Circulating bone morphogenetic protein-7 and transforming growth factor-β1 are better predictors of renal end points in patients with type 2 diabetes mellitus

Wong, Muh Geot; Perkovic, Vlado; Woodward, Mark; Chalmers, John; Li, Qiang; Hillis, Graham S.; Azari, Dania Yaghobian; Jun, Min; Poulter, Neil; Hamet, Pavel; Williams, Bryan; Neal, Bruce; Mancia, Giuseppe; Cooper, Mark E.; Pollock, Carol

doi:10.1038/ki.2012.383

Cited by 54 publications

(53 citation statements)

References 47 publications

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“…Such biomarkers may also be used to identify new molecular targets and focus clinical trials on participants with the highest risks of progressive disease. Examples of such biomarkers would be components of the pathways already incriminated in the pathophysiology of kidney disease (e.g., RAAS, 24 bone morphogenetic protein, [25][26][27] wingless-type mouse mammary tumour virus integration site, 28,29 Notch, 30 vascular endothelial growth factor, and protein kinase C pathways, to name a few).…”

Section: Discussionmentioning

confidence: 99%

Renal Outcomes in Patients with Type 1 Diabetes and Macroalbuminuria

Boer

Afkarian

Rue

et al. 2014

Journal of the American Society of Nephrology

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Macroalbuminuria, defined as urine albumin excretion rate (AER)$300 mg/d, has long been considered a stage of irreversible kidney damage that leads reliably to GFR loss. We examined the long-term renal outcomes of persons with type 1 diabetes who developed incident macroalbuminuria during the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. One hundred fifty-nine participants developed incident macroalbuminuria and were subsequently followed for a median duration of 9 years (maximum of 25 years). At the time of macroalbuminuria diagnosis, mean (SD) age was 37 (9) years, mean (SD) duration of diabetes was 17 (5) years, median AER was 524 mg/d, and mean (SD) eGFR was 108 (20) ml/min per 1.73 m 2 . Ten years after macroalbuminuria diagnosis, the cumulative incidence of a sustained reduction in AER to ,300 mg/d was 52%, mostly but not entirely under treatment with renin-angiotensin system inhibitors. The cumulative incidence of impaired GFR (sustained eGFR,60 ml/ min per 1.73 m 2 ) 10 years after macroalbuminuria diagnosis was 32%, including 16% who developed ESRD. Lower hemoglobin A1c and BP and regression to AER,300 mg/d were associated with reduced risk of developing impaired GFR. In conclusion, people with type 1 diabetes who develop macroalbuminuria are at high risk of progressive kidney disease. However, through at least 10 years of follow-up, AER could often be controlled, and GFR frequently remained in the normal range.

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Section: Discussionmentioning

confidence: 99%

Renal Outcomes in Patients with Type 1 Diabetes and Macroalbuminuria

Boer

Afkarian

Rue

et al. 2014

Journal of the American Society of Nephrology

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“…Recent studies have highlighted some promising new biomarkers including plasma concentrations of TGF-β to bone morphogenetic protein-7 (BMP-7) ratio [94] and TNF receptors 1 and 2 (TNFR1 and TNFR2) [95, 96]. A number of new and important biomarkers present in the urine have also emerged.…”

Section: Resultsmentioning

confidence: 99%

Urinary biomarkers for early diabetic nephropathy: beyond albuminuria

Lee

Choi

2014

Pediatr Nephrol

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Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease in the United States, and accounts for a significant increase in morbidity and mortality in patients with diabetes. Early detection is critical in improving clinical management. Although microalbuminuria is regarded as the gold standard for diagnosing onset of DN, its predictive powers are limited. There have been great efforts in recent years to identify better strategies for the detection of early stages of DN and progressive kidney function decline in diabetic patients. Here, we review various urinary biomarkers that have emerged and hold promise to be more sensitive for earlier detection of diabetic kidney disease and predictive of progression to end-stage kidney disease. A number of key biomarkers present in the urine have been identified that reflect kidney injury at specific sites along the nephron, including glomerular/podocyte damage and tubular damage, oxidative stress, inflammation, and activation of the intrarenal renin-angiotensin system. Moreover, we describe newer approaches including urinary microRNAs, which are short noncoding mRNAs that regulate gene expression, and urine proteomics used to identify potential novel biomarkers in the development and progression of diabetic kidney disease.

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“…Wong et al demonstrated that decreases in circulating BMP-7 are predictive of ESRD in patients with diabetes. The prognostic value of BMP-7 was increased beyond that of the best available risk markers for diabetic nephropathy when combined with the detection of increased TGF-β levels (Wong et al, 2013). Using an analogous approach, Neuwirt et al (2014) found that a biomarker panel containing BMP-7 accurately predicts the loss of kidney function in patients with proteinuric diseases.…”

Section: Clinical Implications For Bmp-7 In Patients With Ckdmentioning

confidence: 97%