Untangling the Knot in Diabetic Nephropathy: The Unanticipated Role of Glycocalyx in the Antiproteinuric Effect of Endothelin Receptor Antagonists

Buelli, Simona; Perico, Luca; Benigni, Ariela

doi:10.2337/dbi16-0020

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…It was initially thought that the glomerular endothelial layer, due to its fenestrations, could only exclude cellular components of the blood from filtration and that podocytes acted as the ultimate barrier to flow of macromolecules into the urinary filtrate. However, in recent years it has become clear that injury to and dysfunction of any of the components of the glomerular filtration barrier, including the endothelium, can result in the development of albuminuria (42,43). In support of a role of MVD, especially of the endothelium, observational studies in humans with and without T2D have shown a continuous association between albuminuria and lower skin capillary density (44), lower heat-induced skin microvascular dilation (45), and lower flicker-light-induced retinal arteriolar dilation (45).…”

Section: Diabetic Nephropathymentioning

confidence: 99%

Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

2018

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Microvascular and metabolic physiology are tightly linked. This Perspective reviews evidence that ) the relationship between hyperglycemia and microvascular dysfunction (MVD) is bidirectional and constitutes a vicious cycle;) MVD in diabetes affects many, if not all, organs, which may play a role in diabetes-associated comorbidities such as depression and cognitive impairment; and ) MVD precedes, and contributes to, hyperglycemia in type 2 diabetes (T2D) through impairment of insulin-mediated glucose disposal and, possibly, insulin secretion. Obesity and adverse early-life exposures are important drivers of MVD. MVD can be improved through weight loss (in obesity) and through exercise. Pharmacological interventions to improve MVD are an active area of investigation.

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Section: Diabetic Nephropathymentioning

confidence: 99%

Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

2018

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“…Indeed, several randomized controlled trials have demonstrated that medications indicated for treatment of T2DM such as glucagon like peptide-1 (GLP-1) [ 14 , 15 ] and sodium-glucose co-transporter 2 (SGLT-2) inhibitors [ 16 , 17 ] can slow renal disease progression as well as reduce adverse CV outcomes. Other complementary therapeutic approaches such as utilizing selective endothelin receptor type A (ET-A) antagonists may also help delay renal function decline and subsequently lower the risk of related adverse renal outcomes [ 18 ]; albeit the precise beneficial mechanisms conferred from these medications are still undergoing investigation [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Albuminuria, serum creatinine, and estimated glomerular filtration rate as predictors of cardio-renal outcomes in patients with type 2 diabetes mellitus and kidney disease: a systematic literature review

Norris¹,

Smoyer²,

Rolland³

et al. 2018

BMC Nephrol

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BackgroundAlbuminuria, elevated serum creatinine and low estimated glomerular filtration rate (eGFR) are pivotal indicators of kidney decline. Yet, it is uncertain if these and emerging biomarkers such as uric acid represent independent predictors of kidney disease progression or subsequent outcomes among individuals with type 2 diabetes mellitus (T2DM). This study systematically examined the available literature documenting the role of albuminuria, serum creatinine, eGFR, and uric acid in predicting kidney disease progression and cardio-renal outcomes in persons with T2DM.MethodsEmbase, MEDLINE, and Cochrane Central Trials Register and Database of Systematic Reviews were searched for relevant studies from January 2000 through May 2016. PubMed was searched from 2013 until May 2016 to retrieve studies not yet indexed in the other databases. Observational cohort or non-randomized longitudinal studies relevant to albuminuria, serum creatinine, eGFR, uric acid and their association with kidney disease progression, non-fatal cardiovascular events, and all-cause mortality as outcomes in persons with T2DM, were eligible for inclusion. Two reviewers screened citations to ensure studies met inclusion criteria.ResultsFrom 2249 citations screened, 81 studies were retained, of which 39 were omitted during the extraction phase (cross-sectional [n = 16]; no outcome/measure of interest [n = 13]; not T2DM specific [n = 7]; review article [n = 1]; editorial [n = 1]; not in English language [n = 1]). Of the remaining 42 longitudinal study publications, biomarker measurements were diverse, with seven different measures for eGFR and five different measures for albuminuria documented. Kidney disease progression differed substantially across 31 publications, with GFR loss (n = 9 [29.0%]) and doubling of serum creatinine (n = 5 [16.1%]) the most frequently reported outcome measures. Numerous publications presented risk estimates for albuminuria (n = 18), serum creatinine/eGFR (n = 13), or both combined (n = 6), with only one study reporting for uric acid. Most often, these biomarkers were associated with a greater risk of experiencing clinical outcomes.ConclusionsDespite the utility of albuminuria, serum creatinine, and eGFR as predictors of kidney disease progression, further efforts to harmonize biomarker measurements are needed given the disparate methodologies observed in this review. Such efforts would help better establish the clinical significance of these and other biomarkers of renal function and cardio-renal outcomes in persons with T2DM.Electronic supplementary materialThe online version of this article (10.1186/s12882-018-0821-9) contains supplementary material, which is available to authorized users.

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Microvascular Damage and Hemodynamic Alterations in Diabetic Nephropathy

Wenstedt

Vogt

2018

Diabetic Nephropathy

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Untangling the Knot in Diabetic Nephropathy: The Unanticipated Role of Glycocalyx in the Antiproteinuric Effect of Endothelin Receptor Antagonists

Cited by 4 publications

References 19 publications

Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

Albuminuria, serum creatinine, and estimated glomerular filtration rate as predictors of cardio-renal outcomes in patients with type 2 diabetes mellitus and kidney disease: a systematic literature review

Microvascular Damage and Hemodynamic Alterations in Diabetic Nephropathy

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