Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria  A double-blind, placebo-controlled randomized trial

Rodrı́guez-Morán, Martha; González-González, G; Mv, Bermúdez-Barba; Ce, Medina de la Garza; He, Ting; Fj, Martínez-Martínez; Guerrero‐Romero, Fernando

doi:10.5414/cnp66003

Cited by 45 publications

(35 citation statements)

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“…Blood abnormal rheology impairs the microcirculatory blood flow exerting an adverse influence in the glomerular filtration and blood flow rate in peritubular plexus promoting the overload of low-molecular weight proteins into the proximal tubular cells that hinders tubular reabsorption of proteins [34,35]. Among the adverse outcome of augmented glomerular filtration, and therefore of the associated hyperfiltration, is the increase of hemoconcentration in the tubular plexus [36], which impair the postglomerular blood flow stimulating a elevation of intravascular pressure [34].…”

Section: An Approach To the Pathogenesis Of Diabetic Nephropathymentioning

confidence: 98%

“…Recently, we have hypothesized [35] that both rheologic and inflammatory mechanisms, exacerbated by poor glycemic control, Hyperglycemia promotes changes of blood fluidity that exerts an adverse influence in the glomerular filtration and the blood flow rate of peritubular plexus, promoting the overload of low-molecular weight proteins in the proximal tubular cells. The overload of proteins in the lumen of proximal tube exerts toxic and inflammatory effects that hinder tubular reabsorption increasing the urinary protein excretion rate.…”

Section: An Approach To the Pathogenesis Of Diabetic Nephropathymentioning

confidence: 99%

“…(1)). The overload of proteins into the lumen of proximal tube is linked with toxic and inflammatory effects that hinder tubular reabsorption [35][36][37][38].…”

Section: An Approach To the Pathogenesis Of Diabetic Nephropathymentioning

confidence: 99%

“…Recently, in order to identify the effect of pentoxifylline on the urinary protein excretion profile we conducted a clinical trial among 40 patients with type 2 diabetes and microalbuminuria (2-20 mg/mmol urine creatinine) [35]. At the end of follow-up, microalbuminuria significantly decreased from 8.4±4.9 to 2.2±2.6 mg/mmol urine creatinine in the subjects who received pentoxifylline, and remained without significant changes (8.5±4.9 to 7.9±4.7 mg/mmol urine creatinine) in the subjects with placebo, and showed that pentoxifylline significantly reduces the urinary excretion of low and high molecular-weight proteins.…”

Section: Pentoxifylline In Diabetic Nephropathymentioning

confidence: 99%

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Efficacy of Pentoxifylline in the Management of Microalbuminuria in Patients with Diabetes

Rodrı́guez-Morán¹,

Guerrero‐Romero

2008

CDR

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The prevalence of diabetes and its complications is increasing worldwide. Among the microvascular complications, diabetic nephropathy is the most frequent cause of end-stage renal disease. Although angiotensin-converting-enzyme inhibitors have been cited as the first line of therapy for the management of microalbuminuria, the rate of remission from microalbuminuria to normoalbuminuria has been lower than the expected. Furthermore, due to the elevated frequency of side effects of the rennin-angiotensin blockers new approaches for the treatment of microalbuminuria are needed. Pentoxifylline, a xanthine derivate drug with hemorheologic properties and primarily indicated for the therapy of disturbances of blood fluidity, is also an antagonist of adenosine 2 receptors and have anti-inflammatory and immunomodulatory effects, properties that promote beneficial changes in the blood flow conditions and kidney function. Current evidence shows that the short-term use of pentoxifylline has low side-effects, reduces both proteinuria and microalbuminuria in subjects with diabetes, and is as effective as captopril in the reduction of microalbuminuria in non-hypertensive type 2 diabetic patients. Although this data suggests that pentoxifylline could be useful for preventing the development of end-stage renal disease is necessary to conduct long-term studies to evaluate the role of pentoxifylline in the treatment of diabetic nephropathy and the prevention of chronic renal failure. In this article, we review the clinical evidence that show the efficacy of pentoxifylline in the management of microalbuminuria in diabetic patients.

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Section: An Approach To the Pathogenesis Of Diabetic Nephropathymentioning

confidence: 98%

Section: An Approach To the Pathogenesis Of Diabetic Nephropathymentioning

confidence: 99%

“…(1)). The overload of proteins into the lumen of proximal tube is linked with toxic and inflammatory effects that hinder tubular reabsorption [35][36][37][38].…”

Section: An Approach To the Pathogenesis Of Diabetic Nephropathymentioning

confidence: 99%

Section: Pentoxifylline In Diabetic Nephropathymentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of Pentoxifylline in the Management of Microalbuminuria in Patients with Diabetes

Rodrı́guez-Morán¹,

Guerrero‐Romero

2008

CDR

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“…CTP-499 also demonstrated efficacy in in vivo rodent models of diabetes and kidney fibrosis by attenuating renal hypertrophy and proteinuria and reducing kidney collagen deposition and tubule apoptosis. 21,22 In clinical studies, treatment with pentoxifylline has resulted in decreased proteinuria in patients with CKD, particularly those with diabetic nephropathy, 14,15,[23][24][25][26] and a reduction in the rate of eGFR decline. [27][28][29] CTP-499 is being developed as a potential treatment for CKD in patients with type 2 diabetes who are concurrently treated with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker.…”

mentioning

confidence: 99%

A First‐in‐Patient, Multicenter, Double‐Blind, 2‐Arm, Placebo‐Controlled, Randomized Safety and Tolerability Study of a Novel Oral Drug Candidate, CTP‐499, in Chronic Kidney Disease

Sabounjian

Graham

et al. 2016

Clinical Pharm in Drug Dev

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The prevalence of chronic kidney disease (CKD) related to type 2 diabetes is increasing worldwide.In addition to standard of care, treatment with anti-inflammatory and antifibrotic agents such as CTP-499, a novel oral, multisubtype selective inhibitor of phosphodiesterases, may be important in CKD treatment. A phase 1b randomized, double-blind, placebocontrolled clinical trial of CTP-499 in CKD patients (25 active, 8 placebo) with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m 2 was conducted to assess safety and tolerability. Secondary outcomes included pharmacokinetics and exploratory effects on inflammatory and hematology markers. Patients received 600 mg CTP-499 or matching placebo tablets orally once daily for 2 weeks, then twice daily for 2 additional weeks. CTP-499 was well tolerated with no serious or severe adverse events, or adverse events leading to discontinuation. CTP-499 was rapidly absorbed and produced acceptable interpatient variability. Of the 5 metabolites (M1-M5), M5 was the most abundant in plasma and urine. Exposure to CTP-499 and metabolites was higher in CKD patients than previously reported in healthy volunteers. No statistically significant differences were detected between the CTP-499-and placebo-treated groups for any of the biomarkers tested. This study provides data supporting further evaluation of CTP-499 in CKD patients.

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Pentoxifylline for diabetic kidney disease

Shan

Yuan³

et al. 2012

Cochrane Database of Systematic Reviews

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From the available evidence, pentoxifylline seems to offer some beneficial effects in renal function improvement and reduction in albuminuria and proteinuria, with no obvious serious adverse effects for patients with DKD. However, most studies were poorly reported, small, and methodologically flawed. Evidence to support the use of pentoxifylline for DKD was insufficient to develop recommendations for its use in this patient population. Rigorously designed, randomised, multicentre, large scale studies of pentoxifylline for DKD are needed to further assess its therapeutic effects.

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Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria A double-blind, placebo-controlled randomized trial

Cited by 45 publications

References 0 publications

Efficacy of Pentoxifylline in the Management of Microalbuminuria in Patients with Diabetes

Efficacy of Pentoxifylline in the Management of Microalbuminuria in Patients with Diabetes

A First‐in‐Patient, Multicenter, Double‐Blind, 2‐Arm, Placebo‐Controlled, Randomized Safety and Tolerability Study of a Novel Oral Drug Candidate, CTP‐499, in Chronic Kidney Disease

Pentoxifylline for diabetic kidney disease

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Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria  A double-blind, placebo-controlled randomized trial

Cited by 45 publications

References 0 publications

Efficacy of Pentoxifylline in the Management of Microalbuminuria in Patients with Diabetes

Efficacy of Pentoxifylline in the Management of Microalbuminuria in Patients with Diabetes

A First‐in‐Patient, Multicenter, Double‐Blind, 2‐Arm, Placebo‐Controlled, Randomized Safety and Tolerability Study of a Novel Oral Drug Candidate, CTP‐499, in Chronic Kidney Disease

Pentoxifylline for diabetic kidney disease

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Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria A double-blind, placebo-controlled randomized trial