Vitamin B and/or its derivatives for diabetic kidney disease

Raval, Amit D.; Gor, Deval; Rangoonwala, Arohi N; Thakker, D.

doi:10.1002/14651858.cd009403

Cited by 7 publications

(10 citation statements)

References 64 publications

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“…The identification of the association of polymorphisms related to the genes of thiamine and TKT with DPN might be a first step in defining a DPN genetic risk profile with potential therapeutic repercussions. There is moderate evidence from preclinical experimental models that high‐dose thiamine and benfotiamine (a lipid‐soluble thiamine derivative with higher bioavailability than thiamine) (1) inhibit the pathways of hexosamine, AGE's formation, and diacylglycerol‐protein kinase C through the TKT activation, (2) target at various surrogate markers of hyperglycaemia‐induced pathological processes, and (3) can delay the progression of microangiopathic complications . Clinical trials in both diabetic nephropathy and DPN have shown some effect on microalbuminuria and symptomatic DPN, although with some controversy due to their limitations such as low number, poor design, short duration, confounding bias of dietary source of thiamine, different phenotypes, and inadequately defined outcomes .…”

Section: Discussionmentioning

confidence: 99%

“…There is moderate evidence from preclinical experimental models that high‐dose thiamine and benfotiamine (a lipid‐soluble thiamine derivative with higher bioavailability than thiamine) (1) inhibit the pathways of hexosamine, AGE's formation, and diacylglycerol‐protein kinase C through the TKT activation, (2) target at various surrogate markers of hyperglycaemia‐induced pathological processes, and (3) can delay the progression of microangiopathic complications . Clinical trials in both diabetic nephropathy and DPN have shown some effect on microalbuminuria and symptomatic DPN, although with some controversy due to their limitations such as low number, poor design, short duration, confounding bias of dietary source of thiamine, different phenotypes, and inadequately defined outcomes . Thus, there is still a need for high‐quality, well‐designed clinical trials of appropriate size and duration to bridge the gap in evidence and to allow final recommendations to be established on the use of thiamine and benfotiamine as a disease‐modifying treatment of diabetic complications …”

Section: Discussionmentioning

confidence: 99%

“…Clinical trials in both diabetic nephropathy and DPN have shown some effect on microalbuminuria and symptomatic DPN, although with some controversy due to their limitations such as low number, poor design, short duration, confounding bias of dietary source of thiamine, different phenotypes, and inadequately defined outcomes . Thus, there is still a need for high‐quality, well‐designed clinical trials of appropriate size and duration to bridge the gap in evidence and to allow final recommendations to be established on the use of thiamine and benfotiamine as a disease‐modifying treatment of diabetic complications …”

Section: Discussionmentioning

confidence: 99%

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Might genetics play a role in understanding and treating diabetic polyneuropathy?

Spallone

2017

Diabetes Metabolism Res

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Despite the high prevalence and impact on quality of life, costs, and survival, there are still unresolved issues regarding diabetic polyneuropathy (DPN): the lack of definite knowledge of its pathogenesis; the limited preventive action of glycaemic control in type 2 diabetes; and the unavailability of evidence-based effective disease-modifying treatment. How can genetics provide the tools to address these gaps? Ziegler et al for the GDS Group explore the novel hypothesis that genetic variability in transketolase (TKT) might contribute to susceptibility to DPN in patients with newly diagnosed type 1 and type 2 diabetes (well characterised for DPN). Transketolase diverts excess glycolytic metabolites from the hexosamine, protein kinase C, and advanced glycation endproduct pathways to the pentose phosphate pathway, with a protective effect against hyperglycaemia-induced damage. Moreover, thiamine and its derivative benfotiamine are among the few disease-modifying agents still under consideration as DPN treatment. The authors find significant associations of single-nucleotide polymorphisms of the TKT gene with the Total Symptom Score and thermal thresholds, in particular in male participants with type 2 diabetes. Moreover, they measure plasma methylglyoxal (a glycating agent, whose availability is hindered by TKT) without however finding a relation with TKT single-nucleotide polymorphisms. The link found between TKT genetic variability and nerve function measures is considered here in the context of DPN genetic studies and of experimental and clinical findings regarding thiamine and benfotiamine. The conclusion is that available data supports the decision to maintain focus on both the search for DPN genetic biomarkers and the therapeutic attempts to target thiamine, TKT, and methylglyoxal.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Might genetics play a role in understanding and treating diabetic polyneuropathy?

Spallone

2017

Diabetes Metabolism Res

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“…The maximal score for an included study was 5 and studies were classi ed as high (score 3-5) or low (0-2) (26). Given the small numbers of trials included in this metaanalysis, publication bias was not formally assessed (27,28).…”

Section: Data Extraction and Methodological Quality Assessmentmentioning

confidence: 99%

Immunomodulatory drug and dexamethasone-containing triple versus doublet combination treatments for relapsed or refractory multiple myeloma: a meta-analysis of phase III randomized controlled trials

Gao

Yan

et al. 2020

Preprint

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Background Triplet therapy has become the standard of care for relapsed or refractory multiple myeloma (RRMM) over the past few years. Prior to that, doublet therapy including dexamethasone and an immunomodulatory were standard. Several systematic studies have been conducted and many combinations with variable triplet therapies but have not always used the former standard therapy as a benchmark. The objective of this meta-analysis was to evaluate the efficacy and safety of triplet combinations that included dexamethasone and an immunomodulatory drug versus a doublet combination of just dexamethasone and an immunomodulatory for the treatment of RRMM. Methods A comprehensive literature search (PubMed, EMBASE, Cochrane Library) for phase III randomized controlled trials for efficacy and safety of triplet versus doublet combinations that specifically included dexamethasone and an immunomodulatory drug for treatment of RRMM. Efficacy (ORR, PFS, OS) and adverse events (≥ grade 3) were assessed using traditional statistical measures for aggregate data. Results Of 235 potential reports, 6 met the inclusion criteria (N = 115–792 participants). The methodological quality was ≥ 4 Jadad score for each. Triplet treatment had higher ORR (HR = 0.74, 95%CI: 0.65–0.84, P ≤ 0.001), PFS (HR = 0.63, 95%CI: 0.52–0.75, P ≤ 0.001), and OS (HR = 0.74, 95%CI: 0.65–0.84, P ≤ 0.001). The incidence of ≥ grade 3 diarrhea and fatigue were significantly higher in the triplet combination group. There was a trend toward increased incidence of ≥ grade 3 neutropenia, thrombocytopenia, thromboembolism, and peripheral neuropathy in the triplet therapy group. Notably, triplet therapy had a significantly lower rate of anemia compared to doublet therapy. Conclusions This study reinforces current guidelines and recommendations for triplet combinations containing dexamethasone and an immunomodulatory drug.

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“…Either lack of efficacy or safety concerns were the reasons for failure. Bardoxolone methyl, inhibitors of protein kinase C (ruboxistaurin) or of AGEs formation ( pimagedine/aminoguanidine , pyridoxamine), and sulodexide, have failed to find a place in the treatment of DKD [ 7 , 22 ]. Pirfenidone, anti-connective tissue growth factor (CTGF) or, anti-TGF-β monoclonal antibodies, and antifibrotic therapies are no longer being pursued in patients with DKD [ 7 ].…”

Section: Current Therapy For Diabetic Kidney Diseasementioning

confidence: 99%

Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade

Perez-Gomez

Sanchez-Niño

Sanz

et al. 2015

JCM

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Diabetic kidney disease is the most frequent cause of end-stage renal disease. This implies failure of current therapeutic approaches based on renin-angiotensin system (RAS) blockade. Recent phase 3 clinical trials of paricalcitol in early diabetic kidney disease and bardoxolone methyl in advanced diabetic kidney disease failed to meet the primary endpoint or terminated on safety concerns, respectively. However, various novel strategies are undergoing phase 2 and 3 randomized controlled trials targeting inflammation, fibrosis and signaling pathways. Among agents currently undergoing trials that may modify the clinical practice on top of RAS blockade in a 5-year horizon, anti-inflammatory agents currently hold the most promise while anti-fibrotic agents have so far disappointed. Pentoxifylline, an anti-inflammatory agent already in clinical use, was recently reported to delay estimated glomerular filtration rate (eGFR) loss in chronic kidney disease (CKD) stage 3–4 diabetic kidney disease when associated with RAS blockade and promising phase 2 data are available for the pentoxifylline derivative CTP-499. Among agents targeting chemokines or chemokine receptors, the oral small molecule C-C chemokine receptor type 2 (CCR2) inhibitor CCX140 decreased albuminuria and eGFR loss in phase 2 trials. A dose-finding trial of the anti-IL-1β antibody gevokizumab in diabetic kidney disease will start in 2015. However, clinical development is most advanced for the endothelin receptor A blocker atrasentan, which is undergoing a phase 3 trial with a primary outcome of preserving eGFR. The potential for success of these approaches and other pipeline agents is discussed in detail.

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Vitamin B and/or its derivatives for diabetic kidney disease

Cited by 7 publications

References 64 publications

Might genetics play a role in understanding and treating diabetic polyneuropathy?

Might genetics play a role in understanding and treating diabetic polyneuropathy?

Immunomodulatory drug and dexamethasone-containing triple versus doublet combination treatments for relapsed or refractory multiple myeloma: a meta-analysis of phase III randomized controlled trials

Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade

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