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Cited by 155Chronic Kidney Disease and DiabetesBlood Pressure and Hypertension StudiesAcute Kidney Injury Research

Albuminuria testing in hypertension and diabetes: an individual-participant data meta-analysis in a global consortium

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Shin, Jung-Im, Chang, Alex R., Grams, Morgan E., Coresh, Josef, Ballew, Shoshana H., Surapaneni, Aditya, Matsushita, Kunihiro, Bilo, Henk J.G. +57 more·2021·Hypertension
DOI 10.1161/hypertensionaha.121.17323PMC PMC8429211
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Abstract

Albuminuria is an under-recognized component of chronic kidney disease definition, staging, and prognosis. Guidelines, particularly for hypertension, conflict on recommendations for urine albumin-to-creatinine ratio (ACR) measurement. Separately among 1 344 594 adults with diabetes and 2 334 461 nondiabetic adults with hypertension from the chronic kidney disease Prognosis Consortium, we assessed ACR testing, estimated the prevalence and incidence of ACR ≥30 mg/g and developed risk models for ACR ≥30 mg/g. The ACR screening rate (cohort range) was 35.1% (12.3%–74.5%) in diabetes and 4.1% (1.3%–20.7%) in hypertension. Screening was largely unrelated to the predicted risk of prevalent albuminuria. The median prevalence of ACR ≥30 mg/g across cohorts was 32.1% in diabetes and 21.8% in hypertension. Higher systolic blood pressure was associated with a higher prevalence of albuminuria (odds ratio [95% CI] per 20 mm Hg in diabetes, 1.50 [1.42–1.60]; in hypertension, 1.36 [1.28–1.45]). The ratio of undetected (due to lack of screening) to detected ACR ≥30 mg/g was estimated at 1.8 in diabetes and 19.5 in hypertension. Among those with ACR <30 mg/g, the median 5-year incidence of ACR ≥30 mg/g across cohorts was 23.9% in diabetes and 21.7% in hypertension. Incident albuminuria was associated with initiation of renin-angiotensin-aldosterone system inhibitors (incidence-rate ratio [95% CI], diabetes 3.09 [2.71–3.53]; hypertension 2.87 [2.29–3.59]). In conclusion, despite similar risk of albuminuria to those with diabetes, ACR screening in patients with hypertension was low. Our findings suggest that regular albuminuria screening should be emphasized to enable early detection of chronic kidney disease and initiation of treatment with cardiovascular and renal benefits.

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  • Screening using two tests with either being positive increases sensitivity to 97% but reduces specificity to 83%.

    “Screening using two tests with either being positive interpreted as a positive (leading to subsequent quantitative testing) increases the sensitivity to 97% but reduces the specificity to 83% (500,501).”

    From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [501]

    The Results section on ACR testing rates reports how often patients were tested, and the Methods section describes repeat ACR measurements. Neither evaluates a two-test screening rule in which either positive result triggers quantitative testing, or reports 97% sensitivity and 83% specificity. Searches for those figures and the two-test rule found no supporting passage in our copy; page numbers were not available. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Pooling results from a bivariate random-effects model gave sensitivity and specificity estimates of 76% and 93%, respectively, for the semiquantitative test.

    “Pooling results from a bivariate randomeffects model gave sensitivity and specificity estimates of 76% (95% CI, 63-86%) and 93% (CI, 84-97%), respectively, for the semiquantitative test (501).”

    From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [501]

    The Methods (Statistical Analyses; page unavailable) describe logistic prediction models whose estimates were combined by random-effects meta-analysis, not a bivariate diagnostic-accuracy model. A search for the semiquantitative test and the stated sensitivity and specificity found no passage reporting the 76% and 93% estimates or their confidence intervals. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • A negative semiquantitative POC test result does not rule out albuminuria, whereas quantitative POC testing meets required performance standards and can be used to rule out albuminuria.

    “The authors concluded that a negative semiquantitative POC test result does not rule out albuminuria, whereas quantitative POC testing meets required performance standards and can be used to rule out albuminuria.”

    From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [501]

    The Introduction (page unavailable) mentions routine urine dipstick testing, but does not evaluate negative semiquantitative results. The Discussion (page unavailable) concerns ACR screening rates, not point-of-care test accuracy. Searches for semiquantitative and quantitative POC testing found no passage addressing rule-out performance or required standards. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Sensitivity and specificity estimates for the quantitative POC test were 96% and 98%, respectively.

    “Sensitivity and specificity estimates for the quantitative test were 96% (95% CI, 78-99%) and 98% (95% CI, 93-99%), respectively.”

    From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [501]

    The Methods (Outcomes and Statistical Analyses) and Results (ACR Testing Rate and Prevalence of ACR ≥30 mg/g) describe albumin-to-creatinine ratio testing rates and albuminuria prevalence, not the diagnostic accuracy of a quantitative point-of-care test. Searches for the quantitative test, sensitivity, specificity, and the stated confidence intervals found no passage supporting the 96% and 98% estimates. Page numbers were not available in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Shin, J.-I., Chang, A. R., Grams, M. E., Coresh, J., Ballew, S. H., Surapaneni, A., Matsushita, K., Bilo, H. J. G., Carrero, J. J., Chodick, G., Daratha, K. B., Jassal, S. K., Nadkarni, G. N., Nelson, R. G., Nowak, C., Stempniewicz, N., Sumida, K., Traynor, J. P., Woodward, M., Sang, Y., Gansevoort, R. T., Chalmers, J., Tuttle, K., Alicic, R., McPherson, S., Jones, C., Singh, G., Green, J., Kirchner, H. L., Shalev, V., Bottinger, E. P., Loos, R. J. F., Ellis, S. B., Cuddeback, J., Ciemins, E., Carbonara, E., Dunning, S., Knowler, W. C., Looker, H. C., Kieneker, L. M., Bakker, S. J. L., Hillege, H. L., van der Harst, P., Jassal, S. K., Bergstrom, J., Ix, J., Kovesdy, C. P., Potukuchi, P., Trevisan, M., Elinder, C. G., Wettermark, B., Ärnlöv, J., Mark, P. B., Thomson, P. C., Geddes, C. C., Landman, G. W. D., van Hateren, K. J. J., Kleefstra, N., Gutierrez, O., Konta, T., Levey, A. S., Polkinghorne, K., Schäffner, E., Chen, J., & Surapeneni, A.
Affiliations
  • Johns Hopkins University (US)
  • Geisinger Medical Center (US)
  • University Medical Center Groningen (NL)
  • Karolinska Institutet (SE)
  • Tel Aviv University (IL)
  • Providence St. Joseph Health on behalf of CURE-CKD Investigators, Spokane, WA (K.B.D.)
  • Icahn School of Medicine at Mount Sinai (US)
  • National Institutes of Health (US)
  • American Medical Group Association (US)
  • University of Tennessee Health Science Center (US)
  • Queen Elizabeth University Hospital (GB)
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-10
Volume
78
Issue
4
Pages
1042-1052
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.121.17323
PMC
PMC8429211
OpenAlex
W3188495695
Semantic Scholar
9fd2f82a888974bc1547c07692b4c2ec79ecb7a5
Cited by
155
References
29
Citations by year
2026: 31 · 2025: 51 · 2024: 26 · 2023: 28 · 2022: 18 · 2021: 1
FWCI
2.99
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Hypertension (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Funders
  • National Heart, Lung, and Blood Institute (K24HL155861)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K01DK121825, R01DK100446, R01DK115534, P30DK079626)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
albuminuria, albumin-creatinine ratio, chronic kidney disease, diabetes mellitus, prevalence, incidence, risk model, systolic blood pressure, renin-angiotensin-aldosterone system inhibitors, early detection
MeSH terms
Adult, Aged, Albuminuria, Creatinine, Diabetes Mellitus, Glomerular Filtration Rate, Humans, Hypertension, Middle Aged, Renal Insufficiency, Chronic

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