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, HbA 1c , 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 logtransformed 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. 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.

Growth differentiation factor-15 and fibroblast growth factor-23 are associated with mortality in type 2 diabetes – An observational follow-up study

“…The three predefined endpoints have previously been described [ 28 , 29 ]. The combined CVD endpoint was defined as cardiovascular mortality, non-fatal myocardial infarction, stroke, ischaemic CVD and heart failure.…”

Symmetric and asymmetric dimethylarginine as risk markers of cardiovascular disease, all-cause mortality and deterioration in kidney function in persons with type 2 diabetes and microalbuminuria

“…No participants were lost to follow-up. Definitions of the three predefined endpoints have previously been described [18, 19]. The combined cardiovascular endpoint was defined as cardiovascular mortality, stroke, ischaemic cardiovascular disease and heart failure.…”

Diabetic kidney disease: New clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on “The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function”

“…Other biomarkers that have been associated with eGFR loss include: urinary high molecular weight adiponectin [118], adiponectin [119], type IV collagen [120,121], and haptoglobin [122,123]; circulating arginine vasopressin, as measured as copeptin [124], adipocyte FABP [125], fibroblast growth factor 21 [126], kininogen and kininogen fragments [127], the angiogenic factor leucine-rich a-2 glycoprotein 1 [128], the anti-ageing hormone soluble Klotho (low levels) [129], and leptin (both high and low levels) [130]; and erythrocyte total polyunsaturated fatty acids (PUFAs), n-3 PUFAs, and n-3/n-6 PUFA ratio, but not n-6 PUFAs (low levels) [106], all in T2D patients (except urinary collagen IV, in both T1D and T2D individuals). In addition, CKD273, a multidimensional urinary proteome classifier consisting of 273 protein fragments, predicted deterioration of renal function in patients with [131] and without [132] albuminuria and also development of microalbuminuria in normoalbuminuric individuals [133].…”