Phosphodiesterase type 5 inhibitors and kidney disease

Afsar, Barış; Ortíz, Alberto; Covic, Adrian; Gaipov, Abduzhappar; Esen, Tarık; Goldsmith, David; Kanbay, Mehmet

doi:10.1007/s11255-015-1071-4

Cited by 34 publications

(24 citation statements)

References 57 publications

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“…Pentoxifylline, a methylxanthine derivative and non-specific phosphodiesterase inhibitor, has long been proposed as a therapy for diabetic nephropathy 236 . The recently completed PREDIAN study tested the effects of 24 months of pentoxyfylline treatment on proteinuria and eGFR decline in 160 subjects with type 2 diabetes and nephropathy 237 .…”

Section: Additional Agents In Developmentmentioning

confidence: 99%

The next generation of therapeutics for chronic kidney disease

Breyer

Suszták

2016

Nat Rev Drug Discov

210

162

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Chronic kidney disease (CKD) represents a leading cause of death in the United States. There is no cure for the disease, with current treatment strategies relying on blood pressure control through blockade of the renin angiotensin system and glycemic control. Such approaches only delay end stage kidney disease development, and can be associated with significant side effects. Recent identification of several novel mechanisms contributing to CKD development - including vascular changes, loss of podocytes and renal epithelial cells, matrix deposition, inflammation and metabolic dysregulation – has revealed new potential therapeutic approaches for CKD. This review will assess emerging strategies and agents for CKD treatment, highlighting associated challenges in their clinical development.

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Section: Additional Agents In Developmentmentioning

confidence: 99%

The next generation of therapeutics for chronic kidney disease

Breyer

Suszták

2016

Nat Rev Drug Discov

210

162

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“…PDE5 inhibitors represent a class of drugs traditionally used to treat erectile dysfunction and pulmonary hypertension. Recent evidence suggests that PDE5 inhibitors may have additional therapeutic effects such as cardioprotection and cerebrovascular protection . However, the direct effect and mechanism of PDE5 inhibitors in renal fibrosis are not fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence suggests that PDE5 inhibitors may have additional therapeutic effects such as cardioprotection and cerebrovascular protection. 21 However, the direct effect and mechanism of PDE5 inhibitors in renal fibrosis are not fully understood. Recently the long-acting PDE5…”

Section: Discussionmentioning

confidence: 99%

The mechanism of attenuation of epithelial‐mesenchymal transition by a phosphodiesterase 5 inhibitor via renal klotho expression

Han

Kim

Lee

et al. 2017

Clin Exp Pharma Physio

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SummaryPhosphodiesterase‐5 (PDE‐5) inhibitors induces vasodilation in several organs by blocking cyclic GMP (guanosine monophosphate) degradation. However, the existence of alternative mechanism of action in case of an impaired nitric oxide (NO) system remains controversial. Previous studies suggested that decreased NO bioavailability may result in the downregulation of klotho expression, but the relationship between klotho and NO remains obscure. Therefore, we investigated whether a PDE‐5 inhibitor could preserve epithelial–mesenchymal transition (EMT) and relationship exists between the NO and renal klotho expression. Ten‐week‐old SD rats (N = 24, 200 g, male) were divided (N = 6) into four groups, which received: A LSD, L‐NAME 1 mg/mL in drinking water, Udenafil 5 mg/kg subcutaneously and both for 4 weeks. Urine nitrate/nitrite, NGAL (Neutrophil gelatinase‐associated lipocalin), and cGMP were measured using ELISA. Kidney was subjected to evaluate PCNA (proliferative cell nuclear antigen), α‐SMA (smooth muscle cell antigen), E‐cadherin, and klotho expression. Urine cGMP decreased after treatment of PDE‐5 inhibitor compared with control due to blocking degradation of cGMP (P < .05, control vs Udenafil and L‐NAME with Udenafil groups). Urine NGAL increased after treating of L‐NAME and attenuated after using PDE‐5 inhibitor (P < .05, control vs L‐NAME and L‐NAME with Udenafil). PCNA, α‐SMA, and E‐cadherin (EMT markers) increased after L‐NAME treatment and normalized after using PDE‐5 inhibitor. Klotho expression showed trend to increase in the L‐NAME with PDE‐5 inhibitor group compared with the L‐NAME group, however, eNOS expression did not change after treatment of L‐NAME or PDE‐5 inhibitor compared with control. PDE‐5 inhibitor alleviates EMT in the kidney via klotho modulation independent of the NO system.

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“…The authors suggested the urgent need for a RCT of daily dosing of PDE5i for cardio‐prevention. PDE5is, already licensed to treat LUTS/BPH and Pulmonary Hypertension, have been shown to have benefits on endothelial dysfunction, heart failure, renal disease and even cancer prevention …”

Section: Ed and Cvd—evidence For Causation And The Impact Of Modificamentioning

confidence: 99%

Erectile dysfunction and testosterone deficiency as cardiovascular risk factors?

Hackett

Kirby

2018

Int J Clin Pract

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Graham Jackson introduced the concept that erectile dysfunction was a marker for undiagnosed cardiovascular disease and future events. Unfortunately this had had modest impact on CVD management as ED is not incorporated into current risk calculators. In this paper, we examine recent evidence as to whether ED should be upgraded to a risk factor, especially with the high predictive value in younger men. In the Princeton 3 guidelines, he recognised the important impact of testosterone deficiency (TD) on all-cause and cardiovascular mortality. Recent evidence suggests that testosterone therapy to target levels and for sufficient duration, reduces cardiovascular events. In this paper, we also produce a case for testosterone deficiency to be considered as an independent risk factor. The evidence for inclusion of both ED and TD may now be stronger than accepted risk factors and have the advantages of being easily assessed, being quantitative, symptomatic and clinically relevant, especially in younger men.

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Phosphodiesterase type 5 inhibitors and kidney disease

Cited by 34 publications

References 57 publications

The next generation of therapeutics for chronic kidney disease

The next generation of therapeutics for chronic kidney disease

The mechanism of attenuation of epithelial‐mesenchymal transition by a phosphodiesterase 5 inhibitor via renal klotho expression

Erectile dysfunction and testosterone deficiency as cardiovascular risk factors?

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