Optimal strategies for identifying kidney disease in diabetes: Properties of screening tests, progression of renal dysfunction and impact of treatment - Systematic review and modelling of progression and cost-effectiveness

Andrew J. Farmer, Richard Stevens, Jennifer Hirst, Tom Lung, Jason Oke, Philip Clarke, Paul Glasziou, Andrew Neil, David Dunger, Helen M. Colhoun, Christopher Pugh, Germain Wong, Rafael Perera, Brian Shine

Research output: Contribution to journalReview articleResearchpeer-review

14 Citations (Scopus)

Abstract

Background: Annual screening for adults with type 2 diabetes to detect the early onset of kidney disease is widely recommended, but the recommendations are based on a limited methodological approach. In addition, there are continuing uncertainties about underlying rates of progression of the condition and the benefits of treatments with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Objectives: We aimed to estimate the clinical value and cost-effectiveness of different screening intervals to diagnose early diabetic kidney disease. Data sources: We used the following databases for the literature review (searched January 2005 to August 2010): MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Individual patient data were obtained from the Oxford Regional Prospective Diabetes Study and the Collaborative Atorvastatin Diabetes Study. Methods: Data from systematically identified randomised trials reporting the impact on renal outcomes of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers for type 1 and type 2 diabetes patients with normoalbuminuria and microalbuminuria were pooled to derive estimates of effect. Individual patient data for type 1 and type 2 diabetes patients were used to obtain parameters describing progression and variability of measurement over time for the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate. Based on accepted diagnostic thresholds, we modelled whether these tests accurately identified patients who were developing early diabetic kidney disease and required intensification of treatment. Cost-effectiveness analyses were carried out using simulation outcome models to estimate the incremental costs per quality-adjusted life-year (QALY) for different screening intervals. Results: In total, 49 trials (n = 34,082 patients) were eligible for inclusion in the systematic review. For type 1 diabetes, pooled estimates of urinary albumin excretion (UAE) for treated patients with microalbuminuria were on average 67% [95% confidence interval (CI) 54% to 77%] lower at the end of the trial than for untreated patients. There was no significant treatment effect for patients with normoalbuminuria (p interaction = 0.006). For treated patients with type 2 diabetes and normoalbuminuria or microalbuminuria, UAE was lower by, on average, 21% (95% CI 97% to 32%) or 27% (95% CI 15% to 38%), respectively. The proportion (95% CI) of men and women with type 1 diabetes screened annually for microalbuminuria over 6 years and inaccurately identified as having microalbuminuria would be 48% (43% to 53%) and 55% (48% to 61%), respectively. The corresponding proportions for type 2 diabetes are 36% (32% to 42%) and 48% (41% to 55%). Decreasing the screening interval to 3-yearly would reduce this for men with type 1 diabetes to 38% (33% to 44%), with an increase in those not identified over 6 years from 1.5% (95% CI 1% to 2%) to 4% (95% CI 3% to 5%). For type 1 diabetes, incremental cost per QALY [standard deviation (SD)] of a 5-yearly compared with a 4-yearly screening interval was £3612 (£6586), increasing to £9601 (£34,112) for annual compared with 2-yearly screening. The probability that the intervention is cost saving is around 25%, and it has around an 80% chance of being below a cost-effectiveness threshold of £30,000. For type 2 diabetes, incremental cost per QALY (SD) of a yearly compared with a 2-yearly screening interval was £606 (£1782). The intervention is almost certainly below a cost-effectiveness threshold of £5000. Conclusions: These results support current UK guidance, which recommends annual screening with ACR to identify early kidney disease in patients with diabetes, despite a high false-positive rate leading to, at worst, unnecessary or, at best, early therapeutic intervention. For type 1 diabetes, screening costs for annual compared with 2-yearly screening are well within the bounds of accepted cost-effectiveness. Annual screening is even more cost-effective in type 2 diabetes than in type 1 diabetes. Identification of alternative markers for developing diabetic nephropathy may improve targeting of treatment for those at high risk.

Original languageEnglish
Pages (from-to)1-127
Number of pages127
JournalHealth Technology Assessment
Volume18
Issue number14
DOIs
Publication statusPublished - 2014

Fingerprint

Kidney Diseases
Cost-Benefit Analysis
Type 1 Diabetes Mellitus
Kidney
Type 2 Diabetes Mellitus
Confidence Intervals
Costs and Cost Analysis
Quality-Adjusted Life Years
Albumins
Diabetic Nephropathies
Therapeutics
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Creatinine
Databases
Information Storage and Retrieval
Glomerular Filtration Rate
MEDLINE
Uncertainty
Prospective Studies

Cite this

Farmer, Andrew J. ; Stevens, Richard ; Hirst, Jennifer ; Lung, Tom ; Oke, Jason ; Clarke, Philip ; Glasziou, Paul ; Neil, Andrew ; Dunger, David ; Colhoun, Helen M. ; Pugh, Christopher ; Wong, Germain ; Perera, Rafael ; Shine, Brian. / Optimal strategies for identifying kidney disease in diabetes : Properties of screening tests, progression of renal dysfunction and impact of treatment - Systematic review and modelling of progression and cost-effectiveness. In: Health Technology Assessment. 2014 ; Vol. 18, No. 14. pp. 1-127.
@article{1598783874a240c78f9c9a8c53e58ba2,
title = "Optimal strategies for identifying kidney disease in diabetes: Properties of screening tests, progression of renal dysfunction and impact of treatment - Systematic review and modelling of progression and cost-effectiveness",
abstract = "Background: Annual screening for adults with type 2 diabetes to detect the early onset of kidney disease is widely recommended, but the recommendations are based on a limited methodological approach. In addition, there are continuing uncertainties about underlying rates of progression of the condition and the benefits of treatments with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Objectives: We aimed to estimate the clinical value and cost-effectiveness of different screening intervals to diagnose early diabetic kidney disease. Data sources: We used the following databases for the literature review (searched January 2005 to August 2010): MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Individual patient data were obtained from the Oxford Regional Prospective Diabetes Study and the Collaborative Atorvastatin Diabetes Study. Methods: Data from systematically identified randomised trials reporting the impact on renal outcomes of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers for type 1 and type 2 diabetes patients with normoalbuminuria and microalbuminuria were pooled to derive estimates of effect. Individual patient data for type 1 and type 2 diabetes patients were used to obtain parameters describing progression and variability of measurement over time for the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate. Based on accepted diagnostic thresholds, we modelled whether these tests accurately identified patients who were developing early diabetic kidney disease and required intensification of treatment. Cost-effectiveness analyses were carried out using simulation outcome models to estimate the incremental costs per quality-adjusted life-year (QALY) for different screening intervals. Results: In total, 49 trials (n = 34,082 patients) were eligible for inclusion in the systematic review. For type 1 diabetes, pooled estimates of urinary albumin excretion (UAE) for treated patients with microalbuminuria were on average 67{\%} [95{\%} confidence interval (CI) 54{\%} to 77{\%}] lower at the end of the trial than for untreated patients. There was no significant treatment effect for patients with normoalbuminuria (p interaction = 0.006). For treated patients with type 2 diabetes and normoalbuminuria or microalbuminuria, UAE was lower by, on average, 21{\%} (95{\%} CI 97{\%} to 32{\%}) or 27{\%} (95{\%} CI 15{\%} to 38{\%}), respectively. The proportion (95{\%} CI) of men and women with type 1 diabetes screened annually for microalbuminuria over 6 years and inaccurately identified as having microalbuminuria would be 48{\%} (43{\%} to 53{\%}) and 55{\%} (48{\%} to 61{\%}), respectively. The corresponding proportions for type 2 diabetes are 36{\%} (32{\%} to 42{\%}) and 48{\%} (41{\%} to 55{\%}). Decreasing the screening interval to 3-yearly would reduce this for men with type 1 diabetes to 38{\%} (33{\%} to 44{\%}), with an increase in those not identified over 6 years from 1.5{\%} (95{\%} CI 1{\%} to 2{\%}) to 4{\%} (95{\%} CI 3{\%} to 5{\%}). For type 1 diabetes, incremental cost per QALY [standard deviation (SD)] of a 5-yearly compared with a 4-yearly screening interval was £3612 (£6586), increasing to £9601 (£34,112) for annual compared with 2-yearly screening. The probability that the intervention is cost saving is around 25{\%}, and it has around an 80{\%} chance of being below a cost-effectiveness threshold of £30,000. For type 2 diabetes, incremental cost per QALY (SD) of a yearly compared with a 2-yearly screening interval was £606 (£1782). The intervention is almost certainly below a cost-effectiveness threshold of £5000. Conclusions: These results support current UK guidance, which recommends annual screening with ACR to identify early kidney disease in patients with diabetes, despite a high false-positive rate leading to, at worst, unnecessary or, at best, early therapeutic intervention. For type 1 diabetes, screening costs for annual compared with 2-yearly screening are well within the bounds of accepted cost-effectiveness. Annual screening is even more cost-effective in type 2 diabetes than in type 1 diabetes. Identification of alternative markers for developing diabetic nephropathy may improve targeting of treatment for those at high risk.",
author = "Farmer, {Andrew J.} and Richard Stevens and Jennifer Hirst and Tom Lung and Jason Oke and Philip Clarke and Paul Glasziou and Andrew Neil and David Dunger and Colhoun, {Helen M.} and Christopher Pugh and Germain Wong and Rafael Perera and Brian Shine",
year = "2014",
doi = "10.3310/hta18140",
language = "English",
volume = "18",
pages = "1--127",
journal = "Health Technology Assessment",
issn = "1366-5278",
publisher = "GRAY PUBLISHING",
number = "14",

}

Optimal strategies for identifying kidney disease in diabetes : Properties of screening tests, progression of renal dysfunction and impact of treatment - Systematic review and modelling of progression and cost-effectiveness. / Farmer, Andrew J.; Stevens, Richard; Hirst, Jennifer; Lung, Tom; Oke, Jason; Clarke, Philip; Glasziou, Paul; Neil, Andrew; Dunger, David; Colhoun, Helen M.; Pugh, Christopher; Wong, Germain; Perera, Rafael; Shine, Brian.

In: Health Technology Assessment, Vol. 18, No. 14, 2014, p. 1-127.

Research output: Contribution to journalReview articleResearchpeer-review

TY - JOUR

T1 - Optimal strategies for identifying kidney disease in diabetes

T2 - Properties of screening tests, progression of renal dysfunction and impact of treatment - Systematic review and modelling of progression and cost-effectiveness

AU - Farmer, Andrew J.

AU - Stevens, Richard

AU - Hirst, Jennifer

AU - Lung, Tom

AU - Oke, Jason

AU - Clarke, Philip

AU - Glasziou, Paul

AU - Neil, Andrew

AU - Dunger, David

AU - Colhoun, Helen M.

AU - Pugh, Christopher

AU - Wong, Germain

AU - Perera, Rafael

AU - Shine, Brian

PY - 2014

Y1 - 2014

N2 - Background: Annual screening for adults with type 2 diabetes to detect the early onset of kidney disease is widely recommended, but the recommendations are based on a limited methodological approach. In addition, there are continuing uncertainties about underlying rates of progression of the condition and the benefits of treatments with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Objectives: We aimed to estimate the clinical value and cost-effectiveness of different screening intervals to diagnose early diabetic kidney disease. Data sources: We used the following databases for the literature review (searched January 2005 to August 2010): MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Individual patient data were obtained from the Oxford Regional Prospective Diabetes Study and the Collaborative Atorvastatin Diabetes Study. Methods: Data from systematically identified randomised trials reporting the impact on renal outcomes of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers for type 1 and type 2 diabetes patients with normoalbuminuria and microalbuminuria were pooled to derive estimates of effect. Individual patient data for type 1 and type 2 diabetes patients were used to obtain parameters describing progression and variability of measurement over time for the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate. Based on accepted diagnostic thresholds, we modelled whether these tests accurately identified patients who were developing early diabetic kidney disease and required intensification of treatment. Cost-effectiveness analyses were carried out using simulation outcome models to estimate the incremental costs per quality-adjusted life-year (QALY) for different screening intervals. Results: In total, 49 trials (n = 34,082 patients) were eligible for inclusion in the systematic review. For type 1 diabetes, pooled estimates of urinary albumin excretion (UAE) for treated patients with microalbuminuria were on average 67% [95% confidence interval (CI) 54% to 77%] lower at the end of the trial than for untreated patients. There was no significant treatment effect for patients with normoalbuminuria (p interaction = 0.006). For treated patients with type 2 diabetes and normoalbuminuria or microalbuminuria, UAE was lower by, on average, 21% (95% CI 97% to 32%) or 27% (95% CI 15% to 38%), respectively. The proportion (95% CI) of men and women with type 1 diabetes screened annually for microalbuminuria over 6 years and inaccurately identified as having microalbuminuria would be 48% (43% to 53%) and 55% (48% to 61%), respectively. The corresponding proportions for type 2 diabetes are 36% (32% to 42%) and 48% (41% to 55%). Decreasing the screening interval to 3-yearly would reduce this for men with type 1 diabetes to 38% (33% to 44%), with an increase in those not identified over 6 years from 1.5% (95% CI 1% to 2%) to 4% (95% CI 3% to 5%). For type 1 diabetes, incremental cost per QALY [standard deviation (SD)] of a 5-yearly compared with a 4-yearly screening interval was £3612 (£6586), increasing to £9601 (£34,112) for annual compared with 2-yearly screening. The probability that the intervention is cost saving is around 25%, and it has around an 80% chance of being below a cost-effectiveness threshold of £30,000. For type 2 diabetes, incremental cost per QALY (SD) of a yearly compared with a 2-yearly screening interval was £606 (£1782). The intervention is almost certainly below a cost-effectiveness threshold of £5000. Conclusions: These results support current UK guidance, which recommends annual screening with ACR to identify early kidney disease in patients with diabetes, despite a high false-positive rate leading to, at worst, unnecessary or, at best, early therapeutic intervention. For type 1 diabetes, screening costs for annual compared with 2-yearly screening are well within the bounds of accepted cost-effectiveness. Annual screening is even more cost-effective in type 2 diabetes than in type 1 diabetes. Identification of alternative markers for developing diabetic nephropathy may improve targeting of treatment for those at high risk.

AB - Background: Annual screening for adults with type 2 diabetes to detect the early onset of kidney disease is widely recommended, but the recommendations are based on a limited methodological approach. In addition, there are continuing uncertainties about underlying rates of progression of the condition and the benefits of treatments with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Objectives: We aimed to estimate the clinical value and cost-effectiveness of different screening intervals to diagnose early diabetic kidney disease. Data sources: We used the following databases for the literature review (searched January 2005 to August 2010): MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Individual patient data were obtained from the Oxford Regional Prospective Diabetes Study and the Collaborative Atorvastatin Diabetes Study. Methods: Data from systematically identified randomised trials reporting the impact on renal outcomes of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers for type 1 and type 2 diabetes patients with normoalbuminuria and microalbuminuria were pooled to derive estimates of effect. Individual patient data for type 1 and type 2 diabetes patients were used to obtain parameters describing progression and variability of measurement over time for the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate. Based on accepted diagnostic thresholds, we modelled whether these tests accurately identified patients who were developing early diabetic kidney disease and required intensification of treatment. Cost-effectiveness analyses were carried out using simulation outcome models to estimate the incremental costs per quality-adjusted life-year (QALY) for different screening intervals. Results: In total, 49 trials (n = 34,082 patients) were eligible for inclusion in the systematic review. For type 1 diabetes, pooled estimates of urinary albumin excretion (UAE) for treated patients with microalbuminuria were on average 67% [95% confidence interval (CI) 54% to 77%] lower at the end of the trial than for untreated patients. There was no significant treatment effect for patients with normoalbuminuria (p interaction = 0.006). For treated patients with type 2 diabetes and normoalbuminuria or microalbuminuria, UAE was lower by, on average, 21% (95% CI 97% to 32%) or 27% (95% CI 15% to 38%), respectively. The proportion (95% CI) of men and women with type 1 diabetes screened annually for microalbuminuria over 6 years and inaccurately identified as having microalbuminuria would be 48% (43% to 53%) and 55% (48% to 61%), respectively. The corresponding proportions for type 2 diabetes are 36% (32% to 42%) and 48% (41% to 55%). Decreasing the screening interval to 3-yearly would reduce this for men with type 1 diabetes to 38% (33% to 44%), with an increase in those not identified over 6 years from 1.5% (95% CI 1% to 2%) to 4% (95% CI 3% to 5%). For type 1 diabetes, incremental cost per QALY [standard deviation (SD)] of a 5-yearly compared with a 4-yearly screening interval was £3612 (£6586), increasing to £9601 (£34,112) for annual compared with 2-yearly screening. The probability that the intervention is cost saving is around 25%, and it has around an 80% chance of being below a cost-effectiveness threshold of £30,000. For type 2 diabetes, incremental cost per QALY (SD) of a yearly compared with a 2-yearly screening interval was £606 (£1782). The intervention is almost certainly below a cost-effectiveness threshold of £5000. Conclusions: These results support current UK guidance, which recommends annual screening with ACR to identify early kidney disease in patients with diabetes, despite a high false-positive rate leading to, at worst, unnecessary or, at best, early therapeutic intervention. For type 1 diabetes, screening costs for annual compared with 2-yearly screening are well within the bounds of accepted cost-effectiveness. Annual screening is even more cost-effective in type 2 diabetes than in type 1 diabetes. Identification of alternative markers for developing diabetic nephropathy may improve targeting of treatment for those at high risk.

UR - http://www.scopus.com/inward/record.url?scp=84895742355&partnerID=8YFLogxK

U2 - 10.3310/hta18140

DO - 10.3310/hta18140

M3 - Review article

VL - 18

SP - 1

EP - 127

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 14

ER -