Palmitoylethanolamide against (diabetic) neprhopathy, a new kidney protectant

For patients suffering from (diabetic) nephropathy, kidney disease, a new simple therapy is already available, in the form of the supplement palmitoylethanolamide (PeaPure, Glialia). PEA will be further explored and since 2013 new information also support its amazing safety, up to 100 mg/kg Body Weight. As PEA is metabolized in each cell, it will not burden the kidney and will thus be easily taken by patients, without dose-adaptations or reductions.

Kidney disease and global burden

In the Lancet The global issue of kidney disease editorial ( Vol 382 July 13, 2013 ) the following:

Kai-Uwe Eckardt and colleagues report on the global burden of kidney disease: they estimate that chronic kidney disease affects more than 10% of the world’s population, a similar burden to diabetes.

The prevalence of kidney disease is likely to be underestimated. Simple methods of screening for kidney diseases are available—such as serum creatinine, urinalysis, and blood pressure measurements—which, if they lead to appropriate treatment, might prevent progressive loss of renal function and its consequences.

However, a recent systematic review did not show an improvement in clinical outcomes—such as kidney failure, cardiovascular events, and death—owing to screening for chronic kidney disease in the general population, although selective testing is beneficial in old age, diabetes, or hypertension.

So new therapeutic inroads are welcomed!

Palmitoylethanolamide in renal dysfunction

Palmitoyleythanolamide recently was explored in a renal dysfunction model, and the conclusion was:

Our results clearly demonstrate that PEA significantly attenuated the degree of renal dysfunction, injury, and inflammation caused by ischemia-reperfusion injury.

Palmitoylethanolamide: further development to treat renal pathology

This is the reason for a US based company to further support and explore Palmitoylethanolamide (PEA), as they call it: ‘a novel non-steroidal, kidney-friendly anti-inflammatory and anti-fibrotic agent with a well-documented safety profile in humans.’

Their Medical Officer, recently (2013) said:

“Inflammation and oxidative stress play a key role in the induction and the progression of Chronic Kidney Disease (CKD). This is particularly so in diabetic patients, and it is most likely that inflammation is a major factor in the pathogenesis and progression of diabetic nephropathy. In addition, an increase in inflammatory cytokine levels in diabetes may increase oxidative stress as renal injury becomes more pronounced, thereby establishing a vicious cycle. Prismic, therefore, plans to undertake further clinical development with PEA to prove the concept that this molecule is capable of interrupting this cycle without adversely affecting renal function.”

He also stated that by reducing low grade chronic inflammation and by inhibiting oxidative stress, PEA may reduce risk factors associated with the progression of Chronic Kidney Disease (CKD) and have the potential to offer significant benefit to patients with CKD at early and, quite possibly, even at late stages of the disease.

Inflammation and kidney damage

The pathogenetic cascade of inflammation and nepropathy is recently nicely put in perspected. We quote Kanasaki K, Taduri G, Koya D in: Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis. Front Endocrinol (Lausanne). 2013;4:7. doi: 10.3389/fendo.2013.00007. Epub 2013 Feb 6.

“Once tissue is injured, inflammatory cells infiltrate the site of injury due to the enrichment of pro-inflammatory niches at the site of injury and directional guidance mediated by chemotac- tic cytokine concentration gradients (Chung and Lan, 2011). The infiltration of inflammatory cells, such as lymphocytes, mono- cytes/macrophages, dendritic cells (DCs) and mast cells, precedes the process of tissue fibrosis (Chung and Lan, 2011). At the injury site, activated infiltrated inflammatory cells can synthesize tissue damage factors such as reactive oxygen species (ROS) and produce fibrogenic cytokines and several growth factors (Ricardo etal., 2008; Duffield, 2010; Vernon et al., 2010).
Sustained inflammatory cell activation results in profibrotic cytokine pressure within the local microenvironment. The cytokine pressure subsequently primes the fibroblasts at the site of injury and induces tubular epithelial cell phenotypic changes into a mesenchymal-like phenotype that produces a large amount of profibrotic extracellular matrix (ECM) components (Liu, 2011).” And the authors summerizes:

Therefore, sustained inflammation after the tissue injury could be the initiator, the trigger and the activator of tissue fibrosis progression.

That is exactly the reason why palmitoylethanolamide might be of use, to inhibit this detrimental cascade. Palmitoylethanolamide is a natural and endogenous PPARα agonist.
PPARα is abundantly expressed in the proximal tubules and the medullary thick ascending limbs, and to a less- er extent, in the glomerular mesangial cells. Given the high level of expression in the renal proximal tubules, PPARα has been implicated in the metabolic control of the kidney in maintaining a sustained balance of energy production and expenditure, as Chung et al (2011) pointed out.

They also stated, that: “in association with their critical role as a primary sensor and regulator of lipid metabolism, PPARα agonists have been reported to decrease inflammation. According to numerous experimental studies, PPARα appears to influence both acute and chronic inflammatory disorders involving neutrophils and

Di Paola R, Impellizzeri D, Mondello P, Velardi E, Aloisi C, Cappellani A, Esposito E, Cuzzocrea S. Palmitoylethanolamide reduces early renal dysfunction and injury caused by experimental ischemia and reperfusion in mice. Shock. 2012 Oct;38(4):356-66.

Chung S, Park CW. Role of Peroxisome Proliferator-Activated Receptor α in Diabetic Nephropathy. Diabetes Metab J. 2011 Aug;35(4):327-36. doi: 10.4093/dmj.2011.35.4.327. Epub 2011 Aug 31.

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