Psoriasis, also known as “psoriasis”, is not actually a fungal infection that causes ringworm, but a chronic disease characterized by erythematous skin and white flakes caused by multiple factors.
As psoriasis, which often grows on poles or on various small advertisements, it often tops the list of the “most troubling diseases” because it is persistent and recurrent. But the harm of psoriasis is not only the skin lesions, in recent years several studies at home and abroad found that psoriasis is an independent risk factor for chronic kidney disease and end-stage renal disease, and successively put forward the concept of “psoriasis nephropathy”.
1.Pathogenesis of psoriatic nephropathy
(1) Inflammatory response
Experiments on mice with psoriasis model showed that psoriasis-like inflammation activated TLR receptors in skin lesions, which increased TLR2 and TLR4 expression, and then promoted My D88 protein expression, further activating NF-κB-related protein expression.
That is, increased NF-κBp65 protein expression and decreased IκBα protein expression increase the levels of various inflammatory factors in serum and renal tissues, damaging renal podocytes and thylakoid cells, ultimately leading to kidney injury and thus inducing chronic kidney disease.
(2) Oxidative stress plus
In addition, psoriasis-like inflammation is also able to cause kidney damage by upregulating the expression of renal NADPH oxidase and inducible nitric oxide synthase, leading to a series of consequences such as overproduction of reactive oxygen species, enhanced lipid peroxidation in the body, and decreased antioxidant capacity, which eventually leads to elevated blood creatinine and blood urea nitrogen.
(3) Immune complex deposition
Experimental studies have concluded that serum IgA levels in patients with psoriasis are significantly higher than those in the healthy population and are positively correlated with disease severity PASI scores. Among them, patients with moderate to severe psoriasis had a significantly increased risk of developing IgA nephropathy.
This is mainly related to the deposition of serum immune complex IgA in the glomerular thylakoid membrane, which stimulates glomerular thylakoid cells and induces the secretion of inflammatory factors, chemokines and extracellular matrix proteins through activation of the complement pathway, followed by glomerular inflammation, interstitial fibrosis of the glomerulus and tubules, and ultimately renal injury.
(4) Over-activation of the renin-angiotensin-aldosterone system
In patients with psoriasis, there are both RAAS alterations and elevated renin-angiotensin converting enzyme activity, and the activation of intrarenal RAAS is one of the key factors in the progression of chronic kidney disease. Angiotensin II and aldosterone can cause glomerular small artery constriction, which has a greater effect on the efferent small arteries than the afferent small arteries, increasing the hydraulic pressure difference across the capillaries and the glomerular filtration rate.
Second, angiotensin II promotes Na+ reabsorption and also activates AT1 receptors directly leading to podocyte injury, as well as inducing oxidative stress and prompting overexpression of several cytokines, including TNF-α, IL-6, TGF-β, and platelet-derived growth factors, which play an important role in thylakoid cell proliferation and fibrosis formation through local fibroblast proliferation.
Thus, RAAS activation can induce epithelial-to-mesenchymal cell transformation through TGF-dependent and non-dependent pathways and participate in renal fibrosis.
(5) Endothelial dysfunction
It has been reported that platelet activation in patients with psoriasis can promote inflammatory responses in vascular endothelial cells. Meanwhile, some related studies have shown that endothelial inflammatory response and endothelial dysfunction exist in patients with psoriasis. The endothelial inflammatory response and endothelial dysfunction also play an important role in the pathogenesis of chronic kidney disease.
The inflammatory response causes the renal microvasculature to be unresponsive to regulators, affecting renal microvascular endothelial cells, inducing leukocyte infiltration and increasing local pro-inflammatory factors, thus reducing endothelial barrier function, causing irreversible damage to renal tubules and renal units, and participating in the development of chronic kidney disease.
(6) Insulin resistance
There are multiple co-regulatory mechanisms between psoriasis and insulin resistance, including fat metabolism and adipokines, inflammatory cytokines, and insulin receptor signaling pathways.
The phenomenon of insulin resistance in patients with psoriasis is associated with serum levels of inflammatory factors and disease severity.
The mechanism is that insulin resistance causes renal damage including endothelial dysfunction, increased vascular permeability, increased glomerular capillary pressure, thylakoid hyperplasia, renal hypertrophy and endothelial cell proliferation by affecting renal hemodynamics, releasing inflammatory cytokines and increasing renal endoplasmic reticulum stress.
(7) Other mechanisms
The co-morbidity of psoriasis with chronic kidney disease may also be related to adipokine disorders in patients, as well as genetic susceptibility factors. Among them, psoriasis and IgA nephropathy have several identical genetic susceptibility genes, such as HLA-B, HLA-DR and HLA-DQ.
2.Combined treatment of psoriasis nephropathy
It is not rare for psoriasis to be complicated by nephropathy, but for patients with such complications, active intervention is imminent. In addition to the treatment of psoriasis, such as the use of topical medications, like salicylic acid preparations, coal tar, or phototherapy, proper treatment of the complications is required.
ACEI drugs are angiotensin-converting enzyme inhibitors, represented by captopril, benazepril and enalapril, among others. They can be effective for those with non-nephrotic syndrome manifestations of psoriatic nephropathy.
Although the number of clinically relevant cases of psoriatic nephropathy is relatively small, it does exist. It is also because it exists that it reminds us that psoriasis is really not just a single disease, but it has countless co-morbidities, ranging from cardiovascular to cerebrovascular to urinary system, so scientific prevention and treatment of psoriasis and its co-morbidities has become urgent.
References
[1]Tang W,Chen A-J. Pathogenesis of psoriasis-related renal damage [J]. Medical Information,2021,34(06):36-39.
[2]Li Yinan. A case of psoriasis complicated by nephropathy[J]. Chinese Journal of General Practitioners,2006,(01):49-50.