Background: Serum creatinine is routinely measured to estimate glomerular filtration rate (GFR). Long-term cohort studies report that death is a likelier outcome than progression to kidney failure. However, it is unclear how short-term changes in estimated GFR (eGFR) over a 1-year period relate to subsequent mortality risk. Methods: Using a provincial laboratory registry from Alberta, Canada, we identified 598,397 adults who had ≥2 outpatient eGFR measurements at least 6 months apart during a 1-year accrual period. Change in kidney function was categorized by both changes in eGFR category and percent change ≥25% into 5 groups: certain drop, uncertain drop, stable (no change in CKD category), uncertain rise, and certain rise. Cox proportional hazards models, adjusting for baseline covariates, kidney function, and proteinuria were used to estimate the risk of all-cause mortality associated with each group change in kidney function in reference to stable kidney function. Results: Among the study participants, 447,570 (74.8%) had stable kidney function, 19,591 (3.3%) had a certain drop, and 22,171 (3.7%) had a certain rise in kidney function. Participants with change in kidney function (both drop and rise) were older, more likely to be female, and had a higher prevalence of comorbidities in comparison to those with stable kidney function. There were 51,473 (8.6%) deaths during a median follow-up of 3.5 years. Compared to participants with stable kidney function, those with a certain drop had an almost twofold increased mortality risk (hazard ratio 1.89, 95% CI 1.83–1.95) adjusted for baseline eGFR, proteinuria, and covariates. Participants with a certain rise (3.7%) in kidney function also experienced an increased mortality risk (hazard ratio 1.51, 95% CI 1.46–1.56) compared to those with stable kidney function. Risk of death was similarly increased with adjustment for eGFR at the last visit. Conclusion: Change in kidney function of ≥25% in any direction over a 1-year period is associated with a substantially increased risk of mortality.

1.
K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1–S266.
2.
Levey A, Atkins R, Coresh J, Cohen E, Collins A, Eckardt K, et al: Chronic kidney disease as a global public health problem: approaches and initiatives – a position statement from Kidney Disease Improving Global Outcomes. Kidney Int 2007;72:247–259.
3.
Drey N, Roderick P, Mullee M, Rogerson M: A population-based study of the incidence and outcomes of diagnosed chronic kidney disease. Am J Kidney Dis 2003;42:677–684.
4.
Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al: Prevalence of chronic kidney disease in the United States. JAMA 2007;298:2038–2047.
5.
Zhang LX, Zhang PH, Wang F, Zuo L, Zhou Y, Shi Y, et al: Prevalence and factors associated with CKD: a population study from Beijing. Am J Kidney Dis 2008;51:373–384.
6.
Fried LF, Katz R, Sarnak MJ, Shlipak MG, Chaves PHM, Jenny NS, et al: Kidney function as a predictor of noncardiovascular mortality. J Am Soc Nephrol 2005;16:3728–3735.
7.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296–1305.
8.
Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR, et al: Relation between kidney function, proteinuria, and adverse outcomes. JAMA 2010;303:423–429.
9.
Rifkin DE, Shlipak MG, Katz R, Fried LF, Siscovick D, Chonchol M, et al: Rapid kidney function decline and mortality risk in older adults. Arch Intern Med 2008;168:2212–2218.
10.
Perkins R, Bucaloiu I, Kirchner H, Ashouian N, Hartle J, Yahya T: GFR decline and mortality risk among patients with chronic kidney disease. Clin J Am Soc Nephrol 2011;6:1879–1886.
11.
Matsushita K, Selvin E, Bash LD, Franceschini N, Astor BC, Coresh J: Change in estimated GFR associates with coronary heart disease and mortality. J Am Soc Nephrol 2009;20:2617–2624.
12.
Cheng TYD, Wen SF, Astor BC, Tao XG, Samet JM, Wen CP: Mortality risks for all causes and cardiovascular diseases and reduced GFR in a middle-aged working population in Taiwan. Am J Kidney Dis 2008;52:1051–1060.
13.
Al-Aly Z, Zeringue A, Fu J, Rauchman MI, McDonald JR, El-Achkar TM, et al: Rate of kidney function decline associates with mortality. J Am Soc Nephrol 2010;21:1961–1969.
14.
Hemmelgarn BR, Clement F, Manns BJ, Klarenbach S, James MT, Ravani P, et al: Overview of the Alberta Kidney Disease Network. BMC Nephrol 2009;10:30.
15.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et al: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604–612.
16.
Ethnocultural portrait of Canada highlight tables, 2006 census. Statistics Canada. http://www12.statcan.ca/english/census06/data/highlights/ethnic/index.cfm?Lang=E (accessed June 15, 2010).
17.
Gowans E, Fraser C: Biological variation of serum and urine creatinine and creatinine clearance: ramifications for interpretation of results and patient care. Ann Clin Biochem 1988;25:259–263.
18.
Bash LD, Coresh J, Köttgen A, Parekh RS, Fulop T, Wang Y, et al: Defining incident chronic kidney disease in the research setting. Am J Epidemiol 2009;170:414–424.
19.
Premium assistance program: premium subsidy. 2010. http://www.health.alberta.ca/AHCIP/premium-subsidy.html (accessed October 5, 2011).
20.
Hux JE, Ivis F, Flintoft V, Bica A: Diabetes in Ontario: determination of prevalence and incidence using a validated administrative data algorithm. Diabetes Care 2002;25:512–516.
21.
Quan H, Khan N, Hemmelgarn BR, Tu K, Chen G, Campbell N, et al: Validation of a case definition to define hypertension using administrative data. Hypertension 2009;54:1423–1428.
22.
Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, et al: Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 2005;43:1130–1139.
23.
Lamb EJ, MacKenzie F, Stevens PE: How should proteinuria be detected and measured? Ann Clin Biochem 2009;46:205–217.
24.
Gardner W, Mulvey E, Shaw E: Regression analyses of counts and rates: Poisson, overdispersed Poisson, and negative binomial models. Psychol Bull 1995;118:392–404.
25.
Manjunath G, Tighiouart H, Ibrahim H, MacLeod B, Salem DN, Griffith JL, et al: Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community. J Am Coll Cardiol 2003;41:47–55.
26.
Weiner DE, Tighiouart H, Amin MG, Stark PC, MacLeod B, Griffith JL, et al: Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004;15:1307–1315.
27.
Shlipak MG, Stehman-Breen C, Fried LF, Song X, Siscovick D, Fried LP, et al: The presence of frailty in elderly persons with chronic renal insufficiency. Am J Kidney Dis 2004;43:861–867.
28.
Odden MC, Chertow GM, Fried LF, Newman AB, Connelly S, Angleman S, et al: Cystatin C and measures of physical function in elderly adults. Am J Epidemiol 2006;164:1180–1189.
29.
Kovesdy CP, George SM, Anderson JE, Kalantar-Zadeh K: Outcome predictability of biomarkers of protein-energy wasting and inflammation in moderate and advanced chronic kidney disease. Am J Clin Nutr 2009;90:407–414.
30.
Shlipak MG, Katz R, Kestenbaum B, Siscovick D, Fried L, Newman A, et al: Rapid decline of kidney function increases cardiovascular risk in the elderly. J Am Soc Nephrol 2009;20:2625–2630.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.