A prospective study of multiple protein biomarkers to predict progression in diabetic chronic kidney disease

Agarwal, Rajiv; Duffin, Kevin L.; Laska, D. A.; Voelker, James R.; Breyer, Matthew D.; Mitchell, Peter G.

doi:10.1093/ndt/gfu255

Cited by 64 publications

(57 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Not only is albuminuria a very strong (if not strongest) renal risk marker among all clinical characteristics, it also stands out against novel renal risk markers. A recent prospective observational study in patients with type 2 diabetes and CKD reported that multiple novel renal risk markers predicted the progression of renal disease (34). However, when Agarwal et al (34) adjusted their analyses for albuminuria, only fibroblast growth factor-23 remained statistically significantly associated with renal outcome.…”

Section: Albuminuria Predicts Renal Outcomementioning

confidence: 99%

“…A recent prospective observational study in patients with type 2 diabetes and CKD reported that multiple novel renal risk markers predicted the progression of renal disease (34). However, when Agarwal et al (34) adjusted their analyses for albuminuria, only fibroblast growth factor-23 remained statistically significantly associated with renal outcome. This indicates that a large part of the renal risk predicted by these novel renal risk markers can be explained by their association with albuminuria.…”

Section: Albuminuria Predicts Renal Outcomementioning

confidence: 99%

See 1 more Smart Citation

Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD

Heerspink¹,

Gansevoort

2015

Clinical Journal of the American Society of Nephrology

136

View full text Add to dashboard Cite

The presence of elevated levels of albuminuria is associated with an increased risk of progressive renal function loss over time. This association is found in various pathophysiological conditions, including diabetic nephropathy, hypertensive nephropathy, and various primary renal diseases, but also, the general, otherwise healthy population. Emerging data report that elevated albuminuria causes tubulointerstitial damage through activation of proinflammatory mediators, which ultimately leads to a progressive decline in renal function. Nowadays, various drugs are available that decrease the rate of GFR loss in patients with kidney disease. Well known are renin-angiotensin-aldosterone system inhibitors, but there are also other drugs and interventions, like intensive glucose control, anti-inflammatory agents (pentoxifylline), or a low-protein diet. These interventions have an additional effect beyond their original target, namely lowering albuminuria. Analyses from clinical trials show that the reduction in albuminuria observed during the first months of treatment with these drugs correlates with the degree of long-term renal protection: the larger the initial reduction in albuminuria, the lower the risk of ESRD during treatment. In addition, in treated patients, residual albuminuria is again the strongest risk marker for renal disease progression. These observations combined provide a strong argument that albuminuria is an appropriate therapeutic target in patients with CKD.

show abstract

Section: Albuminuria Predicts Renal Outcomementioning

confidence: 99%

Section: Albuminuria Predicts Renal Outcomementioning

confidence: 99%

Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD

Heerspink¹,

Gansevoort

2015

Clinical Journal of the American Society of Nephrology

136

View full text Add to dashboard Cite

show abstract

“…A filtration marker (serum cystatin C), tubule-associated markers (neutrophil-gelatinase associated lipocalin, kidney injury molecule-1, liver fatty acid binding protein, N-acetyl-beta-D-glucosaminidase), and inflammatory markers (soluble tumor necrosis factor receptors) have been reported to improve prediction of DKD and progression to end-stage renal disease (ESRD) in type 2 diabetes (T2DM) [8, 9]. In the last 5 years, microRNA, a class of small non-coding RNAs, has emerged as additional potential diagnostic and prognostic biomarkers in renal diseases.…”

Section: Introductionmentioning

confidence: 99%

Uromodulin mRNA from Urinary Extracellular Vesicles Correlate to Kidney Function Decline in Type 2 Diabetes Mellitus

Yamamoto¹,

Murakami²,

Oakes³

et al. 2018

Am J Nephrol

View full text Add to dashboard Cite

Background: Extracellular vesicles (EVs) enclose mRNA derived from their cell of origin and are considered a source of potential biomarkers. We examined urinary EV mRNA from individuals with diabetic kidney disease (DKD), chronic kidney disease, type 2 diabetes (T2DM), and obese and healthy controls to determine if such biomarkers had the potential to classify kidney disease and predict patients at higher risk of renal function decline. Methods: A total of 242 participants enrolled in this study. Urinary EV mRNA from all subjects were isolated by a filter-based platform, and the expression of 8 target genes were determined by quantitative polymerase chain reaction (qPCR). Changes in estimated glomerular filtration rate (eGFR) in 161 T2DM patients were evaluated for 2 consecutive years and compared with EV RNA profiles at baseline. Results: We observe that mild and severe DKD groups show a significant 3.2- and 4.4-fold increase in UMOD compared to healthy controls and expression increases linearly from healthy, diabetic, and DKD subjects. UMOD expression is significantly correlated to albumin creatinine ratio (ACR), eGFR, and HbA1c. Using linear discriminant analyses with mRNA from severe DKD and T2DM as training data, a multi-gene signature classified DKD and non-DKD with a sensitivity of 93% and specificity of 73% with area under the receiver operating characteristic (ROC) curve (AUC) = 0.90. Although 6% of T2DM were determined to have a > 80% posterior probability of developing DKD based on this mRNA profile, eGFR changes observed within the 2-year follow-up did not reveal a decline in kidney function. Conclusion: Urinary EV UMOD mRNA levels are progressively elevated from T2DM to DKD groups and correlate with widely used eGFR and ACR diagnostic criteria. An EV mRNA signature could identify DKD with greater than 90% sensitivity and 70% specificity.

show abstract

“…Also, intensive research has sought to identify biomarkers of diabetic kidney disease (DKD) progression. However, the performance of those markers for predicting DN or ESRD progression has been insufficient compared to the “gold standard” clinical measurements, estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) [11]. In particular, circulating blood or urinary microRNAs have been proposed to be novel tools for the diagnosis and prognosis of diabetes [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Urinary and Blood MicroRNA-126 and -770 are Potential Noninvasive Biomarker Candidates for Diabetic Nephropathy: a Meta-Analysis

Park

Moon

Lee

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Diabetic nephropathy (DN), a major diabetic microvascular complication, has a long and growing list of biomarkers, including microRNA biomarkers, which have not been consistent across preclinical and clinical studies. This meta-analysis aims to identify significant blood- and urine-incident microRNAs as diagnostic/prognostic biomarker candidates for DN. Methods: PubMed, Web of Science, and Cochrane Library were searched from their earliest records through 12th Dec 2016. Relevant publications for the meta-analysis included (1) human participants; (2) microRNAs in blood and urine; (3) DN studies; and (4) English language. Four reviewers, including two physicians, independently and blindly extracted published data regarding microRNA profiles in blood and/or urine from subjects with diabetic nephropathy. A random-effect model was used to pool the data. Statistical associations between diabetic nephropathy and urinary or blood microRNA expression levels were assessed. Results: Fourteen out of 327 studies (n=2,747 patients) were selected. Blood or urinary microRNA expression data of diabetic nephropathy were pooled for this analysis. The hsa-miR-126 family was significantly (OR: 0.57; 95% CI: 0.44-0.74; p-value < 0.0001) downregulated in blood from patients with diabetic kidney disease, while its urinary level was upregulated (OR: 2931.12; 95% CI: 9.96-862623.21; p-value = 0.0059). The hsa-miR-770 family microRNA were significantly (OR: 10.24; 95% CI: 2.37-44.25; p-value = 0.0018) upregulated in both blood and urine from patients with diabetic nephropathy. Conclusions: Our meta-analysis suggests that hsa-miR-126 and hsa-miR-770 family microRNA may have important diagnostic and pathogenetic implications for DN, which warrants further systematic clinical studies.

show abstract

A prospective study of multiple protein biomarkers to predict progression in diabetic chronic kidney disease

Cited by 64 publications

References 23 publications

Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD

Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD

Uromodulin mRNA from Urinary Extracellular Vesicles Correlate to Kidney Function Decline in Type 2 Diabetes Mellitus

Urinary and Blood MicroRNA-126 and -770 are Potential Noninvasive Biomarker Candidates for Diabetic Nephropathy: a Meta-Analysis

Contact Info

Product

Resources

About