Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients

Viktor Rotbain Curovic; Tine W Hansen; Mie K Eickhoff; Bernt Johan von Scholten; Henrik Reinhard; Peter Karl Jacobsen; Frederik Persson; Hans-Henrik Parving; Peter Rossing

doi:10.1007/s00592-018-1205-0

Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients

Viktor Rotbain Curovic, Tine W Hansen, Mie K Eickhoff, Bernt Johan von Scholten, Henrik Reinhard, Peter Karl Jacobsen, Frederik Persson, Hans-Henrik Parving, Peter Rossing

Institut for Klinisk Medicin

13 Citationer (Scopus)

Abstract

AIMS: Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology and have been proposed as risk markers for development of complications in patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1 and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause mortality in patients with T2D and persistent microalbuminuria without clinical cardiovascular disease.

METHODS: This is a prospective study that included 200 patients. u-KIM-1 and u-NGAL were measured at baseline and were available in 192 patients. Endpoints comprised: decline in eGFR > 30%, a composite of fatal and nonfatal CVE consisting of: cardiovascular mortality, myocardial infarction, stroke, ischemic heart disease and heart failure based on national hospital discharge registries, and all-cause mortality. Adjusted Cox models included traditional risk factors, including eGFR. Hazard ratios (HR) are provided per 1 standard deviation (SD) increment of log2-transformed values. Relative integrated discrimination improvement (rIDI) was calculated.

RESULTS: During the 6.1 years' follow-up, higher u-KIM-1 was a predictor of eGFR decline (n = 29), CVE (n = 34) and all-cause mortality (n = 29) in adjusted models: HR (95% CI) 1.68 (1.04-2.71), p = 0.034; 2.26 (1.24-4.15), p = 0.008; and 1.52 (1.00-2.31), p = 0.049. u-KIM-1 contributed significantly to risk prediction for all-cause mortality evaluated by rIDI (63.1%, p = 0.001). u-NGAL was not a predictor of any of the outcomes after adjustment.

CONCLUSIONS: In patients with T2D and persistent microalbuminuria, u-KIM-1, but not u-NGAL, was an independent risk factor for decline in eGFR, CVE and all-cause mortality, and contributed significant discrimination for all-cause mortality, beyond traditional risk factors.

Originalsprog	Engelsk
Tidsskrift	Acta Diabetologica
Vol/bind	55
Udgave nummer	11
Sider (fra-til)	1143-1150
Antal sider	8
ISSN	0940-5429
DOI	https://doi.org/10.1007/s00592-018-1205-0
Status	Udgivet - 1 nov. 2018

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10.1007/s00592-018-1205-0

Citationsformater

Rotbain Curovic, V., Hansen, T. W., Eickhoff, M. K., von Scholten, B. J., Reinhard, H., Jacobsen, P. K., Persson, F., Parving, H-H., & Rossing, P. (2018). Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients. Acta Diabetologica, 55(11), 1143-1150. https://doi.org/10.1007/s00592-018-1205-0

Rotbain Curovic, V, Hansen, TW, Eickhoff, MK, von Scholten, BJ, Reinhard, H, Jacobsen, PK, Persson, F, Parving, H-H & Rossing, P 2018, 'Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients', Acta Diabetologica, bind 55, nr. 11, s. 1143-1150. https://doi.org/10.1007/s00592-018-1205-0

@article{91fab1e9cf584e5ba64e0da7482e1534,

title = "Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients",

abstract = "AIMS: Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology and have been proposed as risk markers for development of complications in patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1 and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause mortality in patients with T2D and persistent microalbuminuria without clinical cardiovascular disease.METHODS: This is a prospective study that included 200 patients. u-KIM-1 and u-NGAL were measured at baseline and were available in 192 patients. Endpoints comprised: decline in eGFR > 30%, a composite of fatal and nonfatal CVE consisting of: cardiovascular mortality, myocardial infarction, stroke, ischemic heart disease and heart failure based on national hospital discharge registries, and all-cause mortality. Adjusted Cox models included traditional risk factors, including eGFR. Hazard ratios (HR) are provided per 1 standard deviation (SD) increment of log2-transformed values. Relative integrated discrimination improvement (rIDI) was calculated.RESULTS: During the 6.1 years' follow-up, higher u-KIM-1 was a predictor of eGFR decline (n = 29), CVE (n = 34) and all-cause mortality (n = 29) in adjusted models: HR (95% CI) 1.68 (1.04-2.71), p = 0.034; 2.26 (1.24-4.15), p = 0.008; and 1.52 (1.00-2.31), p = 0.049. u-KIM-1 contributed significantly to risk prediction for all-cause mortality evaluated by rIDI (63.1%, p = 0.001). u-NGAL was not a predictor of any of the outcomes after adjustment.CONCLUSIONS: In patients with T2D and persistent microalbuminuria, u-KIM-1, but not u-NGAL, was an independent risk factor for decline in eGFR, CVE and all-cause mortality, and contributed significant discrimination for all-cause mortality, beyond traditional risk factors.",

keywords = "Aged, Albuminuria/urine, Biomarkers/blood, Cholesterol/blood, Creatinine/blood, Diabetes Mellitus, Type 2/complications, Diabetic Angiopathies/blood, Diabetic Nephropathies/blood, Female, Glomerular Filtration Rate, Hepatitis A Virus Cellular Receptor 1/analysis, Humans, Lipocalin-2/urine, Male, Middle Aged, Mortality",

author = "{Rotbain Curovic}, Viktor and Hansen, {Tine W} and Eickhoff, {Mie K} and {von Scholten}, {Bernt Johan} and Henrik Reinhard and Jacobsen, {Peter Karl} and Frederik Persson and Hans-Henrik Parving and Peter Rossing",

year = "2018",

month = nov,

day = "1",

doi = "10.1007/s00592-018-1205-0",

language = "English",

volume = "55",

pages = "1143--1150",

journal = "Acta Diabetologica",

issn = "0940-5429",

publisher = "Springer",

number = "11",

}

TY - JOUR

T1 - Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients

AU - Rotbain Curovic, Viktor

AU - Hansen, Tine W

AU - Eickhoff, Mie K

AU - von Scholten, Bernt Johan

AU - Reinhard, Henrik

AU - Jacobsen, Peter Karl

AU - Persson, Frederik

AU - Parving, Hans-Henrik

AU - Rossing, Peter

PY - 2018/11/1

Y1 - 2018/11/1

N2 - AIMS: Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology and have been proposed as risk markers for development of complications in patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1 and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause mortality in patients with T2D and persistent microalbuminuria without clinical cardiovascular disease.METHODS: This is a prospective study that included 200 patients. u-KIM-1 and u-NGAL were measured at baseline and were available in 192 patients. Endpoints comprised: decline in eGFR > 30%, a composite of fatal and nonfatal CVE consisting of: cardiovascular mortality, myocardial infarction, stroke, ischemic heart disease and heart failure based on national hospital discharge registries, and all-cause mortality. Adjusted Cox models included traditional risk factors, including eGFR. Hazard ratios (HR) are provided per 1 standard deviation (SD) increment of log2-transformed values. Relative integrated discrimination improvement (rIDI) was calculated.RESULTS: During the 6.1 years' follow-up, higher u-KIM-1 was a predictor of eGFR decline (n = 29), CVE (n = 34) and all-cause mortality (n = 29) in adjusted models: HR (95% CI) 1.68 (1.04-2.71), p = 0.034; 2.26 (1.24-4.15), p = 0.008; and 1.52 (1.00-2.31), p = 0.049. u-KIM-1 contributed significantly to risk prediction for all-cause mortality evaluated by rIDI (63.1%, p = 0.001). u-NGAL was not a predictor of any of the outcomes after adjustment.CONCLUSIONS: In patients with T2D and persistent microalbuminuria, u-KIM-1, but not u-NGAL, was an independent risk factor for decline in eGFR, CVE and all-cause mortality, and contributed significant discrimination for all-cause mortality, beyond traditional risk factors.

AB - AIMS: Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology and have been proposed as risk markers for development of complications in patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1 and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause mortality in patients with T2D and persistent microalbuminuria without clinical cardiovascular disease.METHODS: This is a prospective study that included 200 patients. u-KIM-1 and u-NGAL were measured at baseline and were available in 192 patients. Endpoints comprised: decline in eGFR > 30%, a composite of fatal and nonfatal CVE consisting of: cardiovascular mortality, myocardial infarction, stroke, ischemic heart disease and heart failure based on national hospital discharge registries, and all-cause mortality. Adjusted Cox models included traditional risk factors, including eGFR. Hazard ratios (HR) are provided per 1 standard deviation (SD) increment of log2-transformed values. Relative integrated discrimination improvement (rIDI) was calculated.RESULTS: During the 6.1 years' follow-up, higher u-KIM-1 was a predictor of eGFR decline (n = 29), CVE (n = 34) and all-cause mortality (n = 29) in adjusted models: HR (95% CI) 1.68 (1.04-2.71), p = 0.034; 2.26 (1.24-4.15), p = 0.008; and 1.52 (1.00-2.31), p = 0.049. u-KIM-1 contributed significantly to risk prediction for all-cause mortality evaluated by rIDI (63.1%, p = 0.001). u-NGAL was not a predictor of any of the outcomes after adjustment.CONCLUSIONS: In patients with T2D and persistent microalbuminuria, u-KIM-1, but not u-NGAL, was an independent risk factor for decline in eGFR, CVE and all-cause mortality, and contributed significant discrimination for all-cause mortality, beyond traditional risk factors.

KW - Aged

KW - Albuminuria/urine

KW - Biomarkers/blood

KW - Cholesterol/blood

KW - Creatinine/blood

KW - Diabetes Mellitus, Type 2/complications

KW - Diabetic Angiopathies/blood

KW - Diabetic Nephropathies/blood

KW - Female

KW - Glomerular Filtration Rate

KW - Hepatitis A Virus Cellular Receptor 1/analysis

KW - Humans

KW - Lipocalin-2/urine

KW - Male

KW - Middle Aged

KW - Mortality

U2 - 10.1007/s00592-018-1205-0

DO - 10.1007/s00592-018-1205-0

M3 - Journal article

C2 - 30105469

SN - 0940-5429

VL - 55

SP - 1143

EP - 1150

JO - Acta Diabetologica

JF - Acta Diabetologica

IS - 11

ER -

Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients

Abstract

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