Cyclic nucleotide phosphodiesterase inhibition as a potential therapeutic target in renal ischemia reperfusion injury

Ischemia/reperfusion (I/R) occurs in renal artery stenosis, partial nephrectomy and most commonly during kidney transplantation. It brings serious consequences such as DGF (Delayed Graft Function) or organ dysfunction leading to renal failure and ultimate death. There is no effective therapy to handle the consequences of Renal Ischemia/Reperfusion (I/R) injury. Cyclic nucleotides, cAMP and cGMP are the important second messengers that stimulate intracellular signal transduction for cell survival in response to growth factors and peptide hormones in normal tissues and in kidneys plays significant role that involves vascular tone regulation, inflammation and proliferation of parenchymal cells. Renal ischemia and subsequent reperfusion injury stimulate signal transduction pathways involved in oxidative stress, inflammation, alteration in renal blood flow leading to necrosis and apoptosis of renal cell. An extensive literature review of various search engines like PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out. To understand the functioning of Phosphodiesterases (PDEs) and its pharmacological modulation in Renal Ischemia-Reperfusion Injury. Current therapeutic options may not be enough to treat renal I/R injury in group of patients and therefore, the current review has discussed the general characteristics and physiology of PDEs and preclinical-studies defining the relationship between PDEs expression in renal injury due to I/R and its outcome on renal function. The role of PDE inhibitors in renal I/R injury and the clinical status of drugs for various renal diseases have been summarized in this review. [Display omitted] •Renal I/R injury commonly observed in kidney transplantation•Phosphodiesterases (PDEs) family and its expression in renal tissue•PDEs pathophysiological role in Renal I/R injury•Inhibition of PDEs as a potential therapeutic target in Renal I/R injury•Various PDEs inhibitors and drugs in clinical trial for various renal diseases