Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria

Bernt Johan von Scholten; Henrik Reinhard; Tine W Hansen; Jens Oellgaard; Hans-Henrik Parving; Peter K Jacobsen; Peter Rossing

doi:10.1007/s00125-016-3937-0

Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria

Bernt Johan von Scholten, Henrik Reinhard, Tine W Hansen, Jens Oellgaard, Hans-Henrik Parving, Peter K Jacobsen, Peter Rossing

Department of Clinical Medicine

17 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: We evaluated two urinary biomarkers reflecting different aspects of renal pathophysiology as potential determinants of incident cardiovascular disease (CVD), all-cause mortality and a reduced estimated GFR (eGFR) in patients with type 2 diabetes and microalbuminuria but without clinical features of coronary artery disease.

METHODS: In a prospective study of 200 patients, all received multifactorial treatment. Baseline measurements of urinary hepatocyte growth factor (HGF) and adiponectin were available for 191 patients. Cox models were adjusted for sex, age, LDL-cholesterol, smoking, HbA1c, plasma creatinine, systolic BP and urinary AER (UAER). The pre-defined endpoint of chronic kidney disease progression was a decline in the eGFR of >30% during follow-up. HRs per 1 SD increment of log-transformed values are presented.

RESULTS: Patients had a mean ± SD age of 59 ± 9 years with a median (interquartile range) UAER of 103 (39-230) mg/24 h. During a median 6.1 years of follow-up, there were 40 incident CVD events, 26 deaths and 42 patients reached the pre-defined chronic kidney disease progression endpoint after 4.9 years (median). Higher urinary HGF was a determinant of CVD in unadjusted (HR 1.9 [95% CI 1.3, 2.8], p = 0.001) and adjusted (HR 2.0 [95% CI 1.2, 3.2], p = 0.004) models, and of all-cause mortality in unadjusted (HR 2.3 [95% CI 1.3, 3.9], p = 0.003) and adjusted (HR 2.5 [95% CI 1.3, 4.8], p = 0.005) models. A higher adiponectin level was associated with CVD in unadjusted (HR 1.4 [95% CI 1.0, 1.9], p = 0.04) and adjusted (HR 1.4 [95% CI 1.1, 2.3], p = 0.013) models, and with a decline in the eGFR of >30% in unadjusted (HR 1.6 [95% CI 1.2, 2.2], p = 0.008) and adjusted (HR 1.5 [95% CI 1.1, 2.2], p = 0.007) models.

CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes and microalbuminuria receiving multifactorial treatment, higher urinary HGF was associated with incident CVD and all-cause mortality, and higher adiponectin was associated with CVD and deterioration in renal function.

Original language	English
Journal	Diabetologia
Volume	59
Issue number	7
Pages (from-to)	1549–1557
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-016-3937-0
Publication status	Published - 1 Jul 2016

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von Scholten, B. J., Reinhard, H., Hansen, T. W., Oellgaard, J., Parving, H-H., Jacobsen, P. K., & Rossing, P. (2016). Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria. Diabetologia, 59(7), 1549–1557. https://doi.org/10.1007/s00125-016-3937-0

Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria. / von Scholten, Bernt Johan; Reinhard, Henrik; Hansen, Tine W et al.

In: Diabetologia, Vol. 59, No. 7, 01.07.2016, p. 1549–1557.

Research output: Contribution to journal › Journal article › Research › peer-review

von Scholten, BJ, Reinhard, H, Hansen, TW, Oellgaard, J, Parving, H-H, Jacobsen, PK & Rossing, P 2016, 'Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria', Diabetologia, vol. 59, no. 7, pp. 1549–1557. https://doi.org/10.1007/s00125-016-3937-0

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title = "Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria",

abstract = "AIMS/HYPOTHESIS: We evaluated two urinary biomarkers reflecting different aspects of renal pathophysiology as potential determinants of incident cardiovascular disease (CVD), all-cause mortality and a reduced estimated GFR (eGFR) in patients with type 2 diabetes and microalbuminuria but without clinical features of coronary artery disease.METHODS: In a prospective study of 200 patients, all received multifactorial treatment. Baseline measurements of urinary hepatocyte growth factor (HGF) and adiponectin were available for 191 patients. Cox models were adjusted for sex, age, LDL-cholesterol, smoking, HbA1c, plasma creatinine, systolic BP and urinary AER (UAER). The pre-defined endpoint of chronic kidney disease progression was a decline in the eGFR of >30% during follow-up. HRs per 1 SD increment of log-transformed values are presented.RESULTS: Patients had a mean ± SD age of 59 ± 9 years with a median (interquartile range) UAER of 103 (39-230) mg/24 h. During a median 6.1 years of follow-up, there were 40 incident CVD events, 26 deaths and 42 patients reached the pre-defined chronic kidney disease progression endpoint after 4.9 years (median). Higher urinary HGF was a determinant of CVD in unadjusted (HR 1.9 [95% CI 1.3, 2.8], p = 0.001) and adjusted (HR 2.0 [95% CI 1.2, 3.2], p = 0.004) models, and of all-cause mortality in unadjusted (HR 2.3 [95% CI 1.3, 3.9], p = 0.003) and adjusted (HR 2.5 [95% CI 1.3, 4.8], p = 0.005) models. A higher adiponectin level was associated with CVD in unadjusted (HR 1.4 [95% CI 1.0, 1.9], p = 0.04) and adjusted (HR 1.4 [95% CI 1.1, 2.3], p = 0.013) models, and with a decline in the eGFR of >30% in unadjusted (HR 1.6 [95% CI 1.2, 2.2], p = 0.008) and adjusted (HR 1.5 [95% CI 1.1, 2.2], p = 0.007) models.CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes and microalbuminuria receiving multifactorial treatment, higher urinary HGF was associated with incident CVD and all-cause mortality, and higher adiponectin was associated with CVD and deterioration in renal function.",

author = "{von Scholten}, {Bernt Johan} and Henrik Reinhard and Hansen, {Tine W} and Jens Oellgaard and Hans-Henrik Parving and Jacobsen, {Peter K} and Peter Rossing",

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T1 - Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria

AU - von Scholten, Bernt Johan

AU - Reinhard, Henrik

AU - Hansen, Tine W

AU - Oellgaard, Jens

AU - Parving, Hans-Henrik

AU - Jacobsen, Peter K

AU - Rossing, Peter

PY - 2016/7/1

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N2 - AIMS/HYPOTHESIS: We evaluated two urinary biomarkers reflecting different aspects of renal pathophysiology as potential determinants of incident cardiovascular disease (CVD), all-cause mortality and a reduced estimated GFR (eGFR) in patients with type 2 diabetes and microalbuminuria but without clinical features of coronary artery disease.METHODS: In a prospective study of 200 patients, all received multifactorial treatment. Baseline measurements of urinary hepatocyte growth factor (HGF) and adiponectin were available for 191 patients. Cox models were adjusted for sex, age, LDL-cholesterol, smoking, HbA1c, plasma creatinine, systolic BP and urinary AER (UAER). The pre-defined endpoint of chronic kidney disease progression was a decline in the eGFR of >30% during follow-up. HRs per 1 SD increment of log-transformed values are presented.RESULTS: Patients had a mean ± SD age of 59 ± 9 years with a median (interquartile range) UAER of 103 (39-230) mg/24 h. During a median 6.1 years of follow-up, there were 40 incident CVD events, 26 deaths and 42 patients reached the pre-defined chronic kidney disease progression endpoint after 4.9 years (median). Higher urinary HGF was a determinant of CVD in unadjusted (HR 1.9 [95% CI 1.3, 2.8], p = 0.001) and adjusted (HR 2.0 [95% CI 1.2, 3.2], p = 0.004) models, and of all-cause mortality in unadjusted (HR 2.3 [95% CI 1.3, 3.9], p = 0.003) and adjusted (HR 2.5 [95% CI 1.3, 4.8], p = 0.005) models. A higher adiponectin level was associated with CVD in unadjusted (HR 1.4 [95% CI 1.0, 1.9], p = 0.04) and adjusted (HR 1.4 [95% CI 1.1, 2.3], p = 0.013) models, and with a decline in the eGFR of >30% in unadjusted (HR 1.6 [95% CI 1.2, 2.2], p = 0.008) and adjusted (HR 1.5 [95% CI 1.1, 2.2], p = 0.007) models.CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes and microalbuminuria receiving multifactorial treatment, higher urinary HGF was associated with incident CVD and all-cause mortality, and higher adiponectin was associated with CVD and deterioration in renal function.

AB - AIMS/HYPOTHESIS: We evaluated two urinary biomarkers reflecting different aspects of renal pathophysiology as potential determinants of incident cardiovascular disease (CVD), all-cause mortality and a reduced estimated GFR (eGFR) in patients with type 2 diabetes and microalbuminuria but without clinical features of coronary artery disease.METHODS: In a prospective study of 200 patients, all received multifactorial treatment. Baseline measurements of urinary hepatocyte growth factor (HGF) and adiponectin were available for 191 patients. Cox models were adjusted for sex, age, LDL-cholesterol, smoking, HbA1c, plasma creatinine, systolic BP and urinary AER (UAER). The pre-defined endpoint of chronic kidney disease progression was a decline in the eGFR of >30% during follow-up. HRs per 1 SD increment of log-transformed values are presented.RESULTS: Patients had a mean ± SD age of 59 ± 9 years with a median (interquartile range) UAER of 103 (39-230) mg/24 h. During a median 6.1 years of follow-up, there were 40 incident CVD events, 26 deaths and 42 patients reached the pre-defined chronic kidney disease progression endpoint after 4.9 years (median). Higher urinary HGF was a determinant of CVD in unadjusted (HR 1.9 [95% CI 1.3, 2.8], p = 0.001) and adjusted (HR 2.0 [95% CI 1.2, 3.2], p = 0.004) models, and of all-cause mortality in unadjusted (HR 2.3 [95% CI 1.3, 3.9], p = 0.003) and adjusted (HR 2.5 [95% CI 1.3, 4.8], p = 0.005) models. A higher adiponectin level was associated with CVD in unadjusted (HR 1.4 [95% CI 1.0, 1.9], p = 0.04) and adjusted (HR 1.4 [95% CI 1.1, 2.3], p = 0.013) models, and with a decline in the eGFR of >30% in unadjusted (HR 1.6 [95% CI 1.2, 2.2], p = 0.008) and adjusted (HR 1.5 [95% CI 1.1, 2.2], p = 0.007) models.CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes and microalbuminuria receiving multifactorial treatment, higher urinary HGF was associated with incident CVD and all-cause mortality, and higher adiponectin was associated with CVD and deterioration in renal function.

U2 - 10.1007/s00125-016-3937-0

DO - 10.1007/s00125-016-3937-0

M3 - Journal article

C2 - 27033561

SN - 0012-186X

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SP - 1549

EP - 1557

JO - Diabetologia

JF - Diabetologia

IS - 7

ER -

Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria

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