Elsevier

The Lancet

Volume 376, Issue 9758, 18–31 December 2010, Pages 2096-2103
The Lancet

Articles
Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study

https://doi.org/10.1016/S0140-6736(10)61271-8Get rights and content

Summary

Background

Low values of estimated glomerular filtration rate (eGFR) predispose to acute kidney injury, and proteinuria is a marker of kidney disease. We aimed to investigate how eGFR and proteinuria jointly modified the risks of acute kidney injury and subsequent adverse clinical outcomes.

Methods

We did a cohort study of 920 985 adults residing in Alberta, Canada, between 2002 and 2007. Participants not needing chronic dialysis at baseline and with at least one outpatient measurement of both serum creatinine concentration and proteinuria (urine dipstick or albumin-creatinine ratio) were included. We assessed hospital admission with acute kidney injury with validated administrative codes; other outcomes were all-cause mortality and a composite renal outcome of end-stage renal disease or doubling of serum creatinine concentration.

Findings

During median follow-up of 35 months (range 0–59 months), 6520 (0·7%) participants were admitted with acute kidney injury. In those with eGFR 60 mL/min per 1·73 m2 or greater, the adjusted risk of admission with this disorder was about 4 times higher in those with heavy proteinuria measured by dipstick (rate ratio 4·4 vs no proteinuria, 95% CI 3·7–5·2). The adjusted rates of admission with acute kidney injury and kidney injury needing dialysis remained high in participants with heavy dipstick proteinuria for all values of eGFR. The adjusted rates of death and the composite renal outcome were also high in participants admitted with acute kidney injury, although the rise associated with this injury was attenuated in those with low baseline eGFR and heavy proteinuria.

Interpretation

These findings suggest that information on proteinuria and eGFR should be used together when identifying people at risk of acute kidney injury, and that an episode of acute kidney injury provides further long-term prognostic information in addition to eGFR and proteinuria.

Funding

The study was funded by an interdisciplinary team grant from Alberta Heritage Foundation for Medical Research.

Introduction

Acute kidney injury is common, preventable, and associated with adverse short-term and long-term outcomes in various clinical settings.1, 2 Acute kidney injury needing dialysis is associated with inhospital mortality, ranging from 30% to 80%, but even slight declines in kidney function are associated with excess mortality, extended length of hospital stay, and increased costs.3, 4 Survivors of acute kidney injury could have persistent loss of kidney function and are at increased risk of end-stage renal disease.5, 6, 7, 8

Chronic kidney disease is also associated with adverse outcomes.9, 10 Specifically, at every level of estimated glomerular filtration rate (eGFR), the presence of proteinuria is associated with several-fold variation in the risks of mortality, cardiovascular events, and end-stage renal disease.11, 12, 13 Although people with low eGFR are at increased risk of acute kidney injury,14, 15, 16 the usefulness of proteinuria in combination with eGFR to predict the risk of this disorder is unknown. Furthermore, whether associations between acute kidney injury and subsequent adverse outcomes occur independently of the effects of pre-existing kidney disease remains controversial. Currently, assessment of the risk or outcomes of acute kidney injury does not incorporate information about both proteinuria and eGFR.17, 18, 19, 20

We examined the associations of eGFR and proteinuria with the risk of hospital admission with acute kidney injury, as well as the risk of needing dialysis. We hypothesised that patients with both reduced eGFR and proteinuria would be at higher risk of these outcomes than were those with one or neither characteristic. We also examined the rates of death and progression of kidney disease associated with acute kidney injury, in combination with baseline eGFR and proteinuria. We also hypothesised that the rates of death and end-stage renal disease would be further increased after acute kidney injury at all levels of these markers at baseline.

Section snippets

Participants

We studied all adults aged 18 years and older with at least one outpatient measurement of serum creatinine and one of proteinuria within the province of Alberta, Canada, from May 1, 2002, to Dec 31, 2006, for seven of the nine provincial health regions, and for the other two regions from July 1, 2003, to Dec 31, 2006, and from Jan 1, 2005, to Dec 31, 2006. We excluded those with end-stage renal disease at study entry (eGFR <15 mL/min per 1·73 m2; chronic dialysis; previous kidney transplant).

Procedures

Results

A total of 1 530 447 participants (about 66% of the estimated adult Alberta population) had at least one eligible outpatient measurement of serum creatinine during the study. We excluded 3728 people with end-stage renal disease before study entry on the basis of records for dialysis or kidney transplantation or index eGFR lower than 15 mL/min per 1·73 m2 and 282 people who had died on their index date. Of the 1 526 437 remaining participants, 920 985 (60%) had at least one urine dipstick

Discussion

In this large community-based cohort of adults who received laboratory testing in a Canadian province, the risk of admission with acute kidney injury increased substantially with the presence and severity of proteinuria, in addition to reduced eGFR. Furthermore, such admission was independently associated with two clinically important outcomes (mortality and the composite of end-stage renal disease or doubling of serum creatinine values), although differences in risk between participants with

References (33)

  • P Ruggenenti et al.

    Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial

    Lancet

    (1998)
  • LA Stevens et al.

    Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD

    Am J Kidney Dis

    (2008)
  • GM Chertow et al.

    Acute kidney injury, mortality, length of stay, and costs in hospitalized patients

    J Am Soc Nephrol

    (2005)
  • CR Parikh et al.

    Long-term prognosis of acute kidney injury after acute myocardial infarction

    Arch Intern Med

    (2008)
  • A Ishani et al.

    Acute kidney injury increases risk of ESRD among elderly

    J Am Soc Nephrol

    (2009)
  • BB Newsome et al.

    Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction

    Arch Intern Med

    (2008)
  • Cited by (265)

    • Newer Glucose-Lowering Therapies in Older Adults with Type 2 Diabetes

      2023, Endocrinology and Metabolism Clinics of North America
    View all citing articles on Scopus
    View full text