Association of Kidney Disease Outcomes With Risk Factors for CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

doi:10.1053/j.ajkd.2013.08.028

American Journal of Kidney Diseases

Volume 63, Issue 2, February 2014, Pages 236-243

https://doi.org/10.1053/j.ajkd.2013.08.028 Get rights and content

Background

Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized.

Study Design

Prospective cohort study.

Setting & Participants

The Chronic Renal Insufficiency Cohort (CRIC) Study (N = 3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race.

Predictors

Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors.

Outcomes

Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR < 15 mL/min/1.73 m², (3) eGFR halving and <15 mL/min/1.73 m², (4) eGFR decrease of 20 mL/min/1.73 m², (5) eGFR halving or decrease of 20 mL/min/1.73 m², and (6) eGFR decrease of 25% and change in CKD stage.

Results

Mean entry eGFR was 44.9 mL/min/1.73 m². Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively.

Limitations

Participants may not be representative of the entire CKD population.

Conclusions

Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression.

Section snippets

Study Population

The CRIC Study is a multicenter prospective cohort study of a racially and ethnically diverse group of adults aged 21-74 years at baseline with mild to moderate CKD and diabetes in approximately half. The primary objective of the study is to identify new risk factors for the progression of CKD and cardiovascular disease in men and women with CKD. A total of 3,939 participants were recruited from clinical centers in Philadelphia, PA; Baltimore, MD; Cleveland, OH; Ann Arbor and Detroit, MI;

Study Participants and Baseline Characteristics

A total of 3,939 men and women were enrolled in the CRIC Study (Table 1). Mean age was 58.2 ± 11.0 (SD) years, with 29% of participants older than 65 years. Forty-two percent were black and 45% were women. Forty-eight percent of participants had diabetes. Mean eGFR at baseline was 44.9 ± 16.8 mL/min/1.73 m². Median 24-hour urine protein excretion at study entry was 0.18 (interquartile range, 0.07-0.91) g. Mean duration of follow-up was approximately 5.4 years.

Event Rates

Six hundred one participants died (2.8

Discussion

A wide variety of outcomes, either singly or in combination, have been used in studies to characterize progression of CKD, including measures of kidney function, initiation of renal replacement therapy (maintenance hemodialysis or kidney transplantation), and death. The relationship of outcomes that include different levels of kidney function decline and the association with putative risk factors for CKD has been reported infrequently. Using a large ethnically and racially diverse cohort of men

Acknowledgements

The CRIC Study Investigators additionally include Lawrence J. Appel, MD, MPH; Alan S. Go, MD; and Raymond R. Townsend, MD.

Support: Funding for the CRIC Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the Perelman School of Medicine at the University of

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Ultraprocessed foods are industrial formulations produced using ingredients and processes that are not commonly used in culinary preparations and contain few, if any, intact unprocessed foods. Ultraprocessed foods are widely consumed in the United States, and high intakes of such foods have been linked to cardiovascular disease, kidney disease, and mortality in the general population. In this study, we found that greater intake of ultraprocessed foods was associated with higher risk of kidney disease progression and mortality in adults with chronic kidney disease. Our findings suggest that patients with kidney disease may benefit from greater consumption of fresh, whole, and homemade or hand-prepared foods and fewer highly processed foods.
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A total of 712 participants were enrolled in 18 months with 1256 24-hour urine and 1260 dietary recalls. Barriers to enrollment were the following: (i) a lack of understanding of research, (ii) the burden of research visits, and (iii) incorporating cultural and traditional nuances when designing research protocols. Factors facilitating enrollment were the following: (i) designing convenient research visits, (ii) building rapport and increased communication between the research team and participants, and (iii) cultural sensitivity – adapting research protocols for the populations involved. Offering home visits, providing free dietary counseling, reducing the volume of study blood collection, and reducing the frequency of visits were some changes made in the study protocol that increased participant satisfaction.
Adopting a participant-centered approach with accommodations in the protocol for cultural adaptability and incorporating participant feedback is vital for carrying out research in low-income and middle-income regions.
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This long-term pragmatic trial found that in patients with CKD under stable nephrology care, adherence to protein restriction is low. Prescribing sVLPD compared with standard LPD is safe but does not provide additional advantage to the kidney or patient survival.
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^∗: W.Y. and D.X. contributed equally to this work.

^†: A list of additional CRIC Study Investigators appears in the Acknowledgements.

View full text

Original InvestigationPathogenesis and Treatment of Kidney DiseaseAssociation of Kidney Disease Outcomes With Risk Factors for CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Background

Study Design

Setting & Participants

Predictors

Outcomes

Results

Limitations

Conclusions

Section snippets

Study Population

Study Participants and Baseline Characteristics

Event Rates

Discussion

Acknowledgements

Am J Kidney Dis

Am J Kidney Dis

Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial

JAMA

The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group

N Engl J Med

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial

JAMA

Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD Study shown? Modification of Diet in Renal Disease Study Group

J Am Soc Nephrol

Validation of creatinine-based estimates of GFR when evaluating risk factors in longitudinal studies of kidney disease

J Am Soc Nephrol

Original Investigation
Pathogenesis and Treatment of Kidney Disease
Association of Kidney Disease Outcomes With Risk Factors for CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study