Urinary adiponectin excretion rises with increasing albuminuria in type 1 diabetes

Jorsal, Anders; Petersen, Emilie Hein; Tarnow, Lise; Heß, Georg; Zdunek, Dietmar; Frystyk, Jan; Flyvbjerg, Allan; Lajer, Maria; Rossing, Peter

doi:10.1016/j.jdiacomp.2013.06.008

Cited by 15 publications

(12 citation statements)

References 38 publications

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“…An increase in uADP in parallel with AER in patients with type 1 diabetes was previously observed only in a small study that could not explore the relationship further due to insufficient power (24). We show that uADP not only strongly predicted progression to ESRD but also is a better predictor than AER and adds a significant predictive benefit when used together with eGFR or AER.…”

Section: Discussionmentioning

confidence: 47%

Urinary Adiponectin Is an Independent Predictor of Progression to End-Stage Renal Disease in Patients With Type 1 Diabetes and Diabetic Nephropathy

et al. 2015

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OBJECTIVEWe investigated the predictive value of urinary adiponectin (uADP) for the progression of diabetic nephropathy (DN) as well as for the principal determinants of uADP concentrations. RESEARCH DESIGN AND METHODSuADP was measured in 2,090 patients with type 1 diabetes followed for a median of 5.8 (4.4-6.9) years and in 111 subjects without diabetes. Progression was defined as a change in albuminuria (albumin excretion rate [AER]) to a higher stage or development of end-stage renal disease (ESRD). Various Cox regression and competing risk models were used to evaluate the predictive value of uADP for DN progression. The added predictive benefit to AER or estimated glomerular filtration rate (eGFR) was estimated by the area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), continuous net reclassification improvement (NRI), and other statistical indexes. The determinants of uADP were investigated by multiple regression analyses. RESULTSuADP was an independent predictor of progression to ESRD (hazard ratio 1.60, P < 0.001) and was an even better predictor than AER (P = 0.04) or as good as eGFR (P = 0.79). Furthermore, uADP added a significant benefit when used together with AER (NRI 0.794, P = 0.03; IDI 0.115, P < 0.0001) or eGFR (NRI 0.637, P < 0.001; IDI 0.087, P < 0.0001). The common determinants of uADP were glycemic control, tubular injury, and AER. CONCLUSIONSuADP is a strong independent predictor of DN progression from macroalbuminuria to ESRD and adds a significant predictive benefit to current biomarkers in patients with type 1 diabetes.

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Section: Discussionmentioning

confidence: 47%

Urinary Adiponectin Is an Independent Predictor of Progression to End-Stage Renal Disease in Patients With Type 1 Diabetes and Diabetic Nephropathy

et al. 2015

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“…The urinary adiponectin excretion rate has been reported to be positively correlated with UAE and negatively with GFR (Koshimura et al 2004, Fujita et al 2006, Jorsal et al 2013. The positive relationship between urinary adiponectin excretion rate and UAE has been shown to strengthen with increasing UAE; this association has been found to exist mainly in patients with macroalbuminuria (UAE O300 mg/24 h) or microalbuminuria (UAE between 30 and 300 mg/24 h) and less consistently in subjects with normoalbuminuria (Koshimura et al 2004, Fujita et al 2006, Jorsal et al 2013. Thus, in patients with increased UAE or decreased GFR, the adiponectin production rate -hepatic adiponectin excretion rateappears to be increased.…”

Section: Urinary Adiponectin Excretion Rate In Patients With Albuminuriamentioning

confidence: 99%

“…Taking into account the use of ACE-I and ARBs preferentially in subjects with advanced albuminuria to reduce further increases in UAE, these drugs could have confounded the adiponectin-UAE relationship. Another limitation of some studies investigating the relationship between adiponectin and UAE is that patients with previously persistent macroalbuminuria, but with UAE !300 mg/24 h at the time of investigation (due to appropriate treatment), were analysed as having macroalbuminuria ( Jorsal et al 2013). In addition, the investigation of adiponectin-albuminuria relationship has been performed mostly in diabetics.…”

Section: Serum Adiponectin Levels In Patients With Albuminuriamentioning

confidence: 99%

The role of adiponectin in renal physiology and development of albuminuria

Christou¹,

Kiortsis²

2014

Journal of Endocrinology

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Adiponectin is secreted by the adipose tissue and is downregulated in states of obesity and insulin resistance. There is a growing body of evidence indicating that adiponectin has renoprotective effects and protects against the development of albuminuria in rodent experiments. Adiponectin crossing the glomerular filtration barrier possibly inhibits inflammation, fibrosis and oxidative stress in kidneys through activation of AMP-activated protein kinase. Moreover, microalbuminuria is a well established early sign of progressive cardiovascular and renal disease, even in subjects with preserved glomerular filtration rate. Studies investigating the relationship between serum adiponectin levels and urinary albumin excretion rate (UAE) have yielded conflicting data and the mechanisms underlying the interplay between adiponectin and albuminuria remain to be elucidated. This article constitutes a critical review attempting to clarify any remaining confusion about this matter. Furthermore, this article examines the clinical significance of adiponectin-albuminuria interplay, suggesting that adiponectin is possibly involved in the development of albuminuria that is associated with obesity, diabetes and cardiovascular disease and may mediate, at least in part, the actions of medical treatments that influence UAE, such as angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, thiazolidinediones, fenofibrate and diet. Further studies to investigate more thoroughly the renoprotective role of adiponectin in the human setting should be carefully planned, focusing on causality and the possible influence of adiponectin on the development of albuminuria in specific clinical settings.

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“…Studies have reported that HGF is markedly elevated in patients with end-stage renal disease, and may be considered a novel vascular modulator in humans [8]. In a cross-sectional study, we previously found urinary adiponectin excretion to be positively related to albuminuria in type 1 diabetes [9]. Moreover, prospective studies have shown that high urinary adiponectin is associated with the development of end-stage renal disease [10,11].…”

Section: Introductionmentioning

confidence: 90%

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

et al. 2016

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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.

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Urinary adiponectin excretion rises with increasing albuminuria in type 1 diabetes

Cited by 15 publications

References 38 publications

Urinary Adiponectin Is an Independent Predictor of Progression to End-Stage Renal Disease in Patients With Type 1 Diabetes and Diabetic Nephropathy

Urinary Adiponectin Is an Independent Predictor of Progression to End-Stage Renal Disease in Patients With Type 1 Diabetes and Diabetic Nephropathy

The role of adiponectin in renal physiology and development of albuminuria

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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