Paricalcitol for reduction of albuminuria in diabetes

Delanaye, Pierre; Mariat, Christophe; Krzesinski, Jean-Marie; Cavalier, Étienne

doi:10.1016/s0140-6736(11)60222-5

Cited by 7 publications

(3 citation statements)

References 7 publications

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“…Though the 1 µg/day dose was unable to show a significant reduction in albuminuria, but the 2 µg/day regimen decreased albuminuria by a 20% difference compared to placebo. The benefits seen in this study have been attributed to Vitamin D insufficiency and repletion improved albuminuria [210].…”

Section: Vitamin Dmentioning

confidence: 58%

Renal Disease in Diabetes Mellitus: Recent Studies and Potential Therapies

Iqbal¹

2013

http://www.omicsonline.org/jdmhome.php

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Diabetic kidney disease is the predominant cause of end stage kidney disease in North America, estimated to be 152 per million population in 2010. New guidelines published by KDIGO on Chronic Kidney Disease classification are discussed. In light of recent clinical trials, better insight has been gained on how improve management of diabetic patients to prevent renal disease and its progression, especially with regards to metabolic and blood pressure control. Unfortunately, studies of newer therapies such as endothelin 1 antagonists and bardoxolone methyl have been disappointing, but several other possible therapeutic agents are under investigation and may provide hope for patients with diabetes mellitus in the future.

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Section: Vitamin Dmentioning

confidence: 58%

Renal Disease in Diabetes Mellitus: Recent Studies and Potential Therapies

Iqbal¹

2013

http://www.omicsonline.org/jdmhome.php

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“…Kidney disease therapeutics face the challenge of having a narrow therapeutic index. − Current treatment options for chronic kidney disease only prevent or delay the progression of end-stage renal disease, and it can be accompanied by serious side effects. Limited therapeutic windows have led to failures of many drug candidates to treat kidney disease in clinical trials. ,− Drug concentrations in the kidney play an important role in therapeutic drug potency. Targeted drug delivery to the kidneys has the potential to improve efficacy and reduce off-target toxicity, providing new opportunities for kidney disease treatment. − …”

Section: Introductionmentioning

confidence: 99%

Antibody Fragment F(ab′)₂ Targeting Caveolae-Associated Protein PV1 for Selective Kidney Targeting and Retention

Peterson

Hanna

et al. 2019

Mol. Pharmaceutics

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Targeted strategies to deliver and retain drugs to kidneys are needed to improve drug accumulation and efficacy in a myriad of kidney diseases. These drug delivery systems show potential for improving the therapeutic windows of drugs acting in the kidney. Biodistribution of antibody-based therapeutics in vivo is governed by several factors including binding affinity, size, and valency. Investigations of how the biophysical and biochemical properties of biologics enable them to overcome biological barriers and reach kidneys are therefore of interest. Although renal accumulation of antibody fragments in cancer diagnostics and treatment has been observed, reports on effective delivery of antibody fragments to the kidneys remain scarce. Previously, we demonstrated that targeting plasmalemma vesicle-associated protein (PV1), a caveolae-associated protein, can promote accumulation of antibodies in both the lungs and the kidneys. Here, by fine-tuning the binding affinity of an antibody toward PV1, we observe that the anti-PV1 antibody with reduced binding affinity lost the capability for kidney targeting while retaining the lung targeting activity, suggesting that binding affinity is a critical factor for kidney targeting of the anti-PV1 antibody. We next use the antibody fragment F(ab′)2 targeting PV1 to assess the dual effects of rapid kidney filtration and PV1 targeting on kidney-selective targeting. Ex vivo fluorescence imaging results demonstrated that after rapidly accumulating in kidneys at 4 h, PV1-targeted F(ab′)2 was continually retained in the kidney at 24 h, whereas the isotype control F(ab′)2 underwent urinary elimination with significantly reduced signaling in the kidney. Confocal imaging studies confirmed the localization of PV1-targeted F(ab′)2 in the kidney. In addition, the monovalent antibody fragment (Fab-C4) lost the capability for kidney homing, indicating that the binding avidity of anti-PV1 F(ab′)2 is important for kidney targeting. Our findings suggest that PV1-targeted F(ab′)2 might be useful as a drug carrier for renal targeting and highlight the importance of affinity optimization for tissue targeting antibodies.

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“…Currently, the only treatment option for CKD is prevention or retardation of the progression of further kidney damage. However, long-term therapy of CKD is accompanied by serious side effects and numerous promising drug candidates failed during clinic trials due to safety issues and lack of efficacy, e.g., bardoxolone methyl , and paricalcitol in CKD, − avosentan in diabetic nephropathy, and sirolimus and everolimus in autosomal dominant polycystic kidney disease (ADPKD). , Consequently, renal targeted drug delivery would broaden the therapeutic window of drugs acting in the kidneys, reduce systemic side effects, and thus enable new treatment opportunities.…”

Section: Introductionmentioning

confidence: 99%

Renal Targeting: Peptide-Based Drug Delivery to Proximal Tubule Cells

et al. 2016

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Kidney-specific drug targeting is an attractive strategy to reduce unwanted side effects and to enhance drug efficacy within the renal tissue. For this purpose a novel kidney-specific drug carrier was developed. The peptide sequence (KKEEE)3K triggers exceptional renal specificity at high accumulation rates. Micro-PET imaging studies of megalin-deficient mice indicate that the cellular endocytosis of this carrier is mediated by megalin. This assumption is supported by immunohistochemical analysis of FITC-labeled carrier peptide, which exclusively accumulated at the apical side of proximal tubule cells within the renal cortex. Scintigraphic studies of modified ciprofloxacin conjugated to (KKEEE)3K confirmed the excellent drug targeting potential of the peptide carrier. The conjugate accumulated entirely in the kidneys, revealing flawless redirection of ciprofloxacin, a compound that is mainly excreted by the liver. In conclusion, these results suggest the potential of (KKEEE)3K as a promising candidate for kidney-targeted drug delivery to proximal tubule cells.

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Paricalcitol for reduction of albuminuria in diabetes

Cited by 7 publications

References 7 publications

Renal Disease in Diabetes Mellitus: Recent Studies and Potential Therapies

Renal Disease in Diabetes Mellitus: Recent Studies and Potential Therapies

Antibody Fragment F(ab′)₂ Targeting Caveolae-Associated Protein PV1 for Selective Kidney Targeting and Retention

Renal Targeting: Peptide-Based Drug Delivery to Proximal Tubule Cells

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Paricalcitol for reduction of albuminuria in diabetes

Cited by 7 publications

References 7 publications

Renal Disease in Diabetes Mellitus: Recent Studies and Potential Therapies

Renal Disease in Diabetes Mellitus: Recent Studies and Potential Therapies

Antibody Fragment F(ab′)2 Targeting Caveolae-Associated Protein PV1 for Selective Kidney Targeting and Retention

Renal Targeting: Peptide-Based Drug Delivery to Proximal Tubule Cells

Contact Info

Product

Resources

About

Antibody Fragment F(ab′)₂ Targeting Caveolae-Associated Protein PV1 for Selective Kidney Targeting and Retention