.1053/j.ajkd.2013.01.005


Chronic kidney disease may complicate diabetes, often manifesting with reduced glomerular filtration rate (GFR), albuminuria, or both. Although greater albuminuria and lower estimated GFR both predict adverse prognosis, whether a synergistic prognostic interaction occurs in patients with diabetes has not been defined in a large national cohort study.

We used 2000-2011 data from the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) for 42,761 participants with diabetes. Kaplan-Meier survival analysis and multivariable Cox regression were used to ascertain the association of estimated GFR, albumin-creatinine ratio (ACR), and their interaction on all-cause mortality and progression to end-stage renal disease (ESRD) at a median 4 years of follow-up.

Of 42,761 participants with diabetes, 8,618 (20.2%) had estimated GFR <60 mL/min/1.73 m2, 7,715 (18.0%) had ACR >30 mg/g, and 2,641 (6.2%) had both. The unadjusted incidence (per 1,000 person-years) of all-cause mortality increased from 3.1 (95% CI, 2.4-3.8) in participants with estimated GFR ≥105 mL/min/1.73 m2 and no albuminuria to 73.7 (95% CI, 54.9-92.5) in participants with estimated GFR <30 mL/min/1.73 m2 and macroalbuminuria (P < 0.001). Progression to ESRD likewise increased from 0.2 (95% CI, 0-0.4) to 220.4 (95% CI, 177.2-263.6) per 1,000 person-years (P < 0.001). After adjustment for confounders, both estimated GFR and albuminuria were associated independently with mortality and progression to ESRD, with a strong synergistic interaction (P for interaction < 0.001); estimated GFR <30 mL/min/1.73 m2 and macroalbuminuria together were associated with a 5-fold higher risk of mortality and a more than 1,000-fold higher risk of progression to ESRD (compared with patients with estimated GFR >60 mL/min/1.73 m2 and ACR <30 mg/g; P < 0.001 for both outcomes).

In this large cohort of diabetic KEEP participants with more than 170,000 person-years of follow-up, both estimated GFR and albuminuria were associated independently with mortality and progression to ESRD, with a strong synergistic interaction.

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    ABSTRACT: NKF-KEEP has been the only sustained chronic disease screening, detection, and awareness program in the United States. Its success should be attributed to the renal community and to a detection method that places a premium on patient care. Understanding of barriers to care and factors that influence disease progression in early CKD stages is limited, but crucial to improving CKD-related morbidity and mortality. KEEP data provide unique opportunities for the renal community to increase understanding of the role of detection on a largescale as related to variable CKD progression (Fig 2), related complications, and mortality. In 2012, data derived from KEEP continued to provide important information regarding CKD complications, such as control of blood pressure and mineral metabolism, and regarding awareness and access issues. In this supplement, we report factors that influence disease progression in highrisk participants with preserved eGFR, whether combined use of eGFR and albuminuria enhances risk prediction, 15 and the role of insurance status. The KEEP steering committee continues to develop novel methods to reach patients and providers, expand understanding of barriers to care, and increase CKD awareness and general measures to improve diseaserelated morbidity. We anticipate that future work also will improve the complex interface between disease detection, navigation of the health care system, and CKD-related outcomes. Of greatest importance will be movement toward enhanced scalability of KEEP to achieve even greater reach across the United States and in partnership with primary care physicians, specialists, and our international colleagues around the world. This inflection point in the history of KEEP is important as the program moves from site-driven screening events to more global internet-based selfreported data, advanced kidney learning systems, and clinical involvement from practicing physicians caring for individuals at risk for CKD and ESRD.
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