Validation of the kidney failure risk equation for end-stage kidney disease in Southeast Asia

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Abstract

Background

Patients with chronic kidney disease (CKD) are at high risk of end-stage kidney disease (ESKD). The Kidney Failure Risk Equation (KFRE), which predicts ESKD risk among patients with CKD, has not been validated in primary care clinics in Southeast Asia (SEA). Therefore, we aimed to (1) evaluate the performance of existing KFRE equations, (2) recalibrate KFRE for better predictive precision, and (3) identify optimally feasible KFRE thresholds for nephrologist referral and dialysis planning in SEA.

Methods

All patients with CKD visiting nine primary care clinics from 2010 to 2013 in Singapore were included and applied 4-variable KFRE equations incorporating age, sex, estimated glomerular filtration rate (eGFR), and albumin-to-creatinine ratio (ACR). ESKD onset within two and five years were acquired via linkage to the Singapore Renal Registry. A weighted Brier score (the squared difference between observed vs predicted ESKD risks), bias (the median difference between observed vs predicted ESKD risks) and precision (the interquartile range of the bias) were used to select the best-calibrated KFRE equation.

Results

The recalibrated KFRE (named Recalibrated Pooled KFRE SEA) performed better than existing and other recalibrated KFRE equations in terms of having a smaller Brier score (square root: 2.8% vs. 4.0–9.3% at 5 years; 2.0% vs. 6.1–9.1% at 2 years), less bias (2.5% vs. 3.3–5.2% at 5 years; 1.8% vs. 3.2–3.6% at 2 years), and improved precision (0.5% vs. 1.7–5.2% at 5 years; 0.5% vs. 3.8–4.2% at 2 years). Area under ROC curve for the Recalibrated Pooled KFRE SEA equations were 0.94 (95% confidence interval [CI]: 0.93 to 0.95) at 5 years and 0.96 (95% CI: 0.95 to 0.97) at 2 years. The optimally feasible KFRE thresholds were > 10–16% for 5-year nephrologist referral and > 45% for 2-year dialysis planning. Using the Recalibrated Pooled KFRE SEA, an estimated 82 and 89% ESKD events were included among 10% of subjects at highest estimated risk of ESKD at 5-year and 2-year, respectively.

Conclusions

The Recalibrated Pooled KFRE SEA performs better than existing KFREs and warrants implementation in primary care settings in SEA.

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Most cited references 31

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Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

Josef Coresh, Tanvir Turin, Kunihiro Matsushita … (2014)

The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

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How should proteinuria be detected and measured?

K Stevens, Edmund Lamb, Finlay MacKenzie (2009)

Proteinuria is a classic sign of kidney disease and its presence carries powerful prognostic information. Although proteinuria testing is enshrined in clinical practice guidelines, there is surprising variation among such guidelines as to the definition of clinically significant proteinuria. There is also poor agreement as to whether proteinuria should be defined in terms of albumin or total protein loss, with a different approach being used to stratify diabetic and non-diabetic nephropathy. Further, the role of reagent strip devices in the detection and assessment of proteinuria is unclear. This review explores these issues in relation to recent national and international guidelines on chronic kidney disease (CKD) and epidemiological evidence linking proteinuria and clinical outcome. The authors argue that use of urinary albumin measurement as the front-line test for proteinuria detection offers the best chance of improving the sensitivity, quality and consistency of approach to the early detection and management of CKD.

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GFR decline as an alternative end point to kidney failure in clinical trials: a meta-analysis of treatment effects from 37 randomized trials.

Lesley A. Inker, Hiddo Lambers Heerspink, Hasi Mondal … (2014)

There is increased interest in using alternative end points for trials of kidney disease progression. The currently established end points of end-stage renal disease and doubling of serum creatinine level, equivalent to a 57% decline in estimated glomerular filtration rate (eGFR), are late events in chronic kidney disease (CKD), requiring large clinical trials with long follow-up. As part of a comprehensive evaluation of lesser declines in eGFR as alternative end points, we describe the consistency of treatment effects of intervention on the alternative and established end points in past trials.

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Author and article information

Contributors

Tazeen H. Jafar: tazeen.jafar@duke-nus.edu.sg

Journal

Journal ID (nlm-ta): BMC Nephrol

Journal ID (iso-abbrev): BMC Nephrol

Title: BMC Nephrology

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2369

Publication date (Electronic): 4 December 2019

Publication date PMC-release: 4 December 2019

Publication date Collection: 2019

Volume: 20

Electronic Location Identifier: 451

Affiliations

[1 ]ISNI 0000 0004 0385 0924, GRID grid.428397.3, Program in Health Services and Systems Research, , Duke-NUS Medical School, ; 8 College Road, Singapore, Singapore

[2 ]ISNI 0000 0004 0469 9402, GRID grid.453420.4, Health Services Research Centre, , SingHealth, ; Singapore, Singapore

[3 ]ISNI 0000 0004 0385 0924, GRID grid.428397.3, Center for Quantitative Medicine, Office of Clinical Sciences, , Duke-NUS Medical School, ; Singapore, Singapore

[4 ]Heal Doctors, Los Angeles, CA USA

[5 ]ISNI 0000 0004 0620 9761, GRID grid.490507.f, SingHealth Polyclinics, ; Singapore, Singapore

[6 ]ISNI 0000 0001 2180 6431, GRID grid.4280.e, SingHealth-Duke NUS Family Academic Clinical Program, ; Singapore, Singapore

[7 ]ISNI 0000 0000 9486 5048, GRID grid.163555.1, Department of Renal Medicine, , Singapore General Hospital, ; Singapore, Singapore

[8 ]ISNI 0000 0004 1936 7961, GRID grid.26009.3d, Duke Global Health Institute, , Duke University, ; Durham, NC USA

Article

Publisher ID: 1643

DOI: 10.1186/s12882-019-1643-0

PMC ID: 6894117

PubMed ID: 31801468

SO-VID: 56c4e3e0-a451-461e-b827-663951dab439

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 13 June 2019

Date accepted : 25 November 2019

Funding

Funded by: SingHealth

Award ID: Analytics and Research Technologies grant

Funded by: SingHealth Duke-NUS Health Services Research Institute

Award ID: NA

Funded by: National Medical Research Council

Award ID: NA

Custom metadata

ScienceOpen disciplines: Nephrology

Keywords: chronic kidney disease,end-stage kidney disease,kidney failure risk equation,prediction,southeast asia

Data availability:

ScienceOpen disciplines: Nephrology

Keywords: chronic kidney disease, end-stage kidney disease, kidney failure risk equation, prediction, southeast asia

Validation of the kidney failure risk equation for end-stage kidney disease in Southeast Asia

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Abstract

Background

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Conclusions

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Karger: Nephrology

Most cited references 31

Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

How should proteinuria be detected and measured?

GFR decline as an alternative end point to kidney failure in clinical trials: a meta-analysis of treatment effects from 37 randomized trials.

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